Publications by authors named "Jun Feng"

719 Publications

Discovery of 2-(Ortho-Substituted Benzyl)-Indole Derivatives as Potent and Orally Bioavailable RORγ Agonists with Antitumor Activity.

J Med Chem 2021 Oct 13. Epub 2021 Oct 13.

Eternity Bioscience Inc., 6 Cedarbrook Drive, Cranbury, New Jersey 08512, United States.

RORγ is a dual-functional drug target, which involves not only induction of inflammation but also promotion of cancer immunity. The development of agonists of RORγ promoting Th17 cell differentiation could provide a novel mechanism of action (MOA) as an immune-activating anticancer agent. Herein, we describe new 2-(ortho-substituted benzyl)-indole derivatives as RORγ agonists by scaffold hopping based on clinical RORγ antagonist VTP-43742. Interestingly, subtle structural differences of the compounds led to the opposite biological MOA. After rational optimization for structure-activity relationship and pharmacokinetic profile, we identified a potent RORγ agonist compound that was able to induce the production of IL-17 and IFNγ in tumor tissues and elicit antitumor efficacy in MC38 syngeneic mouse colorectal tumor model. This is the first comprehensive work to demonstrate the antitumor efficacy of an RORγ agonist.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00828DOI Listing
October 2021

The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients.

Sci Rep 2021 10 5;11(1):19752. Epub 2021 Oct 5.

Division of Cardiothoracic Surgery, Department of Surgery and, The Warren Alpert Medical School, Brown University, Providence, RI, 02903, USA.

Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.
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http://dx.doi.org/10.1038/s41598-021-99143-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492658PMC
October 2021

Malaria Deaths - China, 2011-2020.

China CDC Wkly 2021 Apr;3(17):360-365

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, China.

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http://dx.doi.org/10.46234/ccdcw2021.098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392890PMC
April 2021

China-UK-Tanzania Pilot Project on Malaria Control.

China CDC Wkly 2020 Oct;2(42):820-822

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Ministry of Science and Technology; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China.

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http://dx.doi.org/10.46234/ccdcw2020.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393141PMC
October 2020

High Frequency Mutations in and of in Response to Sulfadoxine-Pyrimethamine: A Cross-Sectional Survey in Returning Chinese Migrants From Africa.

Front Cell Infect Microbiol 2021 8;11:673194. Epub 2021 Sep 8.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China.

Background: Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against infection. However, increasing SP resistance (SPR) of affects the therapeutic efficacy of SP, and (encoding dihydrofolate reductase) and (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of and in isolated from infected Chinese migrant workers returning from Africa.

Methods: In total, 159 blood samples from -infected workers who had returned from Africa to Anhui, Shangdong, and Guangxi provinces were successfully detected and analyzed from 2017 to 2019. The SNPs in and were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview.

Results: High frequencies of the Asn51Ile (N51I), Cys59Arg(C59R), and Ser108Asn(S108N) mutant alleles were observed, with mutation frequencies of 97.60, 87.43, and 97.01% in , respectively. A triple mutation (IRN) in was the most prevalent haplotype (86.83%). Six point mutations were detected in DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in . In total, 5 haplotypes of the gene and 13 haplotypes of the gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA).

Conclusion: A high prevalence of point mutations in the and genes of isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous molecular monitoring of Sulfadoxine-Pyrimethemine combined therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.
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http://dx.doi.org/10.3389/fcimb.2021.673194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456993PMC
October 2021

Improving Arabic Sentiment Analysis Using CNN-Based Architectures and Text Preprocessing.

Comput Intell Neurosci 2021 6;2021:5538791. Epub 2021 Sep 6.

School of Information Science and Technology, Northwest University China, Xi'an, China.

Sentiment analysis is an essential process which is important to many natural language applications. In this paper, we apply two models for Arabic sentiment analysis to the ASTD and ATDFS datasets, in both 2-class and multiclass forms. Model MC1 is a 2-layer CNN with global average pooling, followed by a dense layer. MC2 is a 2-layer CNN with max pooling, followed by a BiGRU and a dense layer. On the difficult ASTD 4-class task, we achieve 73.17%, compared to 65.58% reported by Attia et al., 2018. For the easier 2-class task, we achieve 90.06% with MC1 compared to 85.58% reported by Kwaik et al., 2019. We carry out experiments on various data splits, to match those used by other researchers. We also pay close attention to Arabic preprocessing and include novel steps not reported in other works. In an ablation study, we investigate the effect of two steps in particular, the processing of emoticons and the use of a custom stoplist. On the 4-class task, these can make a difference of up to 4.27% and 5.48%, respectively. On the 2-class task, the maximum improvements are 2.95% and 3.87%.
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http://dx.doi.org/10.1155/2021/5538791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449738PMC
September 2021

Discovery of potent and selective Bcl-2 inhibitors with acyl sulfonamide skeleton.

Bioorg Med Chem 2021 Oct 8;47:116350. Epub 2021 Aug 8.

State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 201203 Shanghai, China. Electronic address:

The antiapoptotic protein B-cell lymphoma 2 (Bcl-2), overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, a series of novel derivatives with acyl sulfonamide skeleton was designed, synthesized, and evaluated as Bcl-2 inhibitors by means of bioisosteric replacement. Among them, compound 24g demonstrated equal efficient inhibition activity against RS4;11 cell line compared to positive control ABT-199. Moreover, it showed improved selectivity for Bcl-2/Bcl-xL inhibitory effects, the result of which was consistent with platelet toxicity studies. In vitro and in vivo pharmacokinetic properties of compound 24g had a significantly improved profiles. Taken together, those results suggested it as a promising candidate for development of novel therapeutics targeting Bcl-2 in cancer.
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http://dx.doi.org/10.1016/j.bmc.2021.116350DOI Listing
October 2021

Decreased albumin-to-alkaline phosphatase ratio predicted poor survival of resectable gastric cancer patients.

J Gastrointest Oncol 2021 Aug;12(4):1338-1350

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

Background: The albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown.

Methods: We retrospectively reviewed 227 resectable GC patients in our center. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS prediction.

Results: The AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ for both DFS (35.58 34.51, P<0.001) and OS (32.92 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 1,065, P<0.001) and OS (869 898, P<0.001) compared to the TNM system.

Conclusions: The AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.
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http://dx.doi.org/10.21037/jgo-21-430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421886PMC
August 2021

The molecular mechanism of GADD153 in apoptosis of keloid fibroblasts exposed to botulinum toxin type A.

J Cell Mol Med 2021 Oct 2;25(19):9402-9410. Epub 2021 Sep 2.

Department of plastic surgery, Peking University Shenzhen Hospital, Shenzhen, China.

Apoptosis plays a key role in keloids. Growth arrest and DNA damage-inducible gene 153 (GADD153) is regulated by apoptosis. Botulinum toxin type A (BTXA) can induce apoptosis in keloid fibroblasts. This research aimed to explore the hypothesis that GADD153 mediates apoptosis in keloid fibroblasts exposed to BTXA. BTXA significantly induced GADD153 protein and mRNA expression in keloid fibroblasts. Treatment with c-Jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and tumour necrosis factor-alpha (TNF-α) antibodies reversed the BTXA-induced GADD153 expression. BTXA enhanced the transcriptional activity of GADD153, whereas the GADD153 mutant plasmid, JNK siRNA and anti-TNF-α antibody treatment abolished the BTXA-induced transcriptional activity of GADD153. The addition of TNF-α to keloid fibroblasts markedly increased GADD153 protein expression. The addition of GADD153 siRNA, SP600125 and anti-TNF-α antibodies reversed cell death and caspase 3 and 9 activity induced by BTXA.
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http://dx.doi.org/10.1111/jcmm.16881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500951PMC
October 2021

A Novel CD73 Inhibitor SHR170008 Suppresses Adenosine in Tumor and Enhances Anti-Tumor Activity with PD-1 Blockade in a Mouse Model of Breast Cancer.

Onco Targets Ther 2021 24;14:4561-4574. Epub 2021 Aug 24.

R&D Center, Shanghai Hengrui Pharmaceutical Co. Ltd., Shanghai, 200245, People's Republic of China.

Introduction: CD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cells, and promote anti-PD-1 mAb therapy-induced immune escape. Consequently, developing a CD73 inhibitor as monotherapy and a potential beneficial combination partner with immune-checkpoint inhibitors needs investigation.

Methods: CD73 inhibitors were evaluated in vitro with soluble and membrane-bound CD73 enzymes, as well as its PD biomarker responses in human peripheral blood mononuclear cells (PBMC) by flow cytometry and ELISA. The binding modes of the molecules were analyzed via molecular modeling. The anti-tumor activity and synergistic effect of SHR170008 in combination with anti-PD-1 mAb were evaluated in a syngeneic mouse breast cancer model.

Results: SHR170008 was discovered during the initial structural modifications on the link between the ribose and the α-phosphate of AMPCP, which significantly improved the stability of the compound confirmed by the metabolite identification study. Further modifications on the adenine base of AMPCP improved the potency due to forming stronger interactions with CD73 protein. It exhibited potent inhibitory activities on soluble and endogenous membrane-bound CD73 enzymes, and induced IFNγ production, reversed AMP-suppressed CD25 and CD8/CD25 expression, and enhanced granzyme B production on CD8 T cells in human PBMC. SHR170008 showed dose-dependent anti-tumor efficacy with suppression of adenosine in the tumors in EMT6 mouse breast tumor model. The increase of adenosine in tumor tissue by anti-PD-1 mAb alone was suppressed by SHR170008 in the combination groups. Simultaneous inhibition of CD73 and PD-1 neutralization synergistically enhanced antitumor immunity and biomarkers in response, and exposures of SHR170008 were correlated with the efficacy readouts.

Conclusion: Our findings suggest that CD73 may serve as an immune checkpoint by generating adenosine, which suppresses the antitumor activity of anti-PD-1 mAb, and inhibition of CD73 may be a potential beneficial combination partner with immune-checkpoint inhibitors to improve their therapeutic outcomes in general.
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http://dx.doi.org/10.2147/OTT.S326178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403083PMC
August 2021

Quantitative X-ray tomographic analysis reveals calcium precipitation in cataractogenesis.

Sci Rep 2021 08 31;11(1):17401. Epub 2021 Aug 31.

Vision Science Program and School of Optometry, University of California, Berkeley, 693 Minor Hall, Berkeley, CA, 94720-2020, USA.

Cataracts, named for pathological light scattering in the lens, are known to be associated with increased large protein aggregates, disrupted protein phase separation, and/or osmotic imbalances in lens cells. We have applied synchrotron phase contrast X-ray micro-computed tomography to directly examine an age-related nuclear cataract model in Cx46 knockout (Cx46KO) mice. High-resolution 3D X-ray tomographic images reveal amorphous spots and strip-like dense matter precipitates in lens cores of all examined Cx46KO mice at different ages. The precipitates are predominantly accumulated in the anterior suture regions of lens cores, and they become longer and dense as mice age. Alizarin red staining data confirms the presence of calcium precipitates in lens cores of all Cx46KO mice. This study indicates that the spatial and temporal calcium precipitation is an age-related event associated with age-related nuclear cataract formation in Cx46KO mice, and further suggests that the loss of Cx46 promotes calcium precipitates in the lens core, which is a new mechanism that likely contributes to the pathological light scattering in this age-related cataract model.
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http://dx.doi.org/10.1038/s41598-021-96867-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408149PMC
August 2021

Mitoquinone Protects Podocytes from Angiotensin II-Induced Mitochondrial Dysfunction and Injury via the Keap1-Nrf2 Signaling Pathway.

Oxid Med Cell Longev 2021 13;2021:1394486. Epub 2021 Aug 13.

Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Podocyte mitochondrial dysfunction plays a critical role in the pathogenesis of chronic kidney disease (CKD). Previous studies demonstrated that excessive mitochondrial fission could lead to the overproduction of reactive oxygen species (ROS) and promote podocyte apoptosis. Therefore, the maintenance of stable mitochondrial function is a newly identified way to protect podocytes and prevent the progression of CKD. As a mitochondria-targeted antioxidant, mitoquinone (MitoQ) has been proven to be a promising agent for the prevention of mitochondrial injury in cardiovascular disease and Parkinson's disease. The present study examined the effects of MitoQ on angiotensin II- (Ang II-) induced podocyte injury both and . Podocyte mitochondria in Ang II-infused mice exhibited morphological and functional alterations. The observed mitochondrial fragmentation and ROS production were alleviated with MitoQ treatment. , alterations in mitochondrial morphology and function in Ang II-stimulated podocytes, including mitochondrial membrane potential reduction, ROS overproduction, and adenosine triphosphate (ATP) deficiency, were significantly reversed by MitoQ. Moreover, MitoQ rescued the expression and translocation of Nrf2 (nuclear factor E2-related factor 2) and decreased the expression of Keap1 (Kelch-like ECH-associated protein 1) in Ang II-stimulated podocytes. Nrf2 knockdown partially blocked the protective effects of MitoQ on Ang II-induced mitochondrial fission and oxidative stress in podocytes. These results demonstrate that MitoQ exerts a protective effect in Ang II-induced mitochondrial injury in podocytes via the Keap1-Nrf2 signaling pathway.
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http://dx.doi.org/10.1155/2021/1394486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380182PMC
August 2021

Genetic mapping high protein content QTL from soybean 'Nanxiadou 25' and candidate gene analysis.

BMC Plant Biol 2021 Aug 20;21(1):388. Epub 2021 Aug 20.

Southwest University, Chongqing, 400715, China.

Background: Soybean is a globally important legume crop that provides a primary source of high-quality vegetable protein and oil. Seed protein content (SPC) is a valuable quality trait controlled by multiple genes in soybean.

Results: In this study, we performed quantitative trait loci (QTL) mapping, QTL-seq, and RNA sequencing (RNA-seq) to reveal the genes controlling protein content in the soybean by using the high protein content variety Nanxiadou 25. A total of 50 QTL for SPC distributed on 14 chromosomes except chromosomes 4, 12, 14, 17, 18, and 19 were identified by QTL mapping using 178 recombinant inbred lines (RILs). Among these QTL, the major QTL qSPC_20-1 and qSPC_20-2 on chromosome 20 were repeatedly detected across six tested environments, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. 329 candidate DEGs were obtained within the QTL region of qSPC_20-1 and qSPC_20-2 via gene expression profile analysis. Nine of which were associated with SPC, potentially representing candidate genes. Clone sequencing results showed that different single nucleotide polymorphisms (SNPs) and indels between high and low protein genotypes in Glyma.20G088000 and Glyma.16G066600 may be the cause of changes in this trait.

Conclusions: These results provide the basis for research on candidate genes and marker-assisted selection (MAS) in soybean breeding for seed protein content.
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http://dx.doi.org/10.1186/s12870-021-03176-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377855PMC
August 2021

Treatment and outcomes of POEMS syndrome: changes in the past 20 years.

Blood Cancer J 2021 Aug 14;11(8):145. Epub 2021 Aug 14.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1038/s41408-021-00540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364551PMC
August 2021

Interplay between Cation and Anion Redox in Ni-Based Disordered Rocksalt Cathodes.

ACS Nano 2021 Aug 4. Epub 2021 Aug 4.

Energy Storage and Distributed Resources Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

The reversibility of the redox processes plays a crucial role in the electrochemical performance of lithium-excess cation-disordered rocksalt (DRX) cathodes. Here, we report a comprehensive analysis of the redox reactions in a representative Ni-based DRX cathode. The aim of this work is to elucidate the roles of multiple cations and anions in the charge compensation mechanism that is ultimately linked to the electrochemical performance of Ni-based DRX cathode. The low-voltage reduction reaction results in the low energy efficiency and strong voltage hysteresis. Our data reveal that the Mo migration between octahedral and tetrahedral sites enhances the O reduction potential, thus offering a potential strategy to improve energy efficiency. This work highlights the important role that the high-valence transition metal plays in the redox chemistry and provides useful insights into the potential pathway to further address the challenges in Ni-based DRX systems.
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http://dx.doi.org/10.1021/acsnano.1c03289DOI Listing
August 2021

SERS-ELISA determination of human carboxylesterase 1 using metal-organic framework doped with gold nanoparticles as SERS substrate.

Mikrochim Acta 2021 07 30;188(8):280. Epub 2021 Jul 30.

Guangxi Key Laboratory of Green Processing of Sugar Resources, College of Biological and Chemical Engineering, Guangxi University of Science and Technology, No.268 Donghuan Road, Chengzhong District, Liuzhou City, 545006, Guangxi Zhuang Autonomous Region, China.

By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 × 10 mol·L, and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determine hCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1-120 ng·mL, the SERS signal intensity of benzidine at 1609 cm gradually decreases with the increase of hCE 1 concentration (R = 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed.
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http://dx.doi.org/10.1007/s00604-021-04928-5DOI Listing
July 2021

LncRNA TMPO-AS1 suppresses the maturation of miR-335-5p to participate in polycystic ovary syndrome.

J Ovarian Res 2021 Jul 30;14(1):99. Epub 2021 Jul 30.

Department of Obstetrics and Gynecology, Suzhou Wuzhong People's Hospital, No.61, Dongwu North Road, Suzhou City, Jiangsu Province, 215128, P. R. China.

Background: TMPO-AS1 is a recently characterized oncogenic lncRNA in ovarian cancer. Its role in other ovary diseases is unknown. This study explored its role in polycystic ovary syndrome (PCOS).

Methods: Follicular fluid was extracted from both PCOS patients and controls. The levels of TMPO-AS1 and mature and premature miR-335-5p were analyzed by RT-qPCR. The role of TMPO-AS1 in regulating miR-355-5p maturation in granulosa-like tumor (KGN) cells was analyzed by overexpression experiments. The interaction between TMPO-AS1 and premature miR-335-5p was analyzed by RNA pull-down assay. The subcellular location of TMPO-AS1 in KGN cells was analyzed by nuclear fractionation assay. The role of TMPO-AS1 and miR-335-5p in KGN cell proliferation was analyzed by BrdU assay.

Results: TMPO-AS1 was increased in PCOS, while mature miR-355-5p was decreased in PCOS. TMPO-AS1 overexpression decreased mature miR-355-5p level but increased premature miR-355-5p. TMPO-AS1 was localized in both nucleus and cytoplasm. TMPO-AS1 directly interacted with premature miR-355-5p in KGN cells. TMPO-AS1 increased KGN cell proliferation while miR-355-5p decreased cell proliferation. The co-transfection assay showed that TMPO-AS1 reduced the suppressive effects of miR-355-5p on cell proliferation.

Conclusions: TMPO-AS1 might suppress miR-335-5p maturation to participate in PCOS.
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http://dx.doi.org/10.1186/s13048-021-00848-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325176PMC
July 2021

Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study.

Int J Environ Res Public Health 2021 07 9;18(14). Epub 2021 Jul 9.

Center for Tobacco Products, Food and Drug Administration, Silver Spring, MD 20993, USA.

Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case-control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds' ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use.
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http://dx.doi.org/10.3390/ijerph18147349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306295PMC
July 2021

Inhibition of mitochondrial reactive oxygen species improves coronary endothelial function after cardioplegic hypoxia/reoxygenation.

J Thorac Cardiovasc Surg 2021 Jun 26. Epub 2021 Jun 26.

Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address:

Objective: Cardioplegic ischemia-reperfusion and diabetes mellitus are correlated with coronary endothelial dysfunction and inactivation of small conductance calcium-activated potassium channels. Increased reactive oxidative species, such as mitochondrial reactive oxidative species, may contribute to oxidative injury. Thus, we hypothesized that inhibition of mitochondrial reactive oxidative species may protect coronary small conductance calcium-activated potassium channels and endothelial function against cardioplegic ischemia-reperfusion-induced injury.

Methods: Small coronary arteries and endothelial cells from the hearts of mice with and without diabetes mellitus were isolated and examined by using a cardioplegic hypoxia and reoxygenation model to determine whether the mitochondria-targeted antioxidant Mito-Tempo could protect against coronary endothelial and small conductance calcium-activated potassium channel dysfunction. The microvessels or mouse heart endothelial cells were treated with or without Mito-Tempo (0-10 μM) 5 minutes before and during cardioplegic hypoxia and reoxygenation. Microvascular function was assessed in vitro by vessel myography. K currents of mouse heart endothelial cells were measured by whole-cell patch clamp. The levels of intracellular cytosolic free calcium (Ca) concentration, mitochondrial reactive oxidative species, and small conductance calcium-activated potassium protein expression of mouse heart endothelial cells were measured by Rhod-2 fluorescence staining, MitoSox, and Western blotting, respectively.

Results: Cardioplegic hypoxia and reoxygenation significantly attenuated endothelial small conductance calcium-activated potassium channel activity, caused calcium overload, and increased mitochondrial reactive oxidative species of mouse heart endothelial cells in both the nondiabetic and diabetes mellitus groups. In addition, treating mouse heart endothelial cells with Mito-Tempo (10 μM) reduced cardioplegic hypoxia and reoxygenation-induced Ca and mitochondrial reactive oxidative species overload in both the nondiabetic and diabetes mellitus groups, respectively (P < .05). Treatment with Mito-Tempo (10 μM) significantly enhanced coronary relaxation responses to adenosine 5'-diphosphate and NS309 (P < .05), and endothelial small conductance calcium-activated potassium channel currents in both the nondiabetic and diabetes mellitus groups (P < .05).

Conclusions: Administration of Mito-Tempo improves endothelial function and small conductance calcium-activated potassium channel activity, which may contribute to its enhancement of endothelium-dependent vasorelaxation after cardioplegic hypoxia and reoxygenation.
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http://dx.doi.org/10.1016/j.jtcvs.2021.06.029DOI Listing
June 2021

Renewable fatty acid ester production in Clostridium.

Nat Commun 2021 07 16;12(1):4368. Epub 2021 Jul 16.

Department of Biosystems Engineering, Auburn University, Auburn, AL, USA.

Bioproduction of renewable chemicals is considered as an urgent solution for fossil energy crisis. However, despite tremendous efforts, it is still challenging to generate microbial strains that can produce target biochemical to high levels. Here, we report an example of biosynthesis of high-value and easy-recoverable derivatives built upon natural microbial pathways, leading to improvement in bioproduction efficiency. By leveraging pathways in solventogenic clostridia for co-producing acyl-CoAs, acids and alcohols as precursors, through rational screening for host strains and enzymes, systematic metabolic engineering-including elimination of putative prophages, we develop strains that can produce 20.3 g/L butyl acetate and 1.6 g/L butyl butyrate. Techno-economic analysis results suggest the economic competitiveness of our developed bioprocess. Our principles of selecting the most appropriate host for specific bioproduction and engineering microbial chassis to produce high-value and easy-separable end products may be applicable to other bioprocesses.
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http://dx.doi.org/10.1038/s41467-021-24038-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285483PMC
July 2021

Evaluation of the combination of rapid diagnostic tests and microscopy for imported malaria surveillance in Anhui Province, China.

Acta Trop 2021 Oct 10;222:106042. Epub 2021 Jul 10.

School Health Service Management, Anhui Medical University, Hefei 230032, China. Electronic address:

Background: In the Anhui Province, China, efforts to interrupt the local malaria transmission were successful, with no endemic cases reported since 2014. Contrastingly, imported malaria cases are still being reported, indicating a disease reintroduction risk after years of elimination. A good surveillance system is key for avoiding the risk, detecting imported cases and possible cases associated with local transmission early. Therefore, rapid diagnostic tests (RDTs) were combined with microscopy to strengthen malaria surveillance in the province. Herein, we aimed to evaluate the efficacy of this surveillance strategy.

Methods: We conducted a retrospective study using malaria surveillance data from January 2016 to June 2020. Epidemiological characteristics and diagnostic information were analysed using descriptive and comparative statistics. The diagnostic performance of the combined toolbox (Wondfo RDTs plus microscopy) was evaluated based on its sensitivity, specificity, positive and negative predictive values, and Cohen's kappa coefficient, using real-time polymerase chain reaction as the gold standard.

Results: The combined toolbox displayed a higher overall sensitivity for malaria cases than that of microscopy alone (93.74% vs 89.37%; p <0.05), which could detect 94.65%, 88.16%, 95.00%, and 100.00% of Plasmodium falciparum, P. ovale, P. vivax, and P. malariae infections, respectively. In clinical practice, Wondfo RDTs ability to detect P. falciparum infections was better than that of microscopy (97.55% vs 89.67%, p < 0.05). In contrast, microscopy displayed a higher specificity than that of Wondfo RDTs (81.82% vs 63.28%, p <0.05). Moreover, the consistency between microscopy and the gold standard results was also better than that of RDTs (Kappa value:0.669 vs 0.596).

Conclusions: The combination of microscopy and RDTs is an effective strategy for malaria surveillance because it possibly detected more P. falciparum infections due to the introduction of RDTs. In contrast, microscopy is complementary to some limitations related to the use of RDTs in field practice. Thus, monitoring malaria cases in non-endemic areas may require employing more than one diagnostic tool in surveillance strategies. Moreover, further understanding of the advantages and disadvantages of different detection methods is necessary for applying optimum combinations in field settings.
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http://dx.doi.org/10.1016/j.actatropica.2021.106042DOI Listing
October 2021

Sirt6-mediated Nrf2/HO-1 activation alleviates angiotensin II-induced DNA DSBs and apoptosis in podocytes.

Food Funct 2021 Sep 9;12(17):7867-7882. Epub 2021 Jul 9.

Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Recent studies suggested that DNA double-strand breaks (DSBs) were associated with the pathogenesis of chronic kidney disease (CKD). The purpose of this investigation was to determine the role of Sirtuin6 (Sirt6), a histone deacetylase related to DNA damage repair, in angiotensin (Ang) II-induced DNA DSBs and the cell injury of podocytes and explore the possible mechanism. Here we showed that an increase of DNA DSBs was accompanied by a reduction in Sirt6 expression in the glomeruli of patients with hypertensive nephropathy (HN). Similar results were found in rat kidneys infused with Ang II and in cultured podocytes stimulated with Ang II. Sirt6 overexpression inhibited Ang II-induced ROS generation and DNA DSBs, and thus served as a protection against Ang II-induced apoptosis in podocytes. Moreover, Sirt6 activation enhanced Nrf2 and HO-1 gene expressions in podocytes after Ang II treatment. Furthermore, Nrf2 knockdown could partly reverse the cytoprotective effects of Sirt6 activation. In conclusion, our observations demonstrated that the Sirt6-Nrf2-HO-1 pathway played a vital role in relieving Ang II-mediated oxidative DNA damage and podocyte injury.
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http://dx.doi.org/10.1039/d0fo03467cDOI Listing
September 2021

Isolation and characterization of a newly identified Clostridium butyricum strain SCUT343-4 for 1,3-propanediol production.

Bioprocess Biosyst Eng 2021 Nov 7;44(11):2375-2385. Epub 2021 Jul 7.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, China.

A novel 1,3-propanediol (1,3-PDO) producing strain was isolated and identified as Clostridium butyricum with respect to its morphological and physiological characteristics, as well as 16S rDNA. The results of substrates test and stress tolerance indicated that C. butyricum SCUT343-4 could produce 1,3-PDO efficiently from glycerol. The optimal fermentation conditions were determined to be 5 g/L yeast extract at 37 °C and pH 6.5. To fully evaluate its 1,3-PDO production capacity, different cultivation strategies have been implemented. The highest 1,3-PDO concentration obtained for batch and fed-batch fermentation were 51.64 and 61.30 g/L, respectively. Immobilized cell fermentation in fibrous-bed bioreactor was also performed, and the concentration of 1,3-PDO further increased to 86 g/L with a yield of 0.52 g/g. In addition, the 1,3-PDO productivity reached 4.20 g/L h, which is the highest level reported for C. butyricum, demonstrating the potential of C. butyricum SCUT343-4 for 1,3-PDO production from glycerol.
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http://dx.doi.org/10.1007/s00449-021-02610-xDOI Listing
November 2021

Novel insights into the pathogenesis of virus-induced ARDS: review on the central role of the epithelial-endothelial barrier.

Expert Rev Clin Immunol 2021 Sep 12;17(9):991-1001. Epub 2021 Jul 12.

Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Respiratory viruses can directly or indirectly damage the pulmonary defense barrier, potentially contributing to acute respiratory distress syndrome (ARDS). Despite developments in the understanding of the pathogenesis of ARDS, the underlying pathophysiology still needs to be elucidated. The PubMed database was reviewed for relevant papers published up to 2021. This review summarizes the currently immunological and clinical studies to provide a systemic overview of the epithelial-endothelial barrier, given the recently published immunological profiles upon viral pneumonia, and the potentially detrimental contribution to respiratory function caused by damage to this barrier. The biophysical structure of host pulmonary defense is intrinsically linked with the ability of alveolar epithelial and capillary endothelial cells, known as the epithelial-endothelial barrier, to respond to, and instruct the delicate immune system to protect the lungs from infections and injuries. Recently published immunological profiles upon viral infection, and its contributions to the damage of respiratory function, suggest a central role for the pulmonary epithelial and endothelial barrier in the pathogenesis of ARDS. We suggest a central role and common pathways by which the epithelial-endothelial barrier contributes to the pathogenesis of ARDS.
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http://dx.doi.org/10.1080/1744666X.2021.1951233DOI Listing
September 2021

Design, synthesis and biological evaluation of double fatty chain-modified glucagon-like peptide-1 conjugates.

Bioorg Med Chem 2021 Aug 24;44:116291. Epub 2021 Jun 24.

China State Institute of Pharmaceutical Industry, Shanghai, China; Shanghai Duomirui Biotechnology Ltd., Shanghai, China. Electronic address:

Twelve double fatty chains and Aib-Arg-GLP-1 (7-37) were designed and obtained by microwave-assisted solid-phase synthesis. Then, twelve conjugates of Aib-Arg-GLP-1 (7-37) were synthesized in 1% triethylamine aqueous solution. Conjugates 2, 3, 6, 7, 10 and 11 showed better GLP-1 receptor activation potency than semaglutide. However, conjugates 2, 6 and 10 showed slightly worse glucose-lowering effects in vivo than semaglutide but better effects than conjugates 3, 7 and 11. The CD spectra of conjugates 2, 6 and 10 indicated that they had the same secondary structure as liraglutide and semaglutide. The receptor affinity results for conjugates 2, 6 and 10 measured by SPR (surface plasmon resonance) showed that conjugate 2 had higher receptor affinity than conjugates 6 and 10. In addition, albumin binding assays indicated that double fatty acid chains had obvious synergistic effects compared with single fatty acid chains. In conclusion, the structure-activity relationship of different side chains was summarized and one candidate, conjugate 2, was screened.
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http://dx.doi.org/10.1016/j.bmc.2021.116291DOI Listing
August 2021

Connectome-based individual prediction of cognitive behaviors via graph propagation network reveals directed brain network topology.

J Neural Eng 2021 07 15;18(4). Epub 2021 Jul 15.

School of Information Science and Technology, Northwest University, Xi'an 710127, People's Republic of China.

. Brain connectivity network supports the information flow underlying human cognitions and should reflect the individual variability in human cognitive behaviors. Various studies have utilized brain connectivity to predict individual differences in human behaviors. However, traditional studies viewed brain connectivity network as a one-dimensional vector, a method which neglects topological properties of brain connectivity network.. To utilize these topological properties, we proposed that graph neural network (GNN) which combines graph theory and neural network can be adopted. Different from previous node-driven GNNs that parameterize on the node feature transformation, we designed an edge-driven GNN named graph propagation network (GPN) that parameterizes on the information propagation within brain connectivity network.Edge-driven GPN outperforms various baseline models such as node-driven GNN and traditional partial least square regression in predicting the individual total cognition based on the resting-state functional connectome. GPN also reveals a directed network topology encoding the information flow, indicating that higher-order association cortices such as dorsolateral prefrontal, inferior frontal and inferior parietal cortices are responsible for the information integration underlying total cognition.. These results suggest that edge-driven GPN can better explore topological structures of brain connectivity network and can serve as a new method to associate brain connectome and human behaviors.
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http://dx.doi.org/10.1088/1741-2552/ac0f4dDOI Listing
July 2021

Pulmonary arterial hypertension and flavonoids: A role in treatment.

Chin J Physiol 2021 May-Jun;64(3):115-124

Department of Pharmacology, College of Pharmacy; Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education; Ningxia Characteristic Traditional Chinese Medicine Modernization Engineering Technology Research Center, Ningxia Medical University, Yinchuan, China.

Pulmonary arterial hypertension (PAH) is a high mortality progressive pulmonary vascular disease that can lead to right heart failure. The use of clinical drugs for the treatment of PAH is limited to a great extent because of its single target and high price. Flavonoids are widely distributed in nature, and have been found in fruits, vegetables, and traditional Chinese medicine. They have diverse biological activities and various pharmacological effects such as antitumor, antioxidation, and anti-inflammatory. This review summarizes the progress in pharmacodynamics and mechanism of flavonoids in the treatment of PAH in recent years, in order to provide some theoretical references for relevant researchers.
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http://dx.doi.org/10.4103/cjp.cjp_25_21DOI Listing
June 2021

Copy number alterations identify a smoking-associated expression signature predictive of poor outcome in head and neck squamous cell carcinoma.

Cancer Genet 2021 08 28;256-257:136-148. Epub 2021 May 28.

Department of Biochemistry, Program in Cancer Cell Biology USA. Electronic address:

Cigarette smoking is a risk factor for the development of head and neck squamous cell carcinoma (HNSCC), partially due to tobacco-induced large-scale chromosomal copy-number alterations (CNAs). Identifying CNAs caused by smoking is essential in determining how gene expression from such regions impact tumor progression and patient outcome. We utilized The Cancer Genome Atlas (TCGA) whole genome sequencing data for HNSCC to directly identify amplified or deleted genes correlating with smoking pack-year based on linear modeling. Internal cross-validation identified 35 CNAs that significantly correlated with patient smoking, independent of human papillomavirus (HPV) status. The most abundant CNAs were chromosome 11q13.3-q14.4 amplification and 9p23.1/9p24.1 deletion. Evaluation of patient amplicons reveals four different patterns of 11q13 gene amplification in HNSCC resulting from breakage-fusion-bridge (BFB) events. . Predictive modeling identified 16 genes from these regions that denote poorer overall and disease-free survival with increased pack-year use, constituting a smoking-associated expression signature (SAES). Patients with altered expression of signature genes have increased risk of death and enhanced cervical lymph node involvement. The identified SAES can be utilized as a novel predictor of increased disease aggressiveness and poor outcome in smoking-associated HNSCC.
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http://dx.doi.org/10.1016/j.cancergen.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273756PMC
August 2021

Traditional Chinese medicine shenhuang granule in patients with severe/critical COVID-19: A randomized controlled multicenter trial.

Phytomedicine 2021 Aug 28;89:153612. Epub 2021 May 28.

LongHua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Xuhui District, Shanghai 200032, China; Leishenshan Hospital of Wuhan, Wuhan, 430200, Hubei, China. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) is still a pandemic, with a high mortality rate in severe/critical cases. Therapies based on the Shenghuang Granule have proved helpful in viral infection and septic shock.

Hypothesis/purpose: The objective of the current study was to compare the efficacy and safety of the traditional Chinese medicine, Shenhuang Granule, with standard care in hospitalized patients with severe/critical COVID-19.

Study Design And Methods: This was an open-label, multicenter, randomized, controlled clinical trial. At 4 medical centers, a total of 111 severe/critical patients were randomly assigned to receive Shenhuang Granule (SHG group) twice a day for 14 days, in addition to standard care, or to receive standard care alone (Control group). The maximal follow up time was 75 days. The clinical endpoint was clinical improvement and mortality.

Results: 54 patients were assigned to the control group and 57 to the SHG group. The overall mortality was 75.9% (41/54) in the control group, and 38.6% (22/57) in the SHG group (p < 0.01 vs. control). The post hoc analysis showed that in the severe category, the mortality of the control group vs. the SHG group was 58.8% (10/17) vs. 5.3% (1/19) (p < 0.01); while in the critical category, it was 83.8% (31/37) vs. 55.3% (21/38) (p < 0.05). In the severe category, the mortality of patients who eventually received an invasive ventilator in the control vs. the SHG group was 58.8% (10/17) vs. 0 (0/19) (p < 0.01). Administration of SHG was associated with increased lymphocytes and decreased adverse events.

Conclusion: Shenhuang Granule is a promising integrative therapy for severe and critical COVID-19.
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http://dx.doi.org/10.1016/j.phymed.2021.153612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161732PMC
August 2021

Automated tumor proportion scoring for PD-L1 expression based on multistage ensemble strategy in non-small cell lung cancer.

J Transl Med 2021 06 7;19(1):249. Epub 2021 Jun 7.

Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Introduction: Programmed cell death ligand-1 (PD-L1) expression is a promising biomarker for identifying treatment related to non-small cell lung cancer (NSCLC). Automated image analysis served as an aided PD-L1 scoring tool for pathologists to reduce inter- and intrareader variability. We developed a novel automated tumor proportion scoring (TPS) algorithm, and evaluated the concordance of this image analysis algorithm with pathologist scores.

Methods: We included 230 NSCLC samples prepared and stained using the PD-L1(SP263) and PD-L1(22C3) antibodies separately. The scoring algorithm was based on regional segmentation and cellular detection. We used 30 PD-L1(SP263) slides for algorithm training and validation.

Results: Overall, 192 SP263 samples and 117 22C3 samples were amenable to image analysis scoring. Automated image analysis and pathologist scores were highly concordant [intraclass correlation coefficient (ICC) = 0.873 and 0.737]. Concordances at moderate and high cutoff values were better than at low cutoff values significantly. For SP263 and 22C3, the concordances in squamous cell carcinomas were better than adenocarcinomas (SP263 ICC = 0.884 vs 0.783; 22C3 ICC = 0.782 vs 0.500). In addition, our automated immune cell proportion scoring (IPS) scores achieved high positive correlation with the pathologists TPS scores.

Conclusions: The novel automated image analysis scoring algorithm permitted quantitative comparison with existing PD-L1 diagnostic assays and demonstrated effectiveness by combining cellular and regional information for image algorithm training. Meanwhile, the fact that concordances vary in different subtypes of NSCLC samples, which should be considered in algorithm development.
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http://dx.doi.org/10.1186/s12967-021-02898-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185941PMC
June 2021
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