TGM1/3-mediated transamidation of Exo70 promotes tumor metastasis upon LKB1 inactivation.

Exo70, a key exocyst complex component, is crucial for cell motility and extracellular matrix (ECM) remodeling in cancer metastasis. Despite its potential as a drug target, Exo70's post-translational modifications (PTMs) are poorly characterized. Here, we report that Exo70 is transamidated on Gln5 with Lys56 of cystatin A by transglutaminases TGM1 and TGM3, promoting tumor metastasis. This modification enhances Exo70's association with other exocyst subunits, essential for secreting matrix metalloproteinases, forming invadopodia, and delivering integrins to the leading edge. Tumor suppressor liver kinase B1 (LKB1), whose inactivation accelerates metastasis, phosphorylates TGM1 and TGM3 at Thr386 and Thr282, respectively, to inhibit their interaction with Exo70 and the following transamidation. Cantharidin, a US Food and Drug Administration (FDA)-approved drug, inhibits Exo70 transamidation to restrain tumor cell migration and invasion. Together, our findings highlight Exo70 transamidation as a key molecular mechanism and target and propose cantharidin as a therapeutic strategy with direct clinical translational value for metastatic cancers, especially those with LKB1 loss.

Complications and Health-related Quality of Life following Lumbosacral Hemivertebra Resection and Short Segmental Fusion: A Retrospective Cohort Study.

BACKGROUND CONTEXT: Previous literature has provided descriptions of postoperative complications. However, these studies have included heterogeneous cohorts of hemivertebra patients undergoing different surgical methods and addressing deformities at various locations. PURPOSE: To assess independent risk factors for complications following lumbosacral hemivertebra (LSHV) resection and to further explored the potential association between complications and health-related quality of life (HRQOL). DESIGN: Retrospective cohort study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent LSHV resection and short segment fusion at our institution between 2010 and 2022. OUTCOME MEASURE: In the current study, the outcome measure were complications and HRQOL. METHODS: Between 2010 and 2022, a total of 64 consecutive patients with LSHV underwent hemivertebra resection. The diagnostic criteria for LSHV were delineated that the hemivertebra resides caudal to L5 and beyond. Electronic patient record and radiographic data were reviewed retrospectively in our electronic database. According to complications, the patients were divided into with and without complications, and further stratified as neurological, mechanical, and infectious complications. HRQOL outcomes were collected preoperatively, 3 months postoperatively, and at last follow-up using the Scoliosis Research Society-22 (SRS-22) questionnaire. Multivariate logistic regression models were used to determine independent risk factors affecting complications. RESULTS: A total of 64 patients were enrolled in this study for at least 2-year follow-up. The mean follow-up was 7.3±4.2 years. In the coronal plane, the mean main curve was corrected from 27.3° preoperatively to 8.0° postoperatively, and 9.3° at last follow-up. Global spine balance was significantly improved after surgery, and kept stable during the follow-up. In all, 18 complications were recorded in 15 (23.4%) patients. In the multivariate logistic regression model, three independent risk factors for complication were screened out, including age (OR=1.16, 95% CI 1.01-1.34, P=0.042), anterior reconstruction (OR=3.40, 95% CI 1.03-11.2, P=0.045), and preoperative CB (OR=1.06, 95% CI 1.00-1.12, P=0.036). The mean SRS-22 total and domain scores for the entire cohort showed improvement at last follow-up. However, in the non-complication group, the improvements in SRS-22 scores were more substantial. CONCLUSION: Postoperative neurological and mechanical complications are common medical events following LSHV resection. The age, anterior column reconstruction, and preoperative coronal balance were the independent risk factors. Compared to the non-complication group, the improvements in HRQOL are blunted in the complication group.

Dose-Response Relationship between Perioperative Allogeneic Blood Transfusion and Surgical Site Infections following Spinal Surgery.

BACKGROUND CONTEXT: Perioperative allogeneic transfusion was generally considered to be safe. However, there had been some literatures reporting a potential association between surgical site infections (SSI) and blood transfusion. PURPOSE: To determine whether perioperative blood transfusion increased the risk of SSI and to further explored whether there was a dose-response relationship. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between July 2011 and July 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: All consecutive patients who underwent elective spinal surgery at our institution between July 2011 and July 2021 formed the retrospective cohort. Electronic patient record and radiographic data were reviewed retrospectively in our electronic database. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Then, we explored the non-linear relationship between perioperative blood transfusion and SSI by a smoothed curve, with the adjustments for potential confounders. If a non-linear relationship was observed, a two-piecewise regression model would be performed to calculate the threshold effect. RESULTS: The average time from surgery to diagnosis of SSI was 20.5 days. We matched 248 controls to 124 SSI cases. Of the 124 patients who developed SSI, 84 patients (67.7%) had deep SSI, 40 patients (32.3%) had superficial SSI. In the fully adjusted model, the risk of SSI increased by 27% for each additional unit of blood transfusion. It can be seen from the curve fitting plot that the risk of SSI has a greater increase after blood transfusion >3U. Subsequent piecewise regression identified an inflection point of 3U. CONCLUSION: We determined that 3U was a threshold volume of allogeneic blood transfusion that shifted the risk of SSI following spinal surgery, and there was a dose-response effect.

Quantitative modelling of Plato and total flavonoids in Qingke wort at mashing and boiling stages based on FT-IR combined with deep learning and chemometrics.

Craft beer brewers need to learn process control strategies from traditional industrial production to ensure the consistent quality of the finished product. In this study, FT-IR combined with deep learning was used for the first time to model and analyze the Plato degree and total flavonoid content of Qingke beer during the mashing and boiling stages and to compare the effectiveness with traditional chemometrics methods. Two deep learning neural networks were designed, the effect of variable input methods on the effectiveness of the models was discussed. The experimental results showed that the CARS-LSTM model had the best predictive performance, not only as the best quantitative model for Plato in the mashing (R2p = 0.9368) and boiling (R2p = 0.9398) phases but also as the best model for TFC in the boiling phase (R2p = 0.9154). This study demonstrates the great potential of deep learning and provides a new approach to quality control analysis in beer brewing.

Lambda-cyhalothrin induces heart injury in chickens by regulating cytochrome P450 enzyme system and inhibiting Nrf2/HO-1 pathway.

Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.

Warming-Induced Vegetation Greening May Aggravate Soil Mercury Levels Worldwide.

Mercury, a neurotoxic substance, circulates globally, significantly stored in soils through atmospheric deposition and plant decay. Despite being deposited, mercury can be remobilized and released into the atmosphere and water, enhancing its global cycle. Recent research suggests that climate warming may amplify the remobilization of soil mercury, facilitating its incorporation into food webs that humans exploit. However, the potential geospatial feedback of soil mercury levels in response to warming remains unclear. By leveraging up-to-date soil measurements and observation-driven models, we determined the amount of mercury stored in global 0-100 cm soils to be 4.3 Tg (interquartile range: 2.5-6.3 Tg). Furthermore, our analysis indicates that warming likely aggravates global soil mercury levels, particularly in many temperate areas in East Asia, North Europe, and North America (>20 ng g-1 increase by 2100) due to warming-induced vegetation greening. Critically, observation-driven models raise the possibility that implementing ambitious mercury-emission-control schemes alone may be insufficient to counterbalance the positive feedback of soil mercury concentration, while process-based biogeochemical modeling demonstrates consistent patterns that reinforce this concern. These findings hold broad implications; for example, such feedback may catalyze mercury remobilization in land-ocean continuums and exacerbate human risks, stressing the necessity for continued reductions in greenhouse gas and mercury emissions.

Prolonged exposure to a music-enriched environment mitigates acute noise-induced inflammation and apoptosis in the chicken spleen by modulating the Keap-1/Nrf2 and NF-κB pathways.

The rise of operational noise as an environmental pollutant for farm animals is an emerging concern. The mechanisms through which music can alleviate oxidative stress, inflammation, and apoptosis induced by noise exposure remain underexplored. This study aims to investigate the alleviating effects and underlying mechanisms of long-term music exposure on noise-induced damage to the chicken spleen. Male Arbor Acres (AA) broilers were divided into four groups: control (C), acute noise stimulation (NS), noise stimulation with music mitigation (NSM), and music only (M). NS and NSM groups were exposed to noise (simulating sudden intensity noise, 115 to 120dB) for 10 minutes daily for a week, starting at 14-days-old. NSM and M groups then received 28 days of 6-hour daily music (Mozart K.448, 60-65 dB). The results showed that noise stimulation significantly activated the Keap-1/Nrf2 and NF-κB signaling pathways. Long-term music intervention has also been demonstrated to successfully mitigate oxidative stress and abnormal apoptosis induced by acute noise stimulation. Microscopic examination of the spleen revealed that acute noise stimulation resulted in an increase in splenic cells, a decrease in lymphocytes, and blurred boundaries between the red and white pulps in the NS group. However, these pathological changes were alleviated in the NSM group following music intervention. Compared with the control group, the NS group exhibited significantly elevated oxidative stress parameters. In contrast, music intervention in the NSM group notably improved antioxidant capacity and partially alleviated morphological abnormalities in the spleen. Additionally, noise stimulation activated the NF-κB pathway, upregulating the downstream genes of the inflammatory factors IL-1ß, IL-6, and TNF-α. Noise-induced mitochondrial damage led to apoptosis, as observed by TUNEL staining, along with increased gene and protein expression of Bcl-2, Bax, Cyt-C, Casp-3, Casp-8, and Casp-9. These findings indicate that acute noise exposure can induce splenic damage via oxidative stress, inflammation, and apoptosis by modulating the Keap-1/Nrf2 and NF-κB pathways. Prolonged music stimulation effectively mitigates noise-induced damage, offering a vital experimental foundation for further research on noise pollution's impact on organisms and music's alleviating role.

The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation.

Psoriasis is a chronic, proliferative, and inflammatory skin disease closely associated with inflammatory cytokine production. Cyclophilin A (CypA) is an important proinflammatory factor; however, its role in psoriasis remains unclear. The present data indicate that CypA levels are increased in the lesion skin and serum of patients with psoriasis, which is positively correlated with the psoriasis area severity index. Furthermore, extracellular CypA (eCypA) triggered psoriasis-like inflammatory responses in keratinocytes. Moreover, anti-CypA mAb significantly reduced pathological injury, keratinocyte proliferation, cytokine expression in imiquimod-induced mice. Notably, the therapeutic effect of anti-CypA mAb was better than that of the clinically used anti-IL-17A mAb and methotrexate. Mechanistically, eCypA binds to ACE2 and CD147 and is blocked by anti-CypA mAb. eCypA not only induces the dimerization and phosphorylation of ACE2 to trigger the JAK1/STAT3 signaling pathway for cytokine expression but also interacts with CD147 to promote PI3K/AKT/mTOR signaling-mediated keratinocyte proliferation. These findings demonstrate that the binding of eCypA to ACE2 and CD147 cooperatively triggers psoriasis-like inflammation and anti-CypA mAb is a promising candidate for the treatment of psoriasis.

The association between abdominal obesity and depressive symptoms among Chinese adults: Evidence from national and regional communities.

BACKGROUND: The association between body shape and depressive symptoms has been reported in adults. The present study aimed to investigate the association between body shape-specific abdominal obesity and depressive symptoms among multi-regional Asian adults. METHODS: The 2011-2012 China Health and Retirement Longitudinal Study and 2022-2023 Hangzhou study were used as the discovery and validation datasets, respectively. Body shape was assessed by body mass index categories. Abdominal obesity was defined as a body shape index (ABSI) ≥ 75th centile. Depression was measured using 10-item Centre for Epidemiological Studies Depression Scale and Geriatric Depression Scale short 15-item version, respectively. General linear and multinomial logistic models were used to explore the association of ABSI, abdominal obesity with depressive scores and presence, respectively. RESULTS: A total of 12,229 and 1210 participants were included in the discovery and validation datasets, respectively. A non-linear reverse L-shaped association was found between ABSI and depressive scores. Participants with abdominal obesity had higher depressive scores (ß = 0.05, 95%CI = 0.01-0.09; and ß = 0.13, 95%CI = 0.01-0.24; respectively). Stratified analyses showed that abdominal obesity was associated with higher depressive scores (ß = 0.09, 95%CI = 0.00-0.17; and ß = 0.25, 95%CI = 0.05-0.46; respectively) and presence (OR = 1.46, 95%CI = 1.02-2.10; and OR = 3.95, 95%CI = 1.58-9.84; respectively) in overweight adults. Furthermore, abdominal obesity was associated with depressive symptoms among overweight females, but not among males. LIMITATION: Causal links weren't addressed because of the observational study design. CONCLUSION: Abdominal obesity exhibited a positive association with depressive symptoms among Asian overweight adults, particularly in females. Prevention and early diagnosis of depressive symptoms should focus on overweight females.

Learning-based distortion correction enables proximal-scanning endoscopic OCT elastography.

Proximal rotary scanning is predominantly used in the clinical practice of endoscopic and intravascular OCT, mainly because of the much lower manufacturing cost of the probe compared to distal scanning. However, proximal scanning causes severe beam stability issues (also known as non-uniform rotational distortion, NURD), which hinders the extension of its applications to functional imaging, such as OCT elastography (OCE). In this work, we demonstrate the abilities of learning-based NURD correction methods to enable the imaging stability required for intensity-based OCE. Compared with the previous learning-based NURD correction methods that use pseudo distortion vectors for model training, we propose a method to extract real distortion vectors from a specific endoscopic OCT system, and validate its superiority in accuracy under both convolutional-neural-network- and transformer-based learning architectures. We further verify its effectiveness in elastography calculations (digital image correlation and optical flow) and the advantages of our method over other NURD correction methods. Using the air pressure of a balloon catheter as a mechanical stimulus, our proximal-scanning endoscopic OCE could effectively differentiate between areas of varying stiffness of atherosclerotic vascular phantoms. Compared with the existing endoscopic OCE methods that measure only in the radial direction, our method could achieve 2D displacement/strain distribution in both radial and circumferential directions.

Flow shear force destabilizes carotid plaques by affecting CHOP and GRP78 proteins.

BACKGROUND: Various factors, including blood, inflammatory, infectious, and immune factors, can cause ischemic stroke. However, the primary cause is often the instability of cervical arteriosclerosis plaque. It is estimated that 18-25% of ischemic strokes are caused by the rupture of carotid plaque.1 Plaque stability is crucial in determining patient prognosis. Developing a highly accurate, non-invasive, or minimally invasive technique to assess carotid plaque stability is crucial for diagnosing and treating stroke.Previous research by our group has demonstrated that the expression levels of CHOP (C/EBP homologous protein) and GRP78 (glucose-regulated protein 78) are correlated with the stability of atherosclerotic plaques.2 OBJECT: This research assesses changes in GRP78 and CHOP expressions in human umbilical vein endothelial cells(HUVEC) following experiments within the hemodynamic influencing factors test system. Additionally, it includes conducting an empirical study on the impact of blood flow shear force on the stability of human carotid atherosclerotic plaques. The objective is to explore the implications of blood flow shear force on the stability of carotid atherosclerotic plaques. METHOD: The hemodynamic influencing factors test bench system was configured with low (Group A, 4 dyns/cm²), medium (Group B, 8 dyns/cm²), and high shear force groups (Group C, 12 dyns/cm²). Relative expression levels of GRP78 and CHOP proteins in human umbilical vein endothelial cells were measured using Western blot analysis, and quantitative analysis of GRP78 and CHOP mRNA was conducted using RT-qPCR. Meanwhile, plaques from 60 carotid artery patients, retrieved via Carotid Endarterectomy (CEA), were classified into stable (S) and unstable (U) groups based on pathological criteria. Shear force at the carotid bifurcation was measured preoperatively using ultrasound. Western blot and RT-qPCR were used to analyze the relative expression levels of GRP78 and CHOP proteins and mRNA, respectively, in the plaque specimens from both groups. RESULT: Expression levels of GRP78, CHOP proteins, and their mRNAs were assessed in groups A, B, and C via Western blot and RT-qPCR. Results showed that in the low-shear group, all markers were elevated in group A compared to groups B and C. Statistical analysis revealed significantly lower shear forces at the carotid bifurcation in group U compared to group S. In group U plaques, GRP78 and CHOP expressions were significantly higher in group U than in group S. CONCLUSION: Blood flow shear forces variably affect the expression of GRP78 and CHOP proteins, as well as their mRNA levels, in vascular endothelial cells. The lower the shear force and fluid flow rate, the higher the expression of GRP78 and CHOP, potentially leading to endoplasmic reticulum stress(ERS), which may destabilize the plaque.

A Novel Hand-held Multi-color Magnetic Particle Imaging Device based on Rapid Frequency Conversion.

OBJECTIVE: Multi-color Magnetic Particle Imaging (MPI) technology offers high sensitivity and non-invasive imaging capabilities. It can simultaneously image multiple superparamagnetic iron oxide nanoparticles (SPIOs), facilitating more precise detection of multiple molecular markers in vivo. However, the fixed drive frequency of existing hand-held MPI devices makes it difficult to fully match the nonlinear magnetic response of different SPIOs, affecting the spatial resolution and quantitative accuracy of multi-color imaging. METHODS: We designed a novel rapid frequency conversion based hand-held multi-color magnetic particle imaging (RFC-MPI) device. This device adjusts the drive frequency based on the nonlinear magnetic response of SPIOs at different frequencies, effectively expanding the system matrix information and thereby improving spatial resolution and multi-color imaging capabilities simultaneously. RESULTS: The device achieved a spatial resolution of 2 mm and an imaging speed of 1 frame/s. The scanning depth is 8 mm. It was used to scan a 22 cm x 22 cm area of a human-shaped phantom, verifying its potential for scanning humans. The ability of the device to identify and quantify SPIOs was validated using mice breast tumors. The quantitative accuracy during simultaneous imaging was determined to be 96.58%. CONCLUSION: Due to its innovative structural design and rapid frequency conversion method, the RFC-MPI device exhibits excellent in vivo imaging performance. Both simulation and phantom experiments have verified the effectiveness of the proposed method. SIGNIFICANCE: The hand-held RFC-MPI device can effectively improve the spatial resolution and quantitative accuracy of multi-color MPI, laying the foundation for future clinical applications.

Monoammonium Modified Dion-Jacobson Quasi-2D Perovskite for High Efficiency Pure-Blue Light Emitting Diodes.

Quasi-2D perovskites exhibit impressive optoelectronic properties and hold significant promise for future light-emitting devices. However, the efficiency of perovskite light-emitting diodes (PeLEDs) is seriously limited by defect-induced nonradiative recombination and imbalanced charge injection. Here, the defect states are passivated and charge injection balance is effectively improved by introducing the additive cyclohexanemethylammonium (CHMA) to bromide-based Dion-Jacobson (D-J) structure quasi-2D perovskite emission layer. CHMA participates in the crystallization of perovskite, leading to high quality film composed of compact and well-contacted grains with enhanced hole transportation and less defects. As a result, the corresponding PeLEDs exhibit stable pure blue emission at 466 nm with a maximum external quantum efficiency (EQE) of 9.22%. According to current knowledge, this represents the highest EQE reported for pure-blue PeLEDs based on quasi-2D bromide perovskite thin films. These findings underscore the potential of quasi-2D perovskites for advanced light-emitting devices and pave the way for further advancements in PeLEDs.

Defining Age-Adjusted PI-LL Targets for Surgical Realignment in Adult Degenerative Scoliosis: A Retrospective Cohort Study.

Objectives: The purpose of this study was to investigate postoperative pelvic incidence minus lumbar lordosis mismatch (PI-LL) and health-related quality of life (HRQOL) outcomes to determine age-adjusted PI-LL targets. Method: The dataset encompassed a range of variables, including age, sex, body mass index, Charlson comorbidity index, presence of osteopenia, hospital stay, operative duration, blood loss, American Society of Anesthesiologists score, number of fusion levels, lumbar lordosis, sagittal vertical axis, pelvic incidence, and PI-LL. The non-linear relationship between PI-LL and clinical outcomes was examined using a curve analysis, with adjustments made for potential confounding variables. Upon identification of a non-linear relationship, a two-piecewise regression model was employed to determine the threshold effect. Results: A total of 280 patients were enrolled. In the fully adjusted model, the optimal PI-LL target for patients aged 45-54 years old was PI-LL < 10°, the optimal target for patients aged 55-74 was 10-20°, and the optimal target for patients older than 75 years was more suitable for PI-LL > 20°. In the curve-fitting graph, it could be seen that the relationship between PI-LL and HRQOL outcomes was not linear in each age group. The peaks of the curves within each group occurred at different locations. Higher and lower thresholds for optimal surgical goals were determined using the two-piecewise regression model from the SRS-22 score and the ODI score. Conclusions: This study showed that the optimal PI-LL after corrective surgery in adult degenerative scoliosis patients should be adjusted according to age.

Psychosocial Clusters and Their Associations with Depression, Anxiety and Stress Among Older Adults in Shanghai Communities: Results from a Longitudinal Study.

Purpose: Psychosocial factors have been found to profoundly impact mental health of older adults, but the main focus in the current literature has been on one particular aspect of these factors. This study aimed to identify latent classes of older adults based on four psychosocial factors (loneliness, social isolation, perceived social support, and social capital) and the transition of classes over 6 months. We also sought to assess the predictive role of changes in these classes in relation to depression, anxiety, and stress at 18-month follow-up. Methods: We analyzed longitudinal data from 581 community-dwelling older adults in Shanghai, China. The data were collected at baseline (T0), 6-month follow-up (T1) and 18-month follow-up (T2) between March 2021 and April 2023. Using latent class analysis, we identified three underlying classes (Social Connectors, Subjective Social Isolates, and Social Isolates) of the sample. We also established five transition categories from T0 to T1 (Social Connectors T0-T1, Subjective Social Isolates T0-T1, Social Isolates T0-T1, Good Transition, and Bad Transition) using latent transition analysis. Logistic regression was employed to examine the temporal relationships between these transition categories and subsequent symptoms of depression, anxiety and stress, adjusting for age, sex, education, marital status, family income level, sleep quality, health status and outcome variables at T0. Results: Multivariable associations revealed that compared to older adults with persistent good social environment (Social Connectors T0-T1), those with persistent high levels of loneliness and social isolation and low levels of perceived social support and social capital (Social Isolates T0-T1), and those who shifted towards a poorer social environment (Bad Transition) were more likely to experience depression, anxiety and stress at T2. Sustained subjective social isolation (Subjective Social Isolates T0-T1) was associated with more severe depressive symptoms at T2. Conclusion: Our study indicated that adverse psychosocial environment worsened mental health in older adults. These findings highlight the importance of early identification of older individuals at long-term psychosocial risk and development of tailored interventions to improve their social environment and mental health.

Sound as a bell: a deep learning approach for health status classification through speech acoustic biomarkers.

BACKGROUND: Human health is a complex, dynamic concept encompassing a spectrum of states influenced by genetic, environmental, physiological, and psychological factors. Traditional Chinese Medicine categorizes health into nine body constitutional types, each reflecting unique balances or imbalances in vital energies, influencing physical, mental, and emotional states. Advances in machine learning models offer promising avenues for diagnosing conditions like Alzheimer's, dementia, and respiratory diseases by analyzing speech patterns, enabling complementary non-invasive disease diagnosis. The study aims to use speech audio to identify subhealth populations characterized by unbalanced constitution types. METHODS: Participants, aged 18-45, were selected from the Acoustic Study of Health. Audio recordings were collected using ATR2500X-USB microphones and Praat software. Exclusion criteria included recent illness, dental issues, and specific medical histories. The audio data were preprocessed to Mel-frequency cepstral coefficients (MFCCs) for model training. Three deep learning models-1-Dimensional Convolution Network (Conv1D), 2-Dimensional Convolution Network (Conv2D), and Long Short-Term Memory (LSTM)-were implemented using Python to classify health status. Saliency maps were generated to provide model explainability. RESULTS: The study used 1,378 recordings from balanced (healthy) and 1,413 from unbalanced (subhealth) types. The Conv1D model achieved a training accuracy of 91.91% and validation accuracy of 84.19%. The Conv2D model had 96.19% training accuracy and 84.93% validation accuracy. The LSTM model showed 92.79% training accuracy and 87.13% validation accuracy, with early signs of overfitting. AUC scores were 0.92 and 0.94 (Conv1D), 0.99 (Conv2D), and 0.97 (LSTM). All models demonstrated robust performance, with Conv2D excelling in discrimination accuracy. CONCLUSIONS: The deep learning classification of human speech audio for health status using body constitution types showed promising results with Conv1D, Conv2D, and LSTM models. Analysis of ROC curves, training accuracy, and validation accuracy showed all models robustly distinguished between balanced and unbalanced constitution types. Conv2D excelled with good accuracy, while Conv1D and LSTM also performed well, affirming their reliability. The study integrates constitution theory and deep learning technologies to classify subhealth populations using noninvasive approach, thereby promoting personalized medicine and early intervention strategies.

Chlormequat chloride induces hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.

Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo, male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21-60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro, HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 µg/mL) for 24 h. And the results showed that CCC above 120 µg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.

Association between Adverse Psychological Emotions and Postoperative Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study with Propensity Score Matching.

OBJECTIVE: Although the advantages of postoperative braces have been verified in many fields, it is not clear whether postoperative braces can help reduce patients' adverse psychological emotions such as kinesiophobia, anxiety, and depression. This study aims to analyze whether the use of a postoperative brace helps reduce adverse psychological emotions in adolescent idiopathic scoliosis (AIS) patients undergoing spinal deformity surgeries. METHODS: All consecutive patients who underwent spinal corrective surgeries at our institution between April 2023 and July 2023 formed the prospective cohort. Outcome measures were collected in the preoperative period, 3 months after surgery, and 6 months after surgery. All patients were assessed using the Tampa scale for kinesiophobia (TSK), the hospital anxiety and depression scale (HADS), and the numerical rating scale (NRS). A statistical model of propensity score matching was used to eliminate potential selection bias and maintain comparability. Multivariate linear regression models were used to determine the relationship between postoperative brace and adverse psychological emotions. RESULTS: After propensity score matching, this study ultimately enrolled 150 patients. There were no significant differences between the two groups in terms of demographic and perioperative variables. The fully adjusted model showed that the TSK scores of the non-brace group at the 3-month (ꞵ = 2.50, 95% CI 0.80-4.20, p = 0.005) and 6-month follow-up (ꞵ = 2.75, 95% CI 0.75-4.74, p = 0.007) were significantly higher than those of the brace group. The HADS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 1.75, 95% CI 0.28-3.22, p = 0.019). The NRS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 0.69, 95% CI 0.05-1.33, p = 0.034). At the 6-month follow-up, there were no significant difference for HADS score or NRS score between the two groups. CONCLUSION: In the early postoperative period, the postoperative brace could provide AIS patients with psychological supports and help them reduce the frequency of adverse psychological emotions. The postoperative brace could continuously improve the fear of movement within 6 months after surgery, and help reduce anxiety, depression, and pain within 3 months after surgery.

The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

TBC1D10B promotes tumor progression in colon cancer via PAK4­mediated promotion of the PI3K/AKT/mTOR pathway.

This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.