Targeted Next Generation Sequencing Revealed a Novel Homozygous Loss-of-Function Mutation in ILDR1 Gene Causes Autosomal Recessive Nonsyndromic Sensorineural Hearing Loss in a Chinese Family

Hereditary hearing impairment is one of the major and common birth defects in Chinese population. Non-syndromic sensorineural hearing loss (NSHL) is the most common types of hereditary hearing impairment. Genotypically and phenotypically NSHL is extremely heterogenous and follow either autosomal dominant or autosomal recessive or X-linked mode of inheritance. Presently, 127 genes have been identified to be associated with both syndromic and (NSHL). Here, we studied a Chinese family with moderate and profound hearing impairment. The proband is a 30-year old Chinese man. The proband was born with normal hearing and at the age of 5-years, the proband was first noticed with hearing impairment. Gradually and progressively the proband was presented with loss of hearing in his both right and left ears at the age of 30 years. The clinical symptoms, age of onset or progression to loss of hearing was similar in both the proband and his younger brother. The proband’s parents are phenotypically normal and non-consanguineous. Clinical diagnosis of the proband and his younger brother has been done by classical pure tone audiogram (PTA). Computed Tomography (CT) found no abnormality in bilateral external ear, middle ear and inner ear. Targeted next generation sequencing was performed with a panel of 127 genes reported to be associated with hereditary hearing impairment. A novel homozygous single nucleotide deletion (c.427delT) in exon 4 of ILDR1 gene has been identified in proband and in his younger brother. Sanger sequencing confirmed that proband’s father and mother are carrying this mutation in a heterozygous manner. This mutation has not been identified in 100 normal healthy control individuals. This mutation (c.427delT) causes frameshift (p.Tyr143Ilefs∗19) which leads to the formation of a truncated ILDR1 protein of 162 amino acids instead of the wild type ILDR1 protein of 546 amino acids. ILDR1 associated hereditary hearing impairment is very rare and this is the first report of identifying a loss-of-function mutation in ILDR1 gene associated with hereditary hearing impairment in Chinese population. Our present study also emphasized the significance of rapid, accurate and cost-effective screening for the patient with hereditary hearing impairment by targeted next generation sequencing

Prolonged Mechanical Ventilation Induces Cell Cycle Arrest in Newborn Rat Lung

Rationale: The molecular mechanism(s) by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. Objective: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. Methods: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg-1). Measurement and Main Results: Ventilation for 24 h (h) decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation) was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27Kip1 was significantly increased. Mechanical ventilation for 24 h also increased levels of p57Kip2, decreased that of p16INK4a, while the levels of p21Waf/Cip1 and p15INK4b were unchanged. Increased p27Ki

Inter-and intra-event rainfall partitioning dynamics of two typical xerophytic shrubs in the Loess Plateau of China

Rainfall is known as the main water replenishment in dryland ecosystems, and rainfall partitioning by vegetation reshapes the spatial and temporal distribution patterns of rainwater entry into the soil. The dynamics of rainfall partitioning have been extensively studied at the inter-event scale, yet very few studies have explored its finer intra-event dynamics and the relating driving factors for shrubs. Here, we conducted a concurrent in-depth investigation of all rainfall partitioning components at inter-and intra-event scales for two typical xerophytic shrubs (Caragana korshinskii and Salix psammophila) in the Liudaogou catchment of the Loess Plateau, China. The event throughfall (TF), stemflow (SF), and interception loss (IC), and their temporal variations within the rainfall event, as well as the meteorological factors and vegetation characteristics, were systematically measured during the 2014-2015 rainy seasons. Our results showed that C. korshinskii had significantly higher SF percentage (9.2%) and lower IC percentage (21.4%) compared to S. psammophila (3.8% and 29.5%, respectively), but their TF percentages were not significantly different (69.4% vs. 66.7%). At the intra-event scale, TF and SF of S. psammophila were initiated (0.1 vs. 0.3h and 0.7 vs. 0.8h) and peaked (1.8 vs. 2.0h and 2.1 vs. 2.2h) more quickly, and TF of S. psammophila lasted longer (5.2 vs. 4.8h) and delivered more intensely (4.3 vs. 3.8mmh-1), whereas SF of C. korshinskii lasted longer (4.6 vs. 4.1h) and delivered more intensely (753.8 vs. 471.2mmh-1). For both shrubs, rainfall amount was the most significant factor influencing inter-event rainfall partitioning, and rainfall intensity and duration controlled the intra-event TF and SF variables. The C. korshinskii with larger branch angle, more small branches, and smaller canopy area, has an advantage over S. psammophila to produce SF more efficiently. The S. psammophila has lower canopy water storage capacity to generate and peak TF and SF earlier, and it has larger aboveground biomass and total canopy water storage of individual plants to produce higher IC compared to C. korshinskii. These findings contribute to the fine characterization of shrub-dominated ecohydrological processes, and improve the accuracy of water balance estimation in dryland ecosystems.This research has been supported by the National Natural Science Foundation of China (grant nos. 41991233 and 41822103) and the Youth Innovation Promotion Association of the Chinese Academy of Sciences (grant no. Y202013).Peer reviewe

Selective Sensing of Gas Mixture via a Temperature Modulation Approach: New Strategy for Potentiometric Gas Sensor Obtaining Satisfactory Discriminating Features

A new strategy to discriminate four types of hazardous gases is proposed in this research. Through modulating the operating temperature and the processing response signal with a pattern recognition algorithm, a gas sensor consisting of a single sensing electrode, i.e., ZnO/In2O3 composite, is designed to differentiate NO2, NH3, C3H6, CO within the level of 50–400 ppm. Results indicate that with adding 15 wt.% ZnO to In2O3, the sensor fabricated at 900 °C shows optimal sensing characteristics in detecting all the studied gases. Moreover, with the aid of the principle component analysis (PCA) algorithm, the sensor operating in the temperature modulation mode demonstrates acceptable discrimination features. The satisfactory discrimination features disclose the future that it is possible to differentiate gas mixture efficiently through operating a single electrode sensor at temperature modulation mode

Rainfall partitioning and its influence on dissolved carbon and nitrogen fluxes through plant-soil system of a xerophytic shrub in northern China

Dissolved carbon (DC) and dissolved nitrogen (DN) driven by rainfall partitioning are critical components of carbon and nitrogen cycles in terrestrial ecosystems, especially in vegetation restoration areas. However, the variations of DC and DN fluxes in the input (throughfall and stemflow) and output (infiltration and surface runoff) water pathways of shrub ecosystem in drylands were poorly understood. In this study, the rainfall partitioning, dissolved organic and inorganic carbon (DOC and DIC) and DN fluxes in 52 rainfall events affecting a xerophytic shrub ecosystem on the heavily eroded Chinese Loess Plateau were measured over the 2019–2021 rainy seasons. The contributions of plants and topsoil (0–5 cm) to the variations in DC and DN fluxes along water pathways were quantified. We found that the DC and DN fluxes in throughfall accounted for more than 80% of net input flux, and the topsoil infiltration of DC and DN fluxes into soil layer below 5 cm depth were the most important output flux (contribution more than 98%). The mean event plant-derived DC and DN fluxes were 52.2 and 5.3 mg m−2, respectively, accounting for 45.4% and 12.2% of net DC and DN input fluxes (115.2 and 43 mg m−2). The soil-buffered DC and DN fluxes (455.6 and 29.5 mg m−2) were 3.95 and 0.69 times greater than the net input fluxes, respectively. The DC and DN fluxes in infiltration had the best correlation and increased most quickly with rainfall depth in the four different water pathways. Furthermore, the soil carbon content in 0–50 cm depth and soil nitrogen content in 0–10 cm depth in shrub-covered land was significantly higher than those in bare land (p < 0.05). This study highlights the important roles of rainfall partitioning in plant-sourced and soil-buffered DC and DN fluxes, which should be considered in soil carbon and nitrogen accumulation in drylands.This research was funded by the National Natural Science Foundation of China (nos. U2243231, 41991233 and 41822103), and the Youth Innovation Promotion Association CAS (no. Y202013). We thank the Shenmu Erosion and Environment Research Station for providing experiment support. We thank the two anonymous reviewers for their professional comments which further improved the quality of the manuscript.Peer reviewe

One step molten salt synthesis of YVO4 nanoparticles and their photocatalytic properties under UV-Visible light

Well-crystalline YVO4 nanoparticles were successfully synthesized by a simple and convenient one-step molten salt synthesis (MSS) method in a wide temperature range of 350-600 °C for only 5 h. The UV-Visible absorption spectra measured by a spectrophotometer suggest that visible light absorption exists in the absorption spectra of all the samples prepared under different temperatures and the smaller the particle size, the stronger the absorption, the smaller the onset of UV absorption and the larger the blue shift. The photodegradation of RB indicates that both particle size and crystallinity have effects on the photocatalytic properties of YVO4 nanoparticles. YVO4 nanoparticles were further demonstrated to have excellent photocatalytic stability

Preliminary Classification of the ABC Transporter Family in Betula halophila and Expression Patterns in Response to Exogenous Phytohormones and Abiotic Stresses

ATP-binding cassette (ABC) transporters comprise a transport system superfamily which is ubiquitous in eukaryotic and prokaryotic cells. In plants, ABC transporters play important roles in hormone transport and stress tolerance. In this study, 15 BhABC transporters encoded by genes identified from the transcriptome of Betula halophila were categorized into four subfamilies (ABCB, ABCF, ABCG, and ABCI) using structural domain and phylogenetic analyses. Upon B. halophila exposure to exogenous phytohormones and abiotic stressors, gene expression patterns and transcriptional responses for each subfamily of genes were obtained using semi-quantitative RT-PCR analysis. The results demonstrated that expression of most genes belonging to ABCB and ABCG subfamilies changed in response to exogenous phytohormone exposures and abiotic stress. These results suggest that BhABC genes may participate in hormone transport and that their expression may be influenced by ABA-dependent signaling pathways involved in abiotic stress responses to various stressors

Rapid synthesis, structure and photocatalysis of pure bismuth A-site perovskite of Bi(Mg3/8Fe2/8Ti3/8)O3

Bi(Mg3/8Fe2/8Ti3/8)O3, a member of a small group of pure Bi3+ A site perovskites, exhibiting a high ferroelectric Curie point (Tc), was rapidly synthesized by a sample method of molten salt synthesis. The purity of Bi(Mg3/8Fe2/8Ti3/8) O3 samples is directly affected by the reaction conditions such as the soaking temperature, and the heating and cooling rates. The as-prepared Bi(Mg3/8Fe2/8Ti3/8)O3 particles are well-formed, cube-shaped single-crystals with sizes ranging from 200-300 nm. The chemical states of Bi and Fe ions are Bi3+ and Fe3+ in Bi(Mg3/8Fe2/8Ti3/8)O3. UV-vis diffuse reflectance spectra and preliminary photocatalytic experiments indicate that the pure Bi3+ A site perovskite of Bi(Mg3/8Fe2/8Ti3/8)O3 has a suitable energy bandgap (1.86 eV) and shows obvious photocatalytic activity for the decolorization of methyl blue under visible-light irradiation. The present work suggests potential future applications of Bi(Mg3/8Fe2/8Ti3/8)O3 in photocatalysis and ferroelectric photovoltaic effects

Mitochondrial PKM2 deacetylation by procyanidin B2-induced SIRT3 upregulation alleviates lung ischemia/reperfusion injury

Abstract Apoptosis is a critical event in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Sirtuin 3 (SIRT3), an important deacetylase predominantly localized in mitochondria, regulates diverse physiological processes, including apoptosis. However, the detailed mechanisms by which SIRT3 regulates lung I/R injury remain unclear. Many polyphenols strongly regulate the sirtuin family. In this study, we found that a polyphenol compound, procyanidin B2 (PCB2), activated SIRT3 in mouse lungs. Due to this effect, PCB2 administration attenuated histological lesions, relieved pulmonary dysfunction, and improved the survival rate of the murine model of lung I/R injury. Additionally, this treatment inhibited hypoxia/reoxygenation (H/R)-induced A549 cell apoptosis and rescued Bcl-2 expression. Using Sirt3-knockout mice and specific SIRT3 knockdown in vitro, we further found that SIRT3 strongly protects against lung I/R injury. Sirt3 deficiency or enzymatic inactivation substantially aggravated lung I/R-induced pulmonary lesions, promoted apoptosis, and abolished PCB2-mediated protection. Mitochondrial pyruvate kinase M2 (PKM2) inhibits apoptosis by stabilizing Bcl-2. Here, we found that PKM2 accumulates and is hyperacetylated in mitochondria upon lung I/R injury. By screening the potential sites of PKM2 acetylation, we found that SIRT3 deacetylates the K433 residue of PKM2 in A549 cells. Transfection with a deacetylated mimic plasmid of PKM2 noticeably reduced apoptosis, while acetylated mimic transfection abolished the protective effect of PKM2. Furthermore, PKM2 knockdown or inhibition in vivo significantly abrogated the antiapoptotic effects of SIRT3 upregulation. Collectively, this study provides the first evidence that the SIRT3/PKM2 pathway is a protective target for the suppression of apoptosis in lung I/R injury. Moreover, this study identifies K433 deacetylation of PKM2 as a novel modification that regulates its anti-apoptotic activity. In addition, PCB2-mediated modulation of the SIRT3/PKM2 pathway may significantly protect against lung I/R injury, suggesting a novel prophylactic strategy for lung I/R injury