Clinical Application of the 4K-3D Exoscope System in Cochlear Implantation.

PURPOSE: To evaluate a system for otomicrosurgery based on 4K three-dimensional (3D) exoscope technology and apply it to cochlear implantation. METHODS: An open stereoscopic vision-based surgical system, which differs from traditional surgical microscopes, was created by utilizing 4K stereo imaging technology and combining it with low-latency 4K ultra-high-definition 3D display. The system underwent evaluation based on 57 cochlear implantation operations, three designed microscopic manipulations, and a questionnaire survey. RESULTS: The surgical images displayed by the 4K-3D exoscope system (4K-3D-ES) are stereoscopic, clear, and smooth. The use of 4K-3D-ES in cochlear implantation is not inferior to traditional microscopes in terms of intraoperative bleeding and surgical complications, and the surgical duration is not slower or may even be faster than when using traditional microscopes. The results of micromanipulation experiments conducted on 16 students also confirmed this and demonstrated that 4K-3D-ES can be easily adapted. Furthermore, additional advantages of 4K-3D-ES were gathered. Significantly enlarged and high-definition stereoscopic images contribute to the visualization of finer anatomical microstructures such as chordae tympani, ensuring safer surgery. Users feel more comfortable in their necks, shoulders, waists, and backs. Real-time shared stereoscopic view for multiple people, convenient for collaboration and teaching. The ear endoscope and 4K-3D-ES enable seamless switching on the same screen. High-definition 3D images and videos can be saved with just one click, making future publication and communication convenient. CONCLUSION: The feasibility and safety of 4K-3D-ES for cochlear implantation surgery have been demonstrated. The 4K-3D-ES also offers numerous unique advantages and holds clinical application and promotional value.

Associations between sleep duration trajectories and cognitive decline: A longitudinal cohort study in China.

OBJECT: The relationship between sleep duration trajectories and cognitive decline remains uncertain. This study aims to examine the connections between various patterns of sleep duration and cognitive function. METHODS: Group-based trajectory modeling (GBTM) was employed to identify longitudinal trajectories of sleep duration over four-year follow-up period, while considering age, sex and nap duration as adjustments. Logistic regression was utilized to analyze the association between sleep trajectories and cognition, with odds ratios (OR) and 95 % confidence intervals (CI) reported. Subgroup analyses based on various demographic characteristics were conducted to explore potential differences in sleep trajectories and cognitive decline across different population subgroups. RESULTS: A total of 5061 participants were followed for four years, and three sleep duration trajectories were identified: high increasing (n = 2101, 41.6 %), stable increasing (n = 2087, 40.7 %), and low decreasing (n = 873, 17.7 %). After adjustment for basic demographic information, health status, and baseline cognition, the high increasing trajectory was found to be associated with cognitive decline in terms of global cognition (OR:1.52,95 %CI:1.18-1.96), mental intactness (OR:1.36,95 %CI:1.07-1.73) and episodic memory (OR:1.33, 95 %CI:1.05-1.67), as compared to stable increasing trajectory. These associations were particularly prominent among the non-elderly population (≤65 years) and those without depressive symptoms. CONCLUSION: This study suggests that both high increasing and low decreasing sleep duration trajectories are linked to cognitive decline, as compared to the stable increasing trajectory. Long-term attention to changes in sleep duration facilitates early prevention of cognitive decline.

Ionic Liquid Gating Induces Anomalous Permeation through Membrane Channel Proteins.

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.

The efficacy of bracing in the treatment of progressive early-onset scoliosis.

Serial casting as one of the applications to treat early-onset scoliosis has been reported efficiently to improve deformity, but no report has focused on the efficacy of braces in the treatment of congenital early-onset scoliosis and comparison with progressive idiopathic early-onset scoliosis. Patients with progressive EOS treated with braces in our institution with a minimum of 4 years follow-up were reviewed. Two groups according to the etiological diagnosis were analyzed and compared: the congenital scoliosis (CS) group and idiopathic scoliosis (IS) group. The success cases and the failure cases were also compared. 27 patients with an average main Cobb angle of 38.19° (20-55) underwent initial bracing at an average age of 55.7 months (24-108), the average follow-up time was 76.19 months (49-117). In IS group the main Cobb angle was corrected to 18.69 ± 12.06° (48.61%) following the first bracing; the final Cobb angle was 23.08 ± 22.15°(38.76%) after brace removal. In CS group the main Cobb angle was corrected to 33.93 ± 10.31°(17.1%) following the first bracing and 37.93 ± 14.74°(3.53%) after brace removal. Both coronal chest width and T1-T12 height increased dramatically from pre-bracing to the last follow-up. Patients diagnosed as IS tended to have a better result in main Cobb angle correction than that of CS (P = 0.049). By the time of last follow-up, 8 patients had undergone surgery, and the operation time was postponed by 68.88 ± 26.43 months. For patients with progressive early-onset scoliosis, bracing is an efficient nonsurgical alternative to casting, and some of them can be cured; if not, eventual surgical intervention can be delayed for a period of time without restrictions on the thoracic cavity.

Pure-high-even-order dispersion bound solitons complexes in ultra-fast fiber lasers.

Temporal solitons have been the focus of much research due to their fascinating physical properties. These solitons can form bound states, which are fundamentally crucial modes in fiber laser and present striking analogies with their matter molecules counterparts, which means they have potential applications in large-capacity transmission and all-optical information storage. Although traditionally, second-order dispersion has been the dominant dispersion for conventional solitons, recent experimental and theoretical research has shown that pure-high-even-order dispersion (PHEOD) solitons with energy-width scaling can arise from the interaction of arbitrary negative-even-order dispersion and Kerr nonlinearity. Despite these advancements, research on the bound states of PHEOD solitons is currently non-existent. In this study, we obtained PHEOD bound solitons in a fiber laser using an intra-cavity spectral pulse shaper for high-order dispersion management. Specifically, we experimentally demonstrate the existence of PHEOD solitons and PHEOD bound solitons with pure-quartic, -sextic, -octic, and -decic dispersion. Numerical simulations corroborate these experimental observations. Furthermore, vibrating phase PHEOD bound soliton pairs, sliding phase PHEOD bound soliton pairs, and hybrid phase PHEOD bound tri-soliton are discovered and characterized. These results broaden the fundamental understanding of solitons and show the universality of multi-soliton patterns.

Enhancing crystal integrity and structural rigidity of CsPbBr3 nanoplatelets to achieve a narrow color-saturated blue emission.

Quantum-confined CsPbBr3 perovskites are promising blue emitters for ultra-high-definition displays, but their soft lattice caused by highly ionic nature has a limited stability. Here, we endow CsPbBr3 nanoplatelets (NPLs) with atomic crystal-like structural rigidity through proper surface engineering, by using strongly bound N-dodecylbenzene sulfonic acid (DBSA). A stable, rigid crystal structure, as well as uniform, orderly-arranged surface of these NPLs is achieved by optimizing intermediate reaction stage, by switching from molecular clusters to mono-octahedra, while interaction with DBSA resulted in formation of a CsxO monolayer shell capping the NPL surface. As a result, both structural and optical stability of the CsPbBr3 NPLs is enhanced by strong covalent bonding of DBSA, which inhibits undesired phase transitions and decomposition of the perovskite phase potentially caused by ligand desorption. Moreover, rather small amount of DBSA ligands at the NPL surface results in a short inter-NPL spacing in their closely-packed films, which facilitates efficient charge injection and transport. Blue photoluminescence of the produced CsPbBr3 NPLs is bright (nearly unity emission quantum yield) and peaks at 457 nm with an extremely narrow bandwidth of 3.7 nm at 80 K, while the bandwidth of the electroluminescence (peaked at 460 nm) also reaches a record-narrow value of 15 nm at room temperature. This value corresponds to the CIE coordinates of (0.141, 0.062), which meets Rec. 2020 standards for ultra-high-definition displays.

Effects of different sizes of microplastic particles on soil respiration, enzyme activities, microbial communities, and seed germination.

Microplastics (MPs) are emerging pollutants of terrestrial ecosystems. The impacts of MP particle size on terrestrial systems remain unclear. The current study aimed to investigate the effects of six particle sizes (i.e., 4500, 1500, 500, 50, 5, and 0.5 µm) of polyethylene (PE) and polyvinyl chloride (PVC) on soil respiration, enzyme activity, bacteria, fungi, protists, and seed germination. MPs significantly promoted soil respiration, and the stimulating effects of PE were the strongest for medium and small-sized (0.5-1500 µm) particles, while those of PVC were the strongest for small particle sizes (0.5-50 µm). Large-sized (4500 µm) PE and all sizes of PVC significantly improved soil urease activity, while medium-sized (1500 µm) PVC significantly improved soil invertase activity. MPs altered the soil microbial community diversity, and the effects were especially pronounced for medium and small-sized (0.5-1500 µm) particles of PE and PVC on bacteria and fungi and small-sized (0.5 µm) particles of PE on protists. The impacts of MPs on bacteria and fungi were greater than on protists. The seed germination rate of Brassica chinensis decreased gradually with the decrease in PE MPs particle size. Therefore, to reduce the impact of MPs on soil ecosystems, effective measures should be taken to avoid the transformation of MPs into smaller particles in soil environmental management.

Aberrant effort-based reward dynamics in anhedonia.

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.

Spin Crossover in [Fe(qsal-5-Brq)2]+ Complexes with a Quinoline-Substituted Qsal Ligand.

Using a quinoline substituted Qsal ligand, Hqsal-5-Brq (Hqsal-5-Brq = N-(5-bromo-8-quinolyl)salicylaldimine), four FeIII complexes, [Fe(qsal-5-Brq)2]A·CH3OH (Y = NO3- (1NO3), BF4- (2BF4), PF6- (3PF6), OTf- (4OTf), were prepared and characterized. Structure analysis revealed that complex 2BF4 contained two species (2BF4(P1̅) and 2BF4(C2/c)). In these compounds except 3PF6, the [Fe(qsal-5-Brq)2]+ cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3PF6, a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1NO3 and 2BF4(P1̅) displayed abrupt hysteretic SCO with the transition temperature T1/2↓ = 235 K, T1/2↑ = 240 K for 1NO3 and T1/2↓ = 230 K, T1/2↑ = 235 K for 2BF4(P1̅), while compounds 3PF6 and 4OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1NO3 and 2BF4 show a gradual SCO, desolvated 3PF6 undergoes a two-step SCO, and desolvated 4OTf exhibits a hysteretic transition. Overall, this work reported the FeIII-SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting FeIII-SCO materials.

Acid etching post-treatment enhanced fungal sterilization performance of copper-manganese-cerium oxide in liquid and aerosol: Materials and molecular biological mechanisms.

Bioaerosol is one of the main ways to spread respiratory infectious diseases. In order to further improve the sterilization efficiency of copper-manganese-cerium oxide (CuMnCeOx), the post-treatment method based on acid etching was adopted. The results showed that sterilization efficiency of the treated CuMnCeOx could reach 99% in aerosol with space velocity of 1400 h-1. L(+)-ascorbic acid successfully promoted the formation of Cu+, oxygen vacancies and the generation of reactive oxygen species (ROS) on the surface of the treated CuMnCeOx. During sterilization in liquid system, the transcriptome identified 316 differentially expressed genes, including 270 up-regulated genes and 46 down-regulated genes. Differentially expressed genes were significantly enriched in cell wall (GO:0005618) and external encapsulating structure (GO:0030312). Up-regulated genes were shown in regulation of reactive oxygen species biosynthetic processes (GO:1903409, GO:1903426, GO:1903428) and positive regulation all of reactive oxygen species metabolic process (GO:2000379), indicating that ROS induced cell death by destroying cell wall.

Meta-analysis of the clinical efficacy of the Gamma3 nail vs Gamma3U-blade system in the treatment of intertrochanteric fractures.

BACKGROUND: The traditional Gamma3 nail is a mainstream treatment for femoral intertrochanteric fractures. Literature reports that the Gamma3U-blade system can increase the stability of the Gamma3 nail and reduce complication incidence. However, comparative studies between the Gamma3U-blade and Gamma3 systems are limited; hence, this meta-analysis was performed to explore the clinical efficacy of these two surgical methods. AIM: To investigate the clinical efficacy of Gamma3 and Gamma3 U-blade for intertrochanteric fractures. METHODS: A computerized search for Chinese and English literature published from 2010 to 2022 was conducted in PubMed, Cochrane, CNKI, Wanfang, and VIP databases. The search keywords were gamma 3, gamma 3 U blade, and intertrochanteric fracture. Additionally, literature tracking was performed on the references of published literature. The data were analyzed using Revman 5.3 software. Two individuals checked the inputs for accuracy. Continuous variables were described using mean difference and standard deviation, and outcome effect sizes were expressed using ratio OR and 95% confidence interval (CI). High heterogeneity was considered at (P < 0.05, I2 > 50%), moderate heterogeneity at I2 from 25% to 50%, and low heterogeneity at (P ≥ 0.05, I2 < 50%). RESULTS: Following a comprehensive literature search, review, and analysis, six articles were selected for inclusion in this study. This selection comprised five articles in English and one in Chinese, with publication years spanning from 2016 to 2022. The study with the largest sample size, conducted by Seungbae in 2021, included a total of 304 cases. Statistical analysis: A total of 1063 patients were included in this meta-analysis. The main outcome indicators were: Surgical time: The Gamma3U blade system had a longer surgical time compared to Gamma3 nails (P = 0.006, I2 = 76%). Tip-apex distance: No statistical significance or heterogeneity was observed (P = 0.65, I2 = 0%). Harris Hip score: No statistical significance was found, and low heterogeneity was detected (P = 0.26, I2 = 22%). Union time: No statistical significance was found, and high heterogeneity was detected (P = 0.05, I2 = 75%). CONCLUSION: Our study indicated that the Gamma3 system reduces operative time compared to the Gamma3 U-blade system in treating intertrochanteric fractures. Both surgical methods proved to be safe and effective for this patient group. These findings may offer valuable insights and guidance for future surgical protocols in hip fracture patients.

[Identification and expression pattern analysis of a secretory phospholipase A2 gene in Bombyx mori].

Phospholipase A2 (PLA2) is widely distributed in animals, plants, and microorganisms, and it plays an important role in many physiological activities. In a previous study, we have identified a secretory PLA2 in Bombyx mori (BmsPLA2-1-1). In this study, we further identified four new sPLA2 genes (BmsPLA2-1-2, BmsPLA2-2, BmsPLA2-3, and BmsPLA2-4) in B. mori genome. All four genes exhibits the characteristic features of sPLA2, including the sPLA2 domain, metal binding sites, and highly conserved catalytic domain. This study completed the cloning, in vitro expression, and expression pattern analysis of the BmsPLA2-4 gene in B. mori. The full length of BmsPLA2-4 is 585 bp, and the recombinant protein obtained through prokaryotic expression has an estimated size of 25 kDa. qRT-PCR analysis revealed that the expression level of BmsPLA2-4 reached its peak on the first day of the fifth instar larval stage. Tissue expression profiling analysis showed that BmsPLA2-4 had the highest expression level in the midgut, followed by the epidermis and fat body. Western blotting analysis results were consistent with those of qRT-PCR. Furthermore, after infecting fifth instar 1-day-old larvae with Escherichia coli and Staphylococcus aureus, the expression level of the BmsPLA2-4 gene significantly increased in 24 h. The findings of this study provides a theoretical basis and valuable experimental data for future related research.

Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

Adding carbon sources to the substrates enhances Cr and Ni removal and mitigates greenhouse gas emissions in constructed wetlands.

Constructed wetlands for wastewater treatment pose challenges related to long-term operational efficiency and greenhouse gas emissions on a global scale. This study investigated the impact of adding peat, humic acid, and biochar into the substrates of constructed wetlands and focused on Cr, and Ni removal, greenhouse gas emissions, and microbial communities in constructed wetlands. Biochar addition treatment achieved the highest removal efficiencies for total Cr (99.96%), Cr (VI) (100%), and total Ni (91.04%). Humic acid and biochar addition both significantly increased the heavy metal content in wetland plant Leersia hexandra and substrates of constructed wetlands. Further analysis of microbial community proportions by high-throughput sequencing revealed that biochar and humic acid treatments enhanced Cr and Ni removal efficiency by increasing the abundance of Bacteroidetes, Geobacter and Ascomycota. Humic acid addition treatment reduced CO2 emissions by decreasing the abundance of Bacteroidetes and increasing that of Basidiomycota. Peat treatment decreased CH4 emissions by reducing the abundance of the Bacteroidetes. Biochar treatment increased the abundance of the Firmicutes, Bacteroidetes, Proteobacteria as well as Basidiomycota, resulting in reduced N2O emissions. Biochar and humic acid treatments efficiently removed heavy metals from wastewater and mitigated greenhouse gas emissions in constructed wetlands by modifying the microbial communities.

Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum.

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

GTADC: A Graph-Based Method for Inferring Cell Spatial Distribution in Cancer Tissues.

The heterogeneity of tumors poses a challenge for understanding cell interactions and constructing complex ecosystems within cancer tissues. Current research strategies integrate spatial transcriptomics (ST) and single-cell sequencing (scRNA-seq) data to thoroughly analyze this intricate system. However, traditional deep learning methods using scRNA-seq data tend to filter differentially expressed genes through statistical methods. In the context of cancer tissues, where cancer cells exhibit significant differences in gene expression compared to normal cells, this heterogeneity renders traditional analysis methods incapable of accurately capturing differences between cell types. Therefore, we propose a graph-based deep learning method, GTADC, which utilizes Silhouette scores to precisely capture genes with significant expression differences within each cell type, enhancing the accuracy of gene selection. Compared to traditional methods, GTADC not only considers the expression similarity of genes within their respective clusters but also comprehensively leverages information from the overall clustering structure. The introduction of graph structure effectively captures spatial relationships and topological structures between the two types of data, enabling GTADC to more accurately and comprehensively resolve the spatial composition of different cell types within tissues. This refinement allows GTADC to intricately reconstruct the cellular spatial composition, offering a precise solution for inferring cell spatial composition. This method allows for early detection of potential cancer cell regions within tissues, assessing their quantity and spatial information in cell populations. We aim to achieve a preliminary estimation of cancer occurrence and development, contributing to a deeper understanding of early-stage cancer and providing potential support for early cancer diagnosis.

Exosomes for neurodegenerative diseases: diagnosis and targeted therapy.

PURPOSE OF REVIEW: Neurodegenerative diseases are still challenging clinical issues, with no curative interventions available and early, accurate diagnosis remaining difficult. Finding solutions to them is of great importance. In this review, we discuss possible exosomal diagnostic biomarkers and explore current explorations in exosome-targeted therapy for some common neurodegenerative diseases, offering insights into the clinical transformation of exosomes in this field. RECENT FINDINGS: The burgeoning research on exosomes has shed light on their potential applications in disease diagnosis and treatment. As a type of extracellular vesicles, exosomes are capable of crossing the blood - brain barrier and exist in various body fluids, whose components can reflect pathophysiological changes in the brain. In addition, they can deliver specific drugs to brain tissue, and even possess certain therapeutic effects themselves. And the recent advancements in engineering modification technology have further enabled exosomes to selectively target specific sites, facilitating the possibility of targeted therapy for neurodegenerative diseases. The unique properties of exosomes give them great potential in the diagnosis and treatment of neurodegenerative diseases, and provide novel ideas for dealing with such diseases.

Identifying the Active Sites in MoSi2@MoO3 Heterojunctions for Enhanced Hydrogen Evolution.

Developing Two-dimensional (2D) Mo-based heterogeneous nanomaterials is of great significance for energy conversion, especially in alkaline hydrogen evolution reaction (HER), however, it remains a challenge to identify the active sites at the interface due to the structure complexity. Herein, the real active sites are systematically explored during the HER process in varied Mo-based 2D materials by theoretical computational and magnetron sputtering approaches first to filtrate the candidates, then successfully combined the MoSi2 and MoO3 together through Oxygen doping to construct heterojunctions. Benefiting from the synergistic effects between the MoSi2 and MoO3, the obtained MoSi2@MoO3 exhibits an unprecedented overpotential of 72 mV at a current density of 10 mA cm-2. Density functional theory calculations uncover the different Gibbs free energy of hydrogen adsorption (ΔGH*) values achieved at the interfaces with different sites as adsorption sites. The results can facilitate the optimization of heterojunction electrocatalyst design principles for the Mo-based 2D materials.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Targeted Linked-Read Sequencing for Direct Haplotype Phasing of Parental GJB2/SLC26A4 Alleles: A Universal and Dependable Noninvasive Prenatal Diagnosis Method Applied to Autosomal Recessive Nonsyndromic Hearing Loss in At-Risk Families.

Noninvasive prenatal diagnosis (NIPD) for autosomal recessive nonsyndromic hearing loss (ARNSHL) has been rarely reported until recent years. However, the previous method could not be performed on challenging genome loci (eg, copy number variations, deletions, inversions, or gene recombinants) or on families without proband genotype. Here, this study assesses the performance of relative haplotype dosage analysis (RHDO)-based NIPD for identifying fetal genotyping in pregnancies at risk of ARNSHL. Fifty couples carrying pathogenic variants associated with ARNSHL in either GJB2 or SLC26A4 were recruited. The RHDO-based targeted linked-read sequencing combined with whole gene coverage probes was used to genotype the fetal cell-free DNA of 49 families who met the quality control standard. Fetal amniocyte samples were genotyped using invasive prenatal diagnosis (IPD) to assess the performance of NIPD. The NIPD results showed 100% (49/49) concordance with those obtained through IPD. Two families with copy number variation and recombination were also successfully identified. Sufficient specific informative single-nucleotide polymorphisms for haplotyping, as well as the fetal cell-free DNA concentration and sequencing depth, are prerequisites for RHDO-based NIPD. This method has the merits of covering the entire genes of GJB2 and SLC26A4, qualifying for copy number variation and recombination analysis with remarkable sensitivity and specificity. Therefore, it has clinical potential as an alternative to traditional IPD for ARNSHL.