A novel homozygous mutation in LSS gene possibly causes hypotrichosis simplex in two siblings of a Tibetan family from the western Sichuan province of China

Aim: Hypotrichosis simplex (MIM 146520) is a rare form of monogenic hereditary alopecia. Several genes have been identified as being associated with the disease, including LPAR6, LIPH, and DSG4. LSS encoding lanosterol synthase (LSS) has been shown to cause hypotrichosis simplex, but the related mechanisms have not been elucidated to date. This study aims to find mutations in LSS from a Chinese family, among which a 21-year-old male patient and his 9-year-old sister were affected by hypotrichosis simplex.Methods: Dermoscopy and histological analysis were used to examine patients’ scalps, while exome sequencing was used to find the mutations in LSS.Results: The hair loss was only detected on the scalp of the proband and his sister, while other ectodermal structures were normal with no systemic abnormalities. Further, the exome sequencing identified a new homozygous mutation NM_002340.6 (LSS_v001):c.812T>C (p.(Ile271Thr)) in the LSS gene of the proband, which was also found in his sister. In addition, a heterozygous mutation of LSS was found in their asymptomatic parents. Finally, the possible protein structure of the mutational LSS was predicted.Conclusion: The hypotrichosis simplex reported here could be an autosomal recessive disease in this family. The mutation on LSS might reduce the enzyme activity of LSS, thus leading to the disease

Panel 9. Paper 9.2: Maintenance of Water Systems of Cultural Heritage--Case Studies along Silk Roads

Water has become a vital element in studying heritages, since researchers has realized that heritages are not only about sites per se, but also include multiple elements that reflect human social and cultural development along historical evolution, and water is one of the most important sector to study. To study further maintenance of water systems of cultural heritages, it is necessary to understand the authenticity of water which is decided by interactions between human and water into consideration, and notice different interactions would result in different discussion on further water management and preservation, for water systems have been changed and reformed by human to adapt to environment and sustain future generations. In this case, the author would like to discuss further water management and preservation based on different interactions between human, water and sites. The examples of heritages along Silk Roads would be provided to illustrate the author\u27s point that further practical approaches on water maintenance should be based on the relationship among human, water and site

Identification of ONECUT3 as a stemness-related transcription factor regulating NK cell-mediated immune evasion in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a dismal response to the current T cell-based immunotherapies, which is attributed to intratumoral heterogeneity caused by PDAC stem cells and lack of major histocompatibility complex class I required for neoantigen presentation. Although this scenario makes natural killer (NK) cells attractive candidates for immunotherapeutic agents targeting MHC-I-deficient cancer stem cells in heterogeneous PDACs, little is known about PDAC stem cell immunology. In our study, PDAC-specific datasets from public databases were collected for in-depth bioinformatic analysis. We found that the abundance of PDAC stemness negatively influenced the infiltration of NK cells and identified the transcription factor ONECUT3 enriched in PDACs with high stemness index scores and Pan-cancer Stemness Signature levels. A series of NK cell-targeted inhibitory immune checkpoints were highly expressed in ONECUT3high PDACs. The patient group with high levels of ONECUT3 expression had a high risk of poor overall survival, even if accompanied by high infiltration of NK cells. Furthermore, the prostanoid metabolic process was enriched in ONECUT3high PDACs with high levels of NK cell-targeted inhibitory immune checkpoints. ONECUT3 enriched in high-stemness PDACs possessed the potential to transcriptionally regulate the prostanoid metabolism-related genes. Our study reveals ONECUT3 as a candidate stemness-related transcription factor regulating NK cell-targeted inhibitory immune checkpoints in PDAC. ONECUT3-mediated prostanoid metabolism may regulate cancer stemness and immune evasion in PDAC. Synergistic inhibition of prostanoid metabolism may improve the efficacy of NK cell-based immunotherapies targeting intratumoral heterogeneity caused by PDAC stem cells

Exposures to Air Pollution and Noise from Multi-Modal Commuting in a Chinese City

Background: Modern urban travel includes mixtures of transit options, which potentially impact individual pollution exposures and health. This study aims to investigate variations in traffic-related air pollution and noise levels experienced in traffic in Chengdu, China. Methods: Real-time PM2.5, black carbon (BC), and noise levels were measured for four transportation modes (car, bus, subway, and shared bike) on scripted routes in three types of neighborhoods (urban core, developing neighborhood, and suburb). Each mode of transportation in each neighborhood was sampled five times in summer and winter, respectively. After quality control, mixed effect models were built for the three pollutants separately. Results: Air pollutants had much higher concentrations in winter. Urban Core had the highest PM2.5 and BC concentrations across seasons compared to the other neighborhoods. The mixed effect model indicated that car commutes were associated with lower PM2.5 (−34.4 μg/m3; 95% CI: −47.5, −21.3), BC (−2016.4 ng/m3; 95% CI: −3383.8, −648.6), and noise (−9.3 dBA; 95% CI: −10.5, −8.0) levels compared with other modes; subway commutes had lower PM2.5 (−11.9 μg/m3; 95% CI: 47.5, −21.3), but higher BC (2349.6 ng/m3; 95% CI: 978.1, 3722.1) and noise (3.0 dBA; 95% CI: 1.7, 4.3) levels than the other three modes of transportation. Conclusion: Personal exposure to air pollution and noise vary by season, neighborhood, and transportation modes. Exposure models accounting for environmental, meteorological, and behavioral factors, and duration of mixed mode commuting may be useful for health studies of urban traffic microenvironments

Digoxin sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine via inhibiting Nrf2 signaling pathway

Chemoresistance is a major therapeutic obstacle in the treatment of human pancreatic ductal adenocarcinoma (PDAC). As an oxidative stress responsive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of cytoprotective genes. Nrf2 not only plays a critical role in chemoprevention, but also contributes to chemoresistance. In this study, we found that digoxin markedly reversed drug resistance of gemcitabine by inhibiting Nrf2 signaling in SW1990/Gem and Panc-1/Gem cells. Further research revealed that digoxin regulated Nrf2 at transcriptional level. In in vivo study, we found that digoxin and gemcitabine in combination inhibited tumor growth more substantially when compared with gemcitabine treatment alone in SW1990/Gem-shControl cells-derived xenografts. In the meantime, SW1990/Gem-shNrf2 cells-derived xenografts responded to gemcitabine and combination treatment similarly, suggesting that digoxin sensitized gemcitabine-resistant human pancreatic cancer to gemcitabine, which was Nrf2 dependent. These results demonstrated that digoxin might be used as a promising adjuvant sensitizer to reverse chemoresistance of gemcitabine-resistant pancreatic cancer to gemcitabine via inhibiting Nrf2 signaling. Keywords: Digoxin, Pancreatic cancer cells, Gemcitabine, Chemoresistance, Nrf

Exploring the Effect of a MnO₂ Coating on the Electrochemical Performance of a Li_1.2Mn_0.54Ni_0.13Co_0.13O₂ Cathode Material

The effect of electrochemically active MnO2 as a coating material on the electrochemical properties of a Li1.2Mn0.54Ni0.13Co0.13O2 (LTMO) cathode material is explored in this article. The structural analysis indicated that the layered structure of the LTMO was unchanged after the modification with MnO2. The morphology inspection demonstrated that the rod-like LTMO particles were encapsulated by a compact coating layer. The MnO2 layer was able to hinder the electrolyte solution from corroding the LTMO particles and optimized the formation of a solid electrolyte interface (SEI). Meanwhile, lithium ions were reversibly inserted into and extracted from MnO2, which afforded an additional capacity. Compared with the bare LTMO, the MnO2-coated sample exhibited enhanced electrochemical performance. After the MnO2 coating, the first discharge capacity rose from 224.2 to 239.1 mAh/g, and the initial irreversible capacity loss declined from 78.2 to 46.0 mAh/g. Meanwhile, the cyclic retention climbed up to 88.2% after 100 cycles at 0.5 C, which was more competitive than that of the bare LTMO with a value of 71.1%. When discharging at a high current density of 2 C, the capacity increased from 100.5 to 136.9 mAh/g after the modification. These investigations may be conducive to the practical application of LTMO in prospective automotive Li-ion batteries

Exploring the Effect of a MnO2 Coating on the Electrochemical Performance of a Li1.2Mn0.54Ni0.13Co0.13O2 Cathode Material

The effect of electrochemically active MnO2 as a coating material on the electrochemical properties of a Li1.2Mn0.54Ni0.13Co0.13O2 (LTMO) cathode material is explored in this article. The structural analysis indicated that the layered structure of the LTMO was unchanged after the modification with MnO2. The morphology inspection demonstrated that the rod-like LTMO particles were encapsulated by a compact coating layer. The MnO2 layer was able to hinder the electrolyte solution from corroding the LTMO particles and optimized the formation of a solid electrolyte interface (SEI). Meanwhile, lithium ions were reversibly inserted into and extracted from MnO2, which afforded an additional capacity. Compared with the bare LTMO, the MnO2-coated sample exhibited enhanced electrochemical performance. After the MnO2 coating, the first discharge capacity rose from 224.2 to 239.1 mAh/g, and the initial irreversible capacity loss declined from 78.2 to 46.0 mAh/g. Meanwhile, the cyclic retention climbed up to 88.2% after 100 cycles at 0.5 C, which was more competitive than that of the bare LTMO with a value of 71.1%. When discharging at a high current density of 2 C, the capacity increased from 100.5 to 136.9 mAh/g after the modification. These investigations may be conducive to the practical application of LTMO in prospective automotive Li-ion batteries