Publications by authors named "Shiqi Wang"

161 Publications

Canagliflozin Improves Liver Function in Rats by Upregulating Asparagine Synthetase.

Pharmacology 2021 Sep 7:1-10. Epub 2021 Sep 7.

Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, China.

Introduction: Canagliflozin (CANA) is a sodium-glucose cotransporter 2 inhibitor that was recently approved for treating diabetes. However, its effects on liver function are not well understood. The function of asparagine synthetase (ASNS) has been studied in several cancers but not in liver injury. Therefore, we investigated the connection between CANA and ASNS in alleviating damage (i.e., their hepatoprotective effect) in a rat liver injury model.

Methods: The rat model of liver injury was established using carbon tetrachloride treatment. Rats with liver injury were administered CANA orally for 8 weeks daily. After week 8, peripheral blood was collected to measure serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels. Liver histopathology was examined using hematoxylin and eosin staining to determine the degree of liver injury. Protein expression in the rat livers was examined using Western blotting.

Results: CANA treatment decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels compared with those of the untreated group, demonstrating diminished liver injury. Mechanistically, CANA treatment activated AMP-activated protein kinase (AMPK), leading to increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activating transcription factor 4 (ATF4), which upregulated ASNS expression in liver-injured rats.

Conclusion: CANA significantly alleviated liver injury by activating the AMPK/Nrf2/ATF4 axis and upregulating ASNS expression, indicating its potential for treating patients with type 2 diabetes mellitus with impaired liver function.
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http://dx.doi.org/10.1159/000518492DOI Listing
September 2021

Ruminants reveal Eocene Asiatic palaeobiogeographical provinces as the origin of diachronous mammalian Oligocene dispersals into Europe.

Sci Rep 2021 Sep 6;11(1):17710. Epub 2021 Sep 6.

Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing, 100044, China.

Faunal provincialism between the North and South parts of Eastern Asia is shown to have been in place since the late Eocene. This provincialism structured the mammalian dispersals across Eurasia for millions of years and provides insights into both palaeonvironments and palaeoclimate zonation. In addition, this study reveals the oldest record of a crown ruminant (Iberomeryx from Shinao, China). Ecologically, as well as economically, ruminant artiodactyls are one of the most important large mammal groups today. The revision of the ruminants from the Shinao Formation, from the Caijiachong marls and Xiaerhete, resulted in two new taxa and shows that the different provinces were populated by distinct taxa living in different environments, dominated by the monsoon in the South and drier conditions in the North. Evaluating this result in a Eurasian context demonstrates that the dispersals from Asia to Europe was complex. These results confirm that there were at least two dispersal events, distinct in space and time: the Grande-Coupure from Northern and Central Asia along the North ca. 34 Mya and the Bachitherium dispersal event from the Southern province along a southerly route ca. 31 Mya.
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http://dx.doi.org/10.1038/s41598-021-96221-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421421PMC
September 2021

Geometry Auxiliary Salient Object Detection for Light Fields via Graph Neural Networks.

IEEE Trans Image Process 2021 8;30:7578-7592. Epub 2021 Sep 8.

Light field imaging, originated from the availability of light field capture technology, offers a wide range of applications in the field of computational vision. The capability of predicting salient objects of light fields remains technologically challenging due to its complicated geometry structure. In this paper, we propose a light field salient object detection approach that formulates the geometric coherence among multiple views of light fields as graphs, where the angular/central views represent the nodes and their relations compose the edges. The spatial and disparity correlations between multiple views are effectively explored through multi-scale graph neural networks, enabling the more comprehensive understanding of light field content and more representative and discriminative saliency features generation. Moreover, a multi-scale saliency feature consistency learning module is embedded to enhance the saliency features. Finally, an accurate salient object map is produced for the light field based upon the extracted features. In addition, we establish a new light field salient object detection dataset (CITYU-Lytro) that contains 817 light fields with diverse contents and their corresponding annotations, aiming to further promote the research on light field salient object detection. Quantitative and qualitative experiments demonstrate that the proposed method performs favorably compared with the state-of-the-art methods on the benchmark datasets.
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http://dx.doi.org/10.1109/TIP.2021.3108018DOI Listing
September 2021

Sub-Sampled Cross-Component Prediction for Emerging Video Coding Standards.

IEEE Trans Image Process 2021 20;30:7305-7316. Epub 2021 Aug 20.

Cross-component linear model (CCLM) prediction has been repeatedly proven to be effective in reducing the inter-channel redundancies in video compression. Essentially speaking, the linear model is identically trained by employing accessible luma and chroma reference samples at both encoder and decoder, elevating the level of operational complexity due to the least square regression or max-min based model parameter derivation. In this paper, we investigate the capability of the linear model in the context of sub-sampled based cross-component correlation mining, as a means of significantly releasing the operation burden and facilitating the hardware and software design for both encoder and decoder. In particular, the sub-sampling ratios and positions are elaborately designed by exploiting the spatial correlation and the inter-channel correlation. Extensive experiments verify that the proposed method is characterized by its simplicity in operation and robustness in terms of rate-distortion performance, leading to the adoption by Versatile Video Coding (VVC) standard and the third generation of Audio Video Coding Standard (AVS3).
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http://dx.doi.org/10.1109/TIP.2021.3104191DOI Listing
August 2021

Dual-Crosslinked Dynamic Hydrogel Incorporating {Mo } with pH and NIR Responsiveness for Chemo-Photothermal Therapy.

Adv Mater 2021 Aug 11:e2007761. Epub 2021 Aug 11.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.

Polyoxometalates are an emerging class of molecular clusters, with well-defined structures and chemical compositions that are produced through simple, low-cost, and highly reproducible methods. In particular, the wheel-shaped cluster {Mo } is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self-healing hydrogel of easy preparation and administration is developed, incorporating both {Mo } and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N-isopropylacrylamide) functionalized chitosan and {Mo }. The gelation occurs within 60 s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self-healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra-red (NIR) radiation and pH changes. This stimuli-responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo }-based systems, incorporated in self-healing and injectable hydrogels for dual chemo-photothermal therapy.
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http://dx.doi.org/10.1002/adma.202007761DOI Listing
August 2021

Compressed Domain Deep Video Super-Resolution.

IEEE Trans Image Process 2021 12;30:7156-7169. Epub 2021 Aug 12.

Real-world video processing algorithms are often faced with the great challenges of processing the compressed videos instead of pristine videos. Despite the tremendous successes achieved in deep-learning based video super-resolution (SR), much less work has been dedicated to the SR of compressed videos. Herein, we propose a novel approach for compressed domain deep video SR by jointly leveraging the coding priors and deep priors. By exploiting the diverse and ready-made spatial and temporal coding priors (e.g., partition maps and motion vectors) extracted directly from the video bitstream in an effortless way, the video SR in the compressed domain allows us to accurately reconstruct the high resolution video with high flexibility and substantially economized computational complexity. More specifically, to incorporate the spatial coding prior, the Guided Spatial Feature Transform (GSFT) layer is proposed to modulate features of the prior with the guidance of the video information, making the prior features more fine-grained and content-adaptive. To incorporate the temporal coding prior, a guided soft alignment scheme is designed to generate local attention off-sets to compensate for decoded motion vectors. Our soft alignment scheme combines the merits of explicit and implicit motion modeling methods, rendering the alignment of features more effective for SR in terms of the computational complexity and robustness to inaccurate motion fields. Furthermore, to fully make use of the deep priors, the multi-scale fused features are generated from a scale-wise convolution reconstruction network for final SR video reconstruction. To promote the compressed domain video SR research, we build an extensive Compressed Videos with Coding Prior (CVCP) dataset, including compressed videos of diverse content and various coding priors extracted from the bitstream. Extensive experimental results show the effectiveness of coding priors in compressed domain video SR.
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http://dx.doi.org/10.1109/TIP.2021.3101826DOI Listing
August 2021

Quantitative Analysis of Porous Silicon Nanoparticles Functionalization by H NMR.

ACS Biomater Sci Eng 2021 Jul 22. Epub 2021 Jul 22.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.

Porous silicon (PSi) nanoparticles have been applied in various fields, such as catalysis, imaging, and biomedical applications, because of their large specific surface area, easily modifiable surface chemistry, biocompatibility, and biodegradability. For biomedical applications, it is important to precisely control the surface modification of PSi-based materials and quantify the functionalization density, which determines the nanoparticle's behavior in the biological system. Therefore, we propose here an optimized solution to quantify the functionalization groups on PSi, based on the nuclear magnetic resonance (NMR) method by combining the hydrolysis with standard H NMR experiments. We optimized the hydrolysis conditions to degrade the PSi, providing mobility to the molecules for NMR detection. The NMR parameters were also optimized by relaxation delay and the number of scans to provide reliable NMR spectra. With an internal standard, we quantitatively analyzed the surficial amine groups and their sequential modification of polyethylene glycol. Our investigation provides a reliable, fast, and straightforward method in quantitative analysis of the surficial modification characterization of PSi requiring a small amount of sample.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00440DOI Listing
July 2021

Nitric oxide release activated near-Infrared photothermal agent for synergistic tumor treatment.

Biomaterials 2021 09 13;276:121017. Epub 2021 Jul 13.

Key Laboratory of Optoelectronic Devices and Systems of Guangdong Province & Ministry of Education, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong Province, 518060, PR China. Electronic address:

Activatable phototherapeutic agents (PTA) in one system with synergistic gas therapy (GT) and photothermal therapy (PTT) hold great promise for highly efficient tumor treatments. In this study, an activatable multifunctional platform with photothermal conversion "turn on" features via nitric oxide (NO) release for synergistic GT and PTT was rationally designed using an aryl N-nitrosamine (NO-donating unit) functionalized aza-BODIPY framework (S-NO). As expected, after NO release from S-NO, the product (Red-S) showed obviously enhanced heat production performance under a longer excited wavelength via improved near-infrared light absorption and decreased fluorescence emission. Furthermore, water-soluble and biocompatible S-NO nanoparticles (S-NO NPs) with negligible dark cytotoxicity successfully suppressed tumor growth and enhanced the survival rate of mice via synergistic GT and PTT under the guidance of multimode imaging. The study offered rational guidance to design better platforms for synergistic tumor treatments and validated that S-NO NPs can act as potential PTAs in biological applications.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121017DOI Listing
September 2021

Proteomics provides individualized options of precision medicine for patients with gastric cancer.

Sci China Life Sci 2021 Aug 9;64(8):1199-1211. Epub 2021 Jul 9.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.
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http://dx.doi.org/10.1007/s11427-021-1966-4DOI Listing
August 2021

Investigation of the lipidomic changes in differentiated glioblastoma cells after drug treatment using MALDI-MS.

Talanta 2021 Oct 29;233:122570. Epub 2021 May 29.

Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Tsinghua University, Beijing, 100084, China. Electronic address:

Lipids differences between tumor and normal tissue have been proved to be of diagnostic and therapeutic significance. The research of lipidomics in tumor is more and more important. Mass spectrometry like matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) can be more convenient and informative for lipids researching in biological and clinical researches. Most of malignant tumors like glioblastoma are characterized by incomplete differentiation, so differentiation therapy has made important progress in tumor treatment. Lipid profiles changes after therapy are worthy investigating. In our study, glioblastoma cell line U87-MG cells were treated by inducers of sodium phenylbutyrate (SPB) and all-trans retinoic acid (ATRA). The changes in lipids on cell membrane were profiled by MALDI-MS. The differentiation degree was assessed by cell proliferation, cell cycle, morphology and protein expression before MALDI-MS analysis. Comparing the inducer treated and untreated U87-MG cells, reduced proliferation rate, blocked cell cycle, benign nucleus morphology and changed expression of protein CD133 and glial fibrillary acidic protein (GFAP), were found after drug treatment. Moreover, the lipids of cell membrane presented distinguished differences in the drug treated cells. Most of the glycerophosphocholines (PC) with an increasing abundance are unsaturated PCs (PC (38:1), 816 m/z; PC (36:1), 788 m/z; PC (31:1), 725 m/z), and those decreasing are saturated PCs (PC (32:0), 734 m/z). These results provide the lipidomic differentiation which may be a significant guidance for evaluating the therapeutic effect of tumor therapy.
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http://dx.doi.org/10.1016/j.talanta.2021.122570DOI Listing
October 2021

Synthesis of montmorillonite-supported nano-zero-valent iron via green tea extract: Enhanced transport and application for hexavalent chromium removal from water and soil.

J Hazard Mater 2021 Oct 24;419:126461. Epub 2021 Jun 24.

School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China; Jiangsu Key Laboratory of Environmental Functional Materials, Suzhou University of Science and Technology, Suzhou 215009, China.

The nano-zero-valent iron composite ([email protected]) was successfully prepared using a low-cost and environmental-friendly green synthesis via tea leaves extract (tea polyphenols, TPs) and the montmorillonite (Mont). The batch and column experiments and characterization were conducted to investigate the transport behavior and Cr(VI) remediation by [email protected] in water/soil. Due to its particular surface characteristics and morphology (i.e., the Fe core wrapped by TPs, the doped sulfur, and interlayer structure), the [email protected] composite showed a great removal capacity of Cr(VI) and sufficient mobility under different soil conditions. We opine the increase in the Cr(VI) reduction of [email protected] was attributed to the tethering of FeO on the surface of Fe core by the support of Mont interlayer, especially the TP-coverage around [email protected] surface unwrapped, thereby increasing the regenerated reactive Fe and the exposed reaction sites of Fe cores to Cr(VI). The increased transportability of [email protected] slightly depends on the heterogeneous soil properties (i.e., ionic strength, sand/soil ratio, and pH). The two-site kinetic attachment model fitting results suggest Cr(VI)/Cr(III) speciation associated with the agglomerated [email protected] were efficiently immobilized in soil. Therefore, this study would benefit the efficient application of the green-synthesized [email protected] in in-situ remediation of soils contaminated by Cr(VI).
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http://dx.doi.org/10.1016/j.jhazmat.2021.126461DOI Listing
October 2021

Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.

Front Endocrinol (Lausanne) 2021 4;12:659738. Epub 2021 Jun 4.

Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown.

Methods: The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining.

Results: CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells.

Conclusions: Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.
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http://dx.doi.org/10.3389/fendo.2021.659738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211914PMC
June 2021

An Oligocene giant rhino provides insights into Paraceratherium evolution.

Commun Biol 2021 06 17;4(1):639. Epub 2021 Jun 17.

Hezheng Paleozoological Museum, Hezheng, Gansu, China.

As one of the largest land mammals, the origin and evolution of the giant rhino Paraceratherium bugtiense in Pakistan have been unclear. We report a new species Paraceratherium linxiaense sp. nov. from northwestern China with an age of 26.5 Ma. Morphology and phylogeny reveal that P. linxiaense is the highly derived species of the genus Paraceratherium, and its clade with P. lepidum has a tight relationship to P. bugtiense. Based on the paleogeographical literature, P. bugtiense represents a range expansion of Paraceratherium from Central Asia via the Tibetan region. By the late Oligocene, P. lepidum and P. linxiaense were found in the north side of the Tibetan Plateau. The Tibetan region likely hosted some areas with low elevation, possibly under 2000 m during Oligocene, and the lineage of giant rhinos could have dispersed freely along the eastern coast of the Tethys Ocean and perhaps through some lowlands of this region.
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http://dx.doi.org/10.1038/s42003-021-02170-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211792PMC
June 2021

No-Reference Screen Content Image Quality Assessment With Unsupervised Domain Adaptation.

IEEE Trans Image Process 2021 9;30:5463-5476. Epub 2021 Jun 9.

In this paper, we quest the capability of transferring the quality of natural scene images to the images that are not acquired by optical cameras (e.g., screen content images, SCIs), rooted in the widely accepted view that the human visual system has adapted and evolved through the perception of natural environment. Here, we develop the first unsupervised domain adaptation based no reference quality assessment method for SCIs, leveraging rich subjective ratings of the natural images (NIs). In general, it is a non-trivial task to directly transfer the quality prediction model from NIs to a new type of content (i.e., SCIs) that holds dramatically different statistical characteristics. Inspired by the transferability of pair-wise relationship, the proposed quality measure operates based on the philosophy of improving the transferability and discriminability simultaneously. In particular, we introduce three types of losses which complementarily and explicitly regularize the feature space of ranking in a progressive manner. Regarding feature discriminatory capability enhancement, we propose a center based loss to rectify the classifier and improve its prediction capability not only for source domain (NI) but also the target domain (SCI). For feature discrepancy minimization, the maximum mean discrepancy (MMD) is imposed on the extracted ranking features of NIs and SCIs. Furthermore, to further enhance the feature diversity, we introduce the correlation penalization between different feature dimensions, leading to the features with lower rank and higher diversity. Experiments show that our method can achieve higher performance on different source-target settings based on a light-weight convolution neural network. The proposed method also sheds light on learning quality assessment measures for unseen application-specific content without the cumbersome and costing subjective evaluations.
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http://dx.doi.org/10.1109/TIP.2021.3084750DOI Listing
June 2021

Expression Analysis of Circular RNAs in Young and Sexually Mature Boar Testes.

Animals (Basel) 2021 May 17;11(5). Epub 2021 May 17.

Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.

Testicular development is critical for male animals' reproduction and is tightly regulated by epigenetic factors. Circular RNAs (circRNAs) were recently identified in the testes of humans and bulls. However, the expression profile of circRNAs and their potential biological functions in boar testicular development remain unclear. We identified 34,521 and 31,803 circRNAs in piglet (30 d) and adult (210 d) boar testes by high-throughput sequencing, respectively. Bioinformatics analysis revealed that these circRNAs are widely distributed on autosomes and sex chromosomes. Some of the host genes can generate multiple circRNAs. A total of 2326 differentially expressed circRNAs (DECs) derived from 1526 host genes was found in testicular development, of which 1003 circRNAs were up-regulated in adult boar testes and 1323 circRNAs were down-regulated. Furthermore, gene ontology analysis of host genes of DECs revealed that these circRNAs are mainly involved in regulating spermatogenesis, cilia motility, and hormone biosynthesis. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DECs are markedly enriched to stem cell pluripotency regulation, tight junctions, adhesion junctions, and cAMP signaling pathway. These results indicate that circRNAs are abundantly expressed in boar testes and exhibit dynamic changes during testicular development.
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http://dx.doi.org/10.3390/ani11051430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156704PMC
May 2021

Waist to height ratio is associated with an increased risk of mortality in Chinese patients with heart failure with preserved ejection fraction.

BMC Cardiovasc Disord 2021 05 28;21(1):263. Epub 2021 May 28.

Geriatric Cardiology Department of The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853, China.

Background: Abdominal obesity as a predominant comorbidity has played a key role in the incidence and worsening of heart failure with preserved ejection fraction (HFpEF), and waist-to-height ratio (WHtR) behaves better than waist circumference or body mass index in evaluating abdominal obesity. While the association between WHtR and all-cause death in Chinese patients with HFpEF remains unclear.

Methods: Patients with stable HFpEF (N = 2041) who presented to our hospital from January 2008 to July 2019 were divided into low-WHtR (< 0.5, N = 378) and high-WHtR (≥ 0.5, N = 1663). Multivariable Cox proportional-hazard models were used to examine the association of WHtR with all-cause death.

Results: The average age was 76.63 ± 11.44 years, and the mean follow-up was 4.53 years. During follow-up, 185 patients (9.06%) reached the primary outcome of all-cause death. As for the secondary outcome, 79 patients (3.87%) experienced cardiovascular death, 106 (5.19%) had non-cardiovascular death, and 94 (4.61%) had heart failure rehospitalization. After multivariable adjustment, a higher WHtR was significantly associated with the increased risks of all-cause death [adjusted hazard ratios (HR) 1.91, 95% confidence interval (CI) 1.06-3.45, p = 0.032], cardiovascular death (adjusted HR 2.58; 95% CI 1.01-6.67, p = 0.048), and HF rehospitalization (adjusted HR 3.04; 95% CI 1.26-7.31, p = 0.013).

Conclusions: Higher WHtR is an independent risk factor for all-cause death in Chinese patients with HFpEF.
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http://dx.doi.org/10.1186/s12872-021-02080-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164240PMC
May 2021

Recurrent Multi-Frame Deraining: Combining Physics Guidance and Adversarial Learning.

IEEE Trans Pattern Anal Mach Intell 2021 May 24;PP. Epub 2021 May 24.

In this paper, we build a more comprehensive rain model with several degradation factors and construct a novel two-stage video rain removal method that combines the power of synthetic videos and real data. Specifically, a novel two-stage progressive network is proposed: recovery guided by a physics model, and further restoration by adversarial learning. The first stage performs an inverse recovery process guided by our proposed rain model. An initially estimated background frame is obtained based on the input rain frame. The second stage employs adversarial learning to refine the result, i.e. recovering the overall color and illumination distributions of the frame, the background details that are failed to be recovered in the first stage, and removing the artifacts generated in the first stage. Furthermore, we also introduce a more comprehensive rain model that includes degradation factors, e.g. occlusion and rain accumulation, which appear in real scenes yet ignored by existing methods. This model, which generates more realistic rain images, will train and evaluate our models better. Extensive evaluations on synthetic and real videos show the effectiveness of our method in comparisons to the state-of-the-art methods.
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http://dx.doi.org/10.1109/TPAMI.2021.3083076DOI Listing
May 2021

Non-viral nanoparticles for RNA interference: Principles of design and practical guidelines.

Adv Drug Deliv Rev 2021 07 19;174:576-612. Epub 2021 May 19.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland; Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki FI-00014, Finland. Electronic address:

Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed.
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http://dx.doi.org/10.1016/j.addr.2021.05.018DOI Listing
July 2021

Fast denoising and lossless spectrum extraction in stimulated Raman scattering microscopy.

J Biophotonics 2021 Aug 24;14(8):e202100080. Epub 2021 May 24.

Key Laboratory of Optoelectronic Devices and Systems of Guangdong Province and Ministry of Education, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, China.

Stimulated Raman scattering (SRS) microscopy is a nonlinear optical imaging method for visualizing chemical content based on molecular vibrational bonds. However, the imaging speed and sensitivity are currently limited by the noise of the light beam probing the Raman process. In this paper, we present a fast non-average denoising and high-precision Raman shift extraction method, based on a self-reinforcing signal-to-noise ratio (SNR) enhancement algorithm, for SRS spectroscopy and microscopy. We compare the results of this method with the filtering methods and the reported experimental methods to demonstrate its high efficiency and high precision in spectral denoising, Raman peak extraction and image quality improvement. We demonstrate a maximum SNR enhancement of 10.3 dB in fixed tissue imaging and 11.9 dB in vivo imaging. This method reduces the cost and complexity of the SRS system and allows for high-quality SRS imaging without use of special laser, complicated system design and Raman tags.
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http://dx.doi.org/10.1002/jbio.202100080DOI Listing
August 2021

Investigating tunneling nanotubes in ovarian cancer based on two-photon excitation FLIM-FRET.

Biomed Opt Express 2021 Apr 9;12(4):1962-1973. Epub 2021 Mar 9.

Key Laboratory of Optoelectronic Devices and Systems of Guangdong Province & Ministry of Education, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong Province 518060, China.

Precise and efficient cell-to-cell communication is critical to the growth and differentiation of organisms, the formation of various organism, the maintenance of tissue function and the coordination of their various physiological activities, especially to the growth and invasion of cancer cells. Tunneling nanotubes (TNTs) were discovered as a new method of cell-to-cell communication in many cell lines. In this paper, we investigated TNTs-like structures in ovarian cancer cells and proved their elements by fluorescent staining, which showed that TNTs are comprised of natural lipid bilayers with microtubules as the skeleton that can transmit ions and organelles between adjacent cells. We then used fluorescence resonance energy transfer (FRET) based on two-photon excitation fluorescence lifetime imaging microscopy (FLIM) (TP-FLIM-FRET) to detect material transport in TNTs. The experimental results showed that the number of TNTs have an impact on the drug treatment of cancer cells, which provided a new perspective for TNTs involvement in cancer treatment. Our results also showed that TP-FLIM-FRET would potentially become a new optical method for TNTs study.
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http://dx.doi.org/10.1364/BOE.418778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086450PMC
April 2021

HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance.

J Exp Clin Cancer Res 2021 May 14;40(1):170. Epub 2021 May 14.

State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 710032, Xi'an, Shaanxi Province, China.

Background: Pseudouridine synthase (PUS) 7 is a member of the PUS family that catalyses pseudouridine formation. It has been shown to be involved in intellectual development and haematological malignancies. Nevertheless, the role and the underlying molecular mechanisms of PUS7 in solid tumours, such as colorectal cancer (CRC), remain unexplored. This study elucidated, for the first time, the role of PUS7 in CRC cell metastasis and the underlying mechanisms.

Methods: We conducted immunohistochemistry, qPCR, and western blotting to quantify the expression of PUS7 in CRC tissues as well as cell lines. Besides, diverse in vivo and in vitro functional tests were employed to establish the function of PUS7 in CRC. RNA-seq and proteome profiling analysis were also applied to identify the targets of PUS7. PUS7-interacting proteins were further uncovered using immunoprecipitation and mass spectrometry.

Results: Overexpression of PUS7 was observed in CRC tissues and was linked to advanced clinical stages and shorter overall survival. PUS7 silencing effectively repressed CRC cell metastasis, while its upregulation promoted metastasis, independently of the PUS7 catalytic activity. LASP1 was identified as a downstream effector of PUS7. Forced LASP1 expression abolished the metastasis suppression triggered by PUS7 silencing. Furthermore, HSP90 was identified as a client protein of PUS7, associated with the increased PUS7 abundance in CRC. NMS-E973, a specific HSP90 inhibitor, also showed higher anti-metastatic activity when combined with PUS7 repression. Importantly, in line with these results, in human CRC tissues, the expression of PUS7 was positively linked to the expression of HSP90 and LASP1, and patients co-expressing HSP90/PUS7/LASP1 showed a worse prognosis.

Conclusions: The HSP90-dependent PUS7 upregulation promotes CRC cell metastasis via the regulation of LASP1. Thus, targeting the HSP90/PUS7/LASP1 axis may be a novel approach for the treatment of CRC.
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http://dx.doi.org/10.1186/s13046-021-01951-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120699PMC
May 2021

Correction: Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications.

Chem Commun (Camb) 2021 May;57(36):4468

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. and Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland.

Correction for 'Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications' by Shiqi Wang et al., Chem. Commun., 2021, DOI: 10.1039/d1cc00811k.
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http://dx.doi.org/10.1039/d1cc90141aDOI Listing
May 2021

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications.

Chem Commun (Camb) 2021 Apr;57(35):4212-4229

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. and Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland.

Acetalated dextran (Ac-DEX) is a pH-responsive dextran derivative polymer. Prepared by a simple acetalation reaction, Ac-DEX has tunable acid-triggered release profile. Despite its relatively short research history, Ac-DEX has shown great potential in various therapeutic applications. Furthermore, the recent functionalization of Ac-DEX makes versatile derivatives with additional properties. Herein, we summarize the cutting-edge development of Ac-DEX and related polymers. Specifically, we focus on the chemical synthesis, nano- and micro-particle fabrication techniques, the controlled-release mechanisms, and the rational design Ac-DEX-based of drug delivery systems in various biomedical applications. Finally, we briefly discuss the challenges and future perspectives in the field.
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http://dx.doi.org/10.1039/d1cc00811kDOI Listing
April 2021

Facile and Scalable Synthesis of 3D Structures of VO·12HO Nanosheets Coated with Carbon toward Ultrafast and Ultrastable Zinc Storage.

ACS Appl Mater Interfaces 2021 Apr 16;13(16):18704-18712. Epub 2021 Apr 16.

School of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002, China.

Three-dimensional (3D) structures of VO·12HO nanosheets coated with carbon (denoted as [email protected]) are facially and cost-effectively fabricated by reducing the VO-based aqueous solution with ethanol under hydrothermal conditions. By using the 3D [email protected] as the cathode of zinc-ion batteries, the as-obtained 3D [email protected] sample delivers excellent charge-discharge cycling capability, superior rate performance, and reasonable specific capacity, and a specific capacity of ca. 133.3 mA h g and a 94.1% capacity retention are achieved even after 10000 cycles at a high current density of 10 A g (∼80 C). Furthermore, it provides a facile and scalable approach to synthesize the 3D structures of pure-phased vanadium oxide nanosheets or other nanoscale metal oxides coated with carbon.
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http://dx.doi.org/10.1021/acsami.1c00749DOI Listing
April 2021

pH-Responsive Amphiphilic Carboxylate Polymers: Design and Potential for Endosomal Escape.

Authors:
Shiqi Wang

Front Chem 2021 23;9:645297. Epub 2021 Mar 23.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

The intracellular delivery of emerging biomacromolecular therapeutics, such as genes, peptides, and proteins, remains a great challenge. Unlike small hydrophobic drugs, these biotherapeutics are impermeable to the cell membrane, thus relying on the endocytic pathways for cell entry. After endocytosis, they are entrapped in the endosomes and finally degraded in lysosomes. To overcome these barriers, many carriers have been developed to facilitate the endosomal escape of these biomacromolecules. This mini-review focuses on the development of anionic pH-responsive amphiphilic carboxylate polymers for endosomal escape applications, including the design and synthesis of these polymers, the mechanistic insights of their endosomal escape capability, the challenges in the field, and future opportunities.
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http://dx.doi.org/10.3389/fchem.2021.645297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021698PMC
March 2021

Quantitative laser-induced breakdown spectroscopy for discriminating neoplastic tissues from non-neoplastic ones.

Opt Express 2021 Feb;29(3):4159-4173

In this paper, we present a method to distinguish neoplastic tissues from non-neoplastic ones using calibration-free laser-induced breakdown spectroscopy (CF-LIBS). For this propose, plasma emission was collected from neoplastic and non-neoplastic tissues taken from the ovarian cancer mice models. Results were obtained by utilizing the characteristic plasma emission lines of different elements that have been confirmed in the investigated samples. From the temporal evolution of plasma emission, the optimum temporal-observation-windows are identified for LIBS investigation. The concentrations of the detected elements in tissues were measured by a calibration-free approach based on data process of plasma parameters at the local thermodynamic equilibrium. The neoplastic specimens provided more energetic plasma than non-neoplastic ones that resulting in higher peaks intensities, electron density and electron temperature especially in the early windows (between 0.1 µs to 0.8 µs). Results demonstrated higher concentrations of major and trace elements such as Mg, Fe, Ca, Na, and K in the neoplastic tissues. Finally, the results using CF-LIBS method were found to be in good agreement with that of Inductive coupled plasma-optical emission spectroscopy (ICP-OES).
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http://dx.doi.org/10.1364/OE.410878DOI Listing
February 2021

Band Representation-Based Semi-Supervised Low-Light Image Enhancement: Bridging the Gap Between Signal Fidelity and Perceptual Quality.

IEEE Trans Image Process 2021 9;30:3461-3473. Epub 2021 Mar 9.

It has been widely acknowledged that under-exposure causes a variety of visual quality degradation because of intensive noise, decreased visibility, biased color, etc. To alleviate these issues, a novel semi-supervised learning approach is proposed in this paper for low-light image enhancement. More specifically, we propose a deep recursive band network (DRBN) to recover a linear band representation of an enhanced normal-light image based on the guidance of the paired low/normal-light images. Such design philosophy enables the principled network to generate a quality improved one by reconstructing the given bands based upon another learnable linear transformation which is perceptually driven by an image quality assessment neural network. On one hand, the proposed network is delicately developed to obtain a variety of coarse-to-fine band representations, of which the estimations benefit each other in a recursive process mutually. On the other hand, the extracted band representation of the enhanced image in the recursive band learning stage of DRBN is capable of bridging the gap between the restoration knowledge of paired data and the perceptual quality preference to high-quality images. Subsequently, the band recomposition learns to recompose the band representation towards fitting perceptual regularization of high-quality images with the perceptual guidance. The proposed architecture can be flexibly trained with both paired and unpaired data. Extensive experiments demonstrate that our method produces better enhanced results with visually pleasing contrast and color distributions, as well as well-restored structural details.
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http://dx.doi.org/10.1109/TIP.2021.3062184DOI Listing
March 2021

Global research on cognitive behavioural therapy for schizophrenia from 2000 to 2019: a bibliometric analysis via CiteSpace.

Gen Psychiatr 2021 28;34(1):e100327. Epub 2021 Jan 28.

Psychiatry Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

Background: Cognitive behavioural therapy (CBT) is considered to be an effective treatment for schizophrenia. In recent years, researchers have published clinical research results on CBT for schizophrenia. However, there is currently a lack of bibliometric analysis on CBT for schizophrenia.

Aims: To understand the current situation and research trends of CBT for schizophrenia, and to provide valuable information for researchers in this field.

Methods: Literature was retrieved from the Web of Science Core Collection database. CiteSpace was used to visually analyse the current status of research on CBT for schizophrenia, as well as trends and points of general interest on this topic.

Results: A total of 1151 papers were retrieved. The annual number of publications has increased 417.65% from 2000 to 2019. was the most active journal. McGorry enjoys considerable influence. The University of London is deemed to be the most active research institution. England and the USA retain the highest scientific productivity in this field. China and Norway might make more contributions to this field in the future. The most important research topics are randomised controlled trials of CBT for schizophrenia, meta-analysis, scale selection and research on the improvement of quality of life. Results from the following keywords 'psychoeducation', 'insomnia', 'individual', 'mental illness', 'major depressive disorder', 'efficacy', 'internalised stigma' and 'remediation' indicated new research frontiers in this field.

Conclusions: The field of CBT for schizophrenia is progressing and has great potential. The level and quality of research in this field is high. The proposal of research hotspots and frontiers serves as a direction for researchers in this field. Researchers around the world should strengthen their cooperation and communication to promote further development of this field.
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http://dx.doi.org/10.1136/gpsych-2020-100327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845669PMC
January 2021

Highly stable organic photothermal agent based on near-infrared-II fluorophores for tumor treatment.

J Nanobiotechnology 2021 Feb 4;19(1):37. Epub 2021 Feb 4.

Key Laboratory of Optoelectronic Devices and Systems of Guangdong Province & Ministry of Education, College of Physics and Optoelectronic Engineering Shenzhen University, Shenzhen, 518060, Guangdong Province, People's Republic of China.

Background: The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy.

Results: A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza-boron-dipyrromethene (aza-BODIPY) dyes with donor-acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity.

Conclusions: Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.
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http://dx.doi.org/10.1186/s12951-021-00782-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863535PMC
February 2021

Comparison of Full-Reference Image Quality Models for Optimization of Image Processing Systems.

Int J Comput Vis 2021 Jan 21:1-24. Epub 2021 Jan 21.

Howard Hughes Medical Institute, Center for Neural Science, and Courant Institute of Mathematical Sciences, New York University, New York, USA.

The performance of objective image quality assessment (IQA) models has been evaluated primarily by comparing model predictions to human quality judgments. Perceptual datasets gathered for this purpose have provided useful benchmarks for improving IQA methods, but their heavy use creates a risk of overfitting. Here, we perform a large-scale comparison of IQA models in terms of their use as objectives for the optimization of image processing algorithms. Specifically, we use eleven full-reference IQA models to train deep neural networks for four low-level vision tasks: denoising, deblurring, super-resolution, and compression. Subjective testing on the optimized images allows us to rank the competing models in terms of their perceptual performance, elucidate their relative advantages and disadvantages in these tasks, and propose a set of desirable properties for incorporation into future IQA models.
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http://dx.doi.org/10.1007/s11263-020-01419-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817470PMC
January 2021
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