A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/fl mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10afl/fl mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/fl mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10afl/fl molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Directional and Orderly Arranged Ni0.9Mn0.1(OH)2 Enables the Synthesis of Single-Crystal Ni-Rich Co-Free LiNi0.9Mn0.1O2 with Enhanced Internal Structural Stability.

In this paper, the effect of the structure characteristics of the precursor on the electrochemical properties of a single-crystal cobalt-free high-nickel LiNi0.9Mn0.1O2 cathode is systematically studied. Precursors with different morphologies are synthesized by adjusting the coprecipitation reaction conditions. The results of SEM and XRD show that with the increase in the orderly stacking arrangement of internal primary nanosheets of Ni0.9Mn0.1(OH)2, the exposed active {010} planes at the surface increase. The prepared cathode materials finally inherit the structural features of the precursor, and the single-crystal Co-free Ni-rich LiNi0.9Mn0.1O2 cathode with highly exposed active {010} planes shows a well-ordered crystal structure and low Li+/Ni2+ cation mixing. The characterization results reveal that the high percentage of {010} planes will improve the Li+ transportation kinetics, decrease electrochemical impedance, and significantly alleviate the accumulation of rock-salt phases. Therefore, the material with this structure shows good electrochemical performance.

Comparison of Surgical and Colonoscopy Tissue to Establish Colorectal Patient-derived Organoids.

BACKGROUND: Patient-derived organoids (PDOs) are ex vivo models that retain the functions and characteristics of individualized source tissues, including a simulated tumor microenvironment. However, the potential impact of undiscovered differences between tissue sources on PDO growth and progression remains unclear. OBJECTIVE: This study aimed to compare the growth and condition of PDO models originating from surgical resection and colonoscopy and to provide practical insights for PDO studies. METHODS: Tissue samples and relevant patient clinical information were collected to establish organoid models. PDOs were derived from both surgical and colonoscopy tissues. The growth of the organoids, including their state, size, and success rate of establishment, was recorded and analyzed. The activity of the organoids at the end stage of growth was detected using calcein-AM fluorescence staining. RESULTS: The results showed that the early growth phase of 2/3 colonoscopy-derived organoids was faster compared to surgical PDOs, with a growth difference observed within 11-13 days of establishment. However, colonoscopy-derived organoids exhibited a diminished growth trend after this time. There were no significant differences observed in the terminal area and quantity between the two types of tissue-derived organoids. Immunofluorescence assays of the PDOs revealed that the surgical PDOs possessed a denser cell mass with relatively higher viability than colonoscopy-derived PDOs. CONCLUSION: In the establishment of colorectal patient-derived organoids, surgically derived organoids require a slightly longer establishment period, while colonoscopy-derived organoids should be passaged prior to growth inhibition to preserve organoid viability.

Cellulose-Assisted Vertically Heterostructured PEO-Based Solid Electrolytes Mitigating Li-Succinonitrile Corrosion for Lithium Metal Batteries.

In the field of solid-state lithium metal batteries (SSLMBs), constructing vertically heterostructured poly(ethylene oxide) (PEO)-based solid electrolytes is an effective method to realize their tight contact with cathodes and Li anodes at the same time. Succinonitrile (SN) has been widely used in PEO-based solid electrolytes to improve the interface contact with cathodes, enhance the ionic conductivities, and obtain a high electrochemical stability window of PEO, but its application is still hindered by its intrinsic instability to Li anodes, which results in corrosion and side interactions with lithium metal. Herein, the cellulose membrane (CM) is introduced creatively into the vertically heterostructured PEO-based solid electrolytes to match the PEO-SN solid electrolytes at the cathode side. With the advantage of the interaction between -OH groups of CM and -C≡N groups in SN, the movement of free SN molecules from cathodes to Li anodes is limited effectively, resulting in a stable and durable SEI layer. In specific, the Li||LiFePO4 battery with the CM-assisted vertically heterostructured PEO-based solid electrolyte by in situ preparation delivers a discharge capacity of around 130 mAh g-1 after 300 cycles and capacity retention of 95% after 500 cycles at 0.5 C. Our work provides a solution to construct PEO-based solid electrolytes feasible to match cathodes and Li anodes effectively by intimate contact with electrodes.

BMPR2 Variants Underlie Nonsyndromic Oligodontia.

Oligodontia manifests as a congenital reduction in the number of permanent teeth. Despite the major efforts that have been made, the genetic etiology of oligodontia remains largely unknown. Bone morphogenetic protein receptor type 2 (BMPR2) variants have been associated with pulmonary arterial hypertension (PAH). However, the genetic significance of BMPR2 in oligodontia has not been previously reported. In the present study, we identified a novel heterozygous variant (c.814C > T; p.Arg272Cys) of BMPR2 in a family with nonsyndromic oligodontia by performing whole-exome sequencing. In addition, we identified two additional heterozygous variants (c.1042G > A; p.Val348Ile and c.1429A > G; p.Lys477Glu) among a cohort of 130 unrelated individuals with nonsyndromic oligodontia by performing Sanger sequencing. Functional analysis demonstrated that the activities of phospho-SMAD1/5/8 were significantly inhibited in BMPR2-knockout 293T cells transfected with variant-expressing plasmids, and were significantly lower in BMPR2 heterozygosity simulation groups than in the wild-type group, indicating that haploinsufficiency may represent the genetic mechanism. RNAscope in situ hybridization revealed that BMPR2 transcripts were highly expressed in the dental papilla and adjacent inner enamel epithelium in mice tooth germs, suggesting that BMPR2 may play important roles in tooth development. Our findings broaden the genetic spectrum of oligodontia and provide clinical and genetic evidence supporting the importance of BMPR2 in nonsyndromic oligodontia.

A Novel CDH1 Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome.

The goal of the current study was to identify the pathogenic gene variant in a Chinese family with Blepharocheilodontic (BCD) syndrome. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variant. The harmfulness of the variant was predicted by bioinformatics. We identified a novel heterozygous missense variant c.1198G>A (p.Asp400Asn) in the CDH1 gene in the proband and his mother with BCD syndrome. The sequencing results of three healthy individuals in this family are wild type. This result is consistent with familial co-segregation. According to ReVe, REVEL, CADD, gnomAD, dbSNP, and the classification of pathogenic variants with the standards of the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG), c.1198G>A (p.Asp400Asn) is predicted to be a likely pathogenic. We observed that variant c.1198G>A (p.Asp400Asn) was located in the extracellular cadherin-type repeats in CDH1. Amino acid sequence alignment of the CDH1 protein among multiple species showed that Asp400 was highly evolutionarily conserved. The conformational analysis showed that this variant might cause structural damage to the CDH1 protein. Phenotypic analysis revealed unique dental phenotypes in patients with BCD syndrome, such as oligodontia, conical-shaped teeth, and notching of the incisal edges. Our results broaden the variation spectrum of BCD syndrome and phenotype spectrum of CDH1, which can help with the clinical diagnosis, treatment, and genetic counseling in relation to BCD syndrome.

Dose Dependence Effect in Biallelic WNT10A Variant-Associated Tooth Agenesis Phenotype.

The goal of this study was to identify the pathogenic gene variants in patients with odonto-onycho-dermal dysplasia syndrome (OODD) or nonsyndromic tooth agenesis. Four unrelated individuals with tooth agenesis and their available family members were recruited. Peripheral blood was collected from four probands and five family members. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variants. The harmfulness of these variations was predicted by bioinformatics. We identified four biallelic variants of the WNT10A gene in four patients, respectively: the proband#660: c.1176C > A (p.Cys392*) and c.812G > A (p.Cys271Tyr); the proband#681: c.637G > A (p.Gly213Ser) and c.985C > T (p.Arg329*); the proband#829: c.511C > T (p.Arg171Cys) and c.637G > A (p.Gly213Ser); and the proband#338: c.926A> G (p.Gln309Arg) and c.511C > T (p.Arg171Cys). Among them, two variants (c.812G > A; p.Cys271Tyr and c.985C > T; p.Arg329*) were previously unreported. Bioinformatics analysis showed that the pathogenicity of these six variants was different. Tertiary structure analysis showed that these variants were predicted to cause structural damage to the WNT10A protein. Genotype−phenotype analysis showed that the biallelic variants with more harmful effects, such as nonsense variants, caused OODD syndrome (#660 Ⅱ-1) or severe nonsyndromic tooth agenesis (NSTA) (#681 Ⅱ-1); the biallelic variants with less harmful effects, such as missense variants, caused a mild form of NSTA (#829 Ⅱ-2 and #338 Ⅱ-1). Individuals with a heterozygous variant presented a mild form of NSTA or a normal state. Our results further suggest the existence of the dose dependence of WNT10A pathogenicity on the tooth agenesis pattern, which broadens the variation spectrum and phenotype spectrum of WNT10A and could help with clinical diagnosis, treatment, and genetic counseling.

Structure and Properties of Bioactive Glass-Modified Calcium Phosphate/Calcium Sulfate Biphasic Porous Self-Curing Bone Repair Materials and Preliminary Research on Their Osteogenic Effect.

In this study, calcium phosphate (CP)/calcium sulfate biphasic bone repair materials were modified with bioactive-glass (BG) to construct a self-curing bone repair material. Tetracalcium phosphate, calcium hydrogen phosphate dihydrate, and calcium sulfate hemihydrate (CSH) with different BG ratios and phosphate solution were reacted to prepare a porous self-curing bone repair material (CP/CSH/BG). The solidification time was about 12 min, and the material was morphologically stable in 24 h. The porosity was about 50%, with a pore size around 200 µm. The strength of CP/CSH/BG was approaching trabecular bone, and could be gradually degraded in Tris-HCl solution. MC3T3-E1 cells were cultured in the leaching solution of the materials. Cytotoxicity was detected using Cell Counting Kit 8 assays, and the expression of osteogenesis-related biomarkers was detected using quantitative real-time reverse transcription PCR (qRT-PCR). The results showed that all BG groups had increased ALP and ARS staining, implying that the BG groups could promote osteoblast mineralization in vitro. qRT-PCR showed significant upregulation of bone-related gene expression (Osx, Ocn, Runx2, and Col1) in the 20% BG group (p < 0.05). Therefore, the CP/CSH/BG self-curing bone repair materials can promote osteogenesis, and might be applied for bone regeneration, especially for polymorphic bone defect repair.

Bufalin Inhibits Tumorigenesis, Stemness, and Epithelial-Mesenchymal Transition in Colorectal Cancer through a C-Kit/Slug Signaling Axis.

Colorectal cancer (CRC) is a major source of morbidity and mortality, characterized by intratumoral heterogeneity and the presence of cancer stem cells (CSCs). Bufalin has potent activity against many tumors, but studies of its effect on CRC stemness are limited. We explored bufalin's function and mechanism using CRC patient-derived organoids (PDOs) and cell lines. In CRC cells, bufalin prevented nuclear translocation of ß-catenin and down-regulated CSC markers (CD44, CD133, LGR5), pluripotency factors, and epithelial-mesenchymal transition (EMT) markers (N-Cadherin, Slug, ZEB1). Functionally, bufalin inhibited CRC spheroid formation, aldehyde dehydrogenase activity, migration, and invasion. Network analysis identified a C-Kit/Slug signaling axis accounting for bufalin's anti-stemness activity. Bufalin treatment significantly downregulated C-Kit, as predicted. Furthermore, overexpression of C-Kit induced Slug expression, spheroid formation, and bufalin resistance. Similarly, overexpression of Slug resulted in increased expression of C-Kit and identical functional effects, demonstrating a pro-stemness feedback loop. For further study, we established PDOs from diagnostic colonoscopy. Bufalin differentially inhibited PDO growth and proliferation, induced apoptosis, restored E-cadherin, and downregulated CSC markers CD133 and C-Myc, dependent on C-Kit/Slug. These findings suggest that the C-Kit/Slug axis plays a pivotal role in regulating CRC stemness, and reveal that targeting this axis can inhibit CRC growth and progression.

Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with Ectodysplasin-A Variants and the X-Chromosome Inactivation Pattern.

The goal of this study was to identify the pathogenic gene variants in female patients with severe X-linked hypohidrotic ectodermal dysplasia (XLHED). Whole-exome sequencing (WES) and Sanger sequencing were used to screen for the pathogenic gene variants. The harmfulness of these variations was predicted by bioinformatics. Then, skewed X-chromosome inactivation (XCI) was measured by PCR analysis of the CAG repeat region in the human androgen receptor (AR) gene in peripheral blood cells. Two novel Ectodysplasin-A (EDA) heterozygous variants (c.588_606del19bp and c.837G>A) and one heterozygous variant (c.1045G>A, rs132630317) were identified in the three female XLHED patients. The bioinformatics analysis showed that these variants might be pathogenic. The tertiary structure analysis showed that these variants could cause structural damage to EDA proteins. Analysis of the skewed X-chromosome inactivation revealed that extreme skewed X-chromosome inactivation was found in patient #35 (98:2), whereas it was comparatively moderate in patients #347 and #204 (21:79 and 30:70). Our results broaden the variation spectrum of EDA and the phenotype spectrum of XLHED, which could help with clinical diagnosis, treatment, and genetic counseling.

KDF1 Novel Variant Causes Unique Dental and Oral Epithelial Defects.

Keratinocyte differentiation factor 1 (KDF1) is a recently identified and rare candidate gene for human tooth agenesis; however, KDF1-related morphological characteristics and pathological changes in dental tissue and the oral epithelium remain largely unknown. Here, we employed whole-exome sequencing (WES) and Sanger sequencing to screen for the suspected variants in a cohort of 151 tooth agenesis patients, and we segregated a novel KDF1 heterozygous missense variation, c.920G>C (p.R307P), in a non-syndromic tooth agenesis family. Essential bioinformatics analyses and tertiary structural predictions were performed to analyze the structural changes and functional impacts of the novel KDF1 variant. The subsequent functional assessment using a TOP-flash/FOP-flash luciferase reporter system demonstrated that KDF1 variants suppressed the activation of canonical Wnt signaling in 293T cells. To comprehensively investigate the KDF1-related oral morphological anomalies, we performed scanning electron microscopy and ground section of the lower right lateral deciduous incisor extracted from #285 proband, and histopathological assessment of the gingiva. The phenotypic analyses revealed a series of tooth morphological anomalies related to the KDF1 variant R307P, including a shovel-shaped lingual surface of incisors and cornicione-shaped marginal ridges with anomalous morphological occlusal grooves of premolars and molars. Notably, keratinized gingival epithelium abnormalities were revealed in the proband and characterized by epithelial dyskeratosis with residual nuclei, indistinct stratum granulosum, epithelial hyperproliferation, and impaired epithelial differentiation. Our findings revealed new developmental anomalies in the tooth and gingival epithelium of a non-syndromic tooth agenesis individual with a novel pathogenic KDF1 variant, broadening the phenotypic spectrum of KDF1-related disorders and providing new evidence for the crucial role of KDF1 in regulating human dental and oral epithelial development.

Rare compound heterozygous variants of LAMB3 and histological features of enamel and oral mucosa.

Junctional epidermolysis bullosa (JEB) is a group of autosomal recessive disorders characterized by amelogenesis imperfecta (AI) and fragility of the skin and mucous membranes. The purpose of this study was to identify pathogenic gene variants and investigate the phenotypic characteristics of abnormal enamel structure and mucocutaneous lesions in a patient with JEB. Clinical examination of the patient revealed hypoplastic AI, skin lesions, and oral ulcers, whereas her parents were normal. Whole-exome sequencing (WES) and cDNA cloning identified compound heterozygous variants of LAMB3 in the proband: c.125G>C in exon 3, c.1288 + 1G>A in intron 11, and c.1348C>T in exon 12. Among these, c.125G>C was inherited from her father, and the other two variants were inherited from her mother. Functional prediction indicated that the variants might change protein structure and cause disease. Scanning electron microscopy (SEM) examination of the primary and permanent teeth revealed abnormal enamel morphology and microstructures. Hematoxylin-eosin (HE) and immunofluorescence (IF) staining showed significantly abnormal and disorganized epithelial cells in the gingival mucosa. Our results showed that this was a case of intermediate JEB1A (OMIM #226650) with autosomal recessive inheritance. The proband carried rare compound heterozygous variants of LAMB3. Our results broaden the variant spectrum of the LAMB3 gene and JEB cases. Moreover, this is the first study to identify histological malformations of the primary teeth and oral mucosa in LAMB3-related patients.

Role of DCLK1 in oncogenic signaling (Review).

Doublecortin­like kinase 1 (DCLK1) has been identified as a novel biomarker of cancer stem cells among several different cancer types, including colon, breast, pancreas, kidney, liver, stomach and esophageal cancers. Studies have demonstrated that DCLK1 regulates tumorigenesis and epithelial­mesenchymal transformation via several important pathways, such as Notch, Wnt/ß­catenin, RAS and multiple microRNAs. The function and biological mechanisms, including their association with the molecular structure and isoforms of DCLK1, are gradually being elucidated. However, the currently available knowledge regarding DCLK1 in terms of developing effective anti­cancer drugs remains incomplete. In the present review, the molecular characteristics, biomarker function and biological mechanisms of DCLK1 are summarized and DCLK1 is proposed as a potential anti­tumor target via the glucose metabolism pathway.

Four Novel PAX9 Variants and the PAX9-Related Non-Syndromic Tooth Agenesis Patterns.

The purpose of this research was to investigate and identify PAX9 gene variants in four Chinese families with non-syndromic tooth agenesis. We identified pathogenic gene variants by whole-exome sequencing (WES) and Sanger sequencing and then studied the effects of these variants on function by bioinformatics analysis and in vitro experiments. Four novel PAX9 heterozygous variants were identified: two missense variants (c.191G > T (p.G64V) and c.350T > G (p.V117G)) and two frameshift variants (c.352delC (p.S119Pfs*2) and c.648_649insC(p.Y217Lfs*100)). The bioinformatics analysis showed that these variants might be pathogenic. The tertiary structure analysis showed that these four variants could cause structural damage to PAX9 proteins. In vitro functional studies demonstrated that (1) the p.Y217Lfs*100 variant greatly affects mRNA stability, thereby affecting endogenous expression; (2) the p. S119Pfs* 2 variant impairs the subcellular localization of the nuclear expression of the wild-type PAX9 protein; and (3) the four variants (p.G64V, p.V117G, p.S119Pfs*2, and p.Y217Lfs*100) all significantly affect the downstream transcriptional activity of the BMP4 gene. In addition, we summarized and analyzed tooth missing positions caused by PAX9 variants and found that the maxillary second molar (84.11%) and mandibular second molar (84.11%) were the most affected tooth positions by summarizing and analyzing the PAX9-related non-syndromic tooth agenesis positions. Our results broaden the variant spectrum of the PAX9 gene related to non-syndromic tooth agenesis and provide useful information for future genetic counseling.

Li-Deficient Materials-Decoration Restrains Oxygen Evolution Achieving Excellent Cycling Stability of Li-Rich Mn-Based Cathode.

With the increasing demand for high energy density and rapid charging performance, Li-rich materials have been the up and coming cathodes for next-generation lithium-ion batteries. However, because of oxygen evolution and structural instability, the commercialization of Li-rich materials is extremely retarded by their poor electrochemical performances. In this work, Li-deficient materials Li0.3NbO2 and (Nb0.62Li0.15)TiO3 are applied to functionalize the surface of Li1.2Mn0.54Ni0.13Co0.13O2, aiming to suppress oxygen evolution and increase structural stability in LIBs. In addition, a fast Li-ion transport channel is beneficial to enhance Li+ diffusion kinetics. The results demonstrate that the electrodes decorated with Li0.3NbO2 and (Nb0.62Li0.15)TiO3 materials exhibit more stable cycling stability after long-term cycling and outstanding rate capability.

Novel DLX3 variant identified in a family with tricho-dento-osseous syndrome.

OBJECTIVES: To identify DLX3 variants in a Chinese family with typical clinical manifestations of tricho-dento-osseous syndrome (TDO). DESIGN: Sanger sequencing was performed to detect DLX3 variants in the TDO family. Three-dimensional laser scanning microscopy, bioinformatic and conformational analyses were employed to explore the phenotypic characterization and the functional impact. RESULTS: We identified a novel heterozygous variant in the DLX3 gene (c.534G>C; p.Gln178His). Familial co-segregation verified an autosomal dominant inheritance pattern. Bioinformatic prediction demonstrated the deleterious effects of the variant, and DLX3 structure changes suggested the corresponding functional impairments. CONCLUSIONS: We identified a variant in the DLX3 gene in an integrated family of Han nationality for the first time. This study expands the variant spectrum of DLX3 and phenotype spectrum of TDO syndrome.

Reversal of the intrusion of a natural tooth located between two implant-supported crowns: A 7-year follow-up report.

In patients with implant-supported restorations, intrusion rarely occurs in nonconnected natural teeth. This clinical report describes the intrusion of a natural tooth located between 2 implant-supported crowns after 4 months of normal function. The second premolar was intruded by 3 mm. The intrusion was completely reversed after interproximal contact adjustments, and the tooth position was stable at the 7-year follow-up.

Accuracy of a milled digital implant surgical guide: An in vitro study.

STATEMENT OF PROBLEM: An accurate surgical template for guided implant surgery is essential for the success of an implant restoration. However, reports on the accuracy of digitally designed and computer numeric controlled (CNC) machine-milled surgical templates are sparse. PURPOSE: The purpose of this in vitro study was to investigate the accuracy of an implant surgical guide digitally designed by using data from cone beam computed tomography (CBCT) scans and milled with a 5-axis CNC machine. MATERIAL AND METHODS: Six representative radiographic templates were prepared from radiopaque resin plates. For each guide, a CBCT scan was made, and the extracted Digital Imaging and Communications in Medicine (DICOM) data were imported into a planning software program (ORGANICAL Dental Implant). Nine implants were virtually designed for each guide. The design data were imported into a 5-axis CNC machine, and the radiographic guides were fixed onto the CNC machine (Organical Multi S). Bore holes for surgical guide sleeves were milled directly in the radiographic template, which was converted into a surgical template. After the milling process, the surgical guides were scanned by using a laboratory cast scanner. The deviation between the position of the sleeve bore hole in the milled template and that in the virtual implant planning was digitally calculated. RESULTS: The mean global deviation of the surgical guide was 0.16 ±0.06 mm in the circle center of the sleeve top, and the mean angular deviation was 0.61 ±0.40 degrees. The sleeve-implant distance and the sleeve axis angle showed no significant influence on the in vitro accuracy of the implant surgical guide. CONCLUSIONS: The mean deviation of the surgical guide prepared by using the virtual planning software program and 5-axis CNC milling procedure in this study was 0.16 ±0.06 mm in the center of the sleeve top. Thus, the guide had acceptable precision.

Rare phenotype: Hand preaxial polydactyly associated with LRP6-related tooth agenesis in humans.

Low-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported in Lrp6-deficient mice, it has been rarely discovered in humans with LRP6 mutations. Here, we demonstrate an unreported autosomal dominant LRP6 heterozygous mutation (c.2840 T > C;p.Met947Thr) in a tooth agenesis family with hand polydactyly, and another unreported autosomal dominant LRP6 heterozygous mutation (c.1154 G > C;p.Arg385Pro) in a non-syndromic tooth agenesis family. Bioinformatic prediction demonstrated the deleterious effects of the mutations, and LRP6 structure changes suggested the corresponding functional impairments. Analysis on the pattern of LRP6-related tooth agenesis demonstrated the maxillary lateral incisor was the most affected. Our study report that LRP6 mutation might be associated with hand preaxial polydactyly in humans, which broaden the phenotypic spectrum of LRP6-related disorders, and provide valuable information on the characteristics of LRP6-related tooth agenesis.

Surface LiMn1.4Ni0.5Mo0.1O4 Coating and Bulk Mo Doping of Li-Rich Mn-Based Li1.2Mn0.54Ni0.13Co0.13O2 Cathode with Enhanced Electrochemical Performance for Lithium-Ion Batteries.

To improve the initial Coulombic efficiency, cycling stability, and rate performance of the Li-rich Mn-based Li1.2Mn0.54Ni0.13Co0.13O2 cathode, the combination of LiMn1.4Ni0.5Mo0.1O4 coating with Mo doping has been successfully carried out by the sol-gel method and subsequent dip-dry process. This strategy buffers the electrodes from the corrosion of electrolyte and enhances the lattice parameter, which could inhibit the oxygen release and maintain the structural stability, thus improving the cycle stability and rate capability. After LiMn1.4Ni0.5Mo0.1O4 modification, the initial discharge capacity reaches 272.4 mAh g-1 with a corresponding initial Coulombic efficiency (ICE) of 84.2% at 0.1C (1C = 250 mAh g-1), far higher than those (221.5 mAh g-1 and 68.9%) of the pristine sample. Besides, the capacity retention of the coated sample is enhanced by up to 66.8% after 200 cycles at 0.1C. Especially, the rate capability of the coated sample is 95.2 mAh g-1 at 5C. XRD, SEM, TEM, XPS, and Raman spectroscopy are adopted to characterize the morphologies and structures of the samples. This coating strategy has been demonstrated to be an effective approach to construct high-performance energy storage devices.