bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Phase‐Change Heat Transfer by Surface Wettability Control
Authors: Zhou Lei , He Wen , Wang Miao , Hou Xu
Published: February 2022

The phase‐change heat‐transfer coefficient can be improved by several orders of magnitude through the design of micro‐nanostructures on typical surfaces. However, with the rapid development of intelligent and integrated devices, there is an increasing desire to regulate the heat exchange form of the surface to adapt to various environmental requirements. This study concerns the design of a carbon nanotube array‐based phase‐change heat‐transfer surface, which can switch its wettability between superhydrophobicity and superhydrophilicity. By installing this surface on a device that integrates boiling heat transfer and condensation heat transfer, the device can independently adjust the surface wettability for different heat‐transfer requirements. As a result, this surface can enhance condensation heat‐transfer coefficient over 90 % in the superhydrophobic state and enhance the boiling heat‐transfer coefficient over 41 % in the superhydrophilic state. Surfaces with controllable wettability can aid development of a new generation of smart control technologies to actively regulate system and device temperatures.
Os1B11N12/C2N as an Efficient Electrocatalyst for Nitrogen Reduction Reaction
Authors: Yang Xue J. , Wen Zi , Wang Zhi L. , Jiang Qing
Published: February 2022

Ammonia is one of the most important fertilizer feedstocks and chemical precursor besides a promising hydrogen carrier. However, the electrochemical reduction of nitrogen to ammonia is impeded by the low selectivity and high limiting potential of reported catalysts. Herein, the nitrogen reduction reaction (NRR) on Os‐doped BN cluster supported on C2N (Os1B11N12/C2N) was investigated systematically based on density functional theory calculations. It was found that the adjustment of BN cluster on the upper d‐band edge of Os atom enabled the optimal adsorption strength for NRR intermediates. Consequently, Os1B11N12/C2N exhibited high catalytic activity for NRR with the limiting potential of −0.34 V and a remarkable suppressive effect on the hydrogen evolution reaction. This work is not only beneficial for understanding the mechanism of NRR but also provides a fundamental guidance for rational design of catalysts for NRR.
Src kinase as a potential therapeutic target in non‐alcoholic and alcoholic steatohepatitis
Authors: Kurniawan Dhadhang Wahyu , Booijink Richell , Jajoriya Arun Kumar , Dhawan Garima , Mishra Divya , Oosterhuis Dorenda , Argemi Josepmaria , Storm Gert , Olinga Peter , Bataller Ramon , Mohanty Sujit Kumar , Mishra Durga Prasad , Prakash Jai , Bansal Ruchi
Published: February 2022

Non‐alcoholic steatohepatitis (NASH) and alcohol‐associated steatohepatitis (ASH) are the major cause of liver‐related mortality with limited therapeutic options available. In this study, we investigated the role of Src tyrosine kinase in the pathogenesis of (N)ASH. We examined Src kinase expression in livers from patients with NASH, ASH, cirrhosis and biliary atresia, and from preclinical mouse models: methionine choline deficient (MCD)‐diet‐induced NASH, Lieber–DeCarli ethanol (EtOH)‐diet‐induced ASH, carbon tetrachloride (CCl4)‐ and bile duct ligation (BDL)‐induced liver fibrosis. Functional studies, using Src kinase inhibitor KX2‐391, were performed in NASH and ASH mouse models, and in relevant in vitro models. Transcriptomic analysis revealed increased Src kinase expression in human and mouse diseased livers that positively correlated with disease progression. Src kinase inhibition ameliorated lipid biosynthesis (steatosis); monocytes/macrophages infiltration and inflammatory cytokines expression (inflammation) and hepatic stellate cells (HSCs) activation and collagen expression (fibrosis) in MCD‐diet and EtOH‐diet induced liver disease mouse models. In vitro Src inhibition attenuated FFA‐induced hepatocytic lipid accumulation, LPS/IFNγ‐induced nitric oxide release and expression of several inflammatory signatures in macrophages and TGFβ‐induced HSCs activation, contractility and collagen expression. Moreover, Src inhibition diminished gene expression of inflammatory markers in LPS/IFNγ‐stimulated BMDMs and LPS‐stimulated PCLS, and reduced FA accumulation, macrophage activation and collagen deposition in 3D human liver spheroids. Mechanistic studies further revealed that Src kinase mediated the effects through FAK/PI3K/AKT pathway. Our results demonstrate a multicellular and functional role of Src kinase highlighting Src kinase as a promising therapeutic target in (non)alcoholic steatohepatitis.
Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification
Authors: Skenteris Nikolaos T. , Seime Till , Witasp Anna , Karlöf Eva , Wasilewski Grzegorz B. , Heuschkel Marina A. , Jaminon Armand M.G. , Oduor Loureen , Dzhanaev Robert , Kronqvist Malin , Lengquist Mariette , Peeters Frederique E.C.M. , Söderberg Magnus , Hultgren Rebecka , Roy Joy , Maegdefessel Lars , Arnardottir Hildur , Bengtsson Eva , Goncalves Isabel , Quertermous Thomas , Goettsch Claudia , Stenvinkel Peter , Schurgers Leon J. , Matic Ljubica
Published: February 2022

Rationale

Vascular calcification is a prominent feature of late‐stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context.

Methods and results

In patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α‐SMA+ cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE−/− mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFβ1, phosphate and β‐glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues.

Conclusion

We report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α‐SMA+ regions of calcified cardiovascular tissues, induced by pro‐inflammatory and pro‐osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification.
Single‐cell RNA sequencing reveals the multi‐cellular ecosystem in different radiological components of pulmonary part‐solid nodules
Authors: Li Yanmeng , Li Xiao , Chen Haiming , Sun Kunkun , Li Hao , Zhou Ying , Wang Jun , Bai Fan , Yang Fan
Published: February 2022

Background

Early‐stage lung adenocarcinoma that radiologically manifests as part‐solid nodules, consisting of both ground‐glass and solid components, has distinctive growth patterns and prognosis. The characteristics of the tumour microenvironment and transcriptional features of the malignant cells of different radiological phenotypes remain poorly understood.

Methods

Twelve treatment‐naive patients with radiological part‐solid nodules were enrolled. After frozen pathology was confirmed as lung adenocarcinoma, two regions (ground‐glass and solid) from each of the 12 part‐solid nodules and 5 normal lung tissues from 5 of the12 patients were subjected to single‐cell sequencing by 10x Genomics. We used Seurat v3.1.5 for data integration and analysis.

Results

We comprehensively dissected the multicellular ecosystem of the ground‐glass and solid components of part‐solid nodules at the single‐cell resolution. In tumours, these components had comparable proportions of malignant cells. However, the angiogenesis, epithelial‐to‐mesenchymal transition, KRAS, p53, and cell‐cycle signalling pathways were significantly up‐regulated in malignant cells within solid components compared to those within ground‐glass components. For the tumour microenvironment, the relative abundance of myeloid and NK cells tended to be higher in solid components than in ground‐glass components. Slight subtype composition differences existed between the ground‐glass and solid components. The T/NK cell subsets’ cytotoxic function and the macrophages’ pro‐inflammation function were suppressed in solid components. Moreover, pericytes in solid components had a stronger communication related to angiogenesis promotion with endothelial cells and tumour cells.

Conclusion

The cellular landscape of ground‐glass components is significantly different from that of normal tissue and similar to that of solid components. However, transcriptional differences exist in the vital signalling pathways of malignant and immune cells within these components.
An asymmetric CPW‐fed modified bow tie‐shaped antenna with parasitic elements for ultra‐wideband applications
Authors: Alam Md. Mottahir , Azim Rezaul , Sobahi Nebras M. , Khan Asif Irshad , Islam Mohammad Tariqul
Published: February 2022

In this paper, a modified bow tie‐shaped antenna for ultra‐wideband (UWB) communication applications is presented. The anticipated antenna consists of a CPW‐fed modified bow tie‐shaped patch and two asymmetric ground planes with dual parasitic elements. Electromagnetic computation on the antenna demonstrates that the patch and grounds are strongly linked, and the designed antenna can exhibit multiple resonances which overlap to reveal the UWB working spectrum. Experimental verification of the presented antenna shows that the antenna achieved a working band of 3.2–11.0 GHz, with a fractional bandwidth of 109.9%. The antenna also attained a peak gain of 4.32 dBi at 7.3 GHz and peak efficiency of 87.3% at 6.8 GHz and reveals excellent time‐domain behavior and omnidirectional radiation patterns throughout the operating band. A small‐size, large operating band, high gain and efficiency, high fidelity factor, omnidirectional radiation patterns, and very small group delay make the antenna ideal for portable communication devices in the UWB band.
Phylogeography and population genetic structure of the European roe deer in Switzerland following recent recolonization
Authors: Vasiljevic Nina , Morf Nadja V. , Senn Josef , Pérez‐Espona Sílvia , Mattucci Federica , Mucci Nadia , Moore‐Jones Gaia , Pisano Simone Roberto Rolando , Kratzer Adelgunde , Ogden Rob
Published: February 2022

In the early 1800s, the European roe deer (Capreolus capreolus) was probably extirpated from Switzerland, due to overhunting and deforestation. After a federal law was enacted in 1875 to protect lactating females and young, and limiting the hunting season, the roe deer successfully recovered and recolonized Switzerland. In this study, we use mitochondrial DNA and nuclear DNA markers to investigate the recolonization and assess contemporary genetic structure in relation to broad topographic features, in order to understand underlying ecological processes, inform future roe deer management strategies, and explore the opportunity for development of forensic traceability tools. The results concerning the recolonization origin support natural, multidirectional immigration from neighboring countries. We further demonstrate that there is evidence of weak genetic differentiation within Switzerland among topographic regions. Finally, we conclude that the genetic data support the recognition of a single roe deer management unit within Switzerland, within which there is a potential for broad‐scale geographic origin assignment using nuclear markers to support law enforcement.
Face‐off: Novel depredation and nest defense behaviors between an invasive and a native predator in the Greater Everglades Ecosystem, Florida, USA
Authors: Currylow Andrea F. , McCollister Matthew F. , Anderson Gretchen E. , Josimovich Jillian M. , Fitzgerald Austin L. , Romagosa Christina M. , Yackel Adams Amy A.
Published: February 2022

We describe several photo‐documented novel interactions between intraguild predators in southern Florida—the native bobcat (Lynx rufus) and the invasive Burmese python (Python bivittatus). Over several days we documented a bobcat's depredation of an unguarded python nest and subsequent python nest defense behavior following the return of both animals to the nest. This is the first documentation of any animal in Florida preying on python eggs, and the first evidence or description of such antagonistic interactions at a python nest.
Competition and disturbance affect elevational distribution of two congeneric conifers
Authors: Takahashi Koichi , Ikeda Keigo , Okuhara Isao , Kurasawa Rintaro , Kobayashi Suguru
Published: February 2022

Climatic change will affect elevational vegetation distribution because vegetation distribution is related to thermal conditions. However, how elevational species distributions are determined by biotic and abiotic factors is not clear. The long‐term plot census along an elevational gradient is indispensable to clarify mechanisms of elevational distribution of tree species. Two congeneric conifers, the less shade‐tolerant Abies veitchii and shade‐tolerant A. mariesii, dominate at low and high elevations, respectively, in the subalpine zone in Japan. This study investigated the population dynamics of the two species at three elevations (low, middle, high) for 13 years to examine why the two species dominated the different elevations from the viewpoints of competition and disturbance. This study showed that growth and survival rates were not highest at the most dominant elevations for each species. At the high elevation where A. mariesii dominated and small disturbances frequently occurred, the recruitment rate of A. mariesii was highest among the three elevations and that of A. veitchii was largely decreased by tree competition. However, A. veitchii was dominant earlier than A. mariesii at the low elevation after large disturbances by the high growth rate of individual trees. Therefore, A. mariesii was superior to A. veitchii at the high elevation because of its high recruitment rate and large reduction of recruitment of A. veitchii due to competition, while A. veitchii was superior to A. mariesii at the low elevation after large disturbances because of higher growth rate than A. mariesii. It is suggested that the elevational distributions of the two species were determined by elevational changes in population dynamics in relation to competition and disturbance. Long‐term observational studies of forest dynamics among various elevations are indispensable to predict the effects of climatic change on vegetation distribution.
Metapopulation dynamics of multiple species in a heterogeneous landscape
Authors: Pantel Jelena H. , Lamy Thomas , Dubart Maxime , Pointier Jean‐Pierre , Jarne Philippe , David Patrice
Published: February 2022

Characterizing the diversity of demographic strategies among species can inform research in topics such as trait syndromes, community stability, coexistence, and ecological succession. However, this diversity can depend on the spatial scale considered: at the landscape scale, species often form metapopulations, that is sets of local, sometimes short‐lived, populations, inhabiting discrete habitat patches. Metapopulation dynamics are most frequently analyzed in individual species or pairs of interacting species because of the large amount of data required for multiple species, and because species vary in their perceptions of what constitutes a favorable or unfavorable habitat. Here we evaluate, using a case study, whether a metapopulation model can be used to generate accurate estimates of demographic parameters and to describe the diversity of dynamics, responses to environment, and prospects of long‐term persistence in a guild of species inhabiting a common fragmented landscape. We applied this approach to a guild of 22 mollusk species that inhabit freshwater habitats on two islands of Guadeloupe, to compare metapopulation dynamics among species. We analyzed a 15‐year time series of occupancy records for 278 sites using a multistate occupancy model that estimated colonization and extinction rates as a function of site‐specific and year‐specific environmental covariates, then used model results to simulate future island metapopulation dynamics. Despite the diverse array of metapopulation trajectories—a mix of species with either stable, increasing, declining, or fluctuating metapopulations—and the inherent challenges associated with such data (e.g., imperfect detection, spatial and temporal heterogeneity), our model accurately captured among‐patch variation in suitability for many mollusk taxa. The dynamics of rare species or species with habitat preferences not fully captured by the retained set of covariates were less well described. For several species, we detected a negative correlation between extinction and colonization. This variation in habitat suitability created species‐specific extinction‐resistant pockets in the landscape. Our comparative analysis also revealed that species had distinct strategies for metapopulation dynamics, such as “fast‐turnover” species with both a high proportion of occupied sites and a high rate of site extinction in the landscape.
Brominated PEAI as Multi‐Functional Passivator for High‐Efficiency Perovskite Solar Cell
Authors: Li Minghao , Zhou Junjie , Tan Liguo , Liu Yue , Wang Siyang , Jiang Chaofan , Li Hang , Zhao Xing , Gao Xingyu , Tress Wolfgang , Ding Liming , Yi Chenyi
Published: February 2022

The interfaces of perovskite solar cells (PSCs) are well known to be rich in deep‐level carrier traps, which serve as non‐radiative recombination centers and limit the open‐circuit voltage (Voc) and power conversion efficiency (PCE) of PSCs. Defect chemistry and surface passivators have been researched extensively and mainly focused on the neutralization of uncoordinated lead or anion defects. Herein, a novel brominated passivator 2‐bromophenethylammonium iodide (2‐Br‐PEAI) is introduced for a multi‐functional passivation effect at the perovskite interface. The brominated species readily form 2D perovskite on top of the 3D perovskite and multi‐interact with the 3D perovskite surface. Apart from the halide vacancy filling and anion bonding ability, the Br atoms on the benzene ring can interact with the FA cations via strong hydrogen bonding N‐H ⋯ Br and interact with the [PbI6]4− inorganic framework. The interface defects in the PSCs are well passivated, minimizing non‐radiative recombination and enhancing device performance. As a result, a champion PCE of 24.22% was achieved with high Voc and fill factor. In addition, modified devices also showed enhanced operational stability (retention of >95% initial PCE after 400 h) and humidity resistance (>90% initial PCE maintained after 1500 h under ~50% RH).
Synergistic Effect and Electrochromic Mechanism of Nanoflake Li‐doped NiO in LiOH Electrolyte
Authors: Xu Kejun , Wang Liuying , Liu Gu , Ge Chaoqun , Wang Long , Wang Weichao , Chen Mengzhou
Published: February 2022

Inorganic metal oxide electrochromic materials have good application prospects for energy‐saving windows in buildings and smart display applications. Therefore, the development of electrochromic films with good cycling stabilities, fast color‐change response times, and high coloring efficiencies has attracted considerable attention. In this study, nanoflake Li‐doped NiO electrochromic films were prepared using a hydrothermal method, and the films exhibited superior electrochromic performances in the LiOH electrolyte. Li+ ions doping increased the ion transmission rates of the NiO films, and effectively promoted the transportation of ions from the electrolyte into NiO films. Meanwhile, the nanoflake microstructure caused the NiO films to have larger specific surface areas, providing more active sites for electrochemical reactions. It was determined that the NiO‐Li20% film exhibited an ultra‐fast response in the LiOH electrolyte (coloring and bleaching times reached 3 and 1.5 s, respectively). Additionally, the coloration efficiency was 62.1 cm2 C−1, and good cycling stability was maintained beyond 1500 cycles. Finally, the simulation calculation results showed that Li doping weakened the adsorption strengths of the NiO films to OH−, which reduced the generation and decomposition of NiOOH and helped to improve the cycling stabilities of the films. Therefore, the research presented in this article provides a strategy for designing electrochromic materials in the future.
A High‐Performance Solid‐State Na–CO2 Battery with Poly(Vinylidene Fluoride‐co‐Hexafluoropropylene)−Na3.2Zr1.9Mg0.1Si2PO12 Electrolyte
Authors: Lu Liang , Sun Chunwen , Hao Jian , Wang Zelin , Mayer Sergio F. , Fernández‐Díaz Maria Teresa , Alonso José Antonio , Zou Bingsuo
Published: February 2022

The recovery and utilization of carbon dioxide (CO2) is the key to achieve the targets of peak carbon dioxide emissions and carbon neutrality. The Na‐CO2 battery made with cheap alkali metal sodium and greenhouse gas CO2 is an effective strategy to consume CO2 and store clean renewable energy. However, the liquid electrolyte volatilization in the open battery system and inevitable dendrite growth restrict the application of Na‐CO2 batteries. In this work, magnesium‐doped Na3Zr2Si2PO12 (NZSP) was studied as a solid electrolyte for solid‐state Na‐CO2 batteries. The ionic conductivity of Na3.2Zr1.9Mg0.1Si2PO12 reaches 1.16 mS cm−1 at room temperature by replacing Zr ions in Na3Zr2Si2PO12 with Mg ions, and the structural changes are analyzed by neutron powder diffraction. The composite electrolyte consisting of highly conductive Na3.2Zr1.9Mg0.1Si2PO12 and high processability poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) is utilized for the first time to assemble a solid‐state Na‐CO2 battery. The cell shows a full discharge capacity of 7720 mAh g−1 at 200 mA g−1. The middle gap voltage is lower than 2 V after 120 cycles at 200 mA g−1 and at a cut‐off capacity of 500 mAh g−1. This work demonstrates a promising strategy to design high‐performance solid‐state Na‐CO2 batteries.
The Influence of Cell Size on Dynamic Charge Acceptance Tests in Laboratory Lead‐Acid Cells
Authors: Bauknecht Sophia , Kowal Julia , Bozkaya Begüm , Settelein Jochen , Karden Eckhard
Published: February 2022

This study subjected laboratory‐scale test cells to testing methods for dynamic charge acceptance (DCA) that have recently been developed and published for 12 V automotive batteries, particularly enhanced flooded batteries (EFB). The main focus of the study lies on the scaling and geometry effects of different test cell compositions as well as the comparability between the DCA testing methods. The test cells for this study are extracted from industrially manufactured automotive batteries; each cell had either a full set of plates, or a reduced, negative‐limited set of plates. DCA measurements are performed according to SBA S0101:2014, EN 50 342‐6:2015, and a run‐in DCA drive cycle test. The results indicate that DCA generally increases as plate count falls. The correlation between short DCA tests and run‐in DCA under realistic operating conditions is as weak for individual cells as it is known to be for entire batteries. However, DCA stabilized somewhat more quickly in test cells than in batteries.
Organic fluorescent nanoprobes with NIR‐IIb characteristics for deep learning
Authors: Wanderi Kevin , Cui Zongqiang
Published: February 2022

Illumination of biological events with near‐infrared II sub‐channel (NIR‐IIb, 1500–1700 nm) enhances the transparency of biological tissues, which is very attractive for deep imaging. Due to the long‐wavelength, which reduces optical damage, suppresses autofluorescence, and obviates light scattering, NIR‐IIb nanoprobes afford deep tissue penetration with unprecedented spatiotemporal resolution. Hence, NIR‐IIb imaging facilitates deep learning and decipherment of biological proceedings in living organisms with astounding high clarity. In comparison to its predecessors in the visible‐near‐infrared spectrum, imaging in the NIR‐IIb has shown great potential for tissue imaging and extrapolating imaging applications for clinical studies. However, the use of organic fluorescent nanoprobes (OFNPs) in the NIR‐IIb region is still rare since it is in its early stages. Thus, herein we aim to survey the recent development of different organic fluorescent nanomaterials with NIR‐IIb characteristics, their unique photophysical properties, and their utilization in deep imaging in animal models. Further, practical researches on organic fluorescent nanoprobes with NIR‐IIb emission and their transition to clinical applications are highlighted.
Urban Households’ Biomass Energy Fuel Stacking and Its Implications for Sustainable Development Goal Seven: The Case of Jimma Town, Ethiopia
Authors: Tucho Gudina Terefe , Deti Mulunesh , Dadi Dessalegni , Teshome Tizita
Published: February 2022

Sustainable development goal seven aims to provide access to affordable, reliable, sustainable, and modern energy for all by 2030, but its progress and energy stacking conditions have not been evaluated. This study aims to assess the urban household energy profile and link its state to sustainable development goals. This study employs a cross‐sectional study design on 265 households selected by systematic random sampling from a town called Jimma in Ethiopia and collects the data using interview‐based semi‐structured questionnaires. The study obtains information from all the selected households. The results show that more than 80% of the households have a grid electricity connection, but more than 85% of the households regularly use firewood and charcoal for cooking. On average, households use about 1236 kg of firewood and 630 kg of charcoal per year. Most households report power interruption, inability to afford electricity costs, and personal preferences for relying on biomass energy for cooking. Over 98% of the households use electricity for lighting, but few use it for appliances. This shows an inherent challenge attributed to the cooking energy services provided by biomass energy sources despite the accessibility of electricity. This shows the significant impacts of biomass energy stacking which connection to electricity alone cannot solve.
Hypoxia‐driven immunosuppression by Treg and type‐2 conventional dendritic cells in HCC
Authors: Suthen Sheena , Lim Chun Jye , Nguyen Phuong H. D. , Dutertre Charles‐Antoine , Lai Hannah L. H. , Wasser Martin , Chua Camillus , Lim Tony K. H. , Leow Wei Qiang , Loh Tracy Jiezhen , Wan Wei Keat , Pang Yin Huei , Soon Gwyneth , Cheow Peng Chung , Kam Juinn Huar , Iyer Shridhar , Kow Alfred , Tam Wai Leong , Shuen Timothy W. H. , Toh Han Chong , Dan Yock Young , Bonney Glenn K. , Chan Chung Yip , Chung Alexander , Goh Brian K. P. , Zhai Weiwei , Ginhoux Florent , Chow Pierce K. H. , Albani Salvatore , Chew Valerie
Published: February 2022

Background and Aims

Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated.

Approach and Results

We analyzed the immune landscapes of hypoxia‐low and hypoxia‐high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses. The mechanisms of immunosuppression in immune subsets of interest were further explored using in vitro hypoxia assays. Regulatory T cells (Tregs) and a number of immunosuppressive myeloid subsets, including M2 macrophages and human leukocyte antigen–DR isotype (HLA‐DRlo) type 2 conventional dendritic cell (cDC2), were found to be significantly enriched in hypoxia‐high tumor regions. On the other hand, the abundance of active granzyme Bhi PD‐1lo CD8+ T cells in hypoxia‐low tumor regions implied a relatively active immune landscape compared with hypoxia‐high regions. The up‐regulation of cancer‐associated genes in the tumor tissues and immunosuppressive genes in the tumor‐infiltrating leukocytes supported a highly pro‐tumorigenic network in hypoxic HCC. Chemokine genes such as CCL20 (C‐C motif chemokine ligand 20) and CXCL5 (C‐X‐C motif chemokine ligand 5) were associated with recruitment of both Tregs and HLA‐DRlo cDC2 to hypoxia‐high microenvironments. The interaction between Tregs and cDC2 under a hypoxic TME resulted in a loss of antigen‐presenting HLA‐DR on cDC2.

Conclusions

We uncovered the unique immunosuppressive landscapes and identified key immune subsets enriched in hypoxic HCC. In particular, we identified a potential Treg‐mediated immunosuppression through interaction with a cDC2 subset in HCC that could be exploited for immunotherapies.
Quality of biomarker defined subgroups in FDA approvals of PD‐1/PD‐L1 inhibitors 2014 to 2020
Authors: Kim Myung S. , Xu Alexander , Haslam Alyson , Prasad Vinay
Published: February 2022

PD‐L1 expression is associated with differential response in cancers treated with checkpoint inhibitors. Clinical trials for Food and Drug Administration (FDA) approvals of programmed death receptor‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) inhibitors include limited subgroup analyses based on PD‐L1 expression. We aimed to define the characteristics of PD‐L1 defined subgroups of clinical trials leading to FDA approvals for new indications of PD‐1/PD‐L1 inhibitors. FDA approvals for PD‐1/PD‐L1 inhibitors from January 2014 to December 2020 were identified and the clinical trials leading to each drug approval were reviewed. We collected key variables from publicly available information on FDA website and peer‐reviewed publications of clinical trials. We assessed regulatory characteristics (approval date, approved drug[s], cancer type, line of therapy and biomarker‐restricted approval criteria) of each approval. Clinical trials leading to approvals were reviewed for trial design (RCT vs single arm study, primary endpoint) and PD‐L1 defined subgroup design (no subgroup analysis, single threshold 2‐group analysis, nested subgroups and adjacent subgroups). We then compared regulatory and trials characteristics (trial design, primary endpoint and biomarker approval criteria) between studies with nested and adjacent subgroups. There were 60 approvals for PD‐1/PD‐L1 inhibitors between January 2014 and December 2020. Twelve of 60 (20%) did not include any PD‐L1 subgroups. Twenty‐five of 60 (42%) approvals reported only two subgroups, 14 (23%) included adjacent subgroups and 9 (15%) had nested subgroups. Twenty‐five of 60 trials (42%) are single arm studies. Comparison of characteristics between trials with nested subgroup design and adjacent subgroup design did not show differences. We conclude that approvals for new indications of PD‐1/PD‐L1 inhibitors are based on studies that do not include comprehensive reporting of outcomes by PD‐L1 biomarker subgroups.
Regulatory networks and 5′ partner usage of miRNA host gene fusions in breast cancer
Authors: Hafstað Völundur , Søkilde Rolf , Häkkinen Jari , Larsson Malin , Vallon‐Christersson Johan , Rovira Carlos , Persson Helena
Published: February 2022

Genomic rearrangements in cancer cells can create gene fusions where the juxtaposition of two different genes leads to the production of chimeric proteins or altered gene expression through promoter‐swapping. We have previously shown that fusion transcripts involving microRNA (miRNA) host genes contribute to deregulation of miRNA expression regardless of the protein‐coding potential of these transcripts. Many different genes can also be used as 5′ partners by a miRNA host gene in what we named recurrent miRNA‐convergent fusions. Here, we have explored the properties of 5′ partners in fusion transcripts that involve miRNA hosts in breast tumours from The Cancer Genome Atlas (TCGA). We hypothesised that firstly, 5′ partner genes should belong to pathways and transcriptional programmes that reflect the tumour phenotype and secondly, there should be a selection for fusion events that shape miRNA expression to benefit the tumour cell through the known hallmarks of cancer. We found that the set of 5′ partners in miRNA host fusions is non‐random, with overrepresentation of highly expressed genes in pathways active in cancer including epithelial‐to‐mesenchymal transition, translational regulation and oestrogen signalling. Furthermore, many miRNAs were upregulated in samples with host gene fusions, including established oncogenic miRNAs such as mir‐21 and the mir‐106b~mir‐93~mir‐25 cluster. To the list of mechanisms for deregulation of miRNA expression, we have added fusion transcripts that change the promoter region. We propose that this adds material for genetic selection and tumour evolution in cancer cells and that miRNA host fusions can act as tumour ‘drivers’.
Suicide of women and girls during the COVID‐19 pandemic
Authors: Bellizzi Saverio , Lorettu Liliana , Nivoli Alessandra , Molek Katherina
Published: February 2022

While no evidence of significant increase in suicide was detected during the very first phase of the pandemic, death rates and suicide attempts increased in several settings in subsequent phases, especially among women and girls.
Erythroid spectrin binding modulates peroxidase and catalase activity of heme proteins
Authors: Bose Dipayan , Aggarwal Shantanu , Das Debashree , Narayana Chandrabhas , Chakrabarti Abhijit
Published: February 2022

Hemoglobin oxidation due to oxidative stress and disease conditions leads to the generation of ROS (reactive oxygen species) and membrane attachment of hemoglobin in‐vivo, where its redox activity leads to peroxidative damage of membrane lipids and proteins. Spectrin, the major component of the red blood cell (RBC) membrane skeleton, is known to interact with hemoglobin and, here this interaction is shown to increase hemoglobin peroxidase activity in the presence of reducing substrate ABTS (2′, 2′‐Azino‐Bis‐3‐Ethylbenzothiazoline‐6‐Sulfonic Acid). It is also shown that in the absence of reducing substrate, spectrin forms covalently cross‐linked aggregates with hemoglobin which display no peroxidase activity. This may have implications in the clearance of ROS and limiting peroxidative damage. Spectrin is found to modulate the peroxidase activity of different hemoglobin variants like A, E, and S, and of isolated globin chains from each of these variants. This may be of importance in disease states like sickle cell disease and HbE‐β‐thalassemia, where increased oxidative damage and free globin subunits are present due to the defects inherent in the hemoglobin variants associated with these diseases. This hypothesis is corroborated by lipid peroxidation experiments. The modulatory role of spectrin is shown to extend to other heme proteins, namely catalase and cytochrome‐c. Experiments with free heme and Raman spectroscopy of heme proteins in the presence of spectrin show that structural alterations occur in the heme moiety of the heme proteins on spectrin binding, which may be the structural basis of increased enzyme activity.
Differential expression of HNF1A and HNF1A‐AS1 in colon cancer cells
Authors: Sepehri Zahra , Banerjee Archana , Vizeacoumar Frederick S. , Freywald Andrew , Vizeacoumar Franco J. , Dolinsky Vernon W. , Davie James R.
Published: February 2022

The human hepatocyte nuclear factor 1 homeobox A (HNF1A) gene loci express the protein‐coding HNF1A transcript and a long non‐coding RNA in the anti‐sense (HNF1A‐AS1) direction. HNF1A‐AS1 is expressed in numerous types of cancers and poor clinical outcomes such as higher mortality rates, greater metastatic capacity, and poor prognosis of the disease are the results of this expression. In this study, we determined the epigenetic features of the HNF1A gene loci, and expression and cellular localization of HNF1A‐AS1 RNA, HNF1A RNA, and HNF1A protein in colorectal cancer (HT‐29, HTC116, RKO, and SW480) and normal colon epithelial (CCD841) cells. The HT‐29 HNF1A gene had active histone marks (H3K4me3, H3K27ac) and DNase 1 accessible sites at the promoter regions of the HNF1A and HNF1A‐AS1 genes. These epigenetic marks were not observed in the other colorectal cancer cells or in the normal colon epithelial cells. Consistent with the active gene epigenetic signature of the HNF1A gene in HT‐29 cells, HNF1A protein, and HNF1A/HNF1A‐AS1 transcripts were detected in HT‐29 cells but poorly, if at all observed, in the other cell types. In HT‐29 cells, HNF1A‐AS1 localized to the nucleus and was found to bind to the enhancer of zeste homolog 2 (EZH2, a member of PRC2 complex) and potentially form RNA–DNA triplexes with DNase 1 accessible sites in the HT‐29 genome. These activities of HNF1A‐AS1 may contribute to the oncogenic properties of this long non‐coding RNA.
Multicolor light‐sheet microscopy for a large field of view imaging: A comparative study between Bessel and Gaussian light‐sheets configurations
Authors: Luna‐Palacios Yryx Y. , Licea‐Rodriguez Jacob , Camacho‐Lopez M. Dolores , Teichert Ines , Riquelme Meritxell , Rocha‐Mendoza Israel
Published: February 2022

Light‐sheet fluorescence microscopy (LSFM) is useful for developmental biology studies, which require a simultaneous visualization of dynamic microstructures over large fields of views (FOVs). A comparative study between multicolor Bessel and Gaussian‐based LSFM systems is presented. Discussing the chromatic implications to achieve colocalized and large FOVs when both optical arrays are implemented under the same excitation objective is the purpose of this work. The light‐sheets FOVs, optical sectioning, and resolution are experimentally characterized and discussed. The advantages of using Bessel beams and the main drawbacks of using Gaussian beams for multicolor imaging are highlighted. Multiple Bessel excitation minimizes the FOV's mismatch's effects due to the beams chromatic defocusing and alleviates the aside object blurring obtained with multiple Gaussian beams. It also offers a fair homogeneous axial resolution and optical sectioning over a larger effective FOV. Imaging over perithecia samples of the fungus Sordaria macrospora demonstrates such advantages. This work complements previous comparative studies that discuss only single wavelengths light‐sheets excitations.
Low levels of serum IL‐39 are associated with autoimmune thyroid disease
Authors: Weng Linjie , Huang Guoqing , Gong Luping , Xu Jialu , Mao Yushan , Li Yan , Li Mingcai
Published: February 2022

Background

Interleukin (IL)‐39 is a novel member of IL‐12 cytokine family, but its role in autoimmune thyroid diseases (AITD) is unclear. The aim of the present study was to determine serum levels of IL‐39 in Hashimoto's thyroiditis (HT) and Graves' disease (GD) patients.

Methods

A total of 48 patients with HT, 50 patients with GD, and 45 healthy controls (HCs) were recruited for this study. Levels of serum IL‐39 were determined by ELISA.

Results

Compared with HC group, levels of serum IL‐39 in patients with HT (p < 0.05) and GD (p < 0.01) were drastically reduced. Among patients with HT, serum IL‐39 levels had a positive correlation with white blood cell count (WBC) count and free triiodothyronine level. Among patients with GD, the levels of IL‐39 in serum were positively correlated with WBC count and C‐reactive protein levels.

Conclusions

IL‐39 may be a new potential predictor for patients with HT and GD.
Quantification of the impact of factors affecting the technical performance of operating room personnel: Expert judgment approach
Authors: Jafari Nodoushan Reza , Taherzadeh Chenani Khalil , Jahangiri Mehdi , Madadizadeh Farzan , Fallah Hossein
Published: February 2022

Incorrect assessment of the performance shaping factors (PSFs), especially in health care systems, may lead to irreversible consequences such as death. The current study aimed to adapt PSFs taxonomy given in standardized plant analysis risk human reliability analysis (SPAR‐H) technique to surgical context. PSFs taxonomy of the SPAR‐H technique was revised, and more contextspecific definitions to surgical context were suggested. Step‐wise weight assessment ratio analysis (SWARA) and eleven‐digit numerical scale were used for quantification of the weight and negative influence rate of the PSFs during surgical processes, respectively. Nine PSFs were proposed following the SPAR‐H taxonomy. The order of the importance of the PSFs was quietly conflicting in terms of weight and negative influence rate. From the perspective of experts, fatigue and threat stress were assessed as the most important PSFs in terms of both weight and negative influence rate. Current study has offered a domain‐based understanding of the PSFs, particularly in the surgical context. Results of this study could be used to evaluate human error behaviors during the performance of tasks in the operating room. Moreover, these results could be used for improving patient safety programs in health care systems.
Semantic Context Search in Creative Idea Generation
Authors: Johnson Dan R. , Hass Richard W.
Published: February 2022

The ability to search memory for diverse contextual usages of words is proposed to play a role in creative idea generation. However, it is not yet known whether searching for more diverse contextual usages of words enhances the novelty of ideas during idea generation. In three experiments, participants were given a noun as a creativity prompt (e.g., chamber) and generated words creatively linked to the prompt (e.g., secret, relic). We directly manipulated the semantic diversity of creativity prompts to induce differential levels of semantic context search. Semantic diversity refers to the diversity of contexts in which a word is used (e.g., chamber orchestra vs. judge’s chamber). Semantic context search involves searching semantic memory for different contextual usages of a prompt word. Supporting the facilitative role of semantic context search, participants given prompts high in semantic diversity generated responses higher in novelty, compared to participants given prompts low in semantic diversity (Experiments 1 and 3). Capitalizing on recent advances in distributional semantics, our novel experimental approach led to a critical new insight—semantic context search can enhance the novelty of ideas.
Diacerein‐induced interleukin‐1β deficiency reduces the inflammatory infiltrate and immunoexpression of matrix metalloproteinase‐8 in periodontitis in rat molars
Authors: Silva Renata Cristina Lima , Sasso‐Cerri Estela , Cerri Paulo Sérgio
Published: February 2022

Background

Periodontitis is an immunoinflammatory disease that involves the release of cytokines and enzymes, including interleukin‐1 (IL‐1) and matrix metalloproteinases (MMPs). Diacerein is an anti‐IL‐1 drug used for the treatment of osteoarthritis. The aim of the study was to evaluate whether diacerein suppresses the inflammatory reaction and reduces the collagen degradation in the gingival connective tissue in periodontitis.

Methods

Fifty‐four male rats were distributed into three groups (n = 18 animals/group): 1) periodontitis + diacerein group (PDG), 2) periodontitis + saline group (PSG) and control Group (CG; without treatment). Periodontitis was induced for 7 days in the upper right first molars; after 7 days, the animals of PDG received 100 mg/kg of diacerein while in PSG, the animals received saline solution for 7, 15, and 30 days. The animals were killed and fragments of maxilla containing the right molars were processed for paraffin embedding. In hematoxlin & eosin‐stained sections, the volume density of inflammatory cells (VvIC) and fibroblasts (VvFb) in the gingival mucosa, the distances between the junctional epithelium (JE) to the cemento‐enamel junction (CEJ) and the CEJ to the alveolar process crest (AP) were obtained. The number of IL‐1β‒ and MMP‐8‒immunolabeled cells, and collagen content in the gingival mucosa were computed. Data were subjected to two‐way analysis of variance and Tukey post‐test (P≤ 0.05).

Results

The PDG and PSG rats showed a significant increase in the distances of JE‐CEJ and CEJ‐AP. In all periods, the VvIC, the number of IL‐1β‒ and MMP‐8‒immunolabeled cells was significantly lower in PDG than in PSG while the collagen content was significantly greater in PDG than PSG. At 30 days, significant differences in the IL‐1β immunoexpression, collagen content, and in the MMP‐8 immunostaining were not seen between PDG and CG groups.

Conclusions

Our results show an inhibitory effect of diacerein on IL‐1β in the inflamed gingival mucosa of rat molars, decreasing the inflammatory infiltrate and immunoexpression of MMP‐8, and restoring the collagen content.
Detection of multiple endocrine‐disrupting chemicals in milk: Improved and safe high performance liquid chromatography tandem mass spectrometry method
Authors: Yu Yunhan , Kuang Mengya , Zheng Baohua , Wang Meiling , Liu Zhenqiang , Xu Huilan , Wang Jianwu
Published: February 2022

Herein, an improved method for detecting the endocrine‐disrupting chemicals in milk is presented, which is based on high performance liquid chromatography tandem mass spectrometry, coupled with a quick, effective, and safe method. The linearity of the proposed method was in the range of 0.05–100 μg/L, and all correlation coefficients were ≥0.9973. At three concentration levels, the spiked recoveries ranged from 77.7 to 107.5%, relative standard deviations ranged from 0.2 to 14.6%, limits of quantitation ranged from 0.1 to 40 μg/kg, limits of detection ranged from 0.03 to 13.3 μg/kg. The proposed method for the identification and quantitation of 26 endocrine disruptors present in milk is not only easy, fast, and cost‐efficient but also provides a reference for the detection of various endocrine disruptors in milk and other dairy products.