Publications by authors named "Jun Lin"

1,156 Publications

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Research on the Compound Optimization Method of the Electrical and Thermal Properties of SiC/EP Composite Insulating Material.

Polymers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing 102206, China.

In this paper, in order to improve the electrical and thermal properties of SiC/EP composites, the methods of compounding different crystalline SiC and micro-nano SiC particles are used to optimize them. Under different compound ratios, the thermal conductivity and breakdown voltage parameters of the composite material were investigated. It was found that for the SiC/EP composite materials of different crystal types of SiC, when the ratio of α and β silicon carbide is 1:1, the electrical performance of the composite material is the best, and the breakdown strength can be increased by more than 10% compared with the composite material filled with single crystal particles. For micro-nano compound SiC/EP composites, different total filling amounts of SiC correspond to different optimal ratios of micro/nano particles. At the optimal ratio, the introduction of nanoparticles can increase the breakdown strength of the composite material by more than 10%. Compared with the compound of different crystalline SiC, the advantage is that the introduction of a small amount of nanoparticles can play a strong role in enhancing the break-down field strength. For the filled composite materials, the thermal conductivity mainly depends on whether an effective heat conduction channel can be constructed. Through experiments and finite element simulation calculations, it is found that the filler shape and particle size have a greater impact on the thermal conductivity of the composite material, when the filler shape is rounder, the composite material can more effectively construct the heat conduction channel.
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http://dx.doi.org/10.3390/polym13193369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512577PMC
September 2021

Dual C(sp)-H Functionalization of Cyclic Ethers via Singlet Oxygen-Mediated Ring Opening and Ring Closing.

Org Lett 2021 Oct 11. Epub 2021 Oct 11.

Key Laboratory of Medicinal for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.

A metal-free dual C(sp)-H bond functionalization of saturated cyclic ethers via photooxidative singlet oxygen-mediated ring opening and ring closing has been developed, providing a method for generating hydrobenzofurans/pyrans/dioxins. Mechanistic studies have confirmed that ring-opening intermediates were effectively generated by singlet oxygen-mediated C(sp)-H activation and efficiently reacted with aldehydes and activated methylene compounds to form a wide array of products with high diastereoselectivities (up to >95:5 dr). This study is a rare example of α,β-dual C(sp)-H bond functionalization of ethers.
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http://dx.doi.org/10.1021/acs.orglett.1c03008DOI Listing
October 2021

Evaluation of Egg Yolk IgY Degradation in Chicken Gastrointestinal Tract.

Front Immunol 2021 21;12:746831. Epub 2021 Sep 21.

Department of Animal Science, The University of Tennessee, Knoxville, TN, United States.

Egg yolk antibody (immunoglobulin Y, IgY), due to its unique features (e.g., cost-effectiveness for mass production), is emerging as a promising passive immune agent and alternative to antibiotics to combat infectious diseases, particularly in livestock. Oral administration of egg yolk IgY is the most common and convenient route that has been extensively investigated for controlling enteric pathogens. However, the stability of egg yolk IgY in the gastrointestinal (GI) tract, a critical issue for the success of this approach, still has not been clearly elucidated. Our recent study showed instability of orally administered egg yolk IgY in chicken GI tract, as demonstrated by both and evidence. To better understand the magnitude and dynamics of instability of egg yolk IgY , in this study, we conducted comprehensive analyses by spiking hyperimmune egg yolk IgY in fresh GI contents collected from five broilers at each sampling age (2, 4, or 6 weeks). The pH in gizzard slightly increased with age from 2.4 to 3.0, while the pH in the small intestine was around 5.8. ELISA analysis indicated that a short time of treatment (30 or 60 min) of IgY with the gizzard contents from the chickens at 2, 4, and 6 weeks of age greatly reduced specific IgY titer by over 8, 6, and 5 log units, respectively, when compared with saline control. However, small intestine content only had a mild effect on egg yolk IgY, leading to 1 log unit of reduction in IgY titer upon 30 min of treatment. Consistent with these findings, SDS-PAGE and immunoblotting analyses provided direct evidence demonstrating that egg yolk IgY could be drastically degraded to undetectable level in gizzard content upon as short as 5 min of treatment; however, the IgY was only slightly degraded in small intestine content. Immunoblotting also showed that treatment of IgY with HCl (pH 3.0) for 60 min did not affect its integrity at all, further supporting the enzymatic degradation of IgY in gizzard. Collectively, egg yolk IgY could be substantially degraded in chicken gizzard, highly warranting the development of effective approaches, such as encapsulation, for the controlled release and protection of orally administered egg yolk IgY in livestock.
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http://dx.doi.org/10.3389/fimmu.2021.746831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490740PMC
September 2021

The effect of traumatic brain injury on bone healing from a novel exosome centered perspective in a mice model.

J Orthop Translat 2021 Sep 23;30:70-81. Epub 2021 Sep 23.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Background: In patients with traumatic brain injury (TBI) combined with long bone fracture, the fracture healing is always faster than that of patients with single fracture, which is characterized by more callus growth at the fracture site and even ectopic ossification. Exosomes are nanoscale membrane vesicles secreted by cells, which contain cell-specific proteins, miRNAs, and mRNAs.

Methods: In this study, we used exosomes as the entry point to explore the mechanism of brain trauma promoting fracture healing. We established a model of tibia fracture with TBI in mice to observe the callus growth and expression of osteogenic factors at the fracture site. Blood samples of model mice were further collected, exosomes in plasma were extracted by ultra-centrifugation method, and then identified and acted on osteoblasts cultured in vitro. The effects of exosomes on osteoblast differentiation at the cell, protein and gene levels were investigated by Western Blot and q-PCR, respectively. Furthermore, miRNA sequencing of exosomes was performed to identify a pattern of miRNAs that were present at increased or decreased levels.

Results: The results suggested that plasma exosomes after TBI had the ability to promote the proliferation and differentiation of osteoblasts, which might be due to the increased expression of osteoblast-related miRNA in exosomes. They were transmitted to the osteoblasts at the fracture site, so as to achieve the role of promoting osteogenic differentiation.

Conclusion: The TBI-derived exosomes may have potential applications for promoting fracture healing in future.

The Translational Potential Of This Article: Plasma exosomes early after TBI have the ability to promote osteoblast proliferation and differentiation. The mechanism may be achieved by miRNA in exosomes. Plasma exosomes may be used as breakthrough clinical treatment for delayed or non-union fractures.
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http://dx.doi.org/10.1016/j.jot.2021.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476897PMC
September 2021

Clinical value of laboratory indicators for predicting disease progression and death in patients with COVID-19: a retrospective cohort study.

BMJ Open 2021 10 1;11(10):e043790. Epub 2021 Oct 1.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China

Objectives: As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19.

Design: Retrospective cohort study.

Setting: Hospital-based study in China.

Participants: Adult patients with COVID-19 from December 15, 2019 to March 15, 2020.

End Point: Disease severity and mortality.

Methods: Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis.

Results: 29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05).

Conclusions: The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.
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http://dx.doi.org/10.1136/bmjopen-2020-043790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488281PMC
October 2021

Biodegradable Upconversion Nanoparticles Induce Pyroptosis for Cancer Immunotherapy.

Nano Lett 2021 10 30;21(19):8281-8289. Epub 2021 Sep 30.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

Pyroptosis, which is a mode of programmed cell death, has proven effective for cancer therapy. However, efficient pyroptosis inducers for tumor treatment are limited. This study proposes biodegradable KZrF:Yb/Er upconversion nanoparticles (ZrNPs) as pyroptosis inducers for cancer immunotherapy. ZrNPs, which are similar to ion reservoirs, can be dissolved inside cancer cells and release high amounts of K and [ZrF] ions, resulting a surge in intracellular osmolarity and homeostasis imbalance. This further induces an increase in reactive oxygen species (ROS), caspase-1 protein activation, gasdermin D (GSDMD) cleavage, and interleukin-1β (IL-1β) maturity, and results in cytolysis. In vivo tests confirm that ZrNPs-induced pyroptosis exhibits superior antitumor immunity activity confirmed by enhanced dendritic cells (DCs) maturity and frequency of effector-memory T cells, as well as observably inhibiting tumor growth and pulmonary metastasis. This work is believed to extend the biomedical applications of upconversion nanomaterials and deepen the understanding of intrinsic immunomodulatory activity of nanomaterials.
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http://dx.doi.org/10.1021/acs.nanolett.1c02790DOI Listing
October 2021

Admission of Patients With Obstructive Sleep Apnea Undergoing Ambulatory Surgery in Otolaryngology-Head and Neck Surgery.

Ann Otol Rhinol Laryngol 2021 Sep 30:34894211048783. Epub 2021 Sep 30.

Department of Otolaryngology-Head and Neck Surgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Objectives: Within Otolaryngology-Head and Neck Surgery (OHNS), obstructive sleep apnea (OSA) patients are frequently encountered. To implement policies and screening measures for admission of OSA patients undergoing ambulatory surgery, actual rates of admission must first be determined. We aimed to evaluate rates and reasons for admission of OSA patients after ambulatory OHNS surgery.

Methods: Retrospective chart review was undertaken of all OSA patients undergoing elective day-surgery OHNS procedures at a tertiary center from January 1, 2018 to December 31, 2019. The primary outcome measure was percentage of OSA patients admitted to hospital after ambulatory OHNS surgery. Secondary outcome measures included reasons for admission. American Society of Anesthesiologists (ASA) score, perioperative complications, and patient demographics were captured.

Results: There were 118 OSA patients, out of 1942 cases performed during the review period. Thirty-eight were excluded as the procedures were not considered ambulatory. The remaining 80 OSA patients were included for analysis, with an average age of 51.7, SD 13.8, and 30 (38%) females. The admission rate was 47.5% (38/80 patients). Admitted patients were older ( = .0061), and had higher ASA ( = .039). Indication for surgery or type of surgery did not differ among admitted and non-admitted patients. The majority of patients, 97% (37/38 patients), were admitted for post-operative monitoring.

Conclusion: More than half of OSA patients did not require admission to hospital after ambulatory OHNS surgery, unaffected by indications for surgery or type of surgery. Higher ASA score and older age were found in admitted as compared to non-admitted patients.
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http://dx.doi.org/10.1177/00034894211048783DOI Listing
September 2021

Single-cell analysis of COVID-19, sepsis, and HIV infection reveals hyperinflammatory and immunosuppressive signatures in monocytes.

Cell Rep 2021 10 17;37(1):109793. Epub 2021 Sep 17.

Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230021 Hefei, Anhui, China; CAS Center for Excellence in Molecular Cell Sciences, the CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, 230027 Hefei, Anhui, China; School of Data Science, University of Science and Technology of China, 230026 Hefei, Anhui, China. Electronic address:

The mortality risk of coronavirus disease 2019 (COVID-19) patients has been linked to the cytokine storm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the inflammatory responses shared between COVID-19 and other infectious diseases that feature cytokine storms may therefore help in developing improved therapeutic strategies. Here, we use integrative analysis of single-cell transcriptomes to characterize the inflammatory signatures of peripheral blood mononuclear cells from patients with COVID-19, sepsis, and HIV infection. We identify ten hyperinflammatory cell subtypes in which monocytes are the main contributors to the transcriptional differences in these infections. Monocytes from COVID-19 patients share hyperinflammatory signatures with HIV infection and immunosuppressive signatures with sepsis. Finally, we construct a "three-stage" model of heterogeneity among COVID-19 patients, related to the hyperinflammatory and immunosuppressive signatures in monocytes. Our study thus reveals cellular and molecular insights about inflammatory responses to SARS-CoV-2 infection and provides therapeutic guidance to improve treatments for subsets of COVID-19 patients.
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http://dx.doi.org/10.1016/j.celrep.2021.109793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445774PMC
October 2021

Downregulation of activating transcription factor 4 attenuates lysophosphatidycholine-induced inflammation via the NF-κB pathway.

Eur J Pharmacol 2021 Sep 25;911:174457. Epub 2021 Sep 25.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, China. Electronic address:

Lysophosphatidycholine (LPC) is the main active component in oxidized low-density lipoprotein (ox-LDL). The pathological function of ox-LDL has been broadly studied in atherosclerosis. However, the specific relationship between LPC-induced unfolded protein response (UPR) and inflammation in human umbilical vein endothelial cells (HUVECs) remains elusive. In this study, we found elevated serum levels of LPC in atherosclerotic patients. LPC stimulation resulted in elevated secretion of interleukin (IL)-6 and IL-8 in HUVECs, accompanied with the activation of ER stress and NF-κB pathway. Additionally, suppression of ER stress by 4-phenylbutric acid (4-PBA), an ER stress inhibitor, alleviated the activation of the NF-κB pathway and secretion of inflammatory factors. Moreover, activating transcription factor 4 (ATF4) silencing inhibited the transcription and secretion of IL-6 and IL-8, and suppressed the adhesion of THP-1 cells to HUVECs. Activation of the NF-κB pathway and expression of its upstream factors, including Toll like receptor 4 and cellular inhibitor of apoptosis, were also inhibited by ATF4 silencing. The present findings suggest that suppression of UPR alleviates LPC-induced HUVECs inflammation by inhibition of NF-κB pathway, and indicate ATF4 as a potential target for the treatment of atherosclerosis.
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http://dx.doi.org/10.1016/j.ejphar.2021.174457DOI Listing
September 2021

Analysis of the Electrical and Thermal Properties for Magnetic FeO-Coated SiC-Filled Epoxy Composites.

Polymers (Basel) 2021 Sep 7;13(18). Epub 2021 Sep 7.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing 102206, China.

Orderly arranged Silicon carbide (SiC)/epoxy (EP) composites were fabricated. SiC was made magnetically responsive by decorating the surface with iron oxide (FeO) nanoparticles. Three treatment methods, including without magnetization, pre-magnetization and curing magnetization, were used to prepare SiC/EP composites with different filler distributions. Compared with unmodified SiC, magnetic SiC with core-shell structure was conducive to improve the breakdown strength of SiC/EP composites and the maximum enhancement rate was 20.86%. Among the three treatment methods, SiC/EP composites prepared in the curing-magnetization case had better comprehensive properties. Under the action of magnetic field, magnetic SiC were orderly oriented along the direction of an external field, thereby forming SiC chains. The magnetic alignment of SiC restricted the movement of EP macromolecules or polar groups to some extent, resulting in the decrease in the dielectric constant and dielectric loss. The SiC chains are equivalent to heat flow channels, which can improve the heat transfer efficiency, and the maximum improvement rate was 23.6%. The results prove that the orderly arrangement of SiC had a favorable effect on dielectric properties and thermal conductivity of SiC/EP composites. For future applications, the orderly arranged SiC/EP composites have potential for fabricating insulation materials in the power electronic device packaging field.
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http://dx.doi.org/10.3390/polym13183028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471609PMC
September 2021

A radical-mediated multicomponent cascade reaction for the synthesis of azide-biindole derivatives.

Chem Commun (Camb) 2021 Sep 23;57(76):9696-9699. Epub 2021 Sep 23.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China.

A radical-mediated, one-pot, multicomponent cascade reaction was developed for the synthesis of azide-biindole derivatives. Mechanistic studies demonstrated that the nitrogen-centred free radical was formed by the reaction of heterocyclic N-H with Cu and PIFA and initiated the cascade reaction with indole to obtain the biindole intermediate. The biindole intermediate then reacted with sodium azide in the presence of Cu catalyst and PIFA to form the final products. This methodology may be useful for constructing other azido heterocycles.
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http://dx.doi.org/10.1039/d1cc03853bDOI Listing
September 2021

Hepatokine Pregnancy Zone Protein Governs the Diet-Induced Thermogenesis Through Activating Brown Adipose Tissue.

Adv Sci (Weinh) 2021 Sep 13:e2101991. Epub 2021 Sep 13.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter-organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet-induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose-regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK-ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.
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http://dx.doi.org/10.1002/advs.202101991DOI Listing
September 2021

Discovery of novel BTK PROTACs for B-Cell lymphomas.

Eur J Med Chem 2021 Sep 2;225:113820. Epub 2021 Sep 2.

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China. Electronic address:

Bruton's tyrosine kinase (BTK) is a key drug target for B-cell related malignancies. Irreversible covalent BTK inhibitors have been approved for the treatment of B-cell malignancies, yet BTK C481S mutation at the covalent binding site has caused drug-resistance of BTK covalent binding inhibitors. The proteolysis targeting chimera (PROTAC) technology increases the sensitivity to drug-resistant targets compared to classic inhibitors, which provides a new strategy for mutant BTK related B-cell malignancies. ARQ531, a reversible non-covalent BTK inhibitor that inhibits wild type (WT) and mutated BTK with high selectivity, could be an ideal warhead for PROTACs targeting the mutant BTK. Herein, we designed a novel series of PROTACs using the selective non-covalent BTK inhibitor ARQ531 as warhead, with the goal of improving the degradation of both wild-type and C481S mutant BTKs, and increasing the selectivity of BTK over other kinases. This effort will provide some basis for further preclinical study of BTK PROTACs as a novel strategy for treatment of B-cell lymphomas.
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http://dx.doi.org/10.1016/j.ejmech.2021.113820DOI Listing
September 2021

Multifunctional carbon monoxide nanogenerator as immunogenic cell death drugs with enhanced antitumor immunity and antimetastatic effect.

Biomaterials 2021 10 1;277:121120. Epub 2021 Sep 1.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; University of Science and Technology of China, Hefei, 230026, China. Electronic address:

The limited effect of immune checkpoint blockade (ICB) immunotherapy is subjected to the immuno-suppressive tumor microenvironment (TME). It is still a challenge to reverse the immune-suppressive state in clinical cancer therapy. Immunogenic cell death (ICD) is a way for inducing the therapeutical tumor immune system. In this work, carbon monoxide (CO) gas therapy is used to boost antitumor immunity for tumor control, metastasis and recurrence prevention. Briefly, [email protected]@F127 (CCAZF) is proposed to integrate gas therapy and immunotherapy into a photocatalytic nanogenerator for overcoming the limitations of monotherapy. CCAZF exhibits a highly effective light-controllable release behavior of CO, which gradually aggravates the oxidative stress in tumor cells to induce ICD. With the induction of ICD, CO therapy enhances immune responses and enables efficient immune cells activated. When combined with ICB, CCAZF displays an enhanced immune effect, which mediates the regression of primary and distal tumors. This strategy of in-situ photocatalytic CO therapy furthest avoids the toxicity from CO leakage and provides a new method to design novel ICD inducers.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121120DOI Listing
October 2021

Contrast-enhanced ultrasonography promotes differential diagnosis of ureteral neoplasms.

Br J Radiol 2021 Sep 3:20210078. Epub 2021 Sep 3.

Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To compare the diagnostic value of contrast-enhanced ultrasonography (CEUS) with baseline ultrasound (B-US) in ureteral neoplasms.

Methods: Retrospective analysis, comprising clinical presentation, image appearances, and diagnostic results on B-ultrasound and CEUS, considering pathological result as a gold-standard, was conducted on the clinical information of 39 patients with ureteral neoplasms. CT urography was used to detect and confirm the presence of ureteral neoplasms. Both B-ultrasound and CEUS investigations of those 39 patients under study were performed by a senior radiologist.

Results: Pathological outcomes established 27 ureteral malignancies and 12 ureteral benignancies. Ureteral malignancies were observed to occur in older patients than benignancies ( = 0.002). Only the morphological indicator of the ureteric wall on B-ultrasound was different in ureteral malignancies and benignancies ( = 0.030). Tumors with hyperenhancement, larger width, and hyperenhanced ureteric wall were easily diagnosed as malignant on CEUS, whereas iso-/hypoenhanced, narrower, and iso-/hypoenhanced ureteric wall indicated benign tumors. Moreover, the lesion widths, enhanced morphologies of the ureteric wall, and the ureteral wall's linear boundaries on CEUS were different between high- and low-stage ureteral urothelial carcinomas ( = 0.012, 0.002, 0.001, respectively).

Conclusion: The display of microvessels in ureteral neoplasms was significantly enhanced by CEUS, thus contributing to the differential diagnosis of ureteral neoplasms while assisting the staging of ureteral urothelial carcinoma.

Advances In Knowledge: The imaging features of different ureteral neoplasms on CEUS were analyzed in this study. The diagnostic performances of CEUS and B-ultrasound in ureteral urothelial carcinomas were also explored.
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http://dx.doi.org/10.1259/bjr.20210078DOI Listing
September 2021

Lanthanide-Based Peptide-Directed Visible/Near-Infrared Imaging and Inhibition of LMP1.

JACS Au 2021 Jul 20;1(7):1034-1043. Epub 2021 Jun 20.

Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.

A lanthanide-based peptide-directed bioprobe (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that can effectively inactivate the oncogenic cellular pathway nuclear factor κB (NF-κB) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, and were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by is also demonstrated.
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http://dx.doi.org/10.1021/jacsau.1c00187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395644PMC
July 2021

Automatic detection of oral cancer in smartphone-based images using deep learning for early diagnosis.

J Biomed Opt 2021 08;26(8)

Zhejiang University School of Medicine, First Affiliated Hospital, Department of Stomatology, Hangzh, China.

Significance: Oral cancer is a quite common global health issue. Early diagnosis of cancerous and potentially malignant disorders in the oral cavity would significantly increase the survival rate of oral cancer. Previously reported smartphone-based images detection methods for oral cancer mainly focus on demonstrating the effectiveness of their methodology, yet it still lacks systematic study on how to improve the diagnosis accuracy on oral disease using hand-held smartphone photographic images.

Aim: We present an effective smartphone-based imaging diagnosis method, powered by a deep learning algorithm, to address the challenges of automatic detection of oral diseases.

Approach: We conducted a retrospective study. First, a simple yet effective centered rule image-capturing approach was proposed for collecting oral cavity images. Then, based on this method, a medium-sized oral dataset with five categories of diseases was created, and a resampling method was presented to alleviate the effect of image variability from hand-held smartphone cameras. Finally, a recent deep learning network (HRNet) was introduced to evaluate the performance of our method for oral cancer detection.

Results: The performance of the proposed method achieved a sensitivity of 83.0%, specificity of 96.6%, precision of 84.3%, and F1 of 83.6% on 455 test images. The proposed "center positioning" method was about 8% higher than that of a simulated "random positioning" method in terms of F1 score, the resampling method had additional 6% of performance improvement, and the introduced HRNet achieved slightly better performance than VGG16, ResNet50, and DenseNet169, with respect to the metrics of sensitivity, specificity, precision, and F1.

Conclusions: Capturing oral images centered on the lesion, resampling the cases in training set, and using the HRNet can effectively improve the performance of deep learning algorithm on oral cancer detection. The smartphone-based imaging with deep learning method has good potential for primary oral cancer diagnosis.
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http://dx.doi.org/10.1117/1.JBO.26.8.086007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397787PMC
August 2021

Preselectable Optical Fingerprints of Heterogeneous Upconversion Nanoparticles.

Nano Lett 2021 09 18;21(18):7659-7668. Epub 2021 Aug 18.

Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.

The control in optical uniformity of single nanoparticles and tuning their diversity in multiple dimensions, dot to dot, holds the key to unlocking nanoscale applications. Here we report that the entire lifetime profile of the single upconversion nanoparticle (τ profile) can be resolved by confocal, wide-field, and super-resolution microscopy techniques. The advances in both spatial and temporal resolutions push the limit of optical multiplexing from microscale to nanoscale. We further demonstrate that the time-domain optical fingerprints can be created by utilizing nanophotonic upconversion schemes, including interfacial energy migration, concentration dependency, energy transfer, and isolation of surface quenchers. We exemplify that three multiple dimensions, including the excitation wavelength, emission color, and τ profile, can be built into the nanoscale derivative τ-dots. Creating a vast library of individually preselectable nanotags opens up a new horizon for diverse applications, spanning from sub-diffraction-limit data storage to high-throughput single-molecule digital assays and super-resolution imaging.
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http://dx.doi.org/10.1021/acs.nanolett.1c02404DOI Listing
September 2021

Plexiform fibromyxoma: a clinicopathological and immunohistochemical analysis of two cases with a literature review.

J Int Med Res 2021 Aug;49(8):3000605211027878

Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China.

Objective: This article aimed to study the clinicopathological features, immunophenotypes, and differential diagnoses of plexiform fibromyxoma (PF).

Methods: We searched clinical and pathology databases of our hospital for patients with histologically confirmed PF from 2007 to 2020 and reviewed the relevant English and Chinese language literature.

Results: Two cases of PF were identified, a 67-year-old woman and a 23-year-old man. Both patients presented with melena and anemia and underwent partial gastrectomy. Histologically, the tumors exhibited a plexiform growth pattern in the gastric submucosa and the presence of bland-looking spindle cells in the fibromyxoid stroma with the formation of small blood vessels. Immunohistochemically, the two cases were strongly positive for vimentin, smooth muscle actin, and muscle-specific actin and negative for CD117, discovered on gastrointestinal stromal tumors protein 1, CD34, CD10, S100, desmin, H-caldesmon, estrogen receptor, progesterone receptor, β-catenin, and cytokeratin.

Conclusions: PF is a rare mesenchymal tumor of the stomach that can be distinguished from other gastrointestinal mesenchymal tumors based on its distinctive morphology and immunophenotype.
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http://dx.doi.org/10.1177/03000605211027878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358512PMC
August 2021

[Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Aug;29(4):1209-1215

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020,China E-mail:

Objective: To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) .

Methods: Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression.

Results: Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ:36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (|FLC-κ- FLC-λ|) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range.

Conclusion: Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.04.029DOI Listing
August 2021

Anchoring Water Soluble Phosphotungstic Acid by Hybrid Fillers to Construct Three-Dimensional Proton Transport Networks.

Membranes (Basel) 2021 Jul 15;11(7). Epub 2021 Jul 15.

State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing 102206, China.

Phosphotungstic acid (HPW)-filled composite proton exchange membranes possess high proton conductivity under low relative humidity (RH). However, the leaching of HPW limits their wide application. Herein, we propose a novel approach for anchoring water soluble phosphotungstic acid (HPW) by polydopamine (PDA) coated graphene oxide and halloysite nanotubes (DGO and DHNTs) in order to construct hybrid three-dimensional proton transport networks in a sulfonated poly(ether ether ketone) (SPEEK) membrane. The introduction of PDA on the surfaces of the hybrid fillers could provide hydroxyl groups and secondary amine groups to anchor HPW, resulting in the uniform dispersion of HPW in the SPEEK matrix. The SPEEK/DGO/DHNTs/HPW (90/5/5/60) composite membrane exhibited higher water uptake and much better conductivity than the SPEEK membrane at low relative humidity. The best conductivity reached wass 0.062 S cm for the composite membrane, which is quite stable during the water immersion test.
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http://dx.doi.org/10.3390/membranes11070536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303771PMC
July 2021

Dry Exfoliation of Large-Area 2D Monolayer and Heterostructure Arrays.

ACS Nano 2021 Aug 6. Epub 2021 Aug 6.

Key Laboratory for Micro-Nano Optoelectronic Devices of Ministry of Education, School of Physics and Electronics, Hunan University, Changsha 410082, China.

Two-dimensional (2D) semiconductors have attracted considerable attention in recent years. However, to date, there is still no effective approach to produce large-scale monolayers while retaining their intrinsic properties. Here, we report a simple mechanical exfoliation method to produce large-scale and high-quality 2D semiconductors, by designing an atomically flat Au-mesh film as the peeling tape. Using our prefabricated mesh tape, the limited contact region (between the 2D crystal and Au) could provide enough adhesion to mechanically exfoliate uniform 2D monolayers, and the noncontact region (between the mesh holes and monolayers) ensures weak interaction to mechanically release the 2D monolayers on desired substrates. Together, we demonstrate a scalable method to dry exfoliate various 2D monolayer arrays onto different substrates without involving any solutions or contaminations, representing the optimization between material yield, scalability, and quality. Furthermore, detailed optical and electrical characterizations are conducted to confirm their intrinsic quality. With the ability to mechanically exfoliate various 2D arrays and further restacking them, we have demonstrated large-scale van der Waals heterostructure arrays through layer-to-layer assembling. Our study offers a simple and scalable method for dry exfoliating 2D monolayer and heterostructure arrays with intrinsic material quality, which could be crucial to accelerate fundamental investigations as well as practical applications of proof-of-concepts devices.
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http://dx.doi.org/10.1021/acsnano.1c05734DOI Listing
August 2021

A systematic review and meta-analysis: pulmonary mycosis pathogen distribution.

Ann Palliat Med 2021 Jul;10(7):7919-7932

Emergency Department, The Affiliated Urology and Nephrology Hospital of Ningbo University (Ningbo Yinzhou No. 2 Hospital), Ningbo, China.

Background: This study sought to systematically evaluate the distribution characteristics and high-risk factors of pulmonary mycosis pathogens, and provide evidence for the clinical treatment and prognosis of patients with pulmonary mycosis.

Methods: The Embase, Ovid, PubMed, Medline, and Springer databases were searched to find publications on the distribution characteristics and high-risk factors of pulmonary mycosis pathogens that had been published between the establishment of the databases and April 1, 2021. The Cochrane Handbook 5.0.2 was used to evaluate the risk of bias of the articles included in this study, and Review Manager 5.3 was used to conduct a meta-analysis of the included articles.

Results: Eleven articles were included in this study, comprising 6,415 subjects. The meta-analysis results showed that pathogen infection significantly increased the mortality of patients [MD =2.67; 95% confidence interval (CI): (1.52, 4.68); Z=3.43; P=0.0006]. Patient age was significantly correlated with the incidence of pulmonary mycosis [MD =1.21; 95% CI: (0.78, 1.86); Z=0.84; P=0.40]. The use of antibiotics was significantly correlated to the incidence of pulmonary mycosis [MD =1.41; 95% CI: (1.15, 1.72); Z=3.30; P=0.001]. Glucocorticoid use was significantly correlated to the incidence of pulmonary mycosis [MD =1.81; 95% CI: (1.13, 2.91); Z=2.45; P=0.01]. However, gender had no obvious correlation with the incidence of pulmonary mycosis [MD =1.21; 95% CI: (0.78, 1.86); Z=0.84; P=0.40]. Further, no correlation was found between smoking history and the incidence of pulmonary mycosis [MD =0.86; 95% CI: (0.51, 1.45); Z=0.57; P=0.57].

Discussion: The main types of bacterial infections in patients with pulmonary mycosis were Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, Candida albicans, and Helicobacter pylori. In addition to the lungs, pathogens were found to be distributed in the intestines, urinary tract, and digestive tract. Additionally, patient age, antibiotic use, and glucocorticoid use increased the incidence of pulmonary mycosis. Thus, these factors should be paid attention to in the clinical treatment of patients with pulmonary mycosis.
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http://dx.doi.org/10.21037/apm-21-1388DOI Listing
July 2021

Correction: SARS-CoV-2-specific immune response in COVID-19 convalescent individuals.

Signal Transduct Target Ther 2021 Jul 30;6(1):293. Epub 2021 Jul 30.

Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.

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http://dx.doi.org/10.1038/s41392-021-00697-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323081PMC
July 2021

Intestinal hypoxia-inducible factor 2α regulates lactate levels to shape the gut microbiome and alter thermogenesis.

Cell Metab 2021 Oct 29;33(10):1988-2003.e7. Epub 2021 Jul 29.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science (Peking University), Ministry of Education, Beijing, China; Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing, China. Electronic address:

Accumulating evidence suggests that the gut microbiota regulates obesity through metabolite-host interactions. However, the mechanisms underlying such interactions have been unclear. Here, we found that intestinal hypoxia-inducible factor 2α (HIF-2α) positively regulates gut lactate by controlling the expression of intestinal Ldha. Intestine-specific HIF-2α ablation in mice resulted in lower lactate levels, and less Bacteroides vulgatus and greater Ruminococcus torques abundance, respectively. Together, these changes resulted in elevated taurine-conjugated cholic acid (TCA) and deoxycholic acid (DCA) levels and activation of the adipose G-protein-coupled bile acid receptor, GPBAR1 (TGR5). This activation upregulated expression of uncoupling protein (UCP) 1 and mitochondrial creatine kinase (CKMT) 2, resulting in elevation of white adipose tissue thermogenesis. Administration of TCA and DCA mirrored these phenotypes, and colonization with B. vulgatus and R. torques inhibited and induced thermogenesis, respectively. This work deepens our understanding of how host genes regulate the microbiome and provides novel strategies for alleviating obesity.
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http://dx.doi.org/10.1016/j.cmet.2021.07.007DOI Listing
October 2021

A Robust Narrow Bandgap Vanadium Tetrasulfide Sonosensitizer Optimized by Charge Separation Engineering for Enhanced Sonodynamic Cancer Therapy.

Adv Mater 2021 Sep 23;33(36):e2101467. Epub 2021 Jul 23.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

The development and optimization of sonosensitizers for elevating intratumoral reactive oxygen species (ROS) are definitely appealing in current sonodynamic therapy (SDT). Given this, branched vanadium tetrasulfide (VS ) nanodendrites with a narrower bandgap (compared with the most extensively explored sonosensitizers) are presented as a new source of sonosensitizer, which allows a more effortless separation of sono-triggered electron-hole pairs for ROS generation. Specifically, platinum (Pt) nanoparticles and endogenous high levels of glutathione (GSH) are rationally engineered to further optimize its sono-sensitized performance. As cocatalyst, Pt is conducive to trapping electrons, whereas GSH, as a natural hole-scavenger, tends to capture holes. Compared with the pristine VS sonosensitizer, the GSH-Pt-VS nanocomposite can greatly prolong the lifetime of the charge and confer a highly efficacious ROS production activity. Furthermore, such nanoplatforms are capable of reshaping tumor microenvironments to realize ROS overproduction, contributed by overcoming tumor hypoxia to improve SDT-triggered singlet oxygen production, catalyzing endogenic hydrogen peroxide into destructive hydroxyl radicals for chemodynamic therapy, and depleting GSH to amplify intratumoral oxidative stress. All these combined effects result in a significantly efficient tumor suppression outcome. This study enriches sonosensitizer research and proves that sonosensitizers can be rationally optimized by charge separation engineering strategy.
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http://dx.doi.org/10.1002/adma.202101467DOI Listing
September 2021

Manganese oxide nanomaterials boost cancer immunotherapy.

J Mater Chem B 2021 Sep 15;9(35):7117-7131. Epub 2021 Sep 15.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

Immunotherapy, a strategy that leverages the host immune function to fight against cancer, plays an increasingly important role in clinical tumor therapy. In spite of the great success achieved in not only clinical treatment but also basic research, cancer immunotherapy still faces many huge challenges. Manganese oxide nanomaterials (MONs), as ideal tumor microenvironment (TME)-responsive biomaterials, are able to dramatically elicit anti-tumor immune responses in multiple ways, indicating great prospects for immunotherapy. In this review, on the basis of different mechanisms to boost immunotherapy, major highlighted topics are presented, covering adjusting an immunosuppressive TME by generating O (like O-sensitized photodynamic therapy (PDT), programmed cell death ligand-1 (PD-L1) expression downregulation, reprogramming tumor-associated macrophages (TAMs), and restraining tumor angiogenesis and lactic acid exhaustion), inducing immunogenic cell death (ICD), photothermal therapy (PTT) induction, activating the stimulator of interferon gene (STING) pathway and immunoadjuvants for nanovaccines. We hope that this review will provide holistic understanding about MONs and their application in cancer immunotherapy, and thus pave the way to the translation from bench to bedside in the future.
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http://dx.doi.org/10.1039/d1tb01001hDOI Listing
September 2021

Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway.

Reprod Biol Endocrinol 2021 Jul 15;19(1):111. Epub 2021 Jul 15.

Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People's Republic of China.

Background: Endometriosis is a benign gynecological disease that shares some characteristics with malignant tumors and affects approximately 10% of women of reproductive age. Endometrioma refers to endometriosis that appears in the ovary. Metallopanstimulin-1 (MPS-1) is a component of the 40S subunit of ribosomes that has extra-ribosomal functions that contribute to the development of diseases. This study aimed to explore the expression pattern and role of MPS-1 in endometrioma development.

Methods: Quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay were used to determine the expression of MPS-1 in patients with endometrioma. Following the successful knockdown of MPS-1 by siRNA, CCK-8 assays, flow cytometry, and transwell assays were performed to detect ectopic endometrial stromal cells (EcESCs) proliferation, the rate of apoptosis, and cell cycle, migration, and invasion, respectively. Western blotting was used to explore the effect of MPS-1 knockdown on protein levels in the NF-κB signaling pathway.

Results: The expression of MPS-1 was significantly higher in endometrioma and the serum of endometrioma patients than in the patients without endometriosis. In addition, the downregulation of MPS-1 expression inhibited EcESCs proliferation, migration, and invasion. This downregulation led to the arrest of the EcESCs cycle in the G0/G1 phase and apoptosis and depressed the NF-κB signaling pathway.

Conclusion: MPS-1 can regulate EcESCs proliferation, motility, invasion, apoptosis, and cell cycle via the NF-κB signaling pathway in endometrioma. This may contribute to the formation or development of endometriotic foci. This study suggests the potential role of MPS-1 in the pathogenesis of endometriosis and enabled further research into the use of MPS-1 in the clinical diagnosis of endometrioma.
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http://dx.doi.org/10.1186/s12958-021-00796-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281640PMC
July 2021

A Robust Oxygen-Carrying Hemoglobin-Based Natural Sonosensitizer for Sonodynamic Cancer Therapy.

Nano Lett 2021 07 13;21(14):6042-6050. Epub 2021 Jul 13.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

The development of novel sonosensitizers with outstanding reactive oxygen (ROS) generation capacity and great biocompatibility poses a significant challenge for the clinical practice of sonodynamic therapy (SDT). In this work, hemoglobin (Hb) with natural metalloporphyrin was first shown to possess great potential as a sonosensitizer. Compared with traditional organic sonosensitizers, Hb had satisfactory sono-sensitizing efficiency because four the porphyrin molecules were separated by four polypeptide chains. This effectively avoided the problem of low ROS quantum yield caused by the stacking of hydrophobic porphyrins. Meanwhile, Hb is an efficient and safe oxygen carrier that may release O at hypoxic tumors site, which improved tumor oxygenation and subsequently enhanced SDT efficacy. Therefore, Hb was integrated with zeolitic imidazolate framework 8 (ZIF-8) to form a nanoplatform that demonstrated a potent suppression effect on deep-seated tumors under ultrasound irradiation.
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http://dx.doi.org/10.1021/acs.nanolett.1c01220DOI Listing
July 2021
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