Publications by authors named "Liang Fang"

598 Publications

Osteosclerosis and osteoporosis - different bone impairments from high bone turnover of skeletal fluorosis: a case study on the femoral head.

Pathology 2021 Apr 3. Epub 2021 Apr 3.

The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pathol.2020.11.014DOI Listing
April 2021

CASB: a concanavalin A-based sample barcoding strategy for single-cell sequencing.

Mol Syst Biol 2021 04;17(4):e10060

Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Sample multiplexing facilitates single-cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost-effective strategies are rather limited. Here, we reported a concanavalin A-based sample barcoding strategy (CASB), which could be followed by both single-cell mRNA and ATAC (assay for transposase-accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, and high sensitivity in detecting doublets by three applications: 1) CASB followed by scRNA-seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound-specific heterogeneous response; 2) CASB together with both snATAC-seq and scRNA-seq to illustrate the IFN-γ-mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN-γ response; and 3) combinatorial indexing by CASB, which demonstrated its high scalability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/msb.202010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022202PMC
April 2021

Crystallinity and β Phase Fraction of PVDF in Biaxially Stretched PVDF/PMMA Films.

Polymers (Basel) 2021 Mar 24;13(7). Epub 2021 Mar 24.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Materials Science and Engineering, Nanjing Tech University, Nanjing 210009, China.

Polyvinylidene fluoride (PVDF) and poly(methyl methacrylate) (PMMA) blend films were prepared using biaxial stretching. The effects of PMMA content and stretching ratio on the crystallinity and β phase fraction of PVDF in blend films were investigated. The distributions of crystallinity and β phase fraction on variable locations were also studied. The results of FTIR and XRD showed that β phase appeared in PVDF/PMMA blends after extrusion and casting procedures. Although β phase fraction decreased after preheating, there was still an increasing trend during following biaxial stretching. More importantly, the increase in PMMA content improved β phase fraction, and the highest β phase fraction of 93% was achieved at PMMA content of 30 wt% and stretching ratio of 2×2. Besides, the reduction in PMMA content and the increase in stretching ratio improved the crystallinity of PVDF. The mechanical properties of the stretched films were significantly improved by increasing the stretching ratio as well. The uniform stress distribution on different regions of biaxial stretching films contributed to the uniform distribution of β phase fraction and crystallinity of PVDF with the aid of simulation. This work confirmed that biaxial stretching can be a candidate method to prepare PVDF/PMMA blend films with uniform distributions of comparable β phase and crystallinity of PVDF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym13070998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037939PMC
March 2021

The molecular design of drug-ionic liquids for transdermal drug delivery: Mechanistic study of counterions structure on complex formation and skin permeation.

Int J Pharm 2021 Mar 30:120560. Epub 2021 Mar 30.

Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China. Electronic address:

Though ionic liquids (ILs) as novel enhancers had garnered wide attention, detailed studies elucidating molecular design of drug-ILs were missing and mechanisms of their formation and skin permeation were still lacking. Herein, we systematically investigated effects of counterions structures on formation and skin permeation of drug-ILs. Firstly, effects of counterions on formation of drug-ILs were dependent on polarizability, molecular weight (M.W.) and polar surface area of counterions. It was caused by strong charge assisted hydrogen bond and van der Waals interactions revealed through FT-IR, X-ray photoelectron spectroscopy and molecular docking, which undermined ionic interactions and reduced total interaction strength, thereby produced lower lattice energy. Then, skin permeability of drug-ILs had a good parabola relationship with M.W., polarizability and log P of counterions. The underlying mechanism was the increased drug miscibility with stratum corneum, which caused conformational disorder and phase transition of lipid bilayers characterized by ATR-FTIR, DSC and confocal laser scanning microscopy. Finally, the drug-ILs proved to be non-irritating using in vivo skin erythema analysis. In conclusion, the quantitative structure-activity relationship models based on counterions structure to predict formation and skin permeation of drug-ILs were developed, which provided basic theory for design of drug-ILs with high permeation-enhancing efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120560DOI Listing
March 2021

Immune memory in convalescent patients with asymptomatic or mild COVID-19.

Cell Discov 2021 Mar 25;7(1):18. Epub 2021 Mar 25.

Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.

It is important to evaluate the durability of the protective immune response elicited by primary infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we systematically evaluated the SARS-CoV-2-specific memory B cell and T cell responses in healthy controls and individuals recovered from asymptomatic or symptomatic infection approximately 6 months prior. Comparatively low frequencies of memory B cells specific for the receptor-binding domain (RBD) of spike glycoprotein (S) persisted in the peripheral blood of individuals who recovered from infection (median 0.62%, interquartile range 0.48-0.69). The SARS-CoV-2 RBD-specific memory B cell response was detected in 2 of 13 individuals who recovered from asymptomatic infection and 10 of 20 individuals who recovered from symptomatic infection. T cell responses induced by S, membrane (M), and nucleocapsid (N) peptide libraries from SARS-CoV-2 were observed in individuals recovered from coronavirus disease 2019 (COVID-19), and cross-reactive T cell responses to SARS-CoV-2 were also detected in healthy controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41421-021-00250-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993859PMC
March 2021

An investigation on percutaneous permeation of flurbiprofen enantiomers: The role of molecular interaction between drug and skin components.

Int J Pharm 2021 Mar 19;601:120503. Epub 2021 Mar 19.

Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address:

This work aimed to investigate skin permeation profiles of chiral flurbiprofen and clarify the molecular mechanism of transdermal permeation difference of enantiomers. The in vitro transdermal permeation of enantiomers through rat skin was studied by diffusion cells. Physicochemical parameters of model chiral drugs were determined. Molecular interaction between chiral flurbiprofen and ceramides of skin was investigated by FTIR, C NMR and molecular docking. The skin permeation mechanism of chiral drugs was characterized by ATR-FTIR, Raman spectra, DSC and molecular dynamic simulation. The results showed that the amount of the permeation and retention amount of (S)-flurbiprofen was 1.5 times over that of (R)-flurbiprofen. And it was proven that the difference was not induced by physicochemical properties but the molecular interaction between drug-skin components. (S)-flurbiprofen was easy to form stronger hydrogen bonding with -CONH group of skin lipids due to its steric configuration, which disturbed lipids arrangement more easily according to the results of ATR-FTIR (ΔνCH = 1.00 cm), Raman spectra (ΔI/I = 0.32) and the DSC (ΔT = 11.75 °C). It was demonstrated more obvious effect on the second structure of keratin by ATR-FTIR study (Δ Amide I = 3.60 cm and Δ Amide II = 3.38 cm). Better compatibility between (S)-flurbiprofen and lipids was confirmed quantificationally by thermodynamic analysis. In conclusion, the higher interaction between (S)-flurbiprofen and skin components, the higher skin permeation, which contributes to decrease the administration dose and increase the therapeutic effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2021.120503DOI Listing
March 2021

hPER3 promotes adipogenesis via hHSP90AA1-mediated inhibition of Notch1 pathway.

Cell Death Dis 2021 Mar 19;12(4):301. Epub 2021 Mar 19.

Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.

The period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance. Molecularly, hPER3 does not interact with hPPARγ, but represses Notch1 signaling pathway to enhance adipogenesis by interacting with hHSP90AA1, which is able to combine with the promoter of hNotch1 and inactivate its expression. Thus, our study revealed hPER3 as a critical positive regulator of hADSCs adipogenesis, which was different from the other types of cells, providing a critical role of it in treating obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03584-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979882PMC
March 2021

Gut Microbiota Signatures in Gestational Anemia.

Front Cell Infect Microbiol 2021 25;11:549678. Epub 2021 Feb 25.

Department of Laboratory, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, China.

Gestational diseases are associated with altered intestinal microbiota in pregnant women. Characterizing the gut microbiota of gestational anemia (GA) may describe a novel role of gut microbial abnormality in GA. In this study, we investigated differences in gut microbiota between GA patients and healthy pregnant women from the first trimester (n = 24 54) and the third trimester (n = 30 56) based on the 16S rRNA gene sequencing method. No statistically significant differences in α-diversity were identified between GA patients and controls in the first trimester of pregnancy, whereas the Shannon index and observed OTUs were significantly lower in GA patients than in healthy controls in the third trimester. Distance-based redundancy analysis revealed striking differences in microbial communities in the third trimester between GA patients and controls. Four genera were significantly different in relative abundance between GA patients and healthy controls, while 12 genera differentiated significantly between GA patients and healthy controls in the third trimester. At the operational taxonomic unit (OTU) level, 17 OTUs and 30 OTUs were identified to be different between GA patients and healthy controls in the first and third trimesters, respectively. Changes in gut microbial composition of GA patients suggest a potential relation with GA, and provide insights into the prediction and intervention of gestational anemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.549678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947918PMC
February 2021

Synthesis of Ni₃Bi₂S₂ Coupled with N-Doped Carbon Sheets as Electrocatalyst for Triiodide and Oxygen Reduction.

J Nanosci Nanotechnol 2021 Sep;21(9):4740-4748

College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang 443002, China.

Herein, we report a novel composite structure consisting of Ni₃Bi₂S₂ particles coupled with N-doped carbon (NC) sheets. Different from the generally used high vacuum or microwave-assisted technologies, metal-rich Ni₃Bi₂S₂ can be successfully synthesized via a simple pyrolysis procedure, with NC employed as a reducing agent. In addition, the phase purity, size, and dispersity of the Ni₃Bi₂S₂ particles, which were encapsulated by the NC shell, were modulated by the content of NC. The X-ray photoelectron spectroscopy (XPS) analysis demonstrated the metallic state of the Ni and Bi elements, which ensured good Ni₃Bi₂S₂ electrical conductivity. As a result, the resultant Ni₃Bi₂S₂/NC (0.55 II) catalyzed triiodide reduction with a lower charge transfer resistance than commercial Pt/C (1.4 II). Moreover, Ni₃Bi₂S₂/NC catalyzed the oxygen reduction reaction with a positive ORR half-wave potential (0.81 V vs. RHE) and a low Tafel slope (47 mV dec). Our study thus provides the novel exploration of the electrochemical performance of Ni₃Bi₂S₂ and indicates its promising application in electrocatalytic reactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jnn.2021.19345DOI Listing
September 2021

Mechanism insight on drug skin delivery from polyurethane hydrogels: Roles of molecular mobility and intermolecular interaction.

Eur J Pharm Sci 2021 Jun 3;161:105783. Epub 2021 Mar 3.

Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China. Electronic address:

Though polyurethane (PU) hydrogel had great potential in topical drug delivery system, drug skin delivery behavior from hydrogel and the underlying molecular mechanism were still unclear. In this study, PU and Carbomer (CP as control) hydrogels were prepared with lidocaine (LID) and ofloxacin (OFX) as model drugs. In vitro skin permeation and tissue distribution study were conducted to evaluate the drug delivery behaviors. The underlying molecular mechanisms were characterized by drug release with octanol as release medium, rheological study, ATR-FTIR, NMR, and molecular simulation. The results showed that the skin permeation amount of LID-PU (45.50 ± 7.12 μg) was lower than LID-CP (45.50 ± 7.12 μg). And the LID diffusion coefficient of PU (26.21 μg/h) was also lower than CP (31.30 μg/h), which attributed to H-bonding between LID (-CONH) and PU (-NHCOO). However, the OFX-PU showed a higher skin permeation amount (10.06 ± 1.29 μg) than OFX-CP (5.28 ± 1.39 μg). And the OFX-PU also showed a higher diffusion coefficient (30.0 μg/h) than OFX-CP (21.37 μg/h), which was caused by increased mobility of hydrogel when interaction action site was C-O-C in PU. In conclusion, drug skin delivery behavior from PU hydrogel was controlled by molecular mobility and intermolecular interaction, which clarified the influence of the functional group of PU hydrogel on drug skin delivery behavior and broadened our understanding of PU hydrogel application in topical drug delivery system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2021.105783DOI Listing
June 2021

Special AT-rich sequence-binding protein 2 (Satb2) synergizes with Bmp9 and is essential for osteo/odontogenic differentiation of mouse incisor mesenchymal stem cells.

Cell Prolif 2021 Apr 4;54(4):e13016. Epub 2021 Mar 4.

Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.

Objectives: Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs.

Materials And Methods: Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo.

Results: Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo.

Conclusions: Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.13016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016638PMC
April 2021

Special AT-rich sequence-binding protein 2 (Satb2) synergizes with Bmp9 and is essential for osteo/odontogenic differentiation of mouse incisor mesenchymal stem cells.

Cell Prolif 2021 Apr 4;54(4):e13016. Epub 2021 Mar 4.

Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.

Objectives: Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs.

Materials And Methods: Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo.

Results: Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo.

Conclusions: Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.13016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016638PMC
April 2021

A comparative study of contrast-enhanced ultrasound and contrast-enhanced CT for the detection and characterization of renal masses.

Biosci Trends 2021 Mar 26;15(1):24-32. Epub 2021 Feb 26.

Department of Reproductive Immunology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

This study aims to compare the value of contrast-enhanced ultrasound (CEUS) and contrast-enhanced CT (CECT) in the differential diagnosis of benign and malignant renal masses. Included in this retrospective study were 143 renal masses in 141 patients using histopathological findings as the gold standard. A comparison was made of the two modalities in image characteristics for their accuracy in the differential diagnosis of renal masses. CEUS and CECT were both used for 39 masses in 37 patients, with 31 (79.5%) being malignant and 8 (20.5%) benign. The differences between the benign and malignant groups in perfusion intensity, perfusion uniformity and entry and exit of the contrast agent were not statistically significant (P > 0.05). However, CEUS could better display the circular perfusion of renal cell carcinoma than CECT (P < 0.05). CECT alone detected 109 masses in 107 patients, with 93 (85.3%) being malignant and 16 (14.7%) benign. CEUS detected 73 masses in 71 patients, with 56 (76.7%) being malignant and 17 (23.3%) benign. No statistically significant differences were observed between CEUS and CECT in the diagnosis of renal cell carcinoma (92.8% vs. 90.3%), with a specificity of 52.9% vs. 31.2%, an accuracy of 83.5% vs. 81.6%, and a positive predictive value of 86.7% vs. 88.4% or a negative predictive value of 69.2% vs. 35.7% (P > 0.05 for all). These results suggested both CEUS and CECT are highly valuable in the differential diagnosis of renal masses, and CEUS can be used as an important supplement for CECT in diagnosis of renal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5582/bst.2021.01026DOI Listing
March 2021

Development of long-acting rivastigmine drug-in-adhesive patch utilizing ion-pair strategy and characterization of controlled release mechanism.

Eur J Pharm Sci 2021 Jun 25;161:105774. Epub 2021 Feb 25.

College of Pharmacy, Yanbian University, 977 Gongyuan Road, Yanji, Jilin, 133002, China; Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China. Electronic address:

The purpose of present study was to develop a long-acting drug-in-adhesive patch of rivastigmine (RVS) to achieve controlled release under high drug loading. Formulation factors including ion-pair, pressure sensitive adhesive (PSA), drug-loading and permeation enhancers were investigated through in vitro skin permeation experiments. Optimized patch was evaluated by pharmacokinetic study. The mechanism of controlled release was studied by FTIR, Raman, DSC, rheology study and molecular modeling. The optimized patch composed of RVS-SA (equal to 30% RVS), 15% POCC as permeation enhancer and AAOH as PSA matrix. The RVS in optimized patch was basically permeated at a uniform rate, and the ratio of the skin permeation amount (2803.38 ± 153.85 μg/cm) in 72 hours to that of the control group (1000.89 ± 62.45 μg/cm) was 2.8. The plasma concentration of RVS was stable for 72 hours in vivo (AUC = 5721.30 ± 1994.87 h ng/mL, MRT = 29.55 ± 2.49 h), and C was significantly controlled. The results of the study on the controlled release mechanism showed that the addition of counter ion formed hydrogen bonds with RVS and PSA respectively, which reduced the fluidity and molecular mobility of PSA, and enhanced the interaction between RVS and PSA, thus achieving the purpose of long-acting effect. In conclusion, long-acting drug-in-adhesive patch of RVS was developed, and provided a new idea for the long term drug delivery of Alzheimer's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2021.105774DOI Listing
June 2021

Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies.

Cell Mol Immunol 2021 04 25;18(4):1061-1063. Epub 2021 Feb 25.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-021-00648-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905196PMC
April 2021

Corrigendum to "The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer's disease" [Brain Stimul 12 (2019) 161-174].

Brain Stimul 2021 Mar-Apr;14(2):389-390. Epub 2021 Feb 22.

Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai, 200120, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brs.2021.01.019DOI Listing
February 2021

FlsnRNA-seq: protoplasting-free full-length single-nucleus RNA profiling in plants.

Genome Biol 2021 Feb 19;22(1):66. Epub 2021 Feb 19.

Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, 518055, China.

The broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we present a protoplasting-free approach, flsnRNA-seq, for large-scale full-length RNA profiling at a single-nucleus level in plants using isolated nuclei. Combined with 10x Genomics and Nanopore long-read sequencing, we validate the robustness of this approach in Arabidopsis root cells and the developing endosperm. Sequencing results demonstrate that it allows for uncovering alternative splicing and polyadenylation-related RNA isoform information at the single-cell level, which facilitates characterizing cell identities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893963PMC
February 2021

Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties.

Immunity 2021 Mar 8;54(3):454-467.e6. Epub 2021 Feb 8.

Department of Critical Care Medicine and Hematology, The 3rd Xiangya Hospital, Central South University, Changsha, 410000 P.R. China; Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410000 P.R. China; Key Laboratory of sepsis translational medicine of Hunan, Central South University, Changsha, Hunan Province, 410000 P.R. China. Electronic address:

Heparin, a mammalian polysaccharide, is a widely used anticoagulant medicine to treat thrombotic disorders. It is also known to improve outcomes in sepsis, a leading cause of mortality resulted from infection-induced immune dysfunction. Whereas it is relatively clear how heparin exerts its anticoagulant effect, the immunomodulatory mechanisms enabled by heparin remain enigmatic. Here, we show that heparin prevented caspase-11-dependent immune responses and lethality in sepsis independent of its anticoagulant properties. Heparin or a chemically modified form of heparin without anticoagulant function inhibited the alarmin HMGB1-lipopolysaccharide (LPS) interaction and prevented the macrophage glycocalyx degradation by heparanase. These events blocked the cytosolic delivery of LPS in macrophages and the activation of caspase-11, a cytosolic LPS receptor that mediates lethality in sepsis. Survival was higher in septic patients treated with heparin than those without heparin treatment. The identification of this previously unrecognized heparin function establishes a link between innate immune responses and coagulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2021.01.007DOI Listing
March 2021

Retraction Note: LncRNA miR503HG interacts with miR-31-5p through multiple ways to regulate cancer cell invasion and migration in ovarian cancer.

J Ovarian Res 2021 Feb 1;14(1):24. Epub 2021 Feb 1.

Department of Gynecology, Hunan Provincial People's Hospital, Changsha City, Hunan Province, 410005, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-020-00747-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852142PMC
February 2021

Identification and functional characterization of CD154 in T cell-dependent immune response in Nile tilapia (Oreochromis niloticus).

Fish Shellfish Immunol 2021 Apr 26;111:102-110. Epub 2021 Jan 26.

Institute of Modern Aquaculture Science and Engineering, School of Life Sciences, South China Normal University, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, Guangdong, 510631, PR China. Electronic address:

CD154, a member of the TNF superfamily, is a multifunctional molecule highly expressed in activated T cells, and plays important roles in T cell-dependent humoral immune response. In this study, CD154 of Nile tilapia (Oreochromis niloticus) was identified, and its functions in the T cell-dependent immune response were demonstrated. The open reading frame (ORF) of OnCD154 is 699 bp, encoding a protein of 232 amino acids with a 23 amino acid transmembrane region. Amino acid sequence of OnCD154 is highly homologous to that of other teleost fish, especially rainbow trout. Quantitative real-time PCR (qRT-PCR) demonstrated that mRNA of OnCD154 is highly expressed in immune organs, especially in spleen, thymus, gills, head kidney, etc. In addition, the anti-OnCD154 polyclonal antibody (anti-(r)OnCD154) was successfully prepared, and it can react with natural protein in head kidney leukocytes. Following two immunizations with keyhole limpet hemocyanin (KLH) in vivo, the significantly up-regulated expression level of OnCD154 mRNA appeared earlier (fifth day) and higher (42.9 folds) in the second challenge than the first on in head kidney. Further, after stimulation with KLH in vitro, the expressions of T cell-dependent immune response-related molecules (activated T cell specific surface molecules CD3ε and CD154) and B cell differentiation-related molecules (Blimp1 and sIgM) and CD40 were significantly up-regulated in head kidney leukocytes. Moreover, the up-regulated expressions of these molecules were blocked with the treatment of anti-(r)OnCD154 antibody. Taken together, these results indicate that OnCD154 might get involved in T cell-dependent immune response, and provide a new insight into the humoral immune response of teleost fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsi.2021.01.009DOI Listing
April 2021

Enhanced Drug Loading in the Drug-in-Adhesive Transdermal Patch Utilizing a Drug-Ionic Liquid Strategy: Insight into the Role of Ionic Hydrogen Bonding.

Mol Pharm 2021 03 28;18(3):1157-1166. Epub 2021 Jan 28.

Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.

Though pharmaceutical polymers were widely used in inhibiting drug recrystallization via strong intermolecular hydrogen and ionic bonds, the improved drug stability was achieved at the cost of the drug release rate or amount in the drug-in-adhesive transdermal patch. To overcame the difficulty, this study aimed to increase drug loading utilizing a novel drug-ionic liquid (drug-IL) strategy and illustrate the underlying molecular mechanism. Here, naproxen (NPX) and triamylamine (TAA) were chosen as the model drug and corresponding counterion, respectively. In addiiton, carboxylic pressure-sensitive adhesive (PSA) was chosen as the model polymer. The drug-IL (NPX-TAA) was synthesized and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance. The miscibility between NPX-TAA and PSA was assessed using microscopy study, X-ray diffraction, fluorescence spectroscopy, and solubility parameter calculation. In addition, molecular mechanisms of crystallization inhibition were revealed by FT-IR, Raman spectroscopy, DSC, X-ray photoelectron spectroscopy (XPS), and molecular docking. Finally, the release pattern of the high load patch of NPX-TAA was evaluated using drug release and verified by a skin permeation experiment. The results showed that drug loading in PSA was increased by 5.0 times, which was caused by the synergistic effect of strong ionic hydrogen bonding (the decreased intensity and blue shift of the O-H peak of COOH in PSA) formed between NPX-TAA and PSA-COO and normal hydrogen bonding (red shift of the C═O peak in PSA) formed between NPX-TAA and the carbonyl group of PSA. In addition, -NH of TAA was confirmed as the molecular basis of ionic hydrogen bonding through new peak appearance (binding energy: 400.0 eV) in XPS spectra. Moreover, high drug release percent (80.8 ± 1.8%) was achieved even at high drug loading compared with the control group (72.4 ± 2.2%). Thus, this study introduced an effective drug-IL method to enhance drug loading capacity and illustrated the brand-new action mechanism, which provided a powerful instrument for the development of a high drug loading-high release patch.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.0c01054DOI Listing
March 2021

Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression.

Cell Death Dis 2021 Jan 21;12(1):112. Epub 2021 Jan 21.

Department of Head and Neck Surgery, Institute of Micro-Invasive Surgery of Zhejiang University, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou, People's Republic of China.

Papillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-03350-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819993PMC
January 2021

Effect of Nrf2 signaling pathway on the improvement of intestinal epithelial barrier dysfunction by hyperbaric oxygen treatment after spinal cord injury.

Cell Stress Chaperones 2021 Mar 20;26(2):433-441. Epub 2021 Jan 20.

Department of Hyperbaric Oxygen Medicine, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongti South Road, Chaoyang District Beijing, Beijing, 100020, China.

Disruption of the intestinal epithelial barrier following spinal cord injury (SCI) seriously affect long-term quality of life. Oxidative stress-induced epithelial cells' injury contributes to the epithelial barrier dysfunction. Hyperbaric oxygen (HBO) treatment has been proved to alleviate SCI. However, it is unclear whether or not HBO treatment affects intestinal barrier function following SCI. In this study, our purpose was to explore the impact of HBO treatment on intestinal epithelial barrier function and underlying mechanisms following SCI. An SCI model was established in rats, and the rats received HBO treatment. Intestinal injury, mucosal permeability, intercellular junction proteins, and oxidative stress indicators were evaluated in our study. We found that HBO treatment significantly alleviated intestinal histological damage, reduced mucosal permeability, and markedly prevented bacterial translocation. Furthermore, HBO treatment significantly increased the expression of Claudin-1 and E-cadherin, inhibited intestinal tissue oxidative stress as demonstrated by upregulation of superoxide dismutase and glutathione, and HBO downregulated malondialdehyde. Mechanically, we demonstrated that HBO treatment ameliorated intestinal oxidative stress possibly through upregulating nuclear factor E2-related factor 2 (Nrf2) and its downstream targets, Heme oxygenase-1(HO-1), NADH-quinone oxidoreductase-1(NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC). These results suggested that HBO treatment triggered antioxidative effects against intestinal epithelial barrier dysfunction by promoting Nrf2 signaling pathway after SCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12192-020-01190-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925733PMC
March 2021

The complete chloroplast genome of (Staphyleaceae).

Mitochondrial DNA B Resour 2020 Dec 27;5(4):3825-3826. Epub 2020 Dec 27.

YuZhang Normal University, Nanchang, China.

The complete chloroplast genome of was sequenced and assembled for the first time. The chloroplast genome was 160,139 bp in length, containing a large single-copy region (LSC) of 89,625 bp and a small single-copy region (SSC) of 18,262 bp, separated by a pair of inverted repeats (IRs) of 26,126 bp. The genome contained 113 unique genes, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Among them, 15 genes had one intron each and 3 genes containing two introns. The overall GC content was 37.4%, while the corresponding values of LSC, SSC, and IR regions were 35.4%, 31.8%, and 42.8%, respectively. Phylogenetic analysis showed that is more closely related to and provided new insight into the evolution of Staphyleaceae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2020.1841579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782190PMC
December 2020

Artesunate: A natural product-based immunomodulator involved in human complement.

Biomed Pharmacother 2021 Apr 19;136:111234. Epub 2021 Jan 19.

The Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Ole Maaloesvej 26, 2200, Copenhagen N, Denmark.

Complement is an important innate immune defence machinery. Once dysregulated, it is often linked to pathogenesis of diverse autoimmune diseases. Artesunate (ART) is a well-known anti-malarial compound. Recently, ART has been highlighted by its potential therapeutic effects on certain complement-related autoimmune diseases. However, the underlying mechanisms are hitherto unknown. In the present study, we found that ART mediated complement interception as validated by analysis of complement haemolytic assay. In cell-based setup using dying Jurkat cells, ART-mediated complement interception was also confirmed. Further, we newly established an ELISA system selectively allowing complement activation via the classical pathway, the lectin pathway and the alternative pathway, respectively. ELISA analysis revealed that ART dose-dependently inhibited C4 activation, C3 activation and terminal complement complex assembly via the effector pathways. ART was found to blockade C1q, C3 and C5 with a lesser extent to properdin. The interaction of ART with C1q was determined to be mediated via C1q globular head region. FACS analysis using ART-conjugated mesoporous silica particles revealed that ART specifically bound the key therapeutic targets of C1q, C3 and C5 on microparticles. In conclusion, we for the first time report the anti-complement bioactivities of ART and suggest a potential therapeutic benefit of ART in the complement-related human diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111234DOI Listing
April 2021

Physicochemical Excipient-Container Interactions in Prefilled Syringes and their Impact on Syringe Functionality.

PDA J Pharm Sci Technol 2021 Jan 15. Epub 2021 Jan 15.

Eli Lilly

Previous studies have shown that parenteral formulation excipients can interact with the silicone oil in prefilled syringes, thereby causing variations in glide force that affect the performance of autoinjectors. Thus, it is crucial to control the glide force of the prefilled syringes to mitigate the potential risk of dose inaccuracies. This study provided a systematic understanding of the chemical interactions between the excipients, physical interactions between the excipients and the container, as well as their impact on the functional performance of prefilled syringes. The design of experiment approach used in this study generated statistically meaningful data, which confirmed that different excipients caused varying increase in glide force in siliconized prefilled syringes. The data indicated that poloxamer 188 can more effectively maintain stable glide forces during accelerated storage conditions, compared to polysorbate 80. This finding was further enhanced using Hansen solubility parameters theory, which provided a fundamental understanding of the mechanisms behind the physical interactions. Chemical stability analysis of the surfactants suggested that degradation of excipients also impacts syringe functionality. In summary, the results revealed the unique interactions between parenteral pharmaceutical excipients and primary packaging systems and the physicochemical foundation behind them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5731/pdajpst.2020.012278DOI Listing
January 2021

CD226 deficiency attenuates the homeostasis and suppressive capacity of Tr1 cells.

Mol Immunol 2021 04 13;132:192-198. Epub 2021 Jan 13.

Department of Immunology, the Fourth Military Medical University, Xi'an 710032, China; Faculty of Medicine, Northwest University, Xi'an 710069, China. Electronic address:

T regulatory type 1 (Tr1) cells act as a key regulator in maintaining peripheral immune tolerance. Several costimulatory molecules for T cells have been identified in Tr1 cells, but their intrinsic functions are still unclear. Here we showed CD226 was highly expressed in Tr1 cells. CD226-deficient Tr1 cells were defective in proliferation and sensitive to apoptosis. In addition, CD226-deficient Tr1 cells showed lower inhibitory capacity of T cell proliferation and reduced IL-10 production. CD226 deficiency also inhibited Tr1 cell differentiation in vitro. When stimulated with IL-2, CD226-deficient Tr1 cells showed impaired STAT5 signaling. Therefore, our data suggest CD226 might play an important role in Tr1 cell homeostasis, function and differentiation. This study facilitates further biological characterization of this regulatory T cell subset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2021.01.002DOI Listing
April 2021

An Investigation to Examine the Effect of the Elastomeric Surface Treatment on Protein Stability.

PDA J Pharm Sci Technol 2020 Dec 21. Epub 2020 Dec 21.

West Pharmaceutical Services, 530 Herman O West Drive, Exton, PA 19341

Various kinds of treatments on the surface of the elastomeric components can have impacts on the quality of protein therapeutics. We compared the effects of bare (non-siliconized and non-laminated), siliconized and fluoropolymer laminated elastomeric components on the stability of β-Lactoglobulin, human serum albumin, adalimumab, abatacept and immunoglobulin antibodies. The study was conducted in two main parts. Part I was to evaluate the stability of proteins under agitation induced stress. Protein aggregate formation, turbidity and protein recovery were analyzed using dynamic fluid imaging, absorbance @350 nm and SE-HPLC, respectively. Proteins were found to be more stable with laminated stoppers as compared to bare or siliconized stoppers. Part II was to identify chemical modifications when proteins were stored in contact with the same three stoppers. cIEF analysis of the adalimumab samples showed formation of acidic variants in siliconized and bare stoppers. RP-HPLC suggested chemical changes to human serum albumin. Analysis of tryptic human serum albumin by LC/MS/MS indicated that the amino acids most susceptible to oxidation (cysteine, tryptophan and methionine) were also the ones which were modified. Part III of this study investigated the barrier property of the fluoropolymer film with no drug product. Our results are consistent with the suggestion that the fluoropolymer lamination provides a barrier that prevents leachables from the elastomeric components into the protein therapeutics. Our work provides an in-depth understanding of the effects of elastomeric surface treatments on the biophysical and chemical stability of protein drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5731/pdajpst.2020.012120DOI Listing
December 2020

Defining disease progression in Chinese mainland people: Association between bone mineral density and knee osteoarthritis.

J Orthop Translat 2021 Jan 6;26:39-44. Epub 2020 Nov 6.

The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.

Objective: To evaluate change in bone mineral density (BMD) during development of knee osteoarthritis (OA) in elderly Chinese community residents. Further, to monitor disease progression by recording speed of sound (SOS), one parameter of BMD provided by quantitative ultrasound measurement.

Methods: A total of 4173 community residents of the Chinese mainland were organized to complete questionnaires and relevant measurements, including anthropometry, radiology and quantitative ultrasound (QUS). SOS measurements of the distal radius were acquired using QUS measurements. The Kellgren-Lawrence (KL) grade of knee OA was evaluated by two experienced radiographers using X-rays. Finally, a general linear models analysis was performed to determine potential relationships. Further, the area under the receiver operating characteristic curve (ROC AUC) was applied to assess the distinction model.

Results: The SOS score in the OA group was significantly lower than that in the control group ( ​ ​0.001). However, after adjustment for age and body mass index (BMI), no significant difference was observed in the male population ( ​= ​0.841), while a significantly lower SOS score presented in knee OA participants in the female population ( ​= ​0.033). A turning point in SOS scores, from increasing to decreasing trends, occurred around KL grade 2; the SOS score gradually increased with progression in participants from KL grades 0 to 2, whereas the SOS score presented a significant decrease in participants with KL grades 3 and 4. The AUC for the model to distinguish OA progression was 0.891.

Conclusion: There was a non-linear and stage-specific association between SOS score and knee OA, which presented a positive relationship in early stages, but a negative relationship in advanced stages. A decline of SOS score in knee OA patients in early stages should alert clinicians to the possibility of disease progression.

The Translational Potential Of This Article: In the present study, the relationship between OA and BMD had established by SOS. The results suggested that close monitoring of SOS in elderly Chinese communities residents with knee OA could alert disease progression involvement by an easily accessible method, and help early referral to orthopedist consultation for further examination and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jot.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773972PMC
January 2021

Changes in the humoral immunity response in SARS-CoV-2 convalescent patients over 8 months.

Cell Mol Immunol 2021 02 8;18(2):490-491. Epub 2021 Jan 8.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-020-00605-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791534PMC
February 2021