A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.

PurposePreaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown.MethodsA rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model.ResultsA novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression.ConclusionOur results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms

The nature of photogenerated charge separation among different crystal facets of BiVO4 studied by density functional theory

Charge separation among different crystal facets of a semiconductor has been observed experimentally, but the underlying reasons behind this phenomenon are unknown. In this work, the activation energies of carrier hopping and the mobility of electron/hole transport along seven low-index crystal orientations of bulk BiVO4 have been calculated using a small polaron model. The calculated mobility and our previous experimental results reveal that there is a parallel relationship between the carrier mobility along the crystal axis and the carrier preferred accumulation on the corresponding crystal facets. It is proposed that the mobility of electrons (or holes) along the crystal axis [hkl] might be essentially related to the charge separation among the indices of corresponding facets (hkl); namely, the mobility of electrons (or holes) along the crystal axis [hkl] is the largest among all possible crystal axes, and the photogenerated electrons (or holes) tend to be accumulated on the indices of the corresponding facet (hkl) when the surface factors like surface band bending, surface energetic differences, etc. are not considered

Theoretical insight into the roles of cocatalysts in the Ni-NiO/β-Ga2O3 photocatalyst for overall water splitting

The formation and stability of Nin and (NiO)n (n = 1-4) clusters on the β-Ga2O3 surface have been studied by means of first-principles density functional theory calculations. It is found that the optimum interaction of the Nin and (NiO)n clusters with the surface requires different surface sites. This optimizes the formation of interfacial bonds between the atoms from clusters and the coordinatively unsaturated atoms from the surface. The stability of the adsorbed Ni clusters increases with the number of Ni atoms. In a Nin/Ga2O3 system, as the Ga unoccupied states overlap with the unoccupied Ni state, the excited electrons transferred from Ga to Ni participate in the proton reduction reaction. Our calculations show that (NiO)n clusters strongly adsorb on the Ga2O3 surface due to the negative adsorption energies within -1.9 eV to -3.7 eV. For (NiO)n/Ga2O3, occupied states from the (NiO)n cluster may accept the holes from O atoms in the Ga2O3 surface to take part in the photocatalytic water oxidation reaction

Theoretical insight into the roles of cocatalysts in the Ni-NiO/β-Ga2O3 photocatalyst for overall water splitting

The formation and stability of Nin and (NiO)n (n = 1-4) clusters on the β-Ga2O3 surface have been studied by means of first-principles density functional theory calculations. It is found that the optimum interaction of the Nin and (NiO)n clusters with the surface requires different surface sites. This optimizes the formation of interfacial bonds between the atoms from clusters and the coordinatively unsaturated atoms from the surface. The stability of the adsorbed Ni clusters increases with the number of Ni atoms. In a Nin/Ga2O3 system, as the Ga unoccupied states overlap with the unoccupied Ni state, the excited electrons transferred from Ga to Ni participate in the proton reduction reaction. Our calculations show that (NiO)n clusters strongly adsorb on the Ga2O3 surface due to the negative adsorption energies within -1.9 eV to -3.7 eV. For (NiO)n/Ga2O3, occupied states from the (NiO)n cluster may accept the holes from O atoms in the Ga2O3 surface to take part in the photocatalytic water oxidation reaction

Theoretical insight into the roles of cocatalysts in the Ni-NiO/β-Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e photocatalyst for overall water splitting

\u3cp\u3eThe formation and stability of Ni\u3csub\u3en\u3c/sub\u3e and (NiO)\u3csub\u3en\u3c/sub\u3e (n = 1-4) clusters on the β-Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e surface have been studied by means of first-principles density functional theory calculations. It is found that the optimum interaction of the Ni\u3csub\u3en\u3c/sub\u3e and (NiO)\u3csub\u3en\u3c/sub\u3e clusters with the surface requires different surface sites. This optimizes the formation of interfacial bonds between the atoms from clusters and the coordinatively unsaturated atoms from the surface. The stability of the adsorbed Ni clusters increases with the number of Ni atoms. In a Ni\u3csub\u3en\u3c/sub\u3e/Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e system, as the Ga unoccupied states overlap with the unoccupied Ni state, the excited electrons transferred from Ga to Ni participate in the proton reduction reaction. Our calculations show that (NiO)\u3csub\u3en\u3c/sub\u3e clusters strongly adsorb on the Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e surface due to the negative adsorption energies within -1.9 eV to -3.7 eV. For (NiO)\u3csub\u3en\u3c/sub\u3e/Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e, occupied states from the (NiO)\u3csub\u3en\u3c/sub\u3e cluster may accept the holes from O atoms in the Ga\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e3\u3c/sub\u3e surface to take part in the photocatalytic water oxidation reaction.\u3c/p\u3

Comparative Transcriptome Analysis Reveals the Effect of Lignin on Storage Roots Formation in Two Sweetpotato (<i>Ipomoea batatas</i> (L.) Lam.) Cultivars

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important crops with high storage roots yield. The formation and expansion rate of storage root (SR) plays a crucial role in the production of sweet potato. Lignin affects the SR formation; however, the molecular mechanisms of lignin in SR development have been lacking. To reveal the problem, we performed transcriptome sequencing of SR harvested at 32, 46, and 67 days after planting (DAP) to analyze two sweet potato lines, Jishu25 and Jishu29, in which SR expansion of Jishu29 was early and had a higher yield. A total of 52,137 transcripts and 21,148 unigenes were obtained after corrected with Hiseq2500 sequencing. Through the comparative analysis, 9577 unigenes were found to be differently expressed in the different stages in two cultivars. In addition, phenotypic analysis of two cultivars, combined with analysis of GO, KEGG, and WGCNA showed the regulation of lignin synthesis and related transcription factors play a crucial role in the early expansion of SR. The four key genes swbp1, swpa7, IbERF061, and IbERF109 were proved as potential candidates for regulating lignin synthesis and SR expansion in sweet potato. The data from this study provides new insights into the molecular mechanisms underlying the impact of lignin synthesis on the formation and expansion of SR in sweet potatoes and proposes several candidate genes that may affect sweet potato yield

Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells

The type III transforming growth factor-β (TGF-β) receptor (TβRIII), a coreceptor of the TGF-β superfamily, is known to bind TGF-βs and regulate TGF-β signaling. However, the regulatory roles of TβRIII in TGF-β-induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present study examined the effect of TβRIII RNA interference (RNAi) on TGF-β3-induced human MSC (hMSC) chondrogenesis and possible signal mechanisms. A lentiviral expression vector containing TβRIII small interfering RNA (siRNA) (SiTβRIII) or a control siRNA (SiNC) gene was constructed and infected into hMSCs. The cells were cultured in chondrogenic medium containing TGF-β3 or control medium. TβRIII RNAi significantly enhanced TGF-β3-induced chondrogenic differentiation of hMSCs, the ratio of type II (TβRII) to type I (TβRI) TGF-β receptors, and phosphorylation levels of Smad2/3 as compared with cells infected with SiNC. An inhibitor of the TGF-β signal, SB431542, not only inhibited TβRIII RNAi-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also inhibited the effects of TβRIII RNAi on TGF-β3-induced chondrogenic differentiation. These results demonstrate that TβRIII RNAi enhances TGF-β3-induced chondrogenic differentiation in hMSCs by activating TGF-β/Smad2/3 signaling. The finding points to the possibility of modifying MSCs by TβRIII knockdown as a potent future strategy for cell-based cartilage tissue engineering

Automatic Lenke classification of adolescent idiopathic scoliosis with deep learning

Abstract Purpose The Lenke classification system is widely utilized as the preoperative evaluation protocol for adolescent idiopathic scoliosis (AIS). However, manual measurement is susceptible to observer‐induced variability, which consequently impacts the evaluation of progression. The goal of this investigation was to develop an automated Lenke classification system utilizing innovative deep learning algorithms. Methods Using the database from the First Affiliated Hospital of Sun Yat‐sen University, the whole spinal x‐rays images were retrospectively collected. Specifically, images collection was divided into AIS and control group. The control group consisted of individuals who underwent routine health checks and did not have scoliosis. Afterwards, relative features of all images were annotated. Deep learning was implemented through the utilization of the key‐point based detection method to realize the vertebral detection, and Cobb angle measurement and scoliosis classification were performed based on relevant standards. Besides, the segmentation method was employed to achieve the recognition of lumbar vertebral pedicle to determine the type of lumbar spine modifier. Finally, the model performance was further quantitatively analyzed. Results In the study, a total of 2082 spinal x‐ray images were collected from 407 AIS patients and 227 individuals in the control group. The model for vertebral detection achieved an F1‐score of 0.809 for curve type evaluation and an F1‐score of 0.901 for thoracic sagittal profile. The intraclass correlation efficient (ICC) of the Cobb angle measurement was 0.925. In the analysis of performance for vertebra pedicle segmentation model, the F1‐score of lumbar modification profile was 0.942, the intersection over union (IOU) of the target pixels was 0.827, and the Hausdorff distance (HD) was 6.565 ± 2.583 mm. Specifically, the F1‐score for ultimate Lenke type classifier was 0.885. Conclusions This study has constructed an automated Lenke classification system by employing the deep learning networks to achieve the recognition pattern and feature extraction. Our models require further validation in additional cases in the future