Integrating Clay Modeling in Implant Fabrication for Craniofacial Defect.

Manufacturing craniofacial implants using 3-dimensional (3D) methods and computed tomography data has become popular. The image object for the defect is produced as the first step, followed by several methods to create the implant. The authors have used a novel method that combines clay modeling with 3D scanning to create implants for craniofacial contour reconstruction. This approach does not require complicated resources. The method allows for high customization and immediate modifications, resulting in implants that achieve an accurate fit and high patient satisfaction. It is particularly beneficial for addressing complex defects and achieving aesthetic improvements. In addition, it reduces the need for cumbersome digital processing and expensive materials, making it a practical and feasible solution for a wide range of craniofacial deformities.

Dependable Automated Approach for Measuring the Retrograde Superior Ramus Screw Corridor in Pelvic Fracture Fixation.

BACKGROUND: Precise measurement of the intraosseous corridor within the superior pubic ramus is essential for the accurate percutaneous placement of a retrograde superior ramus screw (SRS). However, conventional manual measurement methods are often subjective, leading to variations in results among observers. Our goal was to develop an automated and dependable method for determining the retrograde SRS corridor. METHODS: We developed an automated technique that utilized a computed tomography (CT) image-based search algorithm to identify the retrograde SRS corridor with the maximum diameter. We evaluated the reliability of this automated approach in comparison to a manual method using 17 pelves. Subsequently, we used both methods to measure the diameter, length, and orientation of the retrograde SRS corridor in 204 pelves in a Chinese population and assessed the intra- and interobserver agreement of each method by calculating the root-mean-square error (RMSE) and constructing Bland-Altman plots. We determined the screw applicability (percentages of hemipelves that could be treated with specific sizes of screws) for each method. Additionally, we investigated potential factors influencing the corridor, such as sex, age, height, and weight, through regression analysis. RESULTS: The intra- and interobserver intraclass correlation coefficients (ICCs) for the automated method (0.998 and 0.995) were higher than those for the manual approach (0.925 and 0.918) in the assessment of the corridor diameter. Furthermore, the diameter identified by the automated method was notably larger than the diameter measured with the manual method, with a mean difference and RMSE of 0.9 mm and 1.1 mm, respectively. The automated method revealed a significantly smaller corridor diameter in females than in males (an average of 7.5 and 10.4 mm, respectively). Moreover, use of the automated method allowed 80.6% of the females to be managed with a 4.5-mm screw while a 6.5-mm screw could be utilized in 19.4%, surpassing the capabilities of the manual method. Female sex had the most substantial impact on corridor diameter (ß = -0.583). CONCLUSIONS: The automated method exhibited better reliability than the manual method in measuring the retrograde SRS corridor, and showed a larger corridor diameter for screw placement. Females had a significantly smaller corridor diameter than males. Given the intricate nature of the automated approach, which entails utilizing different software and interactive procedures, our current method is not readily applicable for traumatologists. We are working on developing integrated software with the goal of providing a more user-friendly solution for traumatologists in the near future. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Research on the Mechanism and Material Basis of Corn (Zea mays L.) Waste Regulating Dyslipidemia.

Corn (Zea mays L.) is an essential gramineous food crop. Traditionally, corn wastes have primarily been used in feed, harmless processing, and industrial applications. Except for corn silk, these wastes have had limited medicinal uses. However, in recent years, scholars have increasingly studied the medicinal value of corn wastes, including corn silk, bracts, husks, stalks, leaves, and cobs. Hyperlipidemia, characterized by abnormal lipid and/or lipoprotein levels in the blood, is the most common form of dyslipidemia today. It is a significant risk factor for atherosclerosis and can lead to cardiovascular and cerebrovascular diseases if severe. According to the authors' literature survey, corn wastes play a promising role in regulating glucose and lipid metabolism. This article reviews the mechanisms and material basis of six different corn wastes in regulating dyslipidemia, aiming to provide a foundation for the research and development of these substances.

Stereodivergent Total Synthesis of Tacaman Alkaloids.

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer-Villiger oxidation of cyclohexanone, which was developed to produce seven-membered lactones and establish the required stereochemistry at the C14 position (92 % yield, 99 % ee, 500 mg scale). Cis- and trans-tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid-triggered, tunable acyl-Pictet-Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl-Pictet-Spengler cyclization cascade. By strategically using these two reactions and the late-stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

Association between screen time and self-reported balance disorders in middle-aged and older adults: national health and nutrition examination survey.

BACKGROUND: Balance disorders can give rise to sensations of instability, lightheadedness, vertigo, disequilibrium, or syncope, ultimately leading to grave medical, physical, emotional, and societal ramifications. These conditions are highly prevalent among individuals aged 40 and above. Screen time encompasses activities associated with television viewing, video game playing, and non-work-related computer usage. Prolonged screen exposure may engender a spectrum of health issues and even elevate overall mortality rates. However, the available evidence on the potential link between excessive screen time and balance dysfunction remains limited. AIMS: The primary aim of this study was to explore the possible association between prolonged screen exposure and impaired balance function. METHODS: This cross-sectional study utilized data from participants who completed a comprehensive questionnaire in the NHANES database between 1999 and 2002, all of whom were aged over 40 and under 85 years. Participants' screen time was categorized into two groups (< 4 h/d and ≥4 h/d) for subsequent data analysis. Logistic regression, combined with propensity score matching (PSM), was employed to investigate the correlation between screen time and balance disorders. RESULTS: A total of 5176 participants were enrolled in this study, comprising 2,586 men and 2,590 women, with a prevalence rate of balance disorders at 25.7% (1331/5176). The incidence of balance disorders was found to be significantly higher among individuals who spent 4 hours or more per day on screen time compared to those with less screen time (P<0.001). Multivariate logistic analysis conducted on the unmatched cohort revealed a significant association between screen time and balance disorders, with an odds ratio (OR) 1.8 (95%CI 1.57 ∼ 2.05). These findings remained consistent even after adjusting for confounding factors, yielding an OR 1.43 (95%CI 1.24 ∼ 1.66). Moreover, the association persisted when employing various multivariate analyses such as propensity score matching adjusted model, standardized mortality ratio weighting model and pairwise algorithmic model; all resulting in ORs ranging from 1.38 to 1.43 and p-values < 0.001. CONCLUSIONS: After controlling for all covariates, screen time (watching TV, playing video games, and using computers outside of work) was associated with balance dysfunction among middle-aged and older adults. This finding may offer a possible idea for the prevention of dizziness and balance disorders. Nevertheless, additional research is imperative to further validate these results.

Impacts of audiovisual simultaneity perception on single-task and dual-task gaits in middle-aged and older adults.

BACKGROUND: While dual-task walking requires the ability to integrate sensory information from multiple ongoing sources, it remains unknown whether dual-task walking is more affected than single-task walking by the multisensory integration ability. RESEARCH QUESTION: How does the audiovisual temporal integration ability affect single-task and dual-task gaits in the aging population? METHODS: One hundred and thirty healthy middle-aged and older adults (age = 64.7 ± 6.4 years) completed an audiovisual simultaneity judgment (AVSJ) task and underwent single-task, motor dual-task, and cognitive dual-task gait assessments. In the AVSJ task, participants judged whether a flash and an auditory stimulus presented at different stimulus onset asynchronies were simultaneous. The accuracy and precision of the AVSJ performance were assessed using the point of subjective simultaneity (PSS) and the temporal binding window (δ), respectively. A lower absolute PSS and δ indicated better performance. Participants held a cup of water and performed serial-7 subtraction for motor and cognitive dual-task gait assessments, respectively. The spatiotemporal gait parameters and their variability were calculated. The influences of PSS and δ on the gait parameters of the three gaits were examined with multiple hierarchical regressions. RESULTS: Only the cognitive dual-task gait was significantly affected by PSS and δ. Greater PSS predicted a longer single support time (ß = 0.195, p = 0.024) and its variability (ß = 0.224, p = 0.011). Greater δ predicted greater step time variability (ß = 0.198, p = 0.022). SIGNIFICANCE: Declined perception of audiovisual simultaneity particularly degrades temporal control of cognitive dual-task walking, highlighting the importance of assessing and training this ability after midlife.

SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway.

Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.

The natural history and genotype-phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis.

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype-phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.

Unconventional PDZ Recognition Revealed in α7 nAChR-PICK1 Complexes.

PDZ domains are modular domains that conventionally bind to C terminal or internal motifs of target proteins to control cellular functions through the regulation of protein complex assemblies. Almost all reported structures of PDZ-target protein complexes rely on fragments or peptides as target proteins. No intact target protein complexed with PDZ was structurally characterized. In this study, we used NMR spectroscopy and other biochemistry and biophysics tools to uncover insights into structural coupling between the PDZ domain of protein interacting with C-kinase 1 (PICK1) and α7 nicotinic acetylcholine receptors (α7 nAChR). Notably, the intracellular domains of both α7 nAChR and PICK1 PDZ exhibit a high degree of plasticity in their coupling. Specifically, the MA helix of α7 nAChR interacts with residues lining the canonical binding site of the PICK1 PDZ, while flexible loops also engage in protein-protein interactions. Both hydrophobic and electrostatic interactions mediate the coupling. Overall, the resulting structure of the α7 nAChR-PICK1 complex reveals an unconventional PDZ binding mode, significantly expanding the repertoire of functionally important PDZ interactions.