Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors.

The Notch protein is one of the most mechanistically direct transmembrane receptors-the intracellular domain contains a transcriptional regulator that is released from the membrane when engagement of the cognate extracellular ligand induces intramembrane proteolysis. We find that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways. Synthetic Notch (synNotch) pathways can drive user-defined functional responses in diverse mammalian cell types. Because individual synNotch pathways do not share common signaling intermediates, the pathways are functionally orthogonal. Thus, multiple synNotch receptors can be used in the same cell to achieve combinatorial integration of environmental cues, including Boolean response programs, multi-cellular signaling cascades, and self-organized cellular patterns. SynNotch receptors provide extraordinary flexibility in engineering cells with customized sensing/response behaviors to user-specified extracellular cues.

The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment.

BACKGROUND: The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches. METHODS: Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated. RESULTS: A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3. CONCLUSIONS: PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.

Quantitative comparison of bile acid glucuronides sub-metabolome between intrahepatic cholestasis and healthy pregnant women.

Because of the pathological indication and the physiological functions, bile acids (BAs) have occupied the research hotspot in recent decades. Although extensive efforts have been paid onto BAs sub-metabolome characterization, as the subfamily, BA glucuronides (gluA-BAs) profile is seldom concerned. Here, we made efforts to develop a LC-MS/MS program enabling quantitative gluA-BAs sub-metabolome characterization and to explore the differential species in serum between intrahepatic cholestasis of pregnancy (ICP) patients and healthy subjects. To gain as many authentic gluA-BAs as possible, liver microsomes from humans, rats, and mice were deployed to conjugate glucuronyl group to authentic BAs through in vitro incubation. Eighty gluA-BAs were captured and subsequently served as authentic compounds to correlate MS/MS spectral behaviors to structural features using squared energy-resolved MS program. Optimal collision energy (OCE) of [M-H]->[M-H-176.1]- was jointly administrated by [M-H]- mass and glucuronidation site, and identical exciting energies corresponding to 50% survival rate of 1st-generation fragment ion (EE50) were observed merely when the aglycone of a gluA-BA was consistent with the suspected structure. Through integrating high-resolution m/z, OCE, and EE50 information to identify gluA-BAs in a BAs pool, 97 ones were found and identified, and further, quantitative program was built for all annotated gluA-BAs by assigning OCEs to [M-H]->[M-H-176.1]- ion transitions. Quantitative gluA-BAs sub-metabolome of ICP was different from that of the healthy group. More GCDCA-3-G, GDCA-3-G, TCDCA-7-G, TDCA-3-G, and T-ß-MCA-3-G were distributed in the ICP group. Above all, this study not only offered a promising analytical tool for in-depth gluA-BAs sub-metabolome characterization, but also clarified gluA-BAs allowing the differentiation of ICP and healthy subjects.

A first-principles study of the BC3N2 monolayer and a BC3N2/graphene heterostructure as promising anode materials for sodium-ion batteries.

High-performance sodium-ion batteries (SIBs) require anode materials with high capacity and fast kinetics. Based on first-principles calculations, we propose BC3N2 and BC3N2/graphene (B/G) heterostructure as potential SIB anode materials. The BC3N2 monolayer exhibits intrinsic metallic behavior. In addition, BC3N2 possesses a low Na+ diffusion barrier (0.15 eV), a high storage capacity (777 mA h g-1), a low open-circuit voltage (0.72 V), and a tiny axial expansion (0.36%). Compared with the BC3N2 monolayer, the B/G heterostructure exhibits a lower diffusion barrier of 0.027 eV, suggesting a much faster diffusion. More importantly, although the B/G heterostructure possesses heavier molar weight, its theoretical capacity (689 mA h g-1) is comparable to that of the BC3N2 monolayer. Based on the above-mentioned properties, we hope both the BC3N2 monolayer and the B/G heterostructure would be promising anodes for SIBs.

Neuroimaging prognostic factors for treatment response to motor imagery training after stroke.

The efficacy of motor imagery training for motor recovery is well acknowledged, but with substantial inter-individual variability in stroke patients. To help optimize motor imagery training therapy plans and screen suitable patients, this study aimed to explore neuroimaging biomarkers explaining variability in treatment response. Thirty-nine stroke patients were randomized to a motor imagery training group (n = 22, received a combination of conventional rehabilitation therapy and motor imagery training) and a control group (n = 17, received conventional rehabilitation therapy and health education) for 4 weeks of interventions. Their demography and clinical information, brain lesion from structural MRI, spontaneous brain activity and connectivity from rest fMRI, and sensorimotor brain activation from passive motor task fMRI were acquired to identify prognostic factors. We found that the variability of outcomes from sole conventional rehabilitation therapy could be explained by the reserved sensorimotor neural function, whereas the variability of outcomes from motor imagery training + conventional rehabilitation therapy was related to the spontaneous activity in the ipsilesional inferior parietal lobule and the local connectivity in the contralesional supplementary motor area. The results suggest that additional motor imagery training treatment is also efficient for severe patients with damaged sensorimotor neural function, but might be more effective for patients with impaired motor planning and reserved motor imagery.

Prevalence and associated factors of health anxiety in patients with temporomandibular disorders.

OBJECTIVES: To investigate the prevalence and associated factors of health anxiety (HA) in patients with Temporomandibular Disorders (TMDs) using the 8-item Whiteley Index (WI-8) scale. MATERIALS AND METHODS: Three hundred and twenty-nine TMDs patients completed the Visual Analog Scale (VAS), WI-8, Jaw Functional Limitation Scale-8 (JFLS-8), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) scales. Clinical examinations were conducted following the Diagnostic Criteria for TMDs Axis I. RESULTS: The prevalence of HA among TMDs patients was 18.54%. Patients with HA had higher scores of VAS-current (p = 0.026), VAS-maximum (p = 0.024), VAS-average (p = 0.030), JFLS-8 (p < 0.001), GAD-7 (p < 0.001) and PHQ-9 (p < 0.001), lower maximum mouth opening (p = 0.016), lower proportion of structure-related TMDs (p = 0.028), and higher proportion of pain-related TMDs (p < 0.001) compared to those without HA. The correlation coefficient was 0.61 (p < 0.001) between WI-8 and GAD-7 and 0.64 (p < 0.001) between WI-8 and PHQ-9. CONCLUSION: Approximately one-fifth of patients with TMDs experienced HA. HA was associated with pain perception, functional limitations, depressive, and anxiety symptoms in individuals with TMDs. HA may contribute to heightened subjective pain experiences rather than structural changes in the TMJ.

The association between chronotype profile and temporomandibular disorders among college students.

BACKGROUND: Temporomandibular joint disorders (TMDs) are common in young adults, and the link between chronotype profile and TMDs is unclear. OBJECTIVE: This study examined TMD prevalence and chronotype distribution and explored the relationship between chronotype and TMDs in young adults. MATERIALS AND METHODS: A total of 663 students from Sichuan University completed questionnaires. Chronotype profiles were assessed using the Morningness-Eveningness Questionnaire, and TMDs were screened using the Fonseca Memory Index. To validate the findings, 68 TMD patients and 136 controls were enrolled. RESULTS: The prevalence of TMDs was 69.7%, with significant differences among chronotype profiles. The intermediate profile was the most common chronotype. Eveningness profile was associated with higher TMDs prevalence and severity. Muscle pain and side movement difficulty scores were higher in eveningness and intermediate profiles. Female gender (OR 2.345; 95% CI 1.668-3.297) was a TMD risk factor, while morningness profile (OR 0.537; 95% CI 0.297-0.970) was protective. Validation with TMD patients and controls supported these findings, showing higher eveningness profile prevalence in the TMD groups. CONCLUSIONS: TMDs have a high prevalence in college students, chronotype profiles shown to be associated with TMDs. Morningness is the protection factor in TMDs and PT, eveningness is a risk factor for IT.

Mapping the evolving trend of research on Class III malocclusion: a bibliometric analysis.

OBJECTIVES: This study aimed to provide visualized knowledge maps to show the evolving trends and key focal points of Class III malocclusion research through a comprehensive bibliometric analysis. MATERIALS AND METHODS: Class III malocclusion research published between 2000 and 2023 was retrieved from the Web of Science Core Collection. VOSviewer was utilized to count the citation and publication number of authors, institutions, countries and journals. Co-occurrence, co-citation, and cluster analyses and burst detection were conducted using CiteSpace. RESULTS: A total of 3,682 publications on Class III malocclusion were included in the bibliometric analysis. During 2000-2023, both the annual publication count and citation frequency exhibited a gradual upward trajectory, with a noticeable surge in recent years. In terms of production and citation counts of Class III malocclusion research, the core journal is the American Journal of Orthodontics and Dentofacial Orthopedics. Furthermore, apart from the primary keyword 'Class III malocclusion', 'orthognathic surgery' was identified as keyword with the most frequency. The cluster analysis of cited references reveals that the research focal points have shifted to 'skeletal anchorage' and 'surgery-first approach'. Furthermore, the burst detection identified 'quality of life' as a potential research hotspot since it has recently gained increasing scholarly attention. CONCLUSIONS: The current study provides scholars with the knowledge maps of evolving trends and prominent topics of Class III malocclusion research and a summary of research progress on various priorities during different periods. These findings are expected to provide a valuable guidance to facilitate the future research on Class III malocclusion.

Pain symptoms are associated with two-point discrimination threshold in patients with temporomandibular disorders.

OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.

Research on Ocular Artifacts Removal from Single-Channel Electroencephalogram Signals in Obstructive Sleep Apnea Patients Based on Support Vector Machine, Improved Variational Mode Decomposition, and Second-Order Blind Identification.

The electroencephalogram (EEG) has recently emerged as a pivotal tool in brain imaging analysis, playing a crucial role in accurately interpreting brain functions and states. To address the problem that the presence of ocular artifacts in the EEG signals of patients with obstructive sleep apnea syndrome (OSAS) severely affects the accuracy of sleep staging recognition, we propose a method that integrates a support vector machine (SVM) with genetic algorithm (GA)-optimized variational mode decomposition (VMD) and second-order blind identification (SOBI) for the removal of ocular artifacts from single-channel EEG signals. The SVM is utilized to identify artifact-contaminated segments within preprocessed single-channel EEG signals. Subsequently, these signals are decomposed into variational modal components across different frequency bands using the GA-optimized VMD algorithm. These components undergo further decomposition via the SOBI algorithm, followed by the computation of their approximate entropy. An approximate entropy threshold is set to identify and remove components laden with ocular artifacts. Finally, the signal is reconstructed using the inverse SOBI and VMD algorithms. To validate the efficacy of our proposed method, we conducted experiments utilizing both simulated data and real OSAS sleep EEG data. The experimental results demonstrate that our algorithm not only effectively mitigates the presence of ocular artifacts but also minimizes EEG signal distortion, thereby enhancing the precision of sleep staging recognition based on the EEG signals of OSAS patients.

Alterations of nasal microbiome in eosinophilic chronic rhinosinusitis.

BACKGROUND: Exposure to microbes may be important in the development of chronic rhinosinusitis (CRS). Dysbiosis of the nasal microbiome is considered to be related to CRS with nasal polyps (CRSwNP). The link between the nasal microbiota and eosinophilic CRSwNP (eCRSwNP) has rarely been studied. OBJECTIVE: The aim of this study was to rigorously characterize nasal dysbiosis in a cohort of patients with eCRSwNP and compare the nasal microbiomes of these patients with those of healthy controls (HCs). METHODS: We performed a cross-sectional study of 34 patients with eCRSwNP, 10 patients without CRSwNP, and 44 HCs by using 16S rRNA gene sequencing. An independent cohort of 14 patients with eCRSwNP, 9 patients without CRSwNP, and 11 HCs was used to validate the results. RESULTS: Compared with the nasal microbiome of healthy controls, the nasal microbiome of patients with eCRSwNP was characterized by higher α-diversity (Shannon and Chao1 index) and a distinct composition of microbes. Notably, the distinct differences in microbial composition between patients with eCRSwNP and HCs were significantly correlated with eCRSwNP disease status. Furthermore, in a diagnostic model generated by using these differences, a combination of 15 genera could be used to distinguish patients with eCRSwNP from HCs, with an area under the curve of approximately 0.8 in both the exploration and validation cohorts. CONCLUSION: Our study establishes the compositional alterations in the nasal microbiome in eCRSwNP and suggests the potential for using the nasal microbiota as a noninvasive predictive classifier for the diagnosis of eCRSwNP.

A worldwide bibliometric analysis of the research trends and hotspots of bruxism in adults during 1991-2021.

BACKGROUND AND OBJECTIVES: With the increasing attention to bruxism, the research on bruxism is increasing rapidly. However, there is still a lack of systematic bibliometric analysis in the field of bruxism in adults. This study aimed to comprehensively explore and visualize the global trends and research hotspots in the field of bruxism in adults during 1991-2021. METHODS: The study searched the literature published during 1991-2021 in the Web of Science Core Collection database without language restrictions. VOSviewer, CiteSpace and Microsoft Excel were applied to analyse the authors, institutions, journals, countries, cited references, keywords and other information of the included publications, and construct visualized cooperation networks. RESULTS: A total of 878 articles were finally included. The top two most productive authors in the past 30 years were Lobbezoo F and Manfredini D. ACTA-Amsterdam, Univ Sao Paulo, Univ Helsinki, Univ Padua, Univ Montreal, et al. were prominent institutions in this field. Journal of Oral Rehabilitation made outstanding contributions in this field. The United States produced the most documents in this field, followed by Brazil. Both countries and authors cooperated closely around the world. The two most cited articles focused on the definition, assessment and classification of bruxism. In recent years, diagnostic criteria and stress have begun to receive a lot of attention. CONCLUSION: From 1991 to 2021, the attention to bruxism in adults continued to increase. Diagnostic criteria and stress may be potential research hotspots in this field. This study references relevant scholars on development trends and research hotspots.

Temporomandibular disorder patients with excessive daytime sleepiness present greater pain intensity and reduced jaw function.

BACKGROUND: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. OBJECTIVE: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. METHODS: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non-EDS group (score < 10). The Jaw Functional Limitation Scale 8-item (JFLS-8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire 9-item (PHQ-9). All included patients were diagnosed with pain-related TMD (PT), intra-articular TMD (IT) or combined TMD (CT). RESULTS: Compared with non-EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ-9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD-7 score (B = 0.73) were significantly associated with an increased score on the JFLS-8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007). CONCLUSION: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.

Exploring the effect of disc displacement on the risk and severity of condylar erosion in adult temporomandibular disorder patients: A CBCT and MRI study.

OBJECTIVE: The objective of the study was to investigate the relationship between types of disc displacement (DD) diagnosed by magnetic resonance imaging (MRI), and the risk (presence or absence) and severity of condylar erosion (CE) graded using cone-beam computed tomography (CBCT) in adult Temporomandibular disorders (TMD) patients. METHODS: A total of 353 TMD patients (283 females, 70 males) underwent MRI scans to categorise DD as normal (NA), anterior displacement with reduction (ADDR), or anterior displacement without reduction (ADDNR). CE severity was graded on a scale of 0-3 (absence, mild, moderate or severe) using CBCT. To establish the plausibility and cut-off points for CE diagnosis, the severity of CE was then further divided into three classifications: Grade 0 versus 1 + 2 + 3; Grades 0 + 1 versus 2 + 3; Grades 0 + 1 + 2 versus 3. Logistic regression analysis was performed, adjusting for age, gender and joint correlation. RESULTS: ADDNR significantly increased the risk of CE compared with NA (OR = 10.04, 95% CI: [6.41, 15.73]) and showed a significant increase in CE severity across all classifications (ORs = 10.04-18.95). The effects of ADDNR were significant in both genders (p < .001) and had a greater impact in females. ADDR was predominantly associated with mild CE. CONCLUSIONS: ADDNR significantly increased the risk and severity of CE independent of gender when compared to NA, whereas ADDR was mainly associated with mild CE. Slight cortical discontinuity may represent a subclinical diagnosis requiring further investigation.

Research on mining land subsidence by intelligent hybrid model based on gradient boosting with categorical features support algorithm.

Land subsidence induced by coal mining (MLS) has posed a huge threat to the ecological environment, buildings, roads, and other infrastructure safety in mining areas. However, the prediction and evaluation of MLS is relatively complex, and the reliability of the prediction results is closely related to factors such as the professional knowledge and engineering experience of researchers. This paper aims to combine intelligent optimization algorithms: ant lion optimizer (ALO), bald eagle search (BES), bird swarm algorithm (BSA), harris hawks optimization (HHO), and sparrow search algorithm (SSA), with machine learning model of gradient boosting with categorical features support algorithm (CatBoost) to predict MLS. To achieve this goal, five hybrid models based CatBoost were developed and the prediction accuracy and reliability of the models were compared and analyzed. The prediction performance of the hybrid models has been significantly improved on the basis of a single model, of which the SSA-CatBoost model has the most obvious improvement (from R2 = 0.927 to 0.965, RMSE = 0.541 to 0.377, MAE = 0.386 to 0.297, VAF = 92.720 to 95.837). The importance and predictive contribution of all input features to predictive labels were studied with the Shapley method. The research results indicate that hybrid model technology is a reliable MLS prediction method. This study can help mining technicians use machine learning methods to study the degree of MLS damage to the surface environment and provide scientific advanced prediction and evaluation for the protection and management of the ecological environment in mining areas and the formulation of safety production measures.

Classification of bruxism based on time-frequency and nonlinear features of single channel EEG.

BACKGROUND: In the classification of bruxism patients based on electroencephalogram (EEG), feature extraction is essential. The method of using multi-channel EEG fusing electrocardiogram (ECG) and Electromyography (EMG) signal features has been proved to have good performance in bruxism classification, but the classification performance based on single channel EEG signal is still understudied. We investigate the efficacy of single EEG channel in bruxism classification. METHODS: We have extracted time-domain, frequency-domain, and nonlinear features from single EEG channel to classify bruxism. Five common bipolar EEG recordings from 2 bruxism patients and 4 healthy controls during REM sleep were analyzed. The time domain (mean, standard deviation, root mean squared value), frequency domain (absolute, relative and ratios power spectral density (PSD)), and non-linear features (sample entropy) of different EEG frequency bands were analyzed from five EEG channels of each participant. Fine tree algorithm was trained and tested for classifying sleep bruxism with healthy controls using five-fold cross-validation. RESULTS: Our results demonstrate that the C4P4 EEG channel was most effective for classification of sleep bruxism that yielded 95.59% sensitivity, 98.44% specificity, 97.84% accuracy, and 94.20% positive predictive value (PPV). CONCLUSIONS: Our results illustrate the feasibility of sleep bruxism classification using single EEG channel and provides an experimental foundation for the development of a future portable automatic sleep bruxism detection system.

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

Dramatic Carbon Loss in a Permafrost Thaw Slump in the Tibetan Plateau is Dominated by the Loss of Microbial Necromass Carbon.

Thaw slumps can lead to considerable carbon loss in permafrost regions, while the loss of components from two major origins, i.e., microbial and plant-derived carbon, during this process remains poorly understood. Here, we provide direct evidence that microbial necromass carbon is a major component of lost carbon in a retrogressive permafrost thaw slump by analyzing soil organic carbon (SOC), biomarkers (amino sugars and lignin phenols), and soil environmental variables in a typical permafrost thaw slump in the Tibetan Plateau. The retrogressive thaw slump led to a ∼61% decrease in SOC and a ∼25% SOC stock loss. As evident in the levels of amino sugars (average of 55.92 ± 18.79 mg g-1 of organic carbon, OC) and lignin phenols (average of 15.00 ± 8.05 mg g-1 OC), microbial-derived carbon (microbial necromass carbon) was the major component of the SOC loss, accounting for ∼54% of the SOC loss in the permafrost thaw slump. The variation of amino sugars was mainly related to the changes in soil moisture, pH, and plant input, while changes in lignin phenols were mainly related to the changes in soil moisture and soil bulk density.

The role of miR1 and miR133a in new-onset atrial fibrillation after acute myocardial infarction.

BACKGROUND: The development of new-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is a clinical complication that requires a better understanding of the causative risk factors. This study aimed to explore the risk factors and the expression and function of miR-1 and miR-133a in new atrial fibrillation after AMI. METHODS: We collected clinical data from 172 patients with AMI treated with emergency percutaneous coronary intervention (PCI) between October 2021 and October 2022. Independent predictors of NOAF were determined using binary logistic univariate and multivariate regression analyses. The predictive value of NOAF was assessed using the area under the receiver operating characteristic (ROC) curve for related risk factors. In total, 172 venous blood samples were collected preoperatively and on the first day postoperatively; the expression levels of miR-1 and miR-133a were determined using the polymerase chain reaction. The clinical significance of miR-1 and miR-133a expression levels was determined by Spearman correlation analysis. RESULTS: The Glasgow prognostic score, left atrial diameter, and infarct area were significant independent risk factors for NOAF after AMI. We observed that the expression levels of miR-1 and miR-133a were significantly higher in the NOAF group than in the non-NOAF group. On postoperative day 1, strong associations were found between miR-133a expression levels and the neutrophil ratio and between miR-1 expression levels and an increased left atrial diameter. CONCLUSIONS: Our findings indicate that the mechanism of NOAF after AMI may include an inflammatory response associated with an increased miR-1-related mechanism. Conversely, miR-133a could play a protective role in this clinical condition.

China's environmental solutions.

China emits unproportionately high concentrations of CO2 and, due to rapid population growth and industrialization, suffers from air, water, and soil pollution. However, many of these challenges for sustainable growth are being vigorously addressed, and China aims at a CO2 emission peak by 2030 and carbon neutrality by 2060 ("dual carbon policy"). In addition, nation-wide programs attempt to achieve reforestation and ecological restoration. By 2025, core elements of a "bioeconomy" and a circular economy are expected to be ready. Many of these programs extend into China's international "belt-and-road" initiative (BRI). In this article, we briefly describe the present achievements of China's environmental solutions and the country's visions for a "digital, eco-friendly civilization." KEY POINTS: • China's steps towards environmental cleaning, eco-protection, and decarbonization. • Steps towards a future bioeconomy.