bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis
Authors: Liu Gao , Sun Jian , Yang Zhang-Fu , Zhou Cheng , Zhou Pei-Yun , Guan Ruo-Yu , Sun Bao-Ye , Wang Zhu-Tao , Zhou Jian , Fan Jia , Qiu Shuang-Jian , Yi Yong
Published: March 2021

Cancer-associated fibroblasts (CAFs) are commonly acquired activated extracellular matrix (ECM)-producing myofibroblasts, a phenotypes with multiple roles in hepatic fibrogenesis and carcinogenesis via crosstalk with cohabitating stromal/cancer cells. Here, we discovered a mechanism whereby CAF-derived cytokines enhance hepatocellular carcinoma (HCC) progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells. CAFs secreted significantly higher levels of CXCL11 than normal fibroblasts (NFs), and CXCL11 also had comparatively higher expressions in HCC tissues, particularly in metastatic tissues, than para-carcinoma tissues. Both CAF-derived and experimentally introduced CXCL11 promoted HCC cell migration. Likewise, CAFs promoted tumor migration in orthotopic models, as shown by an increased number of tumor nodules, whereas CXCL11 silencing triggered a decrease of it. CXCL11 stimulation upregulated circUBAP2 expression, which was significantly higher in HCC tissues than para-carcinoma tissues. Silencing circUBAP2 reversed the effects of CXCL11 on the expression of IL-1β/IL-17 and HCC cell migration. Further downstream, the IFIT1 and IFIT3 levels were significantly upregulated in HCC cells upon CXCL11 stimulation, but downregulated upon circUBAP2 silencing. IFIT1 or IFIT3 silencing reduced the expression of IL-17 and IL-1β, and attenuated the migration capability of HCC cells. Herein, circUBAP2 counteracted miR-4756-mediated inhibition on IFIT1/3 via sponging miR-4756. miR-4756 inhibition reversed the effects induced by circUBAP2 silencing on the IL-17 and IL-1β levels and HCC cell migration. In orthotopic models, miR-4756 inhibition also reversed the effects on metastatic progression induced by silencing circUBAP2.
The ubiquitin ligase Peli1 inhibits ICOS and thereby Tfh-mediated immunity
Authors: Huang Xinfang , Hao Shumeng , Liu Junli , Huang Yuanyuan , Liu Manman , Xiao Chunyuan , Wang Yan , Pei Siyu , Yu Tao , Xu Jing , Wang Haikun , Dai Dongfang , Su Xiao , Xiao Yichuan
Published: March 2021

T follicular helper (Tfh) cells are crucial for regulating autoimmune inflammation and protective immunity against viral infection. However, the molecular mechanism controlling Tfh cell differentiation is poorly understood. Here, through two mixed bone marrow chimeric experiments, we identified Peli1, a T cell-enriched E3 ubiquitin ligase, as an intrinsic regulator that inhibits Tfh cell differentiation. Peli1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator (ICOS) expression, and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4+ T cells. Mechanistically, increased ICOS expression on Peli1-KO CD4+ T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2, a transcription factor that inhibits Tfh differentiation. Therefore, reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO cells. As a consequence, Peli1-deficient CD4+ T cells promoted lupus-like autoimmunity but protected against H1N1 influenza virus infection in mouse models. Collectively, our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfh-related autoimmunity or infectious diseases.
Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency
Authors: Runolfsdottir Hrafnhildur L. , Sayer John A. , Indridason Olafur S. , Edvardsson Vidar O. , Jensson Brynjar O. , Arnadottir Gudny A. , Gudjonsson Sigurjon A. , Fridriksdottir Run , Katrinardottir Hildigunnur , Gudbjartsson Daniel , Thorsteinsdottir Unnur , Sulem Patrick , Stefansson Kari , Palsson Runolfur
Published: March 2021

Adenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses may play a role. We assessed the prevalence of APRT deficiency based on the frequency of causally-related APRT sequence variants in a diverse set of large genomic databases. A thorough search was carried out for all APRT variants that have been confirmed as pathogenic under recessive mode of inheritance, and the frequency of the identified variants examined in six population genomic databases: the deCODE genetics database, the UK Biobank, the 100,000 Genomes Project, the Genome Aggregation Database, the Human Genetic Variation Database and the Korean Variant Archive. The estimated frequency of homozygous genotypes was calculated using the Hardy-Weinberg equation. Sixty-two pathogenic APRT variants were identified, including six novel variants. Most common were the missense variants c.407T>C (p.(Met136Thr)) in Japan and c.194A>T (p.(Asp65Val)) in Iceland, as well as the splice-site variant c.400 + 2dup (p.(Ala108Glufs*3)) in the European population. Twenty-nine variants were detected in at least one of the six genomic databases. The highest cumulative minor allele frequency (cMAF) of pathogenic variants outside of Japan and Iceland was observed in the Irish population (0.2%), though no APRT deficiency cases have been reported in Ireland. The large number of cases in Japan and Iceland is consistent with a founder effect in these populations. There is no evidence for widespread underdiagnosis based on the current analysis.
A source of isotopically light organic carbon in a low-pH anoxic marine zone
Authors: Vargas Cristian A. , Cantarero Sebastian I. , Sepúlveda Julio , Galán Alexander , De Pol-Holz Ricardo , Walker Brett , Schneider Wolfgang , Farías Laura , D’Ottone Marcela Cornejo , Walker Jennifer , Xu Xiaomei , Salisbury Joe
Published: March 2021

Geochemical and stable isotope measurements in the anoxic marine zone (AMZ) off northern Chile during periods of contrasting oceanographic conditions indicate that microbial processes mediating sulfur and nitrogen cycling exert a significant control on the carbonate chemistry (pH, AT, DIC and pCO2) of this region. Here we show that in 2015, a large isotopic fractionation between DIC and POC, a DIC and N deficit in AMZ waters indicate the predominance of in situ dark carbon fixation by sulfur-driven autotrophic denitrification in addition to anammox. In 2018, however, the fractionation between DIC and POC was significantly lower, while the total alkalinity increased in the low-pH AMZ core, suggesting a predominance of heterotrophic processes. An isotope mass-balance model demonstrates that variations in the rates of sulfur- and nitrogen-mediated carbon fixation in AMZ waters contribute ~7–35% of the POC exported to deeper waters. Thus, dark carbon fixation should be included in assessments of future changes in carbon cycling and carbonate chemistry due to AMZ expansion.
Polymerase-guided base editing enables in vivo mutagenesis and rapid protein engineering
Authors: Cravens Aaron , Jamil Osman K. , Kong Deze , Sockolosky Jonathan T. , Smolke Christina D.
Published: March 2021

Random mutagenesis is a technique used to generate diversity and engineer biological systems. In vivo random mutagenesis generates diversity directly in a host organism, enabling applications such as lineage tracing, continuous evolution, and protein engineering. Here we describe TRIDENT (TaRgeted In vivo Diversification ENabled by T7 RNAP), a platform for targeted, continual, and inducible diversification at genes of interest at mutation rates one-million fold higher than natural genomic error rates. TRIDENT targets mutagenic enzymes to precise genetic loci by fusion to T7 RNA polymerase, resulting in mutation windows following a mutation targeting T7 promoter. Mutational diversity is tuned by DNA repair factors localized to sites of deaminase-driven mutation, enabling sustained mutation of all four DNA nucleotides at rates greater than 10−4 mutations per bp. We show TRIDENT can be applied to routine in vivo mutagenesis applications by evolving a red-shifted fluorescent protein and drug-resistant mutants of an essential enzyme.
N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA
Authors: Qiu Weinan , Zhang Qingyang , Zhang Rui , Lu Yangxu , Wang Xin , Tian Huabin , Yang Ying , Gu Zijuan , Gao Yanan , Yang Xin , Cui Guanshen , Sun Baofa , Peng Yanan , Deng Hongyu , Peng Hua , Yang Angang , Yang Yun-Gui , Yang Pengyuan
Published: March 2021

Double-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by theN6-methyladenosine (m6A) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the m6A methyltransferase METTL3 translocates into the cytoplasm to increase m6A modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated m6A RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.
Quantum spin liquid and cluster Mott insulator phases in the Mo3O8 magnets
Authors: Nikolaev S. A. , Solovyev I. V. , Streltsov S. V.
Published: March 2021

We unveil the microscopic origin of largely debated magnetism in the Mo3O8 quantum systems. Upon considering an extended Hubbard model at 1/6 filling on the anisotropic kagomé lattice formed by the Mo atoms, we argue that its ground state is determined by the competition between kinetic energy and intersite Coulomb interactions, which is controlled by the trimerisation of the kagomé lattice into the Mo3O13 clusters, and the sign of hopping parameters, specifying the electron localisation at such clusters. Based on first-principles calculations, we show that the strong interaction limit reveals a plaquette charge order with unpaired spins at the resonating hexagons that can be realised in LiZn2Mo3O8, and whose origin is solely related to the opposite signs of intracluster and intercluster hoppings, in contrast to all previous scenarios. On the other hand, both Li2InMo3O8 and Li2ScMo3O8 are demonstrated to fall into the weak interaction limit where the electrons are well localised at the Mo3O13 clusters. While the former is found to exhibit long-range antiferromagnetic order, the latter is more likely to reveal short-range order with quantum spin liquid-like excitations. Our results not only reproduce most of the experimentally observed features of the Mo3O8 systems, but will also help to describe various properties in other quantum cluster magnets.
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors
Authors: Izumi Motohiro , Oyanagi Jun , Sawa Kenji , Fukui Mitsuru , Ogawa Koichi , Matsumoto Yoshiya , Tani Yoko , Suzumura Tomohiro , Watanabe Tetsuya , Kaneda Hiroyasu , Mitsuoka Shigeki , Asai Kazuhisa , Ohsawa Masahiko , Yamamoto Nobuyuki , Koh Yasuhiro , Kawaguchi Tomoya
Published: March 2021

Multiple primary lung cancers (MPLCs) harbour various genetic profiles among the tumours, even from individuals with same non-intrinsic risk factors. Paired mutational analyses were performed to obtain a census of mutational events in MPLC and assess their relationship with non-intrinsic risk factors. Thirty-eight surgical specimens from 17 patients diagnosed as MPLC were used. Extracted DNAs were sequenced for somatic mutations in 409 cancer-associated genes from a comprehensive cancer panel. We statistically analysed the correlation between each driver mutation frequency and non-intrinsic risk factors using Fisher's exact test, and whether genetic mutations occurred concomitantly or randomly in MPLC using an exact test. Comprehensive genetic analyses suggested different mutation profiles in tumours within the same individuals, with some exceptions. EGFR, KRAS, TP53, or PARP1 mutations were concomitantly detected in some MPLC cases. EGFR mutations were significantly more frequent in never or light smokers and females. Concomitant EGFR or KRAS mutations in MPLCs were significantly more frequent than expected by chance (P = .0023 and .0049, respectively) suggesting a more prominent role of non-intrinsic risk factors in EGFR and KRAS mutations than other mutations, which occurred more randomly. Concomitant EGFR or KRAS mutations were particularly prominent in never or light smokers and males.
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance
Authors: Alenazy Maha Fahad , Saheb Sharif-Askari Fatemeh , Omair Mohammed A. , El-Wetidy Mohammad S. , Omair Maha A. , Mitwalli Hussam , Al-Muhsen Saleh , Al-Masri Abeer , Hamid Qutayba , Halwani Rabih
Published: March 2021

Abatacept, an inhibitor of CD28 mediated T-cell activation, has been shown to be effective in controlling inflammation during rheumatoid arthritis (RA). However, its effects on immune regulatory B and T cells (Bregs and Tregs) has not been fully explored. Thirty-one RA patients treated with abatacept for ≥ 6 months along with 31 RA patients treated with other modalities as well as 30 healthy controls were recruited. Of these 62 RA patient, 49 (79%) were females with a mean age of 54 ± 12 years and disease duration of 10 ± 6 years. The blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and Luminex Multiplex assay. Treatment with abatacept significantly enhanced the blood level of IL-35+ IL-10+ Bregs (P = 0.0007). Their levels were higher in the blood of remitted patients (DAS28-CRP < 2.6) compared to the unremitted ones (P = 0.0173), 6 months following abatacept treatment initiation. Moreover, abatacept treatment significantly enhanced the blood levels of LAG3+ conventional and unconventional Tregs of RA patients. This increase in the blood levels of Bregs and Tregs was accompanied with an elevated serum level of IL-35 and IFN-β in abatacept-treated patients. Therefore, Abatacept efficiency to achieve remittance in RA could be attributed, in part, to its ability to enhance immune regulatory cells, especially IL-35+ IL-10+ Bregs.
New species and records of Trichoderma isolated as mycoparasites and endophytes from cultivated and wild coffee in Africa
Authors: del Carmen H. Rodríguez María , Evans Harry C. , de Abreu Lucas M. , de Macedo Davi M. , Ndacnou Miraine K. , Bekele Kifle B. , Barreto Robert W.
Published: March 2021

A survey for species of the genus Trichoderma occurring as endophytes of Coffea, and as mycoparasites of coffee rusts (Hemileia), was undertaken in Africa; concentrating on Cameroon and Ethiopia. Ninety-four isolates of Trichoderma were obtained during this study: 76 as endophytes of healthy leaves, stems and berries and, 18 directly from colonized rust pustules. A phylogenetic analysis of all isolates used a combination of three genes: translation elongation factor-1α (tef1), rpb2 and cal for selected isolates. GCPSR criteria were used for the recognition of species; supported by morphological and cultural characters. The results reveal a previously unrecorded diversity of Trichoderma species endophytic in both wild and cultivated Coffea, and mycoparasitic on Hemileia rusts. Sixteen species were delimited, including four novel taxa which are described herein: T. botryosum, T. caeruloviride, T. lentissimum and T. pseudopyramidale. Two of these new species, T. botryosum and T. pseudopyramidale, constituted over 60% of the total isolations, predominantly from wild C. arabica in Ethiopian cloud forest. In sharp contrast, not a single isolate of Trichoderma was obtained using the same isolation protocol during a survey of coffee in four Brazilian states, suggesting the existence of a ‘Trichoderma void’ in the endophyte mycobiota of coffee outside of Africa. The potential use of these African Trichoderma isolates in classical biological control, either as endophytic bodyguards—to protect coffee plants from Hemileia vastatrix, the fungus causing coffee leaf rust (CLR)—or to reduce its impact through mycoparasitism, is discussed, with reference to the on-going CLR crisis in Central America.
Simulation of the Bell inequality violation based on quantum steering concept
Authors: Ruzbehani Mohsen
Published: March 2021

Violation of Bell’s inequality in experiments shows that predictions of local realistic models disagree with those of quantum mechanics. However, despite the quantum mechanics formalism, there are debates on how does it happen in nature. In this paper by use of a model of polarizers that obeys the Malus’ law and quantum steering concept, i.e. superluminal influence of the states of entangled pairs to each other, simulation of phenomena is presented. The given model, as it is intended to be, is extremely simple without using mathematical formalism of quantum mechanics. However, the result completely agrees with prediction of quantum mechanics. Although it may seem trivial, this model can be applied to simulate the behavior of other not easy to analytically evaluate effects, such as deficiency of detectors and polarizers, different value of photons in each run and so on. For example, it is demonstrated, when detector efficiency is 83% the S factor of CHSH inequality will be 2, which completely agrees with famous detector efficiency limit calculated analytically. Also, it is shown in one-channel polarizers the polarization of absorbed photons, should change to the perpendicular of polarizer angle, at very end, to have perfect violation of the Bell inequality (2 $$\sqrt 2$$

2

) otherwise maximum violation will be limited to (1.5 $$\sqrt{2}$$

2

).
Synthesis and characterization of Cu(OH)2-NWs-PVA-AC Nano-composite and its use as an efficient adsorbent for removal of methylene blue
Authors: Lakkaboyana Sivarama Krishna , Soontarapa Khantong , Asmel Nabel Kalel , Kumar Vinay , Marella Ravi Kumar , Yuzir Ali , Wan Yaacob Wan Zuhairi
Published: March 2021

The present study focused on the synthesis of copper hydroxide nanowires decorated on activated carbon (Cu(OH)2-NWs-PVA-AC). The obtained Cu(OH)2-NWs-PVA-AC Nano-composite was distinguished by XRD, SEM, EDX, BET, FTIR and XPS respectively. Besides, different variables such as solution pH, and initial dye concentration, contact time, and temperature were performed on the adsorption efficiency of MB in a small batch reactor. Further, the experimental results are analyzed by various kinetic models via PFO, PSO, intra-particle diffusion and Elovich models, and the results revealed that among the kinetic models, PSO shows more suitability. In addition, different adsorption isotherms were applied to the obtained experimental data and found that Langmuir–Freundlich and Langmuir isotherm were best fits with the maximum adsorption capacity of 139.9 and 107.6 mg/g, respectively. The Nano-composite has outstanding MB removal efficiency of 94–98.5% with a span of 10 min. and decent adsorption of about 98.5% at a pH of 10. Thermodynamic constants like Gibbs free energy, entropy, and enthalpy were analyzed from the temperature reliance. The results reveal the adsorption processes are spontaneous and exothermic in nature. The high negative value of ΔG° (− 44.11 to − 48.86 kJ/mol) and a low negative value of ΔH° (− 28.96 kJ/mol) show the feasibility and exothermic nature of the adsorption process. The synthesized dye was found to be an efficient adsorbent for the potential removal of cationic dye (methylene blue) from wastewater within a short time.
Obstructive sleep apnea is associated with impaired renal function in patients with diabetic kidney disease
Authors: Zamarrón Ester , Jaureguizar Ana , García-Sánchez Aldara , Díaz-Cambriles Trinidad , Alonso-Fernández Alberto , Lores Vanesa , Mediano Olga , Rodríguez-Rodríguez Paula , Cabello-Pelegrín Sheila , Morales-Ruíz Enrique , Ramírez-Prieto María T. , Valiente-Díaz María Isabel , Gómez-García Teresa , García-Río Francisco ,   Spanish Sleep Network, Arias-Melgar Beatriz , Barceló-Bennasar Antonia , Barquiel Beatriz , Candel-Pizarro Ana , Casitas Raquel , Costero Olga , De-La-Peña-Bravo Mónica , Díaz-Rubio Ana María , Galera Raúl , Giménez-Carrero María Paloma , Lozano-Alcocer Héctor , Mangas Alberto , Martínez-Cerón Elizabet , Peña-Zarza José Antonio , Rodríguez-Pérez Rocío , Romero-Peralta Sofía , Silgado Laura , Troncoso-Acevedo Fernanda
Published: March 2021

Obstructive sleep apnea (OSA) is a recognized risk factor for the development of diabetic kidney disease (DKD). Our objectives were to compare the urinary albumin–creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) of patients with DKD according to OSA severity, and to evaluate the contribution of sleep parameters to their renal function. In a multicenter, observational, cross-sectional study, 214 patients with DKD were recruited. After a sleep study, UACR and eGFR were measured, as well as serum creatinine, fasting glucose, glycated hemoglobin, insulin resistance, lipid profile and C-reactive protein. UACR was higher in severe OSA patients (920 ± 1053 mg/g) than in moderate (195 ± 232 mg/g, p < 0.001) or mild OSA/non-OSA subjects (119 ± 186 mg/g, p < 0.001). At the same time, eGFR showed an OSA severity-dependent reduction (48 ± 23 vs. 59 ± 21 vs. 73 ± 19 ml/min per 1.73 m2, respectively; p < 0.001). Apnea–hypopnea index (AHI and desaturation index (ODI) were identified as independent predictors for UACR and eGFR, respectively. Therefore, in patients with DKD under optimized treatment, severe OSA is associated with a higher UACR and a lower eGFR, reflecting an additional contribution to the impairment of their renal function, although no causality can be inferred.
Four-decade trends in lymph node status of patients with vulvar squamous cell carcinoma in northern Italy
Authors: Preti Mario , Bucchi Lauro , Micheletti Leonardo , Privitera Silvana , Corazza Monica , Cosma Stefano , Gallio Niccolò , Borghi Alessandro , Bevilacqua Federica , Benedetto Chiara
Published: March 2021

The 4-decade (1980–2017) trends in lymph node status of patients with vulvar squamous cell carcinoma (VSCC) in a province of northern Italy were investigated. Information was collected on lymph node dissection, number of lymph nodes dissected, lymph node involvement, and number of positive lymph nodes from a series of 760 patients admitted to a tertiary referral centre for vulvar disease. The adjusted odds ratios (ORs) for lymph node involvement, for ≥ 2 positive nodes, and for a lymph node ratio ≥ 20% were estimated from multiple logistic regression models. The adjusted OR for lymph node dissection was greater in the 2000s and 2010s versus the 1980s. The adjusted OR for lymph node involvement was 1.36 (95% confidence interval (CI), 0.72–2.60) in the 1990s, 1.31 (95% CI, 0.72–2.38) in the 2000s and 1.32 (95% CI, 0.73–2.41) in the 2010s versus the 1980s. The adjusted OR for ≥ 2 positive nodes was 1.36 (95% CI, 0.68–2.72), 0.86 (95% CI, 0.44–1.65) and 0.67 (95% CI, 0.34–1.31), respectively. The adjusted OR for lymph node ratio ≥ 20% was 1.45 (95% CI, 0.62–3.43), 1.21 (95% CI, 0.54–2.72) and 0.81 (95% CI, 0.35–1.89), respectively. This stagnation indicates the need for a serious rethink of the local model for the care of VSCC.
The gut microbiota composition of Trichoplusia ni is altered by diet and may influence its polyphagous behavior
Authors: Leite-Mondin M. , DiLegge M. J. , Manter D. K. , Weir T. L. , Silva-Filho M. C. , Vivanco J. M.
Published: March 2021

Insects are known plant pests, and some of them such as Trichoplusia ni feed on a variety of crops. In this study, Trichoplusia ni was fed distinct diets of leaves of Arabidopsis thaliana or Solanum lycopersicum as well as an artificial diet. After four generations, the microbial composition of the insect gut was evaluated to determine if the diet influenced the structure and function of the microbial communities. The population fed with A. thaliana had higher proportions of Shinella, Terribacillus and Propionibacterium, and these genera are known to have tolerance to glucosinolate activity, which is produced by A. thaliana to deter insects. The population fed with S. lycopersicum expressed increased relative abundances of the Agrobacterium and Rhizobium genera. These microbial members can degrade alkaloids, which are produced by S. lycopersicum. All five of these genera were also present in the respective leaves of either A. thaliana or S. lycopersicum, suggesting that these microbes are acquired by the insects from the diet itself. This study describes a potential mechanism used by generalist insects to become habituated to their available diet based on acquisition of phytochemical degrading gut bacteria.
NTRK fusion in Japanese colorectal adenocarcinomas
Authors: Yamashiro Yuya , Kurihara Taisei , Hayashi Takuo , Suehara Yoshiyuki , Yao Takashi , Kato Shunsuke , Saito Tsuyoshi
Published: March 2021

NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients.
Universal image segmentation for optical identification of 2D materials
Authors: Sterbentz Randy M. , Haley Kristine L. , Island Joshua O.
Published: March 2021

Machine learning methods are changing the way data is analyzed. One of the most powerful and widespread applications of these techniques is in image segmentation wherein disparate objects of a digital image are partitioned and classified. Here we present an image segmentation program incorporating a series of unsupervised clustering algorithms for the automatic thickness identification of two-dimensional materials from digital optical microscopy images. The program identifies mono- and few-layer flakes of a variety of materials on both opaque and transparent substrates with a pixel accuracy of roughly 95%. Contrasting with previous attempts, application generality is achieved through preservation and analysis of all three digital color channels and Gaussian mixture model fits to arbitrarily shaped data clusters. Our results provide a facile implementation of data clustering for the universal, automatic identification of two-dimensional materials exfoliated onto any substrate.
Telocytes are major constituents of the angiogenic apparatus
Authors: Soliman Soha A.
Published: March 2021

The current study investigated role of telocytes (TCs) in angiogenesis during embryonic development of quail using immunohistochemistry (IHC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The angiogenic apparatus consisted of TCs, endothelial cells, and macrophages. TCs were identified morphologically by their telopodes and podoms using TEM and SEM and immunohistochemically using CD34, and vascular endothelial growth factor (VEGF). TCs also expressed CD68. TCs formed a three-dimensional network and established direct contact with blood vessels, sprouting endothelial cells, and active macrophages, while exerting their effect through paracrine signaling. VEGF was also expressed by endothelial cells and macrophages. Matrix metalloproteinase–9 (MMP-9) was expressed by TCs, endothelial cells, and macrophages. In conclusion, the expression of VEGF by TCs, endothelial cells, and macrophages is required for the proliferation and migration of endothelial cells and vascular growth. The expression of MMP-9 by TCs, endothelial cells, and macrophages is essential for the degradation of extracellular matrix (ECM) components during neoangiogenesis. Macrophages may facilitate phagocytosis and elimination of the degraded ECM components.
A modified MRI protocol for the increased detection of sacrococcygeal fractures in patients with thoracolumbar junction fractures
Authors: Khil Eun Kyung , Choi Il , Choi Jung-Ah , Kim Young Woo
Published: March 2021

This study aimed to identify concurrent thoracolumbar junction (TLJ) and sacrococcygeal (SC) fractures using a modified MRI protocol and analyze the risk factors associated with tandem fractures. We retrospectively investigated patients with MRI-confirmed TLJ fractures from January 2017 to March 2020. Patients were divided into two study groups: study 1 with a modified MRI protocol and study 2 with a routine protocol. The modified protocol included an extended field of view of sagittal scans in L-spine MRI covering the full SC spine. In study 1, frequency of concurrent TLJ and SC fractures was investigated. And we analyzed risk factors and compared CT and MRI for detecting SC fractures. In study 2, co-occurrence of both fractures was investigated. A total of 176 and 399 patients with TLJ fractures were enrolled in study 1 and 2, then SC fractures were identified in 53 (30.14%) and 36 patients (9.02%), respectively. An axial loading trauma mechanism was a significant risk factor (Odds ratio 7.0, p < 0.001), and MRI was more sensitive than CT in detecting SC fractures (p < 0.002). Thus, a modified MRI protocol was useful to detect the high occurrence of SC fractures in TLJ fractures, which concurrent fractures increased by an axial loading mechanism.
Enteric reabsorption processes and their impact on drug pharmacokinetics
Authors: Ibarra Manuel , Trocóniz Iñaki F. , Fagiolino Pietro
Published: March 2021

Enteric reabsorption occurs when a drug is secreted into the intestinal lumen and reabsorbed into the systemic circulation. This distribution process is evidenced by multiple peaks in pharmacokinetic profiles. Commonly, hepatobiliary drug secretion is assumed to be the underlying mechanism (enterohepatic reabsorption, EHR), neglecting other possible mechanisms such as gastric secretion (enterogastric reabsorption, EGR). In addition, the impact of drug reabsorption on systemic clearance, volume of distribution and bioavailability has been a subject of long-standing discussions. In this work, we propose semi-mechanistic pharmacokinetic models to reflect EHR and EGR and compare their respective impact on primary pharmacokinetic parameters. A simulation-based analysis was carried out considering three drug types with the potential for reabsorption, classified according to their primary route of elimination and their hepatic extraction: (A) hepatic metabolism—low extraction; (B) hepatic metabolism—intermediate/high extraction; (C) renal excretion. Results show that an increase in EHR can significantly reduce the clearance of drugs A and B, increase bioavailability of B drugs, and increase the volume of distribution for all drugs. Conversely, EGR had negligible impact in all pharmacokinetic parameters. Findings provide background to explain and forecast the role that this process can play in pharmacokinetic variability, including drug-drug interactions and disease states.
Sanger sequencing is no longer always necessary based on a single-center validation of 1109 NGS variants in 825 clinical exomes
Authors: Arteche-López A. , Ávila-Fernández A. , Romero R. , Riveiro-Álvarez R. , López-Martínez M. A. , Giménez-Pardo A. , Vélez-Monsalve C. , Gallego-Merlo J. , García-Vara I. , Almoguera Berta , Bustamante-Aragonés A. , Blanco-Kelly F. , Tahsin-Swafiri S. , Rodríguez-Pinilla E. , Minguez P. , Lorda I. , Trujillo-Tiebas M. J. , Ayuso C.
Published: March 2021

Despite the improved accuracy of next-generation sequencing (NGS), it is widely accepted that variants need to be validated using Sanger sequencing before reporting. Validation of all NGS variants considerably increases the turnaround time and costs of clinical diagnosis. We comprehensively assessed this need in 1109 variants from 825 clinical exomes, the largest sample set to date assessed using Illumina chemistry reported. With a concordance of 100%, we conclude that Sanger sequencing can be very useful as an internal quality control, but not so much as a verification method for high-quality single-nucleotide and small insertion/deletions variants. Laboratories might validate and establish their own thresholds before discontinuing Sanger confirmation studies. We also expand and validate 23 copy number variations detected by exome sequencing in 20 samples, observing a concordance of 95.65% (22/23).
Determinants of SARS-CoV-2 infection in Italian healthcare workers: a multicenter study
Authors: Boffetta Paolo , Violante Francesco , Durando Paolo , De Palma Giuseppe , Pira Enrico , Vimercati Luigi , Cristaudo Alfonso , Icardi Giancarlo , Sala Emma , Coggiola Maurizio , Tafuri Silvio , Gattini Vittorio , Apostoli Pietro , Spatari Giovanna ,   Working Group on SARS-CoV-2 Infection in Italian Healthcare Workers, De Maria Luigi , Caputi Antonio , Sponselli Stefania , Mastrippolito Carmine , Zunarelli Carlotta , Di Felice Giulia , Visci Giovanni , Albini Elisa , Sansone Emanuele , Tomasi Cesare , Bisioli Andrea , Cipriani Lorenzo , De Bellis Alessandro , Tiraboschi Mara Maria , Paraggio Emilio , Rubino Sofia , Capuzzi Michele , Dini Guglielmo , Bruzzone Bianca , Debarbieri Nicoletta , Montecucco Alfredo , Orsi Andrea , Rahmani Alborz , Ricucci Valentina , Guglielmi Giovanni , Fiorentino Leonardo , Brilli Cinzia , Godono Alessandro , Declementi Michael , Mansour Ihab , Milanesio Nicolò , Garzaro Giacomo , Scarmozzino Antonio , Gullino Attilia
Published: March 2021

Healthcare workers (HCWs) are at increased risk of being infected with SARS-CoV-2, yet limited information is available on risk factors of infection. We pooled data on occupational surveillance of 10,654 HCW who were tested for SARS-CoV-2 infection in six Italian centers. Information was available on demographics, job title, department of employment, source of exposure, use of personal protective equipment (PPEs), and COVID-19-related symptoms. We fitted multivariable logistic regression models to calculate odds ratios and 95% confidence intervals of infection. The prevalence of infection ranged from 3.0 to 22.0%, and was correlated with that of the respective areas. Women were at lower risk of infection compared to men. Fever, cough, dyspnea and malaise were the symptoms most strongly associated with infection, together with anosmia and ageusia. No differences in the risk of infection were detected according to job title, or working in a COVID-19 designated department. Reported contact with a patient inside or outside the workplace was a risk factor. Use of a mask was strongly protective against risk of infection as was use of gloves. The use of a mask by the source of exposure (patient or colleague) had an independent effect in reducing infection risk.
Diverse activities and biochemical properties of amylase and proteases from six freshwater fish species
Authors: Champasri Chamaiporn , Phetlum Suthathip , Pornchoo Chanakan
Published: March 2021

This study investigated the biochemical properties, enzyme activities, isoenzyme pattern, and molecular weight of three types of digestive enzyme from six freshwater fish species: Puntius gonionotus (common silver barb), Puntioplites proctozysron (Smith’s barb), Oreochromis niloticus (Nile tilapia), Hemibagrus spilopterus (yellow mystus), Ompok bimaculatus (butter catfish), and Kryptopterus geminus (sheatfish). The optimum pHs for amylase and alkaline protease activities were 7.0–8.0 and 8.0–10.0, and the optimum temperatures were 45–60 °C and 50–55 °C, respectively. A pepsin-like enzyme was detected in all three carnivorous fishes (Ompok bimaculatus, Kryptopterus geminus, and Hemibagrus spilopterus) with optimum reaction pH of 2.0 for each and optimum reaction temperatures 50–55 °C. In optimum reaction conditions, the amylase and alkaline protease from Puntioplites proctozyron showed the highest activities. Lower activities of all enzymes were observed at temperature (29 °C) of Lam Nam Choen swamp than at the optimum reaction temperatures. The fish species contained one to three and five to eight isoforms of amylase and alkaline protease, respectively, with molecular weights from 19.5 to 175 kDa. Both the alkaline proteases and amylases were stable in wide pH and temperature ranges.
Author Correction: Transcriptomic evidence that insulin signalling pathway regulates the ageing of subterranean termite castes
Authors: Haroon  , Ma Xiao-Ming , Li Yu-Xin , Zhang Hong-Xin , Liu Qing , Su Xiao-Hong , Xing Lian-Xi
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
PhyloQuant approach provides insights into Trypanosoma cruzi evolution using a systems-wide mass spectrometry-based quantitative protein profile
Authors: Mule Simon Ngao , Costa-Martins André Guilherme , Rosa-Fernandes Livia , de Oliveira Gilberto Santos , Rodrigues Carla Monadeli F. , Quina Daniel , Rosein Graziella E. , Teixeira Marta Maria Geraldes , Palmisano Giuseppe
Published: March 2021

The etiological agent of Chagas disease, Trypanosoma cruzi, is a complex of seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution requires understanding the parasite origin and population structure. In this study, we introduce the PhyloQuant approach to infer the evolutionary relationships between organisms based on differential mass spectrometry-based quantitative features. In particular, large scale quantitative bottom-up proteomics features (MS1, iBAQ and LFQ) were analyzed using maximum parsimony, showing a correlation between T. cruzi DTUs and closely related trypanosomes’ protein expression and sequence-based clustering. Character mapping enabled the identification of synapomorphies, herein the proteins and their respective expression profiles that differentiate T. cruzi DTUs and trypanosome species. The distance matrices based on phylogenetics and PhyloQuant clustering showed statistically significant correlation highlighting the complementarity between the two strategies. Moreover, PhyloQuant allows the identification of differentially regulated and strain/DTU/species-specific proteins, and has potential application in the identification of specific biomarkers and candidate therapeutic targets.
Nature-inspired hierarchical materials for sensing and energy storage applications
Authors: Xu Chunping , Puente-Santiago Alain R. , Rodríguez-Padrón Daily , Muñoz-Batista Mario J. , Ahsan Md Ariful , Noveron Juan C. , Luque Rafael
Published: March 2021

Nature-inspired hierarchical architectures have recently drawn enormous interest in the materials science community, being considered as promising materials for the development of high-performance wearable electronic devices.
Smartphone-based colorimetric detection systems for glucose monitoring in the diagnosis and management of diabetes
Authors: Kap Özlem , Kılıç Volkan , Hardy John G. , Horzum Nesrin
Published: March 2021

Smartphone-based colorimetric glucose detection methods have the advantageous combination of software and hardware systems that will revolutionize the concept of smartphone-based platforms from glucose measurement to personal health management.
Tryptamine-functionalized magnetic nanoparticles for highly sensitive detection of Salmonella typhimurium
Authors: Lee Seon-Yeong , Chen Feixiong , Lee Tae Yoon
Published: March 2021

A workflow for bacterial pathogen enrichment and DNA extraction and isolation in the single-tube sample preparation method for nucleic acid-based detection of nontyphoidal salmonella is presented.
Covalent-coordination tandem functionalization of a metal–organic framework (UiO-66) as a hybrid probe for luminescence detection of trans,trans-muconic acid as a biomarker of benzene and Fe3+
Authors: Min Jie , Qu Xiang-Long , Yan Bing
Published: March 2021

A green fluorescent hybrid Tb3+@UiO-66–SO3H is prepared via post-synthetic coordination and ligand exchange based on UiO-66. It is developed as a fluorescent probe for the sensing of Fe3+ and tt-MA of a biomarker of toxic benzene.
Effects of ligand functionalization on the band gaps and luminescent properties of a Zr12 oxo-cluster based metal–organic framework
Authors: Zhou Lin , Liu Feiyan , Wang Ji , Chen Rongzhi , Chen Yunlin
Published: March 2021

Herein, effective optical band gap engineering of a robust Zr12 oxo-based hcp UiO-66 has been realized through linker functionalization.
Synthesis of MOF-on-MOF architectures in the context of interfacial lattice matching
Authors: Ha Junsu , Moon Hoi Ri
Published: March 2021

This highlight summarises the previously reported MOF-on-MOF systems, with a focus on the presented crystallographic information and classification of the systems according to lattice parameter matching.
Concentration-induced wettability alteration of nanoscale NaCl solution droplets on the CSH surface
Authors: Hou Dongshuai , Yang Qingrui , Wang Pan , Wang Muhan , Zhang Yue , Wang Xinpeng , Zhang Jinrui
Published: March 2021

The wetting ability of droplets on the CSH surface is weakened with increasing NaCl mass fraction.
Dysprosium-doped zinc tungstate nanospheres as highly efficient heterogeneous catalysts in green oxidation of terpenic alcohols with hydrogen peroxide
Authors: Batalha Daniel Carreira , Mesquita Borges Kellen Cristina , de Fátima Gonçalves Rosana , de Matos Rodrigues Murillo Henrique , Godinho Mário Júnior , Fajardo Humberto Vieira , de Oliveira Bruziquesi Carlos Giovani , da Silva Márcio José
Published: March 2021

Dysprosium-doped zinc tungstate nanospheres efficiently catalyzed the epoxidation of terpenic alcohols using hydrogen peroxide, an inexpensive and environmentally benign oxidant.
Heptose-containing bacterial natural products: structures, bioactivities, and biosyntheses
Authors: Guo Zhengyan , Tang Yue , Tang Wei , Chen Yihua
Published: March 2021

Heptose-containing natural products hold great potential as drugs for the treatment of human and animal diseases.
Chemical reduction-induced surface oxygen vacancies of BiVO4 photoanodes with enhanced photoelectrochemical performance
Authors: Peng Yong , Wu Hao , Yuan Mingjian , Li Fang-Fang , Zou Xingli , Ng Yun Hau , Hsu Hsien-Yi
Published: March 2021

A facile chemical treatment employing a reducing agent sodium sulfite with a mild reduction activity is used to alter the surface states of BiVO4 photoanodes. The sulfite-treated BiVO4 (S-BiVO4) exhibits an enhanced photoelectrochemical performance.
MCR-ALS with sample insertion constraint to enhance the sensitivity of surface-enhanced Raman scattering detection
Authors: Sricharoen Nontawat , Sukmanee Thanyada , Pienpinijtham Prompong , Ekgasit Sanong , Kitahama Yasutaka , Ozaki Yukihiro , Wongravee Kanet
Published: March 2021

Badly overlapped Raman signals between a capping agent and a target analyte.
Chemometrics in forensic science: approaches and applications
Authors: Sauzier Georgina , van Bronswijk Wilhelm , Lewis Simon W.
Published: March 2021

This tutorial review provides an overview of common chemometric methods, and their potential uses within forensic science for evidence interpretation and optimisation of analytical procedures.
Palladium-catalyzed decarbonylative and decarboxylative cross-coupling of acyl chlorides with potassium perfluorobenzoates affording unsymmetrical biaryls
Authors: Fu Liyan , You Jingwen , Nishihara Yasushi
Published: March 2021

Palladium-catalyzed cross-coupling of acyl chlorides with potassium perfluorobenzoates to synthesize perfluorinated biaryls has been reported, which realized the first example involving simultaneous decarbonylation and decarboxylation under redox-neutral conditions.
Defect-mediated electron transfer in photocatalysts
Authors: Xue Jiawei , Fujitsuka Mamoru , Majima Tetsuro
Published: March 2021

In this feature article, we summarize our recent progress in unraveling the defect-mediated electron transfer in photocatalysts.
Dual-MicroRNA-regulation of singlet oxygen generation by a DNA-tetrahedron-based molecular logic device
Authors: Lin Qing , Cai Shijun , Zhou Bing , Wang Kemin , Jian Lixin , Huang Jin
Published: March 2021

A DNA-tetrahedron-based ‘‘AND’’ logic gate is utilized as a molecular device that recognizes dual-miRNA inputs through strand hybridization to activate computation cascades that produce 1O2 in live cells, resulting in the death of target cells.
Hybrids of cationic [4]helicene and N-heterocyclic carbene as ligands for complexes exhibiting (chir)optical properties in the far red spectral window
Authors: Tarrieu Robert , Delgado Irene Hernandez , Zinna Francesco , Dorcet Vincent , Colombel-Rouen Sophie , Crévisy Christophe , Baslé Olivier , Bosson Johann , Lacour Jérôme
Published: March 2021

A cationic Helicene-NHC hybrid is readily prepared and used for the construction of RhI, AuI and AuIII complexes. Ligand controlled chiroptical properties in the far-red spectral window are observed.
Distortion energy-electronic energy compensation determines the nature of solute interactions with irradiation induced vacancies in ferritic steel
Authors: Ahlawat Sarita , Srinivasu K. , Biswas A. , Choudhury Niharendu
Published: March 2021

Fundamental knowledge of vacancy–solute atom (in particular, Cu and Ni) interactions at the electronic level is of utmost importance to understand experimentally observed Cu-precipitation in reactor pressure vessel (RPV) steel.
Quantum computing and quantum information storage
Authors: Krylov Anna I. , Doyle John , Ni Kang-Kuen
Published: March 2021

This themed collection includes a selection of articles on quantum computing and quantum information storage.
Controlling the secondary assembly of porous anionic uranyl–organic polyhedra through organic cationic templates
Authors: Zeng Li-Wen , Hu Kong-Qiu , Huang Zhi-Wei , Mei Lei , Kong Xiang-He , Liu Kang , Zhang Xiao-Lin , Zhang Zhi-Hui , Chai Zhi-Fang , Shi Wei-Qun
Published: March 2021

This work presents a new uranyl–organic polyhedron U4L4 assembled from uranyl and a semirigid ligand. By adjusting the carbon chain length of organic templates, the secondary assembly of U4L4 nanocages is achieved.
Sustainable solvent selection for the manufacture of methylammonium lead triiodide (MAPbI3) perovskite solar cells
Authors: Doolin Alexander James , Charles Rhys Gareth , De Castro Catherine S. P. , Rodriguez Rodrigo Garcia , Péan Emmanuel Vincent , Patidar Rahul , Dunlop Tom , Charbonneau Cecile , Watson Trystan , Davies Matthew Lloyd
Published: March 2021

An approach for screening solvent systems for PSCs to substitute REACH restricted DMF with no loss in device performance.