Neural network aided extended Kalman filtering for inverse imaging of cardiac transmembrane potential.

OBJECTIVE: The aim of this study is to address the limitations in reconstructing the electrical activity of the heart from the body surface electrocardiogram, which is an ill-posed inverse problem. Current methods often assume values commonly used in the literature in the absence of a priori knowledge, leading to errors in the model. Furthermore, most methods ignore the dynamic activation process inherent in cardiomyocytes during the cardiac cycle. Approach: To overcome these limitations, we propose an extended Kalman filter (EKF)-based neural network approach to dynamically reconstruct cardiac transmembrane potential. Specifically, a recurrent neural network is used to establish the state estimation equation of the EKF, while a convolutional neural network is used as the measurement equation. The Jacobi matrix of the network undergoes a correction feedback process to obtain the Kalman gain. Main Results: After repeated iterations, the final estimated state vector, i.e., the reconstructed image of the transmembrane potential, is obtained. The results from both the final simulation and real experiments demonstrate the robustness and accurate quantification of the model. Significance: This study presents a new approach to cardiac transmembrane potential reconstruction that offers higher accuracy and robustness compared to traditional methods. The use of neural networks and EKFs allows dynamic modelling that takes into account the activation processes inherent in cardiomyocytes and does not require a priori knowledge of inputs such as forward transition matrices.

Disulfidptosis in head and neck squamous carcinoma: Integrative bioinformatic and in-vitro analysis.

BACKGROUND: Head and neck squamous carcinoma (HNSC) is a prevalent global malignancy with limited treatment options, which necessitates the development of novel therapeutic strategies. Disulfidptosis, a recently discovered and unique cell death pathway, may offer promise as a treatment target in HNSC. MATERIALS AND METHODS: We identified disulfidptosis-related genes (DRGs) using multiple algorithms and developed a prognostic model based on a disulfidptosis-related gene index (DRGI). The model's predictive accuracy was assessed by ROC-AUC, and patients were stratified by risk scores. We investigated the tumor immune microenvironment, immune responses, tumorigenesis pathways, and chemotherapy sensitivity (IC50). We also constructed a diagnostic model using 20 machine-learning algorithms and validated PCBP2 expression through RT-qPCR and western blot. RESULTS: We developed a 12-DRG DRGI prognostic model, classifying patients into high- and low-risk groups, with the high-risk group experiencing poorer clinical outcomes. Notable differences in tumor immune microenvironment and chemosensitivity were observed, with reduced immune activity and suboptimal treatment responses in the high-risk group. Advanced machine learning and in-vitro experiments supported DRGI's potential as a reliable HNSC diagnostic biomarker. CONCLUSION: We established a novel DRGI-based prognostic and diagnostic model for HNSC, exploring its tumor immune microenvironment implications, and offering valuable insights for future research and clinical trials.

F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin/ß-Catenin pathway.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. METHODS: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. RESULTS: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein ß-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate ß-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. CONCLUSION: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/ß-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

Decoding Gastric Cancer: Machine Learning Insights Into the Significance of COMMDs Family in Immunotherapy and Diagnosis.

Copper, an indispensable trace element for the human body, serves not only as a crucial auxiliary factor in redox reactions within the organism but also as a significant constituent of numerous key metabolic enzymes. The COMMD family plays a vital role in regulating copper at both the cellular and systemic levels, particularly in the realm of tumor research, an area notably deficient in gastric cancer investigations. With the advancement of precision medical techniques, individualized and precise screening and treatment have become paramount considerations in the contemporary medical landscape for gastric cancer therapy. In light of this, we meticulously scrutinized existing transcriptomic datasets for gastric cancer, validating the expression levels and prognostic value of COMMD family genes. Simultaneously, employing the ssGSEA algorithm, we devised the COMMDs score. Enrichment analysis, gene mutations, and clinical features were incorporated into the assessment of this score. Furthermore, we contextualized the COMMDs score within the framework of the immune microenvironment, evaluating the relationship between the COMMDs family and immune factors as well as immune cells. The results suggest a correlation between the COMMDs score and various immune-related features. Based on this foundation, multiple machine learning approaches indicated Logistic Regression, with a remarkable ROC of 0.972, as the optimal diagnostic model. To accentuate the translational medical value of the COMMDs family, we selected COMMD10 as a differential gene in gastric cancer for further validation. Functional experiments revealed a decline in the proliferative and migratory capabilities of gastric cancer cells upon silencing COMMD10. Additionally, through pathway intervention, we unveiled the PI3K-AKT pathway as a potential mechanism through which COMMD10 influences gastric cancer activity. In summary, our study affirms the prospective role of the COMMDs family as potential markers for the diagnosis and treatment of gastric cancer in the future.

Comprehensive bioinformatics analytics and in vivo validation reveal SLC31A1 as an emerging diagnostic biomarker for acute myocardial infarction.

BACKGROUND: Globally, Acute Myocardial Infarction (AMI) is a common cause of heart failure (HF), which has been a leading cause of mortality resulting from non-communicable diseases. On the other hand, increasing evidence suggests that the role of energy production within the mitochondria strongly links to the development and progression of heart diseases, while Cuproptosis, a newly identified cell death mechanism, has not yet been comprehensively analyzed from the aspect of cardiovascular medicine. MATERIALS AND METHODS: 8 transcriptome profiles curated from the GEO database were integrated, from which a diagnostic model based on the Stacking algorithm was established. The efficacy of the model was evaluated in a multifaced manner (i.e., by Precision-Recall curve, Receiver Operative Characteristic curve, etc.). We also sequenced our animal models at the bulk RNA level and conducted qPCR and immunohistochemical staining, with which we further validated the expression of the key contributor gene to the model. Finally, we explored the immune implications of the key contributor gene. RESULTS: A merged machine learning model containing 4 Cuproptosis-related genes (i.e., PDHB, CDKN2A, GLS, and SLC31A1) for robust AMI diagnosis was developed, in which SLC31A1 served as the key contributor. Through in vivo modeling, we validated the aberrant overexpression of SLC31A1 in AMI. Besides, further transcriptome analysis revealed that its high expression was correlated with significant potential immunological implications in the infiltration of many immune cell types, especially monocyte. CONCLUSIONS: We constructed an AMI diagnostic model based on Cuproptosis-related genes and validated the key contributor gene in animal modeling. We also analyzed the effects on the immune system for its overexpression in AMI.

Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future.

Heart failure, a prevailing global health issue, imposes a substantial burden on both healthcare systems and patients worldwide. With an escalating prevalence of heart failure, prolonged survival rates, and an aging demographic, an increasing number of individuals are progressing to more advanced phases of this incapacitating ailment. Against this backdrop, the quest for pharmacological agents capable of addressing the diverse subtypes of heart failure becomes a paramount pursuit. From this viewpoint, the present article focuses on Omecamtiv Mecarbil (OM), an emerging chemical compound said to exert inotropic effects without altering calcium homeostasis. For the first time, as a review, the present article uniquely started from the very basic pathophysiology of heart failure, its classification, and the strategies underpinning drug design, to on-going debates of OM's underlying mechanism of action and the latest large-scale clinical trials. Furthermore, we not only saw the advantages of OM, but also exhaustively summarized the concerns in sense of its effects. These of no doubt make the present article the most systemic and informative one among the existing literature. Overall, by offering new mechanistic insights and therapeutic possibilities, OM has carved a significant niche in the treatment of heart failure, making it a compelling subject of study.

Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study.

BACKGROUND: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. METHODS: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. RESULTS: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167-1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007-1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005-1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147-1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139-1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. CONCLUSION: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.

Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

A Mendelian Randomisation Analysis Reveals No Relationship Between Periodontitis and Coronary Atherosclerosis.

OBJECTIVES: Growing evidence appears to intimate a profound connection between periodontitis and coronary atherosclerosis (CA), yet the existence of a causal relationship remains unclear. Through the implementation of Mendelian randomization analysis, we further evaluated the potential causal link between chronic/acute periodontitis (CP/AP) and CA. METHODS: Utilizing genome-wide association study (GWAS) summary statistics, we incorporated periodontitis data derived from European samples (n1 = 198,441; n2 = 195,762) and CA data from 61,194 cases. We conducted a 2 sample, bidirectional Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the main analytical approach. Supplementary analyses were executed through MR Egger, Weighted median (WM), IVW, Simple mode, and Weighted mode approaches. RESULTS: The IVW analysis revealed no significant causal relationship between CA and periodontitis (CA-CP: OR = 2.110, 95% CI = 0.208-21.317, P = .527; CA-AP: OR = 0.414, 95% CI = 0.051-3.384, P = .644). Similarly, the bidirectional analysis did not identify impact of periodontitis on CA (OR = 1.000, 95% CI = 0.999-1.001, P = .953). The supplementary analyses corroborated these findings. CONCLUSIONS: While studies highlighting a correlation between periodontitis and CA, our comprehensive analysis does not corroborate a causal association between periodontitis and CA. Further research is needed to elucidate other potential shared mechanisms and causal evidence between periodontitis and CA.

Overexpression of forebrain PTP1B leads to synaptic and cognitive impairments in obesity.

Obesity has reached pandemic proportions and is a risk factor for neurodegenerative diseases, including Alzheimer's disease. Chronic inflammation is common in obese patients, but the mechanism between inflammation and cognitive impairment in obesity remains unclear. Accumulative evidence shows that protein-tyrosine phosphatase 1B (PTP1B), a neuroinflammatory and negative synaptic regulator, is involved in the pathogenesis of neurodegenerative processes. We investigated the causal role of PTP1B in obesity-induced cognitive impairment and the beneficial effect of PTP1B inhibitors in counteracting impairments of cognition, neural morphology, and signaling. We showed that obese individuals had negative relationship between serum PTP1B levels and cognitive function. Furthermore, the PTP1B level in the forebrain increased in patients with neurodegenerative diseases and obese cognitive impairment mice with the expansion of white matter, neuroinflammation and brain atrophy. PTP1B globally or forebrain-specific knockout mice on an obesogenic high-fat diet showed enhanced cognition and improved synaptic ultrastructure and proteins in the forebrain. Specifically, deleting PTP1B in leptin receptor-expressing cells improved leptin synaptic signaling and increased BDNF expression in the forebrain of obese mice. Importantly, we found that various PTP1B allosteric inhibitors (e.g., MSI-1436, well-tolerated in Phase 1 and 1b clinical trials for obesity and type II diabetes) prevented these alterations, including improving cognition, neurite outgrowth, leptin synaptic signaling and BDNF in both obese cognitive impairment mice and a neural cell model of PTP1B overexpression. These findings suggest that increased forebrain PTP1B is associated with cognitive decline in obesity, whereas inhibition of PTP1B could be a promising strategy for preventing neurodegeneration induced by obesity.

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications.

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationships as well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

Interplay of Sphingolipid Metabolism in Predicting Prognosis of GBM Patients: Towards Precision Immunotherapy.

Background: In spite of numerous existing bio-surveillance systems for predicting glioma (GBM) prognosis, enhancing the efficacy of immunotherapy remains an ongoing conundrum. The continual scrutiny of the dynamic interplay between the sphingolipid metabolic pathway and tumor immunophenotypes has unveiled potential implications. However, the intricate orchestration of functional and regulatory mechanisms by long non-coding RNAs (lncRNAs) in GBM, particularly in the context of sphingolipid metabolism, remains cryptic. Methods: We harnessed established R packages to intersect gene expression profiles of GBM patients within the The Cancer Genome Atlas (TCGA) database with the compilation of sphingolipid metabolism genes from GeneCards. This enabled us to discern markedly distinct lncRNAs, which were subsequently deployed to construct a robust prognostic model utilizing Lasso-Cox regression analysis. We then scrutinized the immune microenvironment across various risk strata using the ssGSEA and CIBERSORT algorithms. To evaluate mutation patterns and drug resistance profiles within patient subgroups, we devised the "Prophytic" and "Maftools" packages, respectively. Results: Our investigation scrutinized lncRNAs linked to sphingolipid metabolism, utilizing glioma specimens from TCGA. We meticulously curated 1224 sphingolipid-associated genes gleaned from GeneCards and pinpointed 272 differentially expressed mRNAs via transcriptomic analysis. Enrichment analyses underscored their significance in sphingolipid processes. A prognostic model founded on 17 meticulously selected lncRNAs was systematically constructed and validated. This model adeptly stratified GBM patients into high- and low-risk categories, yielding highly precise prognostic insights. We also discerned correlations between immune cell infiltration and genetic mutation discrepancies, along with distinct therapeutic responses through drug sensitivity analysis. Notably, computational findings were corroborated through experimental validation by RT-PCR. Conclusion: In summation, our exhaustive inquiry underscores the multifaceted utility of the sphingolipid metabolic pathway as an autonomous diagnostic and prognostic indicator for glioma patients. Furthermore, we amalgamate a profusion of substantiated evidence concerning immune infiltration and gene mutations, thereby reinforcing the proposition that sphingolipid metabolism may function as a pivotal determinant in the panorama of immunotherapeutic interventions.

Olanzapine attenuates 5-HT2cR and GHSR1a interaction to increase orexigenic hypothalamic NPY: Implications for neuronal molecular mechanism of metabolic side effects of antipsychotics.

The main cause of second-generation antipsychotic (SGA)-induced obesity is considered due to the antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin receptor type 1a (GHSR1a) signalling. It is reported that 5-HT2cR interacted with GHSR1a, however it is unknown whether one of the SGA olanzapine alters the 5-HT2cR/GHSR1a interaction, affecting orexigenic neuropeptide signalling in the hypothalamus. We found that olanzapine treatment increased average energy intake and body weight gain in mice; olanzapine treatment also increased orexigenic neuropeptide (NPY) and GHSR1a signaling molecules, pAMPK, UCP2, FOXO1 and pCREB levels in the hypothalamus. By using confocal fluorescence resonance energy transfer (FRET) technology, we found that 5-HT2cR interacted/dimerised with the GHSR1a in the hypothalamic neurons. As 5-HT2cR antagonist, both olanzapine and S242084 decreased the interaction between 5-HT2cR and GHSR1a and activated GHSR1a signaling. The 5-HT2cR agonist lorcaserin counteracted olanzapine-induced attenuation of interaction between 5-HT2cR and GHSR1a and inhibited activation of GHSR1a signalling and NPY production. These findings suggest that 5-HT2cR antagonistic effect of olanzapine in inhibition of the interaction of 5-HT2cR and GHSR1a, activation GHSR1a downstream signaling and increasing hypothalamic NPY, which may be the important neuronal molecular mechanism underlying olanzapine-induced obesity and target for prevention metabolic side effects of antipsychotic management in psychiatric disorders.

Multi-omics analysis reveals that ferroptosis-related gene CISD2 is a prognostic biomarker of head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy, with high mortality rate and unavailability of accurate therapies. However, its early prevention remains a challenge. In the purview of predictive, preventive, and personalized medicine (PPPM), it is paramount to identify novel and powerful biomarkers. CISD2 is a crucial regulator of iron homeostasis and reactive oxygen species (ROS). Recent studies showed that the NEET protein (NAF-1) encoded by CISD2 is involved in regulating the proliferation and metastasis of tumor cells. Nevertheless, the prognostic value and immunological correlations of CISD2 remain unclear. METHODS: Bioinformatics analyses conducted utilizing data from comprehensive databases The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). All statistical evaluations were executed employing R software. RESULTS: Our investigation of biological function, enrichment pathway, and immune correlation revealed a discernable linkage between CISD2 and the immune response. Moreover, we found that the suppression of CISD2 is associated with immune cell infiltration and various immune signatures. CONCLUSIONS: The present study successfully revealed the potential prognostic and biological function of CISD2 in HNSCC. High expression of CISD2 are linked to gender, race, grade, etc., can notably enhance the early detection, prognosis, and prediction for individuals afflicted with HNSCC.

Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression.

Major depressive disorder (MDD) is a serious psychiatric disorder that in extreme cases can lead to suicide. Evidence suggests that alterations in the kynurenine pathway (KP) contribute to the pathology of MDD. Activation of the KP leads to the formation of neuroactive metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN). To test for changes in the KP, postmortem anterior cingulate cortex (ACC) was obtained from the National Institute of Health NeuroBioBank. Gene expression of KP enzymes and relevant neuroinflammatory markers were investigated via RT-qPCR (Fluidigm) and KP metabolites were measured using liquid chromatography-mass spectrometry in tissue from individuals with MDD (n = 44) and matched nonpsychiatric controls (n = 36). We report increased IL6 and IL1B mRNA in MDD. Subgroup analysis found that female MDD subjects had significantly decreased KYNA and a trend decrease in the KYNA/QUIN ratio compared to female controls. In addition, MDD subjects that died by suicide had significantly decreased KYNA in comparison to controls and MDD subjects that did not die by suicide, while subjects that did not die by suicide had increased KYAT2 mRNA, which we hypothesise may protect against a decrease in KYNA. Overall, we found sex- and suicide-specific alterations in the KP in the ACC in MDD. This is the first molecular evidence in the brain of subgroup specific changes in the KP in MDD, which not only suggests that treatments aimed at upregulation of the KYNA arm in the brain may be favourable for female MDD sufferers but also might assist managing suicidal behaviour.

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.

Monitoring of Single-Track Melting States Based on Photodiode Signal during Laser Powder Bed Fusion.

Single track is the basis for the melt pool modeling and physics work in laser powder bed fusion (LPBF). The melting state of a single track is closely related to defects such as porosity, lack of fusion, and balling, which have a significant impact on the mechanical properties of an LPBF-created part. To ensure the reliability of part quality and repeatability, process monitoring and feedback control are emerging to improve the melting states, which is becoming a hot topic in both the industrial and academic communities. In this research, a simple and low-cost off-axial photodiode signal monitoring system was established to monitor the melting pools of single tracks. Nine groups of single-track experiments with different process parameter combinations were carried out four times and then thirty-six LPBF tracks were obtained. The melting states were classified into three classes according to the morphologies of the tracks. A convolutional neural network (CNN) model was developed to extract the characteristics and identify the melting states. The raw one-dimensional photodiode signal data were converted into two-dimensional grayscale images. The average identification accuracy reached 95.81% and the computation time was 15 ms for each sample, which was promising for engineering applications. Compared with some classic deep learning models, the proposed CNN could distinguish the melting states with higher classification accuracy and efficiency. This work contributes to real-time multiple-sensor monitoring and feedback control.

Circular RNA: A promising new star of vaccine.

Circular RNAs (circRNAs) are a class of single-stranded RNAs with covalently closed structures. Owing to their not having 3' or 5' ends, circRNAs are highly durable and insusceptible to exonuclease-mediated degradation. Moreover, some circRNAs with certain structures are translatable, making them novel vaccines. Vaccines are efficient tools for immunotherapy, such as for the prevention of infectious diseases and cancer treatment. The immune system is activated during immunotherapy to fight against abnormal allies or invaders. CircRNA vaccines represent a potential new avenue in the vaccine era. Recently, several circRNA vaccines have been synthesized and tested in vitro and in vivo. Our review briefly introduces the current understanding of the biology and function of translatable circRNAs, molecular biology, synthetic methods, delivery of circRNA, and current circRNA vaccines. We also discussed the challenges and future directions in the field by summarizing the developments in circRNA vaccines in the past few years.

Quinolinic acid impairs mitophagy promoting microglia senescence and poor healthspan in C. elegans: a mechanism of impaired aging process.

Senescent microglia are a distinct microglial phenotype present in aging brain that have been implicated in the progression of aging and age-related neurodegenerative diseases. However, the specific mechanisms that trigger microglial senescence are largely unknown. Quinolinic acid (QA) is a cytotoxic metabolite produced upon abnormal activation of microglia. Brain aging and age-related neurodegenerative diseases have an elevated concentration of QA. In the present study, we investigated whether QA promotes aging and aging-related phenotypes in microglia and C. elegans. Here, we demonstrate for the first time that QA, secreted by abnormal microglial stimulation, induces impaired mitophagy by inhibiting mitolysosome formation and consequently promotes the accumulation of damaged mitochondria due to reduced mitochondrial turnover in microglial cells. Defective mitophagy caused by QA drives microglial senescence and poor healthspan in C. elegans. Moreover, oxidative stress can mediate QA-induced mitophagy impairment and senescence in microglial cells. Importantly, we found that restoration of mitophagy by mitophagy inducer, urolithin A, prevents microglial senescence and improves healthspan in C. elegans by promoting mitolysosome formation and rescuing mitochondrial turnover inhibited by QA. Thus, our study indicates that mitolysosome formation impaired by QA is a significant aetiology underlying aging-associated changes. QA-induced mitophagy impairment plays a critical role in neuroinflammation and age-related diseases. Further, our study suggests that mitophagy inducers such as urolithin A may offer a promising anti-aging strategy for the prevention and treatment of neuroinflammation-associated brain aging diseases.