Publications by authors named "Rongrong Chen"

160 Publications

Ultra-high mechanical property and multi-layer porous structure of amidoximation ethylene-acrylic acid copolymer balls for efficient and selective uranium adsorption from radioactive wastewater.

Chemosphere 2021 Apr 30;280:130722. Epub 2021 Apr 30.

Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, China; Institute of Advanced Marine Materials, Harbin Engineering University, 150001, China. Electronic address:

Adsorption uranium [U(VI)] from U-containing radioactive wastewater (URW) is a critical strategy for solving the resource shortage and environmental pollution in pace with the sustainable development of nuclear energy. However, the URW universally exhibits acidity and contains co-existing metal ions with high concentration. Herein, the amidoximation ethylene-acrylic acid copolymer balls (EAA-AO) with aciduric and super-high mechanical property were successfully synthesized through grafting diaminomaleonitrile and further treatment of amidoximation. Significantly, the mechanical properties of EAA-AO were not affected by the grafting process and maintained super-high mechanical properties. Furthermore, the -NH and unreacted -CN groups in diaminomaleonitrile adjusted the pK to make the optimal pH be 4. In addition, the microstructure of EAA-AO was transformed from the original dense to multi-layer porous structure, which promoted the mass transfer process and the contact between uranyl ions (UO) and internal adsorption active sites. The adsorption capacity of EAA-AO was about 1.78 times that of EAA at pH = 4, and the adsorption capacity for U(VI) was about 8.17 times that of Ba with the second highest adsorption capacity. Therefore, the EAA-AO exhibited ultra-high adsorption performance (q = 3.196 mg g) in the artificial radioactive wastewater, laying a good foundation for subsequent large-scale industrial adsorption of U(VI) in nuclear industrial wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130722DOI Listing
April 2021

Anti-bacterial and super-hydrophilic bamboo charcoal with amidoxime modified for efficient and selective uranium extraction from seawater.

J Colloid Interface Sci 2021 Mar 29;598:455-463. Epub 2021 Mar 29.

Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China; Institute of Advanced Marine Materials, Harbin Engineering University, 150001, China; Harbin Engineering University Capital Management Co. Ltd, Harbin 150001, China. Electronic address:

With the growing demand for nuclear energy, uranium extraction from seawater (UES) is becoming increasingly important due to the ocean reserves 4.5 billion tons for uranium(VI) [U(VI)]. Herein, two kinds of amidoxime modified bamboo charcoal (AOOBCS and AOOBCH) with porous structure, anti-bacterial, and super-hydrophilic properties were successfully synthetized by two etching methods (soaking and hydrothermal). The super-hydrophilic property of AOOBCH accelerated the contact between the amidoxime group and uranyl ions (UO), and promoted the action of anti-bacterial substances (bamboo-quinone) on bacteria to restrain the form of bacterial membrane. In addition, the amidoxime groups not only didn't destroy the super-hydrophilic surface, but also adjusted the adsorbents' pK by changing the amidoxime grafting rate. Under PH = 7, the adsorption capacity of AOOBCH was about 1.97 times that of AOOBCS and 2.95 times that of BC. Importantly, the AOOBCH exhibited ultra-high uptake capacity (6.37 mg g) and exceptional selectivity for U(VI) in 100-fold interfering ions simulated seawater system due to the chelation between C(NH)NOH and UO to form a more stable coordination structure (E = -36.56 eV). Benefiting from the superior performance and selectivity, the AOOBCH is a potential candidate for UES.
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http://dx.doi.org/10.1016/j.jcis.2021.03.154DOI Listing
March 2021

Identification of the trehalose-6-phosphate synthase gene family in Medicago truncatula and expression analysis under abiotic stresses.

Gene 2021 Jun 18;787:145641. Epub 2021 Apr 18.

College of Biological Sciences and Engineering, Jiangxi Agricultural University, Nanchang 330045, PR China. Electronic address:

Trehalose-6-phosphate synthase (TPS) exerts important functions related to plant desiccation tolerance and responses to environmental stimuli. However, in Medicago truncatula, the TPS family has not been reported to date. This study found 11 MtTPS genes in the genome of M. truncatula, which could be divided into two subfamilies: Class I and Class II. All TPS family members have a TPS domain (Glyco transf_20) at the N-terminus and a TPP domain (Trehalose_PPase) at the C-terminus. Interestingly, the genetic structures differ between Class I and Class II, Class I members have more introns than Class II members. Furthermore, transcriptome and real-time PCR analysis showed that five MtTPS genes could be induced by drought, salt or cold. Specifically, MtTPS2, MtTPS8, MtTPS9, MtTPS11 were up-regulated under both drought and salt treatment, particularly, MtTPS8 and MtTPS9 can also be induced by cold, while MtTPS7 only responded to salt stress. In summary, this study provides the foundation for further research on TPS genes in M. truncatula and their regulatory function in response to abiotic stresses.
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http://dx.doi.org/10.1016/j.gene.2021.145641DOI Listing
June 2021

The influence of STK11 mutation on acquired resistance to immunotherapy in advanced non-small cell lung cancer with Lynch syndrome: a case report and literature review.

Ann Palliat Med 2021 Mar 23. Epub 2021 Mar 23.

Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, China.

Immune checkpoint inhibitors (ICI) monotherapy or combination therapies have become increasingly popular in patients with advanced non-small cell lung cancer (NSCLC). However, there are still many unknowns concerning the predictive bio-markers and resistance mechanisms to immunotherapy. Patients with primary tumor STK11 mutation reportedly to have a lower response rate than the STK11 wildtype and possibly a primary resistance mechanism to ICIs. However, there is presently no data regarding the contribution of STK11 to acquired resistance to ICIs. Herein we report on a patient who was diagnosed with advanced lung squamous cell carcinoma accompanied by Lynch syndrome. The patient developed an STK11 mutation after receiving pembrolizumab as a first-line treatment. Programmed death ligand 1 (PD-L1) was highly expressed (50%) in the biopsy. HRAS Q61L and TP53 R158L were mainly detected. Unexpectedly, the patient carried an MSH6 heterozygous germline mutation, and was classified as proficient mismatch repair (pMMR). The patient subsequently received pembrolizumab (200 mg, ivgtt, q3w) as first line therapy and achieved stable disease (SD) as the best response. After eight treatment cycles, the patient suffered disease progression (PD), and an STK11 frameshift mutation was newly identified in his plasma circulating tumor deoxyribonucleic acid (ctDNA). This case study suggests that STK11 could contribute to pembrolizumab acquired resistance. Furthermore, the patient was also diagnosed with Lynch syndrome, which rarely occurs in lung cancer.
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http://dx.doi.org/10.21037/apm-20-1639DOI Listing
March 2021

Characteristics of T-Cell Receptor Repertoire and Correlation With Mutations in All Stages of Lung Cancer.

Front Oncol 2021 11;11:537735. Epub 2021 Mar 11.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Lung cancer is the leading cause of cancer-related deaths worldwide, and its occurrence is related to the accumulation of gene mutations and immune escape of the tumor. Sequencing of the T-cell receptor (TCR) repertoire can reveal the immunosurveillance status of the tumor microenvironment, which is related to tumor escape and immunotherapy. This study aimed to determine the characteristics and clinical significance of the TCR repertoire in lung cancer. To comprehensively profile the TCR repertoire, results from high-throughput sequencing of samples from 93 Chinese patients with lung cancer were analyzed. We found that the TCR clonality of tissues was related to smoking, with higher clonality in patients who had quit smoking for less than 1 year. As expected, TCR clonality was correlated with stages: patients with stage IV disease showed higher clonality than others. The correlation between TCR repertoire and epidermal growth factor receptor (EGFR) status was also investigated. Patients with non-L858R mutations showed higher clonality and a lower Shannon index than other groups, including patients with L858R mutation and wild-type . Furthermore, we analyzed the TCR similarity metrics-that is, the TCR shared between postoperative peripheral blood and tissue of patients with non-distant metastasis of lung cancer. A similar trend was found, in which patients with L858R mutations had lower overlap index (OLI) and Morisita index (MOI) scores. Moreover, the OLI showed a positive correlation with several clinical characteristics, including the tumor mutational burden of tissues and the maximum somatic allele frequency of blood; OLI showed a negative correlation with the ratio of CD4+CD28+ in CD4+ cells and the ratio of CD8+CD28+ in CD8+ cells. In conclusion, TCR clonality and TCR similarity metrics correlated with clinical characteristics of patients with lung cancer. Differences in TCR clonality, Shannon index, and OLI across subtypes provide information to improve understanding about varied responses to immunotherapy in patients with different mutations.
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http://dx.doi.org/10.3389/fonc.2021.537735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991722PMC
March 2021

Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy.

Front Immunol 2021 25;12:631483. Epub 2021 Feb 25.

Clinical Cancer Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Treatment options for rare tumors are limited, and comprehensive genomic profiling may provide useful information for novel treatment strategies and improving outcomes. The aim of this study is to explore the treatment opportunities of patients with rare tumors using immune checkpoint inhibitors (ICIs) that have already been approved for routine treatment of common tumors. We collected immunotherapy-related indicators data from a total of 852 rare tumor patients from across China, including 136 programmed cell death ligand-1 (PD-L1) expression, 821 tumors mutational burden (TMB), 705 microsatellite instability (MSI) and 355 human leukocyte antigen class I (HLA-I) heterozygosity reports. We calculated the positive rates of these indicators and analyzed the consistency relationship between TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1. The prevalence of PD-L1 positive, TMB-H, MSI-, and HLA-I -heterozygous was 47.8%, 15.5%, 7.4%, and 78.9%, respectively. The consistency ratio of TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1 was 54.8% (78/135), 87.3% (598/685), and 47.4% (54/114), respectively. The prevalence of the four indicators varied widely across tumors systems and subtypes. The probability that neuroendocrine tumors (NETs) and biliary tumors may benefit from immunotherapy is high, since the proportion of TMB-H is as high as 50% and 25.4% respectively. The rates of PD-L1 positivity, TMB-H and MSI-H in carcinoma of unknown primary (CUP) were relatively high, while the rates of TMB-H and MSI-H in soft tissue tumors were both relatively low. Our study revealed the distribution of immunotherapeutic indicators in patients with rare tumors in China. Comprehensive genomic profiling may offer novel therapeutic modalities for patients with rare tumors to solve the dilemma of limited treatment options.
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http://dx.doi.org/10.3389/fimmu.2021.631483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959707PMC
February 2021

Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study.

Oncol Lett 2021 Apr 25;21(4):329. Epub 2021 Feb 25.

Department of Oncology, Hebei Chest Hospital, Research Center of Hebei Lung Cancer Prevention and Treatment, Shijiazhuang, Hebei 050041, P.R. China.

Tumor mutation burden (TMB) is an independent indicator used to select patients sensitive to immunotherapy. The present study aimed to investigate the clinicopathological and molecular characteristics of patients with hypermutant lung cancer to identify an economical, simple and complementary method for predicting TMB and immunotherapy responses. In total, 1,000 patients with lung cancer were randomly selected, and their samples were submitted to next-generation sequencing, with their TMB status reviewed. The threshold of hypermutation was set to 17.24 mutations (muts)/Mb. The proportion of smokers was higher in the hypermutant cohort (n=67) compared with in the non-hypermutant cohort (n=933; 85.1 vs. 46.6%; P<0.0001). Compared with in the non-hypermutant cohort, the proportion of squamous cell carcinoma cases and small cell lung cancer cases was higher in the hypermutant cohort (22.4 vs. 13.1% and 6.0 vs. 2.6%, respectively). In addition, compared with in the non-hypermutant cohort, mutations in the low-density lipoprotein receptor-related protein 1B were more frequently observed in the hypermutant cohort (67.2 vs. 14.3%; P<0.0001). A similar trend was obtained for all genes tested, except for the EGFR gene. Furthermore, in the hypermutant cohort, the prevalence of microsatellite instability was extremely high (9.0%). The mutation frequency in DNA damage response (DDR) genes was notably higher in the hypermutant cohort, where several DDR-associated genes were enriched, compared with in the non-hypermutant cohort. The enrichment analysis revealed a strong association between mutations in Notch signaling and high TMB. To the best of our knowledge, the present study is the first to comprehensively investigate the clinical and genetic characteristics of patients with hypermutant lung cancer in a Chinese population. The results of the current study suggested that hypermutant lung cancer exerted distinctive clinical and genetic features, which may be used as complementary indicators for screening patients sensitive to immunotherapy.
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http://dx.doi.org/10.3892/ol.2021.12590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933761PMC
April 2021

Case Report: Long-Term Response to Pembrolizumab Combined With Endocrine Therapy in Metastatic Breast Cancer Patients With Hormone Receptor Expression.

Front Immunol 2021 22;12:610149. Epub 2021 Feb 22.

Institute of Cancer, Xinqiao Hospital, Army Medical University, Chongqing, China.

Breast cancer is one of the most commonly diagnosed malignancies. Although endocrine therapy improves the survival of patients with hormone receptor (HR)-positive breast cancer, the post-endocrine therapy strategy for metastatic breast cancer remains challenging. Herein, we report two patients who benefited from antiestrogen agents combined with an immunotherapy regimen to support the notion that an immunotherapy combination regimen may be a potential treatment for patients with HR-positive metastatic breast cancer post-endocrine therapy. Case 1 involved a patient with relapsed breast cancer with ovarian and brain metastases after endocrine therapy. After undergoing surgery for the ovarian lesions, she received three cycles of chemotherapy. Given that the lesions in the brain did not change, chemotherapy was discontinued. A high T cell receptor (TCR) repertoire (high Shannon index and clonality) was observed in the tumor. Considering the patient's preference and safety, and the efficacy of immunotherapy, she was administered with letrozole combined with pembrolizumab. The patient achieved a partial response, and the progression-free survival (PFS) was more than 21 months. Case 2 involved a patient with breast cancer with multiple bone metastases. After failure of combined radiotherapy and chemotherapy, the patient received tamoxifen combined with pembrolizumab based on the patient's preference and clinical biomarkers of a positive differentiation cluster of eight tumor-infiltrating lymphocytes and a high TCR repertoire (high Shannon index and clonality) in the tumor. The patient's bone pain and biomarkers were relieved after the treatment. The patients completed six cycles of pembrolizumab, and the PFS was more than 21 months. In conclusion, our study confirmed that antiestrogen agents combined with an immunotherapy regimen is a promising treatment for patients with HR-positive metastatic breast cancer.
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http://dx.doi.org/10.3389/fimmu.2021.610149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939121PMC
February 2021

A New Way of Rice Breeding: Polyploid Rice Breeding.

Plants (Basel) 2021 Feb 24;10(3). Epub 2021 Feb 24.

School of Life Sciences, Hubei University, Wuhan 430062, China.

Polyploid rice, first discovered by Japanese scientist Eiiti Nakamori in 1933, has a history of nearly 90 years. In the following years, polyploid rice studies have mainly focused on innovations in breeding theory, induction technology and the creation of new germplasm, the analysis of agronomic traits and nutritional components, the study of gametophyte development and reproduction characteristics, DNA methylation modification and gene expression regulation, distant hybridization and utilization among subspecies, species and genomes. In recent years, lines and neo-tetraploid rice lines with stable high seed setting rate characteristics have been successively selected, breaking through the bottleneck of low seed setting rate of polyploid rice. Following, a series of theoretical and applied studies on high seed setting rate tetraploid rice were carried out. This has pushed research on polyploid rice to a new stage, opening new prospects for polyploid rice breeding.
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http://dx.doi.org/10.3390/plants10030422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996342PMC
February 2021

BRAF V600E mutation as a novel mechanism of acquired resistance to ALK inhibition in ALK-rearranged lung adenocarcinoma: A case report.

Medicine (Baltimore) 2021 Feb;100(8):e24917

Geneplus-Beijing, Beijing, China.

Rationale: Patients with lung adenocarcinoma harboring EML4-ALK rearrangements respond well to multiple ALK tyrosine kinase inhibitors (TKIs). However, the tumor will invariably progress due to acquired resistance. Comprehensive genomic profiling appears to be a promising strategy to reveal the underlying molecular mechanisms of ALK-TKIs resistance.

Patient Concerns: A patient with right lung adenocarcinoma harboring an ALK rearrangement received targeted therapy with multiple ALK-TKIs. He sought for follow-up treatment after his disease progressed again.

Diagnosis: The patient had a tumor diagnosed with stage I (T1bN0M0) lung adenocarcinoma.

Interventions: Due to the surgical contraindication, the patient did not undergo surgical resection. Instead, he received crizotinib as the first-line therapy with the progression-free survival of 20 months. Then he switched to alectinib treatment, however the disease rapidly progressed again.

Outcomes: Next-generation sequencing was performed and revealed that 7 somatic mutations were identified. Among them, 2 mutations, ALK I1171T and BRAF V600E, may be responsible for the resistance of this patient to ALK-TKIs. BRAF V600E mutation may explain the patient's resistance to lorlatinib.

Lessons: We present a case of ALK-rearranged lung adenocarcinoma with acquired resistance to ALK inhibition, in which the BRAF V600E mutation is a novel resistance mechanism. This provides evidence that BRAF V600E mutation is one mechanism of ALK-TKI resistance.
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http://dx.doi.org/10.1097/MD.0000000000024917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909161PMC
February 2021

Visuomotor predictors of batting performance in baseball players.

J Vis 2021 03;21(3)

Department of Psychology, The University of Hong Kong, Hong Kong SAR.

Hitting a baseball, one of the most difficult skills in all of sports, requires complex hand-eye coordination, but its link with basic visuomotor capabilities remains largely unknown. Here we examined basic visuomotor skills of baseball players and demographically matched nonathletes by measuring their ocular-tracking and manual-control performance. We further investigated how these two capabilities relate to batting performance in baseball players. Compared to nonathletes, baseball players showed better ocular-tracking and manual-control capabilities, which remain unchanged with increasing baseball experience. Both, however, become more correlated with batting accuracy with increasing experience. Ocular-tracking performance is predictive of batting skill, accounting for ≥ 70% of the variance in batting performance across players with ≥ 10 years of experience. A simple linear additive-noise cascade model with shared front-end visual noise that limits batting performance can explain many of our results. Our findings show that fundamental visuomotor capabilities can predict the complex, learned skill of baseball batting.
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http://dx.doi.org/10.1167/jov.21.3.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938007PMC
March 2021

Chinese traditional medicine (GuiZhi-ShaoYao-ZhiMu decoction) as an add-on medication to methotrexate for rheumatoid arthritis: a meta-analysis of randomized clinical trials.

Ther Adv Chronic Dis 2021 12;12:2040622321993438. Epub 2021 Feb 12.

School of Basic Medical Science, Zhejiang Chinese Medical University, Binwen Road 548, Hangzhou, Zhejiang, 310053, China.

Background: GuiZhi-ShaoYao-ZhiMu decoction (GSZD), a traditional Chinese herbal medication, has been frequently used as an add-on medication to methotrexate (MTX) for rheumatoid arthritis (RA) treatment in China. This meta-analysis evaluated the efficacy and safety of adding GSZD to MTX for RA treatment.

Methods: We performed a systematic search of , and the (all databases) for English-language studies and , and for Chinese-language studies up to 28 July 2020. Data from selected studies, mainly the response rates and rate of adverse events (AEs), were extracted independently by two authors, and a random-effects model (Mantel-Haenszel method) was used for the meta-analysis.

Results: A total of 14 randomized controlled trials and 1224 patients were included (623 patients in the GSZD + MTX group and 601 patients in the MTX group). For efficacy, the meta-analysis found that combining GSZD with MTX increased the effective rate [relative risk (RR) = 1.24, 95% confidence interval (CI): 1.18-1.30, based on 1069 patients], defined as >30% efficacy, American College of Rheumatology 20, or a decrease of disease activity score 28 >0.6. Adding GSZD reduced the swollen and tender joint counts, the duration of morning stiffness, the levels of C-reactive protein and rheumatoid factor, and erythrocyte sedimentation rate. The adjuvant therapeutic effect of GSZD was independent of the dose of MTX or the combined utilization of other drugs in both groups. For safety, adding GSZD was associated with a lower rate of total AEs (RR = 0.46, 95% CI: 0.26-0.83, based on 615 patients) and gastrointestinal tract AEs (RR = 0.46, 95% CI: 0.24-0.88, based on 537 patients).

Conclusion: Combining GSZD with MTX may be a more efficacious and safer strategy for treating RA compared with MTX alone. Further large studies are warranted to investigate the long-term efficacy and safety of adding GSZD to MTX for RA treatment.
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http://dx.doi.org/10.1177/2040622321993438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887670PMC
February 2021

Case Report: Fatal Multiorgan Failure and Heterochronous Pneumonitis Following Pembrolizumab Treatment in a Patient With Large-Cell Neuroendocrine Carcinoma of Lung.

Front Pharmacol 2020 29;11:569466. Epub 2021 Jan 29.

State Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Immune checkpoint inhibitors have radically changed the landscape of antitumor therapies in several malignancies. Despite the long-term efficacy, severe immune-related adverse events (irAEs) were not uncommon. However, fatal simultaneous multiorgan failure was rare. Here, we described a patient who developed multiorgan failure, including fulminant myocarditis, myasthenia gravis crisis, hepatic dysfunction, and delayed pneumonitis after pembrolizumab therapy for lung large-cell neuroendocrine carcinoma. After failure of high-dose steroid treatment, implantation of cardiac pacemaker combined with high-dose steroids successfully controlled myocarditis caused by immune checkpoint inhibitors (ICIs). Delayed pneumonitis occurred unexpectedly, and it was treated successfully with steroids. With wild adoption of ICIs in clinical practice, investigations for predictive markers of irAEs are warranted, and more successful treatment strategies are worth sharing.
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http://dx.doi.org/10.3389/fphar.2020.569466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878548PMC
January 2021

The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains.

Front Neurol 2020 20;11:573095. Epub 2021 Jan 20.

Institute of Traditional Chinese Medicine Clinical Basic Medicine, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.

By engaging angiotensin-converting enzyme 2 (ACE2 or Ace2), the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades host cells and affects many organs, including the brain. However, the distribution of ACE2 in the brain is still obscure. Here, we investigated the ACE2 expression in the brain by analyzing data from publicly available brain transcriptome databases. According to our spatial distribution analysis, ACE2 was relatively highly expressed in some brain locations, such as the choroid plexus and paraventricular nuclei of the thalamus. According to cell-type distribution analysis, nuclear expression of ACE2 was found in many neurons (both excitatory and inhibitory neurons) and some non-neuron cells (mainly astrocytes, oligodendrocytes, and endothelial cells) in the human middle temporal gyrus and posterior cingulate cortex. A few ACE2-expressing nuclei were found in a hippocampal dataset, and none were detected in the prefrontal cortex. Except for the additional high expression of Ace2 in the olfactory bulb areas for spatial distribution as well as in the pericytes and endothelial cells for cell-type distribution, the distribution of Ace2 in the mouse brain was similar to that in the human brain. Thus, our results reveal an outline of ACE2/Ace2 distribution in the human and mouse brains, which indicates that the brain infection of SARS-CoV-2 may be capable of inducing central nervous system symptoms in coronavirus disease 2019 (COVID-19) patients. Potential species differences should be considered when using mouse models to study the neurological effects of SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fneur.2020.573095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855591PMC
January 2021

Sequential use of EGFR-tyrosine kinase inhibitors based upon EGFR mutation evolution achieves long-term control in a non-small cell lung cancer patient: a case report.

Ann Palliat Med 2021 Feb 2. Epub 2021 Feb 2.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Tyrosine kinase inhibitor (TKI) has greatly improved the survival of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-TKI sensitive mutations. However, TKI resistance constantly occur, although multiple lines of different generations of TKIs are adopted during the progression. For example, in the case when T790M, which is the most common resistance mechanism of first generation TKIs, occurs, alteration to osimertinib (the third generation TKI) could always be effective. Unfortunately, some cases gradually become resistant even to osimertinib leaving limited therapy choice for clinical practitioners. Few cases have been reported in the situation after EGFR tertiary mutations occurred, such as C797S, G724S, etc. Herein, we report the first clinical evidence that sequential therapy with erlotinib, osimertinib, afatinib plus endostar, brigatinib plus cetuximab, almonertinib, almonertinib plus afatinib achieved long-term control in a NSCLC patient demonstrating EGFR 19Del/T790M/G724S/cis-C797S evolution in response to TKI treatment. EGFR targeted therapy introduced successful management for more than 36 months until now. ctDNA NGS was performed at the time of important clinical event. The EGFR 19Del was discovered in October 2017, and erlotinib was administered for 10 months with PR in the beginning. Then T790M was detected and osimertinib was used for 9 months with SD condition. Subsequently, EGFR G724S was identified in ctDNA with the remaining 19Del and loss of T790M. Afatinib plus endostar was administered and PR was achieved after 1.5 months. PD occurred 6 months later with the emergence of EGFR cis-C797S. Then brigatinib plus cetuximab was chosen and lasted for 4 months with the best response of SD. And then EGFR 19Del and T790M were still detected with loss of G724S and C797S. Almonertinib, another third-generation TKI, was administered for 3 months with SD condition. Finally, 19Del/T790M/G724S/cis-C797S recurred, and whole dose of almonertinib plus afatinib was prescribed until now with a PR at 2 months until now. The side effect was acceptable during the whole period of therapies. Plasma ctDNA NGS provided information of EGFR mutation evolution and inform appropriate therapy regimen during the progression.
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http://dx.doi.org/10.21037/apm-20-1477DOI Listing
February 2021

Novel rare variants in FGFR1 and clinical characteristics analysis in a series of congenital hypogonadotropic hypogonadism patients.

Clin Endocrinol (Oxf) 2021 Feb 6. Epub 2021 Feb 6.

NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Objective: We aimed to analyse FGFR1 rare variants in a series of Chinese congenital hypogonadotropic hypogonadism (CHH) patients. In addition, we intended to understand the clinical characteristics and the response to treatment of CHH patients with FGFR1 rare variants.

Patients And Methods: A total of 357 CHH patients were recruited at Peking Union Medical College Hospital. We used Sanger sequencing to analyse FGFR1 gene. In silico analysis was carried out to study the pathogenicity of novel missense variants. The clinical, endocrinological and therapeutic effects from patients carrying FGFR1 rare variants were analysed retrospectively.

Results: Thimissense mutations.rty patients in this series were found to harbour 29 FGFR1 rare variants, with 8 recurrent and 21 novel variants. After comprehensive analysis, 18 out of 21 novel variants were classified as likely pathogenic (LP) ones. These variants are widely spread throughout the FGFR1 gene and almost all FGFR1 functional domains, which exhibited no hot spot. Cryptorchidism, cleft palate and dental abnormality incidence in this CHH series that possessed FGFR1 LP variants were approximately 38.5%, 7.6% and 3.8%, respectively. Among patients who accepted the fertility-promoting treatment, 8 out of 10 patients succeeded in spermatogenesis.

Conclusions: Eighteen novel LP variants were found to expand the spectrum of FGFR1 rare variants. In CHH patients possessing FGFR1 variants, we found that the rate of spermatogenesis was high following fertility-promoting therapy and the existence of cryptorchidism may represent the underlying factors which affect spermatogenesis.
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http://dx.doi.org/10.1111/cen.14436DOI Listing
February 2021

PLB1-ALK: A novel head-to-head fusion gene identified by next-generation sequencing in a lung adenocarcinoma patient.

Lung Cancer 2021 03 11;153:176-178. Epub 2021 Jan 11.

Department of Pathology, China-Japan Friendship Hospital, No. 2, Yinghuayuan East Street, Beijing, 100029, China. Electronic address:

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http://dx.doi.org/10.1016/j.lungcan.2021.01.002DOI Listing
March 2021

Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis.

Cell Death Dis 2021 Jan 21;12(1):106. Epub 2021 Jan 21.

Department of Radiotherapy, The Cancer Hospital of the University of Chinese Academy of Science (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.

Brain metastasis (BM) is a common malignant event in lung cancer. Here, we recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment (TIME) of the lung and BM independently. For genomic profiling, targeted sequencing was performed. We found that high-frequent ZFHX3 occurred in the lung (40%) and brain tumor (28%), which might relate to brain metastasis event; the vast majority of patients had lesions-shared mutations in primary tumor and BM, confirming the common clonal events; and EGFR was the most frequently clonal gene in both lung and BM, indicating its driver capability. To characterize TIME status, we also sequenced the T cell receptor (TCR) repertoires and performed immunohistochemistry (IHC) on CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in 28 patients who had paired samples. Through the comparison, the TCR clonality of BM was higher than lung tumor, indicating the distinct pattern of the stronger oligoclonal T cell expansion in BM; the primary tumor had a higher TMB than oligo-BM (13.9 vs 8.7 mutations, p = 0.019); CD8 + TILs of BM were significantly lower than lung tumor (10% vs 30%, p = 0.015), revealing the lower level of cytotoxic T cell infiltration; BM showed statistically equivalent level of PD-L1 compared with lung tumor (p = 0.722). We further investigated the potential biomarkers associated with overall survival (OS) after brain surgery. We found that higher TCR clonality was related to prolonged OS in EGFR-treated patients (HR 0.175, p < 0.001) but the worse outcomes in non-EGFR-treated (HR 2.623, p = 0.034). More CD8+ TILs were an independently positive indicator for OS, in EGFR-treated (HR 0.160, p = 0.001) and non-EGFR-treated patients (HR 0.308, p = 0.009). These findings provide a meaningful molecular and clinical understanding of lung carcinoma and brain oligo-metastasis.
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http://dx.doi.org/10.1038/s41419-021-03410-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820277PMC
January 2021

Analysis of cytokines and trace elements in children with febrile seizures.

Transl Pediatr 2020 Dec;9(6):809-817

Department of Pediatrics, Nantong Maternal and Child Health Care Hospital, Nantong, China.

Background: Febrile seizure (FS) is a common neurological condition in children and affects 2-5% of cases of fever. FS occurs with temperature >38 °C without symptoms of central nervous system infection, severe electrolyte imbalance, or clear cause.

Methods: From June 2018 to December 2019, 65 children with FS, and 60 children with acute upper respiratory tract infections without seizures who were admitted to the pediatric department, and 60 healthy children as the control group were selected for the study. The serum iron (SI), serum calcium (SC), interleukin (IL)-6, IL-10 and procalcitonin (PCT) levels in the two groups of children were detected. The FS group was further divided into simple FS (SFS) and complex FS (CFS).

Results: The duration of fever in the FS group was significantly longer than in the control group (P<0.05). The SC and SI levels of the FS group were significantly lower than those in the control group (P<0.05). The SC and SI levels of the CFS group were also lower than those of the SFS group (P<0.05), and the IL-6 levels of the CFS group were significantly higher than in the SFS group (P<0.05).

Conclusions: A decrease in the levels of SI, and SC and an increase of IL-6 were closely related to the occurrence of FS, suggesting that clinical attention should be paid to monitoring changes of SI, SC and IL-6 levels in children with FS. As the levels of SI and SC decrease, the frequency of possible seizures may increase. Care should be taken to correct electrolyte disorders in time.
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http://dx.doi.org/10.21037/tp-20-398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804487PMC
December 2020

Swollen-layer constructed with polyamine on the surface of nano-polyacrylonitrile cloth used for extract uranium from seawater.

Chemosphere 2021 May 4;271:129548. Epub 2021 Jan 4.

Key Laboratory of Superlight Material and Surface Technology, Ministry of Education, Harbin Engineering University, 150001, PR China; College of Material Science and Chemical Engineering, Harbin Engineering University, 150001, PR China; Harbin Engineering University Capital Management Co. Ltd., 150001, PR China; Institute of Advanced Marine Materials, Harbin Engineering University, 150001, PR China. Electronic address:

In this study, a swelling layer was constructed on the surface of the nano-polyacrylonitrile (PAN) fiber fabric prepared by electrospinning to enrich uranium (U (VI)) adsorption from seawater. The constructed swelling layer composes of a polyethyleneimine (PEI) containing a huge amount of amino groups and imino groups with strong hydrophilicity. The molecular chain swelled in an aqueous solution by forming a swelling layer on the PAN surface. In addition, p-aminobenzenesulfonic acid (SA) was used as the side chain end group grafted on the PAN surface, the benzene ring as the side chain can hinder the rotation of the PEI chain, thereby increasing the rigidity. The increasing of the rigidity leads to stretch the conformation of the PEI molecular chain, increasing the probability of collision with U (VI), which is beneficial for adsorption. The adsorption capacity of the prepared adsorbent in the adsorption experiment reached 215.25 mg g, and the adsorption capacity in the 8 ppm spiked simulated seawater reached 144.5 mg g. The adsorption mechanism of U (VI) was analyzed by XPS. The sulfonic acid group in SA as the terminal group and amino group in the swelling layer formed a coordination structure with U (VI). The swelling layer constructed on the surface of polyacrylonitrile fibers is used to effectively extract uranium from seawater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129548DOI Listing
May 2021

Zwitterionic modified electrostatic flocking surfaces for diatoms and mussels resistance.

J Colloid Interface Sci 2021 Apr 17;588:9-18. Epub 2020 Dec 17.

Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin 150001, China; College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China. Electronic address:

Environmentally friendly antifouling coatings without biocide release need to be developed. Herein, a vertical array of nylon fibers coated with poly(sulfobetaine methacrylate) (PSBMA) was prepared by the electrostatic flocking technique and free radical polymerization catalyzed by Fe, which are called zwitterionic electrostatic flocking surfaces (ZEFS). The ZEFS showed resistance to diatoms because the fiber diameter was smaller than the diatom size. At the same time, the ZEFS prevented mussels adhesion. The number of plaques on the ZEFS was reduced by more than 98% and 96% compared with the glass surface and polydimethylsiloxane (PDMS) after a 4-day assay. The special surface morphology of the vertical arrangement of fibers makes it difficult for the mussels to empty seawater. Zwitterionic surface modification further enhanced the resistance to mussel adhesion. The ZEFS showed strong hydrophilicity with an underwater oil contact angle of up to 152 ± 2.4°, which reduces the adhesion work of mussel protein adhesion to the fibers and the wettability of the protein on the fiber surface. In addition, the zwitterionic layer exhibited good stability in artificial seawater, and it retained more than 96% stability after 30 days immersion in artificial seawater.
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http://dx.doi.org/10.1016/j.jcis.2020.12.036DOI Listing
April 2021

Nuclear-Encoded Maturase Protein 3 is Required for the Splicing of Various Group II Introns inMitochondria during Maize (zea mays L.) Seed Development.

Plant Cell Physiol 2020 Dec 30. Epub 2020 Dec 30.

Center of Seed Science and Technology, Beijing Key Laboratory of Crop Genetic Improvement, China Agricultural University, Beijing, China.

Splicing of plant organellar group II introns from precursor-RNA transcripts requires the assistance of nuclear-encoded splicing factors. Maturase (nMAT) is a kind of such factors, as its three homologs (nMAT1, 2, and 4) has been identified for splicing of various mitochondrial introns in Arabidopsis. However, function of nMAT in maize (Zea mays L.) is unknown. In this study, we identified a seed development mutant, Empty Pericarp 2441 (emp2441) from maize, which showed severely arrested embryogenesis and endosperm development. Positional cloning and transgenic complementation assays revealed that Emp2441 encoded a maturase-related protein, ZmnMAT3. ZmnMAT3 highly expressed during seed development and its protein located in the mitochondria. The loss-of-function of ZmnMAT3 resulted in reduced splicing efficiency of various mitochondrial group II introns, particularly of the trans-splicing of nad1 intron 1, 3, and 4, which consequently abolished the transcript of nad1 and severely impaired the assembly and activity of mitochondrial complex I. Moreover, the Zmnmat3 mutant showed defective mitochondrial structure and induced the expression and activity of alternative oxidases. These results indicated that ZmnMAT3 is essential for mitochondrial complex I assembly during kernel development in maize.
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http://dx.doi.org/10.1093/pcp/pcaa161DOI Listing
December 2020

Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma.

Front Oncol 2020 10;10:607130. Epub 2020 Dec 10.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: This study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.

Methods: We retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer-related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.

Results: Of 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.

Conclusions: Significant differences exist among three subtypes of LUSC in molecular characterizations.
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http://dx.doi.org/10.3389/fonc.2020.607130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758445PMC
December 2020

Case Report: Double Germline Mutations in and in a Patient With Mixed Serous-Endometrioid Endometrial Carcinoma.

Front Med (Lausanne) 2020 3;7:581982. Epub 2020 Nov 3.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gynecology, Peking University Cancer Hospital & Institute, Beijing, China.

Mixed serous-endometrioid endometrial carcinoma is a type of endometrial cancer with relatively low incidence. The genetic factors contributing to the tumorigenesis of mixed carcinoma remains to be explored. Here, we report the first identification of two germline mutations in and in a woman with mixed serous papillary adenocarcinoma and endometrioid carcinoma. Immunohistochemistry analysis showed loss of MSH2 and MSH6 protein expression in the endometrioid component. The patient showed partial response to tislelizumab treatment following progression on chemotherapy. Two germline mutations in and may collectively promote the tumorigenesis of uterine endometrium with two distinct histological components.
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http://dx.doi.org/10.3389/fmed.2020.581982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670051PMC
November 2020

ctDNA facilitated the diagnosis of a patient with synchronous urothelial carcinoma and non-small cell lung cancer: case report.

Ann Transl Med 2020 Oct;8(20):1323

Department of Cancer Center, Daping Hospital & Army Medical Center of the PLA, Chongqing, China.

The diagnosis and treatment for multiple primary cancers have been a great challenge in clinical practice. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA that circulates in the blood. Herein we report a case that ctDNA facilitated the diagnosis of synchronous urothelial carcinoma (UC) and lung adenocarcinoma. A 58-year-old male patient was diagnosed with UC initially. Computed tomography (CT) revealed multiple metastases without the brain after surgery and adjuvant chemotherapy. However, the patient had a progressively worsened headache symbol during system therapy. We explored the genome variations using next-generation sequencing (NGS). and mutations were detected from UC surgical tissue and postoperative ctDNA. Unexpectedly, the epidermal growth factor receptor () exon 19 deletion (19del) mutation, which is common in non-small cell lung cancer (NSCLC), was also identified in ctDNA. Pathological analysis of a neck lymph node confirmed adenocarcinoma derived from the lung. Meanwhile, 19del was detected in neck lymph node biopsy. The ctDNA contained both UC and lung adenocarcinoma-derived mutations. Thus, the diagnosis was modified into synchronous UC and lung adenocarcinoma. Interestingly, the lung adenocarcinoma-derived lesions responded well to osimertinib (80mg, once daily), while the UC did not. His headache rapidly subsided and disappeared. This case demonstrates that ctDNA analysis may better capture the molecular heterogeneity harbored by multiple primary tumors in a patient and can facilitate the diagnosis and therapy of patients with simultaneous cancers.
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http://dx.doi.org/10.21037/atm-20-6552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661894PMC
October 2020

Combined treatment with anlotinib and chemotherapy for advanced esophageal squamous cell carcinoma improved patient survival: a case report.

Am J Transl Res 2020 15;12(10):6578-6583. Epub 2020 Oct 15.

Department of Gastrointestinal Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou 510080, China.

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in Eastern Asia. Historically, advanced ESCC treatments have had low efficacy and new treatments, including immunotherapy or combination therapies, are emerging. Here, we report a special case of recurrent ESCC after surgery. The patient had a failed immunotherapy course, but benefited from anlotinib combined with chemotherapy for a fourth-line therapy. Survival after the combined therapy was greater than 19 months, and the overall patient survival was greater than 32 months.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653628PMC
October 2020

Clonal Architecture of Mutation Predicts the Efficacy of EGFR-Tyrosine Kinase Inhibitors in Advanced NSCLC: A Prospective Multicenter Study (NCT03059641).

Clin Cancer Res 2021 Feb 13;27(3):704-712. Epub 2020 Nov 13.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China.

Purpose: Clonal architecture is fundamental for the understanding of cancer biology and therapy; however, multiregional sampling in advanced-stage cancers is not always applicable. This prospective clinical trial was to investigate whether paired tissue and circulating tumor DNA (ctDNA) could describe the clonal architecture of advanced non-small cell lung cancer (NSCLC) and its association with clinical outcome (NCT03059641).

Patients And Methods: Paired tumor and plasma ctDNA samples were sequenced by target-capture deep sequencing of 1,021 genes. Clonal dominance analysis was performed on the basis of PyClone.

Results: Overall, 300 treatment-naïve patients with stage IIIB-IV NSCLC were recruited from 14 centers. Of the 94 patients with available ctDNA data for clonal architecture analysis, 72 (76.6%) showed as the dominant clone. The median progression-free survival was longer for these patients than for the 22 patients whose was nondominant clone [11 vs. 10 months; HR, 0.46; 95% confidence interval (CI), 0.24-0.88; = 0.02]. The difference was more significant if both tissue and ctDNA defined as dominant clone ( = 43) versus those not ( = 8; 11 vs. 6 months; HR, 0.13; 95% CI, 0.04-0.50; = 0.003). Moreover, multivariate Cox proportional HR analysis demonstrated clonal architecture as an independent prognostic indicator of the efficacy of EGFR-tyrosine kinase inhibitors (TKIs).

Conclusions: Paired tissue and ctDNA could be analyzed for clonal architecture in advanced cancer. mutations do not always make up a dominant clone in advanced NSCLC, which was associated with the efficacy of EGFR-TKIs in NSCLC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3063DOI Listing
February 2021

Secretion mechanism and adhesive mechanism of diatoms: Direct evidence from the quantitative analysis.

Micron 2021 01 8;140:102951. Epub 2020 Oct 8.

Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China. Electronic address:

Diatoms are one of the biofouling species attached to the substrate that can cause substrate corrosion, fuel consumption and destruction of the ecological balance. Therefore, the study of single-cellfouling organisms, particularly, the quantitative analysis of extracellular polymeric substances (EPS) is essential for antifouling. Atomic Force Microscope (AFM) was used to quantify three types of diatoms: Nitzschia closterium (N. closterium), Phaeodactylum tricornutum (P. tricornutum) and Halamphora sp. The situation of N. closterium was analyzed multiple times and the results showed that the adhesion value range of N. closterium with nacked chromatophores was three times larger than the mature one. The discovery of the EPS secretion from chromatophore is discussed in this paper, and the proposed mechanism has special implications to study the adhesive protein. Adhesion capabilities of different diatom genera and species were revealed as well. The average adhesion values of N. closterium, P. tricornutum and Halamphora sp. were about 1.7 nN, 3.3 nN and 2.5 nN, respectively, which suggest P. tricornutum could be a better candidate for testing diatom resistance on epoxy materials in the lab. Experimental data and discussions in this paper provide insights for further study of diatoms in the field of antifouling.
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http://dx.doi.org/10.1016/j.micron.2020.102951DOI Listing
January 2021

A multicenter real-world study of tumor-derived DNA from pleural effusion supernatant in genomic profiling of advanced lung cancer.

Transl Lung Cancer Res 2020 Aug;9(4):1507-1515

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Pleural effusion (PE) is commonly observed in advanced lung cancer. Research has suggested that molecular profiling of PE could be used to detect tumor driver mutations, thus informing clinical decision-making. However, the performance of PE samples in a real-world setting has yet to be examined.

Methods: A total of 678 metastatic lung cancer patients with pleural effusion were enrolled in this study. Cohort 1 included 22 patients whose PE and matched plasma samples were simultaneously collected as a pilot study. Cohort 2 comprised 656 patients, from whom 734 samples were collected in a real world setting. These samples were subjected to targeted next-generation sequencing (NGS) of 1,021 cancer-related genes.

Results: PE supernatant was the preferred choice for genetic profiling. While the maximal somatic allele frequency (MSAF) of plasma in patients with M1a stage was significantly lower than that in patients with M1b/c stages (4.4%±9.6% . 9.0%±14.1%, P<0.01), the MSAF of PE supernatant was similar between M1a and M1b/c stages. PE supernatant demonstrated higher sensitivity than plasma in detecting actionable mutations in cohort 1 (81.8% . 45.5%, P=0.01) as well as in M1a disease (84.7% . 42.1%, P<0.01), but not in M1b/c disease, in cohort 2. Known resistant mutations were identified in 72 of the 117 patients who were resistant to first- or second-generation EGFR-TKIs, 22 of the 42 patients who were resistant to osimertinib, and 9 of the 13 patients who were resistant to crizotinib. Remarkably, PE supernatant outperformed plasma in identifying mutations that confer resistance to first- and second-generation EGFR-TKIs (75.4% . 29.8%, P<0.001).

Conclusions: This real-world large cohort study verified that PE supernatant had higher sensitivity than plasma for identifying actionable mutations, including resistance mutations. PE supernatant would be preferred by physicians for assessing tumor genomics in advanced lung cancer when tumor tissue is not available.
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http://dx.doi.org/10.21037/tlcr-20-882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481626PMC
August 2020

Casein kinase 1α inhibits p53 downstream of MDM2‑mediated autophagy and apoptosis in acute myeloid leukemia.

Oncol Rep 2020 Nov 9;44(5):1895-1904. Epub 2020 Sep 9.

Department of Hematology, Wenzhou Key Laboratory of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.

Enhancement of autophagy serves as a promising therapeutic strategy for cancer, including acute myeloid leukemia (AML). Casein kinase 1α (CK1α), encoded by CSNK1A1, regulates Wnt/β‑catenin, p53 and other key signaling pathways, and is critically involved in tumor progression. However, the relationship and mechanism of CK1α with autophagy in AML still remain unclear. In the present study, it was found that AML patients had higher expression of CSNK1A1 mRNA than healthy donors. Furthermore, we analyzed 163 cases of AML patients in the LAML database of TCGA and found that AML patients with high CSNK1A1 had shorter overall survival than those with low or medium CSNK1A1 expression. Furthermore, we demonstrated that CK1α was a negative regulator of autophagy and apoptosis. Pharmacologic inhibition of CK1α using D4476 or CK1α knockdown via lentivirus‑mediated shRNA suppressed proliferation and the clone formation by enhancing autophagic flux and apoptosis in AML cell lines as well as in patient blast cells. Intriguingly, D4476‑induced cell death was aggravated in combination with an autophagy inhibitor, Spautin‑1, suggesting that autophagy may be a pro‑survival signaling. CK1α interacted with murine double minute 2 (MDM2) and p53, and CK1α inhibitor D4476 significantly upregulated p53 and phosphorylated 5' AMP‑activated protein kinase (AMPK), and substantially inhibited the phosphorylation of mammalian target of rapamycin (mTOR). Our findings indicate that CK1α promotes AML by suppressing p53 downstream of MDM2‑mediated autophagy and apoptosis, suggesting that targeting CK1α provides a therapeutic opportunity to treat AML.
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http://dx.doi.org/10.3892/or.2020.7760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550986PMC
November 2020