Parameter identification of Johnson-Cook constitutive model based on genetic algorithm and simulation analysis for 304 stainless steel.

Addressing the significant discrepancy between actual experimental cutting force and its predicted values derived from traditional constitutive model parameter identification methods, a reverse identification research of the Johnson-Cook (J-C) constitutive model for 304 stainless steel was conducted via genetic algorithm. Considering actual cutting zone and the influence of feed motion on the rake (flank) angle, an unequal division shear zone model was established to implement the theoretical calculation for shear zone stress. Through cutting experiments, the spindle speed was negatively correlated with the cutting force at first, and then became positively correlated; The empirical formula (EXP model) for turning force was corrected, revealing that the EXP model was unable to provide optimal predicted values for cutting force. The influence of the J-C constitutive parameter C on the cutting morphology was firstly investigated through simulation analysis, and determined an appropriate value for C, then obtained the precise values for the other four constitutive parameters by genetic algorithm. Moreover, the simulated values of cutting force in JC1 model (obtained from the Split Hopkinson Pressure Bar test) and JCM model (the improved model using genetic algorithm) were obtained by three-dimensional (3-D) simulation via FEM software. The results indicated that, the maximum error between actual experimental cutting force and its simulated values (by JCM model) was 14.8%, with an average error of 6.38%. These results outperformed the JC1 and EXP models, suggesting that the JCM model identified via genetic algorithm was more reliable.

[Clinical application of retroauricular hairline approach in submandibular gland resection assisted by endoscope].

Objective:To investigate the clinical effect of retroauricular hairline approach in submandibular gland resection assisted by endoscope. Methods:A total of 18 patients with submandibular gland benign tumors treated in our hospital from September 2022 to September 2023 were selected. A 5 cm incision was designed in the retroauricular hairline, and the flap was turned over directly to the anterior edge of sternocleidomastoid muscle, then the flap was turned over to build the cavity through endoscopic surgery, and submandibular gland resection was completed with the assistance of endoscope. After operation, a negative pressure drainage was placed into the hairline, and the wound was closed by continuous intracutaneous suture. The clinical effect was evaluated after 3-6 months follow-up. Results:All patients underwent submandibular gland resection with endoscopic assistance as planned, and none of them converted to submaxillary incision during operation. The operation time was 65-97 min, with an average of 75 min. Intraoperative bleeding was 10-20 mL, with an average of 14 mL.No tongue numbness, wound infection, or tumor recurrence occurred after operation. However, there were 10 patients with ear numbness and discomfort of auricle after surgery, which gradually recovered after 6-9 months of follow-up. Two patients had crooked mouth after surgery, and the symptoms were gradually relieved after follow-up. All incisions healed in stage I and were concealed. Conclusion:Endoscopic retroauricular hairline approach is a choice for submandibular gland resection with good cosmetic effect, less trauma and fewer complications.

Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers.

Accurately distinguishing tumor cells from normal cells is a key issue in tumor diagnosis, evaluation, and treatment. Fluorescence-based immunohistochemistry as the standard method faces the inherent challenges of the heterogeneity of tumor cells and the lack of big data analysis of probing images. Here, we have demonstrated a machine learning-driven imaging method for rapid pathological diagnosis of five types of cancers (breast, colon, liver, lung, and stomach) using a perovskite nanocrystal probe. After conducting the bioanalysis of survivin expression in five different cancers, high-efficiency perovskite nanocrystal probes modified with the survivin antibody can recognize the cancer tissue section at the single cell level. The tumor to normal (T/N) ratio is 10.3-fold higher than that of a conventional fluorescent probe, which can successfully differentiate between tumors and adjacent normal tissues within 10 min. The features of the fluorescence intensity and pathological texture morphology have been extracted and analyzed from 1000 fluorescence images by machine learning. The final integrated decision model makes the area under the receiver operating characteristic curve (area under the curve) value of machine learning classification of breast, colon, liver, lung, and stomach above 90% while predicting the tumor organ of 92% of positive patients. This method demonstrates a high T/N ratio probe in the precise diagnosis of multiple cancers, which will be good for improving the accuracy of surgical resection and reducing cancer mortality.

Endothelial α1-adrenergic receptor activation improves cardiac function in septic mice via PKC-ERK/p38MAPK signaling pathway.

Cardiomyopathy is particularly common in septic patients. Our previous studies have shown that activation of the alpha 1 adrenergic receptor (α1-AR) on cardiomyocytes inhibits sepsis-induced myocardial dysfunction. However, the role of cardiac endothelial α1-AR in septic cardiomyopathy has not been determined. Here, we identified α1-AR expression in mouse and human endothelial cells and showed that activation of α1-AR with phenylephrine (PE) improved cardiac function and survival by preventing cardiac endothelial injury in septic mice. Mechanistically, activating α1-AR with PE decreased the expression of ICAM-1, VCAM-1, iNOS, E-selectin, and p-p38MAPK, while promoting PKC and ERK1/2 phosphorylation in LPS-treated endothelial cells. These effects were abolished by a PKC inhibitor or α1-AR antagonist. PE also reduced p65 nuclear translocation, but this suppression is not blocked by PKC inhibition. Treatment with U0126 (a specific ERK1/2 inhibitor) reversed the effects of PE on p38MAPK phosphorylation. Our results demonstrate that cardiac endothelial α1-AR activation prevents sepsis-induced myocardial dysfunction in mice by inhibiting the endothelial injury via PKC-ERK/p38MAPK signaling pathway and a PKC-independent inhibition of p65 nuclear translocation. These findings offer a new perspective for septic patients with cardiac dysfunction by inhibiting cardiac endothelial cell injury through α1-AR activation.

Developing and Validating a Nomogram for Non-Adherence to Inhaler Therapy Among Elderly Chronic Obstructive Pulmonary Disease Patients Based on the Social Ecological Model.

Purpose: This study aimed to identify the risk predictors of non-adherence to inhaler therapy and construct a nomogram prediction model for use in Chinese elderly patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: A cross-sectional study was conducted with 305 participants recruited from a tertiary care hospital in Anhui, China. Adherence was analyzed using the Test of Adherence to Inhalers. Potential predictive factors were incorporated based on the social ecological model, and data were collected through a questionnaire method. R version 4.3.3 was utilized to perform the least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis to identify risk factors and establish a nomogram prediction model. Results: The results of the multivariable analysis revealed that medication beliefs, illness perception, the COPD Assessment Test score, smoking status, and education level were significant risk factors for non-adherence to inhaler therapy in elderly COPD patients (all P < 0.05). The nomogram prediction model for non-adherence to inhaler therapy in elderly COPD patients demonstrated a good discriminative ability, with an area under the receiver operating characteristic curve of 0.912. The C-index was 0.922 (95% CI: 0.879 to 0.965), and the Brier value was 0.070, indicating good consistency and calibration. Decision curve analysis indicated that the use of the nomogram would be more beneficial in clinical practice when the threshold probability of non-adherence exceeds 17%. Conclusion: This study identified predictive factors regarding non-adherence among elderly patients with COPD and constructed a predictive nomogram. By utilizing the nomogram model healthcare professionals could swiftly calculate and comprehend the non-compliance level of COPD patients, thus guiding the development of personalized interventions in clinical practice.

The reduced cortical bone density in vertebral bodies: risk for osteoporotic fractures? Insights from CT analysis.

BACKGROUND: There is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures. METHODS: We retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient's vertebral body was determined. RESULTS: In this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm3, with T12 having the lowest BMD (p < 0.001, T12 vs. L2). Cancellous BMD ranged from 128.5 ± 58.4 to 140.9 ± 58.9 mg/cm3, with L3 having the lowest BMD. OVCF patients had lower cortical BMD of 365.0 ± 78.9 to 429.3 ± 156.7 mg/cm3, with a further decrease in T12 BMD. Cancellous BMD ranged from 71.68 ± 52.07 to 123.9 ± 126.2 mg/cm3, with L3 still having the lowest BMD. Fractured vertebrae in OVCF patients (T12, L1, and L2) had lower cortical bone density compared to their corresponding vertebrae without fractures (p < 0.05). CONCLUSIONS: T12 had the lowest cortical BMD and L3 had the lowest cancellous BMD in OVCF patients, with T12 also having the highest incidence of osteoporotic fractures. These findings suggest that reduction in cortical BMD has a greater impact on OVCF than reduction in cancellous BMD, along with biomechanical factors.

Epitaxial Metal-Organic Framework-Mediated Electron Relay for H2 Detection on Demand.

Hydrogen is regarded as one of the most promising clean substitutes for fossil fuels toward a carbon-zero society. However, the safety management of the upcoming hydrogen energy infrastructure has not been fully prepared, in contrast to the well-established natural gas and gasoline systems. On the frontline is the guard post of hydrogen detectors, which need to be deployed on various structural surfaces and environmental conditions. Conventional hydrogen detectors are usually bulky and environmentally sensitive, limiting their flexible and conformal deployment to various locations, such as pipelines and valves. Herein, we demonstrate the successful synthesis of a palladium-modified epitaxial metal-organic framework (MOF) on single-layer graphene to fabricate a heterostructure material (Epi-MOF-Pd). Device based on the heterostructure demonstrates high sensitivity toward low- concentration H2 (155% resistance response to 1% H2 within 12 s, a theoretical detection limit of 3 ppm). The 25 nm epitaxial MOF acquires electrons from the Pd nanoparticles after the trace amount of H2 is chemically adsorbed and further relays the electrons to the highly conductive graphene. The Epi-MOF-Pd is both flexible and enduring, and maintains stable detection over 10 000 bending cycles. Through photolithography, device arrays with a density of 3000 units/cm2 are successfully fabricated. This versatile material provides a prospective avenue for the mass production of high-performance chemical-sensitive electronics, which could significantly improve the hydrogen safety management on demand.

Machine Learning-Assisted High-Throughput Identification and Quantification of Protein Biomarkers with Printed Heterochains.

Advanced in vitro diagnosis technologies are highly desirable in early detection, prognosis, and progression monitoring of diseases. Here, we engineer a multiplex protein biosensing strategy based on the tunable liquid confinement self-assembly of multi-material heterochains, which show improved sensitivity, throughput, and accuracy compared to standard ELISA kits. By controlling the material combination and the number of ligand nanoparticles (NPs), we observe robust near-field enhancement as well as both strong electromagnetic resonance in polymer-semiconductor heterochains. In particular, their optical signals show a linear response to the coordination number of the semiconductor NPs in a wide range. Accordingly, a visible nanophotonic biosensor is developed by functionalizing antibodies on central polymer chains that can identify target proteins attached to semiconductor NPs. This allows for the specific detection of multiple protein biomarkers from healthy people and pancreatic cancer patients in one step with an ultralow detection limit (1 pg/mL). Furthermore, rapid and high-throughput quantification of protein expression levels in diverse clinical samples such as buffer, urine, and serum is achieved by combining a neural network algorithm, with an average accuracy of 97.3%. This work demonstrates that the heterochain-based biosensor is an exemplary candidate for constructing next-generation diagnostic tools and suitable for many clinical settings.

Application of Multi-Rod Constructs for the Revision of Thoracolumbar Fractures.

OBJECTIVE: The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi-rod constructs in the revision of thoracolumbar fractures. METHODS: Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi-rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow-up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow-up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). RESULTS: The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow-up period. The paired t-test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre-revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post-revision and last follow-up (p = 0.551). VAS and ODI were greatly improved at the last follow-up. CONCLUSION: The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi-rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Urban-rural disparities in the short-term effects of cold and heat on myocardial infarction mortality in Anhui Province, China.

Non-optimal ambient temperatures are risk factors for myocardial infarction (MI) and urban-rural temperature differences in the context of climate change may have caused and will lead to differential association between temperature and MI. We collected daily mean temperature and daily MI deaths from 1 January 2016 to 31 December 2020 in Anhui Province, China. A distributed lag nonlinear model was performed to estimate the area-specific association of heat and cold (defined as the 2.5th and 97.5th percentile of the daily mean temperature) with MI mortality; the random-effects meta-analysis was then used to pool the effects of cold and heat. We found the risk of MI death due to cold was higher in rural areas [relative risk (RR): 1.13, 95% confidence interval (CI): 1.02-1.26, lag0) than in urban areas (RR: 0.99, 95% CI: 0.80-1.21, lag0), whereas the risk of MI death associated with heat was higher in urban areas (RR: 1.14, 95% CI: 1.03-1.27, lag0) than in rural areas (RR: 1.04, 95% CI: 0.99-1.10, lag0). Our findings may help to develop targeted protective strategies to reduce the adverse effects of cold and heat on cardiovascular disease.

YL-109 attenuates sepsis-associated multiple organ injury through inhibiting the ERK/AP-1 axis and pyroptosis by upregulating CHIP.

Sepsis is a severe inflammatory disorder that can lead to life-threatening multiple organ injury. Lipopolysaccharide (LPS)-induced inflammation is the leading cause of multiple organ failure in sepsis. This study aimed to explore the effect of a novel agent, 2-(4-hydroxy-3-methoxyphenyl)-benzothiazole (YL-109), on LPS-induced multiple organ injury and the molecular mechanisms underlying these processes. The results showed that YL-109 protected against LPS-induced high mortality, cardiac dysfunction, pulmonary and intestinal injury through inhibiting the proinflammatory response, NLRP3 expression and pyroptosis-associated indicators in mouse tissues. YL-109 suppressed LPS-initiated cytokine release, pyroptosis and pyroptosis-related protein expression in HL-1, IEC-6 and MLE-12 cells, which was consistent with the results of the in vivo experiments. Mechanistically, YL-109 reduces phosphorylated ERK (extracellular signal-regulated kinase) levels and NF-κB activation, which are achieved through upregulating CHIP (carboxy terminus of Hsc70-interacting protein) expression, thereby inhibiting c-Jun and c-Fos activation as well as NLRP3 expression. As an E3 ligase, CHIP overexpression obviously promoted the degradation of phosphorylated ERK and inhibited the expression of NF-κB-mediated NLRP3 in cells stimulated with LPS. The protective effects of YL-109 against cardiac, pulmonary and intestinal damage, inflammation and pyroptosis caused by LPS were eliminated in CHIP knockout mice. Our results not only reveal the protective effect and molecular mechanism of YL-109 against LPS-mediated organs damage but also provide additional insights into the effect of CHIP on negatively regulating pyroptosis and inflammatory pathways.

ENDOGENOUS ß 3 -ADRENERGIC RECEPTOR ACTIVATION ALLEVIATES SEPSIS-INDUCED CARDIOMYOCYTE APOPTOSIS VIA PI3K/AKT SIGNALING PATHWAY.

ABSTRACT: ß 3 -adrenergic receptor (ß 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of ß 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of ß 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that ß 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of ß 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with ß 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8, and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of ß 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous ß 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.

The awareness rate of knowledge of chronic diseases and influencing factors among 4790 adults in anhui province: An online survey using WeChat.

Objective: To investigate public awareness about core information regarding chronic diseases and identify factors influencing that awareness among Anhui Province residents, provide a scientific basis for policy-making, and formulate corresponding intervention measures. Methods: From March to April 2021, 12 provincial-level representative counties and districts of Anhui province in the China Adult Chronic Disease and Nutrition Surveillance were selected as survey sites, and 4790 residents were recruited for the survey using stratified multi-stage cluster random sampling. Basic details about the study participants were collected and their awareness of core information about major chronic diseases was measured through an online survey using WeChat. Results: In 2021, the awareness rate of core information about chronic diseases among residents of Anhui Province was 54.93%. Multivariate logistic regression analysis showed that a higher awareness rate was associated with the following factors: non-housework occupations (agriculture, forestry, animal husbandry, and fishery: OR = 1.309, commercial services and production and transportation: OR = 1.450, institutions, and professional and technical personnel: OR = 1.461), a high education level (high school/junior high school/technical school OR = 1.357, college and above OR = 2.133), and residence in the southern and northern Anhui areas (southern Anhui OR = 1.282, northern Anhui OR = 1.431); whereas in rural areas (by district and country) (OR = 0.863), the awareness rate was low (all P < 0.05). Conclusions: The awareness rate of core information about chronic diseases among residents of Anhui, China, is low. It is necessary to strengthen awareness about chronic disease prevention and management by targeting specific groups of people in this region.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic 7-9 . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.

Increased Suicide Mortality and Reduced Life Expectancy Associated With Ambient Heat Exposure.

INTRODUCTION: Ambient heat exposure is a risk factor for suicide in many regions of the world. However, little is known about the extent to which life expectancy has been shortened by heat-related suicide deaths. This study aimed to evaluate the short-term effects of heat on suicide mortality and quantify the reduced life expectancy associated with heat in China. METHODS: A time-stratified, case-crossover analysis in 2023 was performed during the warm season (May to September) from 2016 to 2020 to assess the short-term association between extreme heat (the 95th percentile of mean temperature) and suicide mortality in Anhui Province, China. A subgroup analysis was performed according to sex, age, marital status, suicide type, and region. The attributable fraction and years of life lost due to heat were calculated, and the heat-related life expectancy loss was estimated. RESULTS: This study included 9,642 suicide deaths, with an average age of 62.4 years and 58.8% of suicides in males. Suicide risk was associated with an 80.7% increase (95% confidence interval [CI]: 21.4%-68.9%) after exposure to extreme heat (30.6°C) in comparison to daily minimum temperature (7.9°C). Subgroup analysis revealed that heat-related suicide risk was more prominent in the married population than in the unmarried population. Heat was estimated to be associated with 31.7% (95% CI: 18.0%-43.2%) of the suicides, corresponding to 7.0 years of loss in life expectancy for each decedent. CONCLUSIONS: Heat exposure was associated with an increased risk of suicide and reduced life expectancy. However, further prospective studies are required to confirm this relationship.

Quantitative analysis of the impact of respiratory state on the heartbeat-induced movements of the heart and its substructures.

PURPOSE: This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors. METHODS: Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states. RESULTS: Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25-3.66%, while the average Dice similarity coefficient (DSC) increased by - 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left-right (LR) direction, and the displacement of the RV in the anterior-posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08-17.57% and 4.09-20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0-37.04% and - 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,- 1.73 to 3.47 mm and - 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm. CONCLUSION: The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.

Self-Supervised Random Forest on Transformed Distribution for Anomaly Detection.

Anomaly detection, the task of differentiating abnormal data points from normal ones, presents a significant challenge in the realm of machine learning. Numerous strategies have been proposed to tackle this task, with classification-based methods, specifically those utilizing a self-supervised approach via random affine transformations (RATs), demonstrating remarkable performance on both image and non-image data. However, these methods encounter a notable bottleneck, the overlap of constructed labeled datasets across categories, which hampers the subsequent classifiers' ability to detect anomalies. Consequently, the creation of an effective data distribution becomes the pivotal factor for success. In this article, we introduce a model called "self-supervised forest (sForest)", which leverages the random Fourier transform (RFT) and random orthogonal rotations to craft a controlled data distribution. Our model utilizes the RFT to map input data into a new feature space. With this transformed data, we create a self-labeled training dataset using random orthogonal rotations. We theoretically prove that the data distribution formulated by our methodology is more stable compared to one derived from RATs. We then use the self-labeled dataset in a random forest (RF) classifier to distinguish between normal and anomalous data points. Comprehensive experiments conducted on both real and artificial datasets illustrate that sForest outperforms other anomaly detection methods, including distance-based, kernel-based, forest-based, and network-based benchmarks.

UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors.

The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

Methyl jasmonate differentially and tissue-specifically regulated the expression of arginine catabolism-related genes and proteins in Agaricus bisporus mushrooms during storage.

Methyl jasmonate (MeJA)-regulated postharvest quality retention of Agaricus bisporus fruiting bodies is associated with arginine catabolism. However, the mechanism of MeJA-regulated arginine catabolism in edible mushrooms is still unclear. This study aimed to investigate the regulatory modes of MeJA on the expression of arginine catabolism-related genes and proteins in intact and different tissues of A. bisporus mushrooms during storage. Results showed that exogenous MeJA treatment activated endogenous JA biosynthesis in A. bisporus mushrooms, and differentially and tissue-specifically regulated the expression of arginine catabolism-related genes (AbARG, AbODC, AbSPE-SDH, AbSPDS, AbSAMDC, and AbASL) and proteins (AbARG, AbSPE-SDH, AbASL, and AbASS). MeJA caused no significant change in AbASS expression but resulted in a dramatic increase in AbASS protein level. Neither the expression of the AbSAMS gene nor the AbSAMS protein was conspicuously altered upon MeJA treatment. Additionally, MeJA reduced the contents of arginine and ornithine and induced the accumulation of free putrescine and spermidine, which was closely correlated with MeJA-regulated arginine catabolism-related genes and proteins. Hence, the results suggested that the differential and tissue-specific regulation of arginine catabolism-related genes and proteins by MeJA contributed to their selective involvement in the postharvest continuing development and quality retention of button mushrooms.

What happens to the osteoporotic bone mesenchymal stem cells? Evidence from RNA sequencing.

Evidence presented that osteoporosis is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). But most studies are insufficient to reveal what actually happens to the osteoporotic BMSCs. In this study, BMSCs were harvested from ovariectomized and sham-operated rats. After checking the characteristics of rat models and stem cells, the BMSCs were carried out for RNA sequencing. Part of the findings were verified that seven mRNAs (Abi3bp, Aifm3, Ccl11, Cdkn1c, Chst10, Id2, Vcam1) were significantly up-regulated in osteoporotic BMSCs while seven mRNAs (Cep63, Fgfr3, Myc, Omd, Pou2f1, Smarcal1, Timm10b) were down-regulated. In addition, potential miRNA-mRNA and lncRNA-mRNA regulatory networks were illustrated. The changes in osteoporotic BMSCs covered a large set of biological processes, including cell viability, differentiation, immunoreaction, bone repairment and estrogen defect. This study enriched the pathophysiological mechanisms of BMSCs and osteporosis, as well as provided dozens of attractive RNA targets for further treatment.