Publications by authors named "Ke Wang"

2,120 Publications

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RNA sequencing identifies two novel liver-specific long noncoding RNAs with potential diagnostic value in hepatocellular carcinoma.

Biomark Med 2021 Jun 15. Epub 2021 Jun 15.

Department of Epidemiology & Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China.

To explore the expression profiles of long noncoding RNAs (lncRNAs) and identify novel lncRNAs as biomarkers for early diagnosis and therapy of hepatocellular carcinoma (HCC). Expression profiles of lncRNAs and mRNAs in five paired HCC and adjacent normal tissues were obtained by RNA sequencing. Eight lncRNAs, including two novel liver-specific lncRNAs (NONHSAT059247.2 and NONHSAT013897.2), were validated in another 74 pairs of HCC and adjacent normal tissues by quantitative reverse transcription PCR. The results of quantitative reverse transcription PCR showed that NONHSAT252133.1, NONHSAT112116.2 and NONHSAT242657.1 were significantly upregulated in HCC tissues, whereas NONHSAT169790.1, NONHSAT059247.2 and NONHSAT013897.2 were significantly downregulated. Two liver-specific lncRNAs demonstrated excellent diagnostic performance: NONHSAT059247.2 (area under the curve = 0.941, 95% CI: 0.902-0.979, p < 0.0001), NONHSAT013897.2 (area under the curve = 0.944, 95% CI: 0.906-0.983, p < 0.0001). The liver-specific lncRNAs NONHSAT059247.2 and NONHSAT013897.2, may provide new biomarkers for the future study on diagnosis, therapy, and mechanisms of HCC.
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http://dx.doi.org/10.2217/bmm-2020-0825DOI Listing
June 2021

Dopamine-Substituted Multidomain Peptide Hydrogel with Inherent Antimicrobial Activity and Antioxidant Capability for Infected Wound Healing.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.

Wound infection can cause a delay in wound healing or even wound deterioration, threatening patients' lives. The excessive accumulation of reactive oxygen species (ROS) in infected wounds activates a strong inflammatory response to delay wound healing. Therefore, it is highly desired to develop hydrogels with inherent antimicrobial activity and antioxidant capability for infected wound healing. Herein, a dopamine-substituted multidomain peptide () with inherent antimicrobial activity, strong skin adhesion, and ROS scavenging has been developed. can form bilayer β-sheets with dopamine residues on the surface of nanofibers. The enhanced rheological properties of -based hydrogel can be achieved not only through UV irradiation but also by incorporation of multivalent ions (e.g., PO). Furthermore, the hydrogel shows a broad spectrum of antimicrobial activity due to the high positive charges of lysine residues and the β-sheet formation. When applied to full-thickness dermal wounds in mice, the hydrogel results in a significantly shortened inflammatory stage of the healing process because of its remarkable antimicrobial activity and antioxidant capability. Accelerated wound closure with thick granulation tissue, uniform collagen arrangement, and dense vascularization can be achieved. This work suggests that the hydrogel can serve as antimicrobial coating and ROS-scavenging wound dressing for bacterial-infected wound treatment.
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http://dx.doi.org/10.1021/acsami.1c07656DOI Listing
June 2021

Magnetic order-dependent phonon properties in 2D magnet CrI.

Nanoscale 2021 Jun 14. Epub 2021 Jun 14.

Institute of High Performance Computing, A*STAR, 138632, Singapore.

We carried out a systematic theoretical study on how spin affects the phononic properties of CrI3 monolayers. We find that the frequencies of two infrared-active (IR) modes are significantly influenced by the magnetic configuration. Thus an IR spectrum may be applied to identify the magnetic order by utilizing the spin-lattice correlation. The thermal expansion coefficients are 2.21, 3.35 and -5.58 × 10-6 K-1 for ferromagnetic (FM), antiferromagnetic (AFM) and paramagnetic (PM) phases at 30 K, because of the competition between the modes with negative and positive Grüneisen constants. Furthermore, the lattice thermal conductivity is also sensitive to the magnetic phase, which is attributed to the spin-dependent lattice anharmonicity. Our results provide fundamental insights into the spin-lattice coupling and clarify the potential of a spintronic monolayer as a thermal switching device for active heat flow control.
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http://dx.doi.org/10.1039/d1nr00820jDOI Listing
June 2021

A hereditary ovarian cancer family with rare pathogenic splicing mutation: Implications for variant interpretation.

Cancer Genet 2021 May 26;256-257:127-130. Epub 2021 May 26.

Cancer Molecular Diagnostics Core, National Clinical Research Center of Caner, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer Tianjin Medical University Cancer Institute & Hospital, Tianjin, P R China. Electronic address:

The BRCA1/2 gene is important for assessing the risk of familial/hereditary ovarian cancer (OC). This case is a patient with OC, and two of her immediate family members are cancer patients. We sequenced the coding and splicing regions of 42 OC susceptibility genes, and found a rare pathogenic splicing mutation BRCA1:c.132C > T (p.cys44 =) in 2 patients. Although the mutation is synonymous, software prediction and functional verification have shown that it affects alternative splicing and leads to frameshift mutations (c.131_134del). Chromosome microarray analysis of the tissue samples revealed the presence of a BRCA1 gene deletion with a fragment size of 1.42 Mb and an HRD score of 71. In addition, the proband showed a sensitive response to platinum treatment. This case suggests the clinical significance of OC susceptibility genes sequencing and HRD scoring in screening hereditary OC families.
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http://dx.doi.org/10.1016/j.cancergen.2021.05.007DOI Listing
May 2021

Design, synthesis, and biological evaluation of 1-methyl-1H-pyrazolo[4,3-b]pyridine derivatives as novel small-molecule inhibitors targeting the PD-1/PD-L1 interaction.

Bioorg Chem 2021 May 30;114:105034. Epub 2021 May 30.

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address:

Blockade of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signalling pathway is a promising tumour immunotherapeutic approach, and small molecule drugs have more advantages than monoclonal antibody macromolecules in clinical applications. Therefore, a series of 1-methyl-1H-pyrazolo[4,3-b]pyridine derivatives as PD-1/PD-L1 interaction novel small-molecule inhibitors were designed employing a ring fusion strategy. The inhibitory activity of compounds was evaluated by the HTRF assay, among which D38 was identified as the most potent PD-1/PD-L1 interaction inhibitor with an IC value of 9.6 nM. Furthermore, D38 exhibited prominent inhibitory activity against the PD-1/PD-L1 interaction with an EC value of 1.61 μM in a coculture model of PD-L1/TCR activator-expressing CHO cells and PD-1-expressing Jurkat cells. In addition, the preliminary structure-activity relationships (SARs) of compounds were elucidated, and the binding mode of D38 with the PD-L1 dimer was analysed by molecular docking. Overall, D38 could be employed as a prospective lead compound of PD-1/PD-L1 interaction inhibitors for further development.
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http://dx.doi.org/10.1016/j.bioorg.2021.105034DOI Listing
May 2021

Senolytics alleviate the degenerative disorders of temporomandibular joint in old age.

Aging Cell 2021 Jun 8:e13394. Epub 2021 Jun 8.

UConn Center on Aging, UConn Health, Farmington, CT, USA.

Aging is one of the major risk factors for degenerative joint disorders, including those involving the temporomandibular joint (TMJ). TMJ degeneration occurs primarily in the population over 65, significantly increasing the risk of joint discomfort, restricted joint mobility, and reduced quality of life. Unfortunately, there is currently no effective mechanism-based treatment available in the clinic to alleviate TMJ degeneration with aging. We now demonstrate that intermittent administration of senolytics, drugs which can selectively clear senescent cells, preserved mandibular condylar cartilage thickness, improved subchondral bone volume and turnover, and reduced Osteoarthritis Research Society International (OARSI) histopathological score in both 23- to 24-month-old male and female mice. Senolytics had little effect on 4 months old young mice, indicating age-specific benefits. Our study provides proof-of-concept evidence that age-related TMJ degeneration can be alleviated by pharmaceutical intervention targeting cellular senescence. Since the senolytics used in this study have been proven relatively safe in recent human studies, our findings may help justify future clinical trials addressing TMJ degeneration in old age.
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http://dx.doi.org/10.1111/acel.13394DOI Listing
June 2021

Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.

Transl Psychiatry 2021 Jun 3;11(1):343. Epub 2021 Jun 3.

The Affiliated Hospital of Qingdao University & The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, 266003, PR China.

Background: Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN).

Methods: A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC).

Results: The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis.

Conclusions: The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.
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http://dx.doi.org/10.1038/s41398-021-01470-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175348PMC
June 2021

Ginkgolide J protects human synovial cells SW982 via suppression of p38‑dependent production of pro‑inflammatory mediators.

Mol Med Rep 2021 Aug 3;24(2). Epub 2021 Jun 3.

Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.

Fibroblast‑like synoviocytes (FLS) in the synovial lining play a key role in the pathological process of rheumatoid arthritis (RA), which produce pro‑inflammatory mediators to perpetuate inflammation and proteases to contribute to cartilage destruction. Ginkgolide J (GJ) is a subclass of ginkgolides (GGs) that exhibits anti‑inflammatory activity. In the present study, the protective effect of GJ on lipopolysaccharide (LPS)‑treated human synovial cells SW982 and its related mechanisms were investigated using various methods, including ELISA, Griess assay, western blotting, immunofluorescence analysis and p38 kinase activity assay. The results revealed that GJ pretreatment significantly attenuated LPS‑induced excess production of pro‑inflammatory mediators in SW982 cells via suppression of tumor necrosis factor‑α/interleukin (IL)‑1β/IL‑18/NF‑κB/NLR family pyrin domain containing 3, prostaglandin E2/cyclooxygenase‑2 and inducible nitric oxide synthase/nitric oxide signaling. Mechanistic studies revealed that p38 activation contributed to the LPS‑induced inflammatory response, and GJ pretreatment dose‑dependently attenuated p38 activation, indicating that the suppressive effect of GJ was achieved by targeting p38 signaling. These findings may contribute to the prevention and treatment of RA.
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http://dx.doi.org/10.3892/mmr.2021.12194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188640PMC
August 2021

A nomogram based on clinicopathological features and serological indicators predicting breast pathologic complete response of neoadjuvant chemotherapy in breast cancer.

Sci Rep 2021 May 31;11(1):11348. Epub 2021 May 31.

Department of Breast Surgery, First Affiliate Hospital, Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, People's Republic of China.

A single tumor marker is not enough to predict the breast pathologic complete response (bpCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. We aimed to establish a nomogram based on multiple clinicopathological features and routine serological indicators to predict bpCR after NAC in breast cancer patients. Data on clinical factors and laboratory indices of 130 breast cancer patients who underwent NAC and surgery in First Affiliated Hospital of Xi'an Jiaotong University from July 2017 to July 2019 were collected. Multivariable logistic regression analysis identified 11 independent indicators: body mass index, carbohydrate antigen 125, total protein, blood urea nitrogen, cystatin C, serum potassium, serum phosphorus, platelet distribution width, activated partial thromboplastin time, thrombin time, and hepatitis B surface antibodies. The nomogram was established based on these indicators. The 1000 bootstrap resampling internal verification calibration curve and the GiViTI calibration belt showed that the model was well calibrated. The Brier score of 0.095 indicated that the nomogram had a high accuracy. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.941 (95% confidence interval: 0.900-0.982) showed good discrimination of the model. In conclusion, this nomogram showed high accuracy and specificity and did not increase the economic burden of patients, thereby having a high clinical application value.
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http://dx.doi.org/10.1038/s41598-021-91049-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167133PMC
May 2021

A novel all-trans retinoic acid derivative regulates cell cycle and differentiation of myelodysplastic syndrome cells by USO1.

Eur J Pharmacol 2021 May 29;906:174199. Epub 2021 May 29.

Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, China. Electronic address:

4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, has been demonstrated that it had a variety of anti-tumor effects by exerting regulation on cellular proliferation, apoptosis and differentiation. Here, we found that ATPR is critical for alleviating myelodysplastic syndrome (MDS) and acute myelogenous leukemia. USO1, vesicle transport factor, belongs to tether protein family and involved in endoplasmic reticulum to Golgi trafficking of protein which is important to tumorigenesis. How USO1 contribute to MDS remain elusive. USO1 is aberrantly activated in MDS and AML in vivo and vitro, aberration of which might be a dominant mechanism for MDS cell survival. During the ATPR-induced remission of MDS, in vitro, USO1 presents a time and concentration-dependent decrease. Silencing of USO1 promotes myeloid differentiation of MDS cells and inhibits MDS cellular proliferation while USO1 over-expression has the opposite effect, suggesting that reduction of USO1 enhances the sensitivity of SKM-1 cells to ATPR treatment. Mechanistically, USO1 exerts its oncogenic role by inactivating Raf/ERK signaling, while ATPR is access to revise it. Notably, the activity of Raf/ERK pathway is required for the development and maintenance of MDS cell proliferation. Collectively, our results demonstrate the USO1- Raf/ERK signaling axis in MDS and highlight the negative role of USO1 in ATPR-regulated remission of MDS.
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http://dx.doi.org/10.1016/j.ejphar.2021.174199DOI Listing
May 2021

TGFB3 downregulation causing chordomagenesis and its tumor suppression role maintained by Smad7.

Carcinogenesis 2021 May 31. Epub 2021 May 31.

Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing 100101, China.

Chordoma is a rare bone tumor arising from notochordal remnants, but the underlying mechanism remains elusive. By integrated mRNA and microRNA analyses, we found significant downregulation of TGFB3 along with upregulation of its inhibitor, miR-29 family in chordoma comparing with notochord. Somatic copy number gains of miR-29 loci in chordoma highlighted a mechanism of inactivation of TGFB3 signaling in tumor formation. In zebrafish, knockout and knockdown homologous tgfb3 resulted in a chordoma-like neoplasm. On the other hand, Smad7 negative feedback regulation of TGF-β signaling is retentive in chordoma cell UM-Chor1 despite its disruption in most cancer cells (e.g., A549). Therefore, contrary to other cancers, exogenous TGF-β activated Smad7 by downregulating miR-182 and inhibited cell migration and invasion in UM-Chor1. Meanwhile, TGF-β decreased chordoma characteristic protein Brachyury. Altogether, downregulation of TGFB3 causes chordomagenesis, showing a feasible target for therapies. The retention of Smad7 negative regulation may maintain the suppressor role of TGF-β in chordoma.
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http://dx.doi.org/10.1093/carcin/bgab022DOI Listing
May 2021

Breast Ultrasound Image Segmentation: A Coarse-to-Fine Fusion Convolutional Neural Network.

Med Phys 2021 May 30. Epub 2021 May 30.

School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, China.

Purpose: Breast ultrasound (BUS) image segmentation plays a crucial role in computer-aided diagnosis systems for BUS examination, which are useful for improved accuracy of breast cancer diagnosis. However, such performance remains a challenging task owing to the poor image quality and large variations in the sizes, shapes, and locations of breast lesions. In this paper, we propose a new convolutional neural network with coarse-to-fine feature fusion to address the aforementioned challenges.

Methods: The proposed fusion network consists of an encoder path, a decoder path, and a core fusion stream path (FSP). The encoder path is used to capture the context information, and the decoder path is used for localization prediction. The FSP is designed to generate beneficial aggregate feature representations (i.e., various-sized lesion features, aggregated coarse-to-fine information, and high-resolution edge characteristics) from the encoder and decoder paths, which are eventually used for accurate breast lesion segmentation. To better retain the boundary information and alleviate the effect of image noise, we input the super-pixel image along with the original image to the fusion network. Furthermore, a weighted-balanced loss function was designed to address the problem of lesion regions having different sizes. We then conducted exhaustive experiments on three public BUS datasets to evaluate the proposed network.

Results: The proposed method outperformed state-of-the-art (SOTA) segmentation methods on the three public BUS datasets, with average dice similarity coefficients of 84.71(±1.07), 83.76(±0.83), and 86.52(±1.52), average intersection-over-union values of 76.34(±1.50), 75.70(±0.98), and 77.86(±2.07), average sensitivities of 86.66(±1.82), 85.21(±1.98), and 87.21(±2.51), average specificities of 97.92(±0.46), 98.57(±0.19), and 99.42(±0.21), and average accuracies of 95.89(±0.57), 97.17(±0.3), and 98.51(±0.3).

Conclusions: The proposed fusion network could effectively segment lesions from BUS images, thereby presenting a new feature fusion strategy to handle challenging task of segmentation, while outperforming the SOTA segmentation methods. The code is publicly available at https://github.com/mniwk/CF2- NET.
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http://dx.doi.org/10.1002/mp.15006DOI Listing
May 2021

Difference and interplay of microbial communities, metabolic functions, trophic modes and influence factors between sludge and bulking agent in a composting matrix.

Bioresour Technol 2021 Apr 1;336:125085. Epub 2021 Apr 1.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

The difference and interplay of microbial communities, metabolic functions and influence factors between sewage sludge and bulking agent were evaluated in 60 days composting. Results showed that fungal communities were mainly affected by pH (42.4%) and ORP (35.9%) of sludge but by VS (41.1%) and temperature (34.7%) of sawdust in a composting system. Bacterial communities were primarily affected by VS (43.5%) and C/N (34.8%) of sludge but by ORP (44.5%) and temperature (31.0%) of sawdust. Tepidimicrobium dominated in the sludge at thermophilic period, while Alcaligenes prevailed in the sawdust. Bacterial carbon metabolism was significantly higher in the sludge than that in the sawdust except carbohydrate metabolism. Saprophytic fungi were the main trophic mode both in the sludge and sawdust. Water transfer facilitated Aspergillus and Trichosporon moving from sludge to sawdust to decompose lignocellulose. Ammonia transfer promoted the migration of Alcaligenes and Pseudomonas from sludge to sawdust and facilitated ammonia assimilating.
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http://dx.doi.org/10.1016/j.biortech.2021.125085DOI Listing
April 2021

Influence of low tumor content on tumor mutational burden estimation by whole-exome sequencing and targeted panel sequencing.

Clin Transl Med 2021 May;11(5):e415

Department of In Vitro Diagnostic Reagent, National Institutes for Food And Drug Control (NIFDC), Beijing, China.

Background: Tumor mutational burden (TMB) is a promising biomarker for stratifying patient subpopulation who would benefit from immune checkpoint blockade (ICB) therapies. Although great efforts have been made for standardizing TMB measurement, mutation calling and TMB quantification can be challenging in samples with low tumor content including liquid biopsies. The effect of varying tumor content on TMB estimation by different assay methods has never been systematically investigated.

Method: We established a series of reference standard DNA samples derived from 11 pairs of tumor-normal matched human cell lines across different cancer types. Each tumor cell line was mixed with its matched normal at 0% (control), 1%, 2%, 5%, and 10% mass-to-mass ratio to mimic the clinical samples with low tumor content. TMB of these reference standards was evaluated by both ∼1000× whole-exome sequencing (wesTMB) and targeted panel sequencing (psTMB) at four different vendors. Both regression and classification analyses of TMB were performed for theoretical investigation and clinical practice purposes.

Results: Linear regression model was established that demonstrated in silico psTMB determined by regions of interest (ROI) as a great representative of wesTMB based on TCGA dataset. It was also true in our reference standard samples as the predicted psTMB interval based on the observed wesTMB captured the intended 90% of the in silico psTMB values. Although ∼1000× deep WES was applied, reference standard samples with less than 5% of tumor proportions are below the assay limit of detection (LoD) of wesTMB quantification. However, predicted wesTMB based on observed psTMB accurately classify (>0.97 AUC) for TMB high and low patient stratification even in samples with 2% of tumor content, which is more clinically relevant, as TMB determination should be a qualitative assay for TMB high and low patient classification. One targeted panel sequencing vendor using an optimized blood psTMB pipeline can further classify TMB status accurately (>0.82 AUC) in samples with only 1% of tumor content.

Conclusions: We developed a linear model to establish the quantitative correlation between wesTMB and psTMB. A set of DNA reference standards was produced in aid to standardize TMB measurements in samples with low tumor content across different targeted sequencing panels. This study is a significant contribution aiming to harmonize TMB estimation and extend its future application in clinical samples with low tumor content including liquid biopsy.
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http://dx.doi.org/10.1002/ctm2.415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102856PMC
May 2021

Eosinophilic phenotype was associated with better early clinical remission in elderly patients but not middle-aged patients with acute exacerbations of COPD.

Int J Clin Pract 2021 May 28:e14415. Epub 2021 May 28.

Division of Respiratory Diseases, State Key Laboratory of Biotherapy of China & Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Background: There is limited evidence of the relationship between peripheral blood eosinophils and clinical remission of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) at different ages, especially in elderly patients, which was the objective of the present study.

Methods: This retrospective study stratified patients by age (elderly patients >65 years old or middle-aged patients between 45 and 65 years old) and analysed the relationship between blood eosinophils (≥2% or <2%) and AECOPD clinical remission at observing time points of 7, 14, 21 and 28 days of hospitalisation. Student's t tests, Mann-Whitney U tests, Chi-squared or Fisher's exact tests were conditionally used to compare difference between groups. The unadjusted or adjusted Cox proportional hazards model was used to analyse the association between blood eosinophilic levels and cumulative clinical remission.

Results: Of 703 AECOPD cases analysed, 616 were elderly people (>65 years), 312 of whom had eosinophilic exacerbations. There were statistically significant differences in leucocytes, eosinophils, neutrophils, lymphocytes, monocytes, high-sensitivity C-reactive protein levels (hs-CRP), and hospital costs between groups (P < .05, respectively). According to the chi-square analysis, eosinophilic exacerbation had a higher clinical remission rate at 7, 14 and 21 days (all P < .05), but not 28 days (P > .05). Among analysis through adjusted Cox proportional hazards model, eosinophilic exacerbation was significantly associated with a higher cumulative remission rate in elderly patients at 7, 14, 21 days (all P < .05), but not 28 days (P > .05). No significant association was observed in meddle-aged patients at any time points (all P > .05).

Conclusion: Eosinophilic exacerbation was associated with better early clinical remission of AECOPD patients during hospitalisation. As stratified by ages, similar results were observed in elderly patients but not middle-aged patients. Blood eosinophils at different ages may be valuable in personalised management for AECOPD.
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http://dx.doi.org/10.1111/ijcp.14415DOI Listing
May 2021

Crystal Structure Analysis of Cationic Peroxidase from Proso Millet and Identification of Its Phosphatase Active Sites.

J Agric Food Chem 2021 Jun 28;69(22):6251-6259. Epub 2021 May 28.

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan030006, China.

Proso millet peroxidase (PmPOD) belongs to class III plant peroxidases, which are enzymes typically characterized by their heme coenzymes. PmPOD exhibits not only heme-dependent peroxidase activity but also heme-independent phosphatase activity. Crystal structure analysis and sequence alignment showed that PmPOD contained a phosphatase catalytic loop CXXXXXR in its β-domain that is similar to the active site of a dual-specific phosphatase. Recombinant truncated proso millet peroxidase (tPmPOD), which contained only a conserved catalytic loop CXXXXXR of phosphatase, was found to exhibit phosphatase activity. Five tPmPOD mutants containing five different mutations in the phosphatase active sites exhibited significantly lower phosphatase activity compared to that of tPmPOD, indicating that the five amino acids play important roles in the phosphatase activity of tPmPOD. Finally, nucleophilic amino acid Cys192 formed a disulfide bond with Cys219 to protect the stability of a sulfhydryl group; thus, it may play a decisive role in the phosphatase activity of PmPOD.
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http://dx.doi.org/10.1021/acs.jafc.1c01606DOI Listing
June 2021

Thymic iNKT cell differentiation at single-cell resolution.

Cell Mol Immunol 2021 May 25. Epub 2021 May 25.

Department of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China.

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http://dx.doi.org/10.1038/s41423-021-00697-6DOI Listing
May 2021

Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala.

Front Neurosci 2021 7;15:657507. Epub 2021 May 7.

Acupuncture Anesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1β and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1β, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.
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http://dx.doi.org/10.3389/fnins.2021.657507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137986PMC
May 2021

The Mitogen-Activated Protein Kinase Kinase TaMKK5 Mediates Immunity via the TaMKK5-TaMPK3-TaERF3 Module.

Plant Physiol 2021 May 20. Epub 2021 May 20.

Key Laboratory of Biology and Genetic Improvement of Triticeae Crops, Ministry of Agriculture/The National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Sharp eyespot disease, caused by the soil-borne fungus Rhizoctonia cerealis, seriously threatens production of wheat (Triticum aestivum). Despite considerable advances in understanding the mechanisms of mitogen-activated protein kinase (MAPK) cascades in innate immunity in model plant species, the roles of MAPK cascades in wheat are unknown. In this study, we identified a wheat MAPK kinase TaMKK5, located on chromosome 6B, and deciphered its functional role in the innate immune responses to R. cerealis attack. The TaMKK5-6B transcript level was elevated after R. cerealis infection and was higher in resistant wheat genotypes compared to susceptible genotypes. Overexpressing TaMKK5-6B increased resistance to sharp eyespot and up-regulated the expression of multiple defense-related genes in wheat, including the MAPK gene TaMPK3, the ethylene response factor gene TaERF3, the calcium-dependent protein kinase gene TaCPK7-D, the glutathione s-transferase-1 gene TaGST1, Defensin, and Chitinase 2, while TaMKK5 knock-down compromised the resistance and repressed the expression of these defense-related genes. Bimolecular fluorescence complementation, yeast two-hybrid, pull-down, and phosphorylation assays showed that TaMKK5 physically interacted with TaMPK3, and phosphorylated and activated TaMPK3, and that TaMPK3 interacted with and phosphorylated TaERF3. The TaMKK5-TaMPK3 cascade modulates the expression of TaGST1, Defensin, and Chitinase 2 through TaERF3. Collectively, TaMKK5 mediates resistance to sharp eyespot through the TaMKK5-TaMPK3-TaERF3 module and by up-regulating the expression of defense-related genes in wheat. This study provides insights into the role of the wheat MAPK cascades in innate immunity. TaMKK5-6B is a promising gene for breeding wheat cultivars that are resistant to sharp eyespot.
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http://dx.doi.org/10.1093/plphys/kiab227DOI Listing
May 2021

Overexpression of is associated with attenuation of migration and invasion in breast cancer.

Exp Ther Med 2021 Jul 2;22(1):699. Epub 2021 May 2.

Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, Yunnan 650118, P.R. China.

Inhibitor of growth 3 () has been identified as a potential cancer drug target, but little is known about its role in breast cancer. Thus, the present study aimed to investigate expression in breast cancer, its clinical value, and how influences the migration and invasion of breast cancer cells. The Cancer Genome Atlas and UALCAN databases were used to analyze ING3 expression in cancer tissues and normal tissues. Survival analysis was performed using the UALCAN, UCSC Xena and KM-plot databases. In addition, reverse transcription-quantitative PCR and western blot analyses were performed to detect ING3 mRNA and protein expression levels. ING3 was overexpressed via lentiviral vector transfection, while the Transwell and wound healing assays were performed to assess the cell migratory and invasive abilities. Protein interaction and pathway analyses were performed using the GeneMANIA and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The results demonstrated that expression was significantly lower in cancer tissues compared with normal tissues (P<0.05). In addition, luminal A and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer tissues expressed lower levels of compared with normal breast tissues. Notably, statistically significant differences were observed in long-term survival between patients with luminal A (P=0.04) and HER2-enriched (P=0.008) breast cancer, with high and low expression levels of ING3. The results of the Transwell migration and invasion assays demonstrated that overexpression of significantly inhibited the migratory and invasive abilities of MCF7 (P<0.05) and HCC1937 (P<0.05) cells. The results of the wound healing assay demonstrated that the percentage wound closure significantly decreased in cells transfected with LV5-ING3 compared with the negative control group at 12 h (P<0.05) and 24 h (P<0.01). The PI3K/AKT, JAK/STAT, NF-κB and Wnt/β-catenin pathways are the potential pathways regulated by ING3. Notably, overexpression of ING3 inhibited migration and invasion . However, further studies are required to determine whether ING3 regulates the biological behavior of breast cancer via tumor-related pathways.
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http://dx.doi.org/10.3892/etm.2021.10131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120550PMC
July 2021

Gut microbiota as prognosis markers for patients with HBV-related acute-on-chronic liver failure.

Gut Microbes 2021 Jan-Dec;13(1):1-15

Department of Infectious Diseases and Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China.

The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut microbiota in HBV-ACLF and in other HBV associated pathologies. We analyzed the gut microbiome in patients with HBV-ACLF or other HBV associated pathologies and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. 212 patients with HBV-ACLF, 252 with chronic hepatitis B (CHB), 162 with HBV-associated cirrhosis (HBV-LC) and 877 healthy individuals were recruited for the study. CHB and HBV-LC patients are grouped as HBV-Other. We discovered striking differences in the microbiome diversity between the HBV-ACLF, HBV-Other and healthy groups using 16S rRNA sequencing. The ratio of cocci to bacilli was significantly elevated in the HBV-ACLF group compared with healthy group. Further analysis within the HBV-ACLF group identified 52 genera showing distinct richness within the group where was enriched in the progression group whilst was enriched in the regression group. Metagenomic sequencing validated these findings and further uncovered an enrichment of in progression group, while and dominated the regression group. Importantly, our analysis revealed that there was a rapid increase of during the progression of HBV-ACLF. The gut microbiota displayed distinct composition at different phases of HBV-ACLF. High abundance of is associated with progression while that of is associated with regression of HBV-ACLF. Therefore, the microbiota features hold promising potential as prognostic markers for HBV-ACLF.
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http://dx.doi.org/10.1080/19490976.2021.1921925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143260PMC
May 2021

Microarray investigation of glycan remodeling during macrophage polarization reveals α2,6 sialic acid as an anti-inflammatory indicator.

Mol Omics 2021 May 18. Epub 2021 May 18.

Institutes of Biomedical Sciences & Shanghai Stomatological Hospital, Fudan University, Shanghai, 200032, China.

Glycosylation is a widely occurring posttranslational modification. Here, we applied a quick, convenient and high-throughput strategy (lectin array) to investigate the variation in glycans on different macrophage subtypes derived from THP-1 and RAW264.7 cells. For THP-1 cells, there were more significant differences in the glycan on M2 macrophages compared to the other two subtypes. In contrast, M1 macrophages exhibited more significant glycan remodeling than the other subtypes for the RAW264.7 cell line. The response of the lectins which recogonize the N-glycan and α2,6 sialic acid was higher during polarization into anti-inflammatory phase (THP-1 derived M2 subtypes), and lower in pro-inflammatory phase (RAW264.7 M1 subtypes). The regulation of several α2,6 sialyltransferase genes was coincident with the regulation of the α2,6 sialic acid on the two cell lines. The lectin response and glycosyltranferase gene expression confirmed that α2,6 sialic acid showed higher expression in the anti-inflammatory phase. This indicated that α2,6 sialic acid was a potential indicator for the anti-inflammatory response.
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http://dx.doi.org/10.1039/d0mo00192aDOI Listing
May 2021

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Signal Transduct Target Ther 2021 05 17;6(1):194. Epub 2021 May 17.

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.
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http://dx.doi.org/10.1038/s41392-021-00603-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127508PMC
May 2021

Impact of Major Residual Lesions on Outcomes After Surgery for Congenital Heart Disease.

J Am Coll Cardiol 2021 May;77(19):2382-2394

Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

Background: Many factors affect outcomes after congenital cardiac surgery.

Objectives: The RLS (Residual Lesion Score) study explored the impact of severity of residual lesions on post-operative outcomes across operations of varying complexity.

Methods: In a prospective, multicenter, observational study, 17 sites enrolled 1,149 infants undergoing 5 common operations: tetralogy of Fallot repair (n = 250), complete atrioventricular septal defect repair (n = 249), arterial switch operation (n = 251), coarctation or interrupted arch with ventricular septal defect (VSD) repair (n = 150), and Norwood operation (n = 249). The RLS was assigned based on post-operative echocardiography and clinical events: RLS 1 (trivial or no residual lesions), RLS 2 (minor residual lesions), or RLS 3 (reintervention for or major residual lesions before discharge). The primary outcome was days alive and out of hospital within 30 post-operative days (60 for Norwood). Secondary outcomes assessed post-operative course, including major medical events and days in hospital.

Results: RLS 3 (vs. RLS 1) was an independent risk factor for fewer days alive and out of hospital (p ≤ 0.008) and longer post-operative hospital stay (p ≤ 0.02) for all 5 operations, and for all secondary outcomes after coarctation or interrupted arch with VSD repair and Norwood (p ≤ 0.03). Outcomes for RLS 1 versus 2 did not differ consistently. RLS alone explained 5% (tetralogy of Fallot repair) to 20% (Norwood) of variation in the primary outcome.

Conclusions: Adjusting for pre-operative factors, residual lesions after congenital cardiac surgery impacted in-hospital outcomes across operative complexity with greatest impact following complex operations. Minor residual lesions had minimal impact. These findings may provide guidance for surgeons when considering short-term risks and benefits of returning to bypass to repair residual lesions.
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http://dx.doi.org/10.1016/j.jacc.2021.03.304DOI Listing
May 2021

In Situ, Atomic-Resolution Observation of Lithiation and Sodiation of WS Nanoflakes: Implications for Lithium-Ion and Sodium-Ion Batteries.

Small 2021 May 13:e2100637. Epub 2021 May 13.

Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA.

WS nanoflakes have great potential as electrode materials of lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) because of their unique 2D structure, which facilitates the reversible intercalation and extraction of alkali metal ions. However, a fundamental understanding of the electrochemical lithiation/sodiation dynamics of WS nanoflakes especially at the nanoscale level, remains elusive. Here, by combining battery electrochemical measurements, density functional theory calculations, and in situ transmission electron microscopy, the electrochemical-reaction kinetics and mechanism for both lithiation and sodiation of WS nanoflakes are investigated at the atomic scale. It is found that compared to LIBs, SIBs exhibit a higher reversible sodium (Na) storage capacity and superior cyclability. For sodiation, the volume change due to ion intercalation is smaller than that in lithiation. Also, sodiated WS maintains its layered structure after the intercalation process, and the reduced metal nanoparticles after conversion in sodiation are well-dispersed and aligned forming a pattern similar to the layered structure. Overall, this work shows a direct interconnection between the reaction dynamics of lithiated/sodiated WS nanoflakes and their electrochemical performance, which sheds light on the rational optimization and development of advanced WS -based electrodes.
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http://dx.doi.org/10.1002/smll.202100637DOI Listing
May 2021

Asymmetric α-electrophilic difluoromethylation of β-keto esters by phase transfer catalysis.

Org Biomol Chem 2021 Jun;19(21):4788-4795

School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.

An efficient and enantioselective α-electrophilic difluoromethylation of β-keto esters has been achieved by phase-transfer catalysis. This procedure is applicable to different kinds of β-keto esters with a series of cinchona-derived C-2' aryl-substituted phase-transfer catalysts. The reaction gives the corresponding products in good enantioselectivities (up to 83% ee) and yields (up to 92%) with high C/O regioselectivities (up to 98 : 2). Moreover, the C/O selectivity of β-keto esters could be easily reversed and controlled. This asymmetric difluoromethylation provided a novel and efficient way for introducing chiral C-CF2H groups.
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http://dx.doi.org/10.1039/d1ob00511aDOI Listing
June 2021

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma.

Front Oncol 2021 26;11:626566. Epub 2021 Apr 26.

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer (NSCLC) for which there is currently no recognized treatment. Recently, favorable immune checkpoint blockade responses have been observed in PPLELC. This study aimed to review the effects of this regimen in patients with advanced PPLELC. PPLELC patients treated with immune checkpoint inhibitors at West China Hospital between January 2008 and December 2019 were retrospectively identified. Demographic parameters and antitumor treatment details were retrieved and reviewed. Among 128 patients diagnosed with PPLELC, 5 who received immune checkpoint inhibitors at advanced stages were included in the analysis. All of these patients were female nonsmokers with a median age of 55.6 (range 53-58) years at diagnosis. Their median PD-L1 expression was 40% (range, 30-80%). Although the patients underwent surgeries, chemotherapy and radiotherapy, all the treatments failed. Immune checkpoint inhibitors were administered palliatively, and three patients responded favorably, with the best overall response being partial remission (PR). Thus, immune checkpoint inhibitors may be a promising treatment for advanced PPLELC, and large clinical trials are warranted to obtain more evidence regarding this regimen.
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http://dx.doi.org/10.3389/fonc.2021.626566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110193PMC
April 2021

A New Molecular Recognition Concept: Multiple Hydrogen Bonds and Their Optically Triggered Proton Transfer in Confined Metal-Organic Frameworks for Superior Sensing Element.

ACS Appl Mater Interfaces 2021 May 10;13(19):22457-22465. Epub 2021 May 10.

Key Laboratory of Macromolecular Science of Shaanxi Province, Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.

We report a new sensing mechanism based on an indium-dihydroxyterephthalic acid metal-organic framework (MOF, SNNU-153), in which the spatially fitted analyte-MOF hydrogen-bond (H-bond) formation provides selective recognition while the analyte-H-bond assisted excited-state intramolecular proton transfer (ESIPT) and the resulting ratiometric emission act as a superior signal transducer with ultrafast response. The synergy of ESIPT signal transduction and confined MOF pore enables the SNNU-153 sensor selectively sensing hydrazine even among nitrogen-containing hydride analogs such as NH, NHOH, and (Me)NNH. The key of H-bond and associated ESIPT was further counter evidenced by an indium-2,5-dimethoxyterephthalic acid MOF (SNNU-152), where the hydroxyl protons were removed by methylation, showing near inertness to NH. The new molecular recognition concept thus makes SNNU-153 a powerful NH sensor, which should be far-reaching to other sensing elements.
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http://dx.doi.org/10.1021/acsami.1c03410DOI Listing
May 2021

High iodine uptake in two-dimensional covalent organic frameworks.

Chem Commun (Camb) 2021 Jun;57(45):5558-5561

Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry (Ministry of Education), College of Chemistry, Tianjin Normal University, Tianjin, 300387, P. R. China.

Two 2-dimensional covalent organic frameworks (COFs; TJNU-203 and TJNU-204) with high crystallinity and large specific surface area are rationally fabricated using a three-connected distorted building block and linear linkers. The two COFs show high iodine uptake (5.885 g g-1 for TJNU-203 and 5.335 g g-1 for TJNU-204) on account of physical-chemical adsorption, which make them one among the best porous materials for iodine adsorption.
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http://dx.doi.org/10.1039/d1cc00737hDOI Listing
June 2021

Efficacy of Combination Chemo-Immunotherapy as a First-Line Treatment for Advanced Non-Small-Cell Lung Cancer Patients With HER2 Alterations: A Case Series.

Front Oncol 2021 20;11:633522. Epub 2021 Apr 20.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.

Objective: Although the treatment of non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) alterations has been studied for years, the overall response rate (ORR) of these patients is still unsatisfactory, and more therapeutic strategies are needed. Little is known about the combination of chemo- and immunotherapy in HER2-altered lung cancer treatment.

Materials And Methods: We report five cases of advanced NSCLC with HER2 insertion mutation or amplification treated with immunotherapy combined with chemotherapy as the first-line treatment. The HER2 alteration type, duration of treatment and survival were also analyzed.

Results: The five advanced NSCLC patients, three with HER2 mutations and two with HER2 amplifications, received chemo-immunotherapy as the first-line treatment. The average patient age was 54.6 years. Three patients were females, and two were males. Among all the patients, only one had a smoking history. The immunotherapies used were as follows: two patients were treated with sintilimab, and three patients were treated with pembrolizumab. Only one patient had squamous carcinoma, and she was also the only patient with a complete response (CR). The progression-free survival (PFS) ranged from 2-12 months, with a median PFS of 8.0 months.

Conclusions: Chemo-immunotherapy may be a promising first-line treatment option for NSCLC patients with HER2 alterations. Further clinical trials are required to confirm this therapeutic option.
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http://dx.doi.org/10.3389/fonc.2021.633522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093620PMC
April 2021