Search

UnlabelledThe genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation. In the present study, iPSCs were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T; P-iPSCs), the asymptomatic father of the patient (MYO7A c.1184G>A mutation; CF-iPSCs), and a normal donor (MYO7A(WT/WT); C-iPSCs). One of MYO7A mutation sites (c.4118C>T) in the P-iPSCs was corrected using CRISPR/Cas9. The corrected iPSCs (CP-iPSCs) retained cell pluripotency and normal karyotypes. Hair cell-like cells induced from CP-iPSCs showed restored organization of stereocilia-like protrusions; moreover, the electrophysiological function of these cells was similar to that of cells induced from C-iPSCs and CF-iPSCs. These results might facilitate the development of iPSC-based gene therapy for genetic disorders.SignificanceInduced pluripotent stem cells (iPSCs) were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T). One of the MYO7A mutation sites (c.4118C>T) in the iPSCs was corrected using CRISPR/Cas9. The genetic correction of MYO7A mutation resulted in morphologic and functional recovery of hair cell-like cells derived from iPSCs. These findings confirm the hypothesis that MYO7A plays an important role in the assembly of stereocilia into stereociliary bundles. Thus, the present study might provide further insight into the pathogenesis of sensorineural hearing loss and facilitate the development of therapeutic strategies against monogenic disease through the genetic repair of patient-specific iPSCs.

We present systematic U-Pb age data collected by laser ablation multi-collector inductively coupled plasma mass spectrometry, precise geochemical data, and Nd isotope data for igneous rocks from the southeastern Lesser Xing'an Range (SE LXR). The results indicate that the formation ages as follows: Maojiatun alkaline granite, 207.2 [+ or -] 0.84 Ma and 204.6 [+ or -] 0.93 Ma; Diorite porphyrite, 164.5 [+ or -] 0.97 Ma; and Tieli syenogranite, 186.7 [+ or -] 1.50 Ma. The alkaline granite has high silicon, potassium, alkali, and Fe[O.sub.T] contents; it is enriched in high field strength elements, Zr, Hf, Th, Rb, and U; is depleted in Ba, Sr, Nb, Ta, P, Ti, etc.; and has high ratios of 10000Ga/Al. It shows an [A.sub.2]-type granite affinity. The Tieli alkali-feldspar granite has high total alkali contents and is enriched in high field strength elements and rare earth elements and depleted in Sr, Ba, Ti, and P, and shows varying degrees of alkalinity. Rocks from SE LXR display similar [[epsilon].sub.Nd] (t) values with corresponding to Nd model ages of 1095 to 813 Ma. The igneous rocks from the SE LXR are proposed to be derived from melting of the Neoproterozoic lower crust and potential magma mixing with ancient crystalline basement. The formation of the Maojiatun alkaline granite occurred in response to a postorogenic event following the closure of the Paleo-Asian Ocean. However, the SE LXR exhibited an extensional back-arc tectonic setting in the Early Jurassic. The Middle Jurassic diorite porphyrite could be related to the temporary stagnation of the westward subduction of the Paleo-Pacific plate. Key words: alkaline rocks, Lesser Xing'an Range, A-type granite, lithospheric delamination. Nous presentons des donnees de datation U-Pb systematique obtenues par spectrometrie de masse avec plasma a couplage inductif et collection d'ions multiples jumelee a l'ablation au laser, des donnees geochimiques precises et des donnees sur les isotopes du Nd pour des roches ignees du sud-est de la chaine du Petit Xing'an (SE LXR). Les resultats indiquent les ages de formation suivants: granite alcalin de Maojiatun, 207,2 [+ or -] 0.84 Ma et 204,6 [+ or -] 0,93 Ma; porphyre dioritique, 164,5 [+ or -] 0,97 Ma; et syenogranite de Tieli, 186,7 [+ or -] 1,50 Ma. Le granite alcalin a des concentrations elevees en silice, potassium, alcalis et Fe[O.sub.T], et il est enrichi en elements a forte liaison atomique, Zr, Hf, Th, Rb, et U, appauvri en Ba, Sr, Nb, Ta, P, Ti, et ainsi de suite, et est caracterise par des rapports 10000Ga/Al eleves. Il montre une affinite aux granites de type [A.sub.2]. Le granite a feldspaths alcalins de Tieli a de fortes concentrations totales d'alcalis et est enrichi en elements a forte liaison atomique et en terres rares et appauvri en Sr, Ba, Ti et P, et il presente des degres d'alcalinite variables. Les roches de la SE LXR presentent des valeurs de [[epsilon].sub.Nd] (t) semblables correspondant a des ages Nd modeles de 1095 Ma a 813 Ma. Il est propose que les roches ignees de la SE LXR sont derivees de la fusion de la croute inferieure neoproterozoique et du possible melange du magma avec des roches du substrat cristallin ancien. La formation du granite alcalin de Maojiatun s'est produite en reponse a un episode post-orogenique qui a suivi la fermeture de l'ocean paleo-Asiatique. Le contexte tectonique de la SE LXR au Jurassique precoce etait toutefois celui d'un bassin d'extension d'arriere-arc. Le porphyre dioritique d'age jurassique moyen pourrait etre associe a la stagnation temporaire de la subduction vers l'ouest de la plaque paleo-Pacifique. [Traduit par la Redaction] Mots-cles: roches alcalines, chaine du Petit Xing'an, granite de type A, delamination lithospherique., Introduction The southeastern Lesser Xing'an Range (SE LXR) innortheastern China belongs to the northern portion of the Central Asian Orogenic Belt (Sengor and Natal'in 1996; Jahn et al. 2000a, 2000b; [...]

Variations in plant traits are indicative of plant adaptations to forest environments, and studying their relationships with tree growth provides valuable insights into forest regeneration. The spatial arrangement of plant seeds within the forest litter or soil critically influences the variations of root–leaf traits, thereby affecting the adaptive strategies of emerging seedlings. However, our current understanding of the impacts of individual root–leaf traits on seedling growth in different relative position, and whether these traits together affect growth, remains limited. This study focuses on the dominant tree species, Castanopsis kawakamii , within the Sanming C. kawakamii Nature Reserve of China. The present experiment aimed to examine the variations in root–leaf traits of seedling, focus on the relative positions of seeds within different layers: beneath or above the litter layer, or within the bare soil layer (without litter). Our findings provided evidence supporting a coordinated relationship between root and leaf traits, wherein leaf traits varied in conjunction with root traits in the relative positions of seeds. Specifically, we observed that seedlings exhibited higher values for specific leaf area and average root diameter, while displaying lower root tissue density. The mixed model explained 86.1% of the variation in root–leaf traits, surpassing the variation explained by the relative positions. Furthermore, soil nitrogen acted as a mediator, regulating the relationship between seedling growth and root–leaf traits, specifically leaf dry matter content and root tissue density. Therefore, future studies should consider artificially manipulating tree species diversity based on root–leaf traits characteristics to promote forest recovery. [ABSTRACT FROM AUTHOR]

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15–1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05–1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03–1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention. [ABSTRACT FROM AUTHOR]