Helmholtz Plane Regulation Empowers PF6- Permselectivity towards High Coulombic Efficiency Dual Ion Battery of 5.5 V.

High-voltage dual ion battery (DIB) is promising for stationary energy storage applications owing to its cost-effectiveness, which has been a hot topic of research in rechargeable battery fields. However, it still suffers from rapid battery failure caused by the severe solvent co-intercalation and electrolyte oxidation. To address these bottlenecks, herein a functional electrolyte additive hexafluoroglutaric anhydride (HFGA) is presented based on a Helmholtz plane regulation strategy. It is demonstrated that the HFGA can precisely enter into the Helmholtz plane and positively regulate anion solvation behaviors near the graphite electrode surface owing to its considerable H-F affinity with ethyl methyl carbonate (EMC), thus alleviating EMC-related co-intercalation and oxidation decomposition during DIB charging. Meanwhile, HFGA can copolymerize with the presence of PF5 at the Helmholtz plane to participate in forming a CF2-rich CEI layer with excellent PF6- permselectivity, conducive to achieving PF6- de-solvation and simultaneously suppressing electrolyte oxidation decomposition. By virtue of such beneficial effects, the graphite cathode enables a 5.5 V DIB with a prominent capacity retention of 92% and a high average Coulombic efficiency exceeding 99% within 2000 cycles, demonstrating significantly enhanced electrochemical reversibility. The Helmholtz plane regulation strategy marks a milestone in advancing DIB technologies.

Exploration of the role of EMC3­AS1 as a potential diagnostic and prognostic indicator in liver cancer.

The aim of the present study was to evaluate the diagnostic and prognostic significance of the long non-coding RNA (lncRNA) endoplasmic reticulum membrane protein complex subunit 3 antisense RNA 1 (EMC3-AS1) in liver cancer, and its impact on the proliferative and invasive capabilities of liver cancer cells. EMC3-AS1 expression in liver cancer was assessed using data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets, and validated in clinical liver cancer samples using reverse transcription-quantitative PCR. The prognostic and diagnostic potentials of this lncRNA were evaluated using Kaplan-Meier and receiver operating characteristic analyses, respectively. The infiltration of immune cells and differential expression of immune checkpoints (ICs) between high- and low-EMC3-AS1 expression groups were investigated. Therapeutic correlation analyses were also undertaken to assess the impact of EMC3-AS1 in the treatment of liver cancer. In addition, in vitro experiments were conducted using small interfering RNA to knock down the expression of EMC3-AS1 in HepG2, Sk-Hep-1 and Huh-7 cells, and evaluate the effect on cell proliferation, colony formation and migration. The results revealed a significant upregulation of EMC3-AS1 expression in liver cancer tissues compared with that in adjacent normal tissues, which was associated with an unfavorable prognosis and demonstrated diagnostic effectiveness for patients with liver cancer. Furthermore, patients with high EMC3-AS1 expression exhibited increased levels of IC markers in comparison with those with low EMC3-AS1 expression. In addition, EMC3-AS1 was indicated to have clinical significance in the prediction of the response to immunotherapy and chemotherapy. Notably, the in vitro experiments demonstrated that the knockdown of EMC3-AS1 significantly hindered cell proliferation, colony formation and migration. Consequently, it was concluded that EMC3-AS1 is upregulated in liver cancer and serves as a prognostic indicator for unfavorable outcomes in patients with liver cancer. Additionally, targeting EMC3-AS1 through knockdown interventions showed potential in mitigating the ability of liver cancer cells to proliferate and migrate, which highlights its dual role as a biomarker and therapeutic target for liver cancer.

Optimizing Epoxy Molding Compound Processing: A Multi-Sensor Approach to Enhance Material Characterization and Process Reliability.

The in-line control of curing during the molding process significantly improves product quality and ensures the reliability of packaging materials with the required thermo-mechanical and adhesion properties. The choice of the morphological and thermo-mechanical properties of the molded material, and the accuracy of their determination through carefully selected thermo-analytical methods, play a crucial role in the qualitative prediction of trends in packaging product properties as process parameters are varied. This work aimed to verify the quality of the models and their validation using a highly filled molding resin with an identical chemical composition but 10 wt% difference in silica particles (SPs). Morphological and mechanical material properties were determined by dielectric analysis (DEA), differential scanning calorimetry (DSC), warpage analysis and dynamic mechanical analysis (DMA). The effects of temperature and injection speed on the morphological properties were analyzed through the design of experiments (DoE) and illustrated by response surface plots. A comprehensive approach to monitor the evolution of ionic viscosity (IV), residual enthalpy (dHrest), glass transition temperature (Tg), and storage modulus (E) as a function of the transfer-mold process parameters and post-mold-cure (PMC) conditions of the material was established. The reliability of Tg estimation was tested using two methods: warpage analysis and DMA. The noticeable deterioration in the quality of the analytical signal for highly filled materials at high cure rates is discussed. Controlling the temperature by increasing the injection speed leads to the formation of a polymer network with a lower Tg and an increased storage modulus, indicating a lower density and a more heterogeneous structure due to the high heating rate and shear heating effect.

Experimental and theoretical investigation of the influence of post-curing on mixed mode fracture properties of 3d-printed polymer samples.

This study explores the mechanical properties and fracture characteristics of additively manufactured acrylonitrile butadiene styrene specimens, focusing on the impact of raster angle and post-process heat treatment. To this end, a large number of tensile and semi-circular bending samples with three distinct raster angles of 0/90°, 22/ - 68°, and 45/ - 45° were prepared and exposed to four types of heat treatments with different temperature and pressure conditions. Simultaneously, theoretical models of maximum tangential stress (MTS) and generalized MTS (GMTS) were developed to estimate the onset of specimen fracture under mixed-mode in-plane loading conditions. Recognizing the non-linear behavior within the stress-strain curve of tensile test samples, particularly in the annealed samples, an effort was undertaken to transform the original ductile material into a virtual brittle material through the application of the equivalent material concept (EMC). This approach serves the dual purpose of bypassing intricate and tedious elastoplastic analysis, while concurrently enhancing the precision of the GMTS criterion. The experimental findings have revealed that while the annealing process has a minimal effect on the yield strength, it considerably enhances energy absorption capacity, increases fracture toughness, and reduces the anisotropy. Additionally, the combined EMC-GMTS criterion has demonstrated its capability to predict the failure of the additively manufactured parts with an acceptable level of accuracy.

A Study on the Frequency-Domain Black-Box Modeling Method for the Nonlinear Behavioral Level Conduction Immunity of Integrated Circuits Based on X-Parameter Theory.

During circuit conduction immunity simulation assessments, the existing black-box modeling methods for chips generally involve the use of time-domain-based modeling methods or ICIM-CI binary decision models, which can provide approximate immunity assessments but require a high number of tests to be performed when carrying out broadband immunity assessments, as well as having a long modeling time and demonstrating poor reproducibility and insufficient accuracy in capturing the complex electromagnetic response in the frequency domain. To address these issues, in this paper, we propose a novel frequency-domain broadband model (Sensi-Freq-Model) of IC conduction susceptibility that accurately quantifies the conduction immunity of components in the frequency domain and builds a model of the IC based on the quantized data. The method provides high fitting accuracy in the frequency domain, which significantly improves the accuracy of circuit broadband design. The generated model retains as much information within the frequency-domain broadband as possible and reduces the need to rebuild the model under changing electromagnetic environments, thereby enhancing the portability and repeatability of the model. The ability to reduce the modeling time of the chip greatly improves modeling efficiency and circuit design. The results of this study show that the "Sensi-Freq-Model" reduces the broadband modeling time by about 90% compared to the traditional ICIM-CI method and improves the normalized mean square error (NMSE) by 18.5 dB.

In Situ Monitoring of the Curing of Highly Filled Epoxy Molding Compounds: The Influence of Reaction Type and Silica Content on Cure Kinetic Models.

Monitoring of molding processes is one of the most challenging future tasks in polymer processing. In this work, the in situ monitoring of the curing behavior of highly filled EMCs (silica filler content ranging from 73 to 83 wt%) and the effect of filler load on curing kinetics are investigated. Kinetic modelling using the Friedman approach was applied using real-time process data obtained from in situ DEA measurements, and these online kinetic models were compared with curing analysis data obtained from offline DSC measurements. For an autocatalytic fast-reacting material to be processed above the glass transition temperature Tg and for an autocatalytic slow-reacting material to be processed below Tg, time-temperature-transformation (TTT) diagrams were generated to investigate the reaction behavior regarding Tg progression. Incorporating a material containing a lower silica filler content of 10 wt% enabled analysis of the effects of filler content on sensor sensitivity and curing kinetics. Lower silica particle content (and a larger fraction of organic resin, respectively) favored reaction kinetics, resulting in a faster reaction towards Tg1. Kinetic analysis using DEA and DSC facilitated the development of highly accurate prediction models using the Friedman model-free approach. Lower silica particle content resulted in enhanced sensitivity of the analytical method, leading, in turn, to more precise prediction models for the degree of cure.

Process Optimization of the Morphological Properties of Epoxy Resin Molding Compounds Using Response Surface Design.

An epoxy compound's polymer structure can be characterized by the glass transition temperature (Tg) which is often seen as the primary morphological characteristic. Determining the Tg after manufacturing thermoset-molded parts is an important objective in material characterization. To characterize quantitatively the dependence of Tg on the degree of cure, the DiBenedetto equation is usually used. Monitoring polymer network formation during molding processes is therefore one of the most challenging tasks in polymer processing and can be achieved using dielectric analysis (DEA). In this study, the morphological properties of an epoxy resin-based molding compounds (EMC) were optimized for the molding process using response surface analysis. Processing parameters such as curing temperature, curing time, and injection rate were investigated according to a DoE strategy and analyzed as the main factors affecting Tg as well as the degree of cure. A new method to measure the Tg at a certain degree of cure was developed based on warpage analysis. The degree of cure was determined inline via dielectric analysis (DEA) and offline using differential scanning calorimetry (DSC). The results were used as the response in the DoE models. The use of the DiBenedetto equation to refine the response characteristics for a wide range of process parameters has significantly improved the quality of response surface models based on the DoE approach.

EMC10 modulates hepatic ER stress and steatosis in an isoform-specific manner.

BACKGROUND & AIMS: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis. The therapeutic effect of scEMC10-neutralizing antibody on mouse hepatosteatosis was explored. Associations of MASLD with serum scEMC10 and hepatic mEMC10 were determined in two cohorts of participants with MASLD. RESULTS: scEMC10 promoted, while mEMC10 suppressed, the activation of hepatic PERK-eIF2α-ATF4 signaling. Emc10 gene knockout exacerbated, while hepatic overexpression of mEMC10 ameliorated, hepatic ER stress and steatosis in mice challenged with either a methionine- and choline-deficient diet or tunicamycin, highlighting a direct, suppressive role of mEMC10 in MASLD via modulation of hepatic ER stress. Overexpression of scEMC10 promoted, whereas neutralization of circulating scEMC10 prevented, hepatosteatosis in mice with fatty liver, suggesting a role of scEMC10 in MASLD development. Clinically, serum scEMC10 was increased, while hepatic mEMC10 was decreased, in participants with MASLD. Correlative analysis indicated that serum scEMC10 positively, whereas hepatic mEMC10 negatively, correlated with liver fat content and serum ALT, AST, and GGT. CONCLUSIONS: These findings demonstrate a novel isoform-specific role for EMC10 in the pathogenesis of MASLD and identify the secreted isoform as a tractable therapeutic target for MASLD via antibody-based neutralization. IMPACT AND IMPLICATIONS: We have shown the role of EMC10 in the regulation of energy homeostasis and obesity. In this study, we determine the distinct roles of the two isoforms of EMC10 in the regulation of hepatic endoplasmic reticulum stress and steatosis in mice, and report on the associations of the different EMC10 isoforms with metabolic dysfunction-associated steatotic liver disease in humans. Our findings delineate a novel regulatory axis for hepatosteatosis and identify EMC10 as a modulator of the PERK-eIF2α-ATF4 signaling cascade that may be of broad physiological significance. Moreover, our pre-clinical and clinical studies provide evidence of the therapeutic potential of targeting scEMC10 in MASLD.

An unexpected journey for BNIP3.

Mitophagy is a cellular process that enables the selective degradation of damaged, dysfunctional, or superfluous mitochondria. During mitophagy, specific proteins recognize and tag mitochondria for degradation. These tagged mitochondria are engulfed by specialized structures called phagophores that then mature into autophagosomes/mitophagosomes. Mitophagosomes subsequently transport their mitochondrial cargo to lysosomes, where the mitochondria are broken down and recycled. While the PINK1-PRKN-dependent mitophagy pathway is well understood, mitophagy can also occur independently of this pathway. BNIP3 and BNIP3L/NIX, paralogous membrane proteins on the outer mitochondrial membrane (OMM), serve as ubiquitin-independent mitophagy receptors. Historically, BNIP3 regulation was thought to be primarily transcriptional through HIF1A (hypoxia inducible factor 1 subunit alpha). However, recent work has revealed a significant post-translational dimension, highlighting the strong role of the ubiquitin-proteasome system (UPS) in BNIP3 regulation. With these emerging concepts in mind, we aimed to develop a unified understanding of how steady-state levels of BNIP3 are established and maintained and how this regulation governs underlying cell physiology.

Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

Structural insights into human EMC and its interaction with VDAC.

The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in stabilizing and trafficking membrane proteins. However, the structural basis and regulation of its multifunctionality remain elusive. Here, we report cryo-electron microscopy structures of human EMC in apo- and voltage-dependent anion channel (VDAC)-bound states at resolutions of 3.47 Å and 3.32 Å, respectively. We discovered a specific interaction between VDAC proteins and the EMC at mitochondria-ER contact sites, which is conserved from yeast to humans. Moreover, we identified a gating plug located inside the EMC hydrophilic vestibule, the substrate-binding pocket for client insertion. Conformation changes of this gating plug during the apo-to-VDAC-bound transition reveal that the EMC unlikely acts as an insertase in the VDAC1-bound state. Based on the data analysis, the gating plug may regulate EMC functions by modifying the hydrophilic vestibule in different states. Our discovery offers valuable insights into the structural basis of EMC's multifunctionality.

The exposure to UV filters: Prevalence, effects, possible molecular mechanisms of action and interactions within mixtures.

Substances that can absorb sunlight and harmful UV radiation such as organic UV filters are widely used in cosmetics and other personal care products. Since humans use a wide variety of chemicals for multiple purposes it is common for UV filters to co-occur with other substances either in human originating specimens or in the environment. There is increasing interest in understanding such co-occurrence in form of potential synergy, antagonist, or additive effects of biological systems. This review focuses on the collection of data about the simultaneous occurrence of UV filters oxybenzone (OXYB), ethylexyl-methoxycinnamate (EMC) and 4-methylbenzylidene camphor (4-MBC) as well as other classes of chemicals (such as pesticides, bisphenols, and parabens) to understand better any such interactions considering synergy, additive effect and antagonism. Our analysis identified >20 different confirmed synergies in 11 papers involving 16 compounds. We also highlight pathways (such as transcriptional activation of estrogen receptor, promotion of estradiol synthesis, hypothalamic-pituitary-gonadal (HPG) axis, and upregulation of thyroid-hormone synthesis) and proteins (such as Membrane Associated Progesterone Receptor (MAPR), cytochrome P450, and heat shock protein 70 (Hsp70)) that can act as important key nodes for such potential interactions. This article aims to provide insight into the molecular mechanisms on how commonly used UV filters act and may interact with other chemicals.

Commissioning and initial validation of Eclipse eMC algorithm for the electron FLASH research extension (FLEX) system for pre-clinical studies.

PURPOSE: To investigate the feasibility of commissioning the 16 MeV electron FLASH Extension (FLEX) in the commercial treatment planning system (TPS) for biomedical research with cell and mouse models, and in silico treatment planning studies. METHODS: To commission the FLEX system with the electron Monte Carlo (eMC) algorithm in the commercial TPS, radiochromic film was used to measure the vendor-recommended beam data. Once the beam model was generated for the eMC algorithm, supplemental measurements were collected for validation purposes and compared against the TPS-calculated results. Additionally, the newly commissioned 16 MeV FLASH beam was compared to the corresponding 16 MeV conventional electron beam. RESULTS: The eMC algorithm effectively modeled the FLEX system. The eMC-calculated PDDs and profiles for the 16 MeV electron FLASH beam agreed with measured values within 1%, on average, for 6 × 6 cm2 and 10 × 10 cm2 applicators. Flatness and symmetry deviated by less than 1%, while FWHM and penumbra agreed within 1 mm for both eMC-calculated and measured profiles. Additionally, the small field (i.e., 2-cm diameter cutout) that was measured for validation purposes agreed with TPS-calculated results within 1%, on average, for both the PDD and profiles. The FLASH and conventional dose rate 16 MeV electron beam were in agreement in regard to energy, but the profiles for larger field sizes began to deviate (>10 × 10 cm2) due to the forward-peaked nature of the FLASH beam. For cell irradiation experiments, the measured and eMC-calculated in-plane and cross-plane absolute dose profiles agreed within 1%, on average. CONCLUSIONS: The FLEX system was successfully commissioned in the commercial TPS using the eMC algorithm, which accurately modeled the forward-peaked nature of the FLASH beam. A commissioned TPS for FLASH will be useful for pre-clinical cell and animal studies, as well as in silico FLASH treatment planning studies for future clinical implementation.

System biology approaches to identify hub genes linked with ECM organization and inflammatory signaling pathways in schizophrenia pathogenesis.

Schizophrenia (SZ) is a chronic and devastating mental illness that affects around 20 million individuals worldwide. Cognitive deficits and structural and functional changes of the brain, abnormalities of brain ECM components, chronic neuroinflammation, and devastating clinical manifestation during SZ are likely etiological factors shown by affected individuals. However, the pathophysiological events associated with multiple regulatory pathways involved in the brain of this complex disorder are still unclear. This study aimed to develop a pipeline based on bioinformatics and systems biology approaches for identifying potential therapeutic targets involving possible biological mechanisms from SZ patients and healthy volunteers. About 420 overlapping differentially expressed genes (DEGs) from three RNA-seq datasets were identified. Gene ontology (GO), and pathways analysis showed several biological mechanisms enriched by the commonly shared DEGs, including extracellular matrix organization (ECM) organization, collagen fibril organization, integrin signaling pathway, inflammation mediated by chemokines and cytokines signaling pathway, and GABA-B receptor II and IL4 mediated signaling. Besides, 15 hub genes (FN1, COL1A1, COL3A1, COL1A2, COL5A1, COL2A1, COL6A2, COL6A3, MMP2, THBS1, DCN, LUM, HLA-A, HLA-C, and FBN1) were discovered by comprehensive analysis, which was mainly involved in the ECM organization and inflammatory signaling pathway. Furthermore, the miRNA target of the hub genes was analyzed with the random-forest-based approach software miRTarBase. In addition, the transcriptional factors and protein kinases regulating overlapping DEGs in SZ, namely, SUZ12, EZH2, TRIM28, TP53, EGR1, CSNK2A1, GSK3B, CDK1, and MAPK14, were also identified. The results point to a new understanding that the hub genes (fibronectin 1, collagen, matrix metalloproteinase-2, and lumican) in the ECM organization and inflammatory signaling pathways may be involved in the SZ occurrence and pathogenesis.

The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover.

Lysosomal degradation of autophagy receptors is a common proxy for selective autophagy. However, we find that two established mitophagy receptors, BNIP3 and BNIP3L/NIX, are constitutively delivered to lysosomes in an autophagy-independent manner. This alternative lysosomal delivery of BNIP3 accounts for nearly all its lysosome-mediated degradation, even upon mitophagy induction. To identify how BNIP3, a tail-anchored protein in the outer mitochondrial membrane, is delivered to lysosomes, we performed a genome-wide CRISPR screen for factors influencing BNIP3 flux. This screen revealed both known modifiers of BNIP3 stability as well as a pronounced reliance on endolysosomal components, including the ER membrane protein complex (EMC). Importantly, the endolysosomal system and the ubiquitin-proteosome system regulated BNIP3 independently. Perturbation of either mechanism is sufficient to modulate BNIP3-associated mitophagy and affect underlying cellular physiology. More broadly, these findings extend recent models for tail-anchored protein quality control and install endosomal trafficking and lysosomal degradation in the canon of pathways that tightly regulate endogenous tail-anchored protein localization.

High Response and Selectivity of the SnO2 Nanobox Gas Sensor for Ethyl Methyl Carbonate Leakage Detection in a Lithium-Ion battery.

It is well-known that metal-oxide semiconductors (MOS) have significant gas sensing activity and are widely used in harmful gas monitoring in various environments. With the rapid development of new energy vehicles, the monitoring of the gas composition and concentration in LIB has become an effective way to avoid safety problems. However, the study of typical electrolyte solvent detection, such as EMC and DMC detection by the MOS sensor, is still in its infancy. Here, the SnO2 nanoboxes are synthesized by coordination dissolution using cubic Cu2O as the template, and its sensor shows high sensitivity (0.27 to 10 ppb EMC), excellent response (32.46 to 20 ppm EMC), and superior selectivity. Additionally, the sensor possesses fast and clear response to lithium-ion battery (LIB) leakage simulation tests, suggesting that it should be a promising candidate for LIB safety monitors. These sensing performances are attributed to large specific surface area, small grain size, and high size/thickness ratio of nanoboxes. More importantly, DFT calculations confirm the adsorption of EMC on the surface of the SnO2 nanoboxes, and the EMC decomposition processes catalyzed by SnO2 are deduced by in situ FTIR and GC-MS.

Juxta-articular extraskeletal myxoid chondrosarcoma mistaken for a benign cyst presenting with multiple lung metastases.

Extraskeletal myxoid chondrosarcoma (EMC) is a malignant cartilage neoplasm usually encountered in the proximal extremities. We report the case of a 58-year-old male who presented initially with a 3-month history of cough. Initial staging demonstrated a right upper lobe mass with bilateral pulmonary nodules and moderate tracer uptake in the right lung mass and right groin on positron emission tomography imaging. Endobronchial ultrasound biopsy confirmed a histological diagnosis of EMC for which the patient underwent right upper lobe wedge resection. Pelvic MRI revealed a peripherally enhancing juxta-articular lesion within the region of the right obturator externus bursa, which was thought initially to represent either a ganglion or paralabral cyst. However, ultrasound-guided biopsy yielded identical histology to the resected lung mass leading to the diagnosis of primary EMC in the right groin with pulmonary metastases. The patient underwent surgical excision of the right groin mass with no local recurrence on the surveillance computed tomography at 5, 12, and 18 months but eventual disease recurrence in the right groin and further progression of the pulmonary metastases at 29 months. We emphasize that the contrast enhancement pattern of EMC can mimic a benign cystic lesion, in particular, when in a juxta-articular location, which has the potential to mislead radiologists and delay diagnosis and definitive treatment.

Epithelial-Myoepithelial Carcinoma of Nasal Cavity at an Unusual Age: A Case Report and Review of Literature.

Introduction: Epithelial-myoepithelial carcinoma (EMC) was recognised as a distinct pathologic entity in World Health Organisation classification. It is an extremely rare low grade carcinoma of salivary gland, with characteristic biphasic tubular structures. It predominantly occurs in Parotid gland but can also be seen in nasopharynx, lacrimal gland, paranasal sinuses, larynx, lung. Nasal EMC (excluding the paranasal sinuses as primary tumour site) are very rare with only 13 cases reported till date. In this case report, we described a case of nasal EMC extending into nasopharynx, its clinical features and management. We have also done a literature review of all the relevant cases of nasal EMC. Material and Methods: We searched the PubMed database for articles between January 1950 and December 2022 for nasal EMC for this review. Results: We found 13 relevant case reports of nasal EMC and median age was 58 years with female preponderance. We found that our patient was the youngest to be reported till date. Two cases, including the current study, showed epicentre of the tumour in posterior nasal cavity, extending to choana and nasopharynx. Most common presentation was epistaxis, followed by nasal obstruction. Only 4 out of 14 cases had information on surgical margin status, out of which only one has positive surgical margin. Five patients (including the patient in the current study) received adjuvant radiotherapy; however 6 patients (42.8%) did not receive any adjuvant radiotherapy.

Exome sequencing in retinal dystrophy patients reveals a novel candidate gene ER membrane protein complex subunit 3.

Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates the transmembrane peptides into lipid bilayers, and the function of its cytoplasmic carboxyl terminus remains to be elucidated. In this study, an insertional mutation c.768insT in the C-terminal coding region of EMC3 was identified and associated with dominant IRDs in a five-generation family. This mutation caused a frameshift in the coding sequence and a gain of an additional 16 amino acid residues (p.L256F-fs-ext21) to form a helix structure in the C-terminus of the EMC3 protein. The mutation is heterozygous with an incomplete penetrance, and cosegregates in all patients examined. This finding indicates that the C-terminus of EMC3 is essential for EMC functions and that EMC3 may be a novel candidate gene for retinal degenerative diseases.