Typical Signature Research Articles

Gallic acid forms V-amylose complex structure with starch through hydrophobic interaction

This study aimed to investigate the role of amylose and amylopectin in the formation of starch-polyphenol complex and elucidate the interaction mechanisms. Gallic acid (GA) was used to complex with maize starch with various amylose contents. Results showed GA formed V-type crystals with normal maize starch (NMS) and high amylose maize starch (HAMS), while higher relative crystallinity was exhibited in HAMS-GA complexes than NMS counterparts. Molecular structure analysis revealed more amylose in GA-starch complexes than in treated starch counterparts without GA, and this was more apparent in HAMS than NMS, implying amylose is preferred to complex with GA than amylopectin. FTIR detected higher R1047/1022 value in starch-GA complexes than their starch counterparts without GA, suggesting increased short-range ordered structrure of complexes. Typical signatures of hydrophobic interactions were further revealed by isothermal titration calorimetry, indicating the complexation of GA to starch is mainly through hydrophobic bonds. More binding sites were observed for HAMS (72.50) than NMS (11.33), which proves the preferences of amylose to bind with GA. Molecular dynamics simulated the complexation of GA to amylose, and confirmed hydrophobic bond is the main interaction force. These findings would provide guidance for precise design and utilization of starch-polyphenol complexes in functional foods.

PATHOGENETIC PATHWAYS AND POSSIBLE TREATMENT OPTIONS FOR NONUNION FRACTURES

Bone regeneration is pivotal for the healing of fractures. In case this process is disturbed a non-union can occur. This can be induced by environmental factors such as smoking, overloading etc. Co-morbidities such as diabetes, osteoporosis etc. may be more intrinsic factors besides other disturbances in the process. Those pathways negatively influence the bone regeneration process. Several intrinsic signal transduction pathways (WNT, BMP etc.) can be affected. Furthermore, on the transcriptional level, important mRNA expression can be obstructed by deregulated miRNA levels. For instance, several miRNAs have been shown to be upregulated during osteoporotic fractures. They are detrimental for osteogenesis as they block bone formation and accelerate bone resorption. Modulating those miRNAs may revert the physiological homeostasis. Indeed, physiological fracture healing has a typical miRNA signature. Besides using molecular pathways for possible treatment of non-union fractures, providing osteogenic cells is another solution. In 5 clinical cases with non-union fractures with defects larger than 10 cm, successful administration of a 3D printed PCL-TCP scaffold with autologous bone marrow aspirate concentrate and a modulator of the pathogenetic pathway has been achieved. All patients recovered well and showed a complete union of their fractures within one year after start of the regenerative treatment.Thus, non-union fractures are a diverse entity. Nevertheless, there seem to be common pathogenetic disturbances. Those can be counteracted at several levels from molecular to cell. Compositions of those may be the best option for future therapies. They can also be used in a more personalized fashion in case more specific measurements such as miRNA signature and stem cell activity are applied.

Identification and validation of a signature based on myofibroblastic cancer-associated fibroblast marker genes for predicting prognosis, immune infiltration, and therapeutic response in bladder cancer.

Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Quantitative Precipitation Estimation using X-Band Radar for Orographic Rainfall in the San Francisco Bay Area

In the San Francisco Bay Area, precipitation occurs in the wintertime, mostly as rain. Wintertime rainfall can be further classified into cold or stratiform rain with a typical radar bright band signature and warm orographic rain with absence of a radar bright band. Vertical Pointing S-Band profiler radar and disdrometer measurements from two of NOAA’s Hydrometeorology Testbed (HMT) sites in California are used to study the differences in microphysical properties between these two types of rain and their implications in radar rainfall estimation. A methodology has been developed to discriminate non bright band (NBB) rainfall from bright band (BB) rainfall using reflectivity (Z) and differential reflectivity (Z <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DR</sub> ) computed from disdrometer data. Delineating the two rainfall types in this way allowed for an algorithm to be applied to the radar scans to identify rainfall types and apply appropriate reflectivity based and specific differential phase (K <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DP</sub> ) based rainfall estimators. Recently, a gap-filling X-Band weather radar with dual-polarization capabilities was deployed in the San Francisco Bay Area in Santa Rosa to aid in weather monitoring and provide high resolution Quantitative Precipitation Estimation (QPE) products. When applied to real radar observations, this method shows great potential for improving the QPE compared to traditional operational products which more often tend to underestimate rainfall in the California coastal region.

OPTIMIZATION AND CHARACTERIZATION OF SULPHATE BIOPOLYSACCHARIDE PRODUCTION FROM EDIBLE GREEN ALGAE Ulva Lactuca USING SURFACE RESPONSE METHOD

This research focuses on optimizing the production of sulfate biopolysaccharides from the edible green algae Ulva lactuca using surface response analysis. The objective was to identify the ideal conditions for extracting Ulvan, a sulfated polysaccharide from Ulvophyceae, by analyzing critical process factors-namely, temperature, HCl concentration, and heating duration. The study found the best extraction conditions at a temperature of 73°C, HCl concentration of 0.3 M, and heating duration of 4 hours, resulting in a 25.07% yield of Ulvan. The extracted Ulvan had a total sugar content of 0.1767 mg/mL and a sulfate content of 0.3143 mg/mL. Structural analysis conducted through FTIR and NMR spectroscopy confirmed the presence of typical sulfated polysaccharide signatures. Physical properties assessed using SEM, XRD, and TGA indicated that Ulvan is an amorphous material with substantial thermal stability. In biological evaluations, Ulvan demonstrated notable antioxidant properties, with an inhibition rate of 30.52% and a toxicity concentration (LC50) of 288.978 ppm. These findings highlight the potential of Ulvan in biopolymer production and suggest its applicability in developing algae-based products. The results contribute valuable insights into the biopolysaccharide extraction process, paving the way for future applications in the pharmaceutical and food industries.

The potential pathogenic role of gut microbiota in rheumatic diseases: a human-centred narrative review.

A growing amount of evidence suggests that gut microbiota plays an important role in human health, including a possible role in the pathogenesis of rheumatic and musculoskeletal diseases (RMD). We analysed the current evidence about the role of microbiota in rheumatoid arthritis (RA), spondyloarthritis (SpA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). In RA, we found a general consensus regarding a reduction of diversity and a specific bacterial signature, with consistent changes according to the different ethnic and geographical areas. The major pathogenetic role in RA is recognised for P. copri, L. salivarius and Collinsella, even if findings become more heterogeneous when considering established disease. In SpA, we found a relative gut abundance of Akkermansia, Coprococcus, Ruminoccocus and a relative reduction in Bacterioides and Firmicutes spp. Human and preclinical data suggest loss of mucosal barrier, increased permeability and Th1- and Th17-mediated inflammation. Additionally, HLA-B27 seems to play a role in shaping the intestinal microbiota and the consequent inflammation. In SLE, the typical gut microbiota signature was characterised by a reduction in the Firmicutes/Bacteroidetes ratio and by enrichment of Rhodococcus, Eggerthella, Klebsiella, Prevotella, Eubacterium and Flavonifractor, even if their real pathogenic impact remains unclear. In SSc, gastrointestinal dysbiosis is well documented with an increase of pro-inflammatory species (Fusobacterium, Prevotella, Ruminococcus, Akkermansia, γ-Proteobacteria, Erwinia, Trabsulsiella, Bifidobacterium, Lactobacillus, Firmicutes and Actinobacteria) and a reduction of species as Faecalibacterium, Clostridium, Bacteroidetes and Rikenella. In conclusion, seems possible to recognise a distinct gut microbiota profile for each RMD, even if significant differences in bacterial species do exist between different studies and there is a high risk of bias due to the cross-sectional nature of such studies. Therefore longitudinal studies are needed, especially on patients with preclinical and early disease, to investigate the real role of gut microbiota in the pathogenesis of RMD.

Late Cretaceous basalts in the eastern South China Block: The result of slab tearing during retreating subduction of the Paleo-Pacific plate

Cretaceous arc-like, ocean island basalt (OIB)-like, and transitional basalts erupted on the eastern South China Block (SCB), and their petrogenesis was possibly related to the subduction of the Paleo-Pacific plate. However, the detailed petrogenesis in terms of slab subduction, magma sources, and the spatial distribution of the different types in the coastal and inland regions is poorly understood. Here we conduct a comparative study on the Late Cretaceous basalts from both coastal and inland regions. Our compiled age data demonstrate that the basalts in the coastal regions erupted in the period of 104–81 Ma. They show low Nb/La (<0.8), Nb/Y (<0.7), and other typical arc-like signatures, e.g., negative Nb-Ta anomalies, variable enrichment of LILE and LREE, and more radiogenic Sr-Nd isotopic compositions. In contrast, the basalts in the inland regions erupted at 86–71 Ma. They are characterized by high Nb/La (>0.9), slightly negative to positive Nb-Ta anomalies; they mostly possess positive εNd(t) values and geochemical features transitional to OIB-like basalts. The systematic geochemical differences may imply the spatial heterogeneity in their magma sources. The three end-member mixing model suggests that the isotopic signatures of arc-like basalts largely resulted from partial melting of the mantle wedge metasomatized by the subducted sediments, while those of transitional basalts likely resulted from depleted mantle source metasomatized by melts from altered oceanic crust (AOC) with minor sediments. We suggest that the retreating of the Paleo-Pacific plate promoted the melting of sediment-hybridized mantle wedge, and then triggered the opening of a slab window and asthenosphere-slab interactions.

Fibre optic sensing for strain-field measurement in geotechnical laboratory experiments

Strain measurement inside the soil body in three-dimensional (3D) experiments is a real challenge for physical modellers in geotechnics. The use of fibre optic sensing offers the possibility of continuous measurement of the strain at depth with high spatial and temporal resolution in small-scale laboratory experiments. Despite the technology not being fully ready yet for centrifuge experiments, this is an important development in geotechnics. This paper explores the capacities of distributed fibre optic sensing (DFOS) as a solution for direct soil strain profile measurement at depth. A series of small-scale plane-strain experiments is used to simulate the simple case of the formation of a downwards subsidence. DFOS cables are laid in the soil specimen, and strains are directly compared with the soil movement, recorded with cameras through particle image velocimetry. Results indicate the ability of DFOS in detecting soil movements and underline the typical signature strain profile expected during this type of experiments. Finite-element analyses are carried out to further underpin the consequences of performing these tests at 1g and extend the findings to potential applications in 3D and on the geotechnical centrifuge. This shows promising results for detection of soil strain profiles inside the soil body in 3D.

Mutational Changes in Solid Cancer Cells Induce DNA Damage Repair Deficiency in Hematopoietic Cells Leading to a Distinct Spectrum of Clonal Hematopoiesis Independent from Age-Related Clonal Hematopoiesis

Clonal hematopoiesis (CH) is characterized by the acquisition of defined somatic mutations in hematopoietic stem cells (HSC). It is well known that CH contributes to the development of hematological malignancies but also increases the risk of developing non-malignant conditions such as cardiovascular, pulmonary, and inflammatory liver disease. However, less is known about the association between clonal hematopoiesis and solid cancer. Reports suggest that patients with solid cancer have a higher incidence of clonal hematopoiesis at an earlier age and an inferior prognosis. To investigate whether the presence of solid cancer itself can drive the development of clonal hematopoiesis, we analyzed 392 paired tumor and blood samples from patients with advanced cancer. In our cohort, all patients had evidence of clonal hematopoiesis based on a variant allele frequency (VAF) of at least 2%. With respect to a defined set of the 20 most frequently CH-associated genes, we discovered an increased CH rate of 23% of all patients (90 cases, median age of 61 years, defined by a VAF from 2% to 30%). The frequency of mutated genes differed greatly from published data from the general population and cancer patients, with the most common mutations being PABPC1 (39%), KMT2C (28%), RUNX1 (18%), and DNMT3A (10%). In addition, we observed a strong correlation between certain mutations in tumor samples and the frequency of CH. The mutational signature of CH was not mainly associated with a typical chemotherapy-dependent mutational signature, but with an impaired DNA repair capacity. For further investigation, we performed additional experiments in mice, which showed that the presence of malignant cells impairs DNA repair capacity in HSC through inflammatory changes in the stroma. In summary, we were able to show that patients with advanced or recurrent solid tumors have a significantly increased frequency of CH, which is not only the result of prior chemotherapy exposure but the result of diminished DNA repair capacity. This suggests a possible role of solid cancer in promoting the development of CH independent from chemotherapy exposure, which is supported by our additional murine experiments.

R-Loop Defines Neural Stem/Progenitor Cells During Mouse Neurodevelopment.

Neural stem/progenitor cells (NSPCs) are present in the mammalian brain throughout life and are involved in neurodevelopment and central nervous system repair. Although typical epigenetic signatures, including DNA methylation, histone modifications, and microRNAs, play a pivotal role in regulation of NSPCs, several of the epigenetic regulatory mechanisms of NSPCs remain unclear. Thus, defining a novel epigenetic feature of NSPCs is crucial for developing stem cell therapy to address neurologic disorders caused by injury. In this study, we aimed to define the R-loop, a three-stranded nucleic acid structure, as an epigenetic characteristic of NSPCs during neurodevelopment. Our results demonstrated that R-loop levels change dynamically throughout neurodevelopment. Cells with high levels of R-loops consistently decreased and were enriched in the area of neurogenesis. Additionally, these cells costained with SOX2 during neurodevelopment. Furthermore, these cells with high R-loop levels expressed Ki-67 and exhibited a high degree of overlap with the transcriptional activation markers, H3K4me3, ser5, and H3K27ac. These findings suggest that R-loops may serve as an epigenetic feature for transcriptional activation in NSPCs, indicating their role in gene expression regulation and neurogenesis.

Rare earth element and yttrium (REY) geochemistry of 3.46–2.45 Ga greenalite-bearing banded iron formations: New insights into iron deposition and ancient ocean chemistry

Finely laminated cherts enclosing nanoparticles of greenalite and apatite are ubiquitous in Archean-Paleoproterozoic (3.46–2.45 Ga) ferruginous cherts, jaspilites and Banded Iron Formations (BIFs) and the greenalite and apatite are considered to be primary deposits. The cherts and BIFs are chemical sedimentary rocks interpreted to have been precipitated in marine settings prior to the first permanent rise in atmospheric oxygen at the Great Oxidation Event (GOE) ca. 2.45–2.32 M.y. ago. As chemical sediments, they are potential archives of the solutions from which they precipitated, incorporating signals from hydrothermal fluids and ambient seawater. Previous studies of rare earth elements and Y (REY) in pre-GOE BIFs have mostly found an “Archean seawater signature” with positive Eu anomalies, attributed to the influence of high-temperature hydrothermal processes, and positive anomalies for La, Gd and Y, ascribed to seawater. REY abundances determined by in situ LA-ICP-MS are presented for well-preserved, laminated greenalite-bearing cherts from ten formations of pre-GOE ferruginous cherts and BIFs from Western Australia. The samples come from a wide range of depositional environments, e.g., submarine proximal volcanic environments, basin floor, slope and deep marine shelf, and are between 3.46 Ga to 2.45 Ga in age. Five groups with different REY patterns are identified, namely (i) mafic-volcanic-influenced vent-proximal chert from the Marble Bar Chert Member of the Duffer Formation of the Warrawoona Group; (ii) felsic volcanic- and sediment-associated chert from the Kangaroo Caves Formation of the Sulphur Springs Group and the Wilgie Mia Formation of the Murchison Supergroup, (iii) ferruginous cherts in shelf sediments from the Bee Gorge Member of the Wittenoom Formation of the Hamersley Group, (iv) BIFs from the Nammuldi Member of the Marra Mamba Iron Formation and Joffre Member of the Brockman Iron Formation, Hamersley Group, and (v) BIFs from the Dales Gorge Member of the Brockman Iron Formation. Of these, only the Dales Gorge Member BIF has a typical Archean seawater signature while the others have REY patterns likely reflecting differing source fluids and environments of deposition but not necessarily global ocean chemistry. Analyses of chert containing sub-micron-sized particles of greenalite and apatite indicate that the likely hosts of the REEs are apatite, siderite and possibly greenalite. The REY patterns of the greenalite-bearing cherts may differ from those of bulk samples of the same formations, perhaps reflecting a diagenetic overprint in the bulk samples, whereas the greenalite-bearing cherts likely preserve their depositional compositions, locked in by early silicification.

CAPOS: the bulge Cluster APOgee Survey IV elemental abundances of the bulge globular cluster NGC 6558

ABSTRACT This study presents the results concerning six red giant stars members of the globular cluster NGC 6558. Our analysis utilized high-resolution near-infrared spectra obtained through the CAPOS initiative (the APOgee Survey of Clusters in the Galactic Bulge), which focuses on surveying clusters within the Galactic Bulge, as a component of the Apache Point Observatory Galactic Evolution Experiment II survey (APOGEE-2). We employ the Brussels Automatic Code for Characterizing High accUracy Spectra (BACCHUS) code to provide line-by-line elemental-abundances for Fe-peak (Fe, Ni), α-(O, Mg, Si, Ca, Ti), light-(C, N), odd-Z (Al), and the s-process element (Ce) for the four stars with high-signal-to-noise ratios. This is the first reliable measure of the CNO abundances for NGC 6558. Our analysis yields a mean metallicity for NGC 6558 of 〈[Fe/H]〉 = −1.15 ± 0.08, with no evidence for a metallicity spread. We find a Solar Ni abundance, 〈[Ni/Fe]〉 ∼ +0.01, and a moderate enhancement of α-elements, ranging between +0.16 and &amp;lt;+0.42, and a slight enhancement of the s-process element 〈[Ce/Fe]〉 ∼ +0.19. We also found low levels of 〈[Al/Fe]〉 ∼ +0.09, but with a strong enrichment of nitrogen, [N/Fe] &amp;gt; +0.99, along with a low level of carbon, [C/Fe] &amp;lt; −0.12. This behaviour of Nitrogen-Carbon is a typical chemical signature for the presence of multiple stellar populations in virtually all GCs; this is the first time that it is reported in NGC 6558. We also observed a remarkable consistency in the behaviour of all the chemical species compared to the other CAPOS bulge GCs of the same metallicity.

On the Magnetic Nature of Quiet-Sun Chromospheric Grains

Ca ii K grains, i.e., intermittent, short-lived (about 1 minute), periodic (2–4 minutes), pointlike chromospheric brightenings, are considered to be the manifestations of acoustic waves propagating upward from the solar surface and developing into shocks in the chromosphere. After the simulations of Carlsson and Stein, we know that hot shocked gas moving upward interacting with the downflowing chromospheric gas (falling down after having been displaced upward by a previous shock) nicely reproduces the spectral features of the Ca ii K profiles observed in such grains, i.e., a narrowband emission-like feature at the blue side of the line core. However, these simulations are one-dimensional and cannot explain the location or the pointlike shape of the grains. Here, we report on the magnetic nature of these events. Furthermore, we report on similar events occurring at the largest flux concentrations, though they are longer-lived (up to 8 minutes) and exhibit the typical signature of steep velocity gradients traveling across the atmosphere. The spectral signatures of the studied events resemble their counterparts in sunspots, the umbral flashes. We then propose that magnetohydrodynamical waves are not only channeled through the magnetic field in sunspots, but they pervade the whole atmosphere. The propagation along magnetic fields can explain the pointlike appearance of the calcium grains observed in the quiet chromosphere.

Heterogeneous Archean oceanic protoliths in Neoproterozoic retrogressed eclogites from Northeast Brazil: Petrological, geochemical and Sr–Nd–Pb–Hf isotopic constraints

Eclogites are reliable indicators of high to ultrahigh-pressure (HP-UHP) conditions for oceanic and continental crust and are essential rocks to understand the lithospheric convergence from subduction to post-collisional setting. Furthermore, the origin and nature of eclogite precursors may reveal crucial constraints on the crustal history before HP-UHP metamorphism. Here, we provide petrological, geochemical and Pb-Sr-Nd-Hf isotopic constraints from the Campo Grande retrogressed eclogites, Northeast Brazil, to determine the source and evolution of their Archean protoliths. Eclogites were formed under HP conditions (18 ± 1.0 kbar and 680 ± 20 °C) followed by retrogression in the amphibolite facies, which is characterized by Mg-rich garnet porphyroblasts surrounded by clinopyroxene + plagioclase + amphibole + orthopyroxene symplectites (stable at <6.0 kbar). These retrogressed eclogites have chemical compositions corresponding to enriched-type tholeiites such as E-MORB protoliths (G1 eclogitic group). A second group of retrogressed eclogites with higher amphibole content (G2 eclogitic group) shows similar chemical patterns to G1, however with higher enrichment in LILE, REE and incompatible elements. The G1 eclogite is characterized by higher modal concentration of garnet and clinopyroxene, positive εNd(t) (+2.1 to +5.8) with low 87Sr/86Sr(i) ratios (0.7024 to 0.7131), whereas G2 displays dominant coarse-grained amphibole, positive and negative εNd(t) (−7.5 to +8.5) with high radiogenic 87Sr/86Sr(i) ratios (0.7109 to 0.7255). The chemical and isotopic G1 values show typical E-MORB signatures, whereas G2 indicate an E-MORB enriched by crustal components in a supra-subduction zone setting. A LuHf isochron provided the age of 2667.9 ± 30.7 Ma, which is close to the published ∼2.65 Ga crystallization age for the G1 and G2 oceanic protoliths. Therefore, Hf isotopes in whole rock and cogenetic minerals were useful for constraining the crystallization time of metamafic protoliths. In contrast, SmNd isochron age of 606.9 ± 24.8 Ma falls within the range of 623 to 590 Ma HP metamorphism recorded in the G1 and G2 rocks. Lastly, a third type of eclogite group (G3 eclogitic group) is represented by a banded Mn-rich-garnet (spessartite) and Al-rich clinopyroxene with detrital zircon cores from 3.42 to 2.15 Ga and recrystallized rims at 607.7 ± 5.4 Ma. Mineral texture and composition, geochemistry, strongly negative εNd(t) (−4.3 to −1.5) and higher radiogenic 87Sr/86Sr(i) ratios (0.7434–0.7501) suggest a different Mn-rich protolith for the G3 eclogites. Integrated data reveal that retrogressed eclogites retain the memory of the original chemical and isotopic patterns of Archean oceanic protoliths and its diachronous reworking processes at deep crustal levels.

Multi-omics analysis reveals the interaction of gut microbiome and host microRNAs in ulcerative colitis

Background Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with gut microbiota dysbiosis; however, its etiology remains unclear. MicroRNA (miRNA)-microbiome interactions play an essential role in host health and disease. Methods To investigate the gut microbiome and host miRNA profiles in colitis, we used a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis (UC) model. Metagenomic sequencing and metabolome profiling were performed to explore typical microbiota and metabolite signatures in colitis, whereas mRNA and miRNA sequencing were used to determine differentially expressed miRNAs and their target genes in the inflamed colon. Results A total of 986 miRNAs were identified between the two groups, with 41 upregulated and 21 downregulated miRNAs in colitis mice compared to the control group. Notably, the target genes of these significantly altered miRNAs were primarily enriched in the immune and inflammation-related pathways. Second, LEfSe analysis revealed bacterial biomarkers distinguishing the two groups, with significantly higher levels of commonly encountered pathogens such as Escherichia coli and Shigella flexneri in the UC group, whereas beneficial species such as Bifidobacterium pseudolongum were more abundant in the control group. Microbiota metabolites histamine, N-acetylhistamine, and glycocholic acid were found to be downregulated in colitis mice. Spearman correlation further revealed the potential crosstalk between the microbiota profile and colonic miRNA, revealing the possibility of microbiome–miRNA interactions involved in IBD development. Conclusions Our data reveal the relationships between multi-omic features during UC and suggest that targeting specific miRNAs may provide new avenues for the development of effective miRNA-based therapeutics.

Local modulation of thyroid hormone signaling in the retina affects the development of diabetic retinopathy

Thyroid hormone (TH) dyshomeostasis is associated with poor prognosis in acute and prolonged illness, but its role in diabetic retinopathy (DR) has never been investigated. Here, we characterized the TH system in the retinas of db/db mice and highlighted regulatory processes in MIO-M1 cells. In the db/db retinas, typical functional traits and molecular signatures of DR were paralleled by a tissue-restricted reduction of TH levels. A local condition of low T3 (LT3S) was also demonstrated, which was likely to be induced by deiodinase 3 (DIO3) upregulation, and by decreased expression of DIO2 and of TH receptors. Concurrently, T3-responsive genes, including mitochondrial markers and microRNAs (miR-133-3p, 338-3p and 29c-3p), were downregulated. In MIO-M1 cells, a feedback regulatory circuit was evidenced whereby miR-133-3p triggered the post-transcriptional repression of DIO3 in a T3-dependent manner, while high glucose (HG) led to DIO3 upregulation through a nuclear factor erythroid 2-related factor 2–hypoxia-inducible factor-1 pathway. Finally, an in vitro simulated condition of early LT3S and hyperglycemia correlated with reduced markers of both mitochondrial function and stress response, which was reverted by T3 replacement. Together, the data suggest that, in the early phases of DR, a DIO3-driven LT3S may be protective against retinal stress, while, in the chronic phase, it not only fails to limit HG-induced damage, but also increases cell vulnerability likely due to persistent mitochondrial dysfunction.

Multi-wavelength observations and modeling of a microflare: constraining non-thermal particle acceleration

In this work we analyze a small B-class flare that occurred on 29 April 2021 and was observed simultaneously by the Interface Region Imaging Spectrograph (IRIS) and the Nuclear Spectroscopic Telescope Array (NuSTAR) X-ray instrument. The IRIS observations of the ribbon of the flare show peculiar spectral characteristics that are typical signatures of energy deposition by non-thermal electrons in the lower atmosphere. The presence of the non-thermal particles is also confirmed directly by fitting the NuSTAR spectral observations. We show that, by combining IRIS and NuSTAR multi-wavelength observations from the corona to the lower atmosphere with hydrodynamic simulations using the RADYN code, we can provide strict constraints on electron-beam heated flare models. This work presents the first NuSTAR, IRIS and RADYN joint analysis of a non-thermal microflare, and presents a self-consistent picture of the flare-accelerated electrons in the corona and the chromospheric response to those electrons.

MYC-an emerging player in mitochondrial diseases.

The mitochondrion is a major hub of cellular metabolism and involved directly or indirectly in almost all biological processes of the cell. In mitochondrial diseases, compromised respiratory electron transfer and oxidative phosphorylation (OXPHOS) lead to compensatory rewiring of metabolism with resemblance to the Warburg-like metabolic state of cancer cells. The transcription factor MYC (or c-MYC) is a major regulator of metabolic rewiring in cancer, stimulating glycolysis, nucleotide biosynthesis, and glutamine utilization, which are known or predicted to be affected also in mitochondrial diseases. Albeit not widely acknowledged thus far, several cell and mouse models of mitochondrial disease show upregulation of MYC and/or its typical transcriptional signatures. Moreover, gene expression and metabolite-level changes associated with mitochondrial integrated stress response (mt-ISR) show remarkable overlap with those of MYC overexpression. In addition to being a metabolic regulator, MYC promotes cellular proliferation and modifies the cell cycle kinetics and, especially at high expression levels, promotes replication stress and genomic instability, and sensitizes cells to apoptosis. Because cell proliferation requires energy and doubling of the cellular biomass, replicating cells should be particularly sensitive to defective OXPHOS. On the other hand, OXPHOS-defective replicating cells are predicted to be especially vulnerable to high levels of MYC as it facilitates evasion of metabolic checkpoints and accelerates cell cycle progression. Indeed, a few recent studies demonstrate cell cycle defects and nuclear DNA damage in OXPHOS deficiency. Here, we give an overview of key mitochondria-dependent metabolic pathways known to be regulated by MYC, review the current literature on MYC expression in mitochondrial diseases, and speculate how its upregulation may be triggered by OXPHOS deficiency and what implications this has for the pathogenesis of these diseases.

Degradation Mapping and Impact of Device Dimension on IGZO TFTs BTI

We studied the impact of gate and drain stress biases combination on IGZO based TFTs degradation targeting hot carrier regime. We show that typical signatures of this mechanism (e.g., saturation current degradation and SS increase) are not visible even at high drain biases, while a gate bias dependence only (BTI) is present in most of the degradation data. We also identify an unexpected gate-length dependence of BTI, for which different extrinsic causes are investigated.

Effects of Sleep Fragmentation on White Matter Pathology in a Rat Model of Cerebral Small Vessel Disease.

Mounting evidence indicated the correlation between sleep and cerebral small vessel disease (CSVD). However, little is known about the exact causality between poor sleep and white matter injury, a typical signature of CSVD, as well as the underlying mechanisms. Spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats were subjected to sleep fragmentation for 16 weeks. The effects of chronic sleep disruption on the deep white matter and cognitive performance were observed. SHR were validated as a rat model for CSVD. Fragmented sleep induced strain-dependent white matter abnormalities, characterized by reduced myelin integrity, impaired oligodendrocytes precursor cells (OPC) maturation and pro-inflammatory microglial polarization. Partially reversible phenotypes of OPC and microglia were observed in parallel following sleep recovery. Long-term SF induced pathological effects on the deep white matter in a rat model of CSVD. The pro-inflammatory microglial activation and the block of OPC maturation may be involved in the mechanisms linking sleep to white matter injury.