Publications by authors named "Lili Wang"

1,745 Publications

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Iridium(III) complexes as mitochondrial topoisomerase inhibitors against cisplatin-resistant cancer cells.

Chem Commun (Camb) 2021 Jul 28. Epub 2021 Jul 28.

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.

Herein, we developed the first metal-based mitochondrial topoisomerase inhibitors to achieve an effective therapeutic outcome for the therapy of cisplatin-resistant tumour cells.
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http://dx.doi.org/10.1039/d1cc02178hDOI Listing
July 2021

[Determination of furan in canned foods and packaged beverages by headspace gas chromatography-mass spectrometry].

Wei Sheng Yan Jiu 2021 Jul;50(4):641-645

Beijing Center for Disease Prevention and Control, Beijing Center for Prevention Medicine Research, Beijing 100013, China.

Objective: A headspace gas chromatography-mass spectrometry(HS-GC-MS) method for the analysis of furan in canned foods and packaged beverages was established.

Methods: The furan was extracted from the samples by headspace method. D_4-furan was used as internal standard and separated on a HP-Plot Q(30 m×0.32 mm, 20 μm) column. The results were qualitative and quantitative by gas chromatography-mass spectrometry.

Results: The linear range of this method was 2.0-200.0 ng, and the regression equation of the working curve was y=1.14x +0.116(r~2=0.999). The recoveries were 86.3%-96.2% with the relative standard deviations(RSDs) less than 10%(n=6). The limit of quantification of furan was 1.0 ng. Through the detection of 59 samples, it was found that the common canned food and hard packaged drinks were commonly contaminated with furan, and the concentration of furan in coffee, milk tea, canned fish and other products were relatively high, with a maximum value of 153.99 ng.

Conclusion: The method is simple, rapid, accurate and reliable, and could be used for the detection of furan in the two kinds of food.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2021.04.017DOI Listing
July 2021

High-fat diet promotes epithelial-mesenchymal transition through enlarged growth of opportunistic pathogens and the intervention of saturated hydrogen.

Am J Transl Res 2021 15;13(6):6016-6030. Epub 2021 Jun 15.

Department of Medical Microbiology, Xiangya School of Medicine, Central South University Changsha, China.

Objectives: This study investigated the effects and mechanism of high-fat diet on the epithelial-mesenchymal transition (EMT) of respiratory tract and the intervention of saturated hydrogen on it.

Methods: 80 five-week-old C57BL6/J male mice were randomly divided into normal control group, H group, high-fat (HF) group and HF+H group, making 20 mice in each group. The weights of the mice were measured on weekly basis. Six mice from each group were executed at every second week. Blood samples were collected for lipid testing. Lung tissues were collected for 16S rRNA gene sequencing, HE staining, immunofluorescence and quantitative real-time PCR (qPCR).

Results: Compared with the control group, the mice in the HF group showed increased inflammatory cell infiltration, decreased expression of e-cadherin (E-cad) and increased expression of Twist. There were significant differences in the composition of bacteria in the lung, and the expression of isocitrate lyase (ICL) genes in and , which were significantly associated with asthma were seen with a significant increasing trend. After the treatment of saturated hydrogen, the changes in lung microbial population, lung tissue infiltration of inflammatory cells and the transformation of epithelial stroma caused by high-fat diet were moderately alleviated.

Conclusion: High-fat diet can promote inflammation and EMT in the lung by enlarging the growth of glyoxylic acid cycle-dependent bacteria, and the pathological process are partly alleviated by saturated hydrogen.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290812PMC
June 2021

The effect of RNA polymerase V on 24-nt siRNA accumulation depends on DNA methylation contexts and histone modifications in rice.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, 210095 Nanjing, China;

RNA-directed DNA methylation (RdDM) functions in de novo methylation in CG, CHG, and CHH contexts. Here, we performed map-based cloning of , which encodes the largest subunit of RNA polymerase V (Pol V), a key regulator of gene silencing and reproductive development in rice. We found that rice Pol V is required for CHH methylation on RdDM loci by transcribing long noncoding RNAs. Pol V influences the accumulation of 24-nucleotide small interfering RNAs (24-nt siRNAs) in a locus-specific manner. Biosynthesis of 24-nt siRNAs on loci with high CHH methylation levels and low CG and CHG methylation levels tends to depend on Pol V. In contrast, low methylation levels in the CHH context and high methylation levels in CG and CHG contexts predisposes 24-nt siRNA accumulation to be independent of Pol V. H3K9me1 and H3K9me2 tend to be enriched on Pol V-independent 24-nt siRNA loci, whereas various active histone modifications are enriched on Pol V-dependent 24-nt siRNA loci. DNA methylation is required for 24-nt siRNAs biosynthesis on Pol V-dependent loci but not on Pol V-independent loci. Our results reveal the function of rice Pol V for long noncoding RNA production, DNA methylation, 24-nt siRNA accumulation, and reproductive development.
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http://dx.doi.org/10.1073/pnas.2100709118DOI Listing
July 2021

Ti C T MXene Conductive Layers Supported Bio-Derived Fe Se /MXene/Carbonaceous Nanoribbons for High-Performance Half/Full Sodium-Ion and Potassium-Ion Batteries.

Adv Mater 2021 Jul 19:e2101535. Epub 2021 Jul 19.

Sino-Russian International Joint Laboratory for Clean Energy and Energy Conversion Technology, College of Physics, International Center of Future Science, Jilin University, Changchun, 130012, P. R. China.

Owing to their cost-effectiveness and high energy density, sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are becoming the leading candidates for the next-generation energy-storage devices replacing lithium-ion batteries. In this work, a novel Fe Se heterostructure is prepared on fungus-derived carbon matrix encapsulated by 2D Ti C T MXene highly conductive layers, which exhibits high specific sodium ion (Na ) and potassium ion (K ) storage capacities of 610.9 and 449.3 mAh g at a current density of 0.1 A g , respectively, and excellent capacity retention at high charge-discharge rates. MXene acts as conductive layers to prevent the restacking and aggregation of Fe Se sheets on fungus-derived carbonaceous nanoribbons, while the natural fungus functions as natural nitrogen/carbon source to provide bionic nanofiber network structural skeleton, providing additional accessible pathways for the high-rate ion transport and satisfying surface-driven contribution ratios at high sweep rates for both Na/K ions storages. In addition, in situ synchrotron diffraction and ex situ X-ray photoelectron spectroscopy measurements are performed to reveal the mechanisms of storage and de-/alloying conversion process of Na in the Fe Se /MXene/carbonaceous nanoribbon heterostructure. As a result, the assembled Na/K full cells containing MXene-supported Fe Se @carbonaceous anodes possess stable large-ion storage capabilities.
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http://dx.doi.org/10.1002/adma.202101535DOI Listing
July 2021

Enhenced cell adhesion on collagen I treated parylene-C microplates.

J Biomater Sci Polym Ed 2021 Jul 21:1-12. Epub 2021 Jul 21.

Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, PR China.

On account of unique mechanical property and inertia, parylene-C has become a promising material for microdevices especially in three-dimensional microstructures loaded with cells. However, parylene-C is not favorable for cell adhesion, and a routine procedure is to modify it with a new adhesive layer. Herein, the parylene-C substrates with or without collagen I (Col-I) coating were adopted to estimate the influence of micro-environment change on cell attachment and spreading. After modification with Col-I, cauliflower-like particles presented on the substrate surface. Contact angle was significantly decreased after Col-I modification, which suggested the surface hydrophilicity was enhanced. Furthermore, cells cultured on parylene-C surface with Col-I treatment showed increased proliferation rate and spreading areas. In order to test the adhesion strength, a series of fixed size parylene-C microplates was fabricated, and cell suspension concentration was adjusted to culture a single cell on one microplate. The microplate was folded by the autogenous shrinkage force of cell. The folding angles of parylene-C microplates with Col-I treatment exhibited higher folding angle (112.6 ± 15.6°) than untreated samples (46.7 ± 5.9°). The work proved the existence of Col-I layer was particularly important, especially in analysis of cells mechanics using parylene-C microplate as a substrate.
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http://dx.doi.org/10.1080/09205063.2021.1958465DOI Listing
July 2021

A NO/ROS/RNS cascaded-releasing nano-platform for gas/PDT/PTT/immunotherapy of tumors.

Biomater Sci 2021 Jul 16. Epub 2021 Jul 16.

School of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266109, China.

Nitric oxide (NO) gas treatment offers a promising strategy for tumor therapy; however, its practical application is still limited due to its poor efficacy and biotoxicity which were caused by gas leakage during blood delivery. Herein, a nano-platform (CMH-OBN) composed of chlorin e6-melanin-hyaluronic acid nanoparticles (Ce6-MNP-HA, CMH) and oxidized bletilla striata polysaccharide microcapsules (Oxi-BSP) carrying NO donors was prepared for responsive and cascaded release of NO, reactive oxygen species (ROS) and its secondary metabolite reactive nitrogen species (RNS) in tumor sites. Melanin not only endowed CMH with good photothermal properties, but also helped Ce6 to produce a large number of ROS under near-infrared (NIR) irradiation. OBN microcapsules, which were sensitive to ROS, can release NO donors under the stimulation of ROS released by CMH nanoparticles under NIR irradiation and can further release NO in the tumor microenvironment (TME) with high expression of glutathione (GSH). NO could further up-regulate soluble guanylate cyclase-cyclic guanosine monophosphate (sGC-cGMP) signal pathways to relieve hypoxia, thus further enhancing the photodynamic therapy (PDT). Moreover, the cascaded release of ROS and NO could produce RNS with higher lethality, which could sequentially initiate the cellular apoptotic procedure and promote immunotherapy by activating T cells at the tumor sites. More interestingly, the CMH-OBN nano-platform could supply magnetic resonance imaging (MRI) and infrared photothermal imaging guidance for tumor therapy. In conclusion, the development of a CMH-OBN nano-platform provides a satisfactory demonstration by combining NO therapy with photothermal therapy (PTT), PDT and immunotherapy for the treatment of cancer.
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http://dx.doi.org/10.1039/d1bm00726bDOI Listing
July 2021

Upregulation of the long noncoding RNA UBOX5 antisense RNA 1 (UBOX5-AS1) under hypoxic conditions promotes epithelial-mesenchymal transition in endometriosis.

Ann Transl Med 2021 May;9(9):790

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Endometriosis is a debilitating gynecological condition that manifests many common malignant features, including migration and invasion. Hypoxia is a hallmark of endometriosis, characterized by endometrial cell metastasis via epithelial-mesenchymal transition (EMT). The long noncoding RNA (lncRNA) UBOX antisense RNA 1 (UBOX5-AS1) has been shown to be upregulated in ovarian endometriosis. However, the molecular mechanisms and biological functions of lncRNA UBOX5-AS1 in hypoxia-induced endometriosis EMT remain to be explored.

Methods: Normal, eutopic, and ectopic endometrium from ovarian endometriosis tissues were collected, and the expressions of hypoxia inducible factor (HIF)-1α, lncRNA UBOX5-AS1, E-cadherin, and vimentin were analyzed by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting analysis. Primary human endometrial epithelial cells and human endometrial epithelial adenocarcinoma Ishikawa cell lines were cultured under hypoxic conditions, and western blotting analysis and immunocytochemistry were performed to investigate hypoxia-induced EMT. Moreover, and lncRNA UBOX5-AS1 were overexpressed and knocked down in endometrial epithelial cells to explore the role and mechanisms of lncRNA UBOX5-AS1 in hypoxia-triggered EMT. The migration and invasion potential of human endometrial epithelial cells was detected by Transwell migration/invasion assays.

Results: In ovarian endometriosis, the expression of hypoxia-inducible factor-1α () and lncRNA UBOX5-AS1 were significantly increased, and this was accompanied by EMT. Furthermore, endometrial epithelial cells cultured under hypoxic conditions exhibited elevated lncRNA UBOX5-AS1 expression, as well as migration, invasion, and an EMT-like phenotype. This data indicated that signaling was crucial for hypoxia-induced lncRNA UBOX5-AS1 upregulation and the EMT process. Moreover, downregulation of lncRNA UBOX5-AS1 inhibited the hypoxia-induced EMT and attenuated cell migration and invasion.

Conclusions: The present research demonstrated that hypoxia upregulated the expression of lncRNA UBOX5-AS1 via -dependent signaling. The increased expression of lncRNA UBOX5-AS1 plays a vital role in mediating the hypoxia-regulated EMT and invasiveness of endometriosis, suggesting that lncRNA UBOX5-AS1 may be an important potential therapeutic target for endometriosis.
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http://dx.doi.org/10.21037/atm-20-4546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246194PMC
May 2021

Acute Myocardial Infarction Detection Using Deep Learning-Enabled Electrocardiograms.

Front Cardiovasc Med 2021 28;8:654515. Epub 2021 Jun 28.

Department of Cardiology, The Forth Affiliated Hospital of Guangxi Medical University, Liuzhou, China.

Acute myocardial infarction (AMI) is associated with a poor prognosis. Therefore, accurate diagnosis and early intervention of the culprit lesion are of extreme importance. Therefore, we developed a neural network algorithm in this study to automatically diagnose AMI from 12-lead electrocardiograms (ECGs). We used the open-source PTB-XL database as the training and validation sets, with a 7:3 sample size ratio. Twenty-One thousand, eight hundred thirty-seven clinical 12-lead ECGs from the PTB-XL dataset were available for training and validation (15,285 were used in the training set and 6,552 in the validation set). Additionally, we randomly selected 205 ECGs from a dataset built by Chapman University, CA, USA and Shaoxing People's Hospital, China, as the testing set. We used a residual network for training and validation. The model performance was experimentally verified in terms of area under the curve (AUC), precision, sensitivity, specificity, and F1 score. The AUC of the training, validation, and testing sets were 0.964 [95% confidence interval (CI): 0.961-0.966], 0.944 (95% CI: 0.939-0.949), and 0.977 (95% CI: 0.961-0.991), respectively. The precision, sensitivity, specificity, and F1 score of the deep learning model for AMI diagnosis from ECGs were 0.827, 0.824, 0.950, and 0.825, respectively, in the training set, 0.789, 0.818, 0.913, and 0.803, respectively, in the validation set, and 0.830, 0.951, 0.951, and 0.886, respectively, in the testing set. The AUC for automatic AMI location diagnosis of LMI, IMI, ASMI, AMI, ALMI were 0.969 (95% CI: 0.959-0.979), 0.973 (95% CI: 0.962-0.978), 0.987 (95% CI: 0.963-0.989), 0.961 (95% CI: 0.956-0.989), and 0.996 (95% CI: 0.957-0.997), respectively. The residual network-based algorithm can effectively automatically diagnose AMI and MI location from 12-lead ECGs.
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http://dx.doi.org/10.3389/fcvm.2021.654515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273385PMC
June 2021

Developing a second-generation clinical candidate AAV vector for gene therapy of familial hypercholesterolemia.

Mol Ther Methods Clin Dev 2021 Sep 5;22:1-10. Epub 2021 May 5.

Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Gene therapy for hypercholesterolemia offers the potential to sustainably ameliorate disease for life with a single dose. In this study, we demonstrate the combinatorial effects of codon and vector optimization, which significantly improve the efficacy of an adeno-associated virus (AAV) vector in the low-density lipoprotein receptor (LDLR)-deficient mouse model ( , double knockout [DKO]). This study investigated vector efficacy following the combination of intervening sequence 2 (IVS2) of the human beta-globin gene and codon optimization with the previously developed gain-of-function, human LDLR triple-mutant variant (hLDLR-L318D/K809R/C818A) in the treatment of homozygous familial hypercholesterolemia (HoFH). Vector doses as low as 3 × 10 genome copies (GC)/kg achieved a robust reduction of serum low-density lipoprotein cholesterol (LDL-C) by 98% in male LDLR-deficient mice. Less efficient LDL-C reduction was observed in female mice, which was attributable to lower gene transfer efficiency in liver. We also observed persistent and stable transgene expression for 120 days, with LDL-C levels being undetectable in male DKO mice treated with the second-generation vector. In conclusion, codon and vector optimization enhanced transgene expression and reduced serum LDL-C levels effectively at a lower dose in LDLR-deficient mice. The second-generation clinical candidate vector we have developed has the potential to achieve therapeutic effects in HoFH patients.
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http://dx.doi.org/10.1016/j.omtm.2021.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237527PMC
September 2021

Loss of an ABC transporter in Arabidopsis thaliana confers hypersensitivity to the anti-cancer drug bleomycin.

DNA Repair (Amst) 2021 Jul 8;106:103174. Epub 2021 Jul 8.

College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. Electronic address:

Bleomycin (BLM) is used as an anti-cancer drug clinically. However, some cancer cells are resistant to BLM, which limits the usage of BLM in chemotherapy. But the underlying mechanism of such resistance is poorly understood. Here we show that the ATP binding cassette (ABC) transporter ABCC3 is required for the BLM-resistance in Arabidopsis. In a genetic screen for ddrm (DNA damage response mutants), we found that loss of ABCC3 confers the hypersensitivity to BLM. In contrast, overexpression of ABCC3 enhances the resistance to BLM. We further found that the expression of ABCC3 is induced by BLM, which is dependent on the protein kinase ATM and the transcription factor SOG1, two master regulators of DNA damage response. Our study revealed that the ABC transporter contributes to BLM-resistance, indicating that the combination of ABC transporter inhibitors and BLM may enhance the efficacy of BLM in cancer therapy.
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http://dx.doi.org/10.1016/j.dnarep.2021.103174DOI Listing
July 2021

Recent advances in developing small-molecule inhibitors against SARS-CoV-2.

Acta Pharm Sin B 2021 Jul 2. Epub 2021 Jul 2.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 200032, China.

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.apsb.2021.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260826PMC
July 2021

Comparative observation of atmospheric nitrous acid (HONO) in Xi'an and Xianyang located in the GuanZhong basin of western China.

Environ Pollut 2021 Jul 5;289:117679. Epub 2021 Jul 5.

State Key Laboratory for Structural Chemistry of Unstable and Stable Species Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, PR China; University of Chinese Academy of Sciences, Beijing, China.

HONO is an important component of reactive nitrogen (N) and precursors of OH radical. However, the source and removal of HONO are not clear. Here, measurements of HONO (May 18-31, 2018) were conducted in Xi'an and Xianyang simultaneously for the first time. The relationship between HONO and other N (such as NO and NO) in two cities was analyzed. The mixing ratio of HONO in Xi'an was 1.2 ± 0.8 ppbv, and that in Xianyang was 1.2 ± 1.1 ppbv. The nighttime HONO mixing ratio was higher in Xianyang, while the daytime HONO was higher in Xi'an. Compared with the contribution from heterogeneous process of NO, direct emissions and homogeneous processes (NO + OH) were less important for nocturnal HONO formation in these two cities. The relative contribution of heterogeneous process in Xianyang was more important than that in Xi'an. The reaction of NO upon aerosols surface was identified as an important source of HONO for two sites. The conversion of NO on the other surfaces might attend the heterogeneous formation of HONO in Xianyang site. Daytime HONO budget analysis indicated that there was an additional unknown formation process of HONO at two sites. The net OH production rate from HONO (from 08:00 to 17:00) was 1.6 × 10 and 1.3 × 10 molecule/(cm s) for Xian and Xianyang, 5.2 and 3.5 times higher than from O photolysis. Besides, a dust storm appeared during this observation period, and the impact of local emission and transport processes was separately analyzed. The sources, characteristics, and effects of HONO identified in this study laid a foundation for further research on HONO and air pollution in the Guanzhong area.
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http://dx.doi.org/10.1016/j.envpol.2021.117679DOI Listing
July 2021

Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study.

Infect Dis Ther 2021 Sep 9;10(3):1699-1713. Epub 2021 Jul 9.

Department of Pharmacy, Ruijin Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: No clinical study has investigated the use of ceftazidime-avibactam combination schemes with an in vitro non-susceptible antimicrobial that could be superior to ceftazidime-avibactam monotherapy against carbapenem-resistant Klebsiella pneumoniae.

Methods: We performed a retrospective cohort study at two tertiary hospitals in China for patients with carbapenem-resistant Klebsiella pneumoniae infection treated with ceftazidime-avibactam for at least 72 h. A Cox proportional hazards regression model was used to evaluate covariates that potentially affected 30-day mortality.

Results: Sixty-two patients were eligible for our study; 41 (66.1%) received ceftazidime-avibactam combination therapy and 21 (33.9%) received ceftazidime-avibactam monotherapy. The overall 30-day mortality was 33.9% (21 patients): 24.4% (10/41) and 47.6% (11/21), P = 0.028, in combination and monotherapy groups, respectively. Combination therapy was significantly associated with lower 30-day mortality (Hazard ratio, 0.167; 95% Confidence Interval, 0.060-0.465, P = 0.001). At the same time, a higher APACHE II score, use of vasoactive drugs and comorbidity of organ transplantation were considered factors that increased mortality. The propensity score showed no significant alterations with other variables after adding it to the final model. In the subgroup analysis, the protective effect was revealed when combined with carbapenems, tigecycline or fosfomycin were applied, and in the following subgroups of patients: with sepsis, with creatinine clearance > 50 mL/min, stayed in the intensive care unit ≤ 30 days or underwent mechanical ventilation.

Conclusions: Ceftazidime-avibactam combined with another in vitro non-susceptible antimicrobial, especially carbapenems, fosfomycin and tigecycline, could significantly decrease the 30-day mortality rate for critically ill patients with carbapenem-resistant Klebsiella pneumoniae infection. Further investigation should be carried out to confirm this conclusion and identify autofit antimicrobials in ceftazidime-avibactam combination schemes.
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http://dx.doi.org/10.1007/s40121-021-00479-7DOI Listing
September 2021

Micro-Nano Processing of Active Layers in Flexible Tactile Sensors via Template Methods: A Review.

Small 2021 Jul 8:e2100804. Epub 2021 Jul 8.

State Key Laboratory for Superlattices and Microstructures Institute of Semiconductors, Chinese Academy of Sciences and Center of Materials Science and Optoelectronic Engineering, University of Chinese Academy of Sciences, Beijing, 100083, China.

Template methods are regarded as an important method for micro-nano processing in the active layer of flexible tactile sensors. These template methods use physical/chemical processes to introduce micro-nano structures on the active layer, which improves many properties including sensitivity, response/recovery time, and detection limit. However, since the processing process and applicable conditions of the template method have not yet formed a perfect system, the development and commercialization of flexible tactile sensors based on the template method are still at a relatively slow stage. Despite the above obstacles, advances in microelectronics, materials science, nanoscience, and other disciplines have laid the foundation for various template methods, enabling the continuous development of flexible tactile sensors. Therefore, a comprehensive and systematic review of flexible tactile sensors based on the template method is needed to further promote progress in this field. Here, the unique advantages and shortcomings of various template methods are summarized in detail and discuss the research progress and challenges in this field. It is believed that this review will have a significant impact on many fields of flexible electronics, which is beneficial to promote the cross-integration of multiple fields and accelerate the development of flexible electronic devices.
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http://dx.doi.org/10.1002/smll.202100804DOI Listing
July 2021

Correlation Between Calcification Characteristics of Carotid Atherosclerotic Plaque and Plaque Vulnerability.

Ther Clin Risk Manag 2021 1;17:679-690. Epub 2021 Jul 1.

Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China.

Purpose: To investigate the relationship between calcification characteristics of carotid atherosclerotic plaque and lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH).

Methods: Patients with severe carotid stenosis undergoing carotid endarterectomy (CEA) were selected. Ultrasound and CT angiography (CTA) were performed to evaluate the calcification characteristics of the plaque before the surgery.

Results: A total of 142 patients were included and 142 pathological specimens of postoperative plaque were obtained accordingly. There were 78 plaques (54.9%) with LRNC and 41 (28.9%) with IPH. The plaque with LRNC had higher calcification rate (93.6%) compared with the plaque with IPH (87.8%). LRNC was often found in multiple calcification (P = 0.003) and mixed type calcification (P = 0.001). Multiple calcification was more likely to combine with IPH (P = 0.008), while simple basal calcification was not likely to combine IPH (P = 0.002). Smaller granular calcification was more likely to be associated with IPH (P < 0.05). In multivariate regression analysis of IPH and calcification characteristics, simple basal calcification was still a protective factor for IPH (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005), while multiple calcification was closely related to the occurrence of IPH (OR, 3.58; 95% CI, 1.49-8.61; P = 0.004).

Conclusion: Calcification characteristics of carotid atherosclerotic plaques are closely related to the vulnerability of plaques, especially multiple calcification and mixed type calcification.
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http://dx.doi.org/10.2147/TCRM.S303485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257076PMC
July 2021

Pharmacologic Targeting of Mcl-1 Induces Mitochondrial Dysfunction and Apoptosis in B-Cell Lymphoma Cells in a and Dependent Manner.

Clin Cancer Res 2021 Jul 7. Epub 2021 Jul 7.

City of Hope National Medical Center, Duarte, California.

Purpose: Bcl-2 has been effectively targeted in lymphoid malignancies. However, resistance is inevitable, and novel approaches to target mitochondrial apoptosis are necessary. AZD5991, a selective BH3-mimetic in clinical trials, inhibits Mcl-1 with high potency.

Experimental Design: We explored the preclinical activity of AZD5991 in diffuse large B-cell lymphoma (DLBCL) and ibrutinib-resistant mantle cell lymphoma (MCL) cell lines, MCL patient samples, and mice bearing DLBCL and MCL xenografts using flow cytometry, immunoblotting, and Seahorse respirometry assay. Cas9 gene editing and functional drug screen assays helped identify mechanisms of resistance to Mcl-1 inhibition.

Results: Mcl-1 was expressed in DLBCL and MCL cell lines and primary tumors. Treatment with AZD5991 restricted growth of DLBCL cells independent of cell of origin and overcame ibrutinib resistance in MCL cells. Mcl-1 inhibition led to mitochondrial dysfunction as manifested by mitochondrial membrane depolarization, decreased mitochondrial mass, and induction of mitophagy. This was accompanied by impairment of oxidative phosphorylation. and were essential for sensitivity to Mcl-1, and oxidative phosphorylation was implicated in resistance to Mcl-1 inhibition. Induction of prosurvival proteins (e.g., Bcl-xL) in stromal conditions that mimic the tumor microenvironment rendered protection of primary MCL cells from Mcl-1 inhibition, while BH3-mimetics targeting Bcl-2/xL sensitized lymphoid cells to AZD5991. Treatment with AZD5991 reduced tumor growth in murine lymphoma models and prolonged survival of MCL PDX mice.

Conclusions: Selective targeting Mcl-1 is a promising therapeutic approach in lymphoid malignancies. apoptotic network and metabolic reprogramming underlie susceptibility to Mcl-1 inhibition.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0464DOI Listing
July 2021

First Report of Black Spot Caused by Penicillium citreosulfuratum on Saffron in Chongming Island, China.

Plant Dis 2021 Jul 2. Epub 2021 Jul 2.

shanghai, China;

Saffron (Crocus sativus L.) is a world-famous source of dye and spices and an important medicinal plant, which is cultivated on a large scale on Chongming Island (31.62° N, 121.39° E) in Shanghai, China. In August 2020, a survey of saffron was conducted in this area, and black spots were observed on about 10% of plants. Characteristics of the disease were: The bottom of the corm was darkened in the groove and scattered black spots could be observed after peeling off the membranous scale leaves. The junction of lesions and healthy parts was light brown. As the lesions expanded, approximately 80% of the surface of the corm became dark brown to bluish gray. The inside of the corm was also necrotic. In order to isolate the pathogen, ten diseased corms with typical symptoms were selected. All corms were first treated with 75% ethanol for 30 s, 0.1% HgCl2 for 5 min, and then rinsed with sterile water 5 times. Next, tissue pieces (5 mm × 5 mm) at the margin of lesions were cut out and placed on the potato dextrose agar (PDA) medium. After incubating at 28°C for 5 days, fungi were separated and purified by using the hyphal-tip technique. A total of six pure cultures with different colony morphologies were obtained, of which only the isolate MF3 was present in ten diseased corms. The isolate MF3 was inoculated on the PDA and cultured at 28°C for 10 days and characteristics of the fungus colonies were: colonies sub-circular, reaching 28 to 30 mm diam, from above rough, dense, fluffy, blue-gray, with some white spots and central point raised, and outer margin form an irregular, narrow, white ring; from below, yellow with light-green. The hyphae were slender, with many septa. The conidiophores were typically smooth walled, short, and slender and either monoverticillate with very short stipes or as irregularly biverticillate. Phialides were ampulliform, 5 to 10 per metula, 5 to 8 × 2 to 3 µm. Conidia were smooth and globose, and ranged in diameter from 1.4 to 1.7 µm (n=50). Molecular identification of the fungus was made by PCR amplification of the internal transcribed spacer (ITS) region of rDNA and β-tubulin gene using primers ITS1/ITS4 (White et al. 1990), TUB2Fd/TUB4Rd (Aveskamp et al. 2009) respectively. The ITS (MW881446) and β-tubulin (MW911464) sequences of the fungus were similar to the ITS (MN592912) and β-tubulin (KY469126) sequences of the epitype of Penicillium citreosulfuratum with 99.81% and 99.56% identity, respectively. According to the morphological and molecular characterization, the isolate MF3 was identified as P. citreosulfuratum (Visagie et al. 2016). For pathogenicity testing, the fungus was grown on PDA and incubated at 28°C for 5 days. Then mycelial plugs (5 mm diam.) were inoculated on the scalpel incision square wounds of surface-disinfected corms and mock-inoculated corms received only PDA plugs. Corms were placed in sterile plastic bottles and observed after culturing at 28°C for 21 days. Each treatment had three replicates and the experiment was repeated twice. The results showed that corms inoculated with P. citreosulfuratum developed diseased with similar symptoms as in the field. No disease symptoms were observed on control corms. Re-isolations were performed from inoculated corms, and all re-isolated fungi were confirmed as P. citreosulfuratum, verifying the fungus as the pathogen based on Koch's postulates. To our knowledge, this is the first report of the pathogen causing black spot disease of saffron. Although the disease is not fatal to saffron, to a certain extent it will cause a reduction in the production of the crop. In addition, this pathogen has not been reported to be pathogentic to other plant species.
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http://dx.doi.org/10.1094/PDIS-05-21-1038-PDNDOI Listing
July 2021

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Mol Pharmacol 2021 Jul 1. Epub 2021 Jul 1.

Pharmacy, National University of Singapore, Singapore

Mounting evidence have revealed that despite the high degree of sequence homology between cytochrome P450 3A isoforms (i.e. CYP3A4 and CYP3A5), they have the propensities to exhibit vastly different irreversible and reversible interactions with a single substrate. We have previously established that benzbromarone (BBR), a potent uricosuric agent utilized in the management of gout, irreversibly inhibits CYP3A4 via mechanism-based inactivation (MBI). However, it remains unelucidated if CYP3A5 - its highly homologous counterpart - is susceptible to inactivation by BBR. Using three structurally-distinct probe substrates, we consistently demonstrated that MBI was not elicited in CYP3A5 by BBR. Our covalent docking models and molecular dynamics simulations suggested that disparities in the susceptibilities towards MBI could be attributed to the specific effects of BBR covalent adducts on the F-F' loop. Serendipitously, we also discovered that BBR reversibly activated CYP3A5-mediated rivaroxaban hydroxylation where apparent increased and decreased with increasing BBR concentration. Fitting data to the two-site model yielded interaction factors α and β of 0.44 and 5.88, respectively, thereby confirming heterotropic activation of CYP3A5 by BBR. Furthermore, heteroactivation was suppressed by the CYP3A inhibitor ketoconazole in a concentration-dependent manner and decreased with increasing pre-incubation time, implying that activation was incited via binding of parent BBR molecule within the enzymatic active site. Finally, non-covalent docking revealed that CYP3A5 can more favorably accommodate both BBR and rivaroxaban in concert as compared to CYP3A4 which further substantiated our experimental observations. While we have previously demonstrated that BBR inactivates CYP3A4, it remains uninterrogated if it could also elicit MBI in CYP3A5, which possesses considerable sequence homology. Here, we report that BBR exhibits differential irreversible and reversible interactions with CYP3A4 and CYP3A5 and provided potential mechanistic insights on the structural molecular determinants underpinning their diverging interaction profiles. Our findings reinforce the importance of discerning between the kinetic behavior of CYP3A due to their propensities for distinct interaction profiles with a common substrate.
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http://dx.doi.org/10.1124/molpharm.121.000256DOI Listing
July 2021

A prognostic nomogram based on competing endogenous RNA network for clear-cell renal cell carcinoma.

Cancer Med 2021 Jun 30. Epub 2021 Jun 30.

Department of Oncology, Tianjin Medical University Second Hospital, Hexi, Tianjin, China.

Background: Clear-cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts in understanding the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) was involved in the development of varied tumors. However, a comprehensive analysis of the prognostic model based on lncRNA-miRNA-mRNA ceRNA regulatory network of ccRCC with large-scale sample size and RNA-sequencing expression data is still limited.

Methods: RNA-sequencing expression data were taken out from GTEx database and TCGA database, a total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC-specific genes were obtained by WGCNA and differential expression analysis. Following, the communication of mRNAs and lncRNAs with targeted miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was further constructed by univariate Cox regression, Lasso methods, and multivariate Cox regression analysis.

Results: A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dysregulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature including eight genes based on this ceRNA was determined followed by the development of a nomogram predicting 1-, 3-, and 5-year survival probability for ccRCC.

Conclusion: It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.
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http://dx.doi.org/10.1002/cam4.4109DOI Listing
June 2021

Scalable mRNA and siRNA Lipid Nanoparticle Production Using a Parallelized Microfluidic Device.

Nano Lett 2021 07 30;21(13):5671-5680. Epub 2021 Jun 30.

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

A major challenge to advance lipid nanoparticles (LNPs) for RNA therapeutics is the development of formulations that can be produced reliably across the various scales of drug development. Microfluidics can generate LNPs with precisely defined properties, but have been limited by challenges in scaling throughput. To address this challenge, we present a scalable, parallelized microfluidic device (PMD) that incorporates an array of 128 mixing channels that operate simultaneously. The PMD achieves a >100× production rate compared to single microfluidic channels, without sacrificing desirable LNP physical properties and potency typical of microfluidic-generated LNPs. In mice, we show superior delivery of LNPs encapsulating either Factor VII siRNA or luciferase-encoding mRNA generated using a PMD compared to conventional mixing, with a 4-fold increase in hepatic gene silencing and 5-fold increase in luciferase expression, respectively. These results suggest that this PMD can generate scalable and reproducible LNP formulations needed for emerging clinical applications, including RNA therapeutics and vaccines.
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http://dx.doi.org/10.1021/acs.nanolett.1c01353DOI Listing
July 2021

Microwave reheating increases the resistant starch content in cooked rice with high water contents.

Int J Biol Macromol 2021 Aug 25;184:804-811. Epub 2021 Jun 25.

International Institute for Nanocomposites Manufacturing (IINM), WMG, University of Warwick, Coventry CV4 7AL, United Kingdom. Electronic address:

This study explored how microwave reheating (to about 73 °C at different power levels) affects the microstructure and digestion characteristics of cooked rice with different water contents (1.1 and 1.5 times that of rice in weight). Irrespective of water content, mainly the V-type crystallites remained after microwaving reheating, with slight changes in other multi-scale structural features. Only at a relatively high water content (1.5) and with a power level high enough could short-range order be reduced. Such microwave reheating increased the digestion resistance of cooked rice. At a water content of 1.1 times, increasing the microwave power led to a decreased rapid digestible starch (RDS) content and an increased resistant starch (RS) content. With a higher water content (1.5), the enhancement of digestion resistance with higher microwave power was less significant but still, a reduced slowly digestible starch (SDS) content and a higher RS content were observed.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.136DOI Listing
August 2021

Patient manifested as left ventricular non-compaction.

Heart 2021 Jul;107(14):1166-1184

Cardiology Division, West China Hospital, Sichuan University, Chengdu, China

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http://dx.doi.org/10.1136/heartjnl-2021-319370DOI Listing
July 2021

Image-Guided TME-Improving Nano-Platform for Ca Signal Disturbance and Enhanced Tumor PDT.

Adv Healthc Mater 2021 Jun 24:e2100789. Epub 2021 Jun 24.

College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, 700 Changcheng Road, Qingdao, 266109, China.

Dysfunction of the calcium balancing system and disruption of calcium distribution can induce abnormal intracellular calcium overload, further causing serious damage and even cell death, which provides a potential therapeutic approach for tumor treatment. Herein, a nano-platform, which includes [email protected]@mSiO @PL-HA NPs (UCRSPH) and SA-CaO nanoparticles, is prepared for improving the tumor micro-environment (TME), Ca signal disturbance as well as enhanced photodynamic tumor therapy (PDT). UCRSPH combined with SA-CaO can alter TME and relieve hypoxia of the tumor to realize self-reinforcing PDT under near-IR irradiation (980 nm). The ruthenium red (RuR) in the UCRSPH NPs can be released to the cytoplasm after endocytosis of the nanoparticles, target Ca channel proteins on the endoplasmic reticulum and mitochondria, sarcoplasmic reticulum Ca -ATPase (SERCA), and mitochondrial calcium uniporter (MCU). The combined participation of nanoparticles and RuR promotes Ca imbalance and cytoplasmic calcium overload with the assistance of CaO , and provides tumor cells higher sensitivity to PDT. Furthermore, the nano-platform also provides fluorescence imaging and calcification computed tomography imaging for in vivo treatment guidance. In conclusion, this image-guided nano-platform show potential for highly specific, efficient combined therapy against tumor cells with minimal side-effects to normal cells by integrating TME improvement, self-reinforcing PDT, and Ca signal disturbance.
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http://dx.doi.org/10.1002/adhm.202100789DOI Listing
June 2021

A photo-sensitizable phage for multidrug-resistant therapy and biofilm ablation.

Chem Sci 2020 Nov 16;12(3):1054-1061. Epub 2020 Nov 16.

State Key Laboratory of Fine Chemicals, Dalian University of Technology Dalian 116024 China

Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both and experiments prove that APNB can efficiently treat infection. Particularly, the recovery from infection after APNB treatment is faster than that with ampicillin and polymyxin B . Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice.
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http://dx.doi.org/10.1039/d0sc04889eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179032PMC
November 2020

Fructus Ligustri Lucidi aqueous extract promotes calcium balance and short-chain fatty acids production in ovariectomized rats.

J Ethnopharmacol 2021 Jun 19;279:114348. Epub 2021 Jun 19.

Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address:

Ethnopharmacological Relevance: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear.

Aim Of The Study: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats.

Materials And Methods: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy.

Results: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats.

Conclusions: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial.
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http://dx.doi.org/10.1016/j.jep.2021.114348DOI Listing
June 2021

Diverse Right Ventricular Remodeling Evaluated by MRI and Prognosis in Eisenmenger Syndrome With Different Shunt Locations.

J Magn Reson Imaging 2021 Jun 21. Epub 2021 Jun 21.

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, PR China.

Background: Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension.

Purpose: To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location.

Study Type: Prospective observational study.

Population: Fifty-four adults with ES (16 with pre-tricuspid shunt and 38 with post-tricuspid shunt).

Field Strength/sequence: 3.0 T/cine MRI with balanced steady-state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase-sensitive reconstruction, and T1 mapping with modified Look-Locker inversion recovery sequence.

Assessment: Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV-pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all-cause mortality or readmission for heart failure.

Statistical Tests: The independent samples t-test, Fisher's exact test or Chi-squared test, and the Kaplan-Meier method were used. P < 0.05 was considered significant.

Results: Compared to patients with post-tricuspid shunt, patients with pre-tricuspid shunt were significantly older and had higher N-terminal pro-B-type natriuretic peptide concentrations and poorer exercise tolerance. Pre-tricuspid shunt showed significantly larger RV dimensions (end-diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m ), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV-PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre-tricuspid shunt than post-tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre-tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204-7.172).

Data Conclusion: ES with pre-tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis.

Level Of Evidence: 2 Technical Efficacy Stage: 5.
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http://dx.doi.org/10.1002/jmri.27791DOI Listing
June 2021

HCV poly U/UC sequence-induced inflammation leads to metabolic disorders in vulvar lichen sclerosis.

Life Sci Alliance 2021 Aug 18;4(8). Epub 2021 Jun 18.

Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology and School of Life Sciences, Fudan University, Shanghai, China

Vulvar lichen sclerosis (VLS) is a dermatologic disorder that affects women worldwide. Women with VLS have white, atrophic papules on the vulva. They suffer from life-long intense pruritus. Corticosteroids are the first-line of treatments and the most effective medicines for VLS. Although VLS has been speculated as an autoimmune disease for a long time, its pathogenesis and the molecular mechanism is largely unknown. We performed a comprehensive multi-omics analysis of paired samples from VLS patients as well as healthy donors. From the RNA-seq analysis, we found that VLS is correlated to abnormal antivirus response because of the presence of Hepatitis C Virus poly U/UC sequences. Lipidomic and metabolomic analysis revealed that inflammation-induced metabolic disorders of fatty acids and glutathione were likely the reasons for pruritus, atrophy, and pigment loss in the vulva. Thus, the present study provides an initial interpretation of the pathogenesis and molecular mechanism of VLS and suggests that metabolic disorders that affect the vulva may serve as therapeutic targets for VLS.
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http://dx.doi.org/10.26508/lsa.202000906DOI Listing
August 2021

A Rationally Designed Micellar Nanocarrier for the Delivery of Hydrophilic Methotrexate in Psoriasis Treatment.

ACS Appl Bio Mater 2020 Aug 22;3(8):4832-4846. Epub 2020 Jul 22.

Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.

Methotrexate (MTX) is broadly applied in the clinic for the treatments of cancers and autoimmune diseases. Targeted delivery of MTX is attractive to improve its efficacy and reduce off-target toxicity. However, MTX encapsulation in nanoparticle is challenging due to its high water solubility. We rationally designed a well-defined telodendrimer (TD) nanocarrier based on MTX structure to sequester it in nanoparticles. Riboflavin (Rf) and positive charges groups were precisely conjugated on TD to form multivalent hydrogen bonds, π-π stacking and electrostatic interactions with MTX. A reverse micelle approach was developed to preset MTX and TD interactions in the core of micelles, which ensures the effective MTX loading upon dispersion into aqueous solution. As results, MTX loading capacity reaches over 20% (w/w) in the optimized nanocarrier with the particle size of 20-30 nm. The nanoformulations sustain the release of MTX in a controlled manner and exhibit excellent hemocompatibility. The cellular uptake of MTX was significantly improved by the nanoformulations. The potency of MTX nanoformulations is comparable to the free MTX in cytotoxicity. A psoriasis-like skin inflammation model was induced in mouse by imiquimod (IMQ) stimulation. MTX nanoformulations improved the psoriasis targeting and exhibited a superior long-lasting efficacy in reducing skin inflammation compared with the free MTX in psoriasis treatment.
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http://dx.doi.org/10.1021/acsabm.0c00342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204631PMC
August 2020
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