Prenatal chromosomal microarray analysis in a large Chinese cohort of fetuses with congenital heart defects: a single center study.

BACKGROUND AND OBJECTIVES: Congenital heart defect (CHD) is one of the most common birth defects. The aim of this cohort study was to evaluate the prevalence of chromosomal abnormalities and the clinical utility of chromosomal microarray analysis (CMA) in fetuses with different types of CHD, aiming to assist genetic counseling and clinical decision-making. METHODS: In this study, 642 fetuses with CHD were enrolled from a single center over a six-year period (2017-2022). Both conventional karyotyping and CMA were performed simultaneously on these fetuses. RESULTS: The diagnostic yield of CMA in fetuses with CHD in our study was 15.3% (98/642). Our findings revealed a significant increase in the diagnostic yield of CMA compared to karyotyping in fetuses with CHD. Among CHD subgroups, the diagnostic yields were high in complex CHD (34.9%), conotruncal defects (28.6%), right ventricular outflow tract obstructive defects (RVOTO) (25.9%), atrioventricular septal defects (AVSD) (25.0%) and left ventricular outflow tract obstructive defects (LVOTO) (24.1%), while those in other CHD (10.6%) and septal defects (10.9%) were relatively low. The overall detection rate of clinically significant chromosomal abnormalities was significantly higher in the non-isolated CHD group compared to the isolated CHD group (33.1% vs. 9.9%, P < 0.0001). Interestingly, numerical chromosomal abnormalities were more likely to occur in the non-isolated CHD group than in the isolated CHD group (20.3% vs. 2.0%, P < 0.0001). The rate of termination of pregnancy (TOP)/Still birth in the non-isolated CHD group was significantly higher than that in the isolated CHD group (40.5% vs. 20.6%, P < 0.0001). Compared to the isolated CHD group, the detection rate of clinically significant chromosomal abnormalities was significantly higher in the group of CHD with soft markers (35.6% vs. 9.9%, P < 0.0001) and in the group of CHD with additional structural anomalies (36.1% vs. 9.9%, P < 0.0001). CONCLUSIONS: CMA is a reliable and high-resolution technique that should be recommended as the front-line test for prenatal diagnosis of fetuses with CHD. The prevalence of chromosomal abnormalities varies greatly among different subgroups of CHD, and special attention should be given to prenatal non-isolated cases of CHD, especially those accompanied by additional structural anomalies or soft markers.

A comprehensive adsorption and desorption study on the interaction of DNA oligonucleotides with TiO2 nanolayers.

The utilization of TiO2 nanolayers that possess excellent biocompatibility and physical properties in DNA sensing and sequencing remains largely to be explored. To examine their applicability in gene sequencing, a comprehensive study on the interaction of DNA oligonucleotides with TiO2 nanolayers was performed through adsorption and desorption experiments. TiO2 nanolayers with 10 nm thickness were fabricated via magnetron sputtering onto a 6-inch silicon wafer. A simple chip block method, validated via quartz crystal microbalance experiments with dissipation monitoring (QCM-D), was proposed to study the adsorption behaviors and interaction mechanisms under a variety of critical influencing factors, including DNA concentration, length, and type, adsorption time, pH, and metal ions. It is determined that the adsorption takes 2 h to reach saturation in the MES solution and the adsorption capacity is significantly enhanced by lowering the pH due to the isoelectric point being pH = 6 for TiO2. The adsorption percentages of nucleobases are largely similar in the MES solution while following 5T = 5G > 5C > 5A in HEPES buffer for an adsorption duration of 2.5 h. Through pre-adsorption experiments, it is deduced that DNA oligonucleotides are horizontally adsorbed on the nanolayer. This further demonstrates that mono-, di-, and tri-valent metal ions promote the adsorption, whereas Zn2+ has strong adsorption by inducing DNA condensation. Based on the desorption experiments, it is revealed that electrostatic force dominates the adsorption over van der Waals force and hydrogen bonds. The phosphate group is the main functional group for adsorption, and the adsorption strength increases with the length of the oligonucleotide. This study provides comprehensive data on the adsorption of DNA oligonucleotides onto TiO2 nanolayers and clarifies the interaction mechanisms therein, which will be valuable for applications of TiO2 in DNA-related applications.

Revealing the Dynamic Evolution of Electrolyte Configuration on the Cathode-Electrolyte Interface by Visualizing (De)Solvation Processes.

Electrolyte engineering is crucial for improving cathode electrolyte interphase (CEI) to enhance the performance of lithium-ion batteries, especially at high charging cut-off voltages. However, typical electrolyte modification strategies always focus on the solvation structure in the bulk region, but consistently neglect the dynamic evolution of electrolyte solvation configuration at the cathode-electrolyte interface, which directly influences the CEI construction. Herein, we reveal an anti-synergy effect between Li+-solvation and interfacial electric field by visualizing the dynamic evolution of electrolyte solvation configuration at the cathode-electrolyte interface, which determines the concentration of interfacial solvated-Li+. The Li+ solvation in the charging process facilitates the construction of a concentrated (Li+-solvent/anion-rich) interface and anion-derived CEI, while the repulsive force derived from interfacial electric field induces the formation of a diluted (solvent-rich) interface and solvent-derived CEI. Modifying the electrochemical protocols and electrolyte formulation, we regulate the "inflection voltage" arising from the anti-synergy effect and prolong the lifetime of the concentrated interface, which further improves the functionality of CEI architecture.

Achieving High-Capacity Cathode Presodiation Agent Via Triggering Anionic Oxidation Activity in Sodium Oxide.

Compensating for the irreversible loss of limited active sodium (Na) is crucial for enhancing the energy density of practical sodium-ion batteries (SIBs) full-cell, especially when employing hard carbon anode with initially lower coulombic efficiency. Introducing sacrificial cathode presodiation agents, particularly those that own potential anionic oxidation activity with a high theoretical capacity, can provide additional sodium sources for compensating Na loss. Herein, Ni atoms are precisely implanted at the Na sites within Na2O framework, obtaining a (Na0.89Ni0.05□0.06)2O (Ni-Na2O) presodiation agent. The synergistic interaction between Na vacancies and Ni catalyst effectively tunes the band structure, forming moderate Ni-O covalent bonds, activating the oxidation activity of oxygen anion, reducing the decomposition overpotential to 2.8 V (vs Na/Na+), and achieving a high presodiation capacity of 710 mAh/g≈Na2O (Na2O decomposition rate >80%). Incorporating currently-modified presodiation agent with Na3V2(PO4)3 and Na2/3Ni2/3Mn1/3O2 cathodes, the energy density of corresponding Na-ion full-cells presents an essential improvement of 23.9% and 19.3%, respectively. Further, not limited to Ni-Na2O, the structure-function relationship between the anionic oxidation mechanism and electrode-electrolyte interface fabrication is revealed as a paradigm for the development of sacrificial cathode presodiation agent.

Role of EZH2-mediated epigenetic modification on vascular smooth muscle in cardiovascular diseases: A mini-review.

Vascular smooth muscle cells (VSMCs) are integral to the pathophysiology of cardiovascular diseases (CVDs). Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays a crucial role in epigenetic regulation of VSMCs gene expression. Emerging researches suggest that EZH2 has a dual role in VSMCs, contingent on the pathological context of specific CVDs. This mini-review synthesizes the current knowledge on the mechanisms by which EZH2 regulates VSMC proliferation, migration and survival in the context of CVDs. The goal is to underscore the potential of EZH2 as a therapeutic target for CVDs treatment. Modulating EZH2 and its associated epigenetic pathways in VSMCs could potentially ameliorate vascular remodeling, a key factor in the progression of many CVDs. Despite the promising outlook, further investigation is warranted to elucidate the epigenetic mechanisms mediated by EZH2 in VSMCs, which may pave the way for novel epigenetic therapies for conditions such as atherosclerosis and hypertension.

Research progress on the mechanisms of fruit glossiness in cucumber.

Cucumber (Cucumis sativus L.) is an important horticultural crop in China. Consumer requirements for aesthetically pleasing appearances of horticultural crops are gradually increasing, and cucumbers having a good visual appearance, as well as flavor, are important for breeding and industry development. The gloss of cucumber fruit epidermis is an important component of its appeal, and the wax layer on the fruit surface plays important roles in plant growth and forms a powerful barrier against external biotic and abiotic stresses. The wax of the cucumber epidermis is mainly composed of alkanes, and the luster of cucumber fruit is mainly determined by the alkane and silicon contents of the epidermis. Several genes, transcription factors, and transporters affect the synthesis of ultra-long-chain fatty acids and change the silicon content, further altering the gloss of the epidermis. However, the specific regulatory mechanisms are not clear. Here, progress in research on the luster of cucumber fruit epidermis from physiological, biochemical, and molecular regulatory perspectives are reviewed. Additionally, future research avenues in the field are discussed.

The prognostic value of prognostic nutritional index in postoperative onset of PAH in children with isolated VSD: a prospective cohort study based on propensity score matching analysis.

Background: The mechanism of pulmonary arterial hypertension (PAH) after surgery/intervention for isolated venticlular septal defect (VSD) in children is unknown. Reliable prognostic indicators for predicting postoperative PAH are urgently needed. Prognostic nutration index (PNI) is widely used to predict postoperative complications and survival in adults, but it is unclear whether it can be used as an indicator of prognosis in children. Methods: A total of 251 children underwent VSD repair surgery or interventional closure in Hunan Children's Hospital from 2020 to 2023 were collected. A 1:1 propensity score matching (PSM) analysis was performed using the nearest neighbor method with a caliper size of 0.2 Logistics regression analysis is used to examine factors associated with the development of PAH. Results: The cut-off value for PNI was determined as 58.0. After 1:1 PSM analysis, 49 patients in the low PNI group were matched with high PNI group. Children in the low PNI group had higher risk of postoperative PAH (P = 0.002) than those in the high PNI group. Multivariate logistics regression analysis showed that PNI (RR: 0.903, 95% CI: 0.816-0.999, P = 0.049) and tricuspid regurgitation velocity (RR: 4.743, 95% CI: 1.131-19.897, P = 0.033) were independent prognostic factors for the development of PAH. Conclusion: PNI can be used as a prognostic indicator for PAH development after surgery/intervention in children with isolated VSD.

Serum procalcitonin as a marker of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

BACKGROUND: Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. METHODS: In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. RESULTS: There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. CONCLUSION: PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.

A green and facile direct ink writing technique for preparation calibration standards in laser ablation inductively coupled plasma mass spectrometry analysis.

BACKGROUND: Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful tool for microanalysis of solid materials. Nevertheless, one limitation of the method is the lack of well-characterized homogeneous reference materials (RMs), such as BaF2 crystal and BaCO3 ceramics samples, making direct quantification difficult. This work presents a novel Direct Ink Writing (DIW) method to produce RMs for microanalysis. The Mg, Cr, Fe, Co, Ni, Cu, Y, Mo, Pr, Gd, Dy, Ho, Er, Tm, Yb, and Lu solutions were gravimetrically doped into BaCO3 by mixing with the dispersant and then cured with DIW techniques. (94) RESULTS: BaCO3 powder was combined with a dopant analyte to produce a printable slurry, aided by the use of a dispersant and cellulose. The resulting mixture was then printed using DIW equipment. The retention rates of the doped elements were investigated by internal and external standard method, and the results showed that they were completely dispersed in the solid material. After further optimization, it was found that there was no significant heterogeneity among the printed samples. LA-ICP-MS was used to analyze printed samples, to evaluate micro-scale homogeneity. The mass concentration of the doped element was determined by ICP-MS, verify its move closer to nominal value. Compared with the traditional reference materials preparation methods, the DIW technology greatly increased the sample homogeneity and the accuracy of the desired concentration. (132) SIGNIFICANCE: As far as we know, there are few reports on the application of DIW method to prepare calibration standards. In brief, it is proved that the proposed method of preparing calibration standard by DIW technique to quantify analytes is valid and robust. This procedure provides great potential for LA-ICP-MS in-situ analysis in the field of well-prepared products, such as ceramic and crystal samples.(63).

Functional Characterization of the MeSSIII-1 Gene and Its Promoter from Cassava.

Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the MeSSIII-1 gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the MeSSIII-1 gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots. MeSSIII-1 expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava. MeSSIII-1 expression patterns were further confirmed in proMeSSIII-1 transgenic cassava. The promoter deletion analysis showed that the -264 bp to -1 bp MeSSIII-1 promoter has basal activity. The range from -1228 bp to -987 bp and -488 bp to -264 bp significantly enhance promoter activity. The regions from -987 bp to -747 bp and -747 bp to -488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the MeSSIII-1 gene and for further in-depth exploration of the regulatory network of its internal functional elements.

Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.

Causal association of depression, anxiety, cognitive performance, the brain cortical structure with pulmonary arterial hypertension: A Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. METHODS: PAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. RESULTS: PAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. LIMITATIONS: The enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. CONCLUSION: Causal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms.

Visualizing and Regulating Dynamic Evolution of Interfacial Electrolyte Configuration during De-solvation Process on Lithium-Metal Anode.

Acting as a passive protective layer, solid-electrolyte interphase (SEI) plays a crucial role in maintaining the stability of the Li-metal anode. Derived from the reductive decomposition of electrolytes (e.g., anion and solvent), the SEI construction presents as an interfacial process accompanied by the dynamic de-solvation process during Li-metal plating. However, typical electrolyte engineering and related SEI modification strategies always ignore the dynamic evolution of electrolyte configuration at the Li/electrolyte interface, which essentially determines the SEI architecture. Herein, by employing advanced electrochemical in situ FT-IR and MRI technologies, we directly visualize the dynamic variations of solvation environments involving Li+-solvent/anion. Remarkably, a weakened Li+-solvent interaction and anion-lean interfacial electrolyte configuration have been synchronously revealed, which is difficult for the fabrication of anion-derived SEI layer. Moreover, as a simple electrochemical regulation strategy, pulse protocol was introduced to effectively restore the interfacial anion concentration, resulting in an enhanced LiF-rich SEI layer and improved Li-metal plating/stripping reversibility.

Witnessing family violence and adolescent cyberbullying perpetration: A longitudinal moderated mediation model involving anger dysregulation and teacher support.

BACKGROUND: Family violence has been shown to be associated with traditional adolescent bullying perpetration. However, few studies have considered the association between witnessing family violence and adolescent bullying perpetration in cyberspace. OBJECTIVE: The present study aimed to reveal the mechanism explaining the association between witnessing family violence and adolescent cyberbullying perpetration by testing the mediating effect of anger dysregulation and the moderating effect of teacher support. PARTICIPANTS AND SETTING: Participants were 751 Chinese adolescents (Mage at Time 1 = 13.25) who completed the measures of witnessing family violence, anger dysregulation, cyberbullying perpetration, and teacher support at three time points over the year. METHODS: Structural equation modeling was used to assess the direct and indirect effects of witnessing family violence on adolescent cyberbullying perpetration through anger dysregulation as a mediator and perceived teacher support as a moderator. RESULTS: The results showed that witnessing family violence at baseline positively predicted adolescent cyberbullying perpetration at T3, and anger dysregulation at T2 partially mediated this association. The positive relation between witnessing family violence and later anger dysregulation was stronger for adolescents who perceived higher levels of teacher support. CONCLUSIONS: Witnessing family violence could increase the risk for adolescent cyberbullying perpetration, with anger dysregulation mediating this association. The protective effect of perceived teacher support weakens as the levels of witnessing family violence increase. These findings offer insight into the connection between witnessing family violence and adolescent bullying perpetration in the digital age, emphasizing the importance of promoting programs to prevent intrafamilial violence.

Sex and race differences in the association of albumin with cognitive function in older adults.

BACKGROUND: With the increasing aging population, dementia has become a significant socioeconomic burden. However, the effects of albumin on delayed recall (DR) impairment remain unclear, and there are limited reports on sex and race differences in this relationship. This study aimed to investigate the association between albumin levels and DR impairment in older adults. METHODS: A total of 1507 normal cognitive function and 553 DR impairment from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in this cross-sectional analysis. Participants aged 60 years and above were assessed using the Consortium to Establish a Registry for Alzheimer's Disease DR (CERAD-DR) test to evaluate cognitive function. Participants were categorized into DR impairment and normal cognitive function groups according to their CERAD-DR scores. Logistic regression analyses, generalized additive models, and fitted smoothing curves were utilized for data analysis. RESULTS: After adjusting for potential confounders, a negative association was found between albumin levels and cognitive function (odds ratio [OR] = 0.60, 95% confidence interval [CI] 0.41-0.87). Subgroup analysis stratified by sex, race/ethnicity, and age revealed that the negative association remained significant in men (OR = 0.53, 95%CI 032-0.87), Blacks (OR = 0.35, 95%CI 0.17-0.74), and the age group of 60-70 years (OR = 0.48, 95%CI 0.28-0.81). However, no significant association was observed in women (OR = 0.72, 95%CI 0.41-1.28), whites (OR = 0.58, 95%CI 0.31-1.07), or Mexican Americans (OR = 1.11, 95%CI 0.35-3.46), as well as the age group of 71-80 years (OR = 0.62, 95%CI 0.37-1.03). CONCLUSIONS: Our study suggests that elevated albumin levels are associated with a decreased incidence of cognitive function impairment, particularly in older men and Blacks. This finding indicates that maintaining high levels of albumin may be beneficial for cognitive function in older adults.

A chalcone-based ESIPT and AIE fluorophore for ß-gal imaging in living cells.

ß-Galactosidase (ß-gal), which is responsible for the hydrolysis of the glycosidic bond of lactose to galactose, has been recognized as an important biomarker of cell or organism status, especially cell senescence and primary ovarian cancer. Extensive efforts have been devoted to develop probes for detecting and visualizing ß-gal in cells. Herein, a fluorescent probe gal-HCA which possesses both excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) properties was prepared to monitor ß-gal in living cells. The probe consists of 2-hydroxy-4'-dimethylamino-chalcone (HCA) capped with a D-galactose group. The cleavage of the glycosidic bond in gal-HCA triggered by ß-gal releases HCA, which results in a significant bathochromic shift in fluorescence from 532 to 615 nm. The probe exhibited high selectivity and sensitivity toward ß-gal with a detection limit as low as 0.0122 U mL-1. The confocal imaging investigation demonstrated the potential of gal-HCA in monitoring the endocellular overexpressed ß-gal in senescent cells and ovarian cancer cells. This study provides a straightforward approach for the development of fluorescent probes to monitor ß-gal and detection of ß-gal-associated diseases.

Gradient Interphase Engineering Enabled by Anionic Redox for High-Voltage and Long-Life Li-Ion Batteries.

Intelligent utilization of the anionic redox reaction (ARR) in Li-rich cathodes is an advanced strategy for the practical implementation of next-generation high-energy-density rechargeable batteries. However, due to the intrinsic complexity of ARR (e.g., nucleophilic attacks), the instability of the cathode-electrolyte interphase (CEI) on a Li-rich cathode presents more challenges than typical high-voltage cathodes. Here, we manipulate CEI interfacial engineering by introducing an all-fluorinated electrolyte and exploiting its interaction with the nucleophilic attack to construct a gradient CEI containing a pair of fluorinated layers on a Li-rich cathode, delivering enhanced interfacial stability. Negative/detrimental nucleophilic electrolyte decomposition has been efficiently evolved to further reinforce CEI fabrication, resulting in the construction of LiF-based indurated outer shield and fluorinated polymer-based flexible inner sheaths. Gradient interphase engineering dramatically improved the capacity retention of the Li-rich cathode from 43 to 71% after 800 cycles and achieved superior cycling stability in anode-free and pouch-type full cells (98.8% capacity retention, 220 cycles), respectively.

Evaluating ClinGen variant curation expert panels' application of PVS1 code.

BACKGROUND: The 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines articulates that the effects of certain types of variants on gene function can often be seen as a complete absence of the gene product by leading to a lack of transcription or nonsense-mediated decay(NMD). However, detailed information considering different types of loss of function(LOF) variants, refined steps assimilating details concerning location of variant, changes in strength levels, NMD boundary, or any additional information pointing to a true null effect, were all left to expert judgement. As part of its Clinical Genome Resource (ClinGen) initiative, Variant Curation Expert Panels (VCEPs) are designated to make gene/disease-centric specifications in accordance with the ACMG/AMP guidelines, including a more detailed definition of what constitutes an appropriate LOF evidence. Our goal was to evaluate the current LOF guidelines developed by the VCEPs and analyse the prior curated variants concerning the PVS1 criteria, bringing people occupied in genetic data analysis a comprehensive understanding of this code. METHODS: Our study evaluated 7 VCEPs for their LOF criteria (PVS1). Subsequently, we assessed the predictive criteria by considering the underlying disease mechanism, protein transcript, and variant types delineated. Then, we meticulously curated the LOF evidence referenced by each VCEP in their preliminary variant classification, thereby scrutinizing the recommendations put forth by VCEPs and their application in the interpretation of the aforementioned predictive criteria. Based on these, an extensive curation of evidence summary considering PVS1 applied by VCEPs according to their classification of pilot variants for the purpose of analyzing VCEP criteria specifications and their use in the understanding of LOF was conducted. RESULTS: We observed in this article that the VCEPs discussed followed the majority of Sequence Variant Interpretation (SVI) recommendations concerning the application of this LOF criteria, except for some disease/gene specific considerations. We highlighted the wide range of PVS1 strength levels approved by VCEP, reflecting the diversity of evidence for each variants type. In addition, we observed substantial differences in the approach used to determine relative strengths for different types of null variants and in the attitude towards these principles concerning variant location, NMD and influence to protein function between VCEPs. CONCLUSIONS: It is difficult to understand the intricacies of the predictive data(PVS1), which often requires expert-level knowledge of disease/gene. The VCEP criteria specifications for the predictive evidence play an important role in making it more accessible for the curators to apply the predictive data by providing details concerning this complex criteria. Despite this, we believe there is a need for more guidance on standardizing this process and ensuring consistency in the application of this predictive evidence.

Lattice Engineering on Li2CO3-Based Sacrificial Cathode Prelithiation Agent for Improving the Energy Density of Li-Ion Battery Full-Cell.

Developing sacrificial cathode prelithiation technology to compensate for active lithium loss is vital for improving the energy density of lithium-ion battery full-cells. Li2CO3 owns high theoretical specific capacity, superior air stability, but poor conductivity as an insulator, acting as a promising but challenging prelithiation agent candidate. Herein, extracting a trace amount of Co from LiCoO2 (LCO), a lattice engineering is developed through substituting Li sites with Co and inducing Li defects to obtain a composite structure consisting of (Li0.906Co0.043▫0.051)2CO2.934 and ball milled LiCoO2 (Co-Li2CO3@LCO). Notably, both the bandgap and Li─O bond strength have essentially declined in this structure. Benefiting from the synergistic effect of Li defects and bulk phase catalytic regulation of Co, the potential of Li2CO3 deep decomposition significantly decreases from typical >4.7 to ≈4.25 V versus Li/Li+, presenting >600 mAh g-1 compensation capacity. Impressively, coupling 5 wt% Co-Li2CO3@LCO within NCM-811 cathode, 235 Wh kg-1 pouch-type full-cell is achieved, performing 88% capacity retention after 1000 cycles.

Retrospective study of synovial chondromatosis of the temporomandibular joint: clinical and histopathologic analysis and the early-stage imaging features.

OBJECTIVE: Herein, we aimed to study the clinical, radiographical, and histopathologic features of synovial chondromatosis in the temporomandibular joint (SC in TMJ) and provide references for early diagnosis and treatment prognosis. STUDY DESIGN: The medical records and imaging examinations of patients with SC in TMJ, diagnosed using postoperative histopathologic examination, were reviewed and analyzed. Among them, 18 cases who lacked calcified loose bodies on spiral computed tomography or cone beam computed tomography (SCT/CBCT) were selected for further study. Descriptive statistical methods were used to analyze the clinical characteristics of patients. RESULTS: The study included 100 patients with SC in TMJ, who were predominantly female (male to female: 1:3), and were aged from 21 to 77 years (median, 47). Radiopaque calcified lesions on SCT/CBCT were missing in 18 cases, but cartilaginous nodules were observed during surgery. The cases lacking calcification had a relatively shorter disease course, suggesting they were in the early stages of SC. CONCLUSION: In the early stage of SC, although calcified loose bodies cannot be detected on SCT/CBCT, attention should be paid to the widening of the posterior superior joint space and sclerosis or slight erosion of the joint fossa. Magnetic resonance imaging would be helpful to detect the early-stage SC in TMJ.