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Objective To analyze the clinical features and to identify the pathogenic variants in three Chinese families with dyschromatosis symmetrica hereditaria (DSH). Methods Clinical information and peripheral blood samples from three trio families with DSH were collected. The variants were detected by whole exome sequencing and then confirmed by Sanger sequencing. Pathogenicity of the variants was evaluated with a series of bioinformatic software. Results All the probands from the three Chinese families showed a mixture of pigmented and depigmented macules on the extremities. Three heterozygote single-nucleotide-variants, c.3546T＞G (p.Tyr1182*), c.2770T＞G (p.Tyr924Asp) and c.3116A＞C (p.Lys1039Thr), in the ADAR(NM_001111.5) gene were detected by WES in the three probands respectively. The first two variants were not present in the public databases such as gnomAD and HGMD, and the third one was previously reported in HGMD but not presented in the public databases. The relevant variants were undetectable in their parents of the three probands shown by Sanger sequencing, and were consequently regarded as de novo variants. These variants located in the highly conservative sites, all of which were located in the double-stranded RNA adenosine deaminase domain of the protein encoded by ADAR. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the nonsense variant, c.3546T＞G in ADAR, was categorized as a pathogenic variant (PVS1+PS2+PM2+PP3+PP4) and the missense variants, c.2770T＞G and c.3116A＞C in ADAR, were categorized as pathogenic variants (PS2+PM1+PM2+PP3+PP4) and (PS1+PS2+PM1+PM2+PP3+PP4), respectively. Conclusions Three de novo variants in ADAR, c.3546T＞G, c.2770T＞G and c.3116A＞C are probably the genetic pathogenesis of DSH in these three probands respectively, which enriched the genetic profile of ADAR.

The ring current is an important component of the Earth's near‐space environment, as its variations are the direct driver of geomagnetic storms that can disrupt power grids, satellite communications, and navigation systems, thereby impacting a wide range of technological and human activities. Oxygen ions (O+) are one of the major components of the ring current and play a significant role in both the enhancement and depletion of the ring current during geomagnetic storms. Although a standard statistical study can provide average global distributions of ring current ions, it can't offer insight into the short‐term dynamic variations of the global distribution. Therefore, we employed the Artificial Neural Network technique to construct a global ring current O+ ion model based on the Van Allen Probes observations. Through optimization of the combination of input geomagnetic indices and their respective time history lengths, the model can well reproduce the spatiotemporal variation of the oxygen ion flux distributions and demonstrates remarkable accuracy and minimal errors. Additionally, the model effectively reconstructs the temporal variation of ring current O+ ions for non‐training set data. Furthermore, the model provides a comprehensive and dynamic representation of global ring current O+ ion distribution. It accurately captures the dynamics of O+ ions during a geomagnetic storm with the oxygen ion fluxes enhancement and decay, and reveals distinct characteristics for different energy levels, such as injection from the plasma sheet, outflow from the ionosphere, and magnetic local time asymmetry. Plain Language Summary: The ring current, a significant part of Earth's space environment, is closely linked to geomagnetic disturbances that can disrupt power grids, satellite communications, and navigation systems, affecting our daily lives. Oxygen ions (O+) are a key component of the ring current during geomagnetic active time. In our study, we use a powerful tool called Artificial Neural Networks to create a model for ring current O+ behavior. This model only requires F10.7 and geomagnetic indices as inputs. By carefully selecting the best combination of the geomagnetic indices and their time history, we built a model that can accurately mimic the behavior of oxygen ions observed by satellites. Our model demonstrates that the levels of O+ ion fluxes rise and fall at various locations during geomagnetic disturbance, which is consistent with previous observational trend. The model also helps us to understand the global distribution of O+ ions in real time. During a test case of a geomagnetic storm, the model revealed details about energy‐dependent O+ ion flux enhancement and decay. Key Points: An artificial neural network model was built to reconstruct ring current oxygen ions using geomagnetic indices as inputThe model shows high accuracy in predicting non‐training set data and successfully captures the enhancement and decay of oxygen ion fluxesThe model successfully reproduces the variation of global distribution for oxygen ions of different energies during geomagnetic storms [ABSTRACT FROM AUTHOR]

The present study uncovers the fine structures of magnetosonic waves by investigating the EFW waveforms measured by Van Allen Probes. We show that each harmonic of the magnetosonic wave may consist of a series of elementary rising‐tone emissions, implying a nonlinear mechanism for the wave generation. By investigating an elementary rising‐tone magnetosonic wave that spans a wide frequency range, we show that the frequency sweep rate is likely proportional to the wave frequency. We studied compound rising‐tone magnetosonic waves, and found that they typically consist of multiple harmonics in the source region, and may gradually become continuous in frequency as they propagate away from source. Both elementary and compound rising‐tone magnetosonic waves last for ∼1 min which is close to the bounce period of the ring proton distribution, but their relation is not fully understood. Plain Language Summary: Naturally occurring magnetosonic waves are a kind of electromagnetic wave in the Earth's magnetized space. Their frequency spectra typically exhibit a harmonic structure. Sometimes they exhibit a rising‐tone feature, that is, the wave starts at a low pitch and gradually increases its frequency to a high pitch. Using the high‐resolution data measured by Van Allen Probe satellites, the present study uncovers that each harmonic of a magnetosonic wave may have a fine structure: they consist of a series of elementary rising‐tone emissions. The traditionally known rising‐tone magnetosonic waves consist of multiple harmonics, and we name them "compound rising‐tone magnetosonic waves". The compound rising‐tone waves may gradually become continuous in spectrum as they propagate away from source. These findings give new insights to the generation of magnetosonic waves and their impact on space environment. Key Points: Each harmonic of a magnetosonic wave may consist of a series of elementary rising‐tone emissionsThe frequency sweep rate of elementary magnetosonic waves is likely proportional to the frequencyCompound rising‐tone magnetosonic waves consist of harmonics at the source, and gradually develop a continuous spectrum during propagation [ABSTRACT FROM AUTHOR]

BackgroundImmune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration.ObjectiveThe present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology.MethodsA broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age.ResultsAged AD mice displayed severe manifestations of systemic autoimmune/inflammatory dise6ase, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired "cognitive" flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology.ConclusionThe results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD.

Cichoric acid (CA), a natural phenolic compound found in many plants, has been reported to have antioxidant, anti‐inflammatory, hypoglycemic, and other effects. The aim of this study was to determine the potential role and underlying mechanisms of CA in isoproterenol (ISO)‐induced myocardial fibrosis (MF). The MF model was induced by subcutaneous ISO injection in mice. Blood and heart tissue were collected for examination. Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the histopathological changes and collagen deposition. The production of reactive oxygen species markers was observed by fluorescence microscopy, the degree of cardiomyocyte microstructure injury was observed by transmission electron microscope, and oxidative stress factors were detected by kit method, and the effect of CA on inflammatory factors was detected by ELISA. The expression levels of collagen proteins and signaling pathways were further investigated by western blotting. The results showed that CA inhibited the expression of ISO‐induced proinflammatory factors (TNF‐α, IL‐1β, and IL‐18) and proteins (HK1, NLRP3, caspase‐1, cleaved‐caspase‐1, and ASC), and regulated the expression of apoptotic factors (caspase‐3, cleaved‐caspase‐3, Bax, and Bcl‐2). The results indicated that CA may regulate the HK1/NLRP3 inflammasome pathway by inhibiting HK1 expression and play a protective role in MF. [ABSTRACT FROM AUTHOR]

Semen Ziziphi Spinosae (SZS) is the dried and ripe seeds of Ziziphus jujuba var. spinosa. Currently, the yield of naturally grown SZS is unstable owing to environmental factors. Grafting high-quality sour jujube scions onto sour jujube or jujube tree stocks can result in a greater yield. However, the effects of grafting on the quality and gene expression of SZS have rarely been reported. This study used a DNA barcoding technique, high-performance liquid phase-evaporative luminescence detector (HPLC-ELSD), and transcriptomics to investigate the origin and genetic differences between grafted and wild jujube seeds. DNA barcoding identified all samples as Ziziphus jujuba var. spinosa. HPLC-ELSD analysis revealed a higher content of grafted SZS compared to that of the wild SZS. Transcriptome analysis of the metabolic pathways in SZS showed that 22 and 19 differentially expressed gene sequences encoded enzymes related to flavonoids and saponin synthesis, respectively. Weighted correlation network analysis (WGCNA) identified 15 core genes governing the differences in medicinal components between grafted and wild SZS. This study demonstrated the use of DNA barcoding and fingerprint methods to identify jujube seed species and effectively capture ingredient information of medicinal materials. Additionally, transcriptome technology provided data for identifying core differential genes, facilitating studies on quality differences between grafted and wild SZS. [ABSTRACT FROM AUTHOR]