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BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Pele , População do Sudeste Asiático , Humanos , Estudo de Associação Genômica Ampla , Fenótipo , VietnãRESUMO
Covalent organic frameworks (COFs) are an emerging class of highly porous crystalline organic polymers comprised entirely of organic linkers connected by strong covalent bonds. Due to their excellent physicochemical properties (e.g., ordered structure, porosity, and stability), COFs are considered ideal materials for developing state-of-the-art separation membranes. In fact, significant advances have been made in the last six years regarding the fabrication and functionalization of COF membranes. In particular, COFs have been utilized to obtain thin-film, composite, and mixed matrix membranes that could achieve effective rejection (mostly above 80%) of organic dyes and model organic foulants (e.g., humic acid). COF-based membranes, especially those prepared by embedding into polyamide thin-films, obtained adequate rejection of salts in desalination applications. However, the claims of ordered structure and separation mechanisms remain unclear and debatable. In this perspective, we analyze critically the design and exploitation of COFs for membrane fabrication and their performance in water treatment applications. In addition, technological challenges associated with COF properties, fabrication methods, and treatment efficacy are highlighted to redirect future research efforts in realizing highly selective separation membranes for scale-up and industrial applications.
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We report a high throughput evaluation of the Mizoroki-Heck reaction of diverse olefin coupling partners. Comparison of different ligands revealed the 1,5-diaza-3,7-diphosphacyclooctane (P2N2) scaffold to be more broadly applicable than common "gold standard" ligands, demonstrating that this family of readily accessible diphosphines has unrecognized potential in organic synthesis. In particular, two structurally related P2N2 ligands were identified to enable the regiodivergent arylation of styrenes. By simply altering the phosphorus substituent from a phenyl to tert-butyl group, both the linear and branched Mizoroki-Heck products can be obtained in high regioisomeric ratios. Experimental and computational mechanistic studies were performed to further probe the origin of selectivity, which suggests that both ligands coordinate to the metal in a similar manner but that rigid positioning of the phosphorus substituent forces contact with the incoming olefin in a π-π interaction (for P-Ph ligands) or with steric clash (for P-tBu ligands), dictating the regiocontrol.
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PURPOSE: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory. METHODS: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL). RESULTS: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores. CONCLUSIONS: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).
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Neurofibromatose 2 , Neuroma Acústico , Humanos , Biomarcadores , Everolimo , Neurofibromatose 2/diagnóstico por imagem , Neurofibromatose 2/tratamento farmacológico , Neurofibromatose 2/complicações , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/tratamento farmacológico , Neuroma Acústico/etiologia , Qualidade de Vida , Resultado do TratamentoRESUMO
In recent years, spatial atomic layer deposition (SALD) has gained significant attention for its remarkable capability to accelerate ALD growth by several orders of magnitude compared to conventional ALD, all while operating at atmospheric pressure. Nevertheless, the persistent challenge of inadvertent contributions from chemical vapor deposition (CVD) in SALD processes continues to impede control over film homogeneity, and properties. This research underscores the often-overlooked influence of diffusion coefficients and important geometric parameters on the close-proximity SALD growth patterns. We introduce comprehensive physical models complemented by finite element method simulations for fluid dynamics to elucidate SALD growth kinetics across diverse scenarios. Our experimental findings, in alignment with theoretical models, reveal distinctive growth rate trends in ZnO and SnO2films as a function of the deposition gap. These trends are ascribed to precursor diffusion effects within the SALD system. Notably, a reduced deposition gap proves advantageous for both diffusive and low-volatility bulky precursors, minimizing CVD contributions while enhancing precursor chemisorption kinetics. However, in cases involving highly diffusive precursors, a deposition gap of less than 100µm becomes imperative, posing technical challenges for large-scale applications. This can be ameliorated by strategically adjusting the separation distance between reactive gas outlets to mitigate CVD contributions, which in turn leads to a longer deposition time. Furthermore, we discuss the consequential impact on material properties and propose a strategy to optimize the injection head to control the ALD/CVD growth mode.
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INTRODUCTION: Although the use of peripherally inserted central catheters (PICCs) has many advantages, misplacement can lead to serious life-threatening complications such as pericardial effusion (PCE) and cardiac tamponade (CT). This report aims to describe four cases of CT resulting from misplaced PICC, which were successfully managed. METHODS: Retrospective analysis of neonates who required PICC insertion and had PCE leading to CT in the Neonatal Intensive Care Unit (NICU) at The Children's Hospital 2, Ho Chi Minh City, Vietnam, during the year 2022. RESULTS: Four cases involved preterm infants at 28-30 weeks gestational age, weighing between 900-1,500 grams. The PCE/CT developed between 3 and 24 days following PICC insertion. The abrupt onset with clinical manifestations that showed hemodynamic instability included sudden deterioration, lethargy, apnea, bradycardia, pale skin, and cardiovascular collapse. We use cardiac point of care ultrasound (POCUS) to assess the condition of these patients and guide the pericardiocentesis procedure. The analysis of the aspirated fluid used for PCE/CT treatment is consistent with the component of parenteral nutrition. No deaths were encountered. CONCLUSION: Neonates presenting sudden deterioration following PICC insertion should undergo POCUS to prompt identifying PCE/CT. Timely diagnosis via POCUS, prompt pericardiocentesis, and prevention of misplaced PICC-associated serious complications are crucial. Monitoring of the PICC position twice a week is recommended to avoid life-threatening complications. Additionally, incorporating POCUS for identifying the tip of PICC rather than relying solely on X-ray should be considered in the current protocol.
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Background The characteristics of amplitude-integrated electroencephalography (aEEG) are associated with neurological outcomes in neonates with hypoxic-ischemic encephalopathy (HIE). We perform a longitudinal analysis of continuous monitoring of aEEG during therapeutic hypothermia and explore the association between aEEG interpretation and clinical neurological outcomes. Method We conducted a prospective cohort study on HIE neonates undergoing hypothermia with aEEG monitoring. Results A total of 37 HIE infants underwent hypothermia with improved aEEG background activity in 28 (75.7%) neonates, of which 18 (48.6%) neonates had background activity returned to a continuous pattern, and the median recovery time was 26.5 hours. Sleep-wake cycle (SWC) appeared in 14 (37.8%) cases, with a median onset time of 34.5 hours. Seizure activity on aEEG was present in 26 (70.3%) infants. Factors associated with poor outcomes at discharge included low voltage or flat trace background activity, a lack of improvement in background activity after hypothermia, and the absence of SWC. Neonates who took longer than 62 hours to return to continuous background activity (time to normal trace) or did not have SWC before the end of hypothermia were more likely to have unfavorable outcomes at discharge. Conclusions Longitudinal analysis of aEEG during hypothermia should be implemented in neonatal care units. The progression of these features on aEEG may predict neurological outcomes for HIE neonates.
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BACKGROUND: Despite their growing use in health care, pretrained language models (PLMs) often lack clinical relevance due to insufficient domain expertise and poor interpretability. A key strategy to overcome these challenges is integrating external knowledge into PLMs, enhancing their adaptability and clinical usefulness. Current biomedical knowledge graphs like UMLS (Unified Medical Language System), SNOMED CT (Systematized Medical Nomenclature for Medicine-Clinical Terminology), and HPO (Human Phenotype Ontology), while comprehensive, fail to effectively connect general biomedical knowledge with physician insights. There is an equally important need for a model that integrates diverse knowledge in a way that is both unified and compartmentalized. This approach not only addresses the heterogeneous nature of domain knowledge but also recognizes the unique data and knowledge repositories of individual health care institutions, necessitating careful and respectful management of proprietary information. OBJECTIVE: This study aimed to enhance the clinical relevance and interpretability of PLMs by integrating external knowledge in a manner that respects the diversity and proprietary nature of health care data. We hypothesize that domain knowledge, when captured and distributed as stand-alone modules, can be effectively reintegrated into PLMs to significantly improve their adaptability and utility in clinical settings. METHODS: We demonstrate that through adapters, small and lightweight neural networks that enable the integration of extra information without full model fine-tuning, we can inject diverse sources of external domain knowledge into language models and improve the overall performance with an increased level of interpretability. As a practical application of this methodology, we introduce a novel task, structured as a case study, that endeavors to capture physician knowledge in assigning cardiovascular diagnoses from clinical narratives, where we extract diagnosis-comment pairs from electronic health records (EHRs) and cast the problem as text classification. RESULTS: The study demonstrates that integrating domain knowledge into PLMs significantly improves their performance. While improvements with ClinicalBERT are more modest, likely due to its pretraining on clinical texts, BERT (bidirectional encoder representations from transformer) equipped with knowledge adapters surprisingly matches or exceeds ClinicalBERT in several metrics. This underscores the effectiveness of knowledge adapters and highlights their potential in settings with strict data privacy constraints. This approach also increases the level of interpretability of these models in a clinical context, which enhances our ability to precisely identify and apply the most relevant domain knowledge for specific tasks, thereby optimizing the model's performance and tailoring it to meet specific clinical needs. CONCLUSIONS: This research provides a basis for creating health knowledge graphs infused with physician knowledge, marking a significant step forward for PLMs in health care. Notably, the model balances integrating knowledge both comprehensively and selectively, addressing the heterogeneous nature of medical knowledge and the privacy needs of health care institutions.
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Most currently available wearable devices to noninvasively detect hypoxia use the spatially resolved spectroscopy (SRS) method to calculate cerebral tissue oxygen saturation (StO2). This study applies the single source-detector separation (SSDS) algorithm to calculate StO2. Near-infrared spectroscopy (NIRS) data were collected from 26 healthy adult volunteers during a breath-holding task using a wearable NIRS device, which included two source-detector separations (SDSs). These data were used to derive oxyhemoglobin (HbO) change and StO2. In the group analysis, both HbO change and StO2 exhibited significant change during a breath-holding task. Specifically, they initially decreased to minimums at around 10 s and then steadily increased to maximums, which were significantly greater than baseline levels, at 25-30 s (p-HbO < 0.001 and p-StO2 < 0.05). However, at an individual level, the SRS method failed to detect changes in cerebral StO2 in response to a short breath-holding task. Furthermore, the SSDS algorithm is more robust than the SRS method in quantifying change in cerebral StO2 in response to a breath-holding task. In conclusion, these findings have demonstrated the potential use of the SSDS algorithm in developing a miniaturized wearable biosensor to monitor cerebral StO2 and detect cerebral hypoxia.
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A two-stream convolutional neural network (TCNN) for breathing pattern classification has been devised for the continuous monitoring of patients with infectious respiratory diseases. The TCNN consists of a convolutional neural network (CNN)-based autoencoder and classifier. The encoder of the autoencoder generates deep compressed feature maps, which contain the most important information constituting data. These maps are concatenated with feature maps generated by the classifier to classify breathing patterns. The TCNN, single-stream CNN (SCNN), and state-of-the-art classification models were applied to classify four breathing patterns: normal, slow, rapid, and breath holding. The input data consisted of chest tissue hemodynamic responses measured using a wearable near-infrared spectroscopy device on 14 healthy adult participants. Among the classification models evaluated, random forest had the lowest classification accuracy at 88.49%, while the TCNN achieved the highest classification accuracy at 94.63%. In addition, the proposed TCNN performed 2.6% better in terms of classification accuracy than an SCNN (without an autoencoder). Moreover, the TCNN mitigates the issue of declining learning performance with increasing network depth, as observed in the SCNN model. These results prove the robustness of the TCNN in classifying breathing patterns despite using a significantly smaller number of parameters and computations compared to state-of-the-art classification models.
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Culinary sage, Salvia officinalis L., is a popular spice plant commonly used throughout the world. In this study, 35 odorants were identified in dried sage via solvent-assisted flavor evaporation (SAFE) and aroma extract dilution analysis (AEDA), including 9 that were identified in sage for the first time. Fifteen odorants were quantitated by stable isotope dilution analysis (SIDA), and their odor activity values (OAVs) were determined. Odorants with high OAVs included (2E,6Z)-nona-2,6-dienal, 1,8-cineole, and ß-myrcene. A formulated aroma simulation model closely matched the aroma profile of an aqueous infusion of dried sage. Enantiomeric proportions of selected odorants were determined by chiral gas chromatography. Furthermore, 6 different sage cultivars were grown in the greenhouse, dried under the same conditions, and analyzed. Sensory analysis determined that all cultivars were dominated by an herbaceous sensory attribute and had varying intensities of eucalyptus, mint, clove, pine, green, earthy, floral, and citrus notes. Cultivars with varying intensities of herbaceous, eucalyptus, pine, and green sensory notes correlated with the OAVs of α-thujone/ß-thujone, 1,8-cineole, α-pinene, and (2E,6Z)-nona-2,6-dienal, respectively. This study identified the odorants driving the sensory profiles of different sage cultivars and serves as a foundation for future studies on the aroma chemistry of culinary sage.
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Salvia officinalis , Compostos Orgânicos Voláteis , Odorantes/análise , Eucaliptol/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Gasosa , Compostos Orgânicos Voláteis/química , Aromatizantes/química , OlfatometriaRESUMO
In visual perception and information processing, a cascade of associations is hypothesized to flow from the structure of the visual stimulus to neural activity along the retinogeniculostriate visual system to behavior and action. Do visual perception and information processing adhere to this cascade near the beginning of life? To date, this three-stage hypothetical cascade has not been comprehensively tested in infants. In two related experiments, we attempted to expose this cascade in 6-month-old infants. Specifically, we presented infants with two levels of visual stimulus intensity, we measured electrical activity at the infant cortex, and we assessed infants' preferential looking behavior. Chromatic saturation provided a convenient stimulus dimension to test the cascade because greater saturation is known to excite increased activity in the primate visual system and is generally hypothesized to stimulate visual preference. Experiment 1 revealed that infants prefer (look longer) at the more saturated of two colors otherwise matched in hue and brightness. Experiment 2 showed increased aggregate neural cortical excitation in infants (and adults) to the more saturated of the same pair of colors. Thus, experiments 1 and 2 taken together confirm a cascade: Visual stimulation of relatively greater intensity evokes relatively greater levels of bioelectrical cortical activity which in turn is associated with relatively greater visual attention. As this cascade obtains near the beginning of life, it helps to account for early visual preferences and visual information processing.
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Estimulação Luminosa , Percepção Visual , Humanos , Lactente , Percepção Visual/fisiologia , Feminino , Masculino , Córtex Visual/fisiologia , AdultoRESUMO
Fluoride is widely present in nature, and human exposure to it is generally regarded as inevitable. High levels of fluoride intake induce acute and chronic illnesses. To reduce potential harm to the general public, it is essential to create selective fluoride detectors capable of providing a colorimetric response for naked-eye detection without the need for sophisticated equipment. Here, we report a one-pot synthesis of four different diaminomaleonitrile-derived Schiff base sensors. The terephthalaldehyde adduct provided a strong color change visible to the naked eye at a F- concentration level as low as 2 ppm. From the evaluation against other anions, such as CN-, I-, Br-, Cl-, NO3-, PO43-, OAc-, and HSO4-, the molecular sensor displayed a visible color change exclusively upon exposure to fluoride, underscoring exceptional selectivity. As a key intermediate for understanding the mechanism, HF2- was confirmed by 19F nuclear magnetic resonance. Theoretical calculations suggested a deprotonation-triggered bathochromic shift brought about by the unique electronic structure of the sensor. Furthermore, the simple synthetic protocol from economically accessible materials allowed for the preparation of the compound on a large scale, rendering it a highly practical visual fluoride sensor.
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Filling defects within the inferior vena cava (IVC) are common findings on computed tomography (CT); nevertheless, a majority of these defects are attributed to artifacts. The documentation pertaining to pseudothrombosis specifically affecting the infrarenal vena cava is notably insufficient in current literature. The aim of this study is to present a case demonstrating a blood-contrast level in the infrarenal vena cava, resembling an intraluminal filling defect.
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This paper describes the analysis of electrodermal activity (EDA) in the context of students' scholastic activity. Taking a multidisciplinary, citizen science and maker-centric approach, low-cost, bespoken wearables, such as a mini weather station and biometric wristband, were built. To investigate both physical health as well as stress, the instruments were first validated against research grade devices. Following this, a research experiment was created and conducted in the context of students' scholastic activity. Data from this experiment were used to train machine learning models, which were then applied to interpret the relationships between the environment, health, and stress. It is hoped that analyses of EDA data will further strengthen the emerging model describing the intersections between local microclimate and physiological and neurological stress. The results suggest that temperature and air quality play an important role in students' physiological well-being, thus demonstrating the feasibility of understanding the extent of the effects of various microclimatic factors. This highlights the importance of thermal comfort and air ventilation in real-life applications to improve students' well-being. We envision our work making a significant impact by showcasing the effectiveness and feasibility of inexpensive, self-designed wearable devices for tracking microclimate and electrodermal activity (EDA). The affordability of these wearables holds promising implications for scalability and encourages crowd-sourced citizen science in the relatively unexplored domain of microclimate's influence on well-being. Embracing citizen science can then democratize learning and expedite rapid research advancements.
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Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.
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Bioscaffolds, which promote cell regeneration and restore tissues' functions, have emerged as significant need in clinic. The hybrid of several biomaterials in a bioscaffold renders clinically advanced and relevant properties for applications yet add challenges in cost efficiency, production, and clinical investigation. This study proposes a facile and sustainable method to formulate a triple-hybrid bioscaffold based on Vietnamese cocoon origin Silk Fibroin, Chitosan, and nano-Biphasic Calcium Phosphates (nano-BCP) that can be easily molded, has high porosity (55-80%), and swelling capacity that facilitates cell proliferation and nutrient diffusion. Notably, their mechanical properties, in particular compressive strength, can easily be tuned in a range from 50 - 200 kPa by changing the amount of nano-BCP addition, which is comparable to the successful precedents for productive cell regeneration. The latter parts investigate the biopharmaceutical properties of a representative bioscaffold, including drug loading and release studies with two kinds of active compounds, salmon calcitonin and methylprednisolone. Furthermore, the bioscaffold is highly biocompatible as the results of hemocompatibility and hemostasis tests, as well as ovo chick chorioallantoic membrane investigation. The findings of the study suggest the triple-hybrid scaffold as a promising platform for multi-functional drug delivery and bone defect repair.
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Glutamine is a conditionally essential amino acid for the growth and survival of rapidly proliferating cancer cells. Many cancers are addicted to glutamine, and as a result, targeting glutamine metabolism has been explored clinically as a therapeutic approach. Glutamine-catalyzing enzymes are highly expressed in primary and metastatic head and neck squamous cell carcinoma (HNSCC). However, the nature of the glutamine-associated pathways in this aggressive cancer type has not been elucidated. Here, we explored the therapeutic potential of a broad glutamine antagonist, DRP-104 (sirpiglenastat), in HNSCC tumors and aimed at shedding light on glutamine-dependent pathways in this disease. We observed a potent antitumoral effect of sirpiglenastat in HPV- and HPV + HNSCC xenografts. We conducted a whole-genome CRISPR screen and metabolomics analyses to identify mechanisms of sensitivity and resistance to glutamine metabolism blockade. These approaches revealed that glutamine metabolism blockade results in the rapid buildup of polyunsaturated fatty acids (PUFAs) via autophagy nutrient-sensing pathways. Finally, our analysis demonstrated that GPX4 mediates the protection of HNSCC cells from accumulating toxic lipid peroxides; hence, glutamine blockade sensitizes HNSCC cells to ferroptosis cell death upon GPX4 inhibition. These findings demonstrate the therapeutic potential of sirpiglenastat in HNSCC and establish a novel link between glutamine metabolism and ferroptosis, which may be uniquely translated into targeted glutamine-ferroptosis combination therapies.
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Ferroptose , Glutamina , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ensaios Antitumorais Modelo de Xenoenxerto , Glutamina/metabolismo , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Animais , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Linhagem Celular Tumoral , Camundongos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Sistemas CRISPR-CasRESUMO
Mechanically activating (MA) channels transduce numerous physiological functions. Tentonin 3/TMEM150C (TTN3) confers MA currents with slow inactivation kinetics in somato- and barosensory neurons. However, questions were raised about its role as a Piezo1 regulator and its potential as a channel pore. Here, we demonstrate that purified TTN3 proteins incorporated into the lipid bilayer displayed spontaneous and pressure-sensitive channel currents. These MA currents were conserved across vertebrates and differ from Piezo1 in activation threshold and pharmacological response. Deep neural network structure prediction programs coupled with mutagenetic analysis predicted a rectangular-shaped, tetrameric structure with six transmembrane helices and a pore at the inter-subunit center. The putative pore aligned with two helices of each subunit and had constriction sites whose mutations changed the MA currents. These findings suggest that TTN3 is a pore-forming subunit of a distinct slow inactivation MA channel, potentially possessing a tetrameric structure.
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Canais Iônicos , Animais , Humanos , Camundongos , Sequência de Aminoácidos , Células HEK293 , Canais Iônicos/metabolismo , Canais Iônicos/química , Bicamadas Lipídicas/metabolismo , Mecanotransdução Celular , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Mutação , Subunidades Proteicas/metabolismoRESUMO
Sulfurized polyacrylonitrile (SPAN) recently emerges as a promising cathode for high-energy lithium (Li) metal batteries owing to its high capacity, extended cycle life, and liberty from costly transition metals. As the high capacities of both Li metal and SPAN lead to relatively small electrode weights, the weight and specific energy density of Li/SPAN batteries are particularly sensitive to electrolyte weight, highlighting the importance of minimizing electrolyte density. Besides, the large volume changes of Li metal anode and SPAN cathode require inorganic-rich interphases that can guarantee intactness and protectivity throughout long cycles. This work addresses these crucial aspects with an electrolyte design where lightweight dibutyl ether (DBE) is used as a diluent for concentrated lithium bis(fluorosulfonyl)imide (LiFSI)-triethyl phosphate (TEP) solution. The designed electrolyte (d = 1.04 g mL-1) is 40%-50% lighter than conventional localized high-concentration electrolytes (LHCEs), leading to 12%-20% extra energy density at the cell level. Besides, the use of DBE introduces substantial solvent-diluent affinity, resulting in a unique solvation structure with strengthened capability to form favorable anion-derived inorganic-rich interphases, minimize electrolyte consumption, and improve cell cyclability. The electrolyte also exhibits low volatility and offers good protection to both Li metal anode and SPAN cathode under thermal abuse.