Publications by authors named "Yifan Yang"

212 Publications

Shuttle-Shape Carrier-Free Platinum-Coordinated Nanoreactors with O Self-Supply and ROS Augment for Enhanced Phototherapy of Hypoxic Tumor.

ACS Appl Mater Interfaces 2021 Jul 7;13(28):32690-32702. Epub 2021 Jul 7.

Department of Biomaterials, College of Materials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province & Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen 361005, China.

The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O self-supply, self-sufficient singlet oxygen (O), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (HO) into O to alleviate tumor hypoxia. The production of O can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.
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http://dx.doi.org/10.1021/acsami.1c06668DOI Listing
July 2021

Cytosolic Protein Delivery for Intracellular Antigen Targeting Using Supercharged Polypeptide Delivery Platform.

Nano Lett 2021 Jul 6;21(14):6022-6030. Epub 2021 Jul 6.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.

Despite the well-recognized clinical success of therapeutic proteins, especially antibodies, their inability to penetrate the cell membrane restricts them to secretory extracellular or membrane-associated targets. Developing a direct cytosolic protein delivery system would offer unique opportunities for intracellular target-related therapeutic proteins. Here, we generated a supercharged polypeptide (SCP) with high cellular uptake efficiency, endosomal escape ability, and good biosafety and developed an SCP with an unnatural amino acid containing the phenylboronic acid (PBA) group, called PBA-SCP. PBA-SCP is capable of potently delivering proteins with various isoelectric points and molecular sizes into the cytosol of living cells without affecting their bioactivities. Importantly, cytosolically delivered antibodies remain functional and are capable of targeting, labeling, and manipulating diverse intracellular antigens. This study demonstrates an efficient and versatile intracellular protein delivery platform, especially for antibodies, and provides new possibilities for expanding protein-based therapeutics to intracellular "undruggable" targets.
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http://dx.doi.org/10.1021/acs.nanolett.1c01190DOI Listing
July 2021

Multifunctional dopamine modification of green antibacterial hemostatic sponge.

Mater Sci Eng C Mater Biol Appl 2021 Aug 2;127:112227. Epub 2021 Jun 2.

Marine College, Shandong University, Weihai 264209, China. Electronic address:

A novel hemostatic nanocomposite (OBC-PDA/PDA-MMT/Ag NPs) was prepared. As Functional hemostatic particles, hydrochloric acid modified montmorillonite coated with dopamine (PDA-MMT) doped into oxidized bacterial cellulose (OBC). In the presence of carboxyl and dopamine, silver ions (Ag) were reduced into Ag nanoparticles (Ag NPs) distributed homogeneously on the matrix of PDA-MMT and OBC. Then, dopamine was grafted onto the oxidized bacterial cellulose under the crosslinking effect of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). After dopamine was grafted onto the oxidized bacterial cellulose, the interaction between PDA-MMT and the whole material was enhanced, and the flexibility was also improved. OBC-PDA/PDA-MMT/Ag NPs hemostatic sponge have appropriate mechanical strength, broad-spectrum antibacterial properties and excellent biodegradability. The hemostatic sponge with addition of PDA-MMT and Ag NPs is expected to provide functional properties such as rapid hemostasis, bacteriostasis and wound healing. In addition, the hemostatic effect of the compound was confirmed in vivo. The hemostatic sponge showed greater coagulation capacity, higher adherent red blood cells and platelets, and lower blood loss. The results show that hemostatic sponge is a rapid and effective coagulant with good antibacterial properties.
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http://dx.doi.org/10.1016/j.msec.2021.112227DOI Listing
August 2021

Comparative Genomics Reveals Potential Mechanisms of Plant Beneficial Effects of a Novel Bamboo-Endophytic Bacterial Isolate Suichang626.

Front Microbiol 2021 18;12:686998. Epub 2021 Jun 18.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, China.

Plant-beneficial microbes have drawn wide attention due to their potential application as bio-control agents and bio-fertilizers. Moso bamboo, which is among the monocots with the highest growth rate, lives perennially with abundant microbes that may benefit annually growing crops. Genome information of moso bamboo associated bacteria remains underexplored. We isolated and identified a novel strain Suichang626 from moso bamboo roots. Growth promoting effects of Suichang626 on both moso bamboo and seedlings of the model dicot were documented in laboratory conditions. To gain insight into the genetic basis of this growth promotion effect, we sequenced the genome of Suichang626. Evidenced by genome-wide phylogeny data, we propose that Suichang626 is a novel strain of . Gene homologs encoding biosynthesis of the plant growth-promoting chemicals, acetoin and 2,3-butanediol, were identified in the genome of Suichang626. Comparative genomics was further performed with plant-beneficial and plant/animal pathogenic species of and . Genes related to volatile organic compounds, nitrogen fixation, and auxin biosynthesis were discovered specifically in the plant growth-promoting species of both genera.
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http://dx.doi.org/10.3389/fmicb.2021.686998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250432PMC
June 2021

Daphnetin inhibits spinal glial activation via Nrf2/HO-1/NF-κB signaling pathway and attenuates CFA-induced inflammatory pain.

Int Immunopharmacol 2021 Jun 26;98:107882. Epub 2021 Jun 26.

Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China. Electronic address:

Daphnetin (7, 8-dihydroxycoumarin, DAPH), a coumarin derivative isolated from Daphne odora var., recently draws much more attention as a promising drug candidate to treat neuroinflammatory diseases due to its protective effects against neuroinflammation. However, itscontribution to chronic inflammatory pain is largely unknown. In the current work, we investigated the effects of DAPH in a murine model of inflammatory pain induced by complete Freund's adjuvant (CFA) and its possible underlying mechanisms. Our results showed that DAPH treatment significantly attenuated mechanical allodynia provoked by CFA. A profound inhibition of spinal glial activation, followed by attenuated expression levels of spinal pro-inflammatory cytokines, was observed in DAPH-treated inflammatory pain mice. Further study demonstrated that DAPH mediated negative regulation of spinal NF-κB pathway, as well as its preferential activation of Nrf2/HO-1 signaling pathway in inflammatory pain mice. This study, for the first time, indicated that DAPH might preventthe development of mechanical allodynia in mice with inflammatory pain. And more importantly, these data provide evidence for the potential application of DAPH in the treatment of chronic inflammatory pain.
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http://dx.doi.org/10.1016/j.intimp.2021.107882DOI Listing
June 2021

A novel self-targeting theranostic nanoplatform for photoacoustic imaging-monitored and enhanced chemo-sonodynamic therapy.

J Mater Chem B 2021 Jul;9(27):5547-5559

Department of Biomaterials, College of Materials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province & Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen 361005, China.

Sonodynamic therapy has attracted wide attention as a noninvasive therapy due to deep tissue penetration. However, majority sonosensitizers often suffer from poor physiological stability, rapid blood clearance and nonspecific targeting, which seriously hinders their further practical applications. Inspired by the concept of active targeting drug delivery, both dual-functional chemo-drug pemetrexed (PEM, emerges an innate affinity toward the folate receptor) and amphiphilic d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected to be covalently linked by an esterase-responsive ester linkage. The synthesized self-targeting TPGS-PEM prodrug and indocyanine green (ICG) as functional motifs can be self-assembled into a TPGS-PEM-ICG nanoplatform within an aqueous medium. The TPGS-PEM-ICG nanoplatform with outstanding structural and physiological stability not only protects the sonosensitizer from reticular endothelial system clearance but also achieves active targeting drug delivery and efficient tumor enrichment. Moreover, TPGS-PEM-ICG nanoplatform can selectively recognize tumor cells and then realize on-demand drug burst release by multiple stimuli of internal lysosomal acidity, esterase and external ultrasound, which guarantee low side effects toward normal tissues and organs. It is also worth noting that our nanoplatform exhibits protruding tumor enrichment under the precise guidance of photoacoustic/fluorescence imaging. Further in vitro and in vivo experimental results well confirmed that the TPGS-PEM-ICG nanoplatform possesses enhanced chemo-sonodynamic effects. Interestingly, the highly toxic reactive oxygen species can remarkably reduce the blood oxygen saturation signal of the tumor microenvironment via precise, multifunctional and high-resolution photoacoustic imaging. Taken together, the TPGS-PEM-ICG nanoplatform can be expected to hold enormous potential for diagnosis, prognosis and targeted therapy for tumor.
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http://dx.doi.org/10.1039/d1tb01025eDOI Listing
July 2021

Intra-dialytic hypotension following the transition from continuous to intermittent renal replacement therapy.

Ann Intensive Care 2021 Jun 19;11(1):96. Epub 2021 Jun 19.

Division of Nephrology, St. Michaels Hospital and University of Toronto, Toronto, Canada.

Background: Transition from continuous renal replacement therapy (CRRT) to intermittent renal replacement therapy (IRRT) can be associated with intra-dialytic hypotension (IDH) although data to inform the definition of IDH, its incidence and clinical implications, are lacking. We aimed to describe the incidence and factors associated with IDH during the first IRRT session following transition from CRRT and its association with hospital mortality. This was a retrospective single-center cohort study in patients with acute kidney injury for whom at least one CRRT-to-IRRT transition occurred while in intensive care. We assessed associations between multiple candidate definitions of IDH and hospital mortality. We then evaluated the factors associated with IDH.

Results: We evaluated 231 CRRT-to-IRRT transitions in 213 critically ill patients with AKI. Hospital mortality was 43.7% (n = 93). We defined IDH during the first IRRT session as 1) discontinuation of IRRT for hemodynamic instability; 2) any initiation or increase in vasopressor/inotropic agents or 3) a nadir systolic blood pressure of < 90 mmHg. IDH during the first IRRT session occurred in 50.2% of CRRT-to-IRRT transitions and was independently associated with hospital mortality (adjusted odds ratio [OR]: 2.71; CI 1.51-4.84, p < 0.001). Clinical variables at the time of CRRT discontinuation associated with IDH included vasopressor use, higher cumulative fluid balance, and lower urine output.

Conclusions: IDH events during CRRT-to-IRRT transition occurred in nearly half of patients and were independently associated with hospital mortality. We identified several characteristics that anticipate the development of IDH following the initiation of IRRT.
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http://dx.doi.org/10.1186/s13613-021-00885-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214642PMC
June 2021

Corrosion Behavior of Biodegradable Magnesium Alloy by MAF Treatment.

Scanning 2021 3;2021:5530788. Epub 2021 May 3.

The Conversationalist Club, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, Shandong 271016, China.

Coating treatment plays an irreplaceable role in propelling the clinical application of magnesium alloys. This experiment was designed in order to observe the anticorrosion behavior of magnesium fluoride coating in rats. The MgF layer was prepared on the surface of AZ31 magnesium alloy in saturated NHHF solution by microarc fluorination (MAF) at 190 V. The cross-sectional SEM, EDS, and XRD analysis indicated that the alloy surface was covered with MgF. Meanwhile, SEM observation was used to compare the magnesium alloy samples before and after treatment, and it was found that the samples after coating were flatter and smoother. Two sets of experiments were carried out with the subjects, 6-week-old male rats. So that the untreated AZ31 samples and the microarc fluorinated AZ31 samples could be buried under the muscle layer individually. The volume changes and surface morphology of the corroded samples were monitored dynamically using micro-CT over a 16-week period . Comparison of results between the two sets of samples presented that the corrosion of the microarc fluoridated samples was much slower than that of the untreated ones. The MAF coating was shown to be effective in controlling the corrosion rate and progression of the magnesium alloy.
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http://dx.doi.org/10.1155/2021/5530788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112943PMC
May 2021

Effect of dihydromyricetin on hepatic encephalopathy associated with acute hepatic failure in mice.

Pharm Biol 2021 Dec;59(1):557-564

Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.

Context: Hepatic encephalopathy (HE) is a complex neuropsychiatric disease caused by liver failure. Dihydromyricetin (DMY) is a traditional medicine used to treat liver injury.

Objective: To investigate the effects of dihydromyricetin (DMY) on hepatic encephalopathy associated with acute hepatic failure mice models established by thioacetamide (TAA) exposure.

Materials And Methods: Female BALB/c mouse were randomly divided into control, DMY, TAA, and TAA + DMY groups ( = 8). The first two groups were intraperitoneally injected with saline or 5 mg/kg DMY, respectively. The last two groups were injected with 600 mg/kg TAA to establish HE models, and then the mice in the last group were treated with 5 mg/kg DMY. Neurological and cognition functions were evaluated 24 and 48 h after injection. Mice were sacrificed after which livers and brains were obtained for immunoblot and histopathological analysis, while blood was collected for the analysis of liver enzymes.

Results: In the TAA + DMY group, ALT and AST decreased to 145.31 ± 12.88 U/L and 309.51 ± 25.92 U/L, respectively, whereas ammonia and TBIL decreased to 415.67 ± 41.91 μmol/L and 3.31 ± 0.35 μmol/L, respectively. Moreover, MDA decreased to 10.74 ± 3.97 nmol/g, while SOD and GST increased to 398.69 ± 231.30 U/g and 41.37 ± 21.84 U/g, respectively. The neurological score decreased to 2.87 ± 0.63, and the number of GFAP-positive cells decreased to 41.10 ± 1.66. Furthermore, the protein levels of TNF-α, IL-6, and GABA in the cortex decreased.

Conclusions: We speculate that DMY can serve as a novel treatment for HE.
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http://dx.doi.org/10.1080/13880209.2021.1917625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128201PMC
December 2021

Z-scores for comparative analyses of spermatogonial numbers throughout human development.

Fertil Steril 2021 May 8. Epub 2021 May 8.

NORDFERTIL Research Lab Stockholm, Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; New Children's Hospital, Pediatric Research Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address:

Objective: To normalize age-dependent effects on standardized measures of spermatogonial quantity such as the number of spermatogonia per tubular cross-section (S/T) or fertility index.

Design: Published quantitative histologic data on human spermatogonial numbers were used to create Z-scores for reference means and tested on archived testicular tissue samples.

Setting: Retrospective cohort study.

Patient(s): The sample cohort comprised testicular samples from 24 boys with cancer diagnosis and 10 with Klinefelter syndrome, as part of the fertility preservation programs NORDFERTIL and Androprotect, as well as archived histologic samples from 35 prepubertal boys with acute lymphoblastic leukemia and 20 testicular biobank samples.

Intervention(s): None.

Main Outcome Measure(s): Z-score values for S/T and fertility index on the basis of morphology and germ cell-specific markers (MAGEA4 and/or DDX4) were calculated, and the impact of cancer therapy exposure and genetic disorders on Z-score values was evaluated.

Result(s): The Z-scores for S/T values in the nontreated samples (-2.08 ± 2.20, n = 28) and samples treated with nonalkylating agents (-1.90 ± 2.60, n = 25) were comparable within ±3 standard deviations of the reference mean value but differed significantly from samples exposed to alkylating agents (-12.14 ± 9.20, n = 22) and from patients with Klinefelter syndrome (-11.56 ± 4.89, n = 8). The Z-scores for S/T were correlated with increasing cumulative exposure to alkylating agents (r = -0.7020).

Conclusion(s): The Z-score values for S/T allow for the quantification of genetic and cancer treatment-related effects on testicular tissue stored for fertility preservation, facilitating their use for patient counseling.
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http://dx.doi.org/10.1016/j.fertnstert.2021.04.019DOI Listing
May 2021

Ultrahigh-response hydrogen sensor based on PdO/NiO co-doped InO nanotubes.

J Colloid Interface Sci 2021 Oct 28;599:533-542. Epub 2021 Apr 28.

School of Physical Science and Technology, Lanzhou University, Lanzhou 730000, China. Electronic address:

Hydrogen can be regarded as an ideal type of secondary energy considering its potential for achieving renewable and sustainable development due to water being its sole combustion product and its possible production by solar energy-based water electrolysis. Monitoring the presence and concentration of hydrogen during production, transportation, and application requires a hydrogen gas sensor with high response, high selectivity, and fast response and recovery times. In an attempt to meet these requirements, NiO and PdO are used in the co-doping of InO nanotubes by subsequent electrospinning and impregnation under UV irradiation. The fabricated hydrogen gas sensor demonstrates an ultrahigh response of 487.52, a fast response time of 1 s and high selectivity at an operating temperature of 160 °C, which characteristics are superior to reported monometal-doped hydrogen sensors. The remarkable gas sensing performance could be attributed to the synergistic effect of the resistance modulation, the chemical sensitization of PdO, and the catalytic effect of NiO. This study demonstrates that co-doping of PdO and NiO on InO nanotubes is an effective way to improve hydrogen sensing characteristics more effectively than doping with PdO or NiO alone, and provides a potential application for the fast and accurate detection of hydrogen.
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http://dx.doi.org/10.1016/j.jcis.2021.04.125DOI Listing
October 2021

Multifunctional [email protected] nanoparticles cluster synergize chemotherapy and photothermal therapy for tumor metastasis.

Nanomedicine 2021 Jun 14;34:102399. Epub 2021 Apr 14.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The poor drug delivery and unsatisfying therapeutic effects remain to be the primary challenges for cancer therapy. Nanosystem that combines multiple functions into a single platform is an ideal strategy. Here, a smart drug delivery nanoplatform ([email protected]/P) based on [email protected] nanoparticles, loaded with doxorubicin (DOX) and pirfenidone (PFD) was constructed. Importantly, the β-CD-DMA and PEG-DMA could be activated in the mild acidic tumor microenvironment, then the nanosystem underwent charge reversal and PFD release. PFD could inhibit cancer-associated fibroblasts (CAFs) activation and enhance tumor penetration. And the residual nanostructure [email protected] could trigger cascade amplified ROS generation to induce tumor cell death. The photothermal effect further strengthened the anti-tumor efficacy. Finally, the nanosystem showed remarkable inhibition of tumor growth (89.7%) and lung metastasis. The innovatively designed nanosystem integrating chemotherapy and photothermal effect would provide a promising strategy in breast cancer therapy.
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http://dx.doi.org/10.1016/j.nano.2021.102399DOI Listing
June 2021

Knockdown of PNO1 inhibits esophageal cancer progression.

Oncol Rep 2021 05 13;45(5). Epub 2021 Apr 13.

Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.

The present study aimed to investigate the role of partner of NOB1 homolog (PNO1) in esophageal cancer (EC). The expression levels of PNO1 in EC were primarily analyzed using data obtained from databases. PNO1 expression was also knocked down in EC cells (Eca‑109 and TE1) to determine the biological effects of PNO1 on tumorigenesis and . In addition, possible downstream targets of PNO1 in EC were identified. The expression levels of PNO1 were upregulated in the tumor tissues compared with that noted in normal tissues. Moreover, the knockdown (KD) of PNO1 suppressed cell proliferation, migration and invasion, and promoted cell apoptosis (P < 0.05). Furthermore, the protein expression levels of AKT1, Twist, Myc, mTOR, matrix metalloproteinase 2 (MMP2), nuclear factor (NF)‑κB p65 and β‑catenin 1 (CTNNB1) were downregulated following the KD of PNO1 in Eca‑109 cells (P < 0.05). In addition, the overexpression of CTNNB1 reversed the effects of PNO1 KD in Eca‑109 cells (P < 0.05). In conclusion, the findings of the present study suggest that PNO1 promotes EC progression by regulating AKT1, Twist, Myc, mTOR, MMP2, NF‑κB p65 and CTNNB1 expression.
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http://dx.doi.org/10.3892/or.2021.8036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025143PMC
May 2021

LINC00460 Promotes Cell Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Head and Neck Squamous Cell Carcinoma via miR-320a/BGN Axis.

Onco Targets Ther 2021 30;14:2279-2291. Epub 2021 Mar 30.

Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China.

Purpose: Long non-coding RNAs (lncRNAs) play critical roles in cancer onset and development, including head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the biological role of LINC00460 and the mechanisms underlying epithelial-mesenchymal transition (EMT) in HNSCC.

Methods: Aberrantly LINC00460 expression in HNSCC and overall survival outcomes were constructed using the TCGA database. Quantitative real-time polymerase chain reaction (RT-qPCR) was applied to examine the LINC00460 expression level in HNSCC cell lines. The role of LINC00460 knockdown on HNSCC cell growth, migration, invasion, and EMT was investigated in vitro using cell counting kit-8 (CCK-8), colony formation, transwell assay, and Western blot assay. Besides, bioinformatics prediction, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) were performed to reveal the interaction among LINC00460 and its target genes. The function of the LINC00460/miR-320a/BGN axis in HNSCC cells was clarified by rescue assays. Furthermore, the in vivo effects of LINC00460 on tumor growth were investigated using mice xenograft models.

Results: In this study, LINC00460 was upregulated in HNSCC tissues and cells and was associated with poor clinical prognosis. Further functional analysis showed that LINC00460 knockdown decreased HNSCC cell proliferation, migration, invasion, as well as EMT in vitro. Mechanistic investigation indicated that LINC00460 sponged miR-320a to upregulate Biglycan (BGN) expression, thereby facilitating HNSCC progression and induced EMT. Moreover, knockdown of LINC00460 significantly suppressed the progression of HNSCC cells in vivo.

Conclusion: Taken together, LINC00460 mediates miR-320a/BGN signaling axis to promote cell proliferation, migration, invasion, and induce the EMT process in HNSCC cells. Our findings elucidated a novel mechanism underlying the progression of HNSCC. LINC00460 could serve as a potential therapeutic target for the treatment of HNSCC.
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http://dx.doi.org/10.2147/OTT.S282947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019668PMC
March 2021

Microcalcification-Based Tumor Malignancy Evaluation in Fresh Breast Biopsies with Hyperspectral Stimulated Raman Scattering.

Anal Chem 2021 04 7;93(15):6223-6231. Epub 2021 Apr 7.

State Key Laboratory of Surface Physics and Department of Physics, Human Phenome Institute, Multiscale Research Institute of Complex Systems, Academy for Engineering and Technology, Key Laboratory of Micro and Nano Photonic Structures, Ministry of Education, Fudan University, Shanghai 200433, China.

Precise evaluation of breast tumor malignancy based on tissue calcifications has important practical value in the disease diagnosis, as well as the understanding of tumor development. Traditional X-ray mammography provides the overall morphologies of the calcifications but lacks intrinsic chemical information. In contrast, spontaneous Raman spectroscopy offers detailed chemical analysis but lacks the spatial profiles. Here, we applied hyperspectral stimulated Raman scattering (SRS) microscopy to extract both the chemical and morphological features of the microcalcifications, based on the spectral and spatial domain analysis. A total of 211 calcification sites from 23 patients were imaged with SRS, and the results were analyzed with a support vector machine (SVM) based classification algorithm. With optimized combinations of chemical and geometrical features of microcalcifications, we were able to reach a precision of 98.21% and recall of 100.00% for classifying benign and malignant cases, significantly improved from the pure spectroscopy or imaging based methods. Our findings may provide a rapid means to accurately evaluate breast tumor malignancy based on fresh tissue biopsies.
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http://dx.doi.org/10.1021/acs.analchem.1c00522DOI Listing
April 2021

Observation of a Near-Threshold Structure in the K^{+} Recoil-Mass Spectra in e^{+}e^{-}→K^{+}(D_{s}^{-}D^{*0}+D_{s}^{*-}D^{0}).

Phys Rev Lett 2021 Mar;126(10):102001

Institute of High Energy Physics, Beijing 100049, People's Republic of China.

We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7  fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrt[s]=4.681  GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1)  MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0)  MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3  σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
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http://dx.doi.org/10.1103/PhysRevLett.126.102001DOI Listing
March 2021

Longdan Xiegan Tang attenuates liver injury and hepatic insulin resistance by regulating the angiotensin-converting enzyme 2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats.

J Ethnopharmacol 2021 Jun 26;274:114072. Epub 2021 Mar 26.

Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address:

Ethnopharmacological Relevance: The ancient Chinese herbal formula Longdan Xiegan Tang (LXT, also called Gentiana Longdancao Decoction to Drain the Liver) treats insulin resistance- and inflammation-associated liver injuries in clinical practice.

Aim Of The Study: To investigate the molecular mechanisms underlying LXT-elicited improvement of the liver injuries.

Materials And Methods: Male rats were co-treated with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) for eight weeks. Blood parameters were determined enzymatically or by ELISA. Gene/protein expression was analyzed by Real-Time PCR, Western blot and/or immunohistochemistry.

Results: LXT attenuated olanzapine-induced liver injury manifested by hyperactivities of plasma alanine aminotransferase and aspartate aminostransferase, hyperbilirubinemia and hypoalbuminemia. Furthermore, LXT improved hepatic insulin resistance that was indicated by hyperinsulinemia, the increased HOMA-IR index, and hepatic over-phosphorylation of Ser in insulin receptor substrate (IRS)1, Ser in IRS2, Tyr in phosphoinositide 3-kinase p85α and Ser in AKT at baseline. Mechanistically, LXT inhibited olanzapine-triggered hepatic over-phosphorylation of both IκB kinase (IKK)α/β and nuclear factor (NF)κB p65 proteins, and mRNA overexpression of tumor necrosis factor α, interleukin 6, interleukin 1β and CD68. More importantly, LXT restored the decreases in angiotensin-converting enzyme 2 (ACE2) protein level, and its downstream targets Ang (1-7) content and Mas receptor expression.

Conclusions: The present results demonstrate that LXT attenuates liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated liver injuries.
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http://dx.doi.org/10.1016/j.jep.2021.114072DOI Listing
June 2021

Model-Independent Determination of the Spin of the Ω^{-} and Its Polarization Alignment in ψ(3686)→Ω^{-}Ω[over ¯]^{+}.

Phys Rev Lett 2021 Mar;126(9):092002

Istanbul Bilgi University, 34060 Eyup, Istanbul, Turkey.

We present an analysis of the process ψ(3686)→Ω^{-}Ω[over ¯]^{+} (Ω^{-}→K^{-}Λ, Ω[over ¯]^{+}→K^{+}Λ[over ¯], Λ→pπ^{-}, Λ[over ¯]→p[over ¯]π^{+}) based on a dataset of 448×10^{6}  ψ(3686) decays collected with the BESIII detector at the BEPCII electron-positron collider. The helicity amplitudes for the process ψ(3686)→Ω^{-}Ω[over ¯]^{+} and the decay parameters of the subsequent decay Ω^{-}→K^{-}Λ (Ω[over ¯]^{+}→K^{+}Λ[over ¯]) are measured for the first time by a fit to the angular distribution of the complete decay chain, and the spin of the Ω^{-} is determined to be 3/2 for the first time since its discovery more than 50 years ago.
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http://dx.doi.org/10.1103/PhysRevLett.126.092002DOI Listing
March 2021

A novel seven-gene panel predicts the sensitivity and prognosis of head and neck squamous cell carcinoma treated with platinum-based radio(chemo)therapy.

Eur Arch Otorhinolaryngol 2021 Mar 8. Epub 2021 Mar 8.

Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.

Purpose: The aim of the study is to identify a reliable gene panel to predict the prognosis of HNSCC patients by integrated genomic analysis.

Methods: Co-expression gene networks were constructed by WGCNA using GSE113282 gene expression profile. The biological functional investigation was performed by GO and KEGG function enrichment analysis. The hub gene module was screened by PPI. The prognostic gene panel was established by Lasso regression analysis, and further progression-free survival (PFS) analysis was validated by Kaplan-Meier survival analysis using GSE102995 data.

Results: We identified 195 genes associated with the overall survival (OS) status (correlation coefficients: - 0.42, and p value: 2e-05) by WGCNA. These genes were enriched in immune-related cytokines and pathways analyzed by GO and KEGG. Among the 195 genes, the module (42 genes) with the highest score was screened by PPI. A novel seven-gene predictive panel (CD19, CD40LG, CD5, CXCR6, FPR2, NCAM1, and SELL) was established by Lasso regression analysis, and the area under ROC curve (AUC) for 3-year OS status was 0.8298 and 0.7571, respectively, in the training set and the test set. The PFS time of the low-risk patients was significantly longer than the high-risk patients (p < 0.0001; log-rank test) by further validation using GSE102995 data.

Conclusion: The seven-gene panel may serve as a reliable predictive tool for HNSCC patients treated with platinum-based radio (chemo) therapy, and may be potential therapeutic targets for HNSCC patients.
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http://dx.doi.org/10.1007/s00405-021-06717-5DOI Listing
March 2021

Association between serum osteoprotegerin level and mortality in kidney transplant recipients - a prospective observational cohort study.

Transpl Int 2021 05 18;34(5):844-854. Epub 2021 Mar 18.

Department of Medicine, Division of Nephrology and Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada.

Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1 pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.
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http://dx.doi.org/10.1111/tri.13847DOI Listing
May 2021

A Combined Method for MEMS Gyroscope Error Compensation Using a Long Short-Term Memory Network and Kalman Filter in Random Vibration Environments.

Sensors (Basel) 2021 Feb 8;21(4). Epub 2021 Feb 8.

Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

In applications such as carrier attitude control and mobile device navigation, a micro-electro-mechanical-system (MEMS) gyroscope will inevitably be affected by random vibration, which significantly affects the performance of the MEMS gyroscope. In order to solve the degradation of MEMS gyroscope performance in random vibration environments, in this paper, a combined method of a long short-term memory (LSTM) network and Kalman filter (KF) is proposed for error compensation, where Kalman filter parameters are iteratively optimized using the Kalman smoother and expectation-maximization (EM) algorithm. In order to verify the effectiveness of the proposed method, we performed a linear random vibration test to acquire MEMS gyroscope data. Subsequently, an analysis of the effects of input data step size and network topology on gyroscope error compensation performance is presented. Furthermore, the autoregressive moving average-Kalman filter (ARMA-KF) model, which is commonly used in gyroscope error compensation, was also combined with the LSTM network as a comparison method. The results show that, for the -axis data, the proposed combined method reduces the standard deviation (STD) by 51.58% and 31.92% compared to the bidirectional LSTM (BiLSTM) network, and EM-KF method, respectively. For the -axis data, the proposed combined method reduces the standard deviation by 29.19% and 12.75% compared to the BiLSTM network and EM-KF method, respectively. Furthermore, for -axis data and -axis data, the proposed combined method reduces the standard deviation by 46.54% and 22.30% compared to the BiLSTM-ARMA-KF method, respectively, and the output is smoother, proving the effectiveness of the proposed method.
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http://dx.doi.org/10.3390/s21041181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914848PMC
February 2021

Deep Neural Network-Based Semantic Segmentation of Microvascular Decompression Images.

Sensors (Basel) 2021 Feb 7;21(4). Epub 2021 Feb 7.

Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

Image semantic segmentation has been applied more and more widely in the fields of satellite remote sensing, medical treatment, intelligent transportation, and virtual reality. However, in the medical field, the study of cerebral vessel and cranial nerve segmentation based on true-color medical images is in urgent need and has good research and development prospects. We have extended the current state-of-the-art semantic-segmentation network DeepLabv3+ and used it as the basic framework. First, the feature distillation block (FDB) was introduced into the encoder structure to refine the extracted features. In addition, the atrous spatial pyramid pooling (ASPP) module was added to the decoder structure to enhance the retention of feature and boundary information. The proposed model was trained by fine tuning and optimizing the relevant parameters. Experimental results show that the encoder structure has better performance in feature refinement processing, improving target boundary segmentation precision, and retaining more feature information. Our method has a segmentation accuracy of 75.73%, which is 3% better than DeepLabv3+.
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http://dx.doi.org/10.3390/s21041167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915571PMC
February 2021

YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia.

Front Pediatr 2020 21;8:618226. Epub 2021 Jan 21.

Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.

Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model. Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status. The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, , which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model. YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.
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http://dx.doi.org/10.3389/fped.2020.618226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859521PMC
January 2021

Deep Learning Approaches on Defect Detection in High Resolution Aerial Images of Insulators.

Sensors (Basel) 2021 Feb 3;21(4). Epub 2021 Feb 3.

Institute of Human Factors and Ergonomics, College of Mechatronics and Control Engineering, Shenzhen University, Shenzhen 518060, China.

By detecting the defect location in high-resolution insulator images collected by unmanned aerial vehicle (UAV) in various environments, the occurrence of power failure can be timely detected and the caused economic loss can be reduced. However, the accuracies of existing detection methods are greatly limited by the complex background interference and small target detection. To solve this problem, two deep learning methods based on Faster R-CNN (faster region-based convolutional neural network) are proposed in this paper, namely Exact R-CNN (exact region-based convolutional neural network) and CME-CNN (cascade the mask extraction and exact region-based convolutional neural network). Firstly, we proposed an Exact R-CNN based on a series of advanced techniques including FPN (feature pyramid network), cascade regression, and GIoU (generalized intersection over union). RoI Align (region of interest align) is introduced to replace RoI pooling (region of interest pooling) to address the misalignment problem, and the depthwise separable convolution and linear bottleneck are introduced to reduce the computational burden. Secondly, a new pipeline is innovatively proposed to improve the performance of insulator defect detection, namely CME-CNN. In our proposed CME-CNN, an insulator mask image is firstly generated to eliminate the complex background by using an encoder-decoder mask extraction network, and then the Exact R-CNN is used to detect the insulator defects. The experimental results show that our proposed method can effectively detect insulator defects, and its accuracy is better than the examined mainstream target detection algorithms.
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http://dx.doi.org/10.3390/s21041033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913352PMC
February 2021

Highly specific and label-free histological identification of microcrystals in fresh human gout tissues with stimulated Raman scattering.

Theranostics 2021 1;11(7):3074-3088. Epub 2021 Jan 1.

State Key Laboratory of Surface Physics and Department of Physics, Human Phenome Institute, Multiscale Research Institute of Complex Systems, Academy for Engineering and Technology, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China.

Gout is a common metabolic disease with growing burden, caused by monosodium urate (MSU) microcrystal deposition. In situ and chemical-specific histological identification of MSU is crucial in the diagnosis and management of gout, yet it remains inaccessible for current histological methods. Stimulated Raman scattering (SRS) microscopy was utilized to image MSU based on its fingerprint Raman spectra. We first tested SRS for the diagnosis capability of gout and the differentiation power from pseudogout with rat models of acute gout arthritis, calcium pyrophosphate deposition disease (CPDD) and comorbidity. Then, human synovial fluid and surgical specimens (n=120) were were imaged with SRS to obtain the histopathology of MSU and collagen fibers. Finally, quantitative SRS analysis was performed in gout tissue of different physiological phases (n=120) to correlate with traditional histopathology including H&E and immunohistochemistry staining. We demonstrated that SRS is capable of early diagnosis of gout, rapid detection of MSU in synovial fluid and fresh unprocessed surgical tissues, and accurate differentiation of gout from pseudogout in various pathophysiological conditions. Furthermore, quantitative SRS analysis revealed the optical characteristics of MSU deposition at different pathophysiological stages, which were found to matched well with corresponding immunofluorescence histochemistry features. Our work demonstrated the potential of SRS microscopy for rapid intraoperative diagnosis of gout and may facilitate future fundamental researches of MSU-based diseases.
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http://dx.doi.org/10.7150/thno.53755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847673PMC
July 2021

Ex-situ XPS analysis of yolk-shell SbO/WO for ultra-fast acetone resistive sensor.

J Hazard Mater 2021 06 23;412:125175. Epub 2021 Jan 23.

School of Physical Science and Technology, Lanzhou University, Lanzhou 730000, PR China. Electronic address:

The preparation of fast, highly responsive and reliable gas sensing devices for the detection of acetone gas is considered to be a key challenge for the development of accurate disease diagnosis systems through exhaled respiratory gases. In the paper, yolk shell SbO/WO is synthesized and its gas sensing performance was studied by static test system. Special, the maximum response value of 1:1 SbO/WO yolk-shell (WO-1 YSL) sensor to 100 ppm acetone can reach as high as 50.0 at 200 ℃. And it also exhibits excellent response/recover time (4 s/5 s), low detection limit (2 ppm) and superior selectivity towards acetone. More importantly, in mixed selective gas test, the sensor shows high selectivity towards acetone. And the mechanism is analyzed by ex-situ XPS. The excellent gas-sensing performance can be attributed to unique yolk-shell structure, which facilitates the rapid transport of charge carriers from the surface to the bulk and provides more active sites for gas adsorption and desorption; the heterojunction between of SbO and WO, which promotes oxygen pre-adsorption on the surface and increasing the interfacial potential; the increased oxygen vacancies which allowing more chemisorbed oxygen to form.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125175DOI Listing
June 2021

Integrating enzymatic hydrolysis into subcritical water pretreatment optimization for bioethanol production from wheat straw.

Sci Total Environ 2021 May 22;770:145321. Epub 2021 Jan 22.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

The conversion of lignocellulosic biomass to bioethanol is a potential approach to alleviate the energy crisis and environmental deterioration. To improve the conversion efficiency of bioethanol from wheat straw (WS), the optimization of subcritical water pretreatment and high solid hydrolysis were investigated in this study. Response surface methodology (RSM) accompanied with glucose concentration after enzymatic hydrolysis as a more reasonable response value was applied for the pretreatment optimization, and the optimum conditions were obtained as 220.51 °C of extraction temperature, 22.01 min of extraction time and 2.50% (w/v) of substrate loading. After pretreatment, the hemicellulose decreased by 18.37%, and the cellulose and lignin increased by 25.92% and 8.81%, respectively, which were consistent with the destroyed microstructure and raised crystallinity. The high efficiency of separate hydrolysis and fermentation (SHF) was verified by five commercial cellulases, and yields of hydrolysis and fermentation were 77.85-89.59% and 93.34-96.18%, respectively. Based on the high solid (15%) hydrolysis and fermentation, the ethanol concentration was significantly improved to 37.00 g/L. Interestingly, 64.47% of lignin was accumulated in the solid residue after enzymatic hydrolysis and it did not affect the efficiency of SHF, which further suggested that subcritical water mainly affected the structure of WS rather than the removal of lignin. Therefore, subcritical water pretreatment combined with high solid hydrolysis is a more effective solution for bioethanol conversion, which is also a promising strategy to utilize all components of lignocellulosic biomass.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145321DOI Listing
May 2021

Dual-Responsive and Deep-Penetrating Nanomicelles for Tumor Therapy via Extracellular Matrix Degradation and Oxidative Stress.

ACS Biomater Sci Eng 2021 01 29;7(1):166-179. Epub 2020 Dec 29.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Tumor microenvironment (TME), with complex composition, plays a vital role in the occurrence, development, and metastasis of tumors. TME becomes an important obstacle to the accessibility of nanotherapy, thus indicating the need to improve the functional design to overcome this challenge. In this study, we generate an intelligent nano-drug-delivery system ([email protected] NPs) with dual environmental response, which involves heparanase (HPSE) in TME and glutathione (GSH) in tumor cells. The nanosystem consists of a nanoskeleton formed by self-assembly of mPEG-ss-PEI and α-CD (PssP), chemotherapy drug doxorubicin (DOX) for enhancing antitumor efficacy, together with hyaluronidase (HAase), which is designed to degrade extracellular matrix to increase drug penetration, and an outer shell of heparin. Through the process of "responsive disintegration-remodeling tumor microenvironment-enhancing drug penetration-inducing oxidative stress", the semi-rotaxaneself-assembled nanomicelles were constructed to achieve the progressive function. [email protected] NPs with the size of 81.85 ± 1.85 nm exhibited satisfactory cytotoxicity (IC = 0.80 ± 0.33 μg/mL). With the disulfide bond-mediated GSH depletion and DOX-mediated reactive oxygen species (ROS) production, treatment with [email protected] NPs prominently reduced glutathione peroxidase 4 (GPX4) level and would lead to enhanced oxidative stresses. Hyaluronic acid (HA), collagen I, and α-smooth muscle actin (α-SMA) were significantly reduced for TME remodulation. Moreover, the antitumor effect in vivo implied that [email protected] NPs could inhibit tumor growth effectively and reduce tumor interstitial fluid pressure (IFP) evidently. In conclusion, [email protected] NPs improved the penetration of drugs and exhibited enhanced antitumor efficacy.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01394DOI Listing
January 2021

Embedding Perspective Analysis Into Multi-Column Convolutional Neural Network for Crowd Counting.

IEEE Trans Image Process 2021 29;30:1395-1407. Epub 2020 Dec 29.

The crowd counting is challenging for deep networks due to several factors. For instance, the networks can not efficiently analyze the perspective information of arbitrary scenes, and they are naturally inefficient to handle the scale variations. In this work, we deliver a simple yet efficient multi-column network, which integrates the perspective analysis method with the counting network. The proposed method explicitly excavates the perspective information and drives the counting network to analyze the scenes. More concretely, we explore the perspective information from the estimated density maps and quantify the perspective space into several separate scenes. We then embed the perspective analysis into the multi-column framework with a recurrent connection. Therefore, the proposed network matches various scales with the different receptive fields efficiently. Secondly, we share the parameters of the branches with various receptive fields. This strategy drives the convolutional kernels to be sensitive to the instances with various scales. Furthermore, to improve the evaluation accuracy of the column with a large receptive field, we propose a transform dilated convolution. The transform dilated convolution breaks the fixed sampling structure of the deep network. Moreover, it needs no extra parameters and training, and the offsets are constrained in a local region, which is designed for the congested scenes. The proposed method achieves state-of-the-art performance on five datasets (ShanghaiTech, UCF CC 50, WorldEXPO'10, UCSD, and TRANCOS).
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http://dx.doi.org/10.1109/TIP.2020.3043122DOI Listing
December 2020

Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes.

Elife 2020 12 14;9. Epub 2020 Dec 14.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.

Endothelial cells (ECs) are widely heterogenous depending on tissue and vascular localization. Jambusaria et al. recently demonstrated that ECs in various tissues surprisingly possess mRNA signatures of their underlying parenchyma. The mechanism underlying this observation remains unexplained, and could include mRNA contamination during cell isolation, in vivo mRNA paracrine transfer from parenchymal cells to ECs, or cell-autonomous expression of these mRNAs in ECs. Here, we use a combination of bulk RNASeq, single-cell RNASeq datasets, in situ mRNA hybridization, and most importantly ATAC-Seq of FACS-isolated nuclei, to show that cardiac ECs actively express cardiomyocyte myofibril (CMF) genes and have open chromatin at CMF gene promoters. These open chromatin sites are enriched for sites targeted by cardiac transcription factors, and closed upon expansion of ECs in culture. Together, these data demonstrate unambiguously that the expression of CMF genes in ECs is cell-autonomous, and not simply a result of technical contamination or paracrine transfers of mRNAs, and indicate that local cues in the heart in vivo unexpectedly maintain fully open chromatin in ECs at genes previously thought limited to cardiomyocytes.
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http://dx.doi.org/10.7554/eLife.55730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758065PMC
December 2020
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