Publications by authors named "Bing Wang"

2,789 Publications

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Editorial: Medical Application and Radiobiology Research of Particle Radiation.

Front Public Health 2022 22;10:955116. Epub 2022 Jul 22.

Department of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, KY, United States.

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http://dx.doi.org/10.3389/fpubh.2022.955116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356341PMC
August 2022

Structural basis of higher order oligomerization of KSHV inhibitor of cGAS.

Proc Natl Acad Sci U S A 2022 Aug 8;119(33):e2200285119. Epub 2022 Aug 8.

Department of Biological Science, Florida State University, Tallahassee, FL 32306.

Kaposi's sarcoma-associated herpesvirus (KSHV) inhibitor of cyclic GMP-AMP synthase (cGAS) (KicGAS) encoded by ORF52 is a conserved major tegument protein of KSHV and the first reported viral inhibitor of cGAS. In our previous study, we found that KicGAS is highly oligomerized in solution and that oligomerization is required for its cooperative DNA binding and for inhibiting DNA-induced phase separation and activation of cGAS. However, how KicGAS oligomerizes remained unclear. Here, we present the crystal structure of KicGAS at 2.5 Å resolution, which reveals an "L"-shaped molecule with each arm of the L essentially formed by a single α helix (α1 and α2). Antiparallel dimerization of α2 helices from two KicGAS molecules leads to a unique "Z"-shaped dimer. Surprisingly, α1 is also a dimerization domain. It forms a parallel dimeric leucine zipper with the α1 from a neighboring dimer, leading to the formation of an infinite chain of KicGAS dimers. Residues involved in leucine zipper dimer formation are among the most conserved residues across ORF52 homologs of gammaherpesviruses. The self-oligomerization increases the valence and cooperativity of interaction with DNA. The resultant multivalent interaction is critical for the formation of liquid condensates with DNA and consequent sequestration of DNA from being sensed by cGAS, explaining its role in restricting cGAS activation. The structure presented here not only provides a mechanistic understanding of the function of KicGAS but also informs a molecular target for rational design of antivirals against KSHV and related viruses.
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http://dx.doi.org/10.1073/pnas.2200285119DOI Listing
August 2022

Dynamic Predictive Models With Visualized Machine Learning for Assessing Chondrosarcoma Overall Survival.

Front Oncol 2022 21;12:880305. Epub 2022 Jul 21.

Faculty of Medicine, Macau University of Science and Technology, Macao SAR, China.

Chondrosarcoma is a malignant bone tumor with a low incidence rate. Accurate risk evaluation is crucial for chondrosarcoma treatment. Due to the limited reliability of existing predictive models, we intended to develop a credible predictor for clinical chondrosarcoma based on the Surveillance, Epidemiology, and End Results data and four Chinese medical institutes. Three algorithms (Best Subset Regression, Univariate and Cox regression, and Least Absolute Shrinkage and Selector Operator) were used for the joint training. A nomogram predictor including eight variables-age, sex, grade, T, N, M, surgery, and chemotherapy-is constructed. The predictor provides good performance in discrimination and calibration, with area under the curve ≥0.8 in the receiver operating characteristic curves of both internal and external validations. The predictor especially had very good clinical utility in terms of net benefit to patients at the 3- and 5-year points in both North America and China. A convenient web calculator based on the prediction model is available at https://drwenle029.shinyapps.io/CHSSapp, which is free and open to all clinicians.
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http://dx.doi.org/10.3389/fonc.2022.880305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351692PMC
July 2022

Unsupervised Machine Learning Reveals Epicardial Adipose Tissue Subtypes with Distinct Atrial Fibrosis Profiles in Patients with Persistent Atrial fibrillation: a prospective two-center cohort study.

Heart Rhythm 2022 Aug 4. Epub 2022 Aug 4.

Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University. Electronic address:

Background: Epicardial adipose tissue (EAT) accumulation is associated with the progression of atrial fibrillation. However, the histological features of EATs are poorly defined, and their correlation with atrial fibrosis is unclear.

Objective: To identify and characterize EAT subgroups in the PeAF cohorts.

Methods: EATs and corresponding left atrial appendage (LAA) samples were obtained from patients with persistent atrial fibrillation (PeAF) via surgical intervention. Adipocyte markers, i.e., UCP1, TCF21, and CD137, were examined. Based on the expressions of adipocyte markers, PeAF patients were categorized into subgroups using unsupervised clustering analysis. Clinical characteristics, histological analyses, and outcomes were subsequently compared across the clusters. External validation was performed in a validation cohort.

Results: The ranking of feature importance revealed that the three adipocyte markers were the most relevant factors for atrial fibrosis comparing with other clinical indicators. On the k-medoids analysis, the PeAF patients could be categorized into three clusters in the discovery cohort. The histological studies revealed that patients in Cluster 1 exhibited statistically larger size of adipocytes in EATs and severe atrial fibrosis in LAAs. Findings were replicated in the validation cohort, where severe atrial fibrosis was noted in Cluster 1. Moreover, in the validation cohort, there was a high degree of overlap between the supervised classification results and the unsupervised cluster results from the k-medoids method.

Conclusion: Machine learning-based cluster analysis could identify subtypes of PeAF patients with distinct atrial fibrosis profiles. Additionally, EAT whitening (increased proportion of white adipocytes) may be involved in the process of atrial fibrosis.
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http://dx.doi.org/10.1016/j.hrthm.2022.07.030DOI Listing
August 2022

Nickel/nitrogen-doped carbon nanocomposites: Synthesis and electrochemical sensor for determination of p-nitrophenol in local environment.

Environ Res 2022 Aug 5;214(Pt 3):114007. Epub 2022 Aug 5.

School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, China; Engineering Research Center of Medical Biotechnology, Guizhou Medical University, Guiyang, 550025, Guizhou, China. Electronic address:

A novel electrochemical sensor was prepared using N-doped carbon mesoporous materials supported with nickel nanoparticles (Ni-NCs) for environmental p-nitrophenol (p-NP) detection in a specific geographical area. These as-prepared Ni-NCs were dispersed in polyethyleneimine (PEI) solution and modified onto a glassy carbon electrode (GCE) for electrocatalytic reduction of p-NP. The Ni-NCs-PEI/GCE showed a high Faraday current at -0.302 V during p-NP reduction, because of the synergistic effect between Ni-NCs and PEI. Under ideal conditions, the Ni-NCs-PEI/GCE was used in the voltametric determination of p-NP, with high sensitivity. The linear ranges for p-NP are 0.06-10 μM and 10-100 μM with low detection limit (4.0 nM) and high sensitivity (1.465 μA μM cm). In the presence of other phenolic compounds, this sensor showed good selectivity for p-NP detection. The Ni-NCs-PEI/GCE was also used to determine p-NP in environmental water samples of a specific geographical area, with recoveries ranging from 95.9% to 109.4%, and an RSD of less than 3.6%. Therefore, this novel Ni-NCs-PEI/GCE provides a good example for the design of other carbon-based nanocomposite materials, for electrochemical detection of trace p-NP in a specific geographical area.
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http://dx.doi.org/10.1016/j.envres.2022.114007DOI Listing
August 2022

Electrochemiluminescence resonance energy transfer system between ruthenium-based nanosheets and CdS quantum dots for detection of chlorogenic acid.

Mikrochim Acta 2022 08 6;189(9):323. Epub 2022 Aug 6.

Department of Chemistry, School of Sciences, Hebei University of Science and Technology, Shijiazhuang, 050018, China.

A new strategy is proposed for ultrasensitive detection of chlorogenic acid (CGA) by fabricating an electrochemiluminescence resonance energy transfer (ECL-RET) sensing platform. The novel system designed by introducing ruthenium-based 2D metal-organic framework nanosheets ([email protected]) as ECL acceptor and L-cysteine capped CdS quantum dots (L-CdS QDs) as ECL donor, exhibited good ECL response. The possible mechanism of the modified electrode surface reaction was discussed. Modifying of the electrode surface by application of L-CdS QDs directly on ultrathin MOF nanosheets greatly shortened the electron-transfer distance and reduce energy loss, therefore significantly improving the ECL efficiency. The prepared sensor demonstrated good stability and highly selective detection of the target molecule. Under optimal conditions, the constructed sensor for the detection of CGA exhibited a wide linear range from 1.0 × 10 to 1.0 × 10 mol·L and a low detection limit of 3.2 × 10 mol·L with a correction coefficient of 0.995. The recovery for spiked samples was calculated to be 94.4-109% and the RSD was 1.07-1.72% in real samples. The obtained sensor is considered to be a promising platform for CGA detection. Electrochemiluminescence resonance energy transfer (ECL-RET) sensing platform is used for the detection for chlorogenic acid.
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http://dx.doi.org/10.1007/s00604-022-05428-wDOI Listing
August 2022

Global phosphoproteomic analysis identified key kinases regulating male meiosis in mouse.

Cell Mol Life Sci 2022 Aug 5;79(8):467. Epub 2022 Aug 5.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China.

Meiosis, a highly conserved process in organisms from fungi to mammals, is subjected to protein phosphorylation regulation. Due to the low abundance of phosphorylation, there is a lack of systemic characterization of phosphorylation regulation of meiosis in mammals. Using the phosphoproteomic approach, we profiled large-scale phosphoproteome of purified primary spermatocytes undergoing meiosis I, and identified 14,660 phosphorylation sites in 4419 phosphoproteins. Kinase-substrate phosphorylation network analysis followed by in vitro meiosis study showed that CDK9 was essential for meiosis progression to metaphase I and had enriched substrate phosphorylation sites in proteins involved in meiotic cell cycle. In addition, histones and epigenetic factors were found to be widely phosphorylated. Among those, HASPIN was found to be essential for male fertility. Haspin knockout led to misalignment of chromosomes, apoptosis of metaphase spermatocytes and a decreased number of sperm by deregulation of H3T3ph, chromosomal passenger complex (CPC) and spindle assembly checkpoint (SAC). The complicated protein phosphorylation and its important regulatory functions in meiosis indicated that in-depth studies of phosphorylation-mediated signaling could help us elucidate the mechanisms of meiosis.
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http://dx.doi.org/10.1007/s00018-022-04507-8DOI Listing
August 2022

Step-Assisted On-Surface Synthesis of Graphene Nanoribbons Embedded with Periodic Divacancies.

J Am Chem Soc 2022 Aug 4. Epub 2022 Aug 4.

Hefei National Research Center for Physical Sciences at the Microscale and Synergetic Innovation Center of Quantum Information & Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

The bottom-up approach through on-surface synthesis of porous graphene nanoribbons (GNRs) presents a controllable manner for implanting periodic nanostructures to tune the electronic properties of GNRs in addition to bandgap engineering by width and edge configurations. However, owing to the existing steric hindrance in small pores like divacancies, it is still difficult to embed periodic divacancies with a nonplanar configuration into GNRs. Here, we demonstrate the on-surface synthesis of atomically precise eight-carbon-wide armchair GNRs embedded with periodic divacancies (DV8-aGNRs) by utilizing the monatomic step edges on the Au(111) surface. From a single molecular precursor correspondingly following a - and -coupling, the DV8-aGNR and another porous nanographene are respectively formed at step edges and on terraces at 720 and 570 K. Combining scanning tunneling microscopy/spectroscopy, atomic force microscopy, and first-principles calculations, we determine the out-of-plane conformation, wide bandgap (∼3.36 eV), and wiggly shaped frontier orbitals of the DV8-aGNR. Nudged elastic band calculations further quantitatively reveal that the additional steric hindrance effect in the cyclodehydrogenative reactions has a higher barrier of 1.3 eV than that in the planar porous nanographene, which also unveils the important role played by the monatomic Au step and adatoms in reducing the energy barriers and enhancing the thermodynamic preference of the oxidative cyclodehydrogenation. Our results provide the first case of GNRs containing periodic pores as small as divacancies with a nonplanar configuration and demonstrate the strategy by utilizing the chemical heterogeneity of a substrate to promote the formation of novel carbon nanomaterials.
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http://dx.doi.org/10.1021/jacs.2c05570DOI Listing
August 2022

Human iPSC-derived astrocytes generated from donors with globoid cell leukodystrophy display phenotypes associated with disease.

PLoS One 2022 3;17(8):e0271360. Epub 2022 Aug 3.

Lysosomal Storage and Metabolic Disease Cluster, Rare and Neurologic Disease Therapeutic Area, Sanofi, Framingham, MA, United States of America.

Globoid cell leukodystrophy (Krabbe disease) is a fatal neurodegenerative, demyelinating disease caused by dysfunctional activity of galactosylceramidase (GALC), leading to the accumulation of glycosphingolipids including psychosine. While oligodendrocytes have been extensively studied due to their high levels of GALC, the contribution of astrocytes to disease pathogenesis remains to be fully elucidated. In the current study, we generated induced pluripotent stem cells (iPSCs) from two donors with infantile onset Krabbe disease and differentiated them into cultures of astrocytes. Krabbe astrocytes recapitulated many key findings observed in humans and rodent models of the disease, including the accumulation of psychosine and elevated expression of the pro-inflammatory cytokine IL-6. Unexpectedly, Krabbe astrocytes had higher levels of glucosylceramide and ceramide, and displayed compensatory changes in genes encoding glycosphingolipid biosynthetic enzymes, suggesting a shunting away from the galactosylceramide and psychosine pathway. In co-culture, Krabbe astrocytes negatively impacted the survival of iPSC-derived human neurons while enhancing survival of iPSC-derived human microglia. Substrate reduction approaches targeting either glucosylceramide synthase or serine palmitoyltransferase to reduce the sphingolipids elevated in Krabbe astrocytes failed to rescue their detrimental impact on neuron survival. Our results suggest that astrocytes may contribute to the progression of Krabbe disease and warrant further exploration into their role as therapeutic targets.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271360PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348679PMC
August 2022

Amplitude of low-frequency fluctuations in multiple-frequency bands in patients with intracranial tuberculosis: a prospective cross-sectional study.

Quant Imaging Med Surg 2022 Aug;12(8):4120-4134

Department of Radiology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study brain functional alteration, but there have been no reports of research regarding the application of rs-fMRI in intracranial tuberculosis. The purpose of this prospective, cross-sectional study was to investigate spontaneous neural activity at different frequency bands in patients with intracranial tuberculosis using rs-fMRI with amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) methods.

Methods: The rs-fMRI data of 31 patients with intracranial tuberculosis and 30 gender-, age-, and education-matched healthy controls (HCs) were included. The ALFF and fALFF values in the conventional frequency band (0.01-0.08 Hz) and 2 sub-frequency bands (slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz) were calculated and compared between the groups. The resultant T-maps were corrected using the Gaussian random field (GRF) theory (voxel P<0.01, cluster P<0.05). Correlations between the ALFF and fALFF values and neurocognitive scores were assessed.

Results: Compared with the HCs, patients with intracranial tuberculosis showed decreased ALFF in the right paracentral lobule (T=-4.69) in the conventional frequency band, in the right supplementary motor area (T=-4.85) in the slow-4 band, and in the left supplementary motor area (T=-3.76) in the slow-5 band. Compared to the slow-5 band, the voxels with decreased ALFF were spatially more extensive in the slow-4 band. Compared with HCs, patients with intracranial tuberculosis showed decreased fALFF in the opercular parts of the right inferior frontal gyrus (T=-4.50) and the left inferior parietal lobe (T=-4.86) and increased fALFF in the left inferior cerebellum (T=5.84) in the conventional frequency band. In the slow-4 band, fALFF decreased in the opercular parts of the right inferior frontal gyrus (T=-5.29) and right precuneus (T=-4.34). In the slow-5 band, fALFF decreased in the left middle occipital gyrus (T=-4.65) and right middle frontal gyrus (T=-5.05).

Conclusions: Patients with intracranial tuberculosis showed abnormal intrinsic brain activity at different frequency bands, and ALFF abnormalities in different brain regions could be better detected in the slow-4 band. This preliminary study might provide new insights into understanding the pathophysiological mechanism in intracranial tuberculosis.
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http://dx.doi.org/10.21037/qims-22-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338357PMC
August 2022

Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial.

BMC Pediatr 2022 08 3;22(1):465. Epub 2022 Aug 3.

School of Medicine, Xiamen University, Xiamen City, 361005, China.

Background: Milk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas.

Objectives: To evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months.

Methods: In a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months.

Results: Infants (n = 375) completed the study with average dropout of < 20%. Stool frequency, color, and consistency between SF and MF were not significantly different throughout, except the incidence of loose stools in MF at 6 months being lower than for SF (odds ratio 0.216, P < 0.05) and the frequency of green-colored stools at 12 months being higher in MF (CI 95%, odds ratio 8.92, P < 0.05). The BFR had a higher frequency of golden stools and lower rate of green stools (4-6 months) than the two formula-fed groups (P < 0.05). SF displayed more diarrhoea (4.8%) than MF (1%) and BFR (1%) at the 8-month visit (P < 0.05). BFR (0-1%) had significantly less (P < 0.05) lower respiratory infections than MF (4.6-6.5%) and SF (2.9-5.8%) at 6- and 8-months, respectively. Formula intake, frequency of spit-up/vomiting or poor sleep were similar between SF and MF. Growth rate (g/day) was similar at 4, 6, 8 and 12 months between the 3 groups, but growth rate for BFR was significantly higher than for SF and MF at 42 days (95% CI, P = 0.001).

Conclusions: MFGM-enriched formula was safe and well-tolerated in healthy term infants between 0 and 12 months, and total incidences of adverse events were similar to that for the SF group. A few differences in formula tolerance were observed, however these differences were not in any way related to poor growth.
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http://dx.doi.org/10.1186/s12887-022-03507-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347101PMC
August 2022

TRP channels in inflammatory bowel disease: Potential therapeutic targets.

Biochem Pharmacol 2022 Jul 30;203:115195. Epub 2022 Jul 30.

Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, China. Electronic address:

Given the high rate of nonresponse or resistance to current inflammatory bowel disease (IBD) treatments, novel drug targets and biomarkers that aid in therapeutic prediction are eagerly demanded. Transient receptor potential (TRP) channels are distributed in the gastrointestinal tract (GI) and visceral sensory nervous systems with multiple functions. An upsurge is observed in the amount of research that implicates TRP channels in several physiological and pathological process of IBD, suggesting the therapeutic potential of the TRP channels as drug targets for combating IBD. In this review, we focus on the expression levels and functions of TRP channels in GI and discuss their potential roles in IBD, including neuropeptide modulation, immune response, and the effect of TRP channels on the IBD-related pathological activities, and some experimental methods for TRP, providing theoretical support for future research.
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http://dx.doi.org/10.1016/j.bcp.2022.115195DOI Listing
July 2022

Initial research on the effect and mechanism of Tivozanib on pulsed dye laser induced angiogenesis.

Lasers Surg Med 2022 Aug 2. Epub 2022 Aug 2.

Department of Dermatology, The Second Hospital of Jilin University, Changchun, P.R. China.

Introduction: Pulsed dye laser (PDL) is the main treatment for port wine stain (PWS), but a considerable number of patients show low clearances. The reason for the poor efficacy is related to PDL-induced angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in PDL-induced angiogenesis and can activate the tyrosine kinase activity of VEGF receptor (VEGFR) in endothelial cells. It triggers a full range of responses, and then participates in the regulation of angiogenesis. Tivozanib is an inhibitor of VEGFR tyrosine kinase activity, which can block the pro-angiogenic effect of VEGF and reduce vascular permeability.

Method: Different energy densities of PDL were used to irradiate the abdominal skin of rats. According to the general and pathological changes of the irradiated area, the energy density of 8 J/cm with smaller scab and stronger vascular effect was selected for follow-up experiments. Divided the rat abdomen skin into four areas, irradiated three of them uniformly with an energy density of 8 J/cm , and applied different concentrations of Tivozanib coating agent to the laser irradiation area, and grouped them as follows: (1) vacant group, (2) control group, (3) 0.5% Tivozanib group, (4) 1% Tivozanib group. Camera and dermoscopy were used to observe skin changes. Hematoxylin-eosin staining, immunohistochemical staining, and blood vessels were counted to detect dermal vascular regeneration. Transcriptome sequencing and real-time polymerase chain reaction (PCR) were conducted to elucidate the mechanism and validate the reliability.

Results: The number of blood vessels in the 0.5% Tivozanib group and 1% Tivozanib group was significantly reduced on the 7, 10, and 14 days compared with the control group. The number of blood vessels in the 1% Tivozanib group was significantly reduced compared with the 0.5% Tivozanib group, indicating that Tivozanib successfully inhibited PDL-induced angiogenesis, and the inhibitory effect of 1% Tivozanib was more significant than that of 0.5% Tivozanib. Transcriptome sequencing results showed a total of 588 significantly differentially expressed genes, including 90 upregulated genes and 498 downregulated genes. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the significantly differentially expressed genes were mainly enriched in the metabolic pathways which were closely related to angiogenesis. Finally, real-time PCR was used to verify the genes with higher expression differences, the top ranking and closely related to angiogenesis, namely, Cxcl1, Cxcl2, Cxcl3, Cxcl6, Ccl3, Csf3, IL1β, iNOS, Mmp9, Mmp13, Plau, Ets1, Spp1, Nr4a1. The results were consistent with the trend of transcriptome sequencing results, which proved the reliability of this study.

Conclusion: This study explored the inhibitory effect of Tivozanib on PDL-induced angiogenesis, and provided a new idea for the treatment of clinical PWS. Transcriptome sequencing explored the mechanism and provided reliable clues for later in-depth research.
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http://dx.doi.org/10.1002/lsm.23586DOI Listing
August 2022

Accurate identification of kidney injury progression via a fluorescent biosensor array.

Mikrochim Acta 2022 08 1;189(8):304. Epub 2022 Aug 1.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People's Republic of China.

Identifying the progress of kidney injury may aid the effective treatment and intervention. Herein, we developed a fluorescent biosensor array for instantaneous and accurate identification of the kidney injury progression via "doubled" signals. The multichannel biosensor array consisted of polydopamine-polyethyleneimine (PDA-PEI) and multicolor-labelled different length of DNAs including AAAAA-Cyanine7 (5A-Cy7), AAAAAAAAAA-Texas Red (10A-Texas Red), and AAAAAAAAAAAAAAAAAAAA-VIC (20A-VIC). Facing to the variety of protein in urine with alterable charge accompanied with different progress of kidney injury, the composition of urine replaces the DNA signal molecules, forming their special fluorescence patterns. Taking the size of protein into consideration, the original three variables induced by the protein charge were extended to six variables induced by the two factors of protein particle size and charge difference, which could provide a more accurate strategy to identify the progress of kidney injury. Notably, this strategy not only opened up new perspective for identification the progress of kidney injury via the size and charge of urine protein, but also improved the resolving power of sensor array by increasing the number of sensor elements for extending their potential application to various diseases.
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http://dx.doi.org/10.1007/s00604-022-05380-9DOI Listing
August 2022

Ultrasound Image Classification of Thyroid Nodules Based on Deep Learning.

Front Oncol 2022 15;12:905955. Epub 2022 Jul 15.

School of Electrical & Information Engineering, Anhui University of Technology, Ma'anshan, China.

A thyroid nodule, which is defined as abnormal growth of thyroid cells, indicates excessive iodine intake, thyroid degeneration, inflammation, and other diseases. Although thyroid nodules are always non-malignant, the malignancy likelihood of a thyroid nodule grows steadily every year. In order to reduce the burden on doctors and avoid unnecessary fine needle aspiration (FNA) and surgical resection, various studies have been done to diagnose thyroid nodules through deep-learning-based image recognition analysis. In this study, to predict the benign and malignant thyroid nodules accurately, a novel deep learning framework is proposed. Five hundred eight ultrasound images were collected from the Third Hospital of Hebei Medical University in China for model training and validation. First, a ResNet18 model, pretrained on ImageNet, was trained by an ultrasound image dataset, and a random sampling of training dataset was applied 10 times to avoid accidental errors. The results show that our model has a good performance, the average area under curve (AUC) of 10 times is 0.997, the average accuracy is 0.984, the average recall is 0.978, the average precision is 0.939, and the average F1 score is 0.957. Second, Gradient-weighted Class Activation Mapping (Grad-CAM) was proposed to highlight sensitive regions in an ultrasound image during the learning process. Grad-CAM is able to extract the sensitive regions and analyze their shape features. Based on the results, there are obvious differences between benign and malignant thyroid nodules; therefore, shape features of the sensitive regions are helpful in diagnosis to a great extent. Overall, the proposed model demonstrated the feasibility of employing deep learning and ultrasound images to estimate benign and malignant thyroid nodules.
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http://dx.doi.org/10.3389/fonc.2022.905955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335944PMC
July 2022

The Level of HbA1c Evaluates the Extent of Coronary Atherosclerosis Lesions and the Prognosis in Diabetes with Acute Coronary Syndrome.

Comput Math Methods Med 2022 22;2022:7796809. Epub 2022 Jul 22.

Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230001 Anhui, China.

Background: The level of HbA1c can reflect the average level of blood glucose over 3 months, which is the gold standard indicator for monitoring blood glucose. The relationship between the level of HbA1c and the extent of coronary atherosclerosis lesions or the prognosis in diabetes with acute coronary syndrome (ACS) remains poorly understood.

Aims: To explore whether the level of HbA1c can evaluate the extent of coronary atherosclerosis lesions or the prognosis in diabetes with acute coronary syndrome (ACS) using the SYNTAX score, the Global Registry of Acute Coronary Events (GRACE) score, left ventricular function (LVEF), left ventricular end-diastolic volume (LVEDV), and major adverse cardiac events (MACEs) in the hospital and 12 months after discharge.

Methods: This study was a prospective, randomized, open-label, and parallel group study. Patients with diabetes with ACS were recruited into this study indiscriminately, and all the participants were divided into two groups according to the level of HbA1c: HbA1c level ≤ 7%group and HbA1c level > 7%group. The followings were used as the evaluation indicators: SYNTAX score, GRACE score, LVEF, LVEDV, and MACEs in hospital and 12 months after discharge.

Results: A total of 233 patients with diabetes and ACS were enrolled and assigned to two groups according to their level of HbA1c: the HbA1c ≤ 7%group ( = 92) and the HbA1c > 7%group ( = 141). The results showed that the proportion of STEMI was higher in the HbA1c ≤7% group ( < 0.05), while the proportion of NSTEMI has not significantly higher in the HbA1c >7% group ( > 0.05). Regression analysis indicated that HbA1c level was significantly positively correlated with GRACE score ( = 0.156, = 5.784, = 0.017, = 233) and SYNTAX score ( = 0.237, = 13.788, < 0.001, = 233), and there were no statistically significant differences in LVEDV and LVEF between the two groups ( > 0.05). The total MACEs rate showed no significant difference between the two groups during hospitalization ( > 0.05) but showed significant differences at 12 months after discharge ( < 0.05).

Conclusions: This study shows that HbA1c level was positively correlated with the extent of coronary atherosclerosis lesions and the prognosis in diabetes with ACS. The higher the HbA1c level is, the more severe the coronary atherosclerotic lesion and the worse the prognosis in diabetes with ACS are.
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http://dx.doi.org/10.1155/2022/7796809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337927PMC
August 2022

Association of serum vitamin D with active human cytomegalovirus infections in Chinese children with systemic lupus erythematosus, CHINA.

Jpn J Infect Dis 2022 Jul 29. Epub 2022 Jul 29.

Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, China.

Vitamin D (VD) plays an important role in infectious and autoimmune diseases. We investigated the association between serum VD levels and active human cytomegalovirus (HCMV) infections in pediatric systemic lupus erythematosus (SLE) patients. From January 2015 to June 2021, one hundred and twenty children diagnosed with SLE and 100 healthy children were enrolled. Using ELISA, serum 25(OH)D levels were detected. Serum anti-HCMV IgM antibodies were measured by a chemiluminescence immunoassay. Comparisons of 25(OH)D levels between SLE patients and healthy children were performed, as well as subgroups of SLE patients with or without active HCMV infections. Serum 25(OH)D levels of SLE patients were significantly lower than those of healthy children (35.3 ± 12.9 vs 49.3 ± 15.3, P < 0.001). VD deficiency ratio was higher in SLE patients (89.2%) than that in healthy children (52.0%). Serum 25(OH)D levels in the positive anti-HCMV IgM group were significantly lower than those of the negative anti-HCMV IgM group (30.6 ± 12.3 vs 38.2 ± 12.5, P < 0.001). The severe VD deficiency ratio was significantly higher in HCMV-IgM(+)-SLE patients (42.2%) than that in HCMV-IgM(-)-SLE patients (13.3%). This study suggested that serum VD level is associated with active HCMV infections in pediatric SLE patients.
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http://dx.doi.org/10.7883/yoken.JJID.2021.742DOI Listing
July 2022

Bone morphogenetic protein 4 rescues the bone regenerative potential of old muscle-derived stem cells via regulation of cell cycle inhibitors.

Stem Cell Res Ther 2022 Jul 30;13(1):385. Epub 2022 Jul 30.

Department of Orthopaedic Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Bone morphogenetic protein 4 (BMP4) promotes the osteogenic differentiation and the bone regenerative potential of muscle-derived stem cells (MDSCs). BMP4 also promotes the self-renewal of both embryonic and somatic stem cells; however, BMP4 signaling activity significantly decreases with age. Cyclin-dependent kinase inhibitors P16 (P16) and P18 (P18) induce early G1-phase cell cycle blockade by targeting cyclin-dependent kinase 4/6. It is still unclear if BMP4 affects the bone regenerative potential of old MDSCs through regulation of P16 and P18 expression.

Methods: Young and old MDSCs were isolated from 3 week (young) and 2-year-old (old) mice. In vitro cell proliferation and multipotent differentiation were performed for young and old MDSCs both before and after BMP4/GFP transduction. Cell cycle genes were analyzed using Q-PCR. The bone regenerative potential of young and old MDSCs transduced with BMP4/GFP were compared using Micro-CT and histological analysis. The bone regenerative potential of young and old MDSCs was also compared between single and double transduction (higher BMP4 levels expression). The cell proliferation, mitochondrial function and osteogenic differentiation was also compared in vitro between cells that have been transduced with BMP4GFP (single and double transduction). The correlation of bone regeneration capacity of young and old MDSCs with P16 and P18 expression was further evaluated at 10 days after cell transplantation using histology and western blot analysis.

Results: Old murine MDSCs (MDSCs) exhibit reduced proliferation and multi-lineage differentiation potential with or without BMP4 stimulation, when compared to young murine MDSCs. Old MDSCs express significantly higher P16 and lower P18, with more cells in the G0/1 phase and fewer cells in the G2/M phase, compared to young MDSCs. Old MDSCs retrovirally transduced to express BMP4 regenerated less bone in a critical size skull defect in CD-1 nude mice when compared to young retrovirally transduced MDSCs expressing similar BMP4 levels and contribute less to the new regenerated new bone. Importantly, both young and old MDSCs can regenerate more bone when BMP4 expression levels are increased by double-transduction with the retroviral-BMP4/GFP. However, the bone regeneration enhancement with elevated BMP4 was more profound in old MDSCs (400% at 2 weeks) compared to young MDSCs (200%). Accordingly, P18 is upregulated while P16 is downregulated after BMP4 transduction. Double transduction did not further increase cell proliferation nor mitochondrial function but did significantly increase Osx expression in both young and old MDSCs. Old MDSCs had even significant higher Osx levels as compared to young MDSCs following double transduction, while a similar Alp expression was observed between young and old MDSCs after double transduction. In addition, at 10 days after cell transplantation, old MDSCs having undergone double transduction regenerated bone more rapidly as showed by Alcian blue and Von Kossa staining. Western blot assays demonstrated that old MDSCs after retro-BMP4/GFP double transduction have significantly lower P18 expression levels when compared to young BMP4-transduced MDSCs. In addition, P18 expression was slightly increased in old MDSCs after double transduction when compared to single transduction. P16 expression was not detectable for both young and two old BMP4/GFP transduced MDSCs groups.

Conclusions: In summary, BMP4 can offset the adverse effect of aging on the osteogenic differentiation and the bone regenerative potential of old MDSCs via up-regulation of P18 and down-regulation P16 expression.
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http://dx.doi.org/10.1186/s13287-022-03047-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338549PMC
July 2022

Center-environment feature models for materials image segmentation based on machine learning.

Sci Rep 2022 Jul 28;12(1):12960. Epub 2022 Jul 28.

Materials Genome Institute, Shanghai University, 333 Nanchen Road, Shanghai, 200444, China.

Materials properties depend not only on their compositions but also their microstructures under various processing conditions. So far, the analyses of complex microstructure images rely mostly on human experience, lack of automatic quantitative characterization methods. Machine learning provides an emerging vital tool to identify various complex materials phases in an intelligent manner. In this work, we propose a "center-environment segmentation" (CES) feature model for image segmentation based on machine learning method with environment features and the annotation input of domain knowledge. The CES model introduces the information of neighbourhood as the features of a given pixel, reflecting the relationships between the studied pixel and its surrounding environment. Then, an iterative integrated machine learning method is adopted to train and correct the image segmentation model. The CES model was successfully applied to segment seven different material images with complex texture ranging from steels to woods. The overall performance of the CES method in determining boundary contours is better than many conventional methods in the case study of the segmentation of steel image. This work shows that the iterative introduction of domain knowledge and environment features improve the accuracy of machine learning based image segmentation for various complex materials microstructures.
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http://dx.doi.org/10.1038/s41598-022-16824-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334618PMC
July 2022

Peptide Biomarkers Discovery for Seven Species of Deer Antler Using LC-MS/MS and Label-Free Approach.

Molecules 2022 Jul 25;27(15). Epub 2022 Jul 25.

NMPA Key Shandong Engineering Laboratory for Standard Innovation and Quality Evaluation of TCM, Shandong Engineering Research Center for Generic Technologies of Traditional Chinese Medicine Formula Granules, Laboratory for Quality Evaluation of Gelatin Products, Shandong Institute for Food and Drug Control, Jinan 250101, China.

Deer antler is a globally widely used precious natural medicine and the material of deer horn gelatin. However, identification of deer antler species based on traditional approaches are problematic because of their similarity in appearance and physical-chemical properties. In this study, we performed a comprehensive antler peptidome analysis using a label-free approach: nano LC-Orbitrap MS was applied to discover peptide biomarkers in deer adult beta-globin (HBB), and HPLC-Triple Quadrupole MS was used to verify their specificity. Nineteen peptide biomarkers were found, on which foundation a strategy for antlers and a strategy for antler mixtures such as flakes or powder are provided to identify seven species of deer antler including Eurasian elk (), reindeer (), white-tailed deer (), white-lipped deer (), fallow deer (), sika deer (), and red deer () simultaneously. It is worth noting that our search found that the HBB gene of sika deer, red deer, and North American wapiti () in China may have undergone severe genetic drifts.
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http://dx.doi.org/10.3390/molecules27154756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331363PMC
July 2022

DS-Net++: Dynamic Weight Slicing for Efficient Inference in CNNs and Vision Transformers.

IEEE Trans Pattern Anal Mach Intell 2022 Jul 27;PP. Epub 2022 Jul 27.

Dynamic networks have shown their promising capability in reducing theoretical computation complexity by adapting their architectures to the input during inference. However, their practical runtime usually lags behind the theoretical acceleration due to inefficient sparsity. In this paper, we explore a hardware-efficient dynamic inference regime, named dynamic weight slicing, that can generalized well on multiple dimensions in both CNNs and transformers (e.g. kernel size, embedding dimension, number of heads, etc.). Instead of adaptively selecting important weight elements in a sparse way, we pre-define dense weight slices with different importance level by nested residual learning. During inference, weights are progressively sliced beginning with the most important elements to less important ones to achieve different model capacity for inputs with diverse difficulty levels. Based on this conception, we present DS-CNN++ and DS-ViT++, by carefully designing the double headed dynamic gate and the overall network architecture. We further propose dynamic idle slicing to address the drastic reduction of embedding dimension in DS-ViT++. To ensure sub-network generality and routing fairness, we propose a disentangled two-stage optimization scheme. In Stage I, in-place bootstrapping (IB) and multi-view consistency (MvCo) are proposed to stablize and improve the training of DS-CNN++ and DS-ViT++ supernet, respectively. In Stage II, sandwich gate sparsification (SGS) is proposed to assist the gate training. Extensive experiments on 4 datasets and 3 different network architectures demonstrate our methods consistently outperform the state-of-the-art static and dynamic model compression methods by a large margin (up to 6.6%). Typically, we achieves 2-4× computation reduction and up to 61.5% real-world acceleration on MobileNet, ResNet-50 and Vision Transformer, with minimal accuracy drops on ImageNet. Code release: https://github.com/changlin31/DS-Net.
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http://dx.doi.org/10.1109/TPAMI.2022.3194044DOI Listing
July 2022

Positive Correlation of Peripheral CD8 T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Cancers (Basel) 2022 Jul 22;14(15). Epub 2022 Jul 22.

Department of Thoracic Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou 310002, China.

Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8 T lymphocytes at baseline was the independent risk factor for the onset of irAEs ( = 0.008). A higher level of CD8 T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, < 0.001) and OS (27.9 months vs. 11.7 months, = 0.014). Furthermore, patients who had higher baseline CD8 T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, < 0.001) and OS (32.8 months vs. 9.0 months, = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8 T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8 T lymphocytes and experience irAEs would have a superior PFS and OS.
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http://dx.doi.org/10.3390/cancers14153568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331848PMC
July 2022

Preparation of healing promotive alanyl-glutamine-poly(p-dioxanone) electrospun membrane integrated with gentamycin and its application for intestinal anastomosis in rats.

Biomater Adv 2022 Aug 6;139:212977. Epub 2022 Jun 6.

Department of Chemistry, School of Pharmacy, North Sichuan Medical College, Nanchong, China; Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, China. Electronic address:

Anastomosis surgery at the intestinal site is performed on millions of individuals every year. However, several persistent complications, such as anastomotic leakage, abnormal adhesion, and anastomotic stenosis, have been observed after the surgery. For promoting anastomotic healing and to overcome the challenges mentioned above, re-epithelialization at anastomotic sites is crucial. In this study, an epithelialization-promoting macromolecular prodrug Ala-Gln-PPDO was prepared and processed into fibrous membranes by electrospinning. Ala-Gln and gentamicin were sustainably released from the electrospun membranes with degradation of these membranes to promote the proliferation of rat intestinal epithelial cells and suppress the proliferation of Staphylococcus aureus and Escherichia coli. The comprehensive repair effects of Ala-Gln-PPDO membranes have been evaluated in rat models of intestinal anastomosis in this study. Application of Ala-Gln-PPDO membranes, especially the gentamicin-incorporated Ala-Gln-PPDO ones, could prevent adhesion between the injured intestine and surrounding intestinal tissues. In addition, they did not affect the healing strength of anastomotic stoma negatively and could promote re-epithelialization at the anastomotic sites. Furthermore, the gentamicin-incorporated Ala-Gln-PPDO membranes could relieve stenosis at anastomotic sites. The gentamicin-incorporated Ala-Gln-PPDO electrospun membrane is a promising, comprehensive implantable material for promoting healing after gastrointestinal anastomosis owing to its effects involving the promotion of re-epithelialization, prevention of adhesion, and relieving of anastomotic stenosis.
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http://dx.doi.org/10.1016/j.bioadv.2022.212977DOI Listing
August 2022

Right Atrial Fluorodeoxyglucose Uptake Is a Risk Factor for Stroke and Improves Prediction of Stroke Above the CHADS-VASc Score in Patients With Atrial Fibrillation.

Front Cardiovasc Med 2022 8;9:862000. Epub 2022 Jul 8.

Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Background: Atrial fibrillation (AF) is a common arrhythmia, and its most severe and dreaded complication is stroke. The CHADS-VASc score is currently recommended for stroke risk assessment in AF. We aimed to explore the relationship between atrial FDG uptake and stroke and whether atrial FDG uptake could provide incremental value above the CHADS-VAS score to predict stroke in AF by F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT).

Materials And Methods: From September 2017 to December 2020, we retrospectively enrolled 230 patients (115 with AF and 115 without AF as the non-AF group, matched for the date of PET/CT examination and the basic characteristics of the patient) who underwent F-FDG PET/CT due to tumor screening or preoperative staging after prolonged fasting and followed up for at least 12 months from the date of PET/CT examination; the endpoint event is the occurrence of stroke. We visually and quantitatively analyzed F-FDG uptake in the right and left atria (RA/LA), right and left atrial appendage (RAA/LAA), right and left ventricle (RV/LV), and collected clinical features. In addition, according to the endpoint event (stroke), the enrolled population was divided into the stroke group and non-stroke group, and relevant clinical features and atrial FDG uptake indicators of the two groups were analyzed. Univariate and multivariate Cox regression analyzes were used to analyze the risk factors of stroke events. The Kaplan-Meier survival curve of atrial FDG uptake was drawn, and the log-rank method was used to compare the differences in the survival curves of the two groups. Receiver operating characteristic (ROC) curves were used to examine the discriminatory power of atrial FDG uptake in predicting stroke and determine whether the addition of atrial FDG uptake improves predictive value beyond the CHADS-VASc score for stroke.

Results: In the AF group, more than half of patients had RA FDG uptake and one-fifth had LA FDG uptake, while one patient had RA FDG uptake and two patients had LA FDG uptake in the non-AF group. In quantitative analysis, the maximum standardized uptake value (SUV ) of the RA and LA in the AF group was significantly higher than that of the non-AF group (all < 0.001). We followed up the patients for 28 ± 10 months, and finally, 31 patients had stroke. In the stroke group, atrial fibrillation, RA SUV , RAA SUV , LAA SUV , age ≥ 75 years, and left atrial dilation were significantly higher than those of the non-stroke group (all < 0.05). Multivariate Cox regression analysis showed that high RA SUV (RA SUV ≥ 2.62) was an independent risk factor for stroke (HR = 4.264, 95% CI 1.368-13.293, = 0.012). By using the log-rank test, patients with high RA SUV had a significantly higher incidence of stroke compared with patients with low RA SUV ( < 0.001). Addition of high RA SUV to the CHADS-VASc score could predict stroke more effectively, with a larger AUC 0.790 ( < 0.001).

Conclusion: This study found a significant correlation between atrial FDG uptake and AF, especially in RA. Meanwhile, RA FDG uptake is an independent risk factor for stroke, and patients with high RA SUV have a significantly higher risk of stroke. Moreover, RA FDG uptake improves prediction of stroke above the CHADS-VASc score in patients with AF.
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http://dx.doi.org/10.3389/fcvm.2022.862000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304590PMC
July 2022

Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data.

Front Oncol 2022 5;12:925079. Epub 2022 Jul 5.

Science System Department, Geneis Beijing Co., Ltd., Beijing, China.

Microsatellite instability (MSI), an important biomarker for immunotherapy and the diagnosis of Lynch syndrome, refers to the change of microsatellite (MS) sequence length caused by insertion or deletion during DNA replication. However, traditional wet-lab experiment-based MSI detection is time-consuming and relies on experimental conditions. In addition, a comprehensive study on the associations between MSI status and various molecules like mRNA and miRNA has not been performed. In this study, we first studied the association between MSI status and several molecules including mRNA, miRNA, lncRNA, DNA methylation, and copy number variation (CNV) using colorectal cancer data from The Cancer Genome Atlas (TCGA). Then, we developed a novel deep learning framework to predict MSI status based solely on hematoxylin and eosin (H&E) staining images, and combined the H&E image with the above-mentioned molecules by multimodal compact bilinear pooling. Our results showed that there were significant differences in mRNA, miRNA, and lncRNA between the high microsatellite instability (MSI-H) patient group and the low microsatellite instability or microsatellite stability (MSI-L/MSS) patient group. By using the H&E image alone, one can predict MSI status with an acceptable prediction area under the curve (AUC) of 0.809 in 5-fold cross-validation. The fusion models integrating H&E image with a single type of molecule have higher prediction accuracies than that using H&E image alone, with the highest AUC of 0.952 achieved when combining H&E image with DNA methylation data. However, prediction accuracy will decrease when combining H&E image with all types of molecular data. In conclusion, combining H&E image with deep learning can predict the MSI status of colorectal cancer, the accuracy of which can further be improved by integrating appropriate molecular data. This study may have clinical significance in practice.
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http://dx.doi.org/10.3389/fonc.2022.925079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295995PMC
July 2022

Generation of Gal-enhanced bifunctional tumor vaccine.

Acta Pharm Sin B 2022 Jul 9;12(7):3177-3186. Epub 2022 Mar 9.

National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Biotargeting Theranostics, Guangxi Medical University, Nanning 530021, China.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine -1,3-galactose epitopes (Gal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END/Gal-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-). CTLs targeted cells expressing Gal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.
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http://dx.doi.org/10.1016/j.apsb.2022.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293690PMC
July 2022

An Outbreak of Severe Neonatal Pneumonia Caused by Human Respiratory Syncytial Virus BA9 in a Postpartum Care Centre in Shenyang, China.

Microbiol Spectr 2022 Jul 13:e0097422. Epub 2022 Jul 13.

National Health Commission (NHC) Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, WHO WPRO Regional Reference Measles/Rubella Laboratory, Beijing, China.

Human respiratory syncytial virus (HRSV) is a major pathogen of lower respiratory tract infections in children (<5 years) and older individuals, with outbreaks mainly reported among infants in hospital pediatric departments and intensive care units (ICUs). An outbreak of severe neonatal pneumonia occurred in a postpartum center in Shenyang city, China, from January to February 2021. In total, 34 respiratory samples were collected from 21 neonates and 13 nursing staff. The samples were screened for 27 pathogens using a TaqMan low-density array, and 20 samples tested positive for HRSV, including 16 neonates and 4 nursing staff samples. Among the 16 hospitalized neonates, seven were admitted to an ICU and nine to general wards. Four of the nursing staff had asymptomatic infections. To investigate the genetic characteristics of the HRSV responsible for this outbreak, the second hypervariable region (HVR2) sequences of the G gene were obtained from six neonates and two nursing staff. Phylogenetic analyses revealed that all eight sequences (SY strains) were identical, belonging to the HRSV BA9 genotype. Our findings highlight the necessity for strict hygiene and disease control measures so as to prevent cross-infection and further avoid potential outbreaks of severe infectious respiratory diseases. Human respiratory syncytial virus (HRSV) is one of the leading causes of acute lower respiratory infections (ALRI) worldwide. In this study, we first reported an outbreak of severe neonatal pneumonia caused by HRSVB BA9 at a postpartum care center in mainland China. Among 20 confirmed cases, 16 were hospitalized neonates with 7 in the ICU ward, and the other four were nursing staff with asymptomatic infections. Our findings highlighted the importance of preventing cross-infection in such postpartum centers.
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http://dx.doi.org/10.1128/spectrum.00974-22DOI Listing
July 2022

[Effect of unicompartmental knee arthroplasty in patients over 75 years old with knee osteoarthritis].

Zhongguo Gu Shang 2022 Jul;35(7):637-43

Department of Orthopedics, PLA 960th Hospital, Jinan 250000, Shandong, China.

Objective: To investigate the clinical effect of unicompartmental knee arthroplasty in patients with knee osteoarthritis over 75 years old.

Methods: From April 2010 to May 2015, 42 patients with knee medial compartment osteoarthritis were treated with Oxford third-generation unicompartmental knee arthroplasty. According to the single and bilateral replacement, the patients were divided into bilateral simultaneous replacement group and unilateral replacement group:11 patients in the simultaneous replacement group, 3 males and 8 females, aged (79.18±3.06) years;There were 31 cases in the unilateral replacement group, 13 males and 18 females, aged (78.16±3.48) years. The survival status of patients with knee prosthesis, the changes of hematocrit before and after operation, and the total amount of blood loss during and after operation were observed and compared;The HSS (Hospital for Special Surgery knee rating) scores of patients before and after operation were compared.

Results: There was significant difference in perioperative complications between two groups(<0.05). All 42 patients were followed up for(5.7±2.3) years. One patient with a history of previous hypertension developed cerebral thrombosis in the 4th month after operation, one patient developed pad dislocation in the 4th month after operation, and two patients died of other medical diseases(1 myocardial infarction and 1 lung cancer) 3 years after operation. The total amount of postoperative blood loss in bilateral simultaneous replacement group was higher than that in unilateral replacement group(<0.05);Four patients with bilateral simultaneous replacement received 2U blood transfusion after operation. The HSS score and total score of the two groups at 9 months after operation were higher than those before operation(<0.05).

Conclusion: Unicompartmental knee arthroplasty is a feasible surgical treatment for osteoarthritis patients over 75 years old with medial single compartment degeneration. For elderly patients over 75 years old with bilateral knee lesions, bilateral simultaneous unicompartmental knee arthroplasty is more traumatic than unilateral unicompartmental knee arthroplasty, which will increase the incidence of perioperative complications, affect the rapid postoperative recovery and increase the blood loss. Although the long-term effect is equivalent to that of unilateral unicompartmental knee arthroplasty, staged operation is still recommended to ensure the safety of operation.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.07.009DOI Listing
July 2022

Intervention strategies for epidemic spreading on bipartite metapopulation networks.

Phys Rev E 2022 Jun;105(6-1):064305

School of Computer Engineering and Science, Shanghai University, Shanghai 200444, People's Republic of China.

Intervention strategies are of great significance for controlling large-scale outbreaks of epidemics. Since the spread of epidemic depends largely on the movement of individuals and the heterogeneity of the network structure, understanding potential factors that affect the epidemic is fundamental for the design of reasonable intervention strategies to suppress the epidemic. So far, most of previous studies mainly consider intervention strategies on the network composed of a single type of locations, while ignoring the movement behavior of individuals to and from locations that are composed of different types, i.e., residences and public places, which often presents heterogeneous structure. In addition, the transmission rate in public places with different population flows is heterogeneous. Inspired by the above observation, we build a bipartite metapopulation network model and propose intervention strategies based on the importance of public places. With the Markovian Chain approach, we derive the epidemic threshold under intervention strategies. Experimental results show that, compared with the uniform intervention to residences or public places, nonuniform intervention to public places is more effective for suppressing the epidemic with an increased epidemic threshold. Specifically, interventions to public places with large degree can further suppress the epidemic. Our study opens a new path for understanding the spatial epidemic spread and provides guidance for the design of intervention strategies for epidemics in the future.
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http://dx.doi.org/10.1103/PhysRevE.105.064305DOI Listing
June 2022

Intervention of resource allocation strategies on spatial spread of epidemics.

Phys Rev E 2022 Jun;105(6-1):064308

School of Computer Engineering and Science, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China.

Medical resources are crucial in mitigating epidemics, especially during pandemics such as the ongoing COVID-19. Thereby, reasonable resource deployment inevitably plays a significant role in suppressing the epidemic under limited resources. When an epidemic breaks out, people can produce resources for self-protection or donate resources to help others for treatment. That is, the exchange of resources also affects the transmission between individuals, thus, altering the epidemic dynamics. To understand factors on resource deployment and the interplay between resource and transmission we construct a metapopulation network model with resource allocation. Our results indicate actively or promptly donating resources is not helpful to suppress the epidemic under both homogeneous population distribution and heterogeneous population distribution. Besides, strengthening the speed of resources production can significantly increase the recovery rate so that they reduce the final outbreak size. These results may provide policy guidance toward epidemic containment.
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http://dx.doi.org/10.1103/PhysRevE.105.064308DOI Listing
June 2022
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