Publications by authors named "Jing Ye"

1,025 Publications

  • Page 1 of 1

Combination of Hematoma Volume and Perihematoma Radiomics Analysis on Baseline CT Scan Predicts the Growth of Perihematomal Edema.

Clin Neuroradiol 2022 Aug 9. Epub 2022 Aug 9.

Department of Radiology, Northern Jiangsu People's Hospital, 225001, Yangzhou, China.

Purpose: The aim is to explore the potential value of CT-based radiomics in predicting perihematomal edema (PHE) volumes after acute intracerebral hemorrhage (ICH) from admission to 24 h.

Methods: A total of 231 patients newly diagnosed with acute ICH at two institutes were analyzed retrospectively. The patients were randomly divided into training (N = 117) and internal validation cohort (N = 45) from institute 1 with a ratio of 7:3. According to radiomics features extracted from baseline CT, the radiomics signatures were constructed. Multiple logistic regression analysis was used for clinical radiological factors and then the nomogram model was generated to predict the extent of PHE according to the optimal radiomics signature and the clinical radiological factors. The receiver operating characteristic (ROC) curve was used to evaluate the discrimination performance. The calibration curve and Hosmer-Lemeshow test were used to evaluate the consistency between the predicted and actual probability. The support vector regression (SVR) model was constructed to predict the overall value of follow-up PHE. The performance of the models was evaluated on the internal and independent validation cohorts.

Results: The perihematoma 5 mm radiomics signature (AUC: 0.875) showed good ability to discriminate the small relative PHE(rPHE) from large rPHE volumes, comparing to intrahematoma radiomics signature (AUC: 0.711) or perihematoma 10 mm radiomics signature (AUC: 0.692) on the training cohort. The AUC of the combined nomogram model was 0.922 for the training cohort, 0.945 and 0.902 for the internal and independent validation cohorts, respectively. The calibration curves and Hosmer-Lemeshow test of the nomogram model suggested that the predictive performance and actual outcome were in favorable agreement. The SVR model also predicted the overall value of follow-up rPHE (root mean squared error, 0.60 and 0.45; Pearson correlation coefficient, 0.73 and 0.68; P < 0.001).

Conclusion: Among patients with acute ICH, the established nomogram and SVR model with favorable performance can offer a noninvasive tool for the prediction of PHE after ICH.
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http://dx.doi.org/10.1007/s00062-022-01201-xDOI Listing
August 2022

Endocytosis-mediated triple-activable prodrug nanotherapeutics potentiating therapeutic efficacy and security towards solid tumors.

Colloids Surf B Biointerfaces 2022 Jul 30;218:112723. Epub 2022 Jul 30.

Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Self-assembling prodrug nanotherapeutics have emerged as a promising nanoplatform for anticancer drug delivery. The specific and efficient activation of prodrug nanotherapeutics inside tumor cells is vital for the antitumor efficacy and security. Herein, a triple-activable prodrug polymer (TAP) is synthesized by conjugating polyethylene glycol-poly-(caprolactone)-paclitaxel (PTX) polymer with two tumor-responsive bonds, disulfide and acetal. TAP could self-assemble into nanotherapeutics (TAP NTs) free of surfactant with a high drug loading (32.6%). In blood circulation, TAP NTs could remain intact to efficiently accumulate in tumor sites. Thereafter, tumor cells would internalize TAP NTs through multiple endocytosis pathways. Inside tumor cells, TAP NTs could be activated to release PTX and induce tumor cell apoptosis in triple pathways: (i) lysosomal acidity rapid activation; (ii) ROS-acidity tandem activation and (iii) GSH-acidity tandem activation. Compared with Taxol and non-activable control, TAP NTs significantly potentiate the antitumor efficacy and security of PTX against solid tumors including breast cancer and colon cancer.
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http://dx.doi.org/10.1016/j.colsurfb.2022.112723DOI Listing
July 2022

Effect of early inflammatory reaction on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas.

J Obstet Gynaecol 2022 Aug 5:1-5. Epub 2022 Aug 5.

Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

This study aimed to investigate the effect of early inflammatory reaction on ovarian reserve of patients with ovarian endometriomas after laparoscopic cystectomy. Our retrospective case series included 112 patients with ovarian endometriomas that underwent the laparoendoscopic single-site cystectomy. Interleukin-6 (IL-6), hs-CRP, tumour necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and AMH level were detected during perioperative and postoperative period. In our study, ovarian endometriomas with low AMH group were found having higher level of IL-6 than the normal AMH group in the preoperative status. On the 3rd day after operation, the change of AMH level was inversely proportional to the IL-6 level. During the follow-up within one year, it was found that the bilateral nature of the cyst and the postoperative IL-6 increased level were the risk factors for AMH not returning to baseline level. Our results suggested that inflammatory reaction is indeed involved in the damage of ovarian reserve during laparoscopic cystectomy. Hence, the negative impact of inflammatory injury should be fully considered before operation, especially young women with bilateral ovarian endometriomas.Impact Statement Ovarian reserve in women always was reduced after the laparoscopic cystectomy. It is reported that it may be related to the use of energy instruments, haemostatic methods or the size of cysts in minimally invasive surgery. Inflammatory reaction is indeed involved in the damage of ovarian reserve during LESS cystectomy. Interleukin-6 (IL-6) may act as the most main inflammatory factor aggravating damage of the ovarian reserve. Moreover, increased IL-6 level after surgery and bilateral cyst burden are the two risk factors for AMH not returning to baseline level within one year after surgery. In clinic, the negative impact of inflammatory injury on ovarian reserve should be fully considered before operation, especially young women with bilateral ovarian endometriomas. Moreover, this is also the clinical basis for further study on the mechanism of inflammatory ovarian injury or the method of blocking the inflammatory response to reduce the damage of ovarian reserve after surgery.
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http://dx.doi.org/10.1080/01443615.2022.2106559DOI Listing
August 2022

Development of efficient, sensitive, and specific detection method for Encephalomyocarditis virus based on CRISPR/Cas13a.

J Virol Methods 2022 Jul 26:114592. Epub 2022 Jul 26.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address:

The Encephalomyocarditis virus (EMCV) is one of the major zoonosis pathogens, and it can cause acute myocarditis in young pigs or reproductive failure in sows. EMCV has been recognized as a pathogen infecting many species and causes substantial economic losses worldwide. Therefore, the development of a rapid, sensitive, and accurate detection of this virus is essential for the diagnosis and control of the EMCV-induced disease. The RNA-guiding, RNA-targeting CRISPR effector CRISPR/Cas13a (Cas13a, previously known as C2c2) exhibits a "collateral effect" of promiscuous RNase activity upon the target recognition. When the crRNA of LwCas13a binds to the target RNA, the collateral cleavage activity of LwCas13a is activated to degrade the non-targeted RNA. In this study, we developed an efficient, sensitive, and specific EMCV detection method based on the collateral cleavage activity of LwCas13a by combining recombinase-aided amplification (RAA) and a lateral flow strip. This method was an isothermal detection at 37°C, which allowed visual observation by the naked eyes. We also optimized the reaction conditions of this method, and the detection result could be obtained within 60minutes. The sensitivity of our method reached up to 10 copies/μl. Furthermore, no cross-reactions with other 8 major swine viruses were observed, indicating the excellent specificity of this method. At the same time, the assay had a 100% coincidence rate with qPCR detection of the EMCV in 37 clinical samples. In addition, our developed method requires only 2-step operations and basic equipment, and thus it is simple and inexpensive. Overall, CRISPR/Cas13a-based detection has a great application potential for the EMCV detection.
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http://dx.doi.org/10.1016/j.jviromet.2022.114592DOI Listing
July 2022

Bacterial Community Dynamics in Kumamoto Oyster Hatchery During Larval Development.

Front Microbiol 2022 12;13:933941. Epub 2022 Jul 12.

Ninghai Institute of Mariculture Breeding and Seed Industry, Zhejiang Wanli University, Ningbo, China.

Increasing evidence indicates that microbes colonized in early life stages have a long-term effect on animal wellbeing in later life stages. Related research is still limited in aquatic animals, particularly in bivalve mollusks. In this study, we analyzed the dynamics of the bacterial composition of the pelagic larval stages (fertilized egg, trochophore, D-stage, veliger, and pediveliger) and the sessile postlarval stage (spat) of Kumamoto oyster () and their relationships with the rearing water bacterioplankton in a hatchery by using Illumina sequencing of bacterial 16S rRNA gene. Both bacterioplankton and larval bacterial communities changed greatly over larval development, and the two communities remarkably differed ( = 0.956, < 0.001), as highlighted by the differences in the dominant taxa and bacterial diversity. Ecological processes of larval bacterial communities were measured by abundance-unweighted and abundance-weighted standardized effect sizes of the mean nearest taxon distance (ses.MNTD). The unweighted ses.MNTD analysis revealed that the deterministic process constrained the larval bacterial assembly, whereas the weighted ses.MNTD analysis showed that larval bacterial composition was initially governed by stochasticity and then gradually by determinism in the later stages. SourceTracker analysis revealed that the larval bacteria were primarily derived from an internal source, mainly from larvae at the present stage. Additionally, the abundances of larval bacterial-mediated functional pathways that were involved in the amino acid, energy, lipid and carbohydrate metabolisms significantly altered with the larval development. These findings suggest that bacteria assemble into distinct communities in larvae and rearing water in the hatchery system, and the dynamics of bacterial community composition in larvae is likely associated with larval developmental stages.
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http://dx.doi.org/10.3389/fmicb.2022.933941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315157PMC
July 2022

Ultra-Small and Metabolizable Near-Infrared Au/Gd Nanoclusters for Targeted FL/MRI Imaging and Cancer Theranostics.

Biosensors (Basel) 2022 Jul 24;12(8). Epub 2022 Jul 24.

State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

Tumor accurate imaging can effectively guide tumor resection and accurate follow-up targeted therapy. The development of imaging-stable, safe, and metabolizable contrast agents is key to accurate tumor imaging. Herein, ultra-small and metabolizable dual-mode imaging probe Au/[email protected] NCs is rationally engineered by a simple hydrothermal method to achieve accurate FL/MRI imaging of tumors. The probes exhibit ultra-small size (2.5-3.0 nm), near-infrared fluorescence (690 nm), high quantum yield (4.4%), and a better T nuclear magnetic signal compared to commercial MRI contrast agents. By modifying the folic acid (FA) molecules, the uptake and targeting of the probes are effectively improved, enabling specific fluorescence imaging of breast cancer. Au/[email protected] NCs with good biosafety were found to be excreted in the feces after imaging without affecting the normal physiological metabolism of mice. Intracellular reactive oxygen species (ROS) increased significantly after incubation of Au/[email protected] NCs with tumor cells under 660 nm laser irradiation, indicating that Au/[email protected] NCs can promote intracellular ROS production and effectively induce cell apoptosis. Thus, metabolizable Au/[email protected] NCs provide a potential candidate probe for multimodal imaging and tumor diagnosis in clinical basic research. Meanwhile, Au/[email protected] NCs mediated excessive intracellular production of ROS that could help promote tumor cell death.
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http://dx.doi.org/10.3390/bios12080558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329954PMC
July 2022

Abnormal expression of CD96 on natural killer cell in peripheral blood of patients with chronic obstructive pulmonary disease.

Clin Respir J 2022 Jul 22. Epub 2022 Jul 22.

Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital, Anhui Medical University, Hefei, China.

Natural killer (NK) cells are regarded as the host's first line of defense against viral infection. Moreover, the involvement of NK cells in chronic obstructive pulmonary disease (COPD) has been documented. However, the specific mechanism and biological changes of NK cells in COPD development have not been determined. In this study, we extracted NK cells from the peripheral blood of 18 COPD patients who were recovering from an acute exacerbation and 45 healthy donors (HDs), then we labeled NK cells with different antibodies and analyzed with flow cytometry. The data showed that the frequencies of total NK cells in the peripheral blood of COPD patients were lower compared with HDs. Moreover, the inhibitory receptors on NK cells expressed higher levels and the expression of activating receptors were generally low. Importantly, both the expression levels of CD96 in NK cells and the frequencies of CD96 NK cells were significantly upregulated in COPD patients. These findings suggest that surface receptor CD96 from NK cells may be a risk factor in the evolution of COPD.
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http://dx.doi.org/10.1111/crj.13523DOI Listing
July 2022

Upregulation of lncRNA HITT promotes cell apoptosis by suppressing the maturation of miR-602 in gastric cancer.

Histol Histopathol 2022 Jul 19:18495. Epub 2022 Jul 19.

Office of Academic Affairs of Jiangxi University of Traditional Chinese Medicine, Nanchang City, Jiangxi Province, PR China.

It has been reported that HITT can inhibit colon cancer. However, the role of HITT in gastric cancer (GC) is unknown. Our preliminary sequencing data revealed the altered expression of HITT in GC and its close correlation with miR-602, suggesting the involvement of HITT and its potential interaction with miR-602 in GC. This study explored the role of HITT and its crosstalk with miR-602 in GC. In this study, the expression of HITT, premature and mature miR-602 in paired GC and normal tissues (62 patients) was detected by RT-qPCR. RNA pull-down assay was performed to evaluate the direct interaction between HITT and mature miR-602. The subcellular location of HITT was assessed by nuclear fractionation assay. The role of HITT in regulating miR-602 maturation was explored by overexpression assay. Cell apoptosis was analyzed by flow cytometry. Our data illustrated that HITT was highly upregulated and mature miR-602 was downregulated in GC. No alteration in premature miR-602 in GC was observed. HITT was located in both nucleus and cytoplasm, and it can directly interact with miR-602. In addition, overexpression of HITT in GC cells increased the expression levels of mature miR-602 but not premature miR-602. Overexpression of HITT further increased GC cell apoptosis and suppressed the role of miR-602 in inhibiting GC cell apoptosis. In conclusion, HITT may promote GC cell apoptosis by suppressing the maturation of miR-602.
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http://dx.doi.org/10.14670/HH-18-495DOI Listing
July 2022

Quantitative proteomics analysis to assess protein expression levels in the ovaries of pubescent goats.

BMC Genomics 2022 Jul 13;23(1):507. Epub 2022 Jul 13.

Department of Animal Veterinary Science, College of Animal Science and Technology, Anhui Agricultural University, 130 Changjiang West Road, Hefei, 230036, Anhui, China.

Background: Changes in the abundance of ovarian proteins play a key role in the regulation of reproduction. However, to date, no studies have investigated such changes in pubescent goats. Herein we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography-tandem mass spectrometry to analyze the expression levels of ovarian proteins in pre-pubertal (n = 3) and pubertal (n = 3) goats.

Results: Overall, 7,550 proteins were recognized; 301 (176 up- and 125 downregulated) were identified as differentially abundant proteins (DAPs). Five DAPs were randomly selected for expression level validation by Western blotting; the results of Western blotting and iTRAQ analysis were consistent. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that DAPs were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways. Besides, gene ontology functional enrichment analysis revealed that several DAPs enriched in biological processes were associated with cellular process, biological regulation, metabolic process, and response to stimulus. Protein-protein interaction network showed that proteins interacting with CDK1, HSPA1A, and UCK2 were the most abundant.

Conclusions: We identified 301 DAPs, which were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways, suggesting the involvement of these processes in the onset of puberty. Further studies are warranted to more comprehensively explore the function of the identified DAPs and aforementioned signaling pathways to gain novel, deeper insights into the mechanisms underlying the onset of puberty.
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http://dx.doi.org/10.1186/s12864-022-08699-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281040PMC
July 2022

The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats.

Reprod Biol Endocrinol 2022 Jul 12;20(1):100. Epub 2022 Jul 12.

Anhui Provincial Key Laboratory for Local Livestock and Poultry Genetic Resource Conservation and Bio-Breeding, 130 Changjiang West Road, Hefei, 230036, Anhui, China.

Insulin-like growth factor-binding protein-5 (IGFBP-5) has recently been shown to alter the reproductive capacity by regulating insulin-like growth factor (IGF) bioavailability or IGF-independent effects. The present study aimed to investigate the effect and mechanism of IGFBP-5 on the onset of puberty in female rats. Immunofluorescence and real-time quantitative PCR were used to determine the expression and location of IGFBP-5 mRNA and protein distribution in the infant's hypothalamus-pituitary-ovary (HPO) axis prepuberty, peripuberty, puberty and adult female rats. Prepubertal rats with IGFBP-5 intracerebroventricular (ICV) were injected to determine the puberty-related genes expression and the concentrations of reproductive hormones. Primary hypothalamic cells were treated with IGFBP-5 to determine the expression of puberty-related genes and the Akt and mTOR proteins. Results showed that Igfbp-5 mRNA and protein were present on the HPO axis. The addition of IGFBP-5 to primary hypothalamic cells inhibited the expression of Gnrh and Igf-1 mRNAs (P < 0.05) and increased the expression of AKT and mTOR protein (P < 0.01). IGFBP-5 ICV-injection delayed the onset of puberty, reduced Gnrh, Igf-1, and Fshβ mRNAs, and decreased the concentrations of E2, P4, FSH,serum LH levels and the ovaries weight (P < 0.05). More corpus luteum and fewer primary follicles were found after IGFBP-5 injection (P < 0.05).
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http://dx.doi.org/10.1186/s12958-022-00966-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277959PMC
July 2022

Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence.

Nucleic Acids Res 2022 07;50(13):7493-7510

Department of Geriatrics, Medical center on Aging of Shanghai Ruijin Hospital, Shanghai Jiaotong University school of Medicine; International laboratory in Hematology, Cancer and Aging, Pôle Sino-Français de Recherches en Sciences du Vivant et Génomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; CNRS/INSERM/University Côte d'Azur.

Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53-TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2.
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http://dx.doi.org/10.1093/nar/gkac603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303393PMC
July 2022

Altered Coupling Between Cerebral Blood Flow and Voxel-Mirrored Homotopic Connectivity Affects Stroke-Induced Speech Comprehension Deficits.

Front Aging Neurosci 2022 23;14:922154. Epub 2022 Jun 23.

Department of Neurology, Brain Medical Center, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

The neurophysiological basis of the association between interhemispheric connectivity and speech comprehension processing remains unclear. This prospective study examined regional cerebral blood flow (CBF), homotopic functional connectivity, and neurovascular coupling, and their effects on comprehension performance in post-stroke aphasia. Multimodal imaging data (including data from functional magnetic resonance imaging and arterial spin labeling imaging) of 19 patients with post-stroke aphasia and 22 healthy volunteers were collected. CBF, voxel-mirrored homotopic connectivity (VMHC), CBF-VMHC correlation, and CBF/VMHC ratio maps were calculated. Between-group comparisons were performed to identify neurovascular changes, and correlation analyses were conducted to examine their relationship with the comprehension domain. The correlation between CBF and VMHC of the global gray matter decreased in patients with post-stroke aphasia. The total speech comprehension score was significantly associated with VMHC in the peri-Wernicke area [posterior superior temporal sulcus (pSTS): = 0.748, = 0.001; rostroventral area 39: = 0.641, = 0.008]. The decreased CBF/VMHC ratio was also mainly associated with the peri-Wernicke temporoparietal areas. Additionally, a negative relationship between the mean CBF/VMHC ratio of the cingulate gyrus subregion and sentence-level comprehension was observed ( = -0.658, = 0.006). These findings indicate the contribution of peri-Wernicke homotopic functional connectivity to speech comprehension and reveal that abnormal neurovascular coupling of the cingulate gyrus subregion may underly comprehension deficits in patients with post-stroke aphasia.
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http://dx.doi.org/10.3389/fnagi.2022.922154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260239PMC
June 2022

The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.

Nat Commun 2022 06 29;13(1):3750. Epub 2022 Jun 29.

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease's molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45-65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.
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http://dx.doi.org/10.1038/s41467-022-31430-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243087PMC
June 2022

A Radiomics Nomogram for Classifying Hematoma Entities in Acute Spontaneous Intracerebral Hemorrhage on Non-contrast-Enhanced Computed Tomography.

Front Neurosci 2022 10;16:837041. Epub 2022 Jun 10.

Department of Radiology, Northern Jiangsu People's Hospital, Yangzhou, China.

Aim: To develop and validate a radiomics nomogram on non-contrast-enhanced computed tomography (NECT) for classifying hematoma entities in patients with acute spontaneous intracerebral hemorrhage (ICH).

Materials And Methods: One hundred and thirty-five patients with acute intraparenchymal hematomas and baseline NECT scans were retrospectively analyzed, i.e., 52 patients with vascular malformation-related hemorrhage (VMH) and 83 patients with primary intracerebral hemorrhage (PICH). The patients were divided into training and validation cohorts in a 7:3 ratio with a random seed. After extracting the radiomics features of hematomas from baseline NECT, the least absolute shrinkage and selection operator (LASSO) regression was applied to select features and construct the radiomics signature. Multivariate logistic regression analysis was used to determine the independent clinical-radiological risk factors, and a clinical model was constructed. A predictive radiomics nomogram was generated by incorporating radiomics signature and clinical-radiological risk factors. Nomogram performance was assessed in the training cohort and tested in the validation cohort. The capability of models was compared by calibration, discrimination, and clinical benefit.

Results: Six features were selected to establish radiomics signature LASSO regression. The clinical model was constructed with the combination of age [odds ratio (OR): 6.731; 95% confidence interval (CI): 2.209-20.508] and hemorrhage location (OR: 0.089; 95% CI: 0.028-0.281). Radiomics nomogram [area under the curve (AUC), 0.912 and 0.919] that incorporated age, location, and radiomics signature outperformed the clinical model (AUC, 0.816 and 0.779) and signature (AUC, 0.857 and 0.810) in the training cohort and validation cohorts, respectively. Good calibration and clinical benefit of nomogram were achieved in the training and validation cohorts.

Conclusion: Non-contrast-enhanced computed tomography-based radiomics nomogram can predict the individualized risk of VMH in patients with acute ICH.
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http://dx.doi.org/10.3389/fnins.2022.837041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226370PMC
June 2022

Protective Immune Responses Induced by an mRNA-LNP Vaccine Encoding prM-E Proteins against Japanese Encephalitis Virus Infection.

Viruses 2022 05 24;14(6). Epub 2022 May 24.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.

Japanese encephalitis virus (JEV) is an important zoonotic pathogen, which causes central nervous system symptoms in humans and reproductive disorders in swine. It has led to severe impacts on human health and the swine industry; however, there is no medicine available for treating yet. Therefore, vaccination is the best preventive measure for this disease. In the study, a modified mRNA vaccine expressing the prM and E proteins of the JEV P3 strain was manufactured, and a mouse model was used to assess its efficacy. The mRNA encoding prM and E proteins showed a high level of protein expression in vitro and were encapsulated into a lipid nanoparticle (LNP). Effective neutralizing antibodies and CD8+ T-lymphocytes-mediated immune responses were observed in vaccinated mice. Furthermore, the modified mRNA can protect mice from a lethal challenge with JEV and reduce neuroinflammation caused by JEV. This study provides a new option for the JE vaccine and lays a foundation for the subsequent development of a more efficient and safer JEV mRNA vaccine.
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http://dx.doi.org/10.3390/v14061121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227124PMC
May 2022

Topologic Efficiency Abnormalities of the Connectome in Asymptomatic Patients with Leukoaraiosis.

Brain Sci 2022 Jun 15;12(6). Epub 2022 Jun 15.

Department of Medical Imaging, Clinic Medical School, Yangzhou University, Northern Jiangsu Province Hospital, Yangzhou 225000, China.

Leukoaraiosis (LA) is commonly found in aging healthy people but its pathophysiological mechanism is not entirely known. Furthermore, there is still a lack of effective pathological biomarkers that can be used to identify the early stage of LA. Our aim was to investigate the white matter structural network in asymptomatic patients with the early stage of LA. Tractography data of 35 asymptomatic patients and 20 matched healthy controls (HCs) based on diffusion kurtosis imaging (DKI) were analysed by using graph theory approaches and tract-based spatial statistics (TBSS). Diffusion parameters measured within the ALAs and HCs were compared. Decreased clustering coefficient and local efficiency values of the overall topological white matter network were observed in the ALAs compared with those of the HCs. Participants in the asymptomatic group also had lower nodal efficiency in the left triangular part of the inferior frontal gyrus, left parahippocampal gyrus, right calcarine fissure and surrounding cortex, right temporal pole of the superior temporal gyrus and left middle temporal gyrus compared to the ALAs. Moreover, similar hub distributions were found within participants in the two groups. In this study, our data demonstrated a topologic efficiency abnormalities of the structural network in asymptomatic patients with leukoaraiosis. The structural connectome provides potential connectome-based measures that may be helpful for detecting leukoaraiosis before clinical symptoms evolve.
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http://dx.doi.org/10.3390/brainsci12060784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221063PMC
June 2022

Building a novel multivariate nonlinear MGM(1,,|) model to forecast carbon emissions.

Environ Dev Sustain 2022 Jun 10:1-25. Epub 2022 Jun 10.

School of Management Science and Engineering, Nanjing University of Finance & Economics, Nanjing, 210023 China.

With the proposal of the carbon neutrality target, China's attention to carbon emissions has been further enhanced. Effective prediction of future carbon emissions is important for the formulation of carbon neutralization target and action plans in the region. Many factors affecting carbon emissions, cause their development trends may be nonlinear. To forecast the carbon emissions of coal and natural gas in the industrial sector more accurately, a new MGM(1,,|) model considering nonlinear characteristics is proposed in this paper. The new model introduces power function as nonlinear parameter, and the value is solved by nonlinear constraint function. We further deduce the simulation and prediction formula and then apply the improved model to the carbon emission forecast. The comparisons show that the nonlinear parameters can modify the trend of sequences and improve the prediction accuracy, which verifies the validity of the model. Finally, according to the influencing factors and forecast results, this paper analyzes the causes of high carbon emissions and puts forward reasonable suggestions for China's carbon governance.
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http://dx.doi.org/10.1007/s10668-022-02453-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184399PMC
June 2022

Protein-spatiotemporal partition releasing gradient porous scaffolds and anti-inflammatory and antioxidant regulation remodel tissue engineered anisotropic meniscus.

Bioact Mater 2023 Feb 30;20:194-207. Epub 2022 May 30.

Sports Medicine Department, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, No.49, North Garden Road, Haidian District, Beijing 100191, PR China.

Meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Meniscus injuries are difficult to heal and frequently progress into structural breakdown, which then leads to osteoarthritis. Regeneration of heterogeneous tissue engineering meniscus (TEM) continues to be a scientific and translational challenge. The morphology, tissue architecture, mechanical strength, and functional applications of the cultivated TEMs have not been able to meet clinical needs, which may due to the negligent attention on the importance of microenvironment and . Herein, we combined the 3D (three-dimensional)-printed gradient porous scaffolds, spatiotemporal partition release of growth factors, and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures, excellent biomechanical properties and anti-inflammatory and anti-oxidant effects. By observing the results of cell activity and differentiation, and biomechanics under anti-inflammatory and anti-oxidant microenvironments , we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation, with a view to cultivating a high-quality of TEM from bench to bedside.
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http://dx.doi.org/10.1016/j.bioactmat.2022.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160676PMC
February 2023

Increased Cleavage of Japanese Encephalitis Virus prM Protein Promotes Viral Replication but Attenuates Virulence.

Microbiol Spectr 2022 06 13;10(3):e0141722. Epub 2022 Jun 13.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural Universitygrid.35155.37, Wuhan, Hubei, China.

In flavivirus, the furin-mediated cleavage of prM is mandatory to produce infectious particles, and the immature particles containing uncleaved prM cannot undergo membrane fusion and release to the extracellular environment. However, the detailed relationship between viral replication or pathogenicity and furin in Japanese encephalitis virus (JEV) hasn't been clarified. Here, JEV with the mutations in furin cleavage sites and its nearby were constructed. Compared with WT virus, the mutant virus showed enhanced cleavage efficiency of prM protein and increased replication ability. Furthermore, we found that the mutations mainly promote genomic replication and assembly of JEV. However, the mutant formed smaller plaques than WT virus in plaque forming assay, indicating the lower cytopathogenicity of mutant virus. To assess the virulence of JEV mutant, an assay was performed using a mouse model. A higher survival rate and attenuated neuroinflammation were observed in JEV mutant-infected mice than those of WT-infected mice, suggesting the cleavage of prM by furin was closely related to viral virulence. These findings will provide new understanding on JEV pathogenesis and contribute to the development of novel JEV vaccines. Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis epidemics in Southeast Asia, affecting mostly children, with high morbidity and mortality. During the viral maturation process, prM is cleaved into M by the cellular endoprotease furin in the acidic secretory system. After cleavage of the prM protein, mature virions are exocytosed. Here, the mutant in furin cleavage sites and its nearby was constructed, and the results showed that the mutant virus with enhanced replication mainly occurred in the process of genomic replication and assembly. Meanwhile, the mutant showed an attenuated virulence than WT virus . Our study contributes to understanding the function of prM and M proteins and provides new clues for live vaccine designation for JEV.
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http://dx.doi.org/10.1128/spectrum.01417-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241796PMC
June 2022

RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m A-IGF2BP2-dependent manner.

J Clin Lab Anal 2022 Jul 11;36(7):e24514. Epub 2022 Jun 11.

Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Background: Having emerged as the most abundant posttranscriptional internal mRNA modification in eukaryotes, N6-methyladenosine (m A) has attracted tremendous scientific interest in recent years. However, the functional importance of the m A methylation machinery in ferroptosis regulation in hypopharyngeal squamous cell carcinoma (HPSCC) remains unclear.

Methods: We herein performed bioinformatic analysis, cell biological analyses, transcriptome-wide m A sequencing (m A-seq, MeRIP-seq), RNA sequencing (RNA-seq), and RNA immunoprecipitation sequencing (RIP-seq), followed by m A dot blot, MeRIP-qPCR, RIP-qPCR, and dual-luciferase reporter assays.

Results: The results revealed that ALKBH5-mediated m A demethylation led to the posttranscriptional inhibition of NFE2L2/NRF2, which is crucial for the regulation of antioxidant molecules in cells, at two m A residues in the 3'-UTR. Knocking down ALKBH5 subsequently increased the expression of NFE2L2/NRF2 and increased the resistance of HPSCC cells to ferroptosis. In addition, m A-mediated NFE2L2/NRF2 stabilization was dependent on the m A reader IGF2BP2. We suggest that ALKBH5 dysregulates NFE2L2/NRF2 expression in HPSCC through an m A-IGF2BP2-dependent mechanism.

Conclusion: Together, these results have revealed an association between the ALKBH5-NFE2L2/NRF2 axis and ferroptosis, providing insight into the functional importance of reversible mRNA m A methylation and its modulators in HPSCC.
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http://dx.doi.org/10.1002/jcla.24514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279968PMC
July 2022

Synergistic Antifungal Effect of a Combination of Iron Deficiency and Calcium Supplementation.

Microbiol Spectr 2022 06 8;10(3):e0112122. Epub 2022 Jun 8.

Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Centre for Microbiology, College of Life Sciences, Nanjing Normal Universitygrid.260474.3, Nanjing, China.

Fungal diseases have become a major public health issue worldwide. Increasing drug resistance and the limited number of available antifungals result in high morbidity and mortality. Metal-based drugs have been reported to be therapeutic agents against major protozoan diseases, but knowledge of their ability to function as antifungals is limited. In this study, we found that calcium supplementation combined with iron deficiency causes dramatic growth inhibition of the human fungal pathogens Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. Calcium induces the downregulation of iron uptake-related genes and, in particular, causes a decrease in the expression of the transcription factor HapX, which tends to transcriptionally activate siderophore-mediated iron acquisition under iron-deficient conditions. Iron deficiency causes calcium overload and the overproduction of intracellular reactive oxygen species (ROS), and perturbed ion homeostasis suppresses fungal growth. These phenomena are consistently identified in azole-resistant A. fumigatus isolates. The findings here imply that low iron availability lets cells mistakenly absorb calcium as a substitute, causing calcium abnormalities. Thus, there is a mutual effect between iron and calcium in fungal pathogens, and the combination of calcium with an iron chelator could serve to improve antifungal therapy. Millions of immunocompromised people are at a higher risk of developing different types of severe fungal diseases. The limited number of antifungals and the emergence of antimicrobial resistance highlight an urgent need for new strategies against invasive fungal infections. Here, we report that calcium can interfere with iron absorption of fungal pathogens, especially in iron-limited environments. Thus, a combination of calcium supplementation with an iron chelator inhibits the growth of human fungal pathogens, including Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. Moreover, we demonstrate that iron deficiency induces a nonspecific calcium uptake response, which results in toxic levels of metal. Findings in this study suggest that a microenvironment with excess calcium and limited iron is an efficient strategy to curb the growth of fungal pathogens, especially for drug-resistant isolates.
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http://dx.doi.org/10.1128/spectrum.01121-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241635PMC
June 2022

The Role of CXC Chemokines in Cardiovascular Diseases.

Front Pharmacol 2021 20;12:765768. Epub 2022 May 20.

Hubei Key Laboratory of Cardiology, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Wuhan, China.

Cardiovascular disease (CVD) is a class of diseases with high disability and mortality rates. In the elderly population, the incidence of cardiovascular disease is increasing annually. Between 1990 and 2016, the age-standardised prevalence of CVD in China significantly increased by 14.7%, and the number of cardiovascular disease deaths increased from 2.51 million to 3.97 million. Much research has indicated that cardiovascular disease is closely related to inflammation, immunity, injury and repair. Chemokines, which induce directed chemotaxis of reactive cells, are divided into four subfamilies: CXC, CC, CX3C, and XC. As cytokines, CXC chemokines are similarly involved in inflammation, immunity, injury, and repair and play a role in many cardiovascular diseases, such as atherosclerosis, myocardial infarction, cardiac ischaemia-reperfusion injury, hypertension, aortic aneurysm, cardiac fibrosis, postcardiac rejection, and atrial fibrillation. Here, we explored the relationship between the chemokine CXC subset and cardiovascular disease and its mechanism of action with the goal of further understanding the onset of cardiovascular disease.
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http://dx.doi.org/10.3389/fphar.2021.765768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163960PMC
May 2022

Abnormal expression and clinical significance of surface receptors on natural killer cells in the peripheral blood of patients with non-small cell lung cancer.

Neoplasma 2022 Jul 2;69(4):931-939. Epub 2022 Jun 2.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.

Natural killer (NK) cells typically function as frontline lymphocytes against cancer although little is known about their engagement in non-small cell lung cancer (NSCLC). This study compared the performance and activity of NK cells and their subsets in the peripheral blood of NSCLC sufferers and healthy participants. In total, 67 healthy controls (40 males; 59.7%) and 56 patients with NSCLC (35 males; 62.5%) were included (mean age, 66.6 years). Flow cytometry identified NK cells and their subpopulations in external blood, and the total number, proportion, activity, surface activating, and inhibitory receptor expression levels were determined. Results showed that NK cell surface receptors CD107a, IFN-γ, and TNF-α activity were markedly reduced in lung cancer patients compared to healthy controls. The number and ratio of NK cells within the lymphocyte population were decreased in patients. The concentration of the inhibitory receptors TIGIT, TIM-3, CD96, PD-1, and Siglec-7 were increased in patients, whereas the expression level of the activating receptor NKP30 was decreased. Moreover, the expression levels of IFN-γ, TIGIT, CD96, PD-1, and TIM-3 were correlated with the clinical phase of NSCLC. These findings suggest that surface receptors from NK cells are likely to be involved in the evolution of NSCLC.
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http://dx.doi.org/10.4149/neo_2022_220219N188DOI Listing
July 2022

MCC950, a Selective NLRP3 Inhibitor, Attenuates Adverse Cardiac Remodeling Following Heart Failure Through Improving the Cardiometabolic Dysfunction in Obese Mice.

Front Cardiovasc Med 2022 12;9:727474. Epub 2022 May 12.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Obesity is often accompanied by hypertension. Although a large number of studies have confirmed that NLRP3 inhibitors can improve cardiac remodeling in mice with a normal diet, it is still unclear whether NLRP3 inhibitors can improve heart failure (HF) induced by pressure overload in obese mice. The purpose of this study was to explore the role of MCC950, a selective NLRP3 inhibitor, on HF in obese mice and its metabolic mechanism. Obese mice induced with a 10-week high-fat diet (HFD) were used in this study. After 4 weeks of HFD, transverse aortic constriction (TAC) surgery was performed to induce a HF model. MCC950 (10 mg/kg, once/day) was injected intraperitoneally from 2 weeks after TAC and continued for 4 weeks. After echocardiography examination, we harvested left ventricle tissues and performed molecular experiments. The results suggest that in obese mice, MCC950 can significantly improve cardiac hypertrophy and fibrosis caused by pressure overload. MCC950 ameliorated cardiac inflammation after TAC surgery and promoted M2 macrophage infiltration in the cardiac tissue. MCC950 not only restored fatty acid uptake and utilization by regulating the expression of CD36 and CPT1β but also reduced glucose uptake and oxidation regulating the expression of GLUT4 and p-PDH. In addition, MCC950 affected the phosphorylation of AKT and AMPK in obese mice with HF. In summary, MCC950 can alleviate HF induced by pressure overload in obese mice improving cardiac metabolism, providing a basis for the clinical application of NLRP3 inhibitors in obese patients with HF.
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http://dx.doi.org/10.3389/fcvm.2022.727474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133382PMC
May 2022

Nucleotide-Binding Oligomerization Domain 1 (NOD1) Positively Regulates Neuroinflammation during Japanese Encephalitis Virus Infection.

Microbiol Spectr 2022 Jun 31;10(3):e0258321. Epub 2022 May 31.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural Universitygrid.35155.37, Wuhan, Hubei, People's Republic of China.

Japanese encephalitis virus (JEV) is a neurotropic flavivirus that invades the central nervous system and causes neuroinflammation and extensive neuronal cell death. Nucleotide-binding oligomerization domain 1 (NOD1) is a type of pattern recognition receptor that plays a regulatory role in both bacterial and nonbacterial infections. However, the role of NOD1 in JEV-induced neuroinflammation remains undisclosed. In this study, we evaluated the effect of NOD1 activation on the progression of JEV-induced neuroinflammation using a human astrocytic cell line and NOD1 knockout mice. The results showed that JEV infection upregulated the mRNA and protein expression of NOD1, ultimately leading to an enhanced neuroinflammatory response and . Inhibition of NOD1 in cultured cells or mice significantly abrogated the inflammatory response triggered by JEV infection. Moreover, compared to the wild-type mice, the NOD1 knockout mice showed resistance to JEV infection. Mechanistically, the NOD1-mediated neuroinflammatory response was found to be associated with increased expression or activation/phosphorylation of downstream receptor-interacting protein 2 (RIPK2), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), Jun N-terminal protein kinase (JNK), and NF-κB signaling molecules. Thus, NOD1 targeting could be a therapeutic approach to treat Japanese encephalitis. Neuroinflammation is the main pathological manifestation of Japanese encephalitis (JE) and the most important factor leading to morbidity and death in humans and animals infected by JEV. An in-depth understanding of the basic mechanisms of neuroinflammation will contribute to research on JE treatment. This study proved that JEV infection can activate the NOD1-RIPK2 signal cascade to induce neuroinflammation through the proven downstream MAPK, ERK, JNK, and NF-κB signal pathway. Thus, our study unveiled NOD1 as a potential target for therapeutic intervention for JE.
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http://dx.doi.org/10.1128/spectrum.02583-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241932PMC
June 2022

CAA-YOLO: Combined-Attention-Augmented YOLO for Infrared Ocean Ships Detection.

Sensors (Basel) 2022 May 16;22(10). Epub 2022 May 16.

School of Life Science, Beijing Institute of Technology, Beijing 100081, China.

Infrared ocean ships detection still faces great challenges due to the low signal-to-noise ratio and low spatial resolution resulting in a severe lack of texture details for small infrared targets, as well as the distribution of the extremely multiscale ships. In this paper, we propose a CAA-YOLO to alleviate the problems. In this study, to highlight and preserve features of small targets, we apply a high-resolution feature layer (P2) to better use shallow details and the location information. In order to suppress the shallow noise of the P2 layer and further enhance the feature extraction capability, we introduce a TA module into the backbone. Moreover, we design a new feature fusion method to capture the long-range contextual information of small targets and propose a combined attention mechanism to enhance the ability of the feature fusion while suppressing the noise interference caused by the shallow feature layers. We conduct a detailed study of the algorithm based on a marine infrared dataset to verify the effectiveness of our algorithm, in which the AP and AR of small targets increase by 5.63% and 9.01%, respectively, and the mAP increases by 3.4% compared to that of YOLOv5.
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http://dx.doi.org/10.3390/s22103782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144995PMC
May 2022

Profiles of antibiotic- and heavy metal-related resistance genes in animal manure revealed using a metagenomic analysis.

Ecotoxicol Environ Saf 2022 Jul 24;239:113655. Epub 2022 May 24.

Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing, China; Agro-environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin, China. Electronic address:

Farmed animals produce excrement containing excessive amounts of toxic heavy metals as a result of consuming compound feed as well as receiving medical treatments, and the presence of these heavy metals may aggravate the risk of spreading drug-resistance genes through co-selection during manure treatment and application processes. However, research on the association between heavy metals and antimicrobial resistance is still lacking. In this study, metagenomic sequencing was used to explore the effects of the co-selection of environmentally toxic heavy metals on the resistome in manure. A relevance network analysis showed that metal-resistance genes (MRGs), especially for copper (Cu) and zinc (Zn), were positively correlated with multiple types of antibiotic-resistance genes (ARGs) and formed a complex network. Most bacteria that co-occurred with both MRGs and ARGs simultaneously are members of Proteobacteria and accounted for 54.7% of the total microbial species in the relevance network. The remaining bacteria belonged to Firmicutes, Bacteroidetes and Actinobacteria. Among the four phyla, Cu- and Zn-resistance genes had more complex correlations with ARGs than other MRG types, reflecting the occurrence of ARG co-selection under the selective pressure of high Cu and Zn levels. In addition, approximately 64.8%, 59.1% and 68.4% of MRGs that correlated with the presence of plasmids, viruses and prophages, respectively, are Cu- or Zn-resistant, and they co-occurred with various ARGs, indicating that mobile genetic elements participate in mediating ARG co-selection in response to Cu and Zn pressure. The results indicated that the use of heavy-metal additives in feed induces the increases of drug resistance genes in manure through co-selection, aggravating the risk of antimicrobial resistance diffusion from animal farm to manure land applications.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113655DOI Listing
July 2022

IL-37 Expression in Patients with Abdominal Aortic Aneurysm and Its Role in the Necroptosis of Vascular Smooth Muscle Cells.

Oxid Med Cell Longev 2022 11;2022:1806513. Epub 2022 May 11.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.

Background: Our previous studies have shown that interleukin- (IL-) 37 plays a protective role in patients and animal models with coronary artery disease. However, the role of IL-37 in patients with abdominal aortic aneurysm (AAA), another artery disease, is yet to be elucidated.

Methods And Results: AAA tissues and plasma samples were obtained from patients with or without surgical intervention. Normal renal aortic tissues were collected from kidney transplant donors. Our findings established that in AAA, IL-37 was distributed in endothelial cells, macrophages, and vascular smooth muscle cells (VSMCs) and that it was chiefly concentrated in VSMCs. Furthermore, the expression was found to be downregulated compared with that in normal artery tissues. Immunofluorescence showed that, unlike normal arteries, IL-37 was translocated to the nucleus of VSMCs in AAA. Moreover, in patients with AAA, the expressions of IL-37, IL-6, and tumor necrosis factor- (TNF-) were increased in the plasma in comparison with the healthy controls. Correlation analysis revealed that IL-37 was positively correlated with IL-6, TNF-, age, aneurysm diameter, and blood pressure. Furthermore, human aortic vascular smooth muscle cells (HASMCs) were stimulated with angiotensin II (AngII) to simulate smooth muscle cell (SMC) damage in AAA. A decrease in IL-37 expression and an increase in receptor-interacting serine/threonine-protein kinase 3 (RIPK3) expression were observed in HASMCs stimulated with AngII. On this basis, inhibition of RIPK3 with GSK'872 significantly attenuated necroptosis. Moreover, the necroptosis rates were significantly lowered in HASMCs treated with recombinant IL-37, whereas the rates were enhanced when the cells were depleted of the interleukin. Immunoblotting results showed that both exogenous and endogenous IL-37 could affect the expressions of RIPK3, NLRP3, and IL-1. Also, the phosphorylation of RIPK3 and p65 was affected. Meanwhile, IL-37 promoted the transition of SMC from proliferative type to contractile type.

Conclusions: The expression of IL-37 in VSMCs decreases in patients with AAA, whereas IL-37 supplementation suppresses RIPK3-mediated necroptosis and promotes the transition of VSMCs from proliferative to contractile type.
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http://dx.doi.org/10.1155/2022/1806513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117036PMC
May 2022

The role of biomarkers in personalized immunotherapy.

Biomark Res 2022 May 18;10(1):32. Epub 2022 May 18.

Division of Medical Oncology, University of Utah, Salt Lake City, UT, USA.

Background: Immune checkpoint inhibitors have revolutionized cancer therapeutic paradigm and substantially improved the survival of patients with advanced malignancies. However, a significant limitation is the wide variability in clinical response.

Main Text: Several biomarkers have been evaluated in prior and ongoing clinical trials to investigate their prognostic and predictive role of patient response, nonetheless, most have not been comprehensively incorporated into clinical practice. We reviewed published data regarding biomarkers that have been approved by the United States Food and Drug Administration as well as experimental tissue and peripheral blood biomarkers currently under investigation. We further discuss the role of current biomarkers to predict response and response to immune checkpoint inhibitors and the promise of combination biomarker strategies. Finally, we discuss ideal biomarker characteristics, and novel platforms for clinical trial design including enrichment and stratification strategies, all of which are exciting and dynamic to advance the field of precision immuno-oncology.

Conclusion: Incorporation and standardization of strategies to guide selection of combination biomarker approaches will facilitate expansion of the clinical benefit of immune checkpoint inhibitor therapy to appropriate subsets of cancer patients.
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http://dx.doi.org/10.1186/s40364-022-00378-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118650PMC
May 2022

Facile and Green Synthesis of Highly Fluorescent Carbon Quantum Dots from Water Hyacinth for the Detection of Ferric Iron and Cellular Imaging.

Nanomaterials (Basel) 2022 May 1;12(9). Epub 2022 May 1.

College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, China.

Natural biomass is used for facile synthesis of carbon quantum dots (CQDs) with high fluorescence, owing to its abundance, low cost, and eco-friendliness. In this study, a bottom-up hydrothermal method was used to prepare CQDs from water hyacinth (wh) at a constant temperature of 180 °C for 12 h. The synthesized wh-CQDs had uniform size, amorphous graphite structure, high water solubility (containing multiple hydroxyl and carboxyl groups on the surface), excitation light-dependent characteristics, and high photostability. The results showed that the aqueous solution of CQDs could detect Fe rapidly, sensitively, and highly selectively with a detection limit of 0.084 μM in the linear range of 0-330 μM, which is much lower than the detection limit of 0.77 μM specified by the World Health Organization. More importantly, because the wh-CQDs were synthesized without any additives, they exhibited low toxicity to sp. cells even at high concentrations. Moreover, wh-CQDs emitted bright blue fluorescence in sp. cells, indicating its strong penetrating ability. Correspondingly, the fluorescent cell sorting results also revealed that the proportion of cell internalization reached 41.78%. In this study, wh-CQDs derived from natural biomass were used as high-performance fluorescent probes for Fe detection and sp. imaging. This study is expected to have great significance for the application of biomass carbon spots in the field of cellular imaging and biology.
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http://dx.doi.org/10.3390/nano12091528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100092PMC
May 2022
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