bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical development of CD126 CAR-T cells with broad antitumor activity
Authors: Mishra Ameet K. , Kemler Iris , Dingli David
Published: January 2021

Chimeric antigen receptor T (CAR-T) cell therapy is a transformative approach to cancer eradication. CAR-T is expensive partly due to the restricted use of each CAR construct for specific tumors. Thus, a CAR construct with broad antitumor activity can be advantageous. We identified that CD126 is expressed by many hematologic and solid tumors, including multiple myeloma, lymphoma, acute myeloid leukemia, pancreatic and prostate adenocarcinoma, non-small cell lung cancer, and malignant melanoma among others. CAR-T cells targeting CD126 were generated and shown to kill many tumor cells in an antigen-specific manner and with efficiency directly proportional to CD126 expression. Soluble CD126 did not interfere with CAR-T cell killing. The CAR-T constructs bind murine CD126 but caused no weight loss or hepatotoxicity in mice. In multiple myeloma and prostate adenocarcinoma xenograft models, intravenously injected CD126 CAR-T cells infiltrated within, expanded, and killed tumor cells without toxicity. Binding of soluble interleukin-6 receptor (sIL-6R) by CAR-T cells could mitigate cytokine release syndrome. Murine SAA-3 levels were lower in mice injected with CD126 CAR-T compared to controls, suggesting that binding of sIL-6R by CAR-T cells could mitigate cytokine release syndrome. CD126 provides a novel therapeutic target for CAR-T cells for many tumors with a low risk of toxicity.
Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial)
Authors: Ueno Hideki , Ishiguro Megumi , Nakatani Eiji , Ishikawa Toshiaki , Uetake Hiroyuki , Murotani Kenta , Matsui Shigeyuki , Teramukai Satoshi , Sugai Tamotsu , Ajioka Yoichi , Maruo Hirotoshi , Kotaka Masahito , Tsujie Masaki , Munemoto Yoshinori , Yamaguchi Takashi , Kuroda Hisashi , Fukunaga Mutsumi , Tomita Naohiro , Sugihara Kenichi
Published: January 2021

Background

The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial).

Methods

The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration.

Results

The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell’s C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding.

Conclusions

Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.
Indoleamine 2,3-dioxygenase 1 limits hepatic inflammatory cells recruitment and promotes bile duct ligation-induced liver fibrosis
Authors: Mo Chan , Xie Shuwen , Liu Bin , Zhong Weichao , Zeng Ting , Huang Sha , Lai Yuqi , Deng Guanghui , Zhou Chuying , Yan Weixin , Chen Yuyao , Huang Shaohui , Gao Lei , Lv Zhiping
Published: January 2021

Liver fibrosis is a course of chronic liver dysfunction, can develop into cirrhosis and hepatocellular carcinoma. Inflammatory insult owing to pathogenic factors plays a crucial role in the pathogenesis of liver fibrosis. Indoleamine 2,3-dioxygenase 1 (IDO1) can affect the infiltration of immune cells in many pathology processes of diseases, but its role in liver fibrosis has not been elucidated completely. Here, the markedly elevated protein IDO1 in livers was identified, and dendritic cells (DCs) immune-phenotypes were significantly altered after BDL challenge. A distinct hepatic population of CD11c+DCs was decreased and presented an immature immune-phenotype, reflected by lower expression levels of co-stimulatory molecules (CD40, MHCII). Frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+MHCII+, and CD11c+CD40+cells in splenic leukocytes were reduced significantly. Notably, IDO1 overexpression inhibited hepatic, splenic CD11c+DCs maturation, mature DCs-mediated T-cell proliferation and worsened liver fibrosis, whereas above pathological phenomena were reversed in IDO1−/−mice. Our data demonstrate that IDO1 affects the process of immune cells recruitment via inhibiting DCs maturation and subsequent T cells proliferation, resulting in the promotion of hepatic fibrosis. Thus, amelioration of immune responses in hepatic and splenic microenvironment by targeting IDO1 might be essential for the therapeutic effects on liver fibrosis.
FAT10 protects against ischemia-induced ventricular arrhythmia by decreasing Nedd4-2/Nav1.5 complex formation
Authors: Liu Xiao , Ge Jin , Chen Chen , Shen Yang , Xie Jinyan , Zhu Xin , Liu Menglu , Hu Jinzhu , Chen Leifeng , Guo Linjuan , Zhou Qiongqiong , Yan Xia , Qiu Yuming , Wan Rong , Marian Ali J. , Hong Kui
Published: January 2021

The human leukocyte antigen F-associated transcript 10 (FAT10) is a member of the small ubiquitin-like protein family that binds to its target proteins and subjects them to degradation by the ubiquitin–proteasome system (UPS). In the heart, FAT10 plays a cardioprotective role and affects predisposition to cardiac arrhythmias after myocardial ischemia (MI). However, whether and how FAT10 influences cardiac arrhythmias is unknown. We investigated the role of FAT10 in regulating the sodium channel Nav1.5, a major regulator of cardiac arrhythmias. Fat10 was conditionally deleted in cardiac myocytes using Myh6-Cre and Fat10F/F mice (cFat10−/−). Compared with their wild-type littermates, cFat10−/− mice showed prolonged RR, PR, and corrected QT (QTc) intervals, were more likely to develop ventricular arrhythmia, and had increased mortality after MI. Patch-clamp studies showed that the peak Na+ current was reduced, and the late Na+ current was significantly augmented, resulting in a decreased action potential amplitude and delayed depolarization. Immunoblot and immunofluorescence analyses showed that the expression of the membrane protein Nav1.5 was decreased. Coimmunoprecipitation experiments demonstrated that FAT10 stabilized Nav1.5 expression by antagonizing Nav1.5 ubiquitination and degradation. Specifically, FAT10 bound to the lysine residues in the C-terminal fragments of Nav1.5 and decreased the binding of Nav1.5 to the Nedd4-2 protein, a ubiquitin E3 ligase, preventing degradation of the Nav1.5 protein. Collectively, our findings showed that deletion of the Fat10 in cardiac myocytes led to increased cardiac arrhythmias and increased mortality after MI. Thus, FAT10 protects against ischemia-induced ventricular arrhythmia by binding to Nav1.5 and preventing its Neddylation and degradation by the UPS after MI.
A new risk factor indicator for papillary thyroid cancer based on immune infiltration
Authors: Yang Zhou , Wei Xiyi , Pan Yitong , Xu Jingyuan , Si Yan , Min Zhijun , Yu Bo
Published: January 2021

Increasing evidence has indicated a close association between immune infiltration in cancer and clinical outcomes. However, related research in thyroid cancer is still deficient. Our research comprehensively investigated the immune infiltration of thyroid cancer. Data derived from TCGA and GEO databases were analyzed by the CIBERSORT, ESTIMATE, and EPIC algorithms. The CIBERSORT algorithm calculates the proportions of 22 types of immune cells. ESTIMATE algorithm calculates a stromal score to represent all stromal cells in cancer. The EPIC algorithm calculates the proportions of cancer-associated fibroblasts (CAFs) and endothelial cells (ECs), which are the main components of stromal cells. We analyzed the correlation of immune infiltration with clinical characteristics and outcomes of patients. We determined that the infiltration of CD8+ T cells improved the survival of thyroid cancer patients. Overexpression of immune checkpoints was closely related to the development of thyroid cancer. In general, stromal cells were associated with the progression of thyroid cancer. Interestingly, CAFs and ECs had opposite roles in this process. In addition, the BRAFV600E mutation was related to the upregulation of immune checkpoints and CAFs and the downregulation of CD8+ T cells and ECs. Finally, we constructed an immune risk score model to predict the prognosis and development of thyroid cancer. Our research demonstrated a comprehensive panorama of immune infiltration in thyroid cancer, which may provide potential value for immunotherapy.
Targeting XPO1 enhances innate immune response and inhibits KSHV lytic replication during primary infection by nuclear stabilization of the p62 autophagy adaptor protein
Authors: Meng Wen , Gao Shou-Jiang
Published: January 2021

Nucleocytoplasmic transport of signaling modulators is essential for regulating cellular responses to extracellular stimulation and stress, as well as pathogen infection. Exportin 1 (XPO1), also known as chromosomal maintenance 1 (CRM1), mediates nuclear export of proteins, rRNAs, snRNAs, and some mRNAs. In this study, we have identified an essential role of XPO1 in regulating Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic replication during primary infection of primary human umbilical vein endothelial cells. Treatment with an XPO1 inhibitor KPT-8602 and short hairpin RNA (shRNA)-mediated knockdown of XPO1 reduced KSHV lytic replication but had no effect on KSHV entry and trafficking. XPO1 inhibition induced retention of autophagy adaptor protein p62 (SQSTM1) in the nucleus, which enhanced activation of TBK1 and IRF3. As a result, nuclear accumulation of p62 increased expression of innate immune-related genes including IRF7, ISG15, IFIT1, IFIT2, and IFIT3, leading to a reduction of KSHV lytic replication. These results illustrate a novel mechanism by which XPO1 mediates innate immune response and KSHV replication, and identify XPO1 as a potential therapeutic target and KPT-8602 as a promising therapeutic agent for KSHV infection.
STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells
Authors: Pan Shunli , Zhao Xiaoxia , Shao Chen , Fu Bingjie , Huang Yingying , Zhang Ning , Dou Xiaojing , Zhang Zhe , Qiu Yuling , Wang Ran , Jin Meihua , Kong Dexin
Published: January 2021

Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.
Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke
Authors: Yang Jin , Cao Lu-Lu , Wang Xi-Peng , Guo Wei , Guo Ruo-Bing , Sun Yu-Qin , Xue Teng-Fei , Cai Zhen-Yu , Ji Juan , Cheng Hong , Sun Xiu-Lan
Published: January 2021

Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.
Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer
Authors: Long Zhi , Deng Liang , Li Chao , He Qiangrong , He Yao , Hu Xiheng , Cai Yi , Gan Yu
Published: January 2021

The rising of a highly aggressive subtype of castration-resistant prostate cancer (CRPC) named treatment-induced neuroendocrine prostate cancer (t-NEPC) after androgen deprivation therapy (ADT) is well known for its features of the neuroendocrine differentiation (NED) and androgen receptor (AR) independence. However, t-NEPC is still largely unknown. Here, we found that EHF is notably depressed in t-NEPC tumors, patient-derived xenografts, transgenic mice, and cell models. Results from cell lines uncovered that ADT represses EHF expression, which is required for the ADT-induced NED. Mechanism dissection revealed that ADT decreases the EHF transcription via relieving the AR binding to different androgen-responsive elements, which then promotes the expression and enzymatic activity of enhancer of zeste homolog 2 (EZH2), consequently catalyzing tri-methylation lysine 27 of histone H3 for transcriptional repression of its downstream genes to promote the NED. Furthermore, preclinical studies from cell and mice models proved that recovery of EHF expression or using EZH2 inhibitor can attenuate aggressive properties of CRPC cells, hinder the progression of t-NEPC, and promote the response of CPRC cells to enzalutamide. Together, we elucidate that the ADT/AR/EHF/EZH2 signaling is required for the ADT-enhanced NED and plays a critical role in the progression of t-NEPC.
Human primary epidermal organoids enable modeling of dermatophyte infections
Authors: Wang Xuan , Wang Shuyong , Guo Baolin , Su Yuxin , Tan Zuolong , Chang Mingyang , Diao Jinmei , Zhao Yi , Wang Yunfang
Published: January 2021

Technology of generating human epidermal derivatives with physiological relevance to in vivo epidermis is continuously investigated for improving their effects on modeling of human natural dermatological status in basic and clinical studies. Here, we report a method of robust establishment and expansion of human primary epidermal organoids (hPEOs) under a chemically defined condition. hPEOs reconstruct morphological, molecular, and functional features of human epidermis and can expand for 6 weeks. Remarkably, hPEOs are permissive for dermatophyte infections caused by Trichophyton Rubrum (T. rubrum). The T. rubrum infections on hPEOs reflect many aspects of known clinical pathological reactions and reveal that the repression on IL-1 signaling may contribute to chronic and recurrent infections with the slight inflammation caused by T. rubrum in human skin. Thus, our present study provides a new insight into the pathogenesis of T. rubrum infections and indicates that hPEOs are a potential ex vivo model for both basic studies of skin diseases and clinical studies of testing potential antifungal drugs.
SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype
Authors: Bongiovanni Dario , Klug Melissa , Lazareva Olga , Weidlich Simon , Biasi Marina , Ursu Simona , Warth Sarah , Buske Christian , Lukas Marina , Spinner Christoph D. , Scheidt Moritz von , Condorelli Gianluigi , Baumbach Jan , Laugwitz Karl-Ludwig , List Markus , Bernlochner Isabell
Published: January 2021

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients,p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81,p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03,p < 0.0001) and other adhesion molecules involved in platelet activation and platelet–leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.
eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective effects
Authors: Caviedes Ariel , Maturana Barbara , Corvalán Katherina , Engler Alexander , Gordillo Felipe , Varas-Godoy Manuel , Smalla Karl-Heinz , Batiz Luis Federico , Lafourcade Carlos , Kaehne Thilo , Wyneken Ursula
Published: January 2021

Cell death by glutamate excitotoxicity, mediated by N-methyl-d-aspartate (NMDA) receptors, negatively impacts brain function, including but not limited to hippocampal neurons. The NF-κB transcription factor (composed mainly of p65/p50 subunits) contributes to neuronal death in excitotoxicity, while its inhibition should improve cell survival. Using the biotin switch method, subcellular fractionation, immunofluorescence, and luciferase reporter assays, we found that NMDA-stimulated NF-κB activity selectively in hippocampal neurons, while endothelial nitric oxide synthase (eNOS), an enzyme expressed in neurons, is involved in the S-nitrosylation of p65 and consequent NF-κB inhibition in cerebrocortical, i.e., resistant neurons. The S-nitro proteomes of cortical and hippocampal neurons revealed that different biological processes are regulated by S-nitrosylation in susceptible and resistant neurons, bringing to light that protein S-nitrosylation is a ubiquitous post-translational modification, able to influence a variety of biological processes including the homeostatic inhibition of the NF-κB transcriptional activity in cortical neurons exposed to NMDA receptor overstimulation.
KDM6B is an androgen regulated gene and plays oncogenic roles by demethylating H3K27me3 at cyclin D1 promoter in prostate cancer
Authors: Cao Zhi , Shi Xiaolei , Tian Feng , Fang Yu , Wu Jason Boyang , Mrdenovic Stefan , Nian Xinwen , Ji Jin , Xu Huan , Kong Chen , Xu Yalong , Chen Xi , Huang Yuhua , Wei Xuedong , Yu Yongwei , Yang Bo , Chung Leland W. K. , Wang Fubo
Published: January 2021

Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, plays oncogenic or antitumoral roles in malignant tumors depending on the type of tumor cell. However, how this histone modifier affects the progression of prostate cancer (PCa) is still unknown. Here we analyzed sequenced gene expression data and tissue microarray to explore the expression features and prognostic value of KDM6B in PCa. Further, we performed in vitro cell biological experiments and in vivo nude mouse models to reveal the biological function, upstream and downstream regulation mechanism of KDM6B. In addition, we investigated the effects of a KDM6B inhibitor, GSK-J4, on PCa cells. We showed that KDM6B overexpression was observed in PCa, and elevated KDM6B expression was associated with high Gleason Score, low serum prostate-specific antigen level and shorted recurrence-free survival. Moreover, KDM6B prompted proliferation, migration, invasion and cell cycle progression and suppressed apoptosis in PCa cells. GSK-J4 administration could significantly suppress the biological function of KDM6B in PCa cells. KDM6B is involved in the development of castration-resistant prostate cancer (CRPC), and combination of MDV3100 plus GSK-J4 is effective for CRPC and MDV3100-resistant CRPC. Mechanism exploration revealed that androgen receptor can decrease the transcription of KDM6B and that KDM6B demethylates H3K27me3 at the cyclin D1 promoter and cooperates with smad2/3 to prompt the expression of cyclin D1. In conclusion, our study demonstrates that KDM6B is an androgen receptor regulated gene and plays oncogenic roles by promoting cyclin D1 transcription in PCa and GSK-J4 has the potential to be a promising agent for the treatment of PCa.
Global optical coherence tomography measures for detecting the progression of glaucoma have fundamental flaws
Authors: Sun Ashley , Tsamis Emmanouil , Eguia Melvi D. , Liebmann Jeffrey M. , Blumberg Dana M. , Al-Aswad Lama A. , Cioffi George A. , Gustavo De Moraes C. , Hood Donald C.
Published: January 2021

Objective

To understand the problems involved in using global OCT measures for detecting progression in early glaucoma.

Subjects/Methods

Eyes from 76 patients and 28 healthy controls (HC) had a least two OCT scans at least 1 year apart. To determine the 95% confidence intervals (CI), 151 eyes (49 HC and 102 patients) had at least two scans within 6 months. All eyes had 24-2 mean deviation ≥-6dB. The average (global) thicknesses of the circumpapillary retinal nerve fibre layer (cRNFL), GONH, and of the retinal ganglion cell layer plus inner plexiform layer (RGCLP), Gmac, were calculated. Using quantile regression, the 95% CI intervals were determined. Eyes outside the CIs were classified as “progressors.” For a reference standard (RS), four experts evaluated OCT and VF information.

Results

Compared to the RS, 31 of the 76 (40.8%) patient eyes were identified as progressors (RS-P), and 45 patient, and all 28 HC, eyes as nonprogressors (RS-NP). The metrics missed (false negative, FN) 15 (48%) (GONH) and 9 (29%) (Gmac) of the 31 RS-P. Further, GONH and/or Gmac falsely identified (false positive, FP) 10 (22.2%) of 45 patient RS-NP eyes and 7 (25%) of the 28 HC eyes as progressing. Post-hoc analysis identified three reasons (segmentation, centring, and local damage) for these errors.

Conclusions

Global metrics lead to FPs and FNs because of problems inherent in OCT scanning (segmentation and centring), and to FNs because they can miss local damage. These problems are difficult, if not impossible, to correct, and raise concerns about the advisability of using GONH and Gmac for detecting progression.
Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts
Authors:   PDXNET Consortium, Woo Xing Yi ,   EurOPDX Consortium, Giordano Jessica , Srivastava Anuj , Zhao Zi-Ming , Lloyd Michael W. , de Bruijn Roebi , Suh Yun-Suhk , Patidar Rajesh , Chen Li , Scherer Sandra , Bailey Matthew H. , Yang Chieh-Hsiang , Cortes-Sanchez Emilio , Xi Yuanxin , Wang Jing , Wickramasinghe Jayamanna , Kossenkov Andrew V. , Rebecca Vito W. , Sun Hua , Mashl R. Jay , Davies Sherri R. , Jeon Ryan , Frech Christian , Randjelovic Jelena , Rosains Jacqueline , Galimi Francesco , Bertotti Andrea , Lafferty Adam , O’Farrell Alice C. , Modave Elodie , Lambrechts Diether , ter Brugge Petra , Serra Violeta , Marangoni Elisabetta , El Botty Rania , Kim Hyunsoo , Kim Jong-Il , Yang Han-Kwang , Lee Charles , Dean Dennis A. , Davis-Dusenbery Brandi , Evrard Yvonne A. , Doroshow James H. , Welm Alana L. , Welm Bryan E. , Lewis Michael T. , Fang Bingliang , Roth Jack A. , Meric-Bernstam Funda , Herlyn Meenhard , Davies Michael A. , Ding Li , Li Shunqiang , Govindan Ramaswamy , Isella Claudio , Moscow Jeffrey A. , Trusolino Livio , Byrne Annette T. , Jonkers Jos , Bult Carol J. , Medico Enzo , Chuang Jeffrey H.
Published: January 2021

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.
Local sea level trends, accelerations and uncertainties over 1993–2019
Authors: Prandi Pierre , Meyssignac Benoit , Ablain Michaël , Spada Giorgio , Ribes Aurélien , Benveniste Jérôme
Published: January 2021

Satellite altimetry missions provide a quasi-global synoptic view of sea level variations over more than 25 years and provide regional sea level (SL) indicators such as trends and accelerations. Estimating realistic uncertainties on these quantities is crucial to address current climate science questions. While uncertainty estimates are available for the global mean sea level (GMSL), information is not available at local scales so far. We estimate a local satellite altimetry error budget and use it to derive local error variance-covariance matrices, and estimate confidence intervals on trends and accelerations at the 90% confidence level. Over 1993–2019, we find that the average local sea level trend uncertainty is 0.83 mm.yr−1 with values ranging from 0.78 to 1.22 mm.yr−1. For accelerations, uncertainties range from 0.057 to 0.12 mm.yr−1, with a mean value of 0.062. We also perform a sensitivity study to investigate a range of plausible error budgets. Local error levels, error variance-covariance matrices, SL trends and accelerations, along with corresponding uncertainties are provided.
Plasma Hsp90 levels in patients with systemic sclerosis and relation to lung and skin involvement: a cross-sectional and longitudinal study
Authors: Štorkánová Hana , Oreská Sabína , Špiritović Maja , Heřmánková Barbora , Bubová Kristýna , Komarc Martin , Pavelka Karel , Vencovský Jiří , Distler Jörg H. W. , Šenolt Ladislav , Bečvář Radim , Tomčík Michal
Published: January 2021

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.
Mapping leaf metal content over industrial brownfields using airborne hyperspectral imaging and optimized vegetation indices
Authors: Lassalle Guillaume , Fabre Sophie , Credoz Anthony , Hédacq Rémy , Dubucq Dominique , Elger Arnaud
Published: January 2021

Monitoring plant metal uptake is essential for assessing the ecological risks of contaminated sites. While traditional techniques used to achieve this are destructive, Visible Near-Infrared (VNIR) reflectance spectroscopy represents a good alternative to monitor pollution remotely. Based on previous work, this study proposes a methodology for mapping the content of several metals in leaves (Cr, Cu, Ni and Zn) under realistic field conditions and from airborne imaging. For this purpose, the reflectance of Rubus fruticosus L., a pioneer species of industrial brownfields, was linked to leaf metal contents using optimized normalized vegetation indices. High correlations were found between the vegetation indices exploiting pigment-related wavelengths and leaf metal contents (r ≤ − 0.76 for Cr, Cu and Ni, and r ≥ 0.87 for Zn). This allowed predicting the metal contents with good accuracy in the field and on the image, especially Cu and Zn (r ≥ 0.84 and RPD ≥ 2.06). The same indices were applied over the entire study site to map the metal contents at very high spatial resolution. This study demonstrates the potential of remote sensing for assessing metal uptake by plants, opening perspectives of application in risk assessment and phytoextraction monitoring in the context of trace metal pollution.
Author Correction: A small Cretaceous crocodyliform in a dinosaur nesting ground and the origin of sebecids
Authors: Sellés Albert G. , Blanco Alejandro , Vila Bernat , Marmi Josep , López-Soriano Francisco J. , Llácer Sergio , Frigola Jaime , Canals Miquel , Galobart Àngel
Published: January 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Connections of climate change and variability to large and extreme forest fires in southeast Australia
Authors: Abram Nerilie J. , Henley Benjamin J. , Sen Gupta Alex , Lippmann Tanya J. R. , Clarke Hamish , Dowdy Andrew J. , Sharples Jason J. , Nolan Rachael H. , Zhang Tianran , Wooster Martin J. , Wurtzel Jennifer B. , Meissner Katrin J. , Pitman Andrew J. , Ukkola Anna M. , Murphy Brett P. , Tapper Nigel J. , Boer Matthias M.
Published: January 2021

The 2019/20 Black Summer bushfire disaster in southeast Australia was unprecedented: the extensive area of forest burnt, the radiative power of the fires, and the extraordinary number of fires that developed into extreme pyroconvective events were all unmatched in the historical record. Australia’s hottest and driest year on record, 2019, was characterised by exceptionally dry fuel loads that primed the landscape to burn when exposed to dangerous fire weather and ignition. The combination of climate variability and long-term climate trends generated the climate extremes experienced in 2019, and the compounding effects of two or more modes of climate variability in their fire-promoting phases (as occurred in 2019) has historically increased the chances of large forest fires occurring in southeast Australia. Palaeoclimate evidence also demonstrates that fire-promoting phases of tropical Pacific and Indian ocean variability are now unusually frequent compared with natural variability in pre-industrial times. Indicators of forest fire danger in southeast Australia have already emerged outside of the range of historical experience, suggesting that projections made more than a decade ago that increases in climate-driven fire risk would be detectable by 2020, have indeed eventuated. The multiple climate change contributors to fire risk in southeast Australia, as well as the observed non-linear escalation of fire extent and intensity, raise the likelihood that fire events may continue to rapidly intensify in the future. Improving local and national adaptation measures while also pursuing ambitious global climate change mitigation efforts would provide the best strategy for limiting further increases in fire risk in southeast Australia.
Entropy-driven amplification strategy-assisted lateral flow assay biosensor for ultrasensitive and convenient detection of nucleic acids
Authors: Li Shasha , Meng Hong-Min , Zong Hong , Chen Juan , Li Jianjun , Zhang Lin , Li Zhaohui
Published: January 2021

An entropy-driven amplification strategy assisted portable lateral flow assay biosensor was developed for highly sensitive and selective detection of nucleic acids, providing a POCT platform for early diseases diagnosis.
Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
Authors: Pranantyo Dicky , Kang En-Tang , Chan-Park Mary B.
Published: January 2021

Electrostatic nanomicelles remain stable and biocompatible under physiological conditions, but readily burst and spill out cationic antimicrobial peptide to kill bacteria at infection sites.
On-demand responsive nanoplatform mediated targeting of CAFs and down-regulating mtROS-PYK2 signaling for antitumor metastasis
Authors: Zuo Tiantian , Zhang Jun , Yang Jie , Xu Rui , Hu Zongwei , Wang Zhihua , Deng Huizi , Shen Qi
Published: January 2021

The combination therapy of both different mechanisms and drugs such as TPP-RSV prodrug and PFD co-inhibit tumor growth and metastasis via targeting the mtROS-PYK2 pathway and CAFs.
Enhancement of photocurrent by incorporation of Preyssler type polyoxometalate protected nanoparticles in polyporphyrin films
Authors: Huo Zhaohui , Liang Yiming , Lv Yaokang , Melin Frédéric , Hellwig Petra , Ibrahim Helen , Goldmann Michel , Boudon Corinne , Badets Vasilica , Bonnefont Antoine , Ruhlmann Laurent
Published: January 2021

The introduction of polyoxometalate type Preyssler nanoparticles at the surface of cationic bis-porphyrin copolymer induces great enhancement of the photocurrent generation.
A versatile sea anemone-inspired strategy toward 2D hybrid porous carbons from functional molecular brushes
Authors: Lin Xidong , Wang Zelin , Liu Ruliang , Liu Shaohong , Leng Kunyi , Lou He , Du Yang , Zheng Bingna , Fu Ruowen , Wu Dingcai
Published: January 2021

A versatile sea anemone-inspired functional molecular brush is utilized to fabricate 2D hybrid porous carbon.
Recent discoveries in the reaction mechanism of heterogeneous electrocatalytic nitrate reduction
Authors: Wang Zixuan , Richards Danielle , Singh Nirala
Published: January 2021

We review advances in the electrocatalytic nitrate reduction mechanism and evaluate future efforts. Existing work could be supplemented by controlling reaction conditions and quantifying active sites to determine activity on a per-site basis.
MOF-derived PtCo/Co3O4 nanocomposites in carbonaceous matrices as high-performance ORR electrocatalysts synthesized via laser ablation techniques
Authors: Ribeiro Erick L. , Davis Elijah M. , Mokhtarnejad Mahshid , Hu Sheng , Mukherjee Dibyendu , Khomami Bamin
Published: January 2021

ZIF-67-derived carbon-based bimetallic nanocomposites with reduced Pt-loading via laser ablation synthesis in solution (LASiS) as a superior electrocatalyst for oxygen reduction reaction (ORR).
A series of Rb4Ln2(P2S6)(PS4)2 (Ln = La, Ce, Pr, Nd, Sm, Gd) rare earth thiophosphates with two distinct thiophosphate units [PVS4]3− and [PIV2S6]4−
Authors: Kutahyali Aslani Ceren , Breton Logan S. , Klepov Vladislav V. , zur Loye Hans-Conrad
Published: January 2021

A new series of rare earth thiophosphates, Rb4Ln2(P2S6)(PS4)2 (Ln = La, Ce, Pr, Nd, Sm, Gd), containing two unique thiophosphate motifs, [PVS4]3− and [PIV2S6]4−, were synthesized using the high temperature molten flux crystal growth method by RbBr flux.
A uniformly decorated and photostable polydopamine–organic semiconductor to boost the photoelectrochemical water splitting performance of CdS photoanodes
Authors: Ruan Mengnan , Guo Dandan , Jia Qixiang
Published: January 2021

Photoelectrochemical (PEC) water splitting to produce renewable H2 fuel by storage of solar energy has attracted increasing attention as it could reduce carbon footprint and solve the global consumption growth.
Biomass-based materials for green lithium secondary batteries
Authors: Jin Chengbin , Nai Jianwei , Sheng Ouwei , Yuan Huadong , Zhang Wenkui , Tao Xinyong , Lou Xiong Wen (David)
Published: January 2021

This review summarizes the employment of different biomass materials for green lithium secondary batteries.
Monitoring of pesticides in drinking water: finding the right balance between under- and over-monitoring – experience from the Czech Republic
Authors: Kotal Filip , Kožíšek František , Jeligová Hana , Vavrouš Adam , Mayerová Lenka , Gari Daniel W. , Moulisová Alena
Published: January 2021

The modern, risk-based approach requires that only those pollutants which are likely to be present in a given water supply should be monitored in drinking water.
Hydrogeochemical characterization of a possible carbon sink from shallow saline–alkaline groundwater in the eastern Hetao Basin of Inner Mongolia in China
Authors: Yu Junxia , Jiao Yan , Yang Wenzhu , Yang Jie , Liu Lijia
Published: January 2021

The role of saline–alkaline groundwater as a CO2sink was studied in the Hetao Basin, Inner Mongolia. DIC positively correlated with pH and exhibited a downward migration trend. High pH and high DIC groundwater could provide strong carbon sink potential.
Ammonia synthesis using Fe/BZY–RuO2 catalysts and a caesium dihydrogen phosphate-based electrolyte at intermediate temperatures
Authors: Yuan Yao , Tada Shohei , Kikuchi Ryuji
Published: January 2021

We developed an Fe2O3/BZY (yttrium-doped barium zirconate)–RuO2 (Fe/BZY–RuO2) cathode catalyst, which was applied to the electrochemical synthesis of NH3 using a proton-conducting electrolyte, CsH2PO4/SiP2O7, at 220 °C and ambient pressure.
A highly efficient solution and solid state ESIPT fluorophore and its OLED application
Authors: Trannoy Virgile , Léaustic Anne , Gadan Sophie , Guillot Régis , Allain Clémence , Clavier Gilles , Mazerat Sandra , Geffroy Bernard , Yu Pei
Published: January 2021

Readily accessible and functionalized ESIPT dyes with high fluorescence quantum yield in solution, including water, and in crystalline state are presented.
Computational screening of pristine and functionalized ordered TiVC MXenes as highly efficient anode materials for lithium-ion batteries
Authors: Li Yameng , Li Lei , Huang Rao , Zhang Yang , Wen Yuhua
Published: January 2021

We investigated the electrochemical performance of pristine and functionalized ordered TiVC monolayers as highly efficient anode materials for lithium-ion batteries.
Boosting the cycling stability of Ni-rich layered oxide cathode by dry coating of ultrastable Li3V2(PO4)3 nanoparticles
Authors: Wang Dongdong , Yan Qizhang , Li Mingqian , Gao Hongpeng , Tian Jianhua , Shan Zhongqiang , Wang Ning , Luo Jian , Zhou Meng , Chen Zheng
Published: January 2021

Dry coating of ultrastable Li3V2(PO4)3-carbon (LVP-C) nanoparticles on LiNi0.6Co0.2Mn0.2O2 (NCM622) leads to a robust composite cathode with improved rate capability and cycling life without sacrificing the specific energy density compared with pristine NCM622.
Synthesis and conformational analysis of vicinally branched trisaccharide β-d-Galf-(1 → 2)-[β-d-Galf-(1 → 3)-]-α-Galp from Cryptococcus neoformans galactoxylomannan
Authors: Dorokhova Vera S. , Gerbst Alexey G. , Komarova Bozhena S. , Previato José O. , Previato Lúcia Mendonça , Dmitrenok Andrey S. , Shashkov Alexander S. , Krylov Vadim B. , Nifantiev Nikolay E.
Published: January 2021

Two disaccharides and one trisaccharide related to the galactoxylomannan (GalXMan) of Cryptococcus neoformans were synthesized for the first time. Their conformational behavior was studied using computer calculations along with NMR analysis.
A microwave-assisted copper-mediated tandem approach for fused quinazoline derivatives
Authors: Malasala Satyaveni , Polomoni Anusha , Chelli Sai Manohar , Kar Swayamsidda , Madhavi Y. V. , Nanduri Srinivas
Published: January 2021

A method for the microwave-assisted copper-mediated oxidative coupling reaction of different aldehydes and quinazolines/benzimidazoles has been developed for the synthesis of fused-polycyclic systems via new C–N bond formation.
Synthesis of biological based hennotannic acid-based salts over porous bismuth coordination polymer with phosphorous acid tags
Authors: Babaee Saeed , Zarei Mahmoud , Zolfigol Mohammad Ali , Khazalpour Sadegh , Hasani Masoumeh , Rinner Uwe , Schirhagl Romana , Norouzi Neda , Rostamnia Sadegh
Published: January 2021

In this paper, a novel porous polymer capable of coordinating to bismuth (PCPs-Bi) was synthesized.
Low temperature scintillation performance of a Br-doped CH3NH3PbCl3 single-crystalline perovskite
Authors: Liu Jun , Hei Dongwei , Xu Qiang , Tan Xinjian , Ruan Jinlu , Ouyang Xiaoping , Nie Jing , Wei Kun , Xu Qing , Sun Bin
Published: January 2021

Time response and light yield are two of the most important features of a scintillation detector, and are mostly determined by the luminescence properties of the scintillator.
LiYF4-nanocrystal-embedded glass ceramics for upconversion: glass crystallization, optical thermometry and spectral conversion
Authors: Li Xinyue , Qiu Liting , Chen Youli , Zhu Yiwen , Yu Hua , Zhong Jiasong , Yang Tao , Mao Qinan
Published: January 2021

LiYF4NCs embedded GCs were fabricatedviamelt-quenching method and subsequent glass crystallization. It is evidenced that it is favorable of UC, which is promising in optical thermometry and spectral conversion.
Thiol-yne click reaction: an interesting way to derive thiol-provided catechols
Authors: Nador Fabiana , Mancebo-Aracil Juan , Zanotto Duham , Ruiz-Molina Daniel , Radivoy Gabriel
Published: January 2021

An attractive approach to the synthesis of catechol derivates through thiol-yne click reaction is presented. Compounds obtained were used in the preparation of CNPs.
The combination of Al2O3 and BN for enhancing the thermal conductivity of PA12 composites prepared by selective laser sintering
Authors: Yuan Yue , Wu Wei , Hu Huanbo , Liu Dongmei , Shen Hui , Wang Zhengyi
Published: January 2021

The introduction of hybrid fillers in SLS technology is an effective method for the manufacture of thermally conductive polymer composites with high thermal conductivity, complex structures and good mechanical properties.
Oligo(amylene) from the reaction of fusel oil with zinc dihalide
Authors: Davis Matthew C. , Prokai Laszlo , Woodroffe Josanne Dee
Published: January 2021

Fusel oil was converted into the liquid hydrocarbon oligo(amylene) by zinc bromide catalysis.
New atomically precise M1Ag21 (M = Au/Ag) nanoclusters as excellent oxygen reduction reaction catalysts
Authors: Zou Xuejuan , He Shuping , Kang Xi , Chen Shuang , Yu Haizhu , Jin Shan , Astruc Didier , Zhu Manzhou
Published: January 2021

The presence of 1,1′-bis-(diphenylphosphino)ferrocene ligands and ensemble effects in novel nanoclusters M1Ag21(dppf)3(SAdm)12 (M = Au/Ag) provide excellent ORR performances.
Fabrication of hydrophobic NiFe2O4@poly(DVB–LMA) sponge via a Pickering emulsion template method for oil/water separation
Authors: Zhao Caimei , Chen Lei , Yu Chuanming , Hu Binghua , Huang Haoxuan , Chen Yongjie , Wang Xin , Ye Yongshi , Zhuang Xiaohui , Li Yong
Published: January 2021

Super-hydrophobic porous absorbents are convenient, low-cost, efficient and environment-friendly materials in the treatment of oil spills.
Generation and stability of cement soap films
Authors: Ahmed Abdourahman Djilani , Geniere Arthur , Auriol Mélodie , Dalas Florent , Biance Anne-Laure , Le Merrer Marie
Published: January 2021

By withdrawing a frame from a fresh cement suspension at controlled velocity, we find an optimum solid fraction to achieve both generation and stability of the cement soap films.
Abnormal fast dehydration and rehydration of light- and thermo-dual-responsive copolymer films triggered by UV radiation
Authors: Zhang Xuan , Kreuzer Lucas P. , Schwaiger Dominik M. , Lu Min , Mao Zhengwei , Cubitt Robert , Müller-Buschbaum Peter , Zhong Qi
Published: January 2021

Abnormal fast dehydration and rehydration of light- and thermo-dual-responsive copolymer films of poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-(4-phenylazophenoxy)hexyl acrylate), abbreviated as P(OEGMA300-co-PAHA), are triggered by UV radiation.
Smart membranes by electron beam cross-linking of copolymer microgels
Authors: Bookhold Johannes , Dirksen Maxim , Wiehemeier Lars , Knust Sebastian , Anselmetti Dario , Paneff Florian , Zhang Xianghui , Gölzhäuser Armin , Kottke Tilman , Hellweg Thomas
Published: January 2021

Poly(N-isopropylacrylamide) (pNIPAM) based copolymer microgels with aromatic comonomers were cross-linked to create free-standing, transferable, thermoresponsive membranes. Such membranes can be used to control ion flux in electrochemical cells.
Multicore closely packed ultrathin-MnO2@N-doped carbon-gear yolk–shell micro-nanostructures as highly efficient sulfur hosts for Li–S batteries
Authors: Yan Weixi , Chen Shipei , Wen Ming , Wu Qingsheng , Yu Shuhong
Published: January 2021

A novel clustered MnO2–S@NCG micro-nanostructure was successfully constructed, and exhibits superior electrochemical activity and cycling stability, promising as candidate to high-performance Li–S batteries.
Separated redox site strategies for engineering highly efficient photocatalysts: a pagoda-like In2O3/CuO heteroepitaxial structure coated with a N-doped C layer
Authors: Yang Yun , Sun Liming , Zhan Wenwen , Wang Xiaojun , Han Xiguang
Published: January 2021

Novel In2O3/CuO@N-C micro-rods with effective separation of redox sites have been synthesized and they exhibited excellent photocatalytic activity for the CDC reaction.
High-performance composite membrane based on synergistic main-chain/side-chain proton conduction channels for the vanadium redox flow battery
Authors: Qian Penghua , Wang Haixia , Jiang Yunhu , Zhou Yong , Shi Haifeng
Published: January 2021

Synergistic proton conduction channels of side-chain SPPTA and main-chain SPEEK implement a trade-off between conductivity and permeability, and the hydrophilic/hydrophobic phase separation structure exhibits excellent VRFB performance.