Publications by authors named "Ying Wu"

2,219 Publications

  • Page 1 of 1

Cathepsin C (CTSC) contributes to the antibacterial immunity in golden pompano (Trachinotus ovatus).

Fish Shellfish Immunol 2022 Aug 8. Epub 2022 Aug 8.

State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, PR China; Hainan Provincial Key Laboratory for Tropical Hydrobiology and Biotechnology, College of Marine Science, Hainan University, PR China.

Cathepsins, as a class of protein hydrolases, are widely found in the lysosomes of many tissues and play an essential role in various physiological activities. Cathepsin C (CTSC), a lysosomal cysteine protease, is an essential component of the lysosomal hydrolase family. In this study, we identified a CTSC from Trachinotus ovatus (TroCTSC) and analyzed its function. TroCTSC contained an ORF of 1368 bp and encoded 455 amino acids, which included three conserved catalytically active sites (Cys, His, and Asn). It shares high homology (69.47%-90.77%) with the other known CTSC sequences of teleosts, which was most closely related to Seriola dumerili. TroCTSC was most abundant in the muscle, liver, and head kidney. After Vibrio harveyi infection, the expression levels of TroCTSC in liver, spleen, and head kidney were significantly up-regulated. TroCTSC was found in the cytoplasm with some of which were co-located with the lysosome. After V. harveyi stimulation, TroCTSC was translocated to nucleus in golden pompano snout (GPS) cells. In vitro, results revealed that the optimal hydrolase activity of the recombinant protein, rTroCTSC, was at 40 °C and pH 5.5. The activity of rTroCTSC was promoted by Zn and Ca but inhibited by Fe and Cu. However, three mutant proteins, rTroCTSC-C251A, rTroCTSC-H397A, rTroCTSC-N419A, were dramatically reduced the proteolytic activity. Furthermore, in vivo results showed that overexpression of TroCTSC could significantly enhance body's ability to resist V. harveyi and promote the expression of proinflammatory cytokines, including interleukin 1-beta (IL-1β), IL-6, IL-8, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). In contrast, the interference of TroCTSC expression induced a significant increase in the number of bacteria after V. harveyi infection. Our results suggested that TroCTSC was an essential effector of the innate immune system and played a pivotal role in antibacterial immunity.
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http://dx.doi.org/10.1016/j.fsi.2022.07.078DOI Listing
August 2022

Ectopic expression of BOTRYTIS SUSCEPTIBLE1 reveals its function as a positive regulator of wound-induced cell death and plant susceptibility to Botrytis.

Plant Cell 2022 Aug 10. Epub 2022 Aug 10.

Organismal and Evolutionary Biology Research Program, Faculty of Biological and Environmental Sciences, and the Viikki Plant Science Centre, University of Helsinki, P.O. Box 65 (Viikinkaari 1), FI-00014 Helsinki, Finland.

Programmed cell death is integral to plant life and required for stress responses, immunity, and development. Our understanding of the regulation of programmed cell death is incomplete, especially concerning regulators involved in multiple divergent processes. The botrytis-susceptible (bos1) mutant of Arabidopsis is highly susceptible to fungal infection by Botrytis cinerea (Botrytis). BOS1 (also known as MYB108) regulates cell death propagation during plant responses to wounding. The bos1-1 allele contains a T-DNA insertion in the 5' untranslated region upstream of the start codon. This insertion results in elevated expression of BOS1/MYB108. We used Crispr/Cas9 to create new bos1 alleles with disrupted exons, and found that these lines lacked the typical bos1-1 wounding and Botrytis phenotypes. They did exhibit reduced fertility, as was previously observed in other bos1 alleles. Resequencing of the bos1-1 genome confirmed the presence of a MAS promoter at the T-DNA left border. Expression of the BOS1 gene under control of the MAS promoter in wild-type plants conferred the characteristic phenotypes of bos1-1: Botrytis-sensitivity and response to wounding. Multiple overexpression lines demonstrated that BOS1 was involved in regulation of cell death propagation in a dosage dependent manner. Our data indicate that bos1-1 is a gain-of-function mutant and that BOS1 function in regulation of fertility and Botrytis response can both be understood as misregulated cell death.
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http://dx.doi.org/10.1093/plcell/koac206DOI Listing
August 2022

Emergence of plasmid-mediated tigecycline, β-lactam and florfenicol resistance genes tet(X), bla and floR in Riemerella anatipestifer isolated in China.

Poult Sci 2022 Jul 14;101(10):102057. Epub 2022 Jul 14.

Research Center of Avian Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China; Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu, Sichuan, China. Electronic address:

Bacterial antimicrobial resistance (AMR) continues to develop, with the horizontal transfer of antibiotic resistance genes (ARGs) through plasmids playing a major role. Recently, the antimicrobial resistance of R. anatipestifer has become increasingly severe, jeopardizing the development of the poultry industry. In this study, we used PromethION to determine the whole genome sequence of R. anatipestifer RCAD0416, a multidrug-resistant isolate from China. We detected a plasmid in the isolate. We named the plasmid pRCAD0416RA-1; the plasmid was 37356 bp in size with 36 putative open reading frames and included the bla, floR, tet(X), ermF, ereD, and AadS resistance genes. Most resistance genes might be obtained from R. anatipestifer HXb2. Mobile elements and floR might be transmitted by plasmid pB18-2 from Acinetobacter indicus, and the ICEPg6Chn1 mobile elements can be transmitted from Proteus genomosp. The plasmid pRCAD0416RA-1 was transferred to Escherichia coli K-12 × 7232 via electroporation. Subsequent antimicrobial sensitivity tests (AST) showed a noticeable levels of antimicrobial resistance to β-lactams (4-8 fold), tigecycline (8 fold), and florfenicol (8 fold). These types of antibiotics are in common clinical use. The purpose of this article is to elucidate the basic characteristics of pRCAD0416RA-1 and the level of resistance mediated by bla, floR, and tet(X).
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http://dx.doi.org/10.1016/j.psj.2022.102057DOI Listing
July 2022

Omics analyses indicate sdhC/D act as hubs of early response of E. coli to antibiotics.

Arch Microbiol 2022 Aug 7;204(9):544. Epub 2022 Aug 7.

College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, 471023, China.

In recent years, the phenomenon of microbial resistance has become increasingly serious. The generation of reactive oxygen species (ROS) during the bactericidal process of antibiotics has attracted great interest, but little research has been done on the generation of ROS in the early stage of antibiotic action. We confirmed the rapid production of ROS by flow cytometry and transmission electron microscopy (TEM). GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis indicated that the oxidative phosphorylation pathway is the key pathway of ROS production. Protein-protein interaction (PPI) network results indicate that sdhC/D are key genes in the oxidative phosphorylation pathway. The overexpression of sdhC/D resulted in a lower survival rate than the control strain after antibiotic treatments, which might be due to excess ROS induced by sdhC/D overexpression. The production of superoxide anion in the overexpress strain was significantly higher than that in the control strain, which further verified the importance of sdhC/D in the ROS release of bacteria. Current results showed that bacteria produce large amounts of ROS in the early stage of gentamicin and ampicillin action, and the regulation patterns of genes in the key pathway were consistent. sdhC/D are key genes in the early ROS release process of bacteria. Our study provides a basis for the search of ROS-related enhancers of antimicrobial action.
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http://dx.doi.org/10.1007/s00203-022-03156-6DOI Listing
August 2022

Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP.

J Med Chem 2022 Aug 5. Epub 2022 Aug 5.

Department of Neurology, Johns Hopkins School of Medicine, Baltimore Maryland 21205, United States.

Extracellular vesicles (EVs) can carry pathological cargo and play an active role in disease progression. Neutral sphingomyelinase-2 (nSMase2) is a critical regulator of EV biogenesis, and its inhibition has shown protective effects in multiple disease states. 2,6-imethoxy-4-(5-henyl-4-hiophen-2-yl-1-midazol-2-yl)henol (DPTIP) is one of the most potent (IC = 30 nM) inhibitors of nSMase2 discovered to date. However, DPTIP exhibits poor oral pharmacokinetics (PK), limiting its clinical development. To overcome DPTIP's PK limitations, we synthesized a series of prodrugs by masking its phenolic hydroxyl group. When administered orally, the best prodrug () with a 2',6'-diethyl-1,4'-bipiperidinyl promoiety exhibited >fourfold higher plasma (AUC = 1047 pmol·h/mL) and brain exposures (AUC = 247 pmol·h/g) DPTIP and a significant enhancement of DPTIP half-life (2 h ∼0.5 h). In a mouse model of acute brain injury, DPTIP released from significantly inhibited IL-1β-induced EV release into plasma and attenuated nSMase2 activity. These studies report the discovery of a DPTIP prodrug with potential for clinical translation.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00562DOI Listing
August 2022

Reduced choroidal peripapillary capillaries in thyroid-associated ophthalmopathy with early stage of dysthyroid optic neuropathy.

Int J Ophthalmol 2022 18;15(7):1135-1141. Epub 2022 Jul 18.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China.

Aim: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroid-associated ophthalmopathy (TAO) could be an early sign to detect dysthyroid optic neuropathy (DON).

Methods: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography (OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries (RPC), retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated.

Results: Whole choroidal RPC was significantly reduced in DON (48.24%±0.4978%) compared to normal (50.33%±0.3173%) and TAO without DON (49.16%±0.5463%; =0.0041). The reduction of whole choroidal RPC was also correlated with visual field (VF) defect in DON (=0.5422, =39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed.

Conclusion: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.
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http://dx.doi.org/10.18240/ijo.2022.07.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318097PMC
July 2022

A proposed disease classification system for duck viral hepatitis.

Poult Sci 2022 Jul 1;101(9):102042. Epub 2022 Jul 1.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, China; Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, China. Electronic address:

The nomenclature of duck viral hepatitis (DVH) was historically not a problem. However, 14 hepatotropic viruses among 10 different genera are associated with the same disease name, DVH. Therefore, the disease name increasingly lacks clarity and may no longer fit the scientific description of the disease. Because one disease should not be attributed to 10 genera of viruses, this almost certainly causes misunderstanding regarding the disease-virus relationship. Herein, we revisited the problem and proposed an update to DVH disease classification. This classification is based on the nomenclature of human viral hepatitis and the key principle of Koch's postulates ("one microbe and one disease"). In total, 10 types of disease names have been proposed. These names were literately matched with hepatitis-related viruses. We envision that this intuitive nomenclature system will facilitate scientific communication and consistent interpretation in this field, especially in the Asian veterinary community, where these diseases are most commonly reported.
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http://dx.doi.org/10.1016/j.psj.2022.102042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334327PMC
July 2022

MET overexpression in EGFR L858R mutant treatment-naïve advanced lung adenocarcinoma correlated with poor prognosis: a real-world retrospective study.

J Cancer Res Clin Oncol 2022 Jul 29. Epub 2022 Jul 29.

Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.

Background: Mesenchymal epithelial transition (MET) overexpression has been reported in approximately 50-60% of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers. However, the prognostic significance of MET overexpression has not been established in advanced lung adenocarcinoma (ADC) patients with EGFR-sensitive mutations.

Methods: A retrospective study was performed on a total of 406 treatment-naïve advanced ADC patients with EGFR mutation detection and MET expression information. EGFR mutations were detected by next-generation sequencing or amplification refractory mutation system-polymerase chain reaction. Immuno-histochemistry staining of MET expression was evaluated by H-score and overexpression was defined as an H-score ≥ 200. Overall survival (OS) and progression-free survival (PFS) were analyzed according to MET expression.

Results: Among the 406 patients, 208 patients had EGFR mutations, including 102 exon 19_del mutations, 94 L858R mutations and 12 other types of mutations. Of 110 patients with concomitant EGFR mutations and MET overexpression, 61 (59.8%) patients had 19_del mutations, 44 (46.8%) patients had L858R mutations and five (41.7%) patients had others. Patients with MET overexpression had a markedly shorter PFS and OS than patients with MET H-score < 200 in the EGFR L858R mutation subgroup (median PFS: 12 versus 26 months, p = 0.001; median OS: 24 versus 32 months, p = 0.038), whereas no significant difference was observed in 19_del mutation subgroup. Multivariate Cox analysis showed that MET overexpression was an independent poor prognostic factor for PFS and OS in patients with the L858R mutations (HR = 3.064, 95% CI 1.705-5.507, p < 0.001; HR = 2.043, 95% CI 1.000-4.172; p = 0.049), rather than 19_del.

Conclusions: MET overexpression is a poor prognostic factor for advanced ADC patients with the EGFR L858R mutation.
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http://dx.doi.org/10.1007/s00432-022-04225-5DOI Listing
July 2022

The substitution at residue 218 of the NS5 protein methyltransferase domain of Tembusu virus impairs viral replication and translation and may triggers RIG-I-like receptor signaling.

Poult Sci 2022 Jun 20;101(9):102017. Epub 2022 Jun 20.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu City, Sichuan Province, 611130, China. Electronic address:

Flavivirus RNA cap-methylation plays an important role in viral infection, proliferation, and escape from innate immunity. The methyltransferase (MTase) of the flavivirus NS5 protein catalyzes viral RNA methylation. The E218 amino acid of the NS5 protein MTase domain is one of the active sites of flavivirus methyltransferase. In flaviviruses, the E218A mutation abolished 2'-O methylation activity and significantly reduced N-7 methylation activity. Tembusu virus (TMUV, genus Flavivirus) was a pathogen that caused neurological symptoms in ducklings and decreased egg production in laying ducks. In this study, we focused on a comprehensive understanding of the effects of the E218A mutation on TMUV characteristics and the host immune response. E218A mutation reduced TMUV replication and proliferation, but did not affect viral adsorption and entry. Based on a TMUV replicon system, we found that the E218A mutation impaired viral translation. In addition, E218A mutant virus might be more readily recognized by RIG-I-like receptors to activate the corresponding antiviral immune signaling than WT virus. Together, our data suggest that the E218A mutation of TMUV MTase domain impairs viral replication and translation and may activates RIG-I-like receptor signaling, ultimately leading to a reduction in viral proliferation.
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http://dx.doi.org/10.1016/j.psj.2022.102017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334331PMC
June 2022

How Is Professional Identity Associated with Teacher Career Satisfaction? A Cross-Sectional Design to Test the Multiple Mediating Roles of Psychological Empowerment and Work Engagement.

Int J Environ Res Public Health 2022 Jul 25;19(15). Epub 2022 Jul 25.

Research Center of Tin Ka Ping Moral Education, Zhejiang Normal University, Jinhua 321004, China.

(1) Purpose: Previous studies investigated the positive relationship between professional identity and career satisfaction in teachers, but the underlying reasons were not explored. Therefore, the present study explores the mediating effects of two variables, namely, psychological empowerment and work engagement on the relationship between professional identity and career satisfaction. (2) Method: The present study used the professional identity scale, psychological empowerment scale, Utrecht Work Engagement scale and career satisfaction scale to investigate 2104 teachers (Mage = 39.50 years, SD = 8.74) in a province in China. The demographic variables (e.g., gender, age, teaching age) were controlled as covariates to conduct conservative predictions. (3) Result: (a) professional identity is positively related to career satisfaction; (b) psychological empowerment and career satisfaction play parallel mediator roles between professional identity and career satisfaction; (c) psychological empowerment and career satisfaction play serial mediator roles between professional identity and career satisfaction. (4) Limitations: Data were collected by participant self-report. This method may lead to recall bias. Further, we adopted a cross-sectional rather than experimental or longitudinal design, thus precluding causal conclusions. Lastly, it would be useful to validate our findings with a national sample. (5) Conclusions: The present study indicates that the relationship between professional identity is positively associated with teacher career satisfaction. More importantly, professional identity can indirectly make an impact on teacher career satisfaction through the single mediating effects of psychological empowerment and work engagement, and the chain mediating effect, by improving the level of psychological empowerment, and thereby increasing work engagement.
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http://dx.doi.org/10.3390/ijerph19159009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332691PMC
July 2022

Preferential Expansion of Foxp3 T Regulatory Cells in CTLA-4-Deficient and CTLA-4-Haploinsufficient C57BL/6 Mice.

Immunohorizons 2022 Jul 25;6(7):507-514. Epub 2022 Jul 25.

Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA.

Foxp3 cells and CTLA-4 have been ascribed major roles in downregulating immune responses. To address the relationship between CTLA-4 expression and Foxp3 cells, we generated littermate CTLA-4-sufficient ( ), CTLA-4-haploinsufficient ( ), and CTLA-4-deficient ( ) knock-in C57BL/6 mice, permitting us to characterize the phenotype of Foxp3 cells and to test their ex vivo T regulatory (Treg) suppressor activity. CD3, CD4, and CD8 cells, but not CD19 cells, were markedly expanded in mice compared with or mice. In mice, the relative expansion of the Foxp3 population was greater than that of the CD3, CD4, or CD8 populations because of increased survival of Foxp3 cells. Foxp3 Treg cells from mice and Foxp3 Treg cells from mice exerted identical ex vivo suppressor function. This may be related to differential expression of GITR, CD73, and CD39 on Foxp3 Treg cells from mice versus that on corresponding cells from littermate or mice, with GITR and CD39 being upregulated and CD73 being downregulated on Foxp3 Treg cells from mice. Moreover, CTLA-4 expression in , , and mice correlated with their percentages of Foxp3 cells, suggesting an important role for CTLA-4 expression in Treg cell homeostasis. This may have vital ramifications for the treatment of patients for whom augmentation of suppressor function would be beneficial (e.g., patients with autoimmune diseases) and for whom diminution of suppressor function would be beneficial (e.g., patients with cancer).
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http://dx.doi.org/10.4049/immunohorizons.2200049DOI Listing
July 2022

Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway.

Cell Oncol (Dordr) 2022 Jul 23. Epub 2022 Jul 23.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, 200127, China.

Purpose: This study aimed to investigate the efficiency of our chemically synthesized TT-00420, a novel spectrum-selective multiple protein kinase inhibitor, in cultured cells and animal models of gallbladder cancer (GBC) and explore its potential mechanism.

Methods: Multiple GBC models were established to assess the anti-tumor efficiency, toxicity, and pharmacokinetics of TT-00420. Integrated transcriptomic, proteomic and phosphoproteomic analysis was conducted to identify potential downstream effectors of TT-00420. Western blotting, qRT-PCR, nuclear-cytoplasm separation, and immunofluorescence were performed to confirm the multi-omic results and explore the molecular mechanism of TT-00420. Immunohistochemistry was used to detect FGFR1 and p-FGFR1 expression levels in GBC samples. Autodock software was utilized to investigate the potential binding mode between the TT-00420 and the human FGFR1.

Results: We found that TT-00420 exerted potent growth inhibition of GBC cell lines and multiple xenograft models. Treatment of mice with 15 mg/kg TT-00420 via gavage displayed a half-life of 1.8 h in the blood and rapid distribution to the liver, kidneys, lungs, spleen, and tumors at 0.25 h, but no toxicity to these organs over 2 weeks. Multi-omic analysis revealed c-Jun as a potential downstream effector after TT-00420 treatment. Mechanistically, TT-00420 showed rigorous ability to block FGFR1 and its downstream JNK-JUN (S63/S73) signaling pathway, and induce c-Jun S243-dependent MEK/ERK reactivation, leading to FASLG-dependent tumor cell death. Finally, we found that FGFR1 and p-FGFR1 expression was elevated in GBC patients and these levels correlated with decreased patient survival.

Conclusions: TT-00420 shows potent antitumor efficacy and may serve as a novel agent to improve GBC prognosis.
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http://dx.doi.org/10.1007/s13402-022-00692-7DOI Listing
July 2022

Approaching well-dispersed MoS assisted with cellulose nanofiber for highly durable hydrogen evolution reaction.

Carbohydr Polym 2022 Oct 20;294:119754. Epub 2022 Jun 20.

College of Materials Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China. Electronic address:

The agglomeration and low conductivity of molybdenum disulfide (MoS) electrocatalysts restrict the presentation of its real intrinsic reaction activity, which leads to challenges for the high-performance hydrogen evolution reaction (HER). Herein, a well-dispersed and superhydrophilic/superaerophobic MoS catalyst with uniform three-dimensional conductive networks have been prepared assisted with cellulose nanofiber (CNF) and carboxylated multi-walled carbon nanotubes (cMWCNT). The resulted CNF/cMWCNT/MoS catalysts present a superhydrophilic/superaerophobic state with contact angles for water and bubble of 0° and 154.1° respectively. This structure effectively disperses MoS nanoparticles through uniform embeddedness and promotes gas-liquid mass transfer via wettability. Benefiting from these optimizations, the CNF/cMWCNT/MoS exhibits better HER performance and a low overpotential (154 mV @ 10 mA/cm). Encourangingly, CNF/cMWCNT/MoS catalysts have a slight decay of 6.99 % at 10 mA/cm after 100 h, while the cMWCNT/MoS shows a decay of 35.83 %. This approach using natural CNF for well-dispersed catalysts provides a potential for high-performance HER electrode design.
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http://dx.doi.org/10.1016/j.carbpol.2022.119754DOI Listing
October 2022

Evaluation of the Efficiency of MRI-Based Radiomics Classifiers in the Diagnosis of Prostate Lesions.

Front Oncol 2022 5;12:934108. Epub 2022 Jul 5.

Department of Radiology, the First Affiliated Hospital, Nanchang University, Nanchang, China.

Objective: To compare the performance of different imaging classifiers in the prospective diagnosis of prostate diseases based on multiparameter MRI.

Methods: A total of 238 patients with pathological outcomes were enrolled from September 2019 to July 2021, including 142 in the training set and 96 in the test set. After the regions of interest were manually segmented, decision tree (DT), Gaussian naive Bayes (GNB), XGBoost, logistic regression, random forest (RF) and support vector machine classifier (SVC) models were established on the training set and tested on the independent test set. The prospective diagnostic performance of each classifier was compared by using the AUC, F1-score and Brier score.

Results: In the patient-based data set, the top three classifiers of combined sequences in terms of the AUC were logistic regression (0.865), RF (0.862), and DT (0.852); RF "was significantly different from the other two classifiers (P =0.022, P =0.005), while logistic regression and DT had no statistical significance (P =0.802). In the lesions-based data set, the top three classifiers of combined sequences in terms of the AUC were RF (0.931), logistic regression (0.922) and GNB (0.922). These three classifiers were significantly different from.

Conclusion: The results of this experiment show that radiomics has a high diagnostic efficiency for prostate lesions. The RF classifier generally performed better overall than the other classifiers in the experiment. The XGBoost and logistic regression models also had high classification value in the lesions-based data set.
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http://dx.doi.org/10.3389/fonc.2022.934108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295912PMC
July 2022

The mutation spectrum of PD-related genes in early-onset Parkinson's disease in ethnic Chinese.

Eur J Neurol 2022 Jul 21. Epub 2022 Jul 21.

Department of Neurology, Mianyang Central Hospital, Mianyang, Sichuan, China.

Background: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese.

Methods: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤ 45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analyzed.

Results: We identified 82 (11.6%, 82/704) EOPD patients carrying rare pathogenic/ likely pathogenic variants in PD-related genes. The mutation frequency in autosomal recessive inheritance EOPD (AR-EOPD, 42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (AD-EOPD, 0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN, and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6, and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n=1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction.

Conclusions: Our study reveals that the genetic spectrum EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.
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http://dx.doi.org/10.1111/ene.15509DOI Listing
July 2022

In situ bidirectional human-robot value alignment.

Sci Robot 2022 Jul 13;7(68):eabm4183. Epub 2022 Jul 13.

Department of Computer Science, University of California, Los Angeles, Los Angeles, CA 90095, USA.

A prerequisite for social coordination is bidirectional communication between teammates, each playing two roles simultaneously: as receptive listeners and expressive speakers. For robots working with humans in complex situations with multiple goals that differ in importance, failure to fulfill the expectation of either role could undermine group performance due to misalignment of values between humans and robots. Specifically, a robot needs to serve as an effective listener to infer human users' intents from instructions and feedback and as an expressive speaker to explain its decision processes to users. Here, we investigate how to foster effective bidirectional human-robot communications in the context of value alignment-collaborative robots and users form an aligned understanding of the importance of possible task goals. We propose an explainable artificial intelligence (XAI) system in which a group of robots predicts users' values by taking in situ feedback into consideration while communicating their decision processes to users through explanations. To learn from human feedback, our XAI system integrates a cooperative communication model for inferring human values associated with multiple desirable goals. To be interpretable to humans, the system simulates human mental dynamics and predicts optimal explanations using graphical models. We conducted psychological experiments to examine the core components of the proposed computational framework. Our results show that real-time human-robot mutual understanding in complex cooperative tasks is achievable with a learning model based on bidirectional communication. We believe that this interaction framework can shed light on bidirectional value alignment in communicative XAI systems and, more broadly, in future human-machine teaming systems.
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http://dx.doi.org/10.1126/scirobotics.abm4183DOI Listing
July 2022

A qualitative study exploring barriers and facilitators to establishing nurse-led, multidisciplinary psychological care for trauma patients: experiences from doctors and nurses.

BMC Nurs 2022 Jul 19;21(1):191. Epub 2022 Jul 19.

Department of Nursing, Southwest Hospital, the first affiliated hospital to Army Medical University, Chongqing, China.

Background: Trauma patients are often in a state of psychological stress, experiencing helplessness, sadness, frustration, irritation, avoidance, irritability and other adverse emotions. Doctors and nurses are at the forefront of caring trauma patients and they play a crucial role in psychological supports and mental health care. However, few qualitative studies had based on the framework of the Theory of Planned Behavior (TPB) to explore the experiences in providing psychological care for trauma patients. We examined attitudinal, normative, and control beliefs underpinning medical staffs' decisions to perform psychological care.

Method: A qualitative study of in-depth semi-structured interviews was conducted among 14 doctors and nurses engaging in trauma care. The participants came from six tertiary hospitals in Chongqing, China. Data analysis was performed using the approach of Colaizzi. According to the framework of TPB, the researchers identified and summarized the themes.

Results: Important advantages (mutual trust, patients' adherence and recovery), disadvantages (workload, short-term ineffective, practice unconfidently), referents (supportive: managers, patients, kinsfolk, nursing culture; unsupportive: some colleagues and patients), barriers (insufficient time or energy, resources situations), and facilitators (access to psychologist, training/education, reminders) were identified. Some demands, such as training diversity, multidisciplinary cooperation and families' support, reflected by doctors and nurses were important for them to carry out psychological care.

Conclusion: According to the TPB, this article explored the internal and external promotion and hindrance factors that affecting the intentions and behaviors of doctors and nurses in implementing psychological care for trauma patients. We also focused on the experience and demands of health professionals in conducting psychological care, which could provide references for managers to formulate corresponding psychological care procedures and norms.
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http://dx.doi.org/10.1186/s12912-022-00971-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297566PMC
July 2022

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness.

Int J Hyperthermia 2022 ;39(1):935-945

Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Objectives: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness.

Methods: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA ( = 52) or continued TACE ( = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group.

Results: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both  < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure.

Conclusion: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.
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http://dx.doi.org/10.1080/02656736.2022.2093413DOI Listing
July 2022

Branched-chain and aromatic amino acid levels response to an oral glucose load associated with gestational diabetes mellitus.

Sci Rep 2022 Jul 18;12(1):12257. Epub 2022 Jul 18.

Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China.

Serum branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with obesity, insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the levels of these amino acids in women with gestational diabetes mellitus (GDM) and examined their changes in response to an oral glucose tolerance test (OGTT). 110 women were enrolled and underwent a 75-g OGTT during their second trimester; 43 women were diagnosed with GDM and 67 women did not have GDM (non-GDM women). During the OGTT, fasting, 1-h, and 2-h blood samples were obtained. BCAA and AAA levels were measured by liquid chromatography-tandem mass spectrometry. The differences in BCAA and AAA levels between GDM and non-GDM women were not evident during fasting but became significant after glucose loading. Glucose ingestion decreased the levels of BCAAs and AAAs in both groups. Notably, GDM women showed a delayed and blunted decrease in these amino acids compared to non-GDM women. The risks of 2-h changes in BCAAs and AAAs for GDM women were significant. We identified that the differences in BCAA and AAA levels between GDM women and controls, which were not evident during fasting, could be provoked by performing an OGTT.
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http://dx.doi.org/10.1038/s41598-022-16539-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293928PMC
July 2022

Cohort profile: the Liyang cohort study on chronic diseases and risk factors monitoring in China (Liyang Study).

BMJ Open 2022 07 18;12(7):e060978. Epub 2022 Jul 18.

Department of Epidemiology and Biostatistics, Soochow University Medical College, Suzhou, China

Purpose: The Liyang cohort study on chronic diseases and risk factors monitoring in China (Liyang Study) is a prospective population-based study which aims to investigate and identify the determinants of the most prevalent chronic non-communicable diseases (NCDs) and to evaluate the impact of demographic characteristics, lifestyle, dietary habits, cognition, disability and NCDs on the health-related quality of life.

Participants: Between March 2019 and June 2020, 10 056 individuals aged ≥18 years were administered a baseline survey through a multistage cluster random sampling in Liyang City, southern Jiangsu Province, China.

Findings To Date: The Liyang Study included detailed sociodemographic, anthropometric and health-related behaviour, common NCDs and blood sample information. Moreover, the study gathered a series of data on specific scales including the activities of daily living, instrumental activities of daily living, abbreviated mental test, Food Frequency Questionnaire and EuroQol 5-Dimensions 5-Levels Scale. Of the 10 056 participants, 52.92% (n=5322) were female and 92.26% (n=9278) came from rural areas. The mean age was 49.9±16.2 years. Men were more likely to have a higher level of education, annual income and a paid job than women (p<0.05). The top three overall most prevalent NCDs in the study were hypertension (18.06%, n=1815), digestive diseases (7.88%, n=791), and arthritis or rheumatism (5.28%, n=530). Women had a significantly higher prevalence of diabetes (5.46%, n=290 vs 4.42%, n=209, p=0.016) and arthritis (6.04%, n=321 vs 4.42%, n=209, p<0.001) than men, while the opposite was true for chronic lung diseases such as chronic obstructive pulmonary disease (1.37%, n=65 vs 0.92%, n=49, p=0.032) and chronic hepatic diseases (0.80%, n=38 vs 0.47%, n=25, p=0.035).

Future Plans: The current study will give valuable insights into the association between sociodemographic factors, health-related behaviour, diet, cognition, disability and genetic factors and the most prevalent NCDs among local community residents. Starting from 2022, a follow-up survey will be conducted every 3 years to further explore the causal relationship between the above factors and NCDs.
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http://dx.doi.org/10.1136/bmjopen-2022-060978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297217PMC
July 2022

Rare Variant Analysis of PTRHD1 in Parkinson's Disease in the Chinese Population.

J Parkinsons Dis 2022 Jul 11. Epub 2022 Jul 11.

Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, China.

Homozygous missense variants in PTRHD1 have been identified to cause parkinsonism by segregation analysis in families. Further replication in the Parkinson's disease (PD) population might provide additional insight. Here, we analyzed the rare variants in a Chinese PD cohort (Ncase = 1367, Ncontrol = 3298) with whole exome sequencing. We did not identify the variants described in previous studies, and no patient carried other homozygous or compound heterozygous variants of PTRHD1. Three rare variants were identified, but rare variants of PTRHD1 were not enriched in PD. Genetic screening suggested rare variants of PTRHD1 as disease cause were rare in PD in East Asians.
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http://dx.doi.org/10.3233/JPD-223337DOI Listing
July 2022

Concentrations of transparent exopolymer particles (TEPs) and their role in the carbon export in the South China Sea and western tropical North Pacific.

Mar Environ Res 2022 Jul 9;179:105699. Epub 2022 Jul 9.

Jiaozhou Bay National Marine Ecosystem Research Station, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, PR China; Laboratory for Marine Ecology and Environmental Science, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, PR China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:

The role of TEPs in the carbon cycle remains inadequately understood in oligotrophic tropical oceans. This study investigates TEP concentrations, distributions, sinking behavior and fluxes in the oligotrophic South China Sea (SCS) and western tropical North Pacific (WTNP). The results suggested that TEPs levels were relatively low [< 60 μg Xeq. L (μg xanthan gum equivalent per liter)] in both regions, and they were higher in the epipelagic layer than in deeper layers. TEP concentrations correlated significantly positively with Chl a and picophytoplankton biomass, and TEP-associated carbon contributed significantly to particulate organic carbon (POC) pool in the SCS and WTNP. The sinking flux of TEPs constituted a mean of 61% of the total POC flux in the SCS and 46% in the WTNP, highlighting their important role in carbon export in these areas. Generally, this study should provide good insight into the role TEPs play in the carbon cycle in oligotrophic tropical oceans.
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http://dx.doi.org/10.1016/j.marenvres.2022.105699DOI Listing
July 2022

Duck Plague Virus Negatively Regulates IFN Signaling to Promote Virus Proliferation JNK Signaling Pathway.

Front Immunol 2022 28;13:935454. Epub 2022 Jun 28.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu City, China.

Duck plague virus (DPV), a member of the subfamily, can cause severe damage and immunosuppression in ducks and geese in China. Since lacking an available cell model, the antiviral signal transduction pathways induction and regulation mechanisms related to DPV infection in duck cells are still enigmatic. Our previous study developed a monocyte/macrophages cell model, which has been applied to study innate immunity with DPV. In the present study, we compared and analyzed transcriptome associated with the DPV infection of CHv (virulent strain) and CHa (avirulent strain) at 48hpi based on the duck monocyte/macrophages cell model and RNA-seq technology. Differentially expressed genes (DEGs) analysis showed 2,909 and 2,438 genes altered in CHv and CHa infected cells compared with control cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the DEGs were mainly involved in biological processes such as metabolic pathways, viral infectious diseases, immune system, and signal transduction. The CHv and CHa virus differentially regulated MAPK, NF-κB, and IFN signaling pathways based on transcriptome sequencing data and RT-qPCR results. The JNK inhibitor SP600125 enhanced the IFN signaling, but potentially reduced the VSV and DPV titers in the cell culture supernatant, indicating that JNK negatively regulates the IFN pathway and the inflammatory pathway to promote virus proliferation. The research results may provide promising information to understand the pathogenesis of DPV and provide a novel mechanism by which DPV modulates antiviral signaling and facilitate virus proliferation through hijacking the JNK pathway, which provides a new means for the prevention and control of DPV infection.
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http://dx.doi.org/10.3389/fimmu.2022.935454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275408PMC
June 2022

Differential expression profile and in-silico functional analysis of long noncoding RNA and mRNA in duck embryo fibroblasts infected with duck plague virus.

BMC Genomics 2022 Jul 14;23(1):509. Epub 2022 Jul 14.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Sichuan Province, Wenjiang District, Chengdu, 611130, China.

Background: Duck plague virus (DPV), belonging to herpesviruses, is a linear double-stranded DNA virus. There are many reports about the outbreak of the duck plague in a variety of countries, which caused huge economic losses. Recently, increasing reports revealed that multiple long non-coding RNAs (lncRNAs) can possess great potential in the regulation of host antiviral immune response. Furthermore, it remains to be determined which specific molecular mechanisms are responsible for the DPV-host interaction in host immunity. Here, lncRNAs and mRNAs in DPV infected duck embryonic fibroblast (DEF) cells were identified by high-throughput RNA-sequencing (RNA-seq). And we predicted target genes of differentially expressed genes (DEGs) and formed a complex regulatory network depending on in-silico analysis and prediction.

Result: RNA-seq analysis results showed that 2921 lncRNAs were found at 30 h post-infection (hpi). In our study, 218 DE lncRNAs and 2840 DE mRNAs were obtained in DEF after DPV infection. Among these DEGs and target genes, some have been authenticated as immune-related molecules, such as a Macrophage mannose receptor (MR), Anas platyrhynchos toll-like receptor 2 (TLR2), leukocyte differentiation antigen, interleukin family, and their related regulatory factors. Furthermore, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis, we found that the target genes may have important effects on biological development, biosynthesis, signal transduction, cell biological regulation, and cell process. Also, we obtained, the potential targeting relationship existing in DEF cells between host lncRNAs and DPV-encoded miRNAs by software.

Conclusions: This study revealed not only expression changes, but also the possible biological regulatory relationship of lncRNAs and mRNAs in DPV infected DEF cells. Together, these data and analyses provide additional insight into the role of lncRNAs and mRNAs in the host's immune response to DPV infection.
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http://dx.doi.org/10.1186/s12864-022-08739-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281093PMC
July 2022

Lifespan associations of resting-state brain functional networks with ADHD symptoms.

iScience 2022 Jul 26;25(7):104673. Epub 2022 Jun 26.

Department of Physics, Centre for Nonlinear Studies, Beijing-Hong Kong-Singapore Joint Centre for Nonlinear and Complex Systems (Hong Kong), Institute of Computational and Theoretical Studies, Hong Kong Baptist University, Hong Kong.

Attention-deficit/hyperactivity disorder (ADHD) is increasingly being diagnosed in both children and adults, but the neural mechanisms that underlie its distinct symptoms and whether children and adults share the same mechanism remain poorly understood. Here, we used a nested-spectral partition approach to study resting-state brain networks of ADHD patients (n = 97) and healthy controls (HCs, n = 97) across the lifespan (7-50 years). Compared to the linear lifespan associations of brain segregation and integration with age in HCs, ADHD patients have a quadratic association in the whole-brain and in most functional systems, whereas the limbic system dominantly affected by ADHD has a linear association. Furthermore, the limbic system better predicts hyperactivity, and the salient attention system better predicts inattention. These predictions are shared in children and adults with ADHD. Our findings reveal a lifespan association of brain networks with ADHD and provide potential shared neural bases of distinct ADHD symptoms in children and adults.
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http://dx.doi.org/10.1016/j.isci.2022.104673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272385PMC
July 2022

A functional reference map of the RNF8 interactome in cancer.

Biol Direct 2022 07 13;17(1):17. Epub 2022 Jul 13.

Department of Biology and Chemistry, College of Sciences, National University of Defense Technology, Changsha, 410073, Hunan, China.

Background: RNF8 is an E3 ligase identified as a critical DNA damage-responsive protein. Recently, multiple reports have shown that RNF8 could be used as an important therapeutic target for cancer chemo/radiotherapy. However, the understanding of RNF8 remains limited due to the lack of its interactome reference map and comprehensive analysis of RNF8 in diverse cancers, which underscores the need to map the interactome of RNF8 via high-throughput methods.

Results: A two-way identification method based on LC-MS was designed for the identification of the RNF8 interactome with high-specificity. By in silico analysis and in vitro validation, we identified a new reference map of the RNF8 interactome network containing many new targets, such as YBX1, DNMT1, and HDCA1, new biological functions and the gene-disease associations of RNF8. Our results revealed a close relationship between RNF8 and neurodegenerative diseases or tumor-infiltrating immune cells using bulk RNA-seq and scRNA-seq datasets. As a proof of concept of our interactome map, we validated the direct binding between RNF8 and YBX1 and showed that RNF8 catalyzed the ubiquitination of YBX1. These results demonstrated that RNF8 might be a crucial regulator of YBX1.

Conclusions: Our work provides a unique framework for researchers and clinicians who seek to better explore or understand RNF8-regulated biological functions in cancers. This study will hopefully facilitate the rational design and further development of anti-RNF8 therapy in cancers.
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http://dx.doi.org/10.1186/s13062-022-00331-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277853PMC
July 2022

RBM47 inhibits hepatocellular carcinoma progression by targeting UPF1 as a DNA/RNA regulator.

Cell Death Discov 2022 Jul 14;8(1):320. Epub 2022 Jul 14.

School of Stomatology, Weifang Medical University, Weifang, 261053, China.

The mechanisms by which the tumor behaviors of hepatocellular carcinoma (HCC) support growth and metastasis remain largely unknown, and it has become increasingly apparent that molecular dysregulation is of considerable importance for cellular signaling pathways. Recently, RNA-binding motif protein 47 (RBM47) has been suggested to function as a tumor regulator by acting as an RNA binding protein (RBP), but its role in HCC remains ambiguous. Here, in HCC, we identified that RBM47 had an inhibitory influence on tumor behaviors in vitro and accordingly suppressed the growth and metastasis of xenograft tumors in vivo. Additionally, RBM47 was verified to positively regulate Upframeshift 1 (UPF1), which is a crucial protein involved in the nonsense-mediated RNA decay (NMD) process and was previously determined to be an HCC suppressor. Mechanistically, the stability of UPF1 mRNA was demonstrated to be enhanced with its 3'UTR bound by RBM47, which acted as an RNA binding protein. Meanwhile, RBM47 was also proven to promote the transcription of UPF1 as a transcription factor. Taken together, we concluded that RBM47 functioned as a tumor suppressor by upregulating UPF1, acting as a DNA/RNA binding protein at the transcriptional and posttranscriptional levels.
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http://dx.doi.org/10.1038/s41420-022-01112-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279423PMC
July 2022

Ratiometric Detection of HS in Liver Injury by Activated Two-Wavelength Photoacoustic Imaging.

Anal Chem 2022 08 13;94(30):10797-10804. Epub 2022 Jul 13.

Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China, MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, College of Chemical Engineering, Fuzhou University, Fuzhou 350108, P. R. China.

Metformin is commonly used for clinical treatment of type-2 diabetes, but long-term or overdose intake of metformin usually causes selective upregulation of HS level in the liver, resulting in liver injury. Therefore, tracking the changes of HS content in the liver would contribute to the prevention and diagnosis of liver injury. However, in the literature, there are few reports on ratiometric PA molecular probes for HS detection in drug-induced liver injury (DILI). Accordingly, here we developed a HS-activated ratiometric PA probe, namely BDP-HS, based Aza-BODIPY dye for detecting the HS upregulation of metformin-induced liver injury. Due to the intramolecular charge transfer (ICT) effect, BDP-HS exhibited a strong PA signal at 770 nm. Following the response to HS, its ICT effect was recovered which showed a decrement of PA and an enhancement of PA. The ratiometric PA signal (PA/PA) showed excellent HS selectivity response with a low limit of detection (0.59 μM). Bioimaging experiments demonstrated that the probe has been successfully used for ratiometric PA imaging of HS in cells and metformin-induced liver injury in mice. Overall, the designed probe emerges as a powerful tool for noninvasive and accurate imaging of HS level and tracking its distribution and variation in liver in-real time.
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http://dx.doi.org/10.1021/acs.analchem.2c01571DOI Listing
August 2022

Peritumoral Imaging Manifestations on Gd-EOB-DTPA-Enhanced MRI for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Front Oncol 2022 24;12:907076. Epub 2022 Jun 24.

Department of Radiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Purpose: The aim was to investigate the association between microvascular invasion (MVI) and the peritumoral imaging features of gadolinium ethoxybenzyl DTPA-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) in hepatocellular carcinoma (HCC).

Methods: Up until Feb 24, 2022, the PubMed, Embase, and Cochrane Library databases were carefully searched for relevant material. The software packages utilized for this meta-analysis were Review Manager 5.4.1, Meta-DiSc 1.4, and Stata16.0. Summary results are presented as sensitivity (SEN), specificity (SPE), diagnostic odds ratios (DORs), area under the receiver operating characteristic curve (AUC), and 95% confidence interval (CI). The sources of heterogeneity were investigated using subgroup analysis.

Results: An aggregate of nineteen articles were remembered for this meta-analysis: peritumoral enhancement on the arterial phase (AP) was described in 13 of these studies and peritumoral hypointensity on the hepatobiliary phase (HBP) in all 19 studies. The SEN, SPE, DOR, and AUC of the 13 investigations on peritumoral enhancement on AP were 0.59 (95% CI, 0.41-0.58), 0.80 (95% CI, 0.75-0.85), 4 (95% CI, 3-6), and 0.73 (95% CI, 0.69-0.77), respectively. The SEN, SPE, DOR, and AUC of 19 studies on peritumoral hypointensity on HBP were 0.55 (95% CI, 0.45-0.64), 0.87 (95% CI, 0.81-0.91), 8 (95% CI, 5-12), and 0.80 (95% CI, 0.76-0.83), respectively. The subgroup analysis of two imaging features identified ten and seven potential factors for heterogeneity, respectively.

Conclusion: The results of peritumoral enhancement on the AP and peritumoral hypointensity on HBP showed high SPE but low SEN. This indicates that the peritumoral imaging features on Gd-EOB-DTPA-enhanced MRI can be used as a noninvasive, excluded diagnosis for predicting hepatic MVI in HCC preoperatively. Moreover, the results of this analysis should be updated when additional data become available. Additionally, in the future, how to improve its SEN will be a new research direction.
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http://dx.doi.org/10.3389/fonc.2022.907076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263828PMC
June 2022

Health-Related Quality of Life in Cervical Dystonia Using EQ-5D-5L: A Large Cross-Sectional Study in China.

Front Neurol 2022 23;13:895272. Epub 2022 Jun 23.

Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China.

Purpose: The study aimed to evaluate the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in patients with cervical dystonia, and to explore the determinants of HRQoL in patients with cervical dystonia.

Methods: EQ-5D-5L health state profiles were converted into a single aggregated "health utility" score. A calibrated visual analog scale (EQ VAS) was used for self-rating of current health status. Multiple linear regression analysis was used to explore the factors associated with HRQoL in cervical dystonia.

Results: A total of 333 patients with cervical dystonia were enrolled in the analysis, with an average age of 44.3 years old. The most common impaired dimension of health was anxiety/depression (73.6%), followed by pain/discomfort (68.2%) and usual activities (48%). The median health utility score was 0.80, and the median EQ VAS score was 70.2. Multivariate linear regression analysis indicated that disease duration and the scores of the Hamilton Depression Rating Scale (HDRS), Pittsburgh sleep quality index (PSQI), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Part I, and TWSTRS Part III were associated with the health utility scores. After adjusting other parameters, the TWSTRS Part III score and the HDRS score were significantly associated with the EQ VAS scores ( < 0.05).

Conclusion: This study evaluated HRQoL in patients with cervical dystonia using the Chinese version of the EQ-5D-5L scale. We found that, besides motor symptoms, non-motor symptoms, including depression, pain, and sleep quality, could be greater determinants of HRQoL in patients with cervical dystonia. Management of non-motor symptoms, therefore, may help improve HRQoL in patients with cervical dystonia.
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http://dx.doi.org/10.3389/fneur.2022.895272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262169PMC
June 2022
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