Publications by authors named "Xin Pan"

336 Publications

Carbon ion radiotherapy for recurrent calf myxoid liposarcoma: a case report.

J Int Med Res 2021 Apr;49(4):3000605211009701

Heavy Ion Radiotherapy Department of Cancer Hospital, Wuwei, Gansu, China.

Liposarcoma (LPS) is the most common soft tissue sarcoma. Myxoid LPS (MLPS) is the second most common subtype of LPS and accounts for 25% to 50% of all LPSs. Like most other soft tissue sarcomas, the mainstay of treatment for LPS is inevitably surgery. Multidisciplinary approaches, including surgery, chemotherapy, and radiotherapy, have been successful in the treatment of LPS during the last three decades. Even so, recurrence of LPS remains challenging. Carbon ion beams produce increased energy deposition at the end of their range to form a Bragg peak while minimizing irradiation damage to surrounding tissues, which facilitates more precise dosage and localization than that achieved with photon beams. Furthermore, carbon ion beams have high relative biologic effectiveness. We herein describe a patient who developed recurrent MLPS in the right calf after two surgeries and underwent carbon ion radiotherapy (CIRT), achieving complete disappearance of the tumor. The patient developed Grade 1 radiation dermatitis 30 days after CIRT, but no other acute toxicities were observed. The tumor had completely disappeared by 120 days after CIRT, and the patient remained disease-free for 27 months after CIRT. The CARE guidelines were followed in the reporting of this case.
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http://dx.doi.org/10.1177/03000605211009701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074479PMC
April 2021

Functionalised molybdenum disulfide nanosheets for co-delivery of doxorubicin and siRNA for combined chemo/gene/photothermal therapy on multidrug-resistant cancer.

J Pharm Pharmacol 2021 Apr 21. Epub 2021 Apr 21.

Pharmaceutical College, Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi, China.

Objective: Molybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer.

Methods: MoS2 nanosheets were prepared by a hydrothermal reaction and modified. Afterward, the nanocarrier was characterised. In vitro cytotoxicity of the drug delivery systems on human breast adenocarcinoma cell lines was assessed.

Key Findings: The nanocarrier was a flake-like structure with a uniform hydrodynamic diameter and possessing good colloidal stability. The nanocarrier showed the capacity to be deployed for co-delivery of Doxorubicin (DOX) and siRNA. The release of DOX could be triggered and enhanced by pH and application of near-infrared (NIR) laser. The nanocarrier had a good photothermic response and stability. The nanocarrier had little effect on the cells and exhibited good biocompatibility. Measurement of the therapeutic efficacy showed that synergistic therapy combining chemo-, gene- and photothermal therapy deploying this drug delivery system will achieve a better anticancer effect on drug-resistant cancer cells than DOX alone.

Conclusions: Our results suggest that this drug delivery system has potential application in the therapeutic strategy for drug-resistant cancer.
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http://dx.doi.org/10.1093/jpp/rgab059DOI Listing
April 2021

Identifying potential biomarkers of nonalcoholic fatty liver disease via genome-wide analysis of copy number variation.

BMC Gastroenterol 2021 Apr 14;21(1):171. Epub 2021 Apr 14.

Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.

Background: The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population.

Methods: Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized.

Results: A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD.

Conclusions: This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.
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http://dx.doi.org/10.1186/s12876-021-01750-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045212PMC
April 2021

Intravertebral insertion of interbody fusion cage via transpedicular approach for the treatment of stage III Kümmell disease: a technical note and case presentation.

Br J Neurosurg 2021 Apr 10:1-6. Epub 2021 Apr 10.

Department of Orthopaedics, Shandong University Qilu Hospital, Jinan, People's Republic of China.

Background: Kümmell disease usually occurs in the elderly osteoporosis population and develops gradually into symptomatic, progressive kyphosis of the spine. However, current surgical methods to deal with stage III Kümmell disease are less satisfying. The objective of this study was to describe a less invasive technique for treating stage III Kümmell disease.

Technique: A less invasive technique of intravertebral insertion of interbody fusion cage via transpedicular approach with posterior spine stabilization was applied to treat stage III Kümmell disease.

Results: This study details a modified technique applied in a patient with stage III Kümmell disease, showing significant improvement in pain relief, anterior column height recovery, and kyphotic angle correction. And no complications were reported during our follow-up.

Conclusions: Intravertebral insertion of interbody fusion cage via transpedicular approach provides advantages of acceptable correction of kyphosis, bony fusion, minimal invasion. Thus, our method was a good alternative choice for stage III Kümmell disease.
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http://dx.doi.org/10.1080/02688697.2021.1892590DOI Listing
April 2021

The Fecal and Serum Metabolomics of Giant Pandas Based on Untargeted Metabolomics.

Zoolog Sci 2021 Apr;38(2):179-186

College of Resources, Sichuan Agricultural University, Chengdu, Sichuan 611130, China,

Little is comprehensively known or understood about giant panda fecal and serum metabolites, which could serve as important indicators of the physiological metabolism of giant pandas. Therefore, we determined the contents of fecal and serum metabolites of giant pandas based on an untargeted metabolome. Four hundred and 955 metabolites were detected in the feces and serum of giant panda, respectively. Glycerophospholipid and choline metabolism were the main metabolic pathways in feces and serum. A significant correlation between the gut microbiota and fecal metabolites was found ( < 0.01). Fecal metabolites were not greatly affected by the age or gender of giant pandas, but serum metabolites were significantly affected by age and gender. The majority of different metabolites caused by age were higher in serum of younger giant pandas, including fatty acids, lipids, metabolites of bile acids, and intermediate products of vitamin D3. The majority of different metabolites caused by gender included fatty acids, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE). A separate feeding diet should be considered according to different ages and genders of giant panda. Therefore, our results could provide helpful suggestions to further protect captive giant pandas.
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http://dx.doi.org/10.2108/zs200106DOI Listing
April 2021

Modular Design of Membrane-Active Antibiotics: From Macromolecular Antimicrobials to Small Scorpionlike Peptidomimetics.

J Med Chem 2021 Apr 1. Epub 2021 Apr 1.

Department of Chemistry, University of South Florida, Tampa, Florida 33620, United States.

Infections caused by multidrug-resistant bacteria have emerged in recent decades, leading to escalating interest in host defense peptides (HDPs) to reverse this dangerous trend. Inspired by the modular design in bioengineering, herein we report a new class of small amphiphilic scorpionlike peptidomimetics based on this strategy. These HDP mimics show potent antimicrobial activity against both Gram-positive and Gram-negative bacteria without drug resistance but with a high therapeutic index. The membrane-compromising action mode was suggested to be their potential bactericidal mechanism. Pharmacodynamic experiments were conducted using a murine abscess model of methicillin-resistant (MRSA) infections. The lead compound showed impressive in vivo therapeutic efficacy with ∼99.998% (4.7log) reduction in skin MRSA burden, a significantly higher bactericidal efficiency than ciprofloxacin, and good biocompatibility. These results highlight the potential of these HDP mimics as novel antibiotic therapeutics.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00312DOI Listing
April 2021

MicroRNA-1182 and let-7a exert synergistic inhibition on invasion, migration and autophagy of cholangiocarcinoma cells through down-regulation of NUAK1.

Cancer Cell Int 2021 Mar 9;21(1):161. Epub 2021 Mar 9.

Interventional Department, The Fourth Affiliated Hospital of China Medical University, No. 4, Chongshan East Road, Huanggu District, Shenyang, 110032, Liaoning, People's Republic of China.

Background: Cholangiocarcinoma (CCA) is the second most common primary liver malignancy worldwide. Several microRNAs (miRNAs) have been implicated as potential tumor suppressors in CCA. This study aims to explore the potential effects of miR-1182 and let-7a on CCA development.

Methods: Bioinformatics analysis was conducted to screen differentially expressed genes in CCA, Western blot analysis detected NUAK1 protein expression and RT-qPCR detected miR-1182, let-7a and NUAK1 expression in CCA tissues and cell lines. Dual luciferase reporter gene assay and RIP were applied to validate the relationship between miR-1182 and NUAK1 as well as between let-7a and NUAK1. Functional experiment was conducted to investigate the role of miR-1182, let-7a and NUAK1 in cell migration, proliferation and autophagy. Then, the CCA cells that received various treatments were implanted to mice to establish animal model, followed by tumor observation and HE staining to evaluate lung metastasis.

Results: CCA tissues and cells were observed to have a high expression of NUAK1 and poor expression of miR-1182 and let-7a. NUAK1 was indicated as a target gene of miR-1182 and let-7a. Importantly, upregulation of either miR-1182 or let-7a induced autophagy, and inhibited cell progression and in vivo tumor growth and lung metastasis; moreover, combined treatment of miR-1182 and let-7a overexpression presented with enhanced inhibitory effect on NUAK1 expression and CCA progression, but such synergistic effect could be reversed by overexpression of NUAK1.

Conclusion: Taken together, the findings suggest the presence of a synergistic antitumor effect of miR-1182 and let-7a on the development of CCA via the down-regulation of NUAK1, providing novel insight into the targeted therapy against CCA.
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http://dx.doi.org/10.1186/s12935-021-01797-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942015PMC
March 2021

Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity.

Bioact Mater 2021 Oct 11;6(10):3207-3217. Epub 2021 Mar 11.

College of Pharmacy, Jinan University, Guangzhou, Guangdong, 511443, China.

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local "burst" release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6-6.3 μg mL), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947718PMC
October 2021

Chiral-induced spin selectivity enables a room-temperature spin light-emitting diode.

Science 2021 03;371(6534):1129-1133

Chemistry and Nanoscience Center, National Renewable Energy Laboratory, Golden, CO 80401, USA.

In traditional optoelectronic approaches, control over spin, charge, and light requires the use of both electrical and magnetic fields. In a spin-polarized light-emitting diode (spin-LED), charges are injected, and circularly polarized light is emitted from spin-polarized carrier pairs. Typically, the injection of carriers occurs with the application of an electric field, whereas spin polarization can be achieved using an applied magnetic field or polarized ferromagnetic contacts. We used chiral-induced spin selectivity (CISS) to produce spin-polarized carriers and demonstrate a spin-LED that operates at room temperature without magnetic fields or ferromagnetic contacts. The CISS layer consists of oriented, self-assembled small chiral molecules within a layered organic-inorganic metal-halide hybrid semiconductor framework. The spin-LED achieves ±2.6% circularly polarized electroluminescence at room temperature.
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http://dx.doi.org/10.1126/science.abf5291DOI Listing
March 2021

Spatial and temporal distribution of aerobic anoxygenic phototrophic bacteria: key functional groups in biological soil crusts.

Environ Microbiol 2021 Mar 9. Epub 2021 Mar 9.

Chinese Academy of Agricultural Sciences, Key Laboratory of Grassland Ecology and Restoration, Ministry of Agriculture, Institute of Grassland Research, Hohhot, 010010, China.

Several significant ecosystem services are performed by biological soil crusts (BSCs) in drylands, wherein photoautotrophic microorganisms are commonly critical contributors. However, aerobic anoxygenic phototrophic bacteria (AAnPB) are rarely reported in BSCs, despite being the second major branch of Earth's phototrophic microbes. Here, we collected different types of BSCs and their subsoils from temperate deserts, investigated distributions of AAnPB communities among BSCs using cultivation and high-throughput sequencing approaches, predicted keystone species by co-occurrence network analysis, and verified their effects on BSCs formation through microcosm experiments. The absolute abundances and diversity of AAnPB were higher in BSCs and were closely related with BSCs successional stages, as well as soil organic carbon contents. AAnPB communities in both BSCs and their subsoils were dominated by Proteobacteria and Alphaproteobacteria, specifically Acetobacteraceae, Rhodospirillaceae, Roseiflexaceae, Sphingomonadaceae, and Caulobacteraceae families. Mean annual precipitation, pH, and available nutrients were the primary factors that shaped AAnPB community structures. The predicted keystone species belonged to the families Acetobacteraceae, Rhodospirillaceae, and Sphingomonadanceae. Microcosm experiments demonstrated that inoculation with strains from the three families greatly accelerated the formation and development of BSCs. These observations suggest that AAnPB are likely important functional groups in BSCs that significantly contribute to their formation and important ecosystem services. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1462-2920.15459DOI Listing
March 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Improved Bio-Synthesis of 2,5-bis(hydroxymethyl)furan by NJPI-15 With Co-substrate.

Front Chem 2021 3;9:635191. Epub 2021 Feb 3.

Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Upgrading of biomass derived 5-hydroxymethylfurfural (HMF) has attracted considerable interest recently. A new highly HMF-tolerant strain of NJPI-15 was isolated in this study, and the biocatalytic reduction of HMF into 2,5-bis(hydroxymethyl)furan (BHMF) using whole cells was reported. Co-substrate was applied to improve the BHMF yield and selectivity of this strain as well as HMF-tolerant level. The catalytic capacity of the cells can be substantially improved by Mn ion. The strain exhibited good catalytic performance at a pH range of 6.0-9.0 and a temperature range of 25°C-35°C. In addition, 100 mM HMF could be reduced to BHMF by the NJPI-15 resting cells in presence of 70 mM glutamine and 30 mM sucrose, with a yield of 95%. In the fed-batch strategy, 656 mM BHMF was obtained within 48 h, giving a yield of 93.7%. The reported utilization of HMF to produce BHMF is a promising industrially sound biocatalytic process.
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http://dx.doi.org/10.3389/fchem.2021.635191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901908PMC
February 2021

Self-Assembly Nanomicelle Microneedles for Enhanced Photoimmunotherapy Autophagy Regulation Strategy.

ACS Nano 2021 02 12;15(2):3387-3401. Epub 2021 Feb 12.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Although certain therapeutic agents with immunogenic properties may enhance antitumor immunity, cancer cells can eliminate harmful cytoplasmic entities and escape immunosurveillance by orchestrating autophagy. Here, an ingenious self-assembled nanomicelle dissolving microneedle (DMN) patch was designed for intralesional delivery of immunogenic cell death-inducer (IR780) and autophagy inhibitor (chloroquine, CQ) coencapsulated micelles (C/I-Mil) for efficient antitumor therapy. Upon insertion into skin, the self-assembled C/I-Mil was generated, followed by electrostatic binding of hyaluronic acid, the matrix material of DMNs, accompanied by the dissolution of DMNs. Subsequently, photothermal-mediated size-tunable C/I-Mil could effectively penetrate into deep tumor tissue and be massively internalized CD44 receptor-mediated endocytosis, precisely ablate tumors with the help of autophagy inhibition, and promote the release of damage-associated molecular patterns. Moreover, CQ could also act as an immune modulator to remodel tumor-associated macrophages toward the M1 phenotype activating NF-κB. results showed that the localized photoimmunotherapy in synergy with autophagy inhibition could effectively eliminate primary and distant tumors, followed by a relapse-free survival of more than 40 days remodeling the tumor immunosuppressive microenvironment. Our work provides a versatile, generalizable framework for employing self-assembled DMN-mediated autophagy inhibition integrated with photoimmunotherapy to sensitize superficial tumors and initiate optimal antitumor immunity.
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http://dx.doi.org/10.1021/acsnano.0c10396DOI Listing
February 2021

Pulmonary vein stenosis after lung transplantation: a case report and literature review.

Ann Transl Med 2021 Jan;9(2):181

Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Pulmonary vein stenosis (PVS) is a rare event following lung transplantation which increases the risk of morbidity and mortality. Early detection and rapid treatment of this condition is crucial for its management. Although several reports on PVS have been published, there is little consensus regarding its diagnosis and the methods of management. Here we present our experience with PVS. A 31-year-old man received a left lung transplant for chronic hypersensitivity pneumonitis. One year after his single-lung transplant, he began to develop persistent progressive hypoxemia. Computed tomography (CT) of the chest showed left pleural effusion and thickening of the interlobular septa. The results of bronchoscopy and transbronchial biopsies excluded the possibility of acute rejection or infection. The pleural effusion was transudative with lymphocyte predominance. Computed tomography angiography (CTA) in the left atrium and pulmonary veins demonstrated obvious stenosis of both the upper and lower left pulmonary veins (LLPVs) at the transplant anastomotic site. The patient underwent a catheter-guide stent implantation into the stenotic segment of the upper left pulmonary vein (ULPV), and his pleural effusion and hypoxemia problems were ameliorated. Ten months after the intervention, the patient was in excellent clinical condition. In a literature review, we discuss the importance of identifying PVS early after transplantation, the utility of CTA for diagnosis and the use of pulmonary vein stenting intervention. This review provides a basis for further diagnostic strategies and treatments for PVS following lung transplantation.
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http://dx.doi.org/10.21037/atm-20-3972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867883PMC
January 2021

Mitophagy receptor FUNDC1 is regulated by PGC-1α/NRF1 to fine tune mitochondrial homeostasis.

EMBO Rep 2021 Mar 8;22(3):e50629. Epub 2021 Feb 8.

College of Life Sciences, Nankai University, Tianjin, China.

Mitophagy is an essential cellular autophagic process that selectively removes superfluous and damaged mitochondria, and it is coordinated with mitochondrial biogenesis to fine tune the quantity and quality of mitochondria. Coordination between these two opposing processes to maintain the functional mitochondrial network is of paramount importance for normal cellular and organismal metabolism. However, the underlying mechanism is not completely understood. Here we report that PGC-1α and nuclear respiratory factor 1 (NRF1), master regulators of mitochondrial biogenesis and metabolic adaptation, also transcriptionally upregulate the gene encoding FUNDC1, a previously characterized mitophagy receptor, in response to cold stress in brown fat tissue. NRF1 binds to the classic consensus site in the promoter of Fundc1 to upregulate its expression and to enhance mitophagy through its interaction with LC3. Specific knockout of Fundc1 in BAT results in reduced mitochondrial turnover and accumulation of functionally compromised mitochondria, leading to impaired adaptive thermogenesis. Our results demonstrate that FUNDC1-dependent mitophagy is directly coupled with mitochondrial biogenesis through the PGC-1α/NRF1 pathway, which dictates mitochondrial quantity, quality, and turnover and contributes to adaptive thermogenesis.
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http://dx.doi.org/10.15252/embr.202050629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926232PMC
March 2021

Bilayer dissolving microneedle array containing 5-fluorouracil and triamcinolone with biphasic release profile for hypertrophic scar therapy.

Bioact Mater 2021 Aug 27;6(8):2400-2411. Epub 2021 Jan 27.

College of Pharmacy, Jinan University, Guangzhou, 510632, China.

Hypertrophic scar (HS) is an undesirable skin abnormality following deep burns or operations. Although intralesional multi-injection with the suspension of triamcinolone acetonide (TA) and 5-fluorouracil (5-Fu) has exhibited great promise to HS treatment in clinical, the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy. Besides, the traditional injection with great pain is highly dependent on the skill of the experts, which results in poor compliance. Herein, a bilayer dissolving microneedle (BMN) containing TA and 5-Fu (TA-5-Fu-BMN) with biphasic release profile was designed for HS therapy. Equipped with several micro-scale needle tips, the BMN could be self-pressed into the HS with uniform drug distribution and less pain. Both permeation and HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property. Subsequently, the rabbit ear HS model was established to assess therapeutic efficacy. The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition. It was also found that the value of scar elevation index was ameliorated to a basal level, together with the downregulation of mRNA and protein expression of Collagen I (Col I) and transforming growth factor-β1 (TGF-β1) after application of TA-5-Fu-BMN. In conclusion, the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.
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http://dx.doi.org/10.1016/j.bioactmat.2021.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846935PMC
August 2021

Combing multiple site-directed mutagenesis of penicillin G acylase from Achromobacter xylosoxidans PX02 with improved catalytic properties for cefamandole synthesis.

Int J Biol Macromol 2021 Apr 4;175:322-329. Epub 2021 Feb 4.

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu 211816, China. Electronic address:

Penicillin G acylase (PGA) was an important biocatalyst for enzymatic production of second-generation cephalosporin. PGA from Achromobacter xylosoxidans PX02 (AxPGA) showed relatively lower identity to EcPGA (54.9% in α subunit and 51.7% in β subunit), which could synthesize cefamandole in the kinetically controlled N-acylation (kcNa). Semi-rational design of AxPGA and "small and smart" mutant libraries were developed with minimal screening to improve cefamandole production. A triple mutant αR141A/αF142I/βF24G by combining the mutational sites (βF24, αR141, and αF142) from different subunits of AxPGA showed better performance in cefamandole production, with 4.2-fold of improvement in the (k/K) value for activated acyl donor (R)-Methyl mandelate. Meanwhile, the (k/K) value for cefamandole by mutant αR141A/αF142I/βF24G was sharply dropped by 25.5 times, indicating its highly synthetic activity and extremely low hydrolysis of cefamandole. Strikingly, the triple mutant αR141A/αF142I/βF24G could form cefamandole with a yield of 85% at an economical substrate ratio (acyl donor/nucleophile) of 1.3:1 (82% at 1.1:1), which advanced the greener and more sustainable process of cefamandole production than the wild type. Furtherly, the improved synthetic ability and lower hydrolysis of cefamandole by mutant were rationalized using molecular docking.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.194DOI Listing
April 2021

Versatile Nanoscale Metal-Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications.

Small 2021 Feb 28;17(8):e2005064. Epub 2021 Jan 28.

College of Pharmacy, Jinan University, Guangzhou, 510632, P. R. China.

For decades, nanoscale metal-organic frameworks (nMOFs) have attracted extensive interest in biomedicine due to their distinct characteristics, including facile synthesis, porous interior, and tunable biocompatibility. With high porosity, versatile nMOFs allow for the facile encapsulation of various therapeutic agents with exceptionally high payloads. Constructed from metal ions and organic linkers through coordination bonds, nMOFs with plentiful functional groups enable the surface modification for active targeting and enhanced biocompatibility. This review outlines the up-to-date progresses on the exploration of nMOFs in the field of biomedicine. First, the classification and synthesis of nMOFs are discussed, followed by the concrete introduction of drug loading strategies of nMOFs and mechanisms of stimulation-responsive drug release. Second, the smart designs of the nMOFs-based platforms for anticancer and antibacterial treatment are summarized. Finally, the basic challenges faced by nMOFs research and the great potential of biomimetic nMOFs are presented. This review article affords an inspiring insight into the interdisciplinary research of nMOFs and their biomedical applications, which holds great expectation for their further clinical translation.
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http://dx.doi.org/10.1002/smll.202005064DOI Listing
February 2021

Successful application of snare-kissing-catheter technique to implant leadless pacemaker in severely dilated right heart.

Pacing Clin Electrophysiol 2021 May 23;44(5):960-962. Epub 2021 Feb 23.

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, Xuhui District, China.

Implantation of leadless pacemaker is efficacy and safety compared with the traditional pacemaker in structurally normal hearts. However, delivery experience of leadless pacemaker in patients with severe right heart enlargement remains limited. We present the rare case of a patient with giant right heart and moderate to severe tricuspid regurgitation implanted with a leadless Micra transcatheter pacemaker system. The extension of the Micra delivery catheter can be improved by using a single-loop snare on the catheter proximal to appropriate right ventricle (RV) pacing position. The snare-kissing-catheter technique can aid in successful deployment in the setting of challenging right heart enlargement.
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http://dx.doi.org/10.1111/pace.14173DOI Listing
May 2021

Ectopic expression of microRNA-874 represses epithelial mesenchymal transition through the NF-κB pathway via CCNE1 in cholangiocarcinoma.

Cell Signal 2021 Jun 19;82:109927. Epub 2021 Jan 19.

Interventional Department, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, PR China.

Cholangiocarcinoma (CC) is a devastating disease associated with poor survival rate. microRNAs (miRNAs) have recently been reported to assume a great role in CC development. This research aims to explore the functions of miR-874 in regulating epithelial mesenchymal transition (EMT) in CC. In obtained CC tissues and cells, miR-784 expression was assessed by RT-qPCR, and CCNE1 expression by RT-qPCR or immunohistochemistry. Dual-luciferase reporter assay was implemented for relationship between miR-784 and CCNE1. The roles of miR-784, CCNE1 and the NF-κB pathway in CC were investigated on human CC cell lines. CCNE1 was found to be highly expressed in CC while miR-874 expression was lowered in CC tissues and cells, thereby suggesting a negative regulatory effect of CCNE1. In QBC939 and RBE cells, overexpressing miR-874 or silencing CCNE1 led to augmented IκBα and E-cadherin expression, but diminished CCNE1, NF-κB, N-cadherin, and Vimentin expression. Moreover, overexpression of miR-874 or CCNE1 silencing led to reduced cell proliferation, invasion, and migration capabilities. In conclusion, we demonstrated that miR-874 negatively regulated CCNE1 to inhibit the NF-κB pathway, thus consequently suppressing EMT in CC. Therefore, the overexpression of miR-874 might bring favorable outcomes for the treatment of CC.
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http://dx.doi.org/10.1016/j.cellsig.2021.109927DOI Listing
June 2021

Patients Undergoing Primary Total Joint Arthroplasty with Primary Hypercoagulable States.

Orthop Surg 2021 Apr 19;13(2):442-450. Epub 2021 Jan 19.

Department of Orthopaedics, Southern Medical University, Guangzhou, China.

Objective: To analyze perioperative complications, resource consumption, and inpatient mortality of patients who receive total joint arthroplasty (TJA) with a concomitant diagnosis of a primary hypercoagulable state (PHS). The following questions were posed in the present paper. First, do patients undergoing TJA with PHS have increased risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and periprosthetic joint infection (PJI)? Second, what other in-hospital complications are more likely among PHS patients undergoing TJA? Third, do TJA patients with PHS usually consume greater in-hospital resources? Fourth, do PHS patients suffer higher mortality rates compared to non-PHS patients? Finally, have PHS patients received proper anticoagulant management in past arthroplasties?

Methods: The National Inpatient Sample (NIS) database for the years between 2003 and 2014 was searched to identify patients undergoing primary TJA. Patients with PHS were identified with the ICD-9-CM code 289.81. The χ -test, the Pearson test, and adjusted multivariate regression analysis were performed to evaluate the difference and odds ratios between the positive and negative diagnosis groups.

Results: From 2003 to 2014, a total of 2,044,356 patients were identified in the NIS as undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) in the United States. A total of 4664 patients (0.2%) were identified as having PHS. Compared with the non-PHS group, TJA patients with PHS had a higher risk of DVT (THA: odds ratio [OR] = 8.343, 95% CI: 5.362-12.982, P < 0.001; TKA: OR = 4.712, 95% CI: 3.560-6.238, P < 0.001) but did not have increased risk of PE (THA: OR = 1.306, 95% CI: 0.48-3.555, P = 0.602; TKA: OR = 1.143, 95% CI: 0.687-1.903), and only PHS patients in the THA group had higher risks of inpatient mortality (OR = 3.184, 95% CI: 1.348-7.522, P = 0.008) and periprosthetic joint infection (OR = 3.343, 95% CI: 1.084-10.879, P = 0.036). In addition, PHS patients had extended length of stay, higher total costs, and increased risks of certain other complications, such as peripheral vascular disease, hemorrhage, and thrombophlebitis.

Conclusion: In the present study, PHS patients had higher risks of DVT, greater in-hospital resource consumption, and certain other perioperative complications. However, PHS was not associated with increased risk of PE in TJA patients in the United States between 2003 and 2014. While potential hazards of PHS have already been recognized, the present study revealed additional concerns and demonstrated that further improvements in the perioperative management of patients with hereditary hypercoagulable disorders are essential.
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http://dx.doi.org/10.1111/os.12901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957433PMC
April 2021

Rheumatoid Arthritis Versus Osteoarthritis in Patients Receiving Revision Total Knee Arthroplasty in the United States: Increased Perioperative Risks? A National Database-Based Propensity Score-Matching Study.

J Am Acad Orthop Surg 2021 Jan 13. Epub 2021 Jan 13.

From the Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (Pan, Wang, Zhe Shi, Cheng, Lin, Wu, Zhanjun Shi), the First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China (Pan), and the Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (Zhe Shi).

Background: The impacts of rheumatoid arthritis (RA) on perioperative risks among patients undergoing revision total knee arthroplasty (rTKA) have not been investigated yet. Thus, we hypothesized that patients with RA sustained increased perioperative risks and higher resource consumption burdens as compared to patients with osteoarthritis (OA) during the perioperative period.

Patients And Methods: The National Inpatient Sample (NIS) database was used to compare the demographic characteristics, major in-hospital complications, resource consumptions, and in-hospitalization mortality between patients with RA and OA after rTKA. A 1:1 propensity score-matching, χ2 test, independence-sample T-test, and logistic regression analysis were done in statistical analyses to answer our hypotheses.

Results: 4.3% (6363/132,405) of rTKA patients were diagnosed with RA. They tended to be women and received revision for infection but with similar ages as compared to patients with OA. Except for acute postoperative anemia (odds ratio [OR] = 1.196), blood transfusion (OR = 1.179), prolonged hospitalization (OR = 1.049), and higher total cost (OR = 1.145), patients with RA sustained decreased odds of acute renal failure (OR = 0.804) and urinary complications (OR = 0.467). Besides, the other observed in-hospital complications showed no differences between patients with RA and OA.

Conclusion: Despite consuming greater in-hospital resources, patients with RA did not suffer increased odds of most in-hospital complications and in-hospital mortality for a revision TKA during the perioperative period. Compared with patients with OA, patients with RA sustained equivalent perioperative risks in the United States between 2002 and 2014.
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http://dx.doi.org/10.5435/JAAOS-D-20-00979DOI Listing
January 2021

A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility.

Acta Pharm Sin B 2020 Dec 3;10(12):2404-2416. Epub 2020 Aug 3.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation, lung injury markers measurement, and histological analysis. The results of fluorescence imaging showed the high deposition rate of CD-MOF in lungs. Therefore, all results demonstrated that CD-MOF was a promising carrier for pulmonary drug delivery. This study may throw light on the nanoporous particles for effective pulmonary administration.
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http://dx.doi.org/10.1016/j.apsb.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745127PMC
December 2020

Tailored core‒shell dual metal-organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy.

Acta Pharm Sin B 2020 Nov 13;10(11):2198-2211. Epub 2020 Aug 13.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles, with a significantly higher inhibition rate. It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.
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http://dx.doi.org/10.1016/j.apsb.2020.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715426PMC
November 2020

Nondestructive Classification of Soybean Seed Varieties by Hyperspectral Imaging and Ensemble Machine Learning Algorithms.

Sensors (Basel) 2020 Dec 7;20(23). Epub 2020 Dec 7.

Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China.

During the processing and planting of soybeans, it is greatly significant that a reliable, rapid, and accurate technique is used to detect soybean varieties. Traditional chemical analysis methods of soybean variety sampling (e.g., mass spectrometry and high-performance liquid chromatography) are destructive and time-consuming. In this paper, a robust and accurate method for nondestructive soybean classification is developed through hyperspectral imaging and ensemble machine learning algorithms. Image acquisition, preprocessing, and feature selection are used to obtain different types of soybean hyperspectral features. Based on these features, one of ensemble classifiers-random subspace linear discriminant (RSLD) algorithm is used to classify soybean seeds. Compared with the linear discrimination (LD) and linear support vector machine (LSVM) methods, the results show that the RSLD algorithm in this paper is more stable and reliable. In classifying soybeans in 10, 15, 20, and 25 categories, the RSLD method achieves the highest classification accuracy. When 155 features are used to classify 15 types of soybeans, the classification accuracy of the RSLD method reaches 99.2%, while the classification accuracies of the LD and LSVM methods are only 98.6% and 69.7%, respectively. Therefore, the ensemble classification algorithm RSLD can maintain high classification accuracy when different types and different classification features are used.
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http://dx.doi.org/10.3390/s20236980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731448PMC
December 2020

Microneedle-mediated transdermal drug delivery for treating diverse skin diseases.

Acta Biomater 2021 02 5;121:119-133. Epub 2020 Dec 5.

College of Pharmacy, Jinan University, Guangzhou 510632, China; School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

Transdermal drug delivery is an attractive route for dermatological disease therapy because it can directly target the lesion site on the skin, reduce adverse reactions associated with systemic administration, and improve patient compliance. However, the stratum corneum, as the main skin barrier, severely limits transdermal drug penetration, with compromised bioavailability. Microneedles (MNs), which are leveraged to markedly improve the penetration of therapeutic agents by piercing the stratum corneum and creating hundreds of reversible microchannels in a minimally invasive manner, have been envisioned as a milestone for effective transdermal drug delivery, especially for superficial disease therapy. Here, the emergence of versatile MNs for the transdermal delivery of various drugs is reviewed, particularly focusing on the application of MNs for the treatment of diverse skin diseases, including superficial tumors, scars, psoriasis, herpes, acne, and alopecia. Additionally, the promises and challenges of the widespread translation of MN-mediated transdermal drug delivery in the dermatology field are summarized.
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http://dx.doi.org/10.1016/j.actbio.2020.12.004DOI Listing
February 2021

Adsorption kinetics and mechanism of di--butyl phthalate by .

Food Sci Nutr 2020 Nov 12;8(11):6153-6163. Epub 2020 Oct 12.

College of Life Sciences Henan Normal University Xinxiang Henan Province China.

Di-n-butyl phthalate (DBP) poses a risk to humans as a ubiquitous environmental contaminant. A strain of DM12 was chosen from lactic acid bacteria strains to study the DBP binding mechanisms. Adsorption of DBP by strain DM12 reached the highest binding rate of 87% after 11 hr of incubation, which could be explained by pseudo-second-order kinetics. The adsorption isotherm coincided with the model of Langmuir-Freundlich, indicating physical and chemical adsorption processes involved. Further, NaIO and TCA treatments were used to analyze the DBP binding mechanism of strain DM12, which indicated that peptidoglycan on the bacterial cell wall was involved in the process. The O-H, C-O, and N-H bonds were possibly involved in the binding process as the main functional groups.
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http://dx.doi.org/10.1002/fsn3.1908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684587PMC
November 2020

Nano-Silicate-Reinforced and SDF-1α-Loaded Gelatin-Methacryloyl Hydrogel for Bone Tissue Engineering.

Int J Nanomedicine 2020 24;15:9337-9353. Epub 2020 Nov 24.

Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Purpose: Autologous bone grafts are the gold standard for treating bone defects. However, limited bone supply and morbidity at the donor site restrict its extensive use. Therefore, developing bone graft materials as an alternative to autologous grafts has gained considerable attention. Injectable hydrogels endowed with osteogenic potential have the ability to fill irregular bone defects using minimally invasive procedures and have thus been attracting researchers' attention. However, from a clinical perspective, most fabrication methods employed for the current injectable osteogenic hydrogels are difficult and inconvenient. In the current study, we fabricated an injectable osteogenic hydrogel using a simple and convenient strategy.

Materials And Methods: Gelatin-methacryloyl (GelMA) pre-polymer was synthetized. Nano silicate (SN) and stromal cell-derived factor-1 alpha (SDF-1α) were introduced into the pre-polymer to achieve injectability, controlled release property, excellent osteogenic ability, and efficient stem cell homing.

Results: The GelMA-SN-SDF-1α demonstrated excellent injectability via a 17-G needle at room temperature. The loaded SDF-1α exhibited a long-term controlled release pattern and efficiently stimulated MSC migration and homing. The GelMA-SN-SDF-1α hydrogel amplified cell spreading, migration, osteogenic-related biomarker expression, and matrix mineralization. The GelMA-SN-SDF-1α hydrogel filled critical-sized calvaria defects in rats and demonstrated excellent bone regeneration ability, as assessed using micro-CT scanning and histomorphometric staining.

Conclusion: The GelMA-SN-SDF-1α hydrogel provides a simple and convenient strategy for the fabrication of injectable osteogenic graft materials.
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http://dx.doi.org/10.2147/IJN.S270681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699450PMC
December 2020

Spin-Dependent Photovoltaic and Photogalvanic Responses of Optoelectronic Devices Based on Chiral Two-Dimensional Hybrid Organic-Inorganic Perovskites.

ACS Nano 2021 Jan 26;15(1):588-595. Epub 2020 Nov 26.

Department of Physics & Astronomy, University of Utah, Salt Lake City, Utah 84112, United States.

Two-dimensional hybrid organic-inorganic perovskites (2D-HOIPs) that form natural multiple quantum wells have attracted increased research interest due to their interesting physics and potential applications in optoelectronic devices. Recent studies have shown that spintronics applications can also be introduced to 2D-HOIPs upon integrating chiral organic ligands into the organic layers. Here we report spin-dependent photovoltaic and photogalvanic responses of optoelectronic devices based on chiral 2D-HOIPs, namely, (-MBA)PbI and (-MBA)PbI. The out-of-plane photocurrent response in vertical photovoltaic devices exhibits ∼10% difference upon right and left circularly polarized light (CPL) excitation, which originates from selective spin transport through the chiral multilayers. In contrast, the in-plane photocurrent response generated by CPL excitation of planar photoconductive devices shows a typical response of chirality-induced circular photogalvanic effect that originates from the Rashba splitting in the electronic bands of these compounds. Our studies may lead to potential applications of chiral 2D-HOIPs in optoelectronic devices that are sensitive to the light helicity.
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http://dx.doi.org/10.1021/acsnano.0c05980DOI Listing
January 2021

Sirt1 attenuates diabetic keratopathy by regulating the endoplasmic reticulum stress pathway.

Life Sci 2021 Jan 18;265:118789. Epub 2020 Nov 18.

Department of Ophthalmology, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China. Electronic address:

Aims: The objectives of this study were to explore physiological and pathological changes in the corneas of diabetic rats by intervening in the expression of silent information regulator 1 (Sirt1) and to investigate whether Sirt1 can regulate the activation of endoplasmic reticulum stress (ERS) while influencing corneal epithelial cell apoptosis under high glucose conditions.

Materials And Methods: Using 8-week old Sprague-Dawley rats, we established a model of type 1 diabetes, with or without Sirt1 intervention. Clinical evaluation was performed once per week. Primary rat corneal epithelial cells (RCECs) were cultured by combining Sirt1 intervention under high glucose conditions. Generation of reactive oxygen species (ROS), apoptosis, and the expression of Sirt1 and ERS-related proteins were evaluated in rat corneal tissues and RCECs.

Key Findings: During the intervention, clinical evaluation of the ocular surface, ROS generation, apoptosis, and protein expression of ERS-related proteins in corneal tissue and cultured RCECs were altered with Sirt1expression levels.

Significance: Sirt1 expression influences the pathological progression of diabetic keratopathy, plays an important role in regulating the ERS pathway, and decreases corneal epithelial cell apoptosis.
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http://dx.doi.org/10.1016/j.lfs.2020.118789DOI Listing
January 2021