Mechanism of Evolution Shared by Gene and Language

We propose a general mechanism for evolution to explain the diversity of gene and language. To quantify their common features and reveal the hidden structures, several statistical properties and patterns are examined based on a new method called the rank-rank analysis. We find that the classical correspondence, "domain plays the role of word in gene language", is not rigorous, and propose to replace domain by protein. In addition, we devise a new evolution unit, syllgram, to include the characteristics of spoken and written language. Based on the correspondence between (protein, domain) and (word, syllgram), we discover that both gene and language shared a common scaling structure and scale-free network. Like the Rosetta stone, this work may help decipher the secret behind non-coding DNA and unknown languages.Comment: 15 pages, 13 figures, 3 tabl

Gait Disorders in Parkinson's Disease: Assessment and Management

Gait disorder, a major cause of morbidity in the elderly population, is one of the cardinal features of Parkinson's disease. Owing to the characteristics of these gaits varying widely from festination to freezing of gait, analysis can be hardly identified in the clinical setting. Instrumented gait analysis has been widely used in a traditional gait laboratory. Recently, wireless monitoring systems have become highly informative by allowing long-term data collection in a variety of environments outside the labs. The quantitative analysis of gait patterns is probably the first step to a successful management of an individual patient. The presence of abnormal gait usually indicates advanced stages of disease and is often associated with cognitive impairment, falls, and injuries. Besides pharmacological and surgical treatments, parkinsonian gait can benefit from a variety of interventions. Assistive devices prevent patients from falls, and cueing strategies help them decrease episodes of freezing. Therefore, a multidisciplinary team approach to the optimal management is essential for an elderly patient with Parkinson's disease

Walking Turns in Parkinson's Disease Patients with Freezing of Gait: The Short-term Effects of Different Cueing Strategies

Background: This study aimed to evaluate the effects of cueing on circular walking in patients with Parkinson's disease. Methods: Parkinson's disease patients in the “off” state were asked to walk on a designed route at their preferred speed. The experimental protocol was divided into two sessions. The first session was to be performed with no manual task. During the second session, the participant had to perform a manual task. Each session was measured for each of four conditions performed in the following order: without cues, with a visual cue, with an auditory cue, and with dual cues simultaneously. Temporospatial gait parameters and freezing of gait (FOG) events regarding the cueing-on and cueing-off situations were the main measures of gait performance. Results: Twelve patients with Parkinson's disease were recruited. Demographic and clinical characteristics of the participants were the following [median (interquartile range)]: age 63 years (57–67.3 years), Hoehn and Yahr stage 3.0 (3.0–3.25), and Unified Parkinson's Disease Rating Scale motor subsection off medication 22.5 (20.3–35.5). Walking turns of 180° in combination with a manual task were the most important triggers for FOG. On circular walking either with or without a manual task, visual or dual cues improved festinating gait patterns and increased step length. Visual or dual cues further improved the velocity of walking with a manual task. All types of cueing decreased FOG scores either with or without a manual task. Conclusion: Our study suggests that cueing improves festinating gait and decreases the incidence of FOG. Future studies with much larger sample sizes are warranted to support our findings

The skin hydration and anti-inflammatory potential of zerumbone, a natural sesquiterpene of Zingiber zerumbet, enhanced Src/ERK-mediated HAS-2/AQP-3 and inhibited NFκB/AP-1 expression in UVB-irradiated human keratinocytes

We assayed skin hydration and anti-inflammatory efficacies of zerumbone (Zer, 2.5–10 μM), a natural sesquiterpene of Zingiber zerumbet, using non– or UVB (30 mJ/cm2)-irradiated keratinocytes (HaCaT). & Zer increased cell viability, upregulated hyaluronic acid, and inhibited ROS generation in UVB-irradiated HaCaT cells. Zer promoted antioxidant Nrf2 nuclear translocation resulting in HO-1 and γ-GCLC expression. Zer promotes skin hyaluronic acid by increasing protein and mRNA expression of HAS-2 and AQP-3 in non– or UVB-irradiated HaCaT cells. Furthermore, Zer increased Src and ERK phosphorylation. Src silencing or ERK inhibitor (PD98059) diminished Zer-mediated skin hydration, as evidenced by decreased HAS-2 and AQP-3 expression. Interestingly, UVB-induced Src/ERK inhibition was reversed by Zer or N-acetylcysteine. Additionally, Zer inhibited inflammatory iNOS, COX-2, and IL-1β expression through NFκB (p65) and AP-1 (c-Jun/c-Fos) pathway in UVB-irradiated HaCaT cells. HaCaT cells treated with Zer enhanced the growth factors PDGF-A, VEGF, and EGFR expressions. Zerumbone might be utilized in cosmetic formulations

Metatranscriptomic Analysis of Human Lung Metagenomes from Patients with Lung Cancer

This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also performed. The heterogeneous cellular landscape and immune repertoires of the lung samples were examined using xCell and TRUST4, respectively. We found that nine bacteria were significantly enriched in the lung tissues of cancer patients, and associated with reduced overall survival (OS). We also found that subjects with mutations in the epidermal growth factor receptor gene were less likely to experience the presence of Pseudomonas. aeruginosa. We found that the presence of CD8+ T-cells, CD4+ naive T-cells, dendritic cells, and CD4+ central memory T cells were associated with a good prognosis, while the presence of pro B-cells was associated with a poor prognosis. Furthermore, high clone numbers were associated with a high ImmuneScore for all immune receptor repertoires. Clone numbers and diversity were significantly higher in unpresented subjects compared to presented subjects. Our results provide insight into the microbiota of human lung cancer, and how its composition is linked to the tumor immune microenvironment, immune receptor repertoires, and OS

Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection

Dengue is the most widespread arbovirus infection and poses a serious health and economic issue in tropical and subtropical countries. Currently no licensed vaccine or compounds can be used to prevent or manage the severity of dengue virus (DENV) infection. Honokiol, a lignan biphenol derived from the Magnolia tree, is commonly used in Eastern medicine. Here we report that honokiol has profound antiviral activity against serotype 2 DENV (DENV-2). In addition to inhibiting the intracellular DENV-2 replicon, honokiol was shown to suppress the replication of DENV-2 in baby hamster kidney (BHK) and human hepatocarcinoma Huh7 cells. At the maximum non-toxic dose of honokiol treatment, the production of infectious DENV particles was reduced >90% in BHK and Huh7 cells. The underlying mechanisms revealed that the expression of DENV-2 nonstructural protein NS1/NS3 and its replicating intermediate, double-strand RNA, was dramatically reduced by honokiol treatment. Honokiol has no effect on the expression of DENV putative receptors, but may interfere with the endocytosis of DENV-2 by abrogating the co-localization of DENV envelope glycoprotein and the early endosomes. These results indicate that honokiol inhibits the replication, viral gene expression, and endocytotic process of DENV-2, making it a promising agent for chemotherapy of DENV infection

Tranexamic acid improves psoriasis-like skin inflammation: Evidence from in vivo and in vitro studies

The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod (IMQ)-induced psoriasis-like inflammation. Furthermore, this study investigated the effect of noncytotoxic concentrations of TXA on IL-17-induced human keratinocyte (HaCaT) cells to determine the status of proliferative psoriatic keratinocytes. We found that TXA reduced IMQ-induced psoriasis-like erythema, thickness, scaling, and cumulative scores (erythema plus thickness plus scaling) on the back skin of BALB/c mice. Additionally, TXA decreased ear thickness and suppressed hyperkeratosis, hyperplasia, and inflammation of the ear epidermis in IMQ-induced BALB/c mice. Furthermore, TXA inhibited IMQ-induced splenomegaly in BALB/c mouse models. In IL-17-induced HaCaT cells, TXA inhibited ROS production and IL-8 secretion. Interestingly, TXA suppressed the IL-17-induced NFκB signaling pathway via IKK-mediated IκB degradation. TXA inhibited IL-17-induced activation of the NLRP3 inflammasome through caspase-1 and IL1β expression. TXA inhibited IL-17-induced NLRP3 inflammasome activation by enhancing autophagy, as indicated by LC3-II accumulation, p62/SQSTM1 expression, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Notably, TXA suppressed IL-17-induced Nrf2-mediated keratin 17 expression. N-acetylcysteine pretreatment reversed the effects of TXA on NFκB, NLRP3 inflammasomes, and the Nrf2-mediated keratin 17 pathway in IL-17-induced HaCaT cells. Results further confirmed that in the ear skin of IMQ-induced mice, psoriasis biomarkers such as NLRP3, IL1β, Nrf2, and keratin 17 expression were downregulated by TXA treatment. TXA improves IMQ-induced psoriasis-like inflammation in vivo and psoriatic keratinocytes in vitro. Tranexamic acid is a promising future treatment for psoriasis

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell—cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers