bluuebunny/crossref_metadata_2025 huggingface dataset:
Nearly free silanols drive the interaction of crystalline silica polymorphs with membranes: Implications for mineral toxicity
Authors: Pavan Cristina , Escolano-Casado Guillermo , Bellomo Chiara , Cananà Stefania , Tomatis Maura , Leinardi Riccardo , Mino Lorenzo , Turci Francesco
Published: January 2023

Crystalline silica (CS) is a well-known hazardous material that causes severe diseases including silicosis, lung cancer, and autoimmune diseases. However, the hazard associated to crystalline silica is extremely variable and depends on some specific characteristics, including crystal structure and surface chemistry. The crystalline silica polymorphs share the SiO2 stoichiometry and differentiate for crystal structure. The different crystal lattices in turn expose differently ordered hydroxyl groups at the crystal surface, i.e., the silanols. The nearly free silanols (NFS), a specific population of weakly interacting silanols, have been recently advanced as the key surface feature that governs recognition mechanisms between quartz and cell membrane, initiating toxicity. We showed here that the nearly free silanols occur on the other crystalline silica polymorphs and take part in the molecular interactions with biomembranes. A set of crystalline silica polymorphs, including quartz, cristobalite, tridymite, coesite, and stishovite, was physico-chemically characterized and the membranolytic activity was assessed using red blood cells as model membranes. Infrared spectroscopy in highly controlled conditions was used to profile the surface silanol topochemistry and the occurrence of surface nearly free silanols on crystalline silica polymorphs. All crystalline silica polymorphs, but stishovite were membranolytic. Notably, pristine stishovite did not exhibited surface nearly free silanols. The topochemistry of surface silanols was modulated by thermal treatments, and we showed that the occurrence of nearly free silanols paralleled the membranolytic activity for the crystalline silica polymorphs. These results provide a comprehensive understanding of the structure-activity relationship between nearly free silanols and membranolytic activity of crystalline silica polymorphs, offering a possible clue for interpreting the molecular mechanisms associated with silica hazard and bio-minero-chemical interfacial phenomena, including prebiotic chemistry.
Sandwich-type architecture film based on WS2 and ultrafast self-expanded and reduced graphene oxide in a Li-ion battery
Authors: Wenelska Karolina , Kędzierski Tomasz , Bęben Damian , Mijowska Ewa
Published: January 2023

Since its discovery, graphene has been widely considered a great material that has advanced the Li-ion battery field and allowed development in its performance. However, most current graphene-related research is focused on graphene-based composites as electrode materials, highlighting the role of graphene in composite materials. Herein, we focused on a three-dimensional composite film with unique sandwich-type architecture based on ultrafast self-expanded and reduced graphene oxide (userGO) and exfoliated WS2. This strategy allows non-active agents [e.g., carbon black and poly (vinylidene fluoride)] free electrodes in LIBs in the form of a film. The ultra-quick exothermal nature of the USER reaction allows the rapid release of internally generated gases to create highly porous channels inside the film. Hence, the improved Li-ion transport in the LIBs boosted the electrochemical performance of both film components (ex-WS2 and reduced graphene), resulting in a high specific capacity of 762 mAh/g at .05 A/g and high Coulombic efficiency (101%) after 1,000 cycles. Overall, userGO showed the highest capacity at a low current, and ex-WS2 provided a higher reversible capacity. These results showed that the expanded graphene layer is an excellent shield for ex-WS2 to protect against pulverization, promoting both stability and capacity.
Evaluation of feature extraction algorithms for oceanic internal waves based on nighttime detection data of spaceborne low light imager
Authors: Li Hao , Hu Shensen , Ma Shuo , Tan Zhonghui , Ai Weihua , Yan Wei
Published: January 2023

The day/night band channel on the JPSS series of satellites can detect the light and dark fringes of oceanic internal waves due to the reflectivity difference caused by the roughness of the sea surface under moon flare conditions. After optical imaging of oceanic internal waves, three image processing algorithms, i.e., the two-dimensional S transform, windowed Fourier transform, and wavelet packet transform methods, can be used to extract the parameter features of horizontal wavelength and propagation direction. The wave domain with known parameters is established through data simulation, and both image quality and image resolution are analyzed to assess algorithm performance in terms of relative errors. Finally, the experimental conclusions are verified in two examples of satellite observations in the South China Sea in 2020. We found that the windowed Fourier transform and wavelet packet transform methods exhibit better noise immunity, and the two-dimensional S transform method exhibits less calculation error and is more applicable to cases with small wavelengths. For large wavelengths, the windowed Fourier transform method is more suitable for calculating the horizontal wavelength, and the wavelet packet transform method is more suitable for calculating the propagation direction. By evaluating the applicability of these algorithms, this study provides a theoretical basis to support the analysis and processing of internal wave characteristics in future.
Numerical simulations of fatigue failure processes in intermittent jointed rock masses under the action of repeated stress waves
Authors: Ma Shuyin , Xue Sheng , Pan Cheng
Published: January 2023

To study the fatigue failure of an intermittent jointed rock mass under repeated stress waves, numerical models of jointed rock masses with different joint angles were created using Autodyne software, and crack propagation behavior was simulated using the Drucker–Prager strength model and cumulative damage failure criteria. In this numerical simulation, the influence of stress wave amplitude and the mode of disturbance on fatigue failure of the rock mass were analyzed. The simulation results showed a significant difference between the failure process of jointed rock masses subjected to repeated stress waves and those exposed to a single stress wave, including crack initiation locations, propagation paths, and rock mass failure patterns. With increasing angles of inclination, the fatigue life of the rock mass first decreased and then increased under repeated stress waves. As the joint inclination angle, β, increased from 20° to 50°, it had a significant influence on the fatigue life of the rock mass, which decreased rapidly with increases in β. The variation in the disturbance form (the change in amplitude of the stress waves from small to large, or from large to small) did not affect the final macro failure pattern of the rock mass; but the extent of damage to the rock mass was affected.
Experimental study on the fine-scale characteristics of a geogrid-gravelly soil reinforcement influence zone
Authors: Liu Jie , Gao Bin , Du Haoyuan , Bai Qiyu , Yang Haoyuan , Zhong Bo , Wang Bin
Published: January 2023

Based on a specially designed visualization pullout system and digital photographic measurement technology, geogrid pullout tests were conducted by varying the top load, geogrid type, coarse grain content, and particle shape. The evolution and distribution of the reinforcement influence zone and the soil particle displacement field were analyzed, and the effects of various factors on the formation speed of the reinforcement influence zone, gradient layer thickness, and fine-scale particle displacement characteristics were discussed. The study shows that the reinforcement influence zone’s basic form and particle displacement direction do not change with pullout displacement after it is fully developed. The displacement layers in the influence zone are centered at the reinforced soil interface and are distributed in a diffusion gradient. The thickness of each gradient layer in the upper influence zone is greater than that in the lower influence zone. The greater the normal load is, the smaller the particle displacement and thickness of each gradient layer, and the slower the formation of the reinforcement influence zone. Using high-strength geogrids and geogrids with nodes can increase the upper interface thickness and improve the reinforcement influence zone’s formation speed. Horizontal ribs play a major role in forming the reinforcement influence zone, while longitudinal ribs mainly affect the formation speed. The indirect reinforcement effect of the geogrid on angular gravel soil is better than that on pebble soil. As the coarse grain content in the fill increases from 20% to 30%, the reinforcement influence zone forms faster, and the particle displacement of each gradient layer is smaller. When the coarse grain content increases from 30% to 35%, there is no significant change in the forming rate of the reinforcement influence zone.
Anisotropic structure of the Australian continent
Authors: Birkey Andrew , Ford Heather A.
Published: January 2023

The Australian continent preserves some of the oldest lithosphere on Earth in the Yilgarn, Pilbara, and Gawler Cratons. In this study we present shear wave splitting and Ps receiver function results at long running stations across the continent. We use these results to constrain the seismic anisotropic structure of Australia’s cratons and younger Phanerozoic Orogens. For shear wave splitting analysis, we utilize SKS and SKKS phases at 35 broadband stations. For Ps receiver function analysis, which we use to image horizontal boundaries in anisotropy, we utilize 14 stations. Shear wave splitting results at most stations show strong variations in both orientation of the fast direction and delay time as a function of backazimuth, an indication that multiple layers of anisotropy are present. In general, observed fast directions do not appear to be the result of plate motion alone, nor do they typically follow the strike of major tectonic/geologic features at the surface, although we do point out several possible exceptions. Our Ps receiver function results show significant variations in the amplitude and polarity of receiver functions with backazimuth at most stations across Australia. In general, our results do not show evidence for distinctive boundaries in seismic anisotropy, but instead suggest heterogenous anisotropic structure potentially related to previously imaged mid-lithospheric discontinuities. Comparison of Ps receiver function and shear wave splitting results indicates the presence of laterally variable and vertically layered anisotropy within both the thicker cratonic lithosphere to the west, as well as the Phanerozoic east. Such complex seismic anisotropy and seismic layering within the lithosphere suggests that anisotropic fabrics may be preserved for billions of years and record ancient events linked to the formation, stabilization, and evolution of cratonic lithosphere in deep time.
Contribution of soluble organic matter to hydrocarbon generation in saline lacustrine source rocks: Evidence from thermal simulation experiments
Authors: Xing Lantian , Xu Li
Published: January 2023

Soluble organic matter generally exists in the source rocks of saline lacustrine basins. In this paper, we quantified the contribution of soluble organic matter to hydrocarbon generation based on thermal simulation experiments using a saline lacustrine source rock from the Qaidam Basin. Our results show that the yields of gaseous and liquid hydrocarbons in the thermal simulation products are greatly improved in the presence of soluble organic matter. As a comparison, the maximum yields of gaseous and liquid hydrocarbons in series C (without soluble organic matter) were 270 mg/gTOC and 329.78 mg/gTOC, respectively, while in series A (with soluble organic matter) they were 364 and 602.98 mg/gTOC, respectively. The proportion of isoprenoids and n-alkanes in the products also increased from approximately 3%–40%. Meanwhile, the presence of soluble organic matter reduced the temperature corresponding to the hydrocarbon generation peak from 375 to 250°C. Moreover, the presence of soluble organic matter also had a remarkable change on the stable carbon isotope composition of methane, resulting in more 12C enrichment with a range of 2.24‰–5.25‰. The combined evidence indicates that soluble organic matter can promote the formation of immature‒low maturity oil in source rocks.
Methylation status of hypothalamic Mkrn3 promoter across puberty
Authors: Fanis Pavlos , Morrou Maria , Tomazou Marios , Michailidou Kyriaki , Spyrou George M. , Toumba Meropi , Skordis Nicos , Neocleous Vassos , Phylactou Leonidas A.
Published: January 2023

Makorin RING finger protein 3 (MKRN3) is an important factor located on chromosome 15 in the imprinting region associated with Prader-Willi syndrome. Imprinted MKRN3 is expressed in hypothalamic regions essential for the onset of puberty and mutations in the gene have been found in patients with central precocious puberty. The pubertal process is largely controlled by epigenetic mechanisms that include, among other things, DNA methylation at CpG dinucleotides of puberty-related genes. In the present study, we investigated the methylation status of the Mkrn3 promoter in the hypothalamus of the female mouse before, during and after puberty. Initially, we mapped the 32 CpG dinucleotides in the promoter, the 5’UTR and the first 50 nucleotides of the coding region of the Mkrn3 gene. Moreover, we identified a short CpG island region (CpG islet) located within the promoter. Methylation analysis using bisulfite sequencing revealed that CpG dinucleotides were methylated regardless of developmental stage, with the lowest levels of methylation being found within the CpG islet region. In addition, the CpG islet region showed significantly lower methylation levels at the pre-pubertal stage when compared with the pubertal or post-pubertal stage. Finally, in silico analysis of transcription factor binding sites on the Mkrn3 CpG islet identified the recruitment of 29 transcriptional regulators of which 14 were transcriptional repressors. Our findings demonstrate the characterization and differential methylation of the CpG dinucleotides located in the Mkrn3 promoter that could influence the transcriptional activity in pre-pubertal compared to pubertal or post-pubertal period. Further studies are needed to clarify the possible mechanisms and effects of differential methylation of the Mkrn3 promoter.
Composite model predictive control for the boost converter and two-phase interleaved boost converter
Authors: Samad Muhammad Adnan , Xia Yuanqing , Manzoor Tayyab , Mehmood Kashif , Saleem Adeel , Milyani Ahmad H. , Azhari Abdullah Ahmed
Published: January 2023

This article compares the conventional model predictive control (MPC) and active disturbance rejection control (ADRC) with a novel MPADRC technique for controlling a non-minimum phase behavior in the DC–DC boost converter. The control of the boost converter is challenging as it is nonlinear, and it shows non-minimum phase behavior in a continuous conduction mode (CCM). Moreover, in this article, the comparison is presented for the boost converter and the two-phase interleaved boost converter using MPC and ADRC, and the effectiveness of the interleaving technique is shown. Finally, it is proved that the interleaving method has much more efficiency and less output ripple than the simple boost converter. To conclude, a novel technique has been introduced that combines both the techniques, that is, MPC and ADRC, in the outer and inner loop with a boost converter, respectively, and the response is clearly the best when compared to the said techniques individually. The overall impact of this technique includes the advantages of both the techniques, that is, the use of MPC allows us to optimize the current value by predicting the future values, and the use of ADRC ensures that the disturbance factor is well tackled and cancels the effect caused by all the disturbances including ignored quantities as well.
Research on power trade potential and power balance between Lancang-Mekong countries and southern China under long-term operation simulation
Authors: Hao Zhang , Hai Lu , Enbo Luo , Yanting Huang , Zhi Wu , Chong Tang , Wenmeng Zhao , Guo Xie
Published: January 2023

In order to further promote the interconnection development and construction of the power grids between the Lancang-Mekong countries and Southern China region and facilitate multilateral energy interaction, an assessment mechanism of the power balance and power trade potential between the two areas under long-term operation simulation is proposed. The mechanism first analyzes the energy supply structure, energy use forms, cross-border transmission capacity, and multi-area power trade potential of the power grids of the Lancang-Mekong countries and Southern China. Secondly, a power and electricity optimization model considering the long-period operation characteristics of generating units and regional interconnection transmission constraints is constructed, which can optimize the solution of a typical time-series operation scenario of 8760 h a year and improve the accuracy of regional power trade potential analysis. The results show that the Lancang-Mekong countries and the southern region of China have a significant potential for power trading, and the construction of a unified power trading market is vital for promoting the optimal allocation of power resources, achieving power balance, increasing the proportion of energy consumption, and reducing the cost of electricity consumption.
Evolutionary history and diversity in the ball roller beetle Canthon cyanellus
Authors: Nolasco-Soto Janet , González-Astorga Jorge , Espinosa de los Monteros Alejandro , Favila Mario E.
Published: January 2023

To understand the evolutionary history of species, it is necessary to know the mechanisms for reproductive isolation, divergence-time between populations, and the relative action of the evolutionary forces (e.g., mutation, genetic drift, gene flow) within and between populations of the same, or closely related species. AlthoughCanthonis one of the more diverse genera of neotropical beetles, insufficient research has been done to comprehend the divergent patterns that explain its speciation process. The absence of diagnostic morphological characters and the wide geographic variation of qualitative traits in Scarabaeinae obscures species delimitation, genealogical limits between populations, and its taxonomy.Canthon cyanellusis one of the best-known species in ecological and evolutionary aspects. It is a widely distributed species in the tropical forests of America. Also, the current deforestation has facilitated its incursion into open areas. Individuals from different populations have similar morphological characters but show wide variation in body color throughout their distribution, which makes it difficult to delimit the subspecies that comprise it. Recently, studies have been carried out to elucidate the pre-and postzygotic isolation mechanisms between populations and the historical biogeographical processes favoring cladogenesis events during the Pleistocene. Morphological variation of the male genitalia does not correspond to the phylogeographic structure. However, the morphological differences in one of the pieces of the endophallic sclerites have allowed a preliminary delimitation of some genetically differentiated clades. Finally, we consider that the joint analysis of traditional morphological taxonomy and phylogeography is important to understand the speciation process in theC. cyanelluscomplex.
Species morphospace boundary revisited through wing phenotypic variations of Antodynerus species (Hymenoptera: Vespidae: Eumeninae) from the Indian subcontinent
Authors: Anand P. P. , Seena S. , Girish Kumar P. , Shibu Vardhanan Y.
Published: January 2023

The main objective of this study was to investigate the taxonomic significance of wing phenotypic variations (size and shape) for classifying potter wasps. This is the first study investigating the wing size and shape variations, as well as wing asymmetry, sexual dimorphism, wing integration, and phylogenetic signal analysis of all knownAntodynerusspecies from the Indian subcontinent:A. flavescens,A. limbatus, andA. punctatipennis.We used forewings and hindwings for geometric morphometric analysis, and we proved that each species’ wing had unique size and shape variations, as well as significant right–left wing asymmetry and sexual dimorphism across theAntodynerusspecies, as verified by discriminant function analysis. Wings of Vespidae are longitudinally folded; based on that, we tested two alternative wing modular hypotheses for evaluating the wing integration, using two subsets organization, such as anterior–posterior (AP) and proximal-distal (PD) wing modular organization. We proved thatAntodynerusspecies wings are highly integrated units (RV > 0.5), and we rejected our hypothesis atp < 0.05. The morphospace distribution analysis revealed that each species has its unique morphospace boundary, although they share some level of homoplasy, which suggests to us that we can use wing morphometric traits forAntodynerusspecies delimitation. In addition, we revealed the phylogenetic signal ofAntodynerusspecies. Surprisingly, we found a shape-related phylogenetic signal in the forewing, and there is no significant (p > 0.05) phylogenetic signal in forewing size, hindwing shape, and size. We observed that theAntodynerusspecies’ forewing shape is evolutionarily more highly constrained than the hindwing. We found thatA. limbatusandA. flavescenswith distinct geographical distribution share a similar evolutionary history, whileA. punctatipennisevolved independently.
Interferon gamma-related gene signature based on anti-tumor immunity predicts glioma patient prognosis
Authors: Zhang Zhe , Shen Xiaoli , Tan Zilong , Mei Yuran , Lu Tianzhu , Ji Yulong , Cheng Sida , Xu Yu , Wang Zekun , Liu Xinxian , He Wei , Chen Zhen , Chen Shuhui , Lv Qiaoli
Published: January 2023

Background: Glioma is the most common primary tumor of the central nervous system. The conventional glioma treatment strategies include surgical excision and chemo- and radiation-therapy. Interferon Gamma (IFN-γ) is a soluble dimer cytokine involved in immune escape of gliomas. In this study, we sought to identify IFN-γ-related genes to construct a glioma prognostic model to guide its clinical treatment.

Methods: RNA sequences and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and the China Glioma Genome Atlas (CGGA). Using univariate Cox analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, IFN-γ-related prognostic genes were selected to construct a risk scoring model, and analyze its correlation with the clinical features. A high-precision nomogram was drawn to predict prognosis, and its performance was evaluated using calibration curve. Finally, immune cell infiltration and immune checkpoint molecule expression were analyzed to explore the tumor microenvironment characteristics associated with the risk scoring model.

Results: Four out of 198 IFN-γ-related genes were selected to construct a risk score model with good predictive performance. The expression of four IFN-γ-related genes in glioma tissues was significantly increased compared to normal brain tissue (p < 0.001). Based on ROC analysis, the risk score model accurately predicted the overall survival rate of glioma patients at 1 year (AUC: The Cancer Genome Atlas 0.89, CGGA 0.59), 3 years (AUC: TCGA 0.89, CGGA 0.68), and 5 years (AUC: TCGA 0.88, CGGA 0.70). Kaplan-Meier analysis showed that the overall survival rate of the high-risk group was significantly lower than that of the low-risk group (p < 0.0001). Moreover, high-risk scores were associated with wild-type IDH1, wild-type ATRX, and 1P/19Q non-co-deletion. The nomogram predicted the survival rate of glioma patients based on the risk score and multiple clinicopathological factors such as age, sex, pathological grade, and IDH Status, among others. Risk score and infiltrating immune cells including CD8 T-cell, resting CD4 memory T-cell, regulatory T-cell (Tregs), M2 macrophages, resting NK cells, activated mast cells, and neutrophils were positively correlated (p < 0.05). In addition, risk scores closely associated with expression of immune checkpoint molecules such as PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT, CD48, CD226, and CD96.

Conclusion: Our risk score model reveals that IFN-γ -associated genes are an independent prognostic factor for predicting overall survival in glioma, which is closely associated with immune cell infiltration and immune checkpoint molecule expression. This model will be helpful in predicting the effectiveness of immunotherapy and survival rate in patients with glioma.
Biological gene extraction path based on knowledge graph and natural language processing
Authors: Zhang Canlin , Cao Xiaopei
Published: January 2023

The continuous progress of society and the vigorous development of science and technology have brought people the dawn of maintaining health and preventing and controlling diseases. At the same time, with the update and iteration of bioinformatics technology, the current biological gene research has also undergone revolutionary changes. However, a long-standing problem in genetic research has always plagued researchers, that is, how to find the most needed sample genes from a large number of sample genes, so as to reduce unnecessary research and reduce research costs. By studying the extraction path of biological genes, it can help researchers to extract the most valuable research genes and avoid wasting time and energy. In order to solve the above problems, this paper used the Bhattacharyya distance index and the Gini index to screen the sample genes when extracting the characteristic genes of breast cancer. In the selected 49 public genes, 6 principal components were extracted by principal component analysis (PCA), and finally the experimental results were tested. It was found that when the optimal number of characteristic genes was selected as 5, the recognition rate of genes reached the highest 90.31%, which met the experimental requirements. In addition, the experiment also proved that the characteristic gene extraction method designed in this paper had a removal rate of 99.75% of redundant genes, which can greatly reduce the time and money cost of research.
CRISPR-mediated rapid arming of poxvirus vectors enables facile generation of the novel immunotherapeutic STINGPOX
Authors: Whelan Jack T. , Singaravelu Ragunath , Wang Fuan , Pelin Adrian , Tamming Levi A. , Pugliese Giuseppe , Martin Nikolas T. , Crupi Mathieu J. F. , Petryk Julia , Austin Bradley , He Xiaohong , Marius Ricardo , Duong Jessie , Jones Carter , Fekete Emily E. F. , Alluqmani Nouf , Chen Andrew , Boulton Stephen , Huh Michael S. , Tang Matt Y. , Taha Zaid , Scut Elena , Diallo Jean-Simon , Azad Taha , Lichty Brian D. , Ilkow Carolina S. , Bell John C.
Published: January 2023

Poxvirus vectors represent versatile modalities for engineering novel vaccines and cancer immunotherapies. In addition to their oncolytic capacity and immunogenic influence, they can be readily engineered to express multiple large transgenes. However, the integration of multiple payloads into poxvirus genomes by traditional recombination-based approaches can be highly inefficient, time-consuming and cumbersome. Herein, we describe a simple, cost-effective approach to rapidly generate and purify a poxvirus vector with multiple transgenes. By utilizing a simple, modular CRISPR/Cas9 assisted-recombinant vaccinia virus engineering (CARVE) system, we demonstrate generation of a recombinant vaccinia virus expressing three distinct transgenes at three different loci in less than 1 week. We apply CARVE to rapidly generate a novel immunogenic vaccinia virus vector, which expresses a bacterial diadenylate cyclase. This novel vector, STINGPOX, produces cyclic di-AMP, a STING agonist, which drives IFN signaling critical to the anti-tumor immune response. We demonstrate that STINGPOX can drive IFN signaling in primary human cancer tissue explants. Using an immunocompetent murine colon cancer model, we demonstrate that intratumoral administration of STINGPOX in combination with checkpoint inhibitor, anti-PD1, promotes survival post-tumour challenge. These data demonstrate the utility of CRISPR/Cas9 in the rapid arming of poxvirus vectors with therapeutic payloads to create novel immunotherapies.
Metabolic effects of CCL5 deficiency in lean and obese mice
Authors: Zhou Hui , Liao Xiyan , Zeng Qin , Zhang Haowei , Song Jianfeng , Hu Wanyu , Sun Xiaoxiao , Ding Yujin , Wang Dandan , Xiao Yalun , Deng Tuo
Published: January 2023

Accumulation and activation of immunocytes in adipose tissues are essential to obesity-induced inflammation and insulin resistance. Chemokines are pivotal for the recruitment of immunocytes in adipose tissue during obesity. Chemokine (C-C motif) ligand 5 (CCL5) plays a vital role in the recruitment of immunocytes to sites of inflammation. CCL5 expression level is increased in obese adipose tissue from humans and mice. However, the role of CCL5 in obesity-induced adipose inflammation remains unclear. Our study found that the CCL5 expression level was increased in the epididymal white adipose tissue (eWAT) of obese mice, particularly in CD8+ T cells. CCL5 knockout (KO) mice exhibited better glucose tolerance than wild-type (WT) mice under lean conditions. In contrast, CCL5 KO mice were more insulin resistant and had severe hepatic steatosis than WT mice under obese conditions. Increased T cells in adipose tissue heaven adipose inflammation in obese CCL5 KO mice. The compensatory increased T cell-associated chemokines may account for increased T cell content in the eWAT of obese CCL5 KO mice. These findings imply that CCL5 deficiency exacerbates adipose inflammation and impairs insulin sensitivity in the metabolic tissues of obese mice.
Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated
Authors: Maaske Jill , Sproule Stephanie , Falsey Ann R. , Sobieszczyk Magdalena E. , Luetkemeyer Anne F. , Paulsen Grant C. , Riddler Sharon A. , Robb Merlin L. , Rolle Charlotte-Paige , Sha Beverly E. , Tong Tina , Ahani Bahar , Aksyuk Anastasia A. , Bansal Himanshu , Egan Timothy , Jepson Brett , Padilla Marcelino , Patel Nirmeshkumar , Shoemaker Kathryn , Stanley Ann Marie , Swanson Phillip A. , Wilkins Deidre , Villafana Tonya , Green Justin A. , Kelly Elizabeth J.
Published: January 2023

Background

Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in coronavirus disease 2019 (COVID-19) vaccinees typically produces milder disease than infection in unvaccinated individuals.

Methods

To explore disease attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 infection in participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746).

Results

We observed that AZD1222 vaccinees had an overall lower incidence and shorter duration of COVID-19 symptoms compared with placebo recipients, as well as lower SARS-CoV-2 viral loads and a shorter median duration of viral shedding in saliva. Vaccinees demonstrated a robust antibody recall response versus placebo recipients with low-to-moderate inverse correlations with virologic endpoints. Vaccinees also demonstrated an enriched polyfunctional spike-specific Th-1-biased CD4+ and CD8+ T-cell response that was associated with strong inverse correlations with virologic endpoints.

Conclusion

Robust immune responses following AZD1222 vaccination attenuate COVID-19 disease severity and restrict SARS-CoV-2 transmission potential by reducing viral loads and the duration of viral shedding in saliva. Collectively, these analyses underscore the essential role of vaccination in mitigating the COVID-19 pandemic.
Persistent humoral and CD4+ TH cell immunity after mild SARS-COV-2 infection—The CoNAN long-term study
Authors: Schnizer Clara , Andreas Nico , Vivas Wolfgang , Kamradt Thomas , Baier Michael , Kiehntopf Michael , Glöckner Stefan , Scherag André , Löffler Bettina , Kolanos Steffi , Guerra Joel , Pletz Mathias W. , Weis Sebastian
Published: January 2023

Understanding persistent cellular and humoral immune responses to SARS-CoV-2 will be of major importance to terminate the ongoing pandemic. Here, we assessed long-term immunity in individuals with mild COVID-19 up to 1 year after a localized SARS-CoV-2 outbreak. CoNAN was a longitudinal population-based cohort study performed 1.5 months, 6 months, and 12 months after a SARS-CoV-2 outbreak in a rural German community. We performed a time series of five different IgG immunoassays assessing SARS-CoV-2 antibody responses on serum samples from individuals that had been tested positive after a SARS-CoV-2 outbreak and in control individuals who had a negative PCR result. These analyses were complemented with the determination of spike-antigen specific TH cell responses in the same individuals. All infected participants were presented as asymptomatic or mild cases. Participants initially tested positive for SARS-CoV-2 infection either with PCR, antibody testing, or both had a rapid initial decline in the serum antibody levels in all serological tests but showed a persisting TH cell immunity as assessed by the detection of SARS-CoV-2 specificity of TH cells for up to 1 year after infection. Our data support the notion of a persistent T-cell immunity in mild and asymptomatic cases of SARS-CoV-2 up to 1 year after infection. We show that antibody titers decline over 1 year, but considering several test results, complete seroreversion is rare.

Trial registration

German Clinical Trials Register DRKS00022416.
Comprehensive characteristics of pathological subtypes in testicular germ cell tumor: Gene expression, mutation and alternative splicing
Authors: Yao Xiangyang , Zhou Hui , Duan Chen , Wu Xiaoliang , Li Bo , Liu Haoran , Zhang Yangjun
Published: January 2023

Background

Testicular germ cell tumor (TGCT) is the most common tumor in young men, but molecular signatures, especially the alternative splicing (AS) between its subtypes have not yet been explored.

Methods

To investigate the differences between TGCT subtypes, we comprehensively analyzed the data of gene expression, alternative splicing (AS), and somatic mutation in TGCT patients from the TCGA database. The gene ontology (GO) enrichment analyses were used to explore the function of differentially expressed genes and spliced genes respectively, and Spearman correlation analysis was performed to explore the correlation between differential genes and AS events. In addition, the possible patterns in which AS regulates gene expression were elaborated by the ensemble database transcript atlas. And, we identified important transcription factors that regulate gene expression and AS and functionally validated them in TGCT cell lines.

Results

We found significant differences between expression and AS in embryonal carcinoma and seminoma, while mixed cell tumors were in between. GO enrichment analyses revealed that both differentially expressed and spliced genes were enriched in transcriptional regulatory pathways, and obvious correlation between expression and AS events was determined. By analyzing the transcript map and the sites where splicing occurs, we have demonstrated that AS regulates gene expression in a variety of ways. We further identified two pivot AS-related molecules (SOX2 and HDAC9) involved in AS regulation, which were validated in embryonal carcinoma and seminoma cell lines. Differences in somatic mutations between subtypes are also of concern, with our results suggesting that mutations in some genes (B3GNT8, CAPN7, FAT4, GRK1, TACC2, and TRAM1L1) occur only in embryonal carcinoma, while mutations in KIT, KARS, and NRAS are observed only in seminoma.

Conclusions

In conclusion, our analysis revealed the differences in gene expression, AS and somatic mutation among TGCT subtypes, providing a molecular basis for clinical diagnosis and precise therapy of TGCT patients.
Transcriptomic analysis reveals the regulatory mechanism of tetraspore formation in Gracilariopsis lemaneiformis
Authors: Sun Deguang , Zhou Xueyou , Sun Xue , Xu Nianjun
Published: January 2023

With the expansion of seaweed culture and changes in the global climate, large quantities of new seaweed germplasm are urgently needed. It is important to elucidate the process of reproductive development and its regulatory mechanism in seaweed. Gracilariopsis lemaneiformis (Rhodophyta) has an essential economic and ecological value, for example, as a raw material for agar extraction and abalone feed. Here, four phases (I to IV) of G. lemaneiformis tetrasporophyte development were analyzed using physiological assays and transcriptome technologies. The results showed that photosynthetic capacity increased during the period from tetraspore formation to the release (Phase II, III and IV). According to transcriptome results, the expression levels of genes associated with light harvesting, photosynthesis, and carbon fixation pathways were significantly upregulated during tetraspore formation and release. Meanwhile, the expression levels of genes encoding starch and trehalose synthesis enzymes in starch and sucrose metabolism were enhanced during tetraspore formation and release, suggesting that G. lemaneiformis requires more energy supply during reproductive development, and that trehalose-6-phosphate may also act as a signaling molecule to induce tetraspore formation. In addition, genes encoding antioxidant enzymes (APX, TRX, GR, TR, PRX, and CAT) were significantly upregulated during tetraspore formation. These results may help us to understand the transition from nutritional to reproductive development and the molecular mechanism of G. lemaneiformis tetrasporogenesis, which is vital for the development of new germplasm and promoting the growth of the seaweed culture industry.
Effects of submerged macrophytes (Elodea nuttallii) on water quality and microbial communities of largemouth bass (Micropterus salmoides) ponds
Authors: Nie Zhijuan , Zheng Zhaowei , Zhu Haojun , Sun Yi , Gao Jun , Gao Jiancao , Xu Pao , Xu Gangchuan
Published: January 2023

Traditional aquaculture ponds are one of the most vulnerable ecosystems; thus, ecological aquaculture is increasingly valued for its beneficial ecological properties and ecosystem services. However, little is known about ecological aquaculture of largemouth bass with submerged vegetation. Here, we designed three ecological ponds of cultured largemouth bass with submerged macrophytes (the EM group) and three ponds with traditional aquaculture (the M group) to reveal the response of water quality, and phytoplankton and bacterial communities, to submerged macrophyte bioremediation during a 90-day culture period. We observed that Cyanobacterial outbreak occurred in the M group ponds from day 7 to the end of the experiment; however, there were no Cyanobacterial blooms in the EM group ponds throughout the culture period. Compared with the M group ponds, the EM group ponds, which had submerged hydrophytes, had significantly decreased concentrations of TP, TN, and CODMn, but significantly increased DO concentrations throughout the experimental period. Moreover, ecological aquaculture with submerged macrophytes showed strong effects on the phytoplankton and bacterial community compositions. In particular, the M group ponds had higher phytoplankton density and mainly included Cyanobacteria, whereas the EM group had lower phytoplankton density and mainly included Chlorophyta. Moreover, higher alpha diversity, as determined by Ace and Simpson index values, was detected for bacterial communities in the EM group ponds. Furthermore, PCoA clearly grouped the bacterial communities according to the two culture modes throughout the culture period. These results indicate that ecological aquaculture with submerged macrophytes can improve water quality, control Cyanobacterial blooms, and affect the diversity and composition of bacterial communities. These valuable effects seem to be beneficial and consistent to maintaining aquaculture ecosystem stability.
A symbiotic bacterium of Antarctic fish reveals environmental adaptability mechanisms and biosynthetic potential towards antibacterial and cytotoxic activities
Authors: Xiao Yu , Yan Fangfang , Cui Yukun , Du Jiangtao , Hu Guangzhao , Zhai Wanying , Liu Rulong , Zhang Zhizhen , Fang Jiasong , Chen Liangbiao , Yu Xi
Published: January 2023

Antarctic microbes are important agents for evolutionary adaptation and natural resource of bioactive compounds, harboring the particular metabolic pathways to biosynthesize natural products. However, not much is known on symbiotic microbiomes of fish in the Antarctic zone. In the present study, the culture method and whole-genome sequencing were performed. Natural product analyses were carried out to determine the biosynthetic potential. We report the isolation and identification of a symbiotic bacterium Serratia myotis L7-1, that is highly adaptive and resides within Antarctic fish, Trematomus bernacchii. As revealed by genomic analyses, Antarctic strain S. myotis L7-1 possesses carbohydrate-active enzymes (CAZymes), biosynthetic gene clusters (BGCs), stress response genes, antibiotic resistant genes (ARGs), and a complete type IV secretion system which could facilitate competition and colonization in the extreme Antarctic environment. The identification of microbiome gene clusters indicates the biosynthetic potential of bioactive compounds. Based on bioactivity-guided fractionation, serranticin was purified and identified as the bioactive compound, showing significant antibacterial and antitumor activity. The serranticin gene cluster was identified and located on the chrome. Furthermore, the multidrug resistance and strong bacterial antagonism contribute competitive advantages in ecological niches. Our results highlight the existence of a symbiotic bacterium in Antarctic fish largely represented by bioactive natural products and the adaptability to survive in the fish living in Antarctic oceans.
A rapid method for detecting and distinguishing metallo-β-lactamase-and serine carbapenemase-producing Enterobacteriales using MALDI-TOF MS
Authors: Jing Xiaopeng , Hu Yanyan , Wu Tingting , Zhang Xing , Luo Shaofeng , Wang Wei , Min Xiaochun , Sun Ruiling , Zeng Ji
Published: January 2023

Introduction

Carbapenemase-producing Enterobacteriales (CPE) are a major health threat worldwide, and therefore the development of rapid detection methods is needed. Here, we established a method to distinguish metallo-β-lactamase and serine carbapenemases using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with ethylenediaminetetraacetic acid (EDTA) and phenylboronic acid (PB).

Methods

To assess the specificity and sensitivity of the method, 110 carbapenemase-producing and 72 carbapenemase-negative Enterobacteriales isolates were collected, among which 51 strains produced only metallo-β-lactamase, 55 strains only serine carbapenemases, and four strains both metallo-β-lactamase and serine carbapenemases. In the proposed MALDI-TOF MS method, imipenem (IPM) and the bacterial strains to be tested were mixed, EDTA and/or PB was added, and the mixture was incubated for 4 h. The carbapenemase type was confirmed by the IPM waveform spectrum before and after incubation.

Results

Based on the presence, absence, and recovery of the IPM-cyano-4-hydroxy-cinnamic acid-specific waveform peak near 479 m/z, the detection sensitivity and specificity of the method were 98.2 and 100%, respectively.

Discussion

Although CPE detection by MALDI-TOF MS has been studied previously, our method distinguishes between metallo-β-lactamase and serine carbapenemases, which will be very helpful for the clinical selection of antibiotics.
The role of oxidative stress in the pathogenesis of infections with coronaviruses
Authors: Gain Chandrima , Song Sihyeong , Angtuaco Tyler , Satta Sandro , Kelesidis Theodoros
Published: January 2023

Coronaviruses can cause serious respiratory tract infections and may also impact other end organs such as the central nervous system, the lung and the heart. The coronavirus disease 2019 (COVID-19) has had a devastating impact on humanity. Understanding the mechanisms that contribute to the pathogenesis of coronavirus infections, will set the foundation for development of new treatments to attenuate the impact of infections with coronaviruses on host cells and tissues. During infection of host cells, coronaviruses trigger an imbalance between increased production of reactive oxygen species (ROS) and reduced antioxidant host responses that leads to increased redox stress. Subsequently, increased redox stress contributes to reduced antiviral host responses and increased virus-induced inflammation and apoptosis that ultimately drive cell and tissue damage and end organ disease. However, there is limited understanding how different coronaviruses including SARS-CoV-2, manipulate cellular machinery that drives redox responses. This review aims to elucidate the redox mechanisms involved in the replication of coronaviruses and associated inflammation, apoptotic pathways, autoimmunity, vascular dysfunction and tissue damage that collectively contribute to multiorgan damage.
DNA methylation-based patterns for early diagnostic prediction and prognostic evaluation in colorectal cancer patients with high tumor mutation burden
Authors: Huang Hao , Cao Weifan , Long Zhiping , Kuang Lei , Li Xi , Feng Yifei , Wu Yuying , Zhao Yang , Chen Yinggang , Sun Peng , Peng Panxin , Zhang Jinli , Yuan Lijun , Li Tianze , Hu Huifang , Li Gairui , Yang Longkun , Zhang Xing , Hu Fulan , Sun Xizhuo , Hu Dongsheng
Published: January 2023

Background

Immune checkpoint inhibitor (ICI) therapy has proven to be a promising treatment for colorectal cancer (CRC). We aim to investigate the relationship between DNA methylation and tumor mutation burden (TMB) by integrating genomic and epigenetic profiles to precisely identify clinical benefit populations and to evaluate the effect of ICI therapy.

Methods

A total of 536 CRC tissues from the Cancer Genome Atlas (TCGA) with mutation data were collected and subjected to calculate TMB. 80 CRC patients with high TMB and paired normal tissues were selected as training sets and developed the diagnostic and prognostic methylation models, respectively. In the validation set, the diagnostic model was validated in our in-house 47 CRC tissues and 122 CRC tissues from the Gene Expression Omnibus (GEO) datasets, respectively. And a total of 38 CRC tissues with high TMB from the COLONOMICS dataset verified the prognostic model.

Results

A positive correlation between differential methylation positions and TMB level was observed in TCGA CRC cohort (r=0.45). The diagnostic score that consisted of methylation levels of four genes (ADHFE1, DOK6, GPR75, and MAP3K14-AS1) showed high diagnostic performance in the discovery (AUC=1.000) and two independent validation (AUC=0.946, AUC=0.857) datasets. Additionally, these four genes showed significant positive correlations with NK cells. The prognostic score containing three genes (POU3F3, SYN2, and TMEM178A) had significantly poorer survival in the high-risk TMB samples than those in the low-risk TMB samples (P=0.016). CRC patients with low-risk scores combined with TMB levels represent a favorable survival.

Conclusions

By integrating analyses of methylation and mutation data, it is suggested that DNA methylation patterns combined with TMB serve as a novel potential biomarker for early screening in more high-TMB populations and for evaluating the prognostic effect of CRC patients with ICI therapy.