The revelation of characteristic volatile compounds in egg powder and analysis of their adsorption rules based on HS-GC-IMS technology.

The study constructed fingerprints and analyzed adsorption rules of volatile compounds (VOCs) in egg powder (EP) under different production processes, including egg white powder (EWP), egg yolk powder (EYP) and whole egg powder (WEP) by HS-GC-IMS. The 29 VOCs identified were primarily ketones and aldehydes. Characteristic VOCs responsible for flavor differences were clarified by difference comparison, clustering and PCA analysis. Additionally, variations in lipid and protein were the primary causes of the VOCs differences in EP through microscopy imaging, infrared and fluorescence spectroscopy. EWP's stretched structure favored fishy-smelling VOCs adsorption but limited total aldehyde binding due to strong hydrophobic interaction. EYP's higher ß-sheet ratio and fewer hydrogen bond sites weakened its alcohol VOCs binding capacity. The abundance of ketone VOCs in EP was linked to their low steric hindrance. Therefore, this study elucidated the flavor differences reasons among EWP, EYP and WEP, laying foundation for EP applications in food industry.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

On-field Head Acceleration Exposure Measurements Using Instrumented Mouthguards: Multi-stage Screening to Optimize Data Quality.

Instrumented mouthguards (iMGs) are widely applied to measure head acceleration event (HAE) exposure in sports. Despite laboratory validation, on-field factors including potential sensor skull-decoupling and spurious recordings limit data accuracy. Video analysis can provide complementary information to verify sensor data but lacks quantitative kinematics reference information and suffers from subjectivity. The purpose of this study was to develop a rigorous multi-stage screening procedure, combining iMG and video as independent measurements, aimed at improving the quality of on-field HAE exposure measurements. We deployed iMGs and gathered video recordings in a complete university men's ice hockey varsity season. We developed a four-stage process that involves independent video and sensor data collection (Stage I), general screening (Stage II), cross verification (Stage III), and coupling verification (Stage IV). Stage I yielded 24,596 iMG acceleration events (AEs) and 17,098 potential video HAEs from all games. Approximately 2.5% of iMG AEs were categorized as cross-verified and coupled iMG HAEs after Stage IV, and less than 1/5 of confirmed or probable video HAEs were cross-verified with iMG data during stage III. From Stage I to IV, we observed lower peak kinematics (median peak linear acceleration from 36.0 to 10.9 g; median peak angular acceleration from 3922 to 942 rad/s2) and reduced high-frequency signals, indicative of potential reduction in kinematic noise. Our study proposes a rigorous process for on-field data screening and provides quantitative evidence of data quality improvements using this process. Ensuring data quality is critical in further investigation of potential brain injury risk using HAE exposure data.

Magnetocaloric effect of topological excitations in Kitaev magnets.

Traditional magnetic sub-Kelvin cooling relies on the nearly free local moments in hydrate paramagnetic salts, whose utility is hampered by the dilute magnetic ions and low thermal conductivity. Here we propose to use instead fractional excitations inherent to quantum spin liquids (QSLs) as an alternative, which are sensitive to external fields and can induce a very distinctive magnetocaloric effect. With state-of-the-art tensor-network approach, we compute low-temperature properties of Kitaev honeycomb model. For the ferromagnetic case, strong demagnetization cooling effect is observed due to the nearly free Z2 vortices via spin fractionalization, described by a paramagnetic equation of state with a renormalized Curie constant. For the antiferromagnetic Kitaev case, we uncover an intermediate-field gapless QSL phase with very large spin entropy, possibly due to the emergence of spinon Fermi surface and gauge field. Potential realization of topological excitation magnetocalorics in Kitaev materials is also discussed, which may offer a promising pathway to circumvent existing limitations in the paramagnetic hydrates.

O-GlcNAcylation of SERCA protects skeletal muscle in hibernating Spermophilus dauricus from disuse atrophy.

Long-term inactivity of skeletal muscle results in muscular disuse atrophy; however, hibernating animals do not experience muscular disuse atrophy during the hibernation period. The molecular mechanism underlining the anti-atrophy effect in these animals is unclear. O-linked N acetyl-ß-D-glucosaminylation (O-GlcNAcylation) and its effect on cell signaling pathways are important mechanisms underlying muscular disuse atrophy; thus, in this study, we investigated O-GlcNAcylation changes during hibernation in Spermophilus dauricus to explore the role of O-GlcNAcylation in the muscle disuse atrophy resistance of hibernating animals. The results showed that during hibernation, the muscle fiber cross-sectional area and ratio of muscle fiber did not change, and the morphological structure of the muscle remained intact, with normal contractile function. The level of O-GlcNAcylation decreased during hibernation, but quickly returned to normal in the periodic arousal stage. The O-GlcNAcylation level of sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) decreased, whereas its activity increased. The decrease in O-GlcNAcylation of SERCA could result in the decreased binding of phospholamban to SERCA1, thus decreasing its inhibition to SERCA1 activity. This in turn can inhibit muscle cell calcium overload, maintain muscle cell calcium homeostasis, and stabilize the calpain proteolytic pathway, ultimately inhibiting skeletal muscle atrophy. Our results demonstrate that periodic arousal along with returning O-GlcNAcylation level to normal are important mechanisms in preventing disuse atrophy of skeletal muscle during hibernation.

Coinoculation of autochthonous starter cultures: A strategy to improve the flavor characteristics and inhibit biogenic amines of Harbin dry sausage.

The effects of separately coinoculating Lactiplantibacillus plantarum S8 (LP) with Staphylococcus carnosus L8 (LP + SC), Pichia kudriavzevii M6 (LP + PK), and S. carnosus L8 and P. kudriavzevii M6 (LP + SC + PK) on the flavor characteristics and biogenic amines (BAs) production in Harbin dry sausages were investigated. The coinoculated sausages exhibited higher free amino acids (FAAs) content than the noninoculated and LP sausages. Moreover, inoculated dry sausages exhibited lower BA contents (174.45, 239.43, 190.24, and 206.7 mg/kg for the LP, LP + SC, LP + PK, and LP + PK + SC sausages, respectively) than the noninoculated sausage (339.73 mg/kg). Meanwhile, the LP + PK and LP + SC + PK sausages had the highest contents of esters (996.70 µg/kg) and alcohols (603.46 µg/kg), respectively. A sensory evaluation demonstrated that the LP + SC + PK sausage had the highest fermented odor and the lowest fatty odor. Pearson correlation analysis revealed that FAAs were correlated with most key volatile compounds and BAs. This study provides new insights into flavor development and BA inhibition in dry sausages through coinoculation.

RemixFormer++: A Multi-modal Transformer Model for Precision Skin Tumor Differential Diagnosis with Memory-efficient Attention.

Diagnosing malignant skin tumors accurately at an early stage can be challenging due to ambiguous and even confusing visual characteristics displayed by various categories of skin tumors. To improve diagnosis precision, all available clinical data from multiple sources, particularly clinical images, dermoscopy images, and medical history, could be considered. Aligning with clinical practice, we propose a novel Transformer model, named Remix-Former++ that consists of a clinical image branch, a dermoscopy image branch, and a metadata branch. Given the unique characteristics inherent in clinical and dermoscopy images, specialized attention strategies are adopted for each type. Clinical images are processed through a top-down architecture, capturing both localized lesion details and global contextual information. Conversely, dermoscopy images undergo a bottom-up processing with two-level hierarchical encoders, designed to pinpoint fine-grained structural and textural features. A dedicated metadata branch seamlessly integrates non-visual information by encoding relevant patient data. Fusing features from three branches substantially boosts disease classification accuracy. RemixFormer++ demonstrates exceptional performance on four single-modality datasets (PAD-UFES-20, ISIC 2017/2018/2019). Compared with the previous best method using a public multi-modal Derm7pt dataset, we achieved an absolute 5.3% increase in averaged F1 and 1.2% in accuracy for the classification of five skin tumors. Furthermore, using a large-scale in-house dataset of 10,351 patients with the twelve most common skin tumors, our method obtained an overall classification accuracy of 92.6%. These promising results, on par or better with the performance of 191 dermatologists through a comprehensive reader study, evidently imply the potential clinical usability of our method.

A Serious Game for Enhancing Rescue Reasoning Skills in Tactical Combat Casualty Care: Development and Deployment Study.

BACKGROUND: Serious games (SGs) have emerged as engaging and instructional digital simulation tools that are increasingly being used for military medical training. SGs are often compared with traditional media in terms of learning outcomes, but it remains unclear which of the 2 options is more efficient and better accepted in the process of knowledge acquisition. OBJECTIVE: This study aimed to create and test a scenario-based system suitable for enhancing rescue reasoning skills in tactical combat casualty care. METHODS: To evaluate the effectiveness of the SGs, a randomized, observational, comparative trial was conducted. A total of 148 members from mobile medical logistics teams were recruited for training. Pre- and posttraining assessments were conducted using 2 different formats: a video-based online course (n=78) and a game simulation (n=70). We designed 3 evaluation instruments based on the first 2 levels of the Kirkpatrick model (reaction and learning) to measure trainees' satisfaction, knowledge proficiency, and self-confidence. RESULTS: There were 4 elements that made up the learning path for the SGs: microcourses (video-based online courses), self-test, game simulation, and record query. The knowledge test scores in both groups were significantly higher after the intervention (t154=-6.010 and t138=-7.867, respectively; P<.001). For 5 simulation cases, the average operation time was 13.6 (SD 3.3) minutes, and the average case score was 279.0 (SD 57.6) points (from a possible total of 500 points), with a score rate of only 44% (222/500 points) to 67% (336/500 points). The results indicated no significant difference in trainees' satisfaction between the 2 training methods (P=.04). However, the game simulation method outperformed the video-based online course in terms of learning proficiency (t146=-2.324, P=.02) and self-perception (t146=-5.492, P<.001). CONCLUSIONS: Despite the high satisfaction reported by trainees for both training methods, the game simulation approach demonstrated superior efficiency and acceptance in terms of knowledge acquisition, self-perception, and overall performance. The developed SG holds significant potential as an essential assessment tool for evaluating frontline rescue skills and rescue reasoning in mobile medical logistics teams.

BLADE-ON-PETIOLE interacts with CYCLOIDEA to fine-tune CYCLOIDEA-mediated flower symmetry in monkeyflowers (Mimulus).

Morphological novelties, or key innovations, are instrumental to the diversification of the organisms. In plants, one such innovation is the evolution of zygomorphic flowers, which is thought to promote outcrossing and increase flower morphological diversity. We isolated three allelic mutants from two Mimulus species displaying altered floral symmetry and identified the causal gene as the ortholog of Arabidopsis BLADE-ON-PETIOLE. We found that MlBOP and MlCYC2A physically interact and this BOP-CYC interaction module is highly conserved across the angiosperms. Furthermore, MlBOP self-ubiquitinates and suppresses MlCYC2A self-activation. MlCYC2A, in turn, impedes MlBOP ubiquitination. Thus, this molecular tug-of-war between MlBOP and MlCYC2A fine-tunes the expression of MlCYC2A, contributing to the formation of bilateral symmetry in flowers, a key trait in angiosperm evolution.

Using VIS-NIR hyperspectral imaging and deep learning for non-destructive high-throughput quantification and visualization of nutrients in wheat grains.

High-throughput and low-cost quantification of the nutrient content in crop grains is crucial for food processing and nutritional research. However, traditional methods are time-consuming and destructive. A high-throughput and low-cost method of quantification of wheat nutrients with VIS-NIR (400-1700 nm) hyperspectral imaging is proposed in this study. Stepwise linear regression (SLR) was used to predict hundreds of nutrients accurately (R2 > 0.6); results improved when the hyperspectral data was processed with the first derivative. Knockout materials were also used to verify their practical application value. Various nutrients' characteristic wavelengths were mainly concentrated in the visible regions of 400-500 nm and 900-1000 nm. Finally, we proposed an improved pix2pix conditional generative network model to visualize the nutrients distribution and showed better results compared with the original. This research highlights the potential of hyperspectral technology in high-throughput and non-destructive determination and visualization of grain nutrients with deep learning.

Constructing Multi-Electron Reactions by Doping Mn2+ to Increase Capacity and Stability in K3.2V2.8Mn0.2(PO4)4/C of Phosphate Cathodes for Potassium-Ion Batteries.

Vanadium-based phosphate cathode materials (e.g., K3V2(PO4)3) have attracted widespread concentration in cathode materials in potassium-ion batteries owing to their stable structure but suffer from low capacity and poor conductivity. In this work, an element doping strategy is applied to promote its electrochemical performance so that K3.2V2.8Mn0.2(PO4)4/C is prepared via a simple sol-gel method. The heterovalent Mn2+ is introduced to stimulated multiple electron reactions to improve conductivity and capacity, as well as interlayer spacing. Galvanostatic intermittent titration technique (GITT) and in situ X-ray diffraction results further confirm that Mn-doping in the original electrode can obtain superior electrode process kinetics and structural stability. The prepared K3.2V2.8Mn0.2(PO4)4/C exhibits a high-capacity retention of 80.8% after 1 500 cycles at 2 C and an impressive rate capability, with discharge capacities of 87.6 at 0.2 C and 45.4 mA h g-1 at 5 C, which is superior to the majority of reported vanadium-based phosphate cathode materials. When coupled K3.2V2.8Mn0.2(PO4)4/C cathode with commercial porous carbon (PC) anode as the full cell, a prominent energy density of 175 Wh kg-1 is achieved based on the total active mass. Overall, this study provides an effective strategy for meliorating the cycling stability and capacity of the polyanion cathodes for KIB.

Vagus nerve stimulation (VNS) preventing postoperative cognitive dysfunction (POCD): two potential mechanisms in cognitive function.

Postoperative cognitive dysfunction (POCD) impacts a significant number of patients annually, frequently impairing their cognitive abilities and resulting in unfavorable clinical outcomes. Aimed at addressing cognitive impairment, vagus nerve stimulation (VNS) is a therapeutic approach, which was used in many mental disordered diseases, through the modulation of vagus nerve activity. In POCD model, the enhancement of cognition function provided by VNS was shown, demonstrating VNS effect on cognition in POCD. In the present study, we primarily concentrates on elucidating the role of the VNS improving the cognitive function in POCD, via two potential mechanisms: the inflammatory microenvironment and epigenetics. This study provided a theoretical support for the feasibility that VNS can be a potential method to enhance cognition function in POCD.

Possible role of a malfunctioning immune system in discordant lymphoma with peripheral T­cell lymphoma secondary to classical Hodgkin lymphoma: A case report.

The present case report investigated the clinicopathological features and potential mechanisms underlying the transformation to peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), following treatment for classical Hodgkin lymphoma (CHL) in a 73-year-old man. The patient was admitted to hospital in 2012 and underwent a left cervical lymph node biopsy, which confirmed CHL of the nodular sclerosing type, with evident bone marrow involvement. The patient received four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy, after which they achieved complete remission. However, after 3 years, the patient presented with enlarged left inguinal lymph nodes and a biopsy revealed PTCL-NOS. Molecular studies indicated a T-cell receptor-γ gene rearrangement. A literature review, together with the current case, identified 11 patients with CHL that transformed into PTCL-NOS. Among these, nine patients (81.82%) were middle-aged or elderly (>45 years old), and eight (72.73%) experienced transformation within 3 years post-treatment of CHL. Among these eight patients, seven (87.50%) predominantly exhibited the nodular sclerosis subtype, with a median recurrence time of 26 months. Five (45.45%) patients died of the disease. The rare transformation of CHL to PTCL-NOS, primarily among men, underscores its clinical significance. Notably, nodular sclerosing-type CHL appears to be particularly prone to transformation into PTCL-NOS. The poor prognosis in such cases may be attributed to the complex tumor microenvironment of CHL.

Model-predicted brain temperature computational imaging by multimodal noninvasive functional neuromonitoring of cerebral oxygen metabolism and hemodynamics: MRI-derived and clinical validation.

Brain temperature, a crucial yet under-researched neurophysiological parameter, is governed by the equilibrium between cerebral oxygen metabolism and hemodynamics. Therapeutic hypothermia has been demonstrated as an effective intervention for acute brain injuries, enhancing survival rates and prognosis. The success of this treatment hinges on the precise regulation of brain temperature. However, the absence of comprehensive brain temperature monitoring methods during therapy, combined with a limited understanding of human brain heat transmission mechanisms, significantly hampers the advancement of hypothermia-based neuroprotective therapies. Leveraging the principles of bioheat transfer and MRI technology, this study conducted quantitative analyses of brain heat transfer during mild hypothermia therapy. Utilizing MRI, we reconstructed brain structures, estimated cerebral blood flow and oxygen consumption parameters, and developed a brain temperature calculation model founded on bioheat transfer theory. Employing computational cerebral hemodynamic simulation analysis, we established an intracranial arterial fluid dynamics model to predict brain temperature variations across different therapeutic hypothermia modalities. We introduce a noninvasive, spatially resolved, and optimized mathematical bio-heat model that synergizes model-predicted and MRI-derived data for brain temperature prediction and imaging. Our findings reveal that the brain temperature images generated by our model reflect distinct spatial variations across individual participants, aligning with experimentally observed temperatures.

Development and validation of a deep learning-based framework for automated lung CT segmentation and acute respiratory distress syndrome prediction: a multicenter cohort study.

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high incidence and mortality rate in intensive care unit (ICU) admissions. Early identification of patients at high risk for developing ARDS is crucial for timely intervention and improved clinical outcomes. However, the complex pathophysiology of ARDS makes early prediction challenging. This study aimed to develop an artificial intelligence (AI) model for automated lung lesion segmentation and early prediction of ARDS to facilitate timely intervention in the intensive care unit. Methods: A total of 928 ICU patients with chest computed tomography (CT) scans were included from November 2018 to November 2021 at three centers in China. Patients were divided into a retrospective cohort for model development and internal validation, and three independent cohorts for external validation. A deep learning-based framework using the UNet Transformer (UNETR) model was developed to perform the segmentation of lung lesions and early prediction of ARDS. We employed various data augmentation techniques using the Medical Open Network for AI (MONAI) framework, enhancing the training sample diversity and improving the model's generalization capabilities. The performance of the deep learning-based framework was compared with a Densenet-based image classification network and evaluated in external and prospective validation cohorts. The segmentation performance was assessed using the Dice coefficient (DC), and the prediction performance was assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The contributions of different features to ARDS prediction were visualized using Shapley Explanation Plots. This study was registered with the China Clinical Trial Registration Centre (ChiCTR2200058700). Findings: The segmentation task using the deep learning framework achieved a DC of 0.734 ± 0.137 in the validation set. For the prediction task, the deep learning-based framework achieved AUCs of 0.916 [0.858-0.961], 0.865 [0.774-0.945], 0.901 [0.835-0.955], and 0.876 [0.804-0.936] in the internal validation cohort, external validation cohort I, external validation cohort II, and prospective validation cohort, respectively. It outperformed the Densenet-based image classification network in terms of prediction accuracy. Moreover, the ARDS prediction model identified lung lesion features and clinical parameters such as C-reactive protein, albumin, bilirubin, platelet count, and age as significant contributors to ARDS prediction. Interpretation: The deep learning-based framework using the UNETR model demonstrated high accuracy and robustness in lung lesion segmentation and early ARDS prediction, and had good generalization ability and clinical applicability. Funding: This study was supported by grants from the Shanghai Renji Hospital Clinical Research Innovation and Cultivation Fund (RJPY-DZX-008) and Shanghai Science and Technology Development Funds (22YF1423300).

Medium-Chain Chlorinated Paraffins Trigger Thyroid Hormone Synthesis and Interfere with Mitochondrial Function in the Thyroid Gland.

Medium-chain chlorinated paraffins (MCCPs, C14-C17) are frequently detected in diverse environmental media. It has been proposed to be listed in Annex A of the Convention on Persistent Organic Pollutants in 2023. Although MCCPs are a crucial health concern, their toxicity remains unclear. This study investigated the toxic effects of MCCPs (0.1-50 mg/kg body weight/day) on the thyroid gland of female Sprague-Dawley rats and characterized the potential toxic pathways via transcriptomics and metabolomics approaches. MCCPs exposure caused histopathological changes to the endoplasmic reticula and mitochondria in thyroid follicular cells at a dose of 50 mg/kg bw/d and increased serum thyrotropin-releasing hormone, thyroid-stimulating hormones, and thyroxine when exposed to a higher dose of MCCPs. Transcriptomic analysis indicated the excessive expression of key genes related to thyroid hormone synthesis induced by MCCPs. Integrating the dual-omics analysis revealed mitochondrial dysfunction of the thyroid by mediating fatty acid oxidation, Kreb's cycle, and oxidative phosphorylation. Significant metabolic toxicity on the thyroid might be linked to the characteristics of the chlorine content of MCCPs. This study revealed the toxicity of MCCPs to the thyroid gland via triggering thyroid hormone synthesis and interfering with mitochondrial function, which can provide new insights into the modes of action and mechanism-based risk assessment of MCCPs.

Unmasking the silent culprit: recurrent exercise-induced acute kidney injury in a Chinese adolescent with renal hypouricemia.

Primary renal hypouricemia (RHUC) is a rare autosomal recessive disorder with a mean duration of end-stage acute kidney injury (EIAKI) of 14 days. The pathogenesis of EIAKI in patients with RHUC remains unclear. Several hypotheses have been proposed, including those related to the renal vasoconvulsive effect and the elevating effect of xanthine oxidase (XO). The effect of xanthine oxidase (XO) is most often observed following strenuous anaerobic exercise, which is frequently accompanied by low back pain, nausea, and acute kidney injury (AKI). Consequently, we postulate that EIAKI could be prevented by avoiding strenuous exercise, thus preventing the onset and recurrence of EIAKI. In this paper, we present a case of recurrent EIAKI in a patient with RHUC and a mutation in the SLC2A9 gene.

Immune-related gene signature improves prognosis prediction in patients with breast cancer and associates it with tumor immunity and inflammatory response.

BACKGROUND: The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. METHODS: We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. RESULTS: Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. CONCLUSIONS: The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation.

G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Validation of selected targets of GPS2-mediated regulation, including the RNA-binding protein PABPC1 and translation factors RPS1, RACK1 and eIF3M, revealed a mitochondrial-specific strategy for regulating the translation of nuclear-encoded mitochondrial proteins via non-proteolytic ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the import-coupled translation of selected mRNAs leading to the increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.

NQO1 polymorphism and susceptibility to ischemic stroke in a Chinese population.

BACKGROUND: Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. METHODS: Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. RESULTS: The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017-5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073-5.396, P = 0.033). CONCLUSIONS: NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS.