bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualization and modeling of inhibition of IL-1β and TNF-α mRNA transcription at the single-cell level
Authors: Kalb Daniel , Vo Huy D. , Adikari Samantha , Hong-Geller Elizabeth , Munsky Brian , Werner James
Published: July 2021

IL-1β and TNF-α are canonical immune response mediators that play key regulatory roles in a wide range of inflammatory responses to both chronic and acute conditions. Here we employ an automated microscopy platform for the analysis of messenger RNA (mRNA) expression of IL-1β and TNF-α at the single-cell level. The amount of IL-1β and TNF-α mRNA expressed in a human monocytic leukemia cell line (THP-1) is visualized and counted using single-molecule fluorescent in-situ hybridization (smFISH) following exposure of the cells to lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria. We show that the small molecule inhibitors MG132 (a 26S proteasome inhibitor used to block NF-κB signaling) and U0126 (a MAPK Kinase inhibitor used to block CCAAT-enhancer-binding proteins C/EBP) successfully block IL-1β and TNF-α mRNA expression. Based upon this single-cell mRNA expression data, we screened 36 different mathematical models of gene expression, and found two similar models that capture the effects by which the drugs U0126 and MG132 affect the rates at which the genes transition into highly activated states. When their parameters were informed by the action of each drug independently, both models were able to predict the effects of the combined drug treatment. From our data and models, we postulate that IL-1β is activated by both NF-κB and C/EBP, while TNF-α is predominantly activated by NF-κB. Our combined single-cell experimental and modeling efforts show the interconnection between these two genes and demonstrates how the single-cell responses, including the distribution shapes, mean expression, and kinetics of gene expression, change with inhibition.
Angle change of the A-domain in a single SERCA1a molecule detected by defocused orientation imaging
Authors: Katoh Takanobu A. , Daiho Takashi , Yamasaki Kazuo , Danko Stefania , Fujimura Shoko , Suzuki Hiroshi
Published: July 2021

The sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) transports Ca2+ ions across the membrane coupled with ATP hydrolysis. Crystal structures of ligand-stabilized molecules indicate that the movement of actuator (A) domain plays a crucial role in Ca2+ translocation. However, the actual structural movements during the transitions between intermediates remain uncertain, in particular, the structure of E2PCa2 has not been solved. Here, the angle of the A-domain was measured by defocused orientation imaging using isotropic total internal reflection fluorescence microscopy. A single SERCA1a molecule, labeled with fluorophore ReAsH on the A-domain in fixed orientation, was embedded in a nanodisc, and stabilized on Ni–NTA glass. Activation with ATP and Ca2+ caused angle changes of the fluorophore and therefore the A-domain, motions lost by inhibitor, thapsigargin. Our high-speed set-up captured the motion during EP isomerization, and suggests that the A-domain rapidly rotates back and forth from an E1PCa2 position to a position close to the E2P state. This is the first report of the detection in the movement of the A-domain as an angle change. Our method provides a powerful tool to investigate the conformational change of a membrane protein in real-time.
A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism
Authors: Sheraj Ilir , Guray N. Tulin , Banerjee Sreeparna
Published: July 2021

Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.
Spatiotemporal analysis of COVID-19 outbreaks in Wuhan, China
Authors: Liu Wei , Wang Dongming , Hua Shuiqiong , Xie Cong , Wang Bin , Qiu Weihong , Xu Tao , Ye Zi , Yu Linling , Yang Meng , Xiao Yang , Feng Xiaobing , Shi Tingming , Li Mingyan , Chen Weihong
Published: July 2021

Few study has revealed spatial transmission characteristics of COVID-19 in Wuhan, China. We aimed to analyze the spatiotemporal spread of COVID-19 in Wuhan and its influence factors. Information of 32,682 COVID-19 cases reported through March 18 were extracted from the national infectious disease surveillance system. Geographic information system methods were applied to analysis transmission of COVID-19 and its influence factors in different periods. We found decrease in effective reproduction number (Rt) and COVID-19 related indicators through taking a series of effective public health measures including restricting traffic, centralized quarantine and strict stay-at home policy. The distribution of COVID-19 cases number in Wuhan showed obvious global aggregation and local aggregation. In addition, the analysis at streets-level suggested population density and the number of hospitals were associated with COVID-19 cases number. The epidemic situation showed obvious global and local spatial aggregations. High population density with larger number of hospitals may account for the aggregations. The epidemic in Wuhan was under control in a short time after strong quarantine measures and restrictions on movement of residents were implanted.
Bidirectional association between periodontal disease and diabetes mellitus: a systematic review and meta-analysis of cohort studies
Authors: Stöhr Julia , Barbaresko Janett , Neuenschwander Manuela , Schlesinger Sabrina
Published: July 2021

Periodontal disease has been reported to be associated with diabetes mellitus. However, the direction of the association and the influence of bias are not clear. Thus, the aim of this systematic review and meta-analysis was to summarize the existing evidence on the bidirectional prospective association between periodontal disease and diabetes mellitus by accounting for the risk of bias of the original studies. The literature search was conducted on the electronic data sources PubMed and Web of Science up to February 9th, 2021. We included observational studies, which investigated the prospective association between diabetes mellitus and periodontal disease or vice versa. The risk of bias of the primary studies was evaluated by applying the Quality in Prognosis Studies (QUIPS) tool. Random effects models were used to calculate summary relative risk (SRR) with 95% CI. Subgroup analyses were applied to investigate heterogeneity and the robustness of the finding. In total, 15 studies were included . The SRR for incident diabetes mellitus was 1.26 (95% CI 1.12, 1.41; I2: 71%, n = 10; participants = 427,620; identified cases = 114,361), when comparing individuals with periodontitis to individuals without periodontitis. The SRR for incident periodontitis was 1.24 (95% CI 1.13, 1.37; I2: 92%, n = 7; participants = 295,804; identified cases: > 22,500), comparing individuals with diabetes to individuals without diabetes. There were no significant differences between subgroups after stratification for risk of bias. The findings show a positive bidirectional association between periodontal disease and diabetes mellitus, and thus, underline the need for screening of patients with periodontitis regarding diabetes mellitus and vice versa. The main limitation of the study is the high unexplained heterogeneity between the studies including the different assessment methods of the disease diagnosis.
Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats
Authors: Arya Awadhesh K. , Hu Kurt , Subedi Lalita , Li Tieluo , Hu Bingren
Published: July 2021

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.
Bioaugmentation of biofloc system with enzymatic bacterial strains for high health and production performance of Penaeus indicus
Authors: Panigrahi A. , Esakkiraj P. , Das Rashmi Ranjan , Saranya C. , Vinay T. N. , Otta S. K. , Shekhar M. Shashi
Published: July 2021

The beneficial effects of two probiotic bacterial strains Marinilactibacillus piezotolerans and Novosphingobium sp. during the culture of Indian white shrimp, Penaeus indicus, under biofloc and clear water system were evaluated. The experimental variation were CW1 (M. piezotolerans in clear water), BFT1 (biofloc + M. piezotolerans), CW2 (Novosphingobium sp. in clear water), BFT2 (biofloc + Novosphingobium sp.) and control (without bacterial strains and biofloc). Growth and survival considerably increased in probiotic bio-augmented treatments. Probiotic incorporation significantly improved water quality, especially ammonia reduction. Microbiota analysis from gut samples taken from different treatments revealed varied microbial population structure among clear water culture, biofloc culture and control. Proteobacteria and Firmicutes were the top phyla observed in the treatments which were significantly higher in bio-augmented systems than the control. Vibrio genera were predominantly observed in control and clear water system compared to that of biofloc systems. Immune genes were significantly altered in response to probiotic gut microbial supplementation than the control. Higher gene expression profile of important immune genes was observed in the biofloc reared shrimps. Expression of digestive enzyme related genes such as trypsin, chymotrypsin, cathepsin L, cathepsin B and alpha amylase were also upregulated significantly in probiotic supplementation especially in the biofloc treatments. Proteomic analysis of hepatopancreas of shrimps from different treatments was carried out by using 2D gel electrophoresis and MALDI-TOF analysis. The proteins were mostly related to growth and stress tolerance. Eukaryotic initiation factor 4E binding protein was expressed in all the groups and it was high in biofloc treated animals followed by animals treated solely with probiotics compared to those of control groups. The results concludes that biofloc already proved as an effective culture method for healthy shrimp production and supplementation of probiotic bacterial strains registered additional benefit for growth, survival, microbial, immunological status of P, indicus culture.
Intracochlear distortion products are broadly generated by outer hair cells but their contributions to otoacoustic emissions are spatially restricted
Authors: Bowling Thomas , Wen Haiqi , Meenderink Sebastiaan W. F. , Dong Wei , Meaud Julien
Published: July 2021

Detection of low-level sounds by the mammalian cochlea requires electromechanical feedback from outer hair cells (OHCs). This feedback arises due to the electromotile response of OHCs, which is driven by the modulation of their receptor potential caused by the stimulation of mechano-sensitive ion channels. Nonlinearity in these channels distorts impinging sounds, creating distortion-products that are detectable in the ear canal as distortion-product otoacoustic emissions (DPOAEs). Ongoing efforts aim to develop DPOAEs, which reflects the ear’s health, into diagnostic tools for sensory hearing loss. These efforts are hampered by limited knowledge on the cochlear extent contributing to DPOAEs. Here, we report on intracochlear distortion products (IDPs) in OHC electrical responses and intracochlear fluid pressures. Experiments and simulations with a physiologically motivated cochlear model show that widely generated electrical IDPs lead to mechanical vibrations in a frequency-dependent manner. The local cochlear impedance restricts the region from which IDPs contribute to DPOAEs at low to moderate intensity, which suggests that DPOAEs may be used clinically to provide location-specific information about cochlear damage.
Bat aggregational response to pest caterpillar emergence
Authors: Blažek Ján , Konečný Adam , Bartonička Tomáš
Published: July 2021

Moths (Lepidoptera) are major agricultural and forest pests in many parts of the world, including Europe, with many causing great economic damage to crops, horticultural plants, stored items, and wool products. Here, we focus on two ecologically similar inchworms, Operophtera brumata and Erannis defoliaria, known for their high foliage consumption during the spring emergence of caterpillars. We hypothesise that bats could play a role in reducing pests such as caterpillars by switching to this abundant emerging prey. At two infested and one control forest sites, caterpillars were sampled during spring to determine levels of infestation. At the same time, bat flight activity was monitored during the peak in caterpillar abundance. During the spring caterpillar outbreak, we collected faecal samples of forest-dwelling bats capable of using gleaning. The majority of samples were positive for our focus species, being 51.85% for O. brumata and 29.63% for E. defoliaria faecal samples. The foraging activity of two gleaning bats, Myotis nattereri and Myotis bechsteinii, increased at both infested sites, but not at the control site, during caterpillar emergence, as did foraging of Plecotus auritus/austriacus, which used both gleaning and aerial hawking. We conclude that both specialists and occasional gleaners, which prefer different prey but are able to switch their foraging strategies, aggregate at sites during pest emergence and, as such, our results confirm the high potential of bats to reduce numbers of pest species such as caterpillars.
Alterations of sleep quality and circadian rhythm genes expression in elderly thyroid nodule patients and risks associated with thyroid malignancy
Authors: Lou Xudan , Wang Haidong , Tu Yanyuan , Tan Wen , Jiang Cuiping , Sun Jiao , Bao Zhijun
Published: July 2021

To study the alterations of sleep quality and circadian rhythm genes expressions upon elderly thyroid nodule patients, the risk factors associated with thyroid malignancies, and the potential relationship involved. The elderly people enrolled in our study were divided into three groups according to the thyroid histopathology: malignant nodule group, benign nodule group, and normal group, and the clinical data and sleep quality were collected. Among the patients of surgery, 56 fresh thyroid tissues were collected for real-time PCR, immunohistochemistry and western blotting analysis of CLOCK, BMAL1, CRYs and PERs. Poor sleep quality, sleep latency and daytime dysfunction were the independent risk factors of malignant nodule after adjusted by other impacts. The expression levels of CLOCK, BMAL1 and PER2 in thyroid malignant group were significantly higher than benign and normal groups, while CRY2 was decreased, p < 0.05. In addition, CLOCK and BMAL1 protein levels were positively correlated with PSQI of corresponding patients and CRY2 was negatively correlated. Circadian rhythm genes mainly altered in malignant nodules, and sleep disorders may be involved in the occurrence of elderly thyroid malignancy through the high expressions of CLOCK and BMAL1, and low expression of CRY2.
Virtually spatialized sounds enhance auditory processing in healthy participants and patients with a disorder of consciousness
Authors: Heine Lizette , Corneyllie Alexandra , Gobert Florent , Luauté Jacques , Lavandier Mathieu , Perrin Fabien
Published: July 2021

Neuroscientific and clinical studies on auditory perception often use headphones to limit sound interference. In these conditions, sounds are perceived as internalized because they lack the sound-attributes that normally occur with a sound produced from a point in space around the listener. Without the spatial attention mechanisms that occur with localized sounds, auditory functional assessments could thus be underestimated. We hypothesize that adding virtually externalization and localization cues to sounds through headphones enhance sound discrimination in both healthy participants and patients with a disorder of consciousness (DOC). Hd-EEG was analyzed in 14 healthy participants and 18 patients while they listened to self-relevant and irrelevant stimuli in two forms: diotic (classic sound presentation with an “internalized” feeling) and convolved with a binaural room impulse response (to create an “externalized” feeling). Convolution enhanced the brains’ discriminative response as well as the processing of irrelevant sounds itself, in both healthy participants and DOC patients. For the healthy participants, these effects could be associated with enhanced activation of both the dorsal (where/how) and ventral (what) auditory streams, suggesting that spatial attributes support speech discrimination. Thus, virtually spatialized sounds might “call attention to the outside world” and improve the sensitivity of assessment of brain function in DOC patients.
Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
Authors: Whelchel Amy E. , Nicholas Sarah E. , Ma Jian-Xing , Karamichos Dimitrios
Published: July 2021

Corneal innervation plays a major role in the pathobiology of diabetic corneal disease. However, innervation impact has mainly been investigated in the context of diabetic epitheliopathy and wound healing. Further studies are warranted in the corneal stroma-nerve interactions. This study unravels the nerve influence on corneal stroma metabolism. Corneal stromal cells were isolated from healthy (HCFs) and diabetes mellitus (Type1DM and Type2 DM) donors. Cells were cultured on polycarbonate membranes, stimulated by stable Vitamin C, and stroma-only and stroma-nerve co-cultures were investigated for metabolic alterations. Innervated compared to stroma-only constructs exhibited significant alterations in pyrimidine, glycerol phosphate shuttle, electron transport chain and glycolysis. The most highly altered metabolites between healthy and T1DMs innervated were phosphatidylethanolamine biosynthesis, and pyrimidine, methionine, aspartate metabolism. Healthy and T2DMs main pathways included aspartate, glycerol phosphate shuttle, electron transport chain, and gluconeogenesis. The metabolic impact on T1DMs and T2DMs was pyrimidine, purine, aspartate, and methionine. Interestingly, the glucose-6-phosphate and oxaloacetate was higher in T2DMs compared to T1DMs. Our in vitro co-culture model allows the examination of key metabolic pathways corresponding to corneal innervation in the diabetic stroma. These novel findings can pave the way for future studies to fully understand the metabolic distinctions in the diabetic cornea.
A susceptibility locus in the IL12B but not LILRA3 region is associated with vascular damage in Takayasu arteritis
Authors: Kadoba Keiichiro , Watanabe Ryu , Iwasaki Takeshi , Nakajima Toshiki , Kitagori Koji , Akizuki Shuji , Murakami Kosaku , Nakashima Ran , Hashimoto Motomu , Tanaka Masao , Ohmura Koichiro , Morinobu Akio , Terao Chikashi , Yoshifuji Hajime
Published: July 2021

HLA-B*52 is an established genetic factor in Takayasu arteritis (TAK). Recently, single nucleotide polymorphisms (SNPs) in IL12B (rs6871626) and LILRA3 (rs103294) were newly identified as non-HLA susceptibility loci in TAK. Here, we examined how these SNPs contribute to clinical characteristics and vascular damage in TAK. We retrospectively reviewed the medical records of 99 TAK patients enrolled in our previous genome-wide association study, and whose genotypes for IL12B rs6871626, LILRA3 rs103294, and HLA-B*52 were available. Incidence of aortic regurgitation (AR) was significantly associated with the A allele (risk allele) of IL12B rs6871626 (CC 42%, AC 61%, AA 81%; p = 0.0052; odds ratio [OR] 2.45), as well as with the incidence of hypertension (p = 0.049; OR 1.82) and the proportion of patients who underwent aortic valve replacement (p = 0.023; OR 3.64). Regarding vascular damage, there was positive correlation between the Takayasu Arteritis Damage Score and the A allele of IL12B rs6871626 (CC 3.42 ± 2.71, AC 4.06 ± 3.25, AA 6.00 ± 2.81; p = 0.0035; β = 1.35) and between the Vasculitis Damage Index and the A allele (CC 3.47 ± 1.98, AC 4.33 ± 2.40, AA 5.37 ± 2.22; p = 0.0054; β = 0.96). Contrarily, no correlation was found between LILRA3 rs103294 and vascular damage. In the present study, IL12B rs6871626 was associated with vascular damage in TAK, whereas LILRA3 rs103294 was not. Genotyping of IL12B rs6871626 may help to identify patients at risk of disease progression.
A deep learning method for automatic segmentation of the bony orbit in MRI and CT images
Authors: Hamwood Jared , Schmutz Beat , Collins Michael J. , Allenby Mark C. , Alonso-Caneiro David
Published: July 2021

This paper proposes a fully automatic method to segment the inner boundary of the bony orbit in two different image modalities: magnetic resonance imaging (MRI) and computed tomography (CT). The method, based on a deep learning architecture, uses two fully convolutional neural networks in series followed by a graph-search method to generate a boundary for the orbit. When compared to human performance for segmentation of both CT and MRI data, the proposed method achieves high Dice coefficients on both orbit and background, with scores of 0.813 and 0.975 in CT images and 0.930 and 0.995 in MRI images, showing a high degree of agreement with a manual segmentation by a human expert. Given the volumetric characteristics of these imaging modalities and the complexity and time-consuming nature of the segmentation of the orbital region in the human skull, it is often impractical to manually segment these images. Thus, the proposed method provides a valid clinical and research tool that performs similarly to the human observer.
Photoneuromodulation makes a difficult cognitive task less arduous
Authors: Chan Agnes S. , Lee Tsz-lok , Hamblin Michael R. , Cheung Mei-chun
Published: July 2021

A positive effect of photoneuromodulation (PNM) has been found on cognitive and emotional functions in healthy populations. However, the hemodynamic changes associated with improved cognitive functions (i.e., memory and executive functions) are unexplored. Therefore, the present study investigated the hemodynamic changes associated with PNM using functional near-infrared spectroscopy (fNIRS). In this experiment, 33 young healthy adults were recruited and randomly assigned to control and experimental groups. A single PNM stimulation was applied to the forehead in the experimental group, while a sham stimulation (same procedure without machine activation) was performed for the control group. Before and after the stimulation, all participants performed an n-back task with 0-and 3-back conditions to assess their working memory function, and their hemodynamic responses during the tasks were measured by fNIRS. A significant group (experimental vs. control) × time (before vs. after PNM) interaction in memory-related frontal activation was found. Specifically, only the experimental group had a significant reduction in frontal hemodynamic levels during the difficult task. Additionally, the memory-related frontal activation was significantly correlated with the immediate and delayed recall of the Rey–Osterrieth Complex Figure Test assessed at baseline. Therefore, PNM may reduce the cognitive efforts needed to complete tasks with high memory loads.
Trajectories of mortality risk among patients with cancer and associated end-of-life utilization
Authors: Parikh Ravi B. , Liu Manqing , Li Eric , Li Runze , Chen Jinbo
Published: July 2021

Machine learning algorithms may address prognostic inaccuracy among clinicians by identifying patients at risk of short-term mortality and facilitating earlier discussions about hospice enrollment, discontinuation of therapy, or other management decisions. In the present study, we used prospective predictions from a real-time machine learning prognostic algorithm to identify two trajectories of all-cause mortality risk for decedents with cancer. We show that patients with an unpredictable trajectory, where mortality risk rises only close to death, are significantly less likely to receive guideline-based end-of-life care and may not benefit from the integration of prognostic algorithms in practice.
Optical tissue clearing and machine learning can precisely characterize extravasation and blood vessel architecture in brain tumors
Authors: Kostrikov Serhii , Johnsen Kasper B. , Braunstein Thomas H. , Gudbergsson Johann M. , Fliedner Frederikke P. , Obara Elisabeth A. A. , Hamerlik Petra , Hansen Anders E. , Kjaer Andreas , Hempel Casper , Andresen Thomas L.
Published: July 2021

Precise methods for quantifying drug accumulation in brain tissue are currently very limited, challenging the development of new therapeutics for brain disorders. Transcardial perfusion is instrumental for removing the intravascular fraction of an injected compound, thereby allowing for ex vivo assessment of extravasation into the brain. However, pathological remodeling of tissue microenvironment can affect the efficiency of transcardial perfusion, which has been largely overlooked. We show that, in contrast to healthy vasculature, transcardial perfusion cannot remove an injected compound from the tumor vasculature to a sufficient extent leading to considerable overestimation of compound extravasation. We demonstrate that 3D deep imaging of optically cleared tumor samples overcomes this limitation. We developed two machine learning-based semi-automated image analysis workflows, which provide detailed quantitative characterization of compound extravasation patterns as well as tumor angioarchitecture in large three-dimensional datasets from optically cleared samples. This methodology provides a precise and comprehensive analysis of extravasation in brain tumors and allows for correlation of extravasation patterns with specific features of the heterogeneous brain tumor vasculature.
HLA-B and cysteinylated ligands distinguish the antigen presentation landscape of extracellular vesicles
Authors: Bauzá-Martinez Julia , Heck Albert J. R. , Wu Wei
Published: July 2021

Extracellular vesicles can modulate diverse processes ranging from proliferation and tissue repair, to chemo-resistance and cellular differentiation. With the advent of tissue and immunological targeting, extracellular vesicles are also increasingly viewed as promising vectors to deliver peptide-based cancer antigens to the human immune system. Despite the clinical relevance and therapeutic potential of such ‘cell-free’ approaches, the natural antigen presentation landscape exported in extracellular vesicles is still largely uncharted, due to the challenging nature of such preparations and analyses. In the context of therapeutic vesicle production, a critical evaluation of the similarity in vesicular antigen presentation is also urgently needed. In this work, we compared the HLA-I peptide ligandomes of extracellular vesicles against that of whole-cells of the same cell line. We found that extracellular vesicles not only over-represent HLA-B complexes and peptide ligands, but also cysteinylated peptides that may modulate immune responses. Collectively, these findings describe the pre-existing provision of vesicular HLA complexes that may be utilized to carry peptide vaccines, as well as the propensity for different peptide and post-translationally modified ligands to be presented, and will outline critical considerations in devising novel EV vaccination strategies.
Patchy nuclear chain reactions
Authors: Dumonteil Eric , Bahran Rian , Cutler Theresa , Dechenaux Benjamin , Grove Travis , Hutchinson Jesson , McKenzie George , McSpaden Alexander , Monange Wilfried , Nelson Mark , Thompson Nicholas , Zoia Andrea
Published: July 2021

Stochastic fluctuations of the neutron population within a nuclear reactor are typically prevented by operating the core at a sufficient power, since a deterministic (i.e., exactly predictable) behavior of the neutron population is required by automatic safety systems to detect unwanted power excursions. In order to characterize the reactor operating conditions at which the fluctuations vanish, an experiment was designed and took place in 2017 at the Rensselaer Polytechnic Institute Reactor Critical Facility. This experiment however revealed persisting fluctuations and striking patchy spatial patterns in neutron spatial distributions. Here we report these experimental findings, interpret them by a stochastic modeling based on branching random walks, and extend them using a “numerical twin” of the reactor core. Consequences on nuclear safety will be discussed.
A soft on/off switch based on the electrochemically reversible H–J interconversion of a floating porphyrin membrane
Authors: Molina-Osorio Andrés F. , Yamamoto Sho , Robayo-Molina Iván , Gamero-Quijano Alonso , Nagatani Hirohisa , Scanlon Micheál D.
Published: July 2021

The structural rearrangement of a porphyrin membrane self-assembled at a “soft” liquid|liquid interface from a H- to J-molecular configuration is reversibly modulated by externally manipulating the interfacial Galvani potential difference.
An electrostatically regulated organic self-assembly for rapid and sensitive detection of heparin in serum
Authors: He Zhixiao , Nie Hailiang , Cui Jie , Zhang Xiaoling , Yang Xiaoxi , Li Cuiping , Yan Hongyuan
Published: July 2021

A self-assembly composed of a long-wavelength double-charged cationic fluorescent dye is used for rapid, sensitive and reversible detection of heparin in serum.
Mixed H2O/H2 plasma-induced redox reactions of thin uranium oxide films under UHV conditions
Authors: El Jamal Ghada , Gouder Thomas , Eloirdi Rachel , Tereshina-Chitrova Evgenia , Horákd Lukáš , Jonsson Mats
Published: July 2021

X-ray photoelectron spectroscopy (XPS) has been used to study the effect of mixed H2O/H2 gas plasma on the surfaces of UO2, U2O5 and UO3 thin films at 400 °C.
Magnetic anisotropy on demand exploiting high-pressure as remote control: an ab initio proof of concept
Authors: Briganti Matteo , Totti Federico
Published: July 2021

An in silico proof of concept showed that detectable changes in magnetic anisotropies can be achieved by applying pressure on molecular magnetic systems containing lanthanides.
Schiff-base [4]helicene Zn(ii) complexes as chiral emitters
Authors: Savchuk Mariia , Vertueux Steven , Cauchy Thomas , Loumaigne Matthieu , Zinna Francesco , Di Bari Lorenzo , Zigon Nicolas , Avarvari Narcis
Published: July 2021

CPL active enantiopure zinc(ii) complexes based on the first tetradentate salen ligands surrounded by [4]helicene moieties and chiral 1,2-cyclohexane-diamine are reported.
Photo-oxidation of pinic acid in the aqueous phase: a mechanistic investigation under acidic and basic pH conditions
Authors: Amorim Jéssica Vejdani , Guo Xinyang , Gautam Tania , Fang Rongyan , Fotang Christian , Williams Florence J. , Zhao Ran
Published: July 2021

The mechanism of aqueous-phase OH-oxidation of pinic acid was investigated for the first time, and norpinic acid and 3-methyl-1,2,3-butanetricarboxylic acid were identified as major products. The mechanism is pH-dependent, with enhanced yields under basic conditions.
Biological effects of stevia, sucralose and sucrose in citrus–maqui juices on overweight subjects
Authors: Zafrilla Pilar , Masoodi Hedyeh , Cerdá Begoña , García-Viguera Cristina , Villaño Débora
Published: July 2021

Oxidative stress and an inflammatory response were observed after consumption of sweetened beverages, with the exception of stevia, which produced an anti-inflammatory response.
Correction: Anthocyanins from the fruits of Lycium ruthenicum Murray improve high-fat diet-induced insulin resistance by ameliorating inflammation and oxidative stress in mice
Authors: Tian Baoming , Zhao Jianhua , Xie Xiaoqing , Chen Tao , Yin Yan , Zhai Ruohan , Wang Xinlei , An Wei , Li Juxiu
Published: July 2021

Correction for ‘Anthocyanins from the fruits of Lycium ruthenicum Murray improve high-fat diet-induced insulin resistance by ameliorating inflammation and oxidative stress in mice’ by Baoming Tian et al., Food Funct., 2021, 12, 3855–3871, DOI: 10.1039/D0FO02936J.
3D printing of artificial skin patches with bioactive and optically active polymer materials for anti-infection and augmenting wound repair
Authors: Zhao Hao , Xu Jingwen , Yuan Haitao , Zhang Endong , Dai Nan , Gao Zhiqiang , Huang Yiming , Lv Fengting , Liu Libing , Gu Qi , Wang Shu
Published: July 2021

A printable ink composed of a photoactive cationic conjugated polymer (PPV) and gelatin/alginate/hyaluronic acid was developed for 3D printing artificial skin patches with the biofunctions of anti-infection and augmenting wound repair.
A single residue can modulate nanocage assembly in salt dependent ferritin
Authors: Kumar Mantu , Markiewicz-Mizera Joanna , Janna Olmos Julian David , Wilk Piotr , Grudnik Przemysław , Biela Artur P. , Jemioła-Rzemińska Małgorzata , Górecki Andrzej , Chakraborti Soumyananda , Heddle Jonathan G.
Published: July 2021

Modifications to a protein cage whose assembly depends on the presence of metal ions can modulate the extent of its dependence and in some cases convert the assembly to be salt independent.
The selective deprotonation of carbon quantum dots for fluorescence detection of phosphate and visualization of latent fingerprints
Authors: Yang Li , Zhang Qi , Han Ying , Li Hongjuan , Sun Shiguo , Xu Yongqian
Published: July 2021

A water-soluble, stable and selective “turn-on” fluorescence sensing platform based on carbon quantum dots (CQDs) was designed for rapid determination of phosphate (Pi) in aqueous solutions and for visualization of latent fingerprints on paper.
The mechanism of conversion of substituted glycals to chiral acenes via Diels–Alder reaction: a computational study
Authors: Jana Kalyanashis , Wakchaure Padmaja D. , Hussain Nazar , Mukherjee Debaraj , Ganguly Bishwajit
Published: July 2021

Transformation of substituted glycals to chiral fused aromatic cores using DFT calculations reveal that the base catalyzed reaction is favorable over sigmatropic [1,5] hydrogen shift and the product formation is governed by aromaticity.
Direct synthetic routes to functionalised crown ethers
Authors: Nicoli Federico , Baroncini Massimo , Silvi Serena , Groppi Jessica , Credi Alberto
Published: July 2021

Modification of crown ethersviagrafting of functional groups represents a convenient yet underexplored tool.
Rh(iii)-Catalyzed one-pot three-component cyclization reaction: rapid selective synthesis of monohydroxy polycyclic BINOL derivatives
Authors: Liu Hao , Lin Meng-Ling , Chen Yin-Jun , Huang Yin-Hui , Dong Lin
Published: July 2021

A Rh(iii)-catalyzed three-component C–H bond functionalization protocol has been successfully applied to access complex polycyclic BINOL derivatives in which the formation of intermediate amides occurred in situ from aldehydes and amines.
Robust, highly active, and stable supported Co(ii) nanoparticles on magnetic cellulose nanofiber-functionalized for the multi-component reactions of piperidines and alcohol oxidation
Authors: Ghamari Kargar Pouya , Bagherzade Ghodsieh
Published: July 2021

The new recyclable cobalt three-core magnetic catalyst obtained by anchoring a Schiff base ligand sector and cellulose nanofiber slings on MNP (Fe3O4) was prepared and named as MNP@CNF@ATSM–Co(ii).
Comparison of surface-passivation ability of the BAI salt and its induced 2D perovskite for high-performance inverted perovskite solar cells
Authors: Zhang Hanhong , Wang Song , Hou Youzheng , Zhang Fan , Hao Yuying , Song Jun , Qu Junle
Published: July 2021

A BAI layer was formed on the CH3NH3PbI3 surface, which was transformed into a 2D perovskite layer or the organic salt. Many measurements show that the 2D perovskite could effectively reduce the trap-assisted recombination and increase the stability.
Copolymerization of 1,3-butadiene with phenyl/phenethyl substituted 1,3-butadienes: a direct strategy to access pendant phenyl functionalized polydienes
Authors: Lin Juan , Wang Feng , Zhang Chunyu , Liu Heng , Li Dexin , Zhang Xuequan
Published: July 2021

Copolymerization of 1,3-butadiene with various phenyl substituted 1,3-butadiene derivatives to access pendant phenyl functionalized polydiene elastomers is reported.
Mining hydroformylation in complex reaction networkviagraph theory
Authors: Takahashi Keisuke , Satoshi Maeda
Published: July 2021

Data science is introduced to identify the reactant, product, and reaction path in the chemical reaction network.
Water-promoted dehydrative coupling of 2-aminopyridines in heptane via a borrowing hydrogen strategy
Authors: Nakayama Taku , Hikawa Hidemasa , Kikkawa Shoko , Azumaya Isao
Published: July 2021

We describe a novel strategy for the water-promoted dehydrative coupling reaction in heptane, which offers a sustainable direct amination of alcohols.
Construction of a novel step-scheme CdS/Pt/Bi2MoO6 photocatalyst for efficient photocatalytic fuel denitrification
Authors: Hu Weineng , Yan Guiyang , Liang Ruowen , Jiang Mengmeng , Huang Renkun , Xia Yuzhou , Chen Lu , Lu Yi
Published: July 2021

The S-scheme heterojunction in which Pt nanoparticles were anchored between CdS and Bi2MoO6 as ‘bridges’ enhanced the utilization of visible light and efficient separation of photogenerated electron–hole pairs.
Towards the object-oriented design of active hydrogen evolution catalysts on single-atom alloys
Authors: Zhou Chuan , Zhao Jia Yue , Liu Peng Fei , Chen Jianfu , Dai Sheng , Yang Hua Gui , Hu P. , Wang Haifeng
Published: July 2021

An inverse catalyst design workflow in Python (CATIDPy) for discovering unexplored chemical spaces successfully realized the highly accelerated location of active single-atom alloy (SAA) catalysts for the hydrogen evolution reaction (HER).
Sensitization-initiated electron transfer via upconversion: mechanism and photocatalytic applications
Authors: Glaser Felix , Kerzig Christoph , Wenger Oliver S.
Published: July 2021

A full picture of a new multi-photon excitation mechanism relying on sTTA upconversion is provided, together with selected photocatalytic applications. All mechanistic steps are investigated and the catalytically active species is observed directly.
Adapting decarbonylation chemistry for the development of prodrugs capable of in vivo delivery of carbon monoxide utilizing sweeteners as carrier molecules
Authors: De La Cruz Ladie Kimberly , Yang Xiaoxiao , Menshikh Anna , Brewer Maya , Lu Wen , Wang Minjia , Wang Siming , Ji Xingyue , Cachuela Alyssa , Yang Haichun , Gallo David , Tan Chalet , Otterbein Leo , de Caestecker Mark , Wang Binghe
Published: July 2021

1,2-Dicarbonyl compounds with FDA-approved sweeteners as leaving groups deliver CO for protection against acute kidney injury in mice.
Time-encoded bio-fluorochromic supramolecular co-assembly for rewritable security printing
Authors: Gao Zhao , Qiu Shuai , Yan Fei , Zhang Shuyi , Wang Feng , Tian Wei
Published: July 2021

Rewritable security printing has been successfully achieved based on a biofuel-driven transient supramolecular co-assembly mediated by an enzyme, providing fascinating potential for artificial functional materials with a biomimetic mode.
Mechanistic underpinning of cell aspect ratio-dependent emergent collective motions in swarming bacteria
Authors: Bera Palash , Wasim Abdul , Mondal Jagannath , Ghosh Pushpita
Published: July 2021

Mechanistic underpinning reveals an interplay between steric repulsive and size-dependent motility forces, determines the fastest motion for an intermediate cell-size in self-propelled bacterial swarms.
Antimicrobial immunotherapeutics: past, present and future
Authors: Mercer Derry K , Francis Marie-Louise , Fraser-Pitt Douglas
Published: July 2021

In this age of antimicrobial resistance (AMR) there is an urgent need for novel antimicrobials. One area of recent interest is in developing antimicrobial effector molecules, and even cell-based therapies, based on those of the immune system. In this review, some of the more interesting approaches will be discussed, including immune checkpoint inhibitors, Interferons (IFNs), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Chimeric Antigen Receptor (CAR) T cells, Antibodies, Vaccines and the potential role of trained immunity in protection from and/or treatment of infection.
Merging timescale for the supermassive black hole binary in interacting galaxy NGC 6240
Authors: Sobolenko M. , Berczik P. , Spurzem R.
Published: July 2021

Context. One of the mechanisms leading to the creation of a supermassive black hole (SMBH) is the so-called hierarchical merging scenario. Central SMBHs at the final phase of interacting and coalescing host-galaxies are observed as SMBH binary (SMBHB) candidates at different separations from hundreds of parsecs to megaparsecs.

Aims. Today one of the strongest SMBHB candidates is the ultraluminous infrared galaxy NGC 6240 which was spatially and spectroscopically resolved in X-rays by Chandra. Dynamical calculation of central SMBHBs merging in a dense stellar environment allows us to retrace their evolution from kiloparsec to megaparsec scales. The main goal of our dynamical modeling was to reach the final, gravitational wave emission regime for the model BHs.

Methods. We present direct N-body simulations with up to one million particles and relativistic post-Newtonian corrections for the SMBH particles up to 3.5 post-Newtonian terms.

Results. Generally speaking, the set of initial physical conditions can strongly affect our merging time estimations. However, within a certain range of our parameters, we do not find any strong correlation between merging time and BH-to-BH mass or BH-to-bulge mass ratios. Varying the numerical parameters (like particle number – N) does not significantly change the merging time limits. From our 20 models, we find an upper limit on the merging time for central SMBHBs of less than ∼55 Myr. This precise number is only valid for our combination of initial mass ratios.

Conclusions. Further detailed research of rare dual and multiple BHs in dense stellar environments (based on observational data) could clarify the dynamical co-evolution of central BHs and their host-galaxies.
Preparing for LSST data
Authors: Riccio G. , Małek K. , Nanni A. , Boquien M. , Buat V. , Burgarella D. , Donevski D. , Hamed M. , Hurley P. , Shirley R. , Pollo A.
Published: July 2021

Aims.We study how the upcoming Legacy Survey of Space and Time (LSST) data from theVera C. RubinObservatory can be employed to constrain the physical properties of normal star-forming galaxies (main-sequence galaxies). Because the majority of the observed LSST objects will have no auxiliary data, we use simulated LSST data and existing real observations to test the reliability of estimates of the physical properties of galaxies, such as their star formation rate (SFR), stellar mass (Mstar), and dust luminosity (Ldust). We focus on normal star-forming galaxies because they form the majority of the galaxy population in the universe and are therefore more likely to be observed with the LSST.

Methods.We performed a simulation of LSST observations and uncertainties of 50 385 real galaxies within the redshift range 0 < z < 2.5. In order to achieve this goal, we used the unique multi-wavelength data from theHerschelExtragalactic Legacy Project (HELP) survey. Our analysis focused on two fields, ELAIS N1 and COSMOS. To obtain the physical properties of the galaxies, we fit their spectral energy distributions (SEDs) using the Code Investigating GALaxy Emission. We simulated the LSST data by convolving the SEDs fitted by employing the multi-wavelength observations. We compared the main galaxy physical properties, such as SFR,Mstar, andLdustobtained from the fit of the observed multi-wavelength photometry of galaxies (from the UV to the far-IR) to those obtained from the simulated LSST optical measurements alone.

Results.We present the catalogue of simulated LSST observations for 23 291 main-sequence galaxies in the ELAIS N1 field and for 9093 galaxies in the COSMOS field. It is available in the HELP virtual observatory. The stellar masses estimated based on the LSST measurements agree with the full UV to far-IR SED estimates because they mainly depend on the UV and optical emission, which is well covered by LSST in the considered redshift range. Instead, we obtain a clear overestimate of the dust-related properties (SFR,Ldust,Mstar) estimated with the LSST alone. They are highly correlated with redshift. We investigate the cause of this overestimate and conclude that it is related to an overestimate of the dust attenuation in both UV and near-IR. We find that it is necessary to employ auxiliary rest-frame mid-IR observations, simulated UV observations, or the far-UV attenuation (AFUV)-Mstarrelation to correct for the overestimate. We also deliver the correction formula log10(SFRLSST/SFRreal) = 0.26 ⋅ z2 − 0.94 ⋅ z + 0.87. It is based on the 32 384 MS galaxies detected withHerschel.