Publications by authors named "Zhihong Liu"

675 Publications

MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease.

JCI Insight 2021 Apr 13. Epub 2021 Apr 13.

National Clinical Research Center for Kidney Diseases, Nanjing University School of Medicine, Nanjing, China.

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in chronic kidney disease (CKD) patients. MiRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only results in LVH but also suppresses miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuates LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes leads to cardiomyocyte hypertrophy by upregulating the calcineurin signalling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23 (FGF-23), uraemic toxin, angiotensin-II (Ang-II) and transforming growth factor-β (TGF-β), suppress cardiac miRNA-30 expression, while miRNA-30 supplementation blunts cardiomyocyte hypertrophy induced by such factors. These results uncover a novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.
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http://dx.doi.org/10.1172/jci.insight.138027DOI Listing
April 2021

The Role of CD276 in Cancers.

Front Oncol 2021 26;11:654684. Epub 2021 Mar 26.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Objective: Aberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect.

Data Sources: Database including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved.

Results: CD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies.

Conclusion: CD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors.
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http://dx.doi.org/10.3389/fonc.2021.654684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032984PMC
March 2021

Development of EST-SSRs from the ark shell (Scapharca broughtonii) transcriptome and their application in genetic analysis of four populations.

Genes Genomics 2021 Apr 9. Epub 2021 Apr 9.

Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, 266071, People's Republic of China.

Background: The ark shell (Scapharca broughtonii) is one of the most economically important mollusks in the Bohai Sea and Yellow Sea of China. In recent years, ark shells from the Korean population were introduced to China for seed propagation and culture.

Objective: To explore the impact of the introduction of Korean ark shell on the genetic diversity of native population in China.

Methods: Simple sequence repeat (SSR) is effective and widely used tool for genetic analysis. In this study, 180 EST-SSRs were selected and verified by polymerase chain reaction and polyacrylamide gel electrophoresis. Subsequently, five polymorphic EST-SSRs were screened and their primers were modified by fluorescein for use in the genetic analysis of four populations.

Results: Genetic analysis showed that 361 alleles amplified by five SSR loci were detected in the four populations. The number of alleles for the five SSRs ranged from 8 to 30, with a mean of 18.05 (standard deviation, SD = 6.492). The effective number of alleles varied from 2.253 to 22.222, with a mean of 10.596 (SD = 4.713). Observed heterozygosity and expected heterozygosity were 0.167-0.833 and 0.566-0.971, with average values of 0.520 (SD = 0.177) and 0.891 (SD = 0.062), respectively. Polymorphic information content ranged from 0.521 to 0.953, with a mean of 0.865 (SD = 0.070). The pairwise genetic differentiation coefficient (F) of the four populations ranged from 0.0267 to 0.0477, showing low genetic differentiation. The phylogenetic tree constructed by neighbor-joining method showed that the genetic distance between the Chinese Dalian native population and three Korean populations was relatively more far than that among those Korean populations.

Conclusion: The results indicated that the genetic structure of the Dalian wild population was less affected by the introduced Korean wild populations.
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http://dx.doi.org/10.1007/s13258-021-01090-3DOI Listing
April 2021

Integrated transcriptome and metabolome analysis reveals molecular responses of the clams to acute hypoxia.

Mar Environ Res 2021 Mar 26;168:105317. Epub 2021 Mar 26.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Laboratory for Marine Fisheries Science and Food Production Processes, Pilot National Laboratory for Marine Science and Technology, Qingdao, 266071, China. Electronic address:

Mudflat shellfish have evolved well-adapted strategies for coping with dynamic environmental fluxes and stressful conditions, including oxygen availability. The Manila clams Ruditapes philippinarum are worldwide cultured shellfish in marine intertidal zone, which usually encounter great risk of acute hypoxia exposure in coastal habitats. To reveal the effects of acute hypoxia on metabolic changes of the clams, we performed the integrated analysis of transcriptomics and metabolomics to investigate the global changes of genes and metabolites during acute hypoxia stress at the whole-organism level. The comparative transcriptome analysis reveals that the clams show the remarkable depression in a variety of biological performance, such as metabolic rates, neuronal activity, biomineralization activity, and cell proliferation and differentiation at the hypoxic condition. The metabolomic analysis reveals that amino acid metabolism plays a critical role in the metabolic changes of the clams in response to acute hypoxia. A variety of free amino acids may not only be served as the potential osmolytes for osmotic regulation, but also may contribute to energy production during the acute hypoxia exposure. The metabolite analysis also reveals several important biomarkers for metabolic changes, and provides new insights into how clams deal with acute hypoxia. These findings suggest that clams may get through acute hypoxia stress by the adaptive metabolic strategy to survive short-period of acute hypoxia which is likely to occur in their typical habitat. The present findings will not only shed lights on the molecular and metabolic mechanisms of adaptive strategies under stressful conditions, but also provide the signaling metabolites to assess the physiological states of clams in aquaculture.
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http://dx.doi.org/10.1016/j.marenvres.2021.105317DOI Listing
March 2021

Risk Assessment for Longitudinal Trajectories of Modifiable Lifestyle Factors on Chronic Kidney Disease Burden in China: A Population-based Study.

J Epidemiol 2021 Apr 3. Epub 2021 Apr 3.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine.

Background: Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from noncommunicable diseases. We aimed to examine the longitudinal trajectories in risk factors, estimate their impact on CKD burden in China from 1991 to 2011, and project trends in the next 20 years.

Methods: We used data from a cohort of the China Health and Nutrition Survey and applied the comparative risk assessment method to estimate the number of CKD events attributable to all non-optimal levels of each risk factors.

Results: In 2011, current smoking was the leading individual attributable factor for CKD burden in China responsible for 7.9 (95% CI, 7.5-8.3) million CKD cases with a population-attributable fraction of 8.7% (95% CI, 6.0-11.6), while the rates of smoking have reduced and may have mitigated the increase in CKD. High triglyceride (TG) and high systolic blood pressure (SBP) were the leading metabolic risk factors responsible for 6.8 (95% CI, 6.4-7.1) million and 5.8 (95% CI, 5.5-6.1) million CKD-attributable cases, respectively. Additionally, the number of CKD cases associated with high body mass index (BMI), high diastolic blood pressure (DBP), high plasma glucose, and low high-density lipoprotein cholesterol (HDL-C) was 5.4 (95% CI, 5.1-5.6), 3.9 (95% CI, 3.7-4.1), 3.0 (95% CI, 2.8-3.1) and 2.6 (95% CI, 2.5-2.8) million, respectively.

Conclusions: Current smoking, high TG, and high SBP were the top three risk factors that contributed to CKD burden in China. Increased BMI, DBP, plasma glucose, and decreased HDL-C were also associated with the increase in CKD burden.
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http://dx.doi.org/10.2188/jea.JE20200497DOI Listing
April 2021

Generation of the induced pluripotent stem cell line (NCKDi002-A) from a 22-year-old patient with Focal Segmental Glomerular Sclerosis carrying a heterozygous mutation in WT1 gene.

Stem Cell Res 2021 Mar 17;53:102293. Epub 2021 Mar 17.

Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Zhejiang Laboratory for Systems and Precision Medicine, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China. Electronic address:

Focal Segmental Glomerular Sclerosis (FSGS) is a glomerular disease which can be classified into primary, secondary, genetic, and unknown forms. WT1 mutation has been shown to be associated with this disorder. Recently, we identified a mutation in the Zinc finger C2H2 domain of WT1 gene in a patient with FSGS who also carried a family history of end-stage renal disease (ESRD). The Peripheral Blood Mononuclear Cells (PBMCs) of the patient were obtained and a line of induced pluripotent stem cells (iPSCs) was successfully generated. The iPSC line will be useful for further study of the pathogenesis and drug screening for FSGS.
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http://dx.doi.org/10.1016/j.scr.2021.102293DOI Listing
March 2021

Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes.

J Am Soc Nephrol 2021 Mar 26. Epub 2021 Mar 26.

Medical School of Nanjing University, Nanjing, China

Background: Transcriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood.

Methods: The distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance.

Results: Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish.

Conclusions: FOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs' regulatory roles in glomeruli transcription programs.
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http://dx.doi.org/10.1681/ASN.2020081177DOI Listing
March 2021

Chi-miR-370-3p regulates hair follicle development of Inner Mongolian cashmere goats.

G3 (Bethesda) 2021 Mar 23. Epub 2021 Mar 23.

College of Animal Science, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.

Background: MicroRNAs (miRNAs), a class of 22 nucleotide (nt) non-coding RNAs, negatively regulate mRNA post-transcriptional modification in various biological processes. Initiation of skin hair follicles in cashmere goats is a dynamic process involving many key signalling molecules, but the associated cellular biological mechanisms induced by these key signalling molecules have not been reported.

Results: In this study, differential expression, bioinformatics, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on miRNA expression profiles of Inner Mongolian cashmere goats at 45, 55, and 65 days during the foetal period, and chi-miR-370-3p was identified and investigated further. Real-time fluorescence quantification (qRT-PCR), dual luciferase reporting, and western blotting results showed that transforming growth factor beta receptor 2 (TGF-βR2) and fibroblast growth factor receptor 2 (FGFR2) were the target genes of chi-miR-370-3p. Chi-miR-370-3p also regulated the expression of TGF-βR2 and FGFR2 at mRNA and protein levels in epithelial cells and dermal fibroblasts. DNA staining, Cell Counting Kit-8 (CCK8), and fluorescein-labelled Annexin V results showed that chi-miR-370-3p inhibited the proliferation of epithelial cells and fibroblasts, but had no effect on apoptosis. Cell scratch test results showed that chi-miR-370-3p promoted the migration of epithelial cells and fibroblasts.

Conclusion: Chi-miR-370-3p inhibits the proliferation of epithelial cells and fibroblasts by targeting TGF-βR2 and FGFR2, thereby improving cell migration ability, and ultimately regulating the fate of epithelial cells and dermal fibroblasts to develop the placode (PC) and dermal condensate (DC), inducing hair follicle development.
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http://dx.doi.org/10.1093/g3journal/jkab091DOI Listing
March 2021

A Versatile Strategy for Constructing Ratiometric Upconversion Luminescent Probe with Sensitized Emission of Energy Acceptor.

Anal Chem 2021 04 22;93(13):5635-5643. Epub 2021 Mar 22.

College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.

When fabricating ratiometric optical probes using lanthanide-doped upconversion nanoparticles (UCNPs), which are promising luminescent materials that have widely been utilized in biosensing and bioimaging as energy donors, it is still a challenge to obtain the emission signal of energy acceptors with reasons unclear so far. Herein, we reveal that the energy-transfer efficiency and brightness of UCNPs as well as the aggregation-caused quenching (ACQ) of energy accepting dyes are the main factors restricting the emission of energy acceptors, and we have circumvented this problem by modulating the structure of UCNPs and the assembly manner of the energy donor-acceptor pair. On this basis, a proof-of-concept ratiometric upconversion nanoprobe was constructed for hydrogen sulfide (HS) detection with an elaborate dye Fl-1 as an energy acceptor. As the HS concentration increased, the emission intensity of Fl-1 at 525 nm increased gradually, accompanied by a decrease of upconversion luminescence at 480 nm, thus providing a ratiometric signal of / dependent on the HS concentration. This probe was able to track HS in living cells and zebrafish and visualize the HS level of mice in physiological processes.
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http://dx.doi.org/10.1021/acs.analchem.1c00470DOI Listing
April 2021

Machine Learning for Prediction and Risk Stratification of Lupus Nephritis Renal Flare.

Am J Nephrol 2021 Mar 19:1-9. Epub 2021 Mar 19.

National Clinical Research Centre of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China,

Background: Renal flare of lupus nephritis (LN) is strongly associated with poor kidney outcomes, and predicting renal flare and stratifying its risk are important for clinical decision-making and individualized management to reduce LN flare.

Methods: We randomly divided 1,694 patients with biopsy-proven LN, who had achieved remission after treatment, into a derivation cohort (n = 1,186) and an internal validation cohort (n = 508), at a ratio of 7:3. The risk of renal flare 5 years after remission was predicted using an eXtreme Gradient Boosting (XGBoost) method model, developed from 59 variables, including demographic, clinical, immunological, pathological, and therapeutic characteristics. A simplified risk score prediction model (SRSPM) was developed from important variables selected by XGBoost model using stepwise Cox regression for practical convenience.

Results: The 5-year relapse rates were 39.5% and 38.2% in the derivation and internal validation cohorts, respectively. Both the XGBoost model and the SRSPM had good predictive performance, with a C-index of 0.819 (95% confidence interval [CI]: 0.774-0.857) and 0.746 (95% CI: 0.697-0.795), respectively, in the validation cohort. The SRSPM comprised 6 variables, including partial remission and endocapillary hypercellularity at baseline, age, serum Alb, anti-dsDNA, and serum complement C3 at the point of remission. Using Kaplan-Meier analysis, the SRSPM identified significant risk stratification for renal flares (p < 0.001).

Conclusions: Renal flare of LN can be readily predicted using the XGBoost model and the SRSPM, and the SRSPM can also stratify flare risk. Both models are useful for clinical decision-making and individualized management in LN.
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http://dx.doi.org/10.1159/000513566DOI Listing
March 2021

The exposure of gadolinium at environmental relevant levels induced genotoxic effects in Arabidopsis thaliana (L.).

Ecotoxicol Environ Saf 2021 Jun 16;215:112138. Epub 2021 Mar 16.

Faculty of Infrastructure Engineering, Dalian University of Technology, Dalian 116023, China.

Rare Earth Elements (REEs) are increasingly being used in agriculture and are also used to produce high end technological devices, thereby increasing their anthropogenic presence in the environment. However, the ecotoxicological mechanism of REEs on organisms is not fully understood. In this study, the effects of gadolinium (Gd) addition on Arabidopsis thaliana (L.) were investigated at both physiological and molecular levels. Four treatments (0, 10, 50 and 200 μmol·L Gd) were used in the exposure tests. Biomass, root length and chlorophyll content in shoots/roots were measured to investigate the plant's physiological response to Gd stress. Random amplified polymorphic (RAPD)-Polymerase Chain Reaction (PCR) and methylation sensitive arbitrarily primed (MSAP)-PCR were used to investigate changes in genetic variation and DNA methylation of A. thaliana when exposed to Gd. At the physiological level, it was found that low concentration of Gd (10 μmol·L) could significantly increase the plant biomass and root length, while the growth of A. thaliana was significantly inhibited when exposed to 200 μmol·L of Gd, yet the total soluble protein content in aerial plant parts increased significantly by 24.2% when compared to the control group. Among the 12 primers considered in the RAPD assessment, at the molecular level, only four primers revealed different patterns in their genomic DNA. Compared to the control group, the treatment with 50 μmol·L of Gd was associated with lower polymorphism, while the treatment with 200 μmol·L of Gd was associated with higher polymorphism. The polymorphism frequencies for the 50 μmol·L of Gd and the 200 μmol·L of Gd were 4.67% and 20.33%, respectively. The MSAP analysis revealed that the demethylation (D) type of Arabidopsis genomic DNA increased significantly under 10 and 50 μmol·L of Gd, while the methylation (M) type was also significantly increased under 200 μmol·L of Gd. Generally, the total methylation polymorphism (D+M) increased with an increase of Gd concentration. It was found that high concentrations of Gd appeared to cause DNA damage, but low concentrations of Gd (as low as 10 μmol·L) were associated with DNA methylation change. Further, it was verified by Real time Reverse Transcription PCR (RT-PCR) on the bands detected by the MSAP analysis, that the genes relative to processes including cell cycle, oxidative stress and apoptosis, appeared to be regulated by methylation under Gd stress. These findings reveal new insight regarding ecotoxicity mechanisms of REEs on plants.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112138DOI Listing
June 2021

Supplementation with Iron in Pulmonary Arterial Hypertension: Two Randomized Crossover Trials.

Ann Am Thorac Soc 2021 Mar 18. Epub 2021 Mar 18.

Imperial College London, 4615, National Heart and Lung Institute, London, London, United Kingdom of Great Britain and Northern Ireland;

Rationale: Iron deficiency, in the absence of anaemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin levels. The safety and benefit of parenteral iron replacement in this patient population is unclear.

Objectives: To evaluate the safety and efficacy of parenteral iron replacement in pulmonary arterial hypertension.

Methods: In two randomised, double blind, placebo-controlled 12 week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject®) 1000 mg (or 15 mg/kg if weight < 66.7Kg) or saline as placebo and 17 patients in China received iron dextran (Cosmofer®) 20 mg iron/kg body weight or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by: a serum ferritin < 37 µg/l or iron < 10.3 µmol/l or transferrin saturations < 16.4%.

Results: Both iron treatments were well tolerated and improved iron status. Analysed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6 minute walk test) or cardio-pulmonary haemodynamics, as assessed by right heart catheterisation, cardiac magnetic resonance or plasma NT-proBNP, at 12 weeks.

Conclusion: Iron repletion by administration of a slow release iron preparation as a single infusion to PAH patients with iron deficiency without overt anaemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).
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http://dx.doi.org/10.1513/AnnalsATS.202009-1131OCDOI Listing
March 2021

Clinical significance of prognostic nutritional index in renal cell carcinomas.

Medicine (Baltimore) 2021 Mar;100(10):e25127

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan.

Abstract: Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan-Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25-3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil-lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet-lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37-1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45-1.96, P < .001). Furthermore, low PNI (<41-51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26-2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40-2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.
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http://dx.doi.org/10.1097/MD.0000000000025127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969234PMC
March 2021

Effect of Surface Property on the Release and Oral Absorption of Solid Sirolimus-Containing Self-microemulsifying Drug Delivery System.

AAPS PharmSciTech 2021 Mar 14;22(3):108. Epub 2021 Mar 14.

Department of Pharmacy, Fuzong Clinical Medical College of Fujian Medical University (900 Hospital of the Joint Logistics Team), Fuzhou, 350025, People's Republic of China.

The combination of self-microemulsifying drug delivery system (SMEDDS) and mesoporous silica materials favors the oral delivery of poorly water-soluble drugs (PWSD). However, the influence of the surface property of the mesopores towards the drug release and in vivo pharmacokinetics is still unknown. In this study, SBA-15 with hydroxyl groups (SBA-15-H), methyl groups (SBA-15-M), amino groups (SBA-15-A), or carboxyl groups (SBA-15-C) was combined with SMEDDS containing sirolimus (SRL). The diffusion and self-emulsifying of SMEDDS greatly improved the drug release over the raw SRL and SRL-SBA-15-R (R referred to as the functional groups). Results of drug absorption and X-ray photoelectron spectroscopy (XPS) showed strong hydrogen binding between SRL and the amino groups of SBA-15-A, which hindered the drug release and oral bioavailability of SRL-SMEDDS-SBA-15-A. The favorable release of SRL-SMEDDS-SBA-15-C (91.31 ± 0.57%) and SRL-SMEDDS-SBA-15-M (91.76 ± 3.72%) contributed to enhancing the maximum blood concentration (C) and the area under the concentration-time curve (AUC). In conclusion, the release of SRL-SMEDDS-SBA-15-R was determined by the surface affinity of the SBA-15-R and the interaction between the SRL molecules and the surface of SBA-15-R. This study suggested that the SMEDDS-SBA-15 was a favorable carrier for PWSD, and the surface property of the mesopores should be considered for the optimization of the SMEDDS-SBA-15.
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http://dx.doi.org/10.1208/s12249-021-01978-zDOI Listing
March 2021

Chromatin accessibility of kidney tubular cells under stress reveals key transcription factor mediating acute and chronic kidney disease.

FEBS J 2021 Mar 13. Epub 2021 Mar 13.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China.

Cellular injury caused by stimuli plays an important role in the progression of various diseases including acute and chronic kidney diseases. The dynamic transcriptional regulation responding to stimuli underlies the important mechanism of injury. In this study, we investigated the regulatory elements and their dynamic activities in kidney tubular epithelial cells. We captured the chromatin accessibility and gene expression with ATAC-seq and RNA sequencing under a variety of extracellular stimuli including H O , TGF-β1, and FG4592 which is an agonist of hypoxia-inducible factor. Our results revealed both condition-specific and condition-shared transcription regulation. Interestingly, the shared regulation program revealed that the key transcription factor HNF1B-mediated cellular reprogramming leads to a common change among the stimuli. We found the HNF1B regulatory network was significantly disrupted in various kidney diseases.
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http://dx.doi.org/10.1111/febs.15818DOI Listing
March 2021

Gold nanoparticle integrated artificial nanochannels for label-free detection of peroxynitrite.

Chem Commun (Camb) 2021 Apr 12;57(29):3583-3586. Epub 2021 Mar 12.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials & Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.

A label-free method for rapid and highly sensitive detection of peroxynitrite (ONOO) was proposed by employing well-designed N-(4-aminobutyl)-N-ethylisoluminol (ABEI) capped AuNP integrated artificial nanochannels. This work paves a new pathway to develop a versatile platform for the detection of different biological small molecules and reactive species.
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http://dx.doi.org/10.1039/d0cc08410gDOI Listing
April 2021

Origin of regional springtime ozone episodes in the Sichuan Basin, China: Role of synoptic forcing and regional transport.

Environ Pollut 2021 Mar 1;278:116845. Epub 2021 Mar 1.

Plateau Atmosphere and Environment Key Laboratory of Sichuan Province, School of Atmospheric Sciences, Chengdu University of Information Technology, Chengdu, China.

The Sichuan Basin (SCB) located in southwestern China has long been considered the most polluted city cluster with exposure to unhealthy levels of ozone (O) at times. However, the features of O regional transport and source contributions in SCB are poorly understood. In this study, ambient measurements, ERA5 reanalysis dataset, IASI O column, and the Weather Research and Forecasting-Community Multiscale Air Quality (WRF-CMAQ) modeling system coupled with the Integrated Source Apportionment Method (ISAM) module were used to investigate the formation mechanism and sources of a severe O episode in spring 2020 over the SCB. In the first stage of the O episode, a high-pressure system persisted over the western SCB and caused northeasterly wind fields, leading to enhanced regional transport from the northern boundary with the O contribution from the boundary exceeding 50% across the SCB. As the synoptic pattern evolved, southeasterly winds dominated the SCB and the stagnant zone over the Chengdu Plain confined O originating from the southern SCB and Chongqing city, leading to the accumulation of precursors and elevated O levels. During the O episode, transportation and industrial sources were major contributors to O formation especially for the Chengdu Plain and Chongqing city. In addition, the O-rich air mass in the nocturnal residual layer that formed over Chongqing city was transported to the Chengdu Plain through southeastern corridor at 400-1600m above ground-level under the prevailing southeasterly winds. With sunrise and the development of the atmospheric boundary layer, the O-rich air mass in the residual layer (RL) was entrained to the ground-level via vertical mixing, which further enhanced O pollution across the Chengdu Plain. Our results revealed the mechanism of regional transport via northeastern and southeastern corridors during an O episode and demonstrated the need for joint emission regulation across the SCB to mitigate O pollution.
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http://dx.doi.org/10.1016/j.envpol.2021.116845DOI Listing
March 2021

Hexavalent TRAIL fusion protein eftozanermin alfa optimally clusters apoptosis-inducing TRAIL receptors to induce on-target antitumor activity in solid tumors.

Cancer Res 2021 Mar 9. Epub 2021 Mar 9.

Oncology Discovery, AbbVie Inc.

TNF Receptor Apoptosis-Inducing Ligand (TRAIL) can activate cell surface death receptors resulting in potent tumor cell death via induction of the extrinsic apoptosis pathway. Eftozanermin alfa (ABBV-621) is a second-generation TRAIL receptor agonist engineered as an IgG1-Fc mutant backbone linked to two sets of trimeric native single chain TRAIL receptor binding domain monomers. This hexavalent agonistic fusion protein binds to the death-inducing DR4 and DR5 receptors with nanomolar affinity to drive on-target biological activity with enhanced caspase-8 aggregation and DISC formation independent of FcγR-mediated cross-linking, and without clinical signs or pathological evidence of toxicity in non-rodent species. ABBV-621 induced cell death in approximately 36% (45/126) of solid cancer cell lines in vitro at sub-nanomolar concentrations. An in vivo patient-derived xenograft (PDX) screen of ABBV-621 activity across 15 different tumor indications resulted in an overall response (OR) of 29% (47/162). Although DR4 (TNFSFR10A) and/or DR5 (TNFSFR10B) expression levels did not predict the level of response to ABBV-621 activity in vivo, KRAS mutations were associated with elevated TNFSFR10A and TNFSFR10B and were enriched in ABBV-621 responsive colorectal carcinoma (CRC) PDX models. To build upon the OR of ABBV-621 monotherapy in CRC (45%; 10/22) and pancreatic cancer (35%; 7/20), we subsequently demonstrated that inherent resistance to ABBV-621 treatment could be overcome in combination with chemotherapeutics or with selective inhibitors of BCL-XL. In summary, these data provide a pre-clinical rationale for the ongoing Phase-1 clinical trial (NCT03082209) evaluating the activity of ABBV-621 in cancer patients.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2178DOI Listing
March 2021

FRET Modulated Signaling: A Versatile Strategy to Construct Photoelectrochemical Microsensors for in Vivo Analysis.

Angew Chem Int Ed Engl 2021 Mar 2. Epub 2021 Mar 2.

Guangzhou University, School of Chemistry and Chemical Engineering, CHINA.

Microelectrode-based electrochemical (EC) and photoelectrochemical (PEC) sensors are promising candidates for in vivo analysis of biologically important chemicals. However, limited selectivity in complicated biological systems and poor adaptability to electrochemically non-active species restrained their applications. Herein, we propose the concept of modulating the PEC output by a fluorescence resonance energy transfer (FRET) process. The emission of energy donor was dependent on the concentration of target SO2, which in turn served as the modulator of the photocurrent signal of the photoactive material. The employment of optical modulation circumvented the problem of selectivity, and the as-fabricated PEC microelectrode showed good stability and reproducibility in vivo. It was able to monitor fluctuations of SO2 levels in brains of rat models of cerebral ischemia-reperfusion and febrile seizure. More significantly, such a FRET modulated signaling strategy can be extended to diverse analytes.
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http://dx.doi.org/10.1002/anie.202101468DOI Listing
March 2021

Chromatin architecture reveals cell type-specific target genes for kidney disease risk variants.

BMC Biol 2021 Feb 24;19(1):38. Epub 2021 Feb 24.

National Clinical Research Center for Kidney Disease, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.

Background: Cell type-specific transcriptional programming results from the combinatorial interplay between the repertoire of active regulatory elements. Disease-associated variants disrupt such programming, leading to altered expression of downstream regulated genes and the onset of pathological states. However, due to the non-linear regulatory properties of non-coding elements such as enhancers, which can activate transcription at long distances and in a non-directional way, the identification of causal variants and their target genes remains challenging. Here, we provide a multi-omics analysis to identify regulatory elements associated with functional kidney disease variants, and downstream regulated genes.

Results: In order to understand the genetic risk of kidney diseases, we generated a comprehensive dataset of the chromatin landscape of human kidney tubule cells, including transcription-centered 3D chromatin organization, histone modifications distribution and transcriptome with HiChIP, ChIP-seq and RNA-seq. We identified genome-wide functional elements and thousands of interactions between the distal elements and target genes. The results revealed that risk variants for renal tumor and chronic kidney disease were enriched in kidney tubule cells. We further pinpointed the target genes for the variants and validated two target genes by CRISPR/Cas9 genome editing techniques in zebrafish, demonstrating that SLC34A1 and MTX1 were indispensable genes to maintain kidney function.

Conclusions: Our results provide a valuable multi-omics resource on the chromatin landscape of human kidney tubule cells and establish a bioinformatic pipeline in dissecting functions of kidney disease-associated variants based on cell type-specific epigenome.
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http://dx.doi.org/10.1186/s12915-021-00977-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905576PMC
February 2021

Flexible Designing Strategy to Construct Activatable NIR-II Fluorescent Probes with Emission Maxima beyond 1200 nm.

Anal Chem 2021 03 12;93(8):4006-4014. Epub 2021 Feb 12.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.

Activatable second near-infrared (NIR-II) fluorescent probes that can be lighted up by specific targets have attracted great attention because of their high specificity and resolution, which hold great promise in deep-tissue imaging. However, such probes were relatively rarely reported so far, and the emission maximum is still limited (mainly located at 900-1000 nm). To solve the problem, herein, we proposed a flexible strategy to modulate the emission wavelength of NIR-II fluorescent probes, and four proof-of-concept probes (, , , and ) based on D-π-A molecular skeleton were obtained. These probes can be activated by HS and the emission maximum located from 925 to 1205 nm, which was attributed to the cooperation of elongating the π-conjugated system and enhancing the electron-donating ability of the donor region. In these probes, exhibited the combination of long excitation/emission (925/1140 nm) and moderate quantum yield as well as high sensitivity toward HS, enabling us to track and image HS with high contrast. We expected that such a molecular design strategy will become an important approach to developing activatable NIR-II fluorescent probes with long emission.
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http://dx.doi.org/10.1021/acs.analchem.0c04990DOI Listing
March 2021

The value of cardiopulmonary exercise testing in the diagnosis of pulmonary hypertension.

J Thorac Dis 2021 Jan;13(1):178-188

Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Cardiopulmonary exercise testing (CPET) continuously analyzes the gas exchange of patients during rest, exercise, recovery, and simultaneously records the response of the cardiopulmonary system. This study aimed to observe the characteristics of CPET in patients with pulmonary hypertension (PH) and to explore the cutoff value of CPET variables in detecting PH. The diagnostic value of CPET was also investigated in a subgroup of patients who had an incorrect or missed diagnosis of PH by echocardiography.

Methods: Treatment-naïve patients with suspected PH who were admitted to Fuwai Hospital from January 2017 to August 2018 were consecutively enrolled. The gold standard criterion for PH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterization. General clinical materials, echocardiography, hemodynamics, and CPET data of the patients were collected and compared between groups. Logistic regression analyses were performed to explore the CPET variables that were independently associated with PH. To further validate the value of CPET for diagnosing PH, the CPET cutoff values obtained from receiver operating characteristic (ROC) curve analysis were used in patients who had an incorrect or missed diagnosis by echocardiography.

Results: Five hundred and fifty-nine patients were included in the study. Among them, patients with PH had significantly poorer CPET variables. Multivariate logistic regression analysis showed that peak work rate (WR), peak oxygen uptake (VO), and end-tidal carbon dioxide partial pressure (PetCO) at the anaerobic threshold (AT) were independently associated with PH after adjustment for age, sex, and body mass index. The above three CPET variables were all negatively correlated with mPAP. The combined CPET variable including peak WR, peak VO and PetCO at AT had the largest area under the ROC curve for the diagnosis of PH (0.890, 95% CI: 0.852-0.927, P<0.001). The cutoff value was 0.86, and the sensitivity and specificity were 81.8% and 86.5%, respectively. Using this cutoff value, 83.7% of patients who were misdiagnosed and 67.9% of patients who had a missed diagnosis by echocardiography were identified.

Conclusions: PH patients have decreased cardiopulmonary reserve, lower exercise tolerance, and increased ineffective ventilation. The combination of peak WR, peakVO, and PetCO at AT had increased sensitivity and specificity for the diagnosis of PH, and increased the specificity for identifying patients who had been misdiagnosed as PH by echocardiography.
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http://dx.doi.org/10.21037/jtd-20-1061bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867820PMC
January 2021

In silico identification of natural products from Traditional Chinese Medicine for cancer immunotherapy.

Sci Rep 2021 Feb 8;11(1):3332. Epub 2021 Feb 8.

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.

Advances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM.
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http://dx.doi.org/10.1038/s41598-021-82857-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870934PMC
February 2021

Aggregation-Induced Emission of Au/Ag Alloy Nanoclusters for Fluorescence Detection of Inorganic Pyrophosphate and Pyrophosphatase Activity.

Front Bioeng Biotechnol 2020 15;8:628181. Epub 2021 Jan 15.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules & College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China.

The development of sensitive and accurate detection of inorganic pyrophosphate (PPi) and pyrophosphatase activity (PPase) is important as they play vital roles in biological systems. However, it is still not satisfactory for most of the analytical methods for PPi and PPase because of their Cu-dependence and poor accuracy. Although the metal ion triggered aggregation-induced emission (AIE) of metal nanoclusters (NCs) offers a new approach to design a Cu-free strategy for the accurate determination of PPi and PPase recently, current methods are all focused on utilizing pure metal NCs. Alloy NCs incorporating the advantages of diverse metal usually can achieve improved behaviors in the application, such as enhanced sensitivity and stability. In this work, glutathione stabilized alloy Au/Ag NCs were synthesized via a simple method and used for the fluorescence detection of PPi and PPase based on a Zn-regulated AIE strategy. The controlled release of Zn by PPi and PPase could regulate the AIE of Au/Ag NCs and be employed to response PPi concentration and PPase activity. This method processes simple procedure, high sensitivity and stability, and low toxicity. In addition, we also studied the AIE behaviors of this Au/Ag NCs and offer some fundamental understanding of the AIE properties of water-soluble alloy NCs. This study not only provides a straightforward and new approach for PPi and PPase determination but a basis for further study on the AIE properties of alloy NCs and their application.
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http://dx.doi.org/10.3389/fbioe.2020.628181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844307PMC
January 2021

Highly Sensitive Near-Infrared Imaging of Peroxynitrite Fluxes in Inflammation Progress.

Anal Chem 2021 02 25;93(5):3035-3041. Epub 2021 Jan 25.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules & College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.

Inflammation is an important protection reaction in living organisms associated with many diseases. Since peroxynitrite (ONOO) is engaged in the inflammatory processes, illustrating the key nexus between ONOO and inflammation is significant. Due to the lack of sensitive ONOO detection methods, the research still remains at its infancy. Herein, a highly sensitive NIR fluorescence probe DDAO-PN for detection of ONOO in inflammation progress was reported. The probe responded to ONOO with significant NIR fluorescence enhancement at 657 nm (84-fold) within 30 s in solution. Intracellular imaging of exogenous ONOO with the probe demonstrated a 68-fold fluorescence increase (/). Impressively, the probe can detect ONOO fluxes in LPS-induced rear leg inflammation with a 4.0-fold fluorescence increase and LPS-induced peritonitis with an 8.0-fold fluorescence increase The remarkable fluorescence enhancement and quick response enabled real-time tracking of ONOO with a large signal-to-noise (S/N) ratio. These results clearly denoted that DDAO-PN was able to be a NIR fluorescence probe for detection and high-fidelity imaging of ONOO with high sensitivity and will boost the research of inflammation-related diseases.
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http://dx.doi.org/10.1021/acs.analchem.0c05118DOI Listing
February 2021

Adrenal Surgery for Synchronously Metastatic Adrenocortical Carcinoma: A Population-Based Analysis.

World J Surg 2021 May 22;45(5):1457-1465. Epub 2021 Jan 22.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, Sichuan, China.

Background: Metastatic adrenocortical carcinoma (ACC) is an aggressive cancer with poor prognosis, with limited treatment options. The survival benefit of adrenal surgery in patients with synchronous metastatic disease has not been well explored.

Methods: Patients with ACC with synchronous metastases were identified from the Surveillance, Epidemiology, and End Results database (2010-2016). The effect of adrenal surgery on different patterns of distant metastases was assessed. The overall survival was estimated by the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival outcome.

Results: A total of 202 patients with synchronous metastatic ACC were identified from the SEER database, 76 (37.6%) patients underwent adrenal surgery. Compared to nonsurgical patients, patients who underwent adrenal surgery had a better survival (median overall survival: 4 vs. 13 months, P < 0.001). In sub-analyses, except for patients with liver metastases (P = 0.670), adrenalectomy could consistently confer a significant survival benefit in patients with lung metastases (P = 0.003), bone metastases (P = 0.020), and multiple metastases (P = 0.002). Cox regression analysis revealed that in addition to adrenalectomy [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.45-0.92; P = 0.017], metastasectomy (HR = 0.48, 95% CI 0.26-0.86; P = 0.013), and chemotherapy (HR = 0.59, 95% CI 0.42-0.82; P = 0.002) were also associated with improved survival.

Conclusions: Our findings support the view that adrenal surgery may be associated with improved survival in patients with synchronous metastatic ACC (except for patients with liver metastases), and the metastatic sites have significant prognostic implications on survival outcomes with adrenal surgery.
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http://dx.doi.org/10.1007/s00268-021-05957-0DOI Listing
May 2021

The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery.

Nat Commun 2021 01 20;12(1):488. Epub 2021 Jan 20.

State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC of 2.1 μM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLpro in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.
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http://dx.doi.org/10.1038/s41467-020-20718-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817691PMC
January 2021

Malalignment and distal contact of short tapered stems could be associated with postoperative thigh pain in primary total hip arthroplasty.

J Orthop Surg Res 2021 Jan 19;16(1):67. Epub 2021 Jan 19.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.

Purpose: Short tapered stem placement has been extensively employed in total hip arthroplasty (THA). Suboptimal fixation tends to cause postoperative complications, such as thigh pain. However, it remains unclear whether poor seating/alignment of short tapered stems contributes to thigh pain. In this study, we retrospectively examined the factors that might be associated with thigh pain.

Methods: Medical records of 230 patients who had undergone THAs at our hospital were reviewed retrospectively. All patients received the same mediolateral (ML) short tapered femoral stems. The association between thigh pain and patients' demographics, radiographic findings, or the type of fitting of the femoral stems was investigated.

Results: In our cohort, 68 patients (27.8%) presented with thigh pain. Among 203 type I fit patients, 62 (30.5%) developed thigh pain, while only 6 out of 43 (12.2%) type II fit patients had thigh pain, with the differences being statistically significant (x = 6.706, p = 0.01). In addition, hip anteroposterior radiographs exhibited that the stem angulation (mean 2.52°), the variation in angulation (mean 1.32°), and the extent of femoral stem subsidence (mean 0.29 cm) were greater in patients with thigh pain than in their counterparts without thigh pain (all p < 0.05).

Conclusion: Malalignment and improper seating of short tapered stems could be at least one of the reasons for post-THA thigh pain. The distal contact between the stem tip and the medial femoral cortex might result in thigh pain. Our study suggested that distal implant contact should be avoided, and stem alignment should be meticulously performed in the placement of ML short tapered femoral stems for THA.
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http://dx.doi.org/10.1186/s13018-021-02215-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816452PMC
January 2021

Nomogram Predicting Survival to Assist Decision-Making of Metastasectomy in Patients With Metastatic Renal Cell Carcinoma.

Front Oncol 2020 7;10:592243. Epub 2020 Dec 7.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Sichuan, China.

The survival benefit of metastasectomy (MSX) in patients with metastatic renal cell carcinoma (mRCC) remains unclear. A reliable model to predict an individuals' risk of cancer-specific mortality (CSM) and to identify optimal candidates for MSX is needed. We identified 2,911 mRCC patients who underwent cytoreductive nephrectomy from the Surveillance, Epidemiology, and End Results database (2010-2015). Based on the Fine and Gray competing risks analyses, we created a nomogram to predict the survival of mRCC patients. Decision tree analysis was useful for patient stratification. The impact of MSX was assessed among three different subgroups. Overall, 579 (19.9%) cases underwent MSX. In the entire patients, the 1-, 2-, and 3-year cumulative incidence of CSM were 32.8, 47.2, and 57.9%, respectively. MSX was significantly associated with improved survival (hazard ratio [HR] = 0.875, 95% confidence interval [CI] 0.773-0.991; P = 0.015). Based on risk scores, patients were divided into three risk groups using decision tree analysis. In the low-risk group, MSX was significantly associated with a 12.8% risk reduction of 3-year CSM (HR = 0.689, 95% CI 0.507-0.938; P = 0.008), while MSX was not associated with survival in intermediate- and high-risk groups. We proposed a novel nomogram and patient stratification approach to identify suitable patients for MSX. The newly identified patient subgroup with a low-risk of CSM might benefit more from aggressive surgery. These results should be further validated and improved by the prospective trials.
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http://dx.doi.org/10.3389/fonc.2020.592243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793951PMC
December 2020