bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement in lithium-ion transport performance of cathodes by PEGDA-based solid-state electrolyte
Authors: Zhang Yongquan , Zhu Baoshan , Chi Qingguo , Gao Hongchang , Zhang Changhai , Zhang Tiandong , Zhu Kai , Cao Dianxue
Published: August 2022

The transport performance of lithium ions affects the rate performance of the cathode at different current densities. The poor interface contact between a solid electrolyte and the cathode makes it difficult to transport lithium ions. Adding a solid electrolyte into the cathode material can improve lithium ion transport. In this paper, we prepared some cathodes with different doping ratios, including two common cathode materials (LiFePO4 and NCM811), and tested their rate and long cycle performance. LFP-10 has a specific discharge capacity of 79.75 mAh g−1 at 5C, and the Li+ diffusion coefficient of LFP-10 is 4.91 × 10−13 cm−2 s−1, which is about 13.4 times higher than the pure LiFePO4 sample. The rate performance of an all-solid-state battery has also been improved, and there is still more than 100 mAh g−1 capacity reserved at 60°C and 2C current density. This shows that the introduction of a PEGDA-based solid electrolyte can significantly improve the Li+ transport of the cathode, and the composite cathode also provides support for the future application of all-solid-state batteries.
Using State-and-Transition Simulation Models (STSMs) to Explore Dynamic Population Responses to Drought Cycles in Freshwater Ecosystems
Authors: Bond Nick R. , Horne Avril C. , McPhan Luke M. , Coleman Rhys
Published: August 2022

Climate variability and change pose significant threats to aquatic biodiversity, particularly in areas with low and variable streamflow. Quantifying the magnitude of risk from these threats is made more difficult by the variable responses of individual species to hydrologic stress. Patterns of population decline and recovery in response to drought cycles will depend on both the resistance traits (e.g., tolerance to harsh environmental conditions) and resilience traits (e.g., fecundity, age at maturity), both of which vary considerably among species. Collectively these traits can give rise to varied, and lagged patterns of decline and recovery in response to hydrologic variability, which ultimately can affect population viability in drought prone environments and in response to a changing climate. Such population cycles are typically modelled based on demographic rates (mortality and recruitment) under different climate conditions. However, such models are relatively data intensive, limiting their widespread development. A less precise but more tractable approach is to adopt state-and-transition approaches based on semi-quantitative population states (or population size estimates), and modelled transitions between states under different hydrologic conditions. Here we demonstrate the application of such models to a suite of diverse taxa, based on an expert elicitation of expected state-changes across those different taxa under a range of different flow conditions. The model results broadly conform with population changes observed in response to a major drought in the case-study system, mimicking the observed lags in recovery of species with different life-histories. Stochastic simulations of population cycles under scenarios of more protracted drought provide a semi-quantitative measure of the potential risk to different species under each scenario, as well as highlighting the large uncertainties that can arise when taking into account stochastic (rather than deterministic) state-transitions.
ZnO/Zn(OH)2 nanoparticles and self-cleaning coatings for the photocatalytic degradation of organic pollutants
Authors: Faheem Muhammad , Siddiqi Humaira M. , Habib Amir , Shahid Muhammad , Afzal Adeel
Published: August 2022

Zinc oxide (ZnO) nanostructures have emerged as efficient heterogeneous photocatalysts for the degradation of organic pollutants in aqueous solutions and industrial wastewaters. In this work, a simple and effective method is reported for the synthesis of zinc oxide/zinc hydroxide (ZnO/Zn(OH)2) hybrid nanoparticles using a mineral acid to enhance the photocatalytic activity of ZnO. Infrared spectroscopy reveals the presence of hydroxyl groups in ZnO/Zn(OH)2 nanoparticles. X-ray diffraction shows the formation of hexagonal wurtzite ZnO nanoparticles, which retain their wurtzite structure after acid treatment but additional diffractions for Zn(OH)2 are also recorded. The optical bandgap of resulting ZnO and ZnO/Zn(OH)2 nanoparticles is reduced to 3.05 and 3.08 eV, respectively. In the initial photocatalysis experiments, ZnO/Zn(OH)2 nanoparticles exhibit 3.5-times improved degradation and removal of sunset yellow dye, a model organic pollutant, from deionized water compared to pristine ZnO nanoparticles. Hence, for further studies, ZnO/Zn(OH)2 coatings are fabricated on glass slides with a uniform surface morphology as shown by the atomic force microscopy. The time-dependent UV-visible spectroscopy reveals the photocatalytic degradation of sunset yellow over the surface of ZnO/Zn(OH)2 coatings. The degradation reaction follows the pseudofirst-order mechanism with a rate constant of 2.9 × 10–2 min−1. The recyclability and stability experiments reveal the retention of appreciable photocatalytic activity of ZnO/Zn(OH)2 coatings (with >92% degradation efficiency after six successive cycles). The results are compared with recent examples from the pertinent literature. The surface hydroxyl groups on ZnO/Zn(OH)2 nanoparticles and bandgap lowering enhance the anchoring of dye molecules and electron transfer reactions.
Multi-depth evolution characteristics of soil moisture over the Tibetan Plateau in the past 70 years using reanalysis products
Authors: Liu Yangxiaoyue , Yang Yaping
Published: August 2022

Soil moisture (SM) is a crucial component of the hydrological cycle. Both the spatial–temporal distribution and the variation characteristics of SM are effective indicators of regional land surface water resource homogeneity and heterogeneity. With consideration of the crucial role of the Tibetan Plateau (TP) in the hydrological process in Asia, this study investigated the fluctuation of multi-depth soil moisture across the TP during 1950–2020 on a monthly scale against the background of global warming by using ERA5 reanalysis datasets. The correlation and potential causality between soil moisture and associated driving factors were explored. Our research revealed that the soil moisture across the TP shows a slight wetting trend at 0–100 cm depth for the past 70 years against the background of climate warming and increasing precipitation. Additionally, the wetting region (variation trend ≥ 0.005 m3/m3 per decade) had sufficient water supplementation from precipitation and a mild soil temperature increase. By comparison, there is a noteworthy warming tendency and falling precipitation in the sparsely distributed drying region (variation trend ≤ −0.005 m3/m3 per decade). In terms of vertical variation features, the temporal dynamic fluctuation of soil moisture and soil temperature evidently decreases as the depth increases, suggesting high sensitivity of the surface layer soil to atmospheric conditions. Precipitation and snowmelt preliminarily proved to be the dominant drivers causing spatial and temporal variations in soil moisture (occupying over 70% of the TP region), and bidirectional causality (ranging between 15.52% and 50.56%) was found between soil moisture and these two parameters. In summary, this study explored the spatial–temporal fluctuation in the evolutionary characteristics of SM, which is expected to advance our understanding of soil moisture dynamics under the conditions of climate change across the TP.
Using different training strategies for urban land-use classification based on convolutional neural networks
Authors: Qiu Tianqi , He Huagui , Liang Xiaojin , Chen Fei , Chen Zhaoxia , Liu Yang
Published: August 2022

Urban land-use scene classification from high-resolution remote-sensing imagery at high quality and accuracy is of paramount interest for urban planning, government policy-making and urban change detection. In recent years, urban land-use classification has become an ongoing task in areas addressable primarily by remote sensing, and numerous deep learning algorithms have achieved high performance on this task. However, both dataset and methodology problems still exist in the current approaches. Previous studies have relied on limited data sources, resulting in saturated classification results, and they have difficulty achieving comprehensive classification results. The previous methods based on convolutional neural networks (CNNs) focused primarily on model architecture rather than on the hyperparameters. Therefore, to achieve more accurate classification results, in this study, we constructed a new large dataset for urban land-use scene classification. More than thirty thousand remote sensing scene images were collected to create a dataset with balanced class samples that includes both higher intra-class variations and smaller inter-class dissimilarities than do the previously available public datasets. Then, we analysed two possible strategies for exploiting the capabilities of three existing popular CNNs on our datasets: full training and fine tuning. For each strategy, three types of learning rate decay were applied: fixed, exponential and polynomial. The experimental results indicate that fine tuning tends to be the best-performing strategy, and using ResNet-V1-50 and polynomial learning rate decay achieves the best results for the urban land-use scene classification task.
The Role of Habitat Amount and Vegetation Density for Explaining Loss of Small-Mammal Diversity in a South American Woodland Savanna
Authors: Melo Geruza L. , Cerezer Felipe O. , Sponchiado Jonas , Cáceres Nilton C.
Published: August 2022

The focus of research and conservation in tropical regions is mainly devoted to forest ecosystems, usually neglecting the processes underlying widespread, more open biomes, like savannas. Here we test a wide range of sampled woodland sites across the South American savanna for the direct and indirect effects of habitat loss and vegetation density on the diversity of small-mammal species. We quantify the direction and magnitude of the effects of habitat amount (habitat loss), vegetation density (tree or foliage density), and patch size (species-area effect) on species composition and richness. We also test whether the relative effect sizes of landscape and patch-related metrics predict a persistence gradient from habitat specialist to generalist species across 54 sites. We used structural equation models (SEM) to test our predictions. After 22,032 trap-nights considering all sampled sites and 20 small-mammal species identified, the structural equation model explained 23.5% of the variance in the richness of small-mammal species. Overall, we found that landscape-level metrics were more important in explaining species richness, with a secondary role of patch-level metrics such as vegetation density. The direct effect of local landscape was significant for explaining species richness variation, but a strong positive association between regional and local landscapes was also present. Furthermore, considering the direct and indirect paths, SEM explained 46.2% of the species composition gradient. In contrast to species richness, we recorded that the combined landscape-level and patch-level metrics are crucial to determining small-mammal species composition at savanna patches. The small mammals from the South American woodland savanna exhibit clear ecological gradients on their species composition and richness, driven by habitat specialist (e.g.,Thrichomys fosteri,Monodelphis domestica, andThylamys macrurus) and generalist (e.g.,Didelphis albiventris,Rhipidomys macrurus, andCalomys callosus) species’ responses to habitat amount and/or vegetation density, as seen in dense-forest Neotropical biomes.
Enhanced suppression of saprotrophs by ectomycorrhizal fungi under high level of nitrogen fertilization
Authors: Liang Shuang , Wang Wei , Zeng Xiaoyue , Wu Ran , Chen Weile
Published: August 2022

Ectomycorrhizal fungi (EMF) are widespread in northern conifer forests. By competing with the free-living saprotrophic fungal and bacterial communities for limited soil nitrogen, EMF are expected to suppress litter decomposition and thus drive soil carbon accumulation. The EMF may also stimulate rhizosphere microbial growth through inputs of labile plant carbon, and subsequently contribute to the soil carbon pool via microbial necromass. Here we examined the relative strength of these two potential EMF effects in a northern conifer plantation of the Saihanba Forest, the largest plantation in China. The soil fungal and bacterial biomass, as well as their respiration, were quantified within the two types of soil cores that either allow or exclude the ingrowth of EMF. We also set up a nitrogen fertilization gradient (0, 5, 10, 15 g N m–2 y–1) in this plantation to quantify the influence of external inorganic nitrogen on the EMF effects. We found evidence that EMF inhibit the overall fungal and bacteria biomass, confirming the suppression of saprotrophs by EMF. In addition, high levels of external nitrogen fertilization (15 g N m–2 y–1) might further enhance the suppression by EMF. In contrast, the presence of EMF consistently increased soil microbial respiration across all nitrogen fertilization levels, indicating that the carbon allocated to EMF could have been largely consumed by microbial respiration and contributed minimally to the accumulation of microbial biomass. Our results also indicated that the suppression of saprotrophs by EMF may play a critical role in driving continuous soil carbon accumulation in this northern pine plantation under atmospheric nitrogen deposition.
Sex- and tissue-specific expression of chemosensory receptor genes in a hawkmoth
Authors: Tom Megha Treesa , Cortés Llorca Lucas , Bucks Sascha , Bisch-Knaden Sonja , Hansson Bill S.
Published: August 2022

For the nocturnal hawkmoth Manduca sexta, olfactory and gustatory cues are essential for finding partners, food, and oviposition sites. Three chemosensory receptor families, odorant receptors (ORs), ionotropic receptors (IRs), and gustatory receptors (GRs) are involved in the detection of these stimuli. While many chemosensory receptor genes have been identified, knowledge of their expression profile in potentially chemoreceptive organs is incomplete. Here, we studied the expression patterns of chemosensory receptors in different tissues including the antennae, labial palps, proboscis, legs, wings and ovipositor. We compared the receptors’ expression in female and male moths both before and after mating by using the NanoString platform. This tool allowed us to measure expression levels of chemosensory receptor genes in a single reaction using probes designed against 71 OR, 29 IR and 49 GR transcripts. In all tissues investigated, we detected expression of genes from all three receptor families. The highest number of receptors was detected in the antennae (92), followed by the ovipositor (59), while the least number was detected in the hindlegs (21). The highest number of OR genes were expressed in the antennae (63), of which 24 were specific to this main olfactory organ. The highest number of IRs were also expressed in the antennae (16), followed by the ovipositor (15). Likewise, antennae and ovipositor expressed the highest number of GRs (13 and 14). Expression of the OR co-receptor MsexORCo, presumably a prerequisite for OR function, was found in the antennae, labial palps, forelegs and ovipositor. IR co-receptors MsexIR25a and MsexIR76b were expressed across all tested tissues, while expression of the IR co-receptor MsexIR8a was restricted to antennae and ovipositor. Comparing the levels of all 149 transcripts across the nine tested tissues allowed us to identify sex-biased gene expression in the antennae and the legs, two appendages that are also morphologically different between the sexes. However, none of the chemosensory receptors was differentially expressed based on the moths’ mating state. The observed gene expression patterns form a strong base for the functional characterization of chemosensory receptors and the understanding of olfaction and gustation at the molecular level in M. sexta.
Redefining “abandoned” agricultural land in the context of reforestation
Authors: Holl Karen D. , Ashton Mark S. , Bukoski Jacob J. , Culbertson Katherine A. , Curran Sara R. , Harris Thomas B. , Potts Matthew D. , Valverde Yesenia L. , Vincent Jeffrey R.
Published: August 2022

Global mapping efforts to date have relied on vague and oversimplified definitions of “abandoned” agricultural land which results in overestimates of the land area that is likely to support persistent increases in forest cover and associated carbon sequestration. We propose a new conceptualization of abandoned agricultural land that incorporates changes in landholding status over time into determining whether land should be considered as abandoned. In order to develop more realistic estimates of the amount of land available for reforestation, we recommend clearly defining how abandoned land is categorized, discerning who owns and has rights to use the land, and combining remotely sensed data with household/stakeholder surveys to understand landowner motivations for not cropping or grazing land.
Transparent human – (non-) transparent technology? The Janus-faced call for transparency in AI-based health care technologies
Authors: Ott Tabea , Dabrock Peter
Published: August 2022

The use of Artificial Intelligence and Big Data in health care opens up new opportunities for the measurement of the human. Their application aims not only at gathering more and better data points but also at doing it less invasive. With this change in health care towards its extension to almost all areas of life and its increasing invisibility and opacity, new questions of transparency arise. While the complex human-machine interactions involved in deploying and using AI tend to become non-transparent, the use of these technologies makes the patient seemingly transparent. Papers on the ethical implementation of AI plead for transparency but neglect the factor of the “transparent patient” as intertwined with AI. Transparency in this regard appears to be Janus-faced: The precondition for receiving help - e.g., treatment advice regarding the own health - is to become transparent for the digitized health care system. That is, for instance, to donate data and become visible to the AI and its operators. The paper reflects on this entanglement of transparent patients and (non-) transparent technology. It argues that transparency regarding both AI and humans is not an ethical principle per se but an infraethical concept. Further, it is no sufficient basis for avoiding harm and human dignity violations. Rather, transparency must be enriched by intelligibility following Judith Butler’s use of the term. Intelligibility is understood as an epistemological presupposition for recognition and the ensuing humane treatment. Finally, the paper highlights ways to testify intelligibility in dealing with AI in health care ex ante, ex post, and continuously.
AttnTAP: A Dual-input Framework Incorporating the Attention Mechanism for Accurately Predicting TCR-peptide Binding
Authors: Xu Ying , Qian Xinyang , Tong Yao , Li Fan , Wang Ke , Zhang Xuanping , Liu Tao , Wang Jiayin
Published: August 2022

T-cell receptors (TCRs) are formed by random recombination of genomic precursor elements, some of which mediate the recognition of cancer-associated antigens. Due to the complicated process of T-cell immune response and limited biological empirical evidence, the practical strategy for identifying TCRs and their recognized peptides is the computational prediction from population and/or individual TCR repertoires. In recent years, several machine/deep learning-based approaches have been proposed for TCR-peptide binding prediction. However, the predictive performances of these methods can be further improved by overcoming several significant flaws in neural network design. The interrelationship between amino acids in TCRs is critical for TCR antigen recognition, which was not properly considered by the existing methods. They also did not pay more attention to the amino acids that play a significant role in antigen-binding specificity. Moreover, complex networks tended to increase the risk of overfitting and computational costs. In this study, we developed a dual-input deep learning framework, named AttnTAP, to improve the TCR-peptide binding prediction. It used the bi-directional long short-term memory model for robust feature extraction of TCR sequences, which considered the interrelationships between amino acids and their precursors and postcursors. We also introduced the attention mechanism to give amino acids different weights and pay more attention to the contributing ones. In addition, we used the multilayer perceptron model instead of complex networks to extract peptide features to reduce overfitting and computational costs. AttnTAP achieved high areas under the curves (AUCs) in TCR-peptide binding prediction on both balanced and unbalanced datasets (higher than 0.838 on McPAS-TCR and 0.908 on VDJdb). Furthermore, it had the highest average AUCs in TPP-I and TPP-II tasks compared with the other five popular models (TPP-I: 0.84 on McPAS-TCR and 0.894 on VDJdb; TPP-II: 0.837 on McPAS-TCR and 0.893 on VDJdb). In conclusion, AttnTAP is a reasonable and practical framework for predicting TCR-peptide binding, which can accelerate identifying neoantigens and activated T cells for immunotherapy to meet urgent clinical needs.
Case Report: Long-term follow-up of desert hedgehog variant caused 46, XY gonadal dysgenesis with multiple complications in a Chinese child
Authors: Pan Lili , Li Zhuoguang , Su Zhe , Su Wei , Zheng Rongfei , Chen Weiyan , He Xuezhi , Song Jianming , Li Shoulin , Wen Pengqiang
Published: August 2022

Background: Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A DHH variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications.

Case presentation: Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the SRY gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in DHH exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers.

Conclusion: In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a DHH homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.
Genome-wide identification, structural analysis and expression profiles of short internodes related sequence gene family in quinoa
Authors: Zhu Xiaolin , Wang Baoqiang , Wang Xian , Wei Xiaohong
Published: August 2022

Based on the whole genome data information of Chenopodium quinoa Willd, the CqSRS gene family members were systematically identified and analyzed by bioinformatics methods, and the responses of CqSRS genes to NaCl (100 mmol/L), salicylic acid (200 umol/L) and low temperature (4°C) were detected by qRT-PCR. The results showed that a total of 10 SHI related sequence genes were identified in quinoa, and they were distributed on 9 chromosomes, and there were four pairs of duplicated genes. The number of amino acids encoded ranged from 143 aa to 370 aa, and the isoelectric point ranged from 4.81 to 8.90. The secondary structure was mainly composed of random coil (Cc). Most of the SRS gene encoding proteins were located in the cytoplasm (5 CqSRS). Phylogenetic analysis showed that the CqSRS genes were divided into three groups, and the gene structure showed that the number of exons of CqSRS was between two-five. Promoter analysis revealed that there are a total of 44 elements related to plant hormone response elements, light response elements, stress response elements and tissue-specific expression in the upstream regin of the gene. Protein interaction showed that all 10 CqSRS proteins appeared in the known protein interaction network diagram in Arabidopsis. Expression profile analysis showed that CqSRS genes had different expression patterns, and some genes had tissue-specific expression. qRT-PCR showed that all SRS family genes responded to ABA、NaCl、drought and low-temperature treatments, but the expression levels of different CqSRS genes were significantly different under various stresses. This study lays a foundation for further analyzed the function of CqSRS genes.
Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics
Authors: Aychoua Nancy , Schiff Elena , Malka Samantha , Tailor Vijay K , Chan Hwei Wuen , Oluonye Ngozi , Theodorou Maria , Moosajee Mariya
Published: August 2022

Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is predominantly caused by mutations in the FRMD7 gene. IIN poses a diagnostic challenge as underlying pre-symptomatic “multisystem” disorders varying from benign to life-threatening should first be ruled out before nystagmus can be labeled as idiopathic. A multidisciplinary approach including multimodal ocular investigations and next-generation sequencing with whole-genome sequencing (WGS) or targeted gene panel testing is required to delineate the exact etiology. We report the clinical and genetic outcomes of 22 patients, from 22 unrelated families of diverse ethnicities, with IIN seen in the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between 2016 and 2022. Thirty-six percent (8/22) received a confirmed molecular diagnosis with eight mutations identified in two genes (seven in FRMD7 including one novel variant c.706_707del; p. [Lys236Alafs*66], and one in GPR143). This study expands the mutational spectrum of IIN and highlights the significant role of an integrated care pathway and broader panel testing in excluding underlying pathologies.
Aspergillus oryzae accelerates the conversion of ergosterol to ergosterol peroxide by efficiently utilizing cholesterol
Authors: Qiu Shangkun , Liu Qicong , Yuan Ya , Zhou Hong , Zeng Bin
Published: August 2022

It is well-known that excessive cholesterol leads to hypercholesterolemia, arteriosclerosis, coronary heart disease, stroke, and other diseases, which seriously threatens human health. Lactobacillus, a prokaryote, is reported to utilize cholesterol in the environment. However, little research focuses on the cholesterol utilization by eukaryote. Hence, the objectives of the present study were to investigate the mechanism of cholesterol utilization by the eukaryote and determine the role of oxysterol binding protein in this process. Our results showed for the first time that Aspergillus oryzae, a food-safe filamentous fungus, can utilize cholesterol efficiently. Our results also demonstrated that cholesterol utilization by A. oryzae might promote the conversion of ergosterol to ergosterol peroxide. Osh3, an oxysterol binding protein, can bind sterols (e.g., cholesterol, ergosterol, and ergosterol peroxide) and plays an important role in sterols transportation. This research is of considerable significance for developing low-fat food and cholesterol-lowering probiotics.
Dynamic transcriptome analysis suggests the key genes regulating seed development and filling in Tartary buckwheat (Fagopyrum tataricum Garetn.)
Authors: Jiang Liangzhen , Liu Changying , Fan Yu , Wu Qi , Ye Xueling , Li Qiang , Wan Yan , Sun Yanxia , Zou Liang , Xiang Dabing , Lv Zhibin
Published: August 2022

Tartary buckwheat is highly attractive for the richness of nutrients and quality, yet post-embryonic seed abortion greatly halts the yield. Seed development is crucial for determining grain yield, whereas the molecular basis and regulatory network of Tartary buckwheat seed development and filling is not well understood at present. Here, we assessed the transcriptional dynamics of filling stage Tartary buckwheat seeds at three developmental stages by RNA sequencing. Among the 4249 differentially expressed genes (DEGs), genes related to seed development were identified. Specifically, 88 phytohormone biosynthesis signaling genes, 309 TFs, and 16 expansin genes participating in cell enlargement, 37 structural genes involved in starch biosynthesis represented significant variation and were candidate key seed development genes. Cis-element enrichment analysis indicated that the promoters of differentially expressed expansin genes and starch biosynthesis genes are rich of hormone-responsive (ABA-, AUX-, ET-, and JA-), and seed growth-related (MYB, MYC and WRKY) binding sites. The expansin DEGs showed strong correlations with DEGs in phytohormone pathways and transcription factors (TFs). In total, phytohormone ABA, AUX, ET, BR and CTK, and related TFs could substantially regulate seed development in Tartary buckwheat through targeting downstream expansin genes and structural starch biosynthetic genes. This transcriptome data could provide a theoretical basis for improving yield of Tartary buckwheat.
Interferon gamma as an immune modulating adjunct therapy for invasive mucormycosis after severe burn – A case report
Authors: Tawfik Dina M. , Dereux Caroline , Tremblay Jan-Alexis , Boibieux Andre , Braye Fabienne , Cazauran Jean-Baptiste , Rabodonirina Meja , Cerrato Elisabeth , Guichard Audrey , Venet Fabienne , Monneret Guillaume , Payen Didier , Lukaszewicz Anne-Claire , Textoris Julien
Published: August 2022

Background

Mucormycosis is a deadly fungal infection that mainly affects severely immunocompromised patients. We report herein the case of a previously immunocompetent adult woman who developed invasive cutaneous mucormycosis after severe burn injuries. Interferon-gamma (IFN-γ) treatment was added after failure of conventional treatment and confirmation of a sustained profound immunodepression. The diagnosis was based on a reduced expression of HLA-DR on monocytes (mHLA-DR), NK lymphopenia and a high proportion of immature neutrophils. The immune-related alterations were longitudinally monitored using panels of immune-related biomarkers.

Results

Initiation of IFN-γ was associated with a rapid clinical improvement and a subsequent healing of mucormycosis infection, with no residual fungi at the surgical wound repair. The serial immunological assessment showed sharp improvements of immune parameters: a rapid recovery of mHLA-DR and of transcriptomic markers for T-cell proliferation. The patient survived and was later discharged from the ICU.

Conclusion

The treatment with recombinant IFN-γ participated to the resolution of a progressively invasive mucormycosis infection, with rapid improvement in immune parameters. In the era of precision medicine in the ICU, availability of comprehensive immune monitoring tools could help guiding management of refractory infections and provide rationale for immune stimulation strategies in these high risk patients.
Peripheral cytokine levels as novel predictors of survival in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Mao Xin-Cheng , Yang Chun-Cheng , Yang Ya-Fei , Yan Lun-Jie , Ding Zi-Niu , Liu Hui , Yan Yu-Chuan , Dong Zhao-Ru , Wang Dong-Xu , Li Tao
Published: August 2022

Background

Early identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear.

Methods

A systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1β, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-β) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed.

Results

Twenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21–2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67–2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98–2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70–2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method.

Conclusion

The peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment.
Characterization of an intelectin-1 (Itln1) knockout mouse model
Authors: Nonnecke Eric B. , Castillo Patricia A. , Akahoshi Douglas T. , Goley Stephanie M. , Bevins Charles L. , Lönnerdal Bo
Published: August 2022

Intelectins are carbohydrate-binding proteins implicated in innate immunity and highly conserved across chordate evolution, including both ascidians and humans. Human intelectin-1 (ITLN1) is highly abundant within the intestinal mucosa and binds microbial but not host glycans. Genome-wide association studies identified SNPs in ITLN1 that are linked to susceptibility for Crohn’s disease. Moreover, ITLN1 has been implicated in the pathophysiology of obesity and associated metabolic disease. To gain insight on biological activities of human ITLN1 in vivo, we developed a C57BL/6 mouse model genetically targeting the gene encoding the functional mouse ortholog. In wild-type C57BL/6 mice, both mRNA and protein analysis showed high expression of Itln1 in the small intestine, but manifold lower levels in colon and other extraintestinal tissues. Whereas intestinal expression of human ITLN1 localizes to goblet cells, our data confirm that mouse Itln1 is expressed in Paneth cells. Compared to wild-type littermate controls, mice homozygous for the Itln1 hypomorphic trapping allele had reduced expression levels of Itln1 expression (~10,000-fold). The knockout mice exhibited increased susceptibility in an acute model of experimentally induced colitis with 2% w/v dextran sulfate sodium (DSS). In a model of chronic colitis using a lower dose of DSS (1.5% w/v), which enabled a detailed view of disease activity across a protracted period, no differences were observed in body weight, fecal texture, hemoccult scores, food/water intake, or colon length at necropsy, but there was a statistically significant genotype over time effect for the combined fecal scores of disease activity. In model of diet-induced obesity, using two western-style diets, which varied in amounts of sugar (as sucrose) and saturated fat (as lard), mice with Itln1 expression ablated showed no increased susceptibility, in terms of weight gain, food intake, plasma markers of obesity compared to wildtype littermates. While the mouse genetic knockout model for Itln1 holds promise for elucidating physiological function(s) for mammalian intelectins, results reported here suggest that Itln1, a Paneth cell product in C57BL/6 mice, likely plays a minor role in the pathophysiology of chemically induced colitis or diet-induced obesity.
Multiple myeloma metabolism – a treasure trove of therapeutic targets?
Authors: Roman-Trufero Monica , Auner Holger W. , Edwards Claire M.
Published: August 2022

Multiple myeloma is an incurable cancer of plasma cells that is predominantly located in the bone marrow. Multiple myeloma cells are characterized by distinctive biological features that are intricately linked to their core function, the assembly and secretion of large amounts of antibodies, and their diverse interactions with the bone marrow microenvironment. Here, we provide a concise and introductory discussion of major metabolic hallmarks of plasma cells and myeloma cells, their roles in myeloma development and progression, and how they could be exploited for therapeutic purposes. We review the role of glucose consumption and catabolism, assess the dependency on glutamine to support key metabolic processes, and consider metabolic adaptations in drug-resistant myeloma cells. Finally, we examine the complex metabolic effects of proteasome inhibitors on myeloma cells and the extracellular matrix, and we explore the complex relationship between myeloma cells and bone marrow adipocytes.
Core immune cell infiltration signatures identify molecular subtypes and promote precise checkpoint immunotherapy in cutaneous melanoma
Authors: Zhu Zheng , Li Guoyin , Li Zhenning , Wu Yinghua , Yang Yan , Wang Mingyang , Zhang Huihua , Qu Hui , Song Zewen , He Yuanmin
Published: August 2022

Yutao Wang, China Medical University, ChinaThe tumor microenvironment (TME) has been shown to impact the prognosis of tumors in patients including cutaneous melanoma (CM); however, not all components of TME are important. Given the aforementioned situation, the functional immune cell contents correlated with CM patient prognosis are needed to optimize present predictive models and reflect the overall situation of TME. We developed a novel risk score named core tumor-infiltrating immune cell score (cTICscore), which showed certain advantages over existing biomarkers or TME-related signatures in predicting the prognosis of CM patients. Furthermore, we explored a new gene signature named cTILscore−related module gene score (cTMGs), based on four identified TME-associated genes (GCH1, GZMA, PSMB8, and PLAAT4) showing a close correlation with the cTICscore, which was generated by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis to facilitate clinical application. Patients with low cTMGs had significantly better overall survival (OS, P = 0.002,< 0.001, = 0.002, and = 0.03, respectively) in the training and validating CM datasets. In addition, the area under the curve values used to predict the immune response in four CM cohorts were 0.723, 0.723, 0.754, and 0.792, respectively, and that in one gastric cohort was 0.764. Therefore, the four-gene signature, based on cTICscore, might improve prognostic information, serving as a predictive tool for CM patients receiving immunotherapy.cutaneous melanoma, tumor microenvironment, prognosis, immunotherapy, cTICscore
Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer
Authors: Zhou Yanling , Xiao Liang , Long Guo , Cao Jing , Liu Shuang , Tao Yongguang , Zhou Ledu , Tang Jianing
Published: August 2022

Breast cancer is a malignancy with the highest incidence and mortality in women worldwide. Senescence is a model of arrest in the cell cycle, which plays an important role in tumor progression, while the prognostic value of cellular senescence-related genes (SRGs) in evaluating immune infiltration and clinical outcomes of breast cancer needs further investigation. In the present study, we identified two distinct molecular subtypes according to the expression profiles of 278 SRGs. We further explored the dysregulated pathways between the two subtypes and constructed a microenvironmental landscape of breast cancer. Subsequently, we established a senescence-related scoring signature based on the expression of four SRGs in the training set (GSE21653) and validated its accuracy in two validation sets (GSE20685 and GSE25055). In the training set, patients in the high-risk group had a worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed that risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The prognostic value of this signature was further confirmed in the validation sets. We also observed that a lower risk score was associated with a higher pathological response rate in patients with neoadjuvant chemotherapy. We next performed functional experiments to validate the results above. Our study demonstrated that these cellular senescence patterns effectively grouped patients at low or high risk of disease recurrence and revealed their potential roles in the tumor–immune–stromal microenvironment. These findings enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the prognosis of breast cancer patients.
Identification of key molecules in COVID-19 patients significantly correlated with clinical outcomes by analyzing transcriptomic data
Authors: Dong Zehua , Yan Qiyu , Cao Wenxiu , Liu Zhixian , Wang Xiaosheng
Published: August 2022

Background

Although several key molecules have been identified to modulate SARS-CoV-2 invasion of human host cells, the molecules correlated with outcomes in COVID-19 caused by SARS-CoV-2 infection remain insufficiently explored.

Methods

This study analyzed three RNA-Seq gene expression profiling datasets for COVID-19 and identified differentially expressed genes (DEGs) between COVID-19 patients and normal people, commonly in the three datasets. Furthermore, this study explored the correlation between the expression of these genes and clinical features in COVID-19 patients.

Results

This analysis identified 13 genes significantly upregulated in COVID-19 patients’ leukocyte and SARS-CoV-2-infected nasopharyngeal tissue compared to normal tissue. These genes included OAS1, OAS2, OAS3, OASL, HERC6, SERPING1, IFI6, IFI44, IFI44L, CMPK2, RSAD2, EPSTI1, and CXCL10, all of which are involved in antiviral immune regulation. We found that these genes’ downregulation was associated with worse clinical outcomes in COVID-19 patients, such as intensive care unit (ICU) admission, mechanical ventilatory support (MVS) requirement, elevated D-dimer levels, and increased viral loads. Furthermore, this analysis identified two COVID-19 clusters based on the expression profiles of the 13 genes, termed COV-C1 and COV-C2. Compared with COV-C1, COV-C2 more highly expressed the 13 genes, had stronger antiviral immune responses, were younger, and displayed more favorable clinical outcomes.

Conclusions

A strong antiviral immune response is essential in reducing severity of COVID-19.
Innate immune responses to three doses of the BNT162b2 mRNA SARS-CoV-2 vaccine
Authors: Saresella Marina , Piancone Federica , Marventano Ivana , Hernis Ambra , Trabattoni Daria , Invernizzi Mattia , La Rosa Francesca , Clerici Mario
Published: August 2022

To explore the effects of SARS-CoV-2-mRNA vaccines on innate immune responses we enrolled 58 individuals who received 3 doses of the BNT162b2 vaccine in a longitudinal study; 45 of these individuals had never been SARS-CoV-2 infected. Results showed that vaccination significantly increased: 1) classical and intermediate inflammatory monocytes, 2) CD56bright, CD56dim, and CD56dim/CD16dim NK cells, and 3) IFN-γ+ ;production as well as perforin and granzyme content by NK cells. Vaccination also reduced expression of the NK inhibitory receptor ILT-2, increasing that of the stimulatory molecule 2DS2. These effects were long-lasting and were boosted by every vaccine dose. Notably, ILT-2 expressing NK cells were reduced even more robustly in COVID-19-recovereed vaccines. BNT162b1 mRNA vaccine is known to induce potent adaptive immune responses; results herein show its ability to modulate innate immune responses as well, offering further support to the indication to proceed with worldwide vaccination efforts to end the SARS-CoV-2 pandemic.
Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy
Authors: Brochet Pauline , Ianni Barbara Maria , Laugier Laurie , Frade Amanda Farage , Silva Nunes João Paulo , Teixeira Priscila Camillo , Mady Charles , Ferreira Ludmila Rodrigues Pinto , Ferré Quentin , Santos Ronaldo Honorato Barros , Kuramoto Andreia , Cabantous Sandrine , Steffen Samuel , Stolf Antonio Noedir , Pomerantzeff Pablo , Fiorelli Alfredo Inacio , Bocchi Edimar Alcides , Pissetti Cristina Wide , Saba Bruno , Cândido Darlan da Silva , Dias Fabrício C. , Sampaio Marcelo Ferraz , Gaiotto Fabio Antônio , Marin-Neto José Antonio , Fragata Abílio , Zaniratto Ricardo Costa Fernandes , Siqueira Sergio , Peixoto Giselle De Lima , Rigaud Vagner Oliveira-Carvalho , Bacal Fernando , Buck Paula , Almeida Rafael Ribeiro , Lin-Wang Hui Tzu , Schmidt André , Martinelli Martino , Hirata Mario Hiroyuki , Donadi Eduardo Antonio , Costa Pereira Alexandre , Rodrigues Junior Virmondes , Puthier Denis , Kalil Jorge , Spinelli Lionel , Cunha-Neto Edecio , Chevillard Christophe
Published: August 2022

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS’s DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.