TXNDC12 inhibits pancreatic tumor cells ferroptosis by regulating GSH/GGT7 and promotes its growth and metastasis.

Background: Thioredoxin domain-containing protein 12 (TXNDC12) is upregulated in a variety of tumours, including pancreatic cancer (PAAD), and its high expression is closely associated with poor prognosis. However, the regulatory mechanism of TXNDC12 in PAAD has not been reported. The aim of this study is to reveal the precise mechanism of TXNDC12 in regulating PAAD progression. Methods: The expression of TXNDC12 in pan-cancer as well as PAAD was verified by TCGA and GTEx databases, Western blot and RT-qPCR. CCK8 assay, clone formation assay and cell cycle assay were used to observe the effect of TXNDC12 on the proliferation of PAAD cells, the migration and invasion capacities were verified by wound healing assay and Transwell assay. The effect of TXNDC12 on apoptosis of MIA PaCa-2 and PANC-1 cells was detected using Hochest and flow cytometry. Finally, the interaction of TXNDC12 with GGT7 was predicted by STRING database and confirmed by CO-IP assay, the effect of TXNDC12 on ferroptosis through GGT7 was evaluated by GSH assay, MDA assay, ROS assay and Western blot. Results: TXNDC12 is upregulated in PAAD tissues, and patients with high TXNDC12 levels generally have shorter survival times. Knockdown of TXNDC12 significantly inhibited the proliferation, migration and invasion and promoted apoptosis of MIA PaCa-2 and PANC-1 cells. Mechanistically, knockdown of TXNDC12 resulted in a decrease in intracellular GSH content and an increase in GSSG content, as well as elevated levels of pro-ferroptosis factors, such as MDA and ROS. STRING database predicted that TXNDC12 interacts with GGT7, and CO-IP assay was used to validate this result. Finally, the effect of knocking down TXNDC12 on pancreatic cancer cell functions was able to be reversed by overexpression of GGT7. Conclusion: TXNDC12 inhibits ferroptosis in PAAD cells through the GSH/GGT7 axis thereby promoting their development.

Influence of Additives on the Macroscopic Color and Corrosion Resistance of 6061 Aluminum Alloy Micro-Arc Oxidation Coatings.

In this study, we successfully employed the plasma electrolytic oxidation (PEO) technique to create a uniform white ceramic layer on the surface of the 6061 aluminum alloy using K2ZrF6 and Na2WO4 as colorants. A scanning electron microscope (SEM) equipped with an energy-dispersive X-ray spectrometer (EDS) and X-ray diffraction (XRD) were used to characterize the coatings, and we used an electrochemical workstation to test their corrosion protection properties. The corrosion resistance of the coatings was analyzed using potentiodynamic polarization curves. The results showed that K2ZrF6 addition whitened the coating with ZrO2 as the main phase composition, inhibiting Al substrate depletion and enhancing coating corrosion resistance. A small amount of Na2WO4 decreased the coating's L* value, successfully constructing ceramic coatings with L* (coating brightness) values ranging from 70 to 86, offering broad application prospects for decorative coatings.

Effect of Negative Pulse on the Stability of Black Electrolytes for Magnesium Alloy Microarc Oxidation.

The correlation between negative pulse and the black electrolyte properties of magnesium alloy micro-arc oxidation and the treated area was investigated by introducing a negative pulse electric field. The physical phase composition, microstructure, elemental distribution, and content of the coating were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The results showed that the introduction of negative pulses favored the generation of MgO and MgSiO3 contents in the coatings, and an increase in the MgO phase was found in the coatings formed in the failed electrolytes; the microporous size and microcracks of the coatings were gradually and significantly reduced; the average consumption of Cu ions was 0.0453 g/L·dm2, which is only 26% of that in the unipolar condition; the introduction of the negative pulses significantly improved the "anomalous consumption" of Cu ions. The introduction of negative pulse can significantly improve the "abnormal consumption" of copper ions, which is attributed to the change in the electric field by negative pulse, which makes the cathode-enriched Cu ions migrate to the anode and reduces the reduction and precipitation of Cu ions at the cathode.

Online System for Monitoring the Degree of Fermentation of Oolong Tea Using Integrated Visible-Near-Infrared Spectroscopy and Image-Processing Technologies.

During the fermentation process of Oolong tea, significant changes occur in both its external characteristics and its internal components. This study aims to determine the fermentation degree of Oolong tea using visible-near-infrared spectroscopy (vis-VIS-NIR) and image processing. The preprocessed vis-VIS-NIR spectral data are fused with image features after sequential projection algorithm (SPA) feature selection. Subsequently, traditional machine learning and deep learning classification models are compared, with the support vector machine (SVM) and convolutional neural network (CNN) models yielding the highest prediction rates among traditional machine learning models and deep learning models with 97.14% and 95.15% in the prediction set, respectively. The results indicate that VIS-NIR combined with image processing possesses the capability for rapid non-destructive online determination of the fermentation degree of Oolong tea. Additionally, the predictive rate of traditional machine learning models exceeds that of deep learning models in this study. This study provides a theoretical basis for the fermentation of Oolong tea.

A Gas Sensors Detection System for Real-Time Monitoring of Changes in Volatile Organic Compounds during Oolong Tea Processing.

The oxidation step in Oolong tea processing significantly influences its final flavor and aroma. In this study, a gas sensors detection system based on 13 metal oxide semiconductors with strong stability and sensitivity to the aroma during the Oolong tea oxidation production is proposed. The gas sensors detection system consists of a gas path, a signal acquisition module, and a signal processing module. The characteristic response signals of the sensor exhibit rapid release of volatile organic compounds (VOCs) such as aldehydes, alcohols, and olefins during oxidative production. Furthermore, principal component analysis (PCA) is used to extract the features of the collected signals. Then, three classical recognition models and two convolutional neural network (CNN) deep learning models were established, including linear discriminant analysis (LDA), k-nearest neighbors (KNN), back-propagation neural network (BP-ANN), LeNet5, and AlexNet. The results indicate that the BP-ANN model achieved optimal recognition performance with a 3-4-1 topology at pc = 3 with accuracy rates for the calibration and prediction of 94.16% and 94.11%, respectively. Therefore, the proposed gas sensors detection system can effectively differentiate between the distinct stages of the Oolong tea oxidation process. This work can improve the stability of Oolong tea products and facilitate the automation of the oxidation process. The detection system is capable of long-term online real-time monitoring of the processing process.

Study of Coating Growth Direction of 6061 Aluminum Alloy in Soft Spark Discharge of Plasma Electrolytic Oxidation.

Conventional plasma electrolytic oxidation treatments produce oxide coatings with micron-scale discharge pores, resulting in insulation and wear and corrosion resistance far below that expected of highly dense Al2O3 coatings. The introduction of cathodic polarization during the plasma electrolytic oxidation process, especially when the applied cathode-to-anode current ratio (Rpn) is greater than 1, triggers a unique plasma discharge phenomenon known as "soft sparking". The soft spark discharge mode significantly improves the densification of the anode ceramic layer and facilitates the formation of the high-temperature α-Al2O3 phase within the coating. Although the soft spark discharge phenomenon has been known for a long time, the growth behavior of the coating under its discharge mode still needs to be studied and improved. In this paper, the growth behavior of the coating before and after soft spark discharge is investigated with the help of the micro-morphology, phase composition and element distribution of a homemade fixture. The results show that the ceramic layer grows mainly along the oxide-electrolyte direction before the soft spark discharge transformation; after the soft spark discharge, the ceramic layer grows along the oxide-substrate direction. It was also unexpectedly found that, under soft spark discharge, the silicon element only exists on the outside of the coating, which is caused by the large size and slow migration of SiO32-, which can only enter the ceramic layer and participate in the reaction through the discharge channel generated by the strong discharge. In addition, it was also found that the relative phase content of α-Al2O3 in the coating increased from 0.487 to 0.634 after 10 min of rotary spark discharge, which is an increase of 30.2% compared with that before the soft spark discharge transition. On the other hand, the relative phase content of α-Al2O3 in the coating decreased from 0.487 to 0.313 after 20 min of transfer spark discharge, which was a 55.6% decrease compared to that before the soft spark discharge transformation.

Impact of whole grain highland hull-less barley on the denaturing gradient gel electrophoresis profiles of gut microbial communities in rats fed high-fat diets.

Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) is a traditional non-culture technique that can provide a fingerprint of the microbial community. In the field of gut microbiota analysis, PCR-DGGE still holds potential for development. In the present study, we utilized an improved nested PCR-DGGE approach targeting the V3 region of 16S ribosomal DNA to investigate the impact of whole grain highland hull-less barley (WHLB), a cereal known for its significant hypocholesterolemic effect, on the gut microbiota profiles of high-fat diet rats. Seventy-two male Sprague-Dawley rats were divided into four groups and fed a normal control diet, a high-fat diet, or a high-fat diet supplemented with a low or high dose of WHLB for 4 or 8 weeks. The results revealed that the dominant bands varied among different dose groups and further changed with different treatment times. The compositions of bacterial communities in feces and cecal content were similar, but the dominant bacterial bands differed. After performing double DGGE, extracting the bands, sequencing the DNA, and aligning the sequences, a total of 19 bands were classified under the Firmicutes and Bacteroidetes phyla, while two bands were identified as unclassified uncultured bacteria. The relative abundance of Lactobacillus gasseri, Uncultured Prevotella sp., and Clostridium sp. increased following the administration of WHLB. Illumina-based sequencing was employed to assess the reliability of DGGE, demonstrating its reliability in analyzing the dominant taxonomic composition, although it may have limitations in accurately detecting the alpha diversity of bacterial species. IMPORTANCE: While next-generation sequencing has overshadowed polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), the latter still holds promise for advancing gut microbiota analysis due to its unique advantages. In this study, we used optimized nested PCR-DGGE to investigate the gut microbiota profile of high-fat diet rats after administering whole grain highland hull-less barley. High-throughput sequencing was employed to validate the DGGE results. Our results proved the reliability of PCR-DGGE for analyzing the dominant taxonomic composition while also providing visual evidence of a notable relationship between the composition of cecal and fecal microbial communities, highlighting substantial differences in both richness and abundance.

Multidrug resistance transporters P-gp and BCRP limit the efficacy of ATR inhibitor ceralasertib in cancer cells.

The therapeutic effect of chemotherapy and targeted therapy are known to be limited by drug resistance. Substantial evidence has shown that ATP-binding cassette (ABC) transporters P-gp and BCRP are significant contributors to multidrug resistance (MDR) in cancer cells. In this study, we demonstrated that a clinical-staged ATR inhibitor ceralasertib is susceptible to P-gp and BCRP-mediated MDR. The drug resistant cancer cells were less sensitive to ceralasertib compared to the parental cells. Moreover, ceralasertib resistance can be reversed by inhibiting the drug efflux activity of P-gp and BCRP. Interestingly, ceralasertib was able to downregulate the level of P-gp but not BCRP, suggesting a potential regulation between ATR signaling and P-gp expression. Furthermore, computational docking analysis predicted high affinities between ceralasertib and the drug-binding sites of P-gp and BCRP. In summary, overexpression of P-gp and BCRP are sufficient to confer cancer cells resistance to ceralasertib, underscoring their role as biomarkers for therapeutic efficacy.

A Comprehensive Review of Vision-Based 3D Reconstruction Methods.

With the rapid development of 3D reconstruction, especially the emergence of algorithms such as NeRF and 3DGS, 3D reconstruction has become a popular research topic in recent years. 3D reconstruction technology provides crucial support for training extensive computer vision models and advancing the development of general artificial intelligence. With the development of deep learning and GPU technology, the demand for high-precision and high-efficiency 3D reconstruction information is increasing, especially in the fields of unmanned systems, human-computer interaction, virtual reality, and medicine. The rapid development of 3D reconstruction is becoming inevitable. This survey categorizes the various methods and technologies used in 3D reconstruction. It explores and classifies them based on three aspects: traditional static, dynamic, and machine learning. Furthermore, it compares and discusses these methods. At the end of the survey, which includes a detailed analysis of the trends and challenges in 3D reconstruction development, we aim to provide a comprehensive introduction for individuals who are currently engaged in or planning to conduct research on 3D reconstruction. Our goal is to help them gain a comprehensive understanding of the relevant knowledge related to 3D reconstruction.

A Novel Grading System for Diffuse Chorioretinal Atrophy in Pathologic Myopia.

INTRODUCTION: This study aims to quantitatively assess diffuse chorioretinal atrophy (DCA) in pathologic myopia and establish a standardized classification system utilizing artificial intelligence. METHODS: A total of 202 patients underwent comprehensive examinations, and 338 eyes were included in the study. The methodology involved image preprocessing, sample labeling, employing deep learning segmentation models, measuring and calculating the area and density of DCA lesions. Lesion severity of DCA was graded using statistical methods, and grades were assigned to describe the morphology of corresponding fundus photographs. Hierarchical clustering was employed to categorize diffuse atrophy fundus into three groups based on the area and density of diffuse atrophy (G1, G2, G3), while high myopic fundus without diffuse atrophy was designated as G0. One-way analysis of variance (ANOVA) and nonparametric tests were conducted to assess the statistical association with different grades of DCA. RESULTS: On the basis of the area and density of DCA, the condition was classified into four grades: G0, G1 (0 < density ≤ 0.093), G2 (0.093 < density ≤ 0.245), and G3 (0.245 < density ≤ 0.712). Fundus photographs depicted a progressive enlargement of atrophic lesions, evolving from punctate-shaped to patchy with indistinct boundaries. DCA atrophy lesions exhibited a gradual shift in color from brown-yellow to yellow-white, originating from the temporal side of the optic disc and extending towards the macula, with severe cases exhibiting widespread distribution throughout the posterior pole. Patients with DCA were significantly older [34.00 (27.00, 48.00) vs 29.00 (26.00, 34.00) years], possessed a longer axial length (28.85 ± 1.57 vs 27.11 ± 1.01 mm), and exhibited a more myopic spherical equivalent [- 13.00 (- 16.00, - 10.50) vs - 9.09 ± 2.41 D] compared to those without DCA (G0) (all P < 0.001). In eyes with DCA, a trend emerged as grades increased from G1 to G3, showing associations with older age, longer axial length, deeper myopic spherical equivalent, larger area of parapapillary atrophy, and increased fundus tessellated density (all P < 0.001). CONCLUSIONS: The novel grading system for DCA, based on assessments of area and density, serves as a reliable measure for evaluating the severity of this condition, making it suitable for widespread application in the screening of pathologic myopia.

Analysis of four hereditary protein C deficiencies associated with vascular thromboembolism.

OBJECTIVE: To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) deficiency and explore their association with vascular thromboembolism. METHODS: The clinical data of four patients with PC deficiency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the probands. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation. RESULTS: Thrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c.541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. In particular, c.1146_1146delT heterozygous deletion mutations not reported previously. Conservativeness and pathogenicity analyses confirmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. According to the American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants, c.1146_1146delT was rated as pathogenic (PVS1 + M2 + PM4 + PP1 + PP3 + PP4). CONCLUSION: The identified mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC deficiency exhibit considerable diversity.

Cross-talk between immunity and behavior: insights from entomopathogenic fungi and their insect hosts.

Insects are one of the most successful animals in nature, and entomopathogenic fungi play a significant role in the natural epizootic control of insect populations in many ecosystems. The interaction between insects and entomopathogenic fungi has continuously coevolved over hundreds of millions of years. Many components of the insect innate immune responses against fungal infection are conserved across phyla. Additionally, behavioral responses, which include avoidance, grooming, and/or modulation of body temperature, have been recognized as important mechanisms for opposing fungal pathogens. In an effort to investigate possible cross-talk and mediating mechanisms between these fundamental biological processes, recent studies have integrated and/or explored immune and behavioral responses. Current information indicates that during discrete stages of fungal infection, several insect behavioral and immune responses are altered simultaneously, suggesting important connections between the two systems. This review synthesizes recent advances in our understanding of the physiological and molecular aspects influencing cross-talk between behavioral and innate immune antifungal reactions, including chemical perception and olfactory pathways.

Time series prediction of insect pests in tea gardens.

BACKGROUND: Tea-garden pest control is crucial to ensure tea quality. In this context, the time-series prediction of insect pests in tea gardens is very important. Deep-learning-based time-series prediction techniques are advancing rapidly but research into their use in tea-garden pest prediction is limited. The current study investigates the time-series prediction of whitefly populations in the Tea Expo Garden, Jurong City, Jiangsu Province, China, employing three deep-learning algorithms, namely Informer, the Long Short-Term Memory (LSTM) network, and LSTM-Attention. RESULTS: The comparative analysis of the three deep-learning algorithms revealed optimal results for LSTM-Attention, with an average root mean square error (RMSE) of 2.84 and average mean absolute error (MAE) of 2.52 for 7 days' prediction length, respectively. For a prediction length of 3 days, LSTM achieved the best performance, with an average RMSE of 2.60 and an average MAE of 2.24. CONCLUSION: These findings suggest that different prediction lengths influence model performance in tea garden pest time series prediction. Deep learning could be applied satisfactorily to predict time series of insect pests in tea gardens based on LSTM-Attention. Thus, this study provides a theoretical basis for the research on the time series of pest and disease infestations in tea plants. © 2024 Society of Chemical Industry.

An analysis of POMC gene methylation and expression in patients with schizophrenia.

Schizophrenia is a chronic mental disorder that affects millions of people and is believed to be caused by both environmental and genetic factors. Despite extensive research, the exact mechanisms underlying schizophrenia are still unclear. Studies have shown that numerous psychiatric disorders are associated with methylation of the POMC gene, which encodes adrenocorticotropic hormone, a critical player in the hypothalamic-pituitary-adrenal axis. However, the association between DNA methylation in POMC patients and schizophrenia remains unclear. In this study, we evaluated three fragments of the POMC promoter region, including 51 CpG sites, in the peripheral blood of schizophrenia patients and healthy controls. The POMC protein level was measured via enzyme-linked immunosorbent assay (ELISA). The schizophrenia group exhibited significantly greater levels of methylation of the POMC gene than those in the control group. The methylation level of the POMC-2 fragment was significantly greater in the patient group than in the control group. There were 17 significantly hypermethylated CpG sites in the patient group. After stratification by sex, POMC methylation levels were found to be significantly greater in male schizophrenia patients than in healthy controls; the methylation levels of POMC-2 fragments were greater in the male patient group; nine CpG sites were significantly hypermethylated in the male patient group; and only one CpG site was significantly hypermethylated in the female patient group. The POMC protein level in patients was significantly lower than that in healthy controls. These findings demonstrate that the DNA methylation of POMC might be associated with the pathophysiology of schizophrenia. Overall, studying the correlation between POMC methylation and schizophrenia may contribute to the diagnosis and evaluation of neuropsychiatric disorders.

Advanced nanozymes possess peroxidase-like catalytic activities in biomedical and antibacterial fields: review and progress.

Infectious diseases caused by bacterial invasions have imposed a significant global health and economic burden. More worryingly, multidrug-resistant (MDR) pathogenic bacteria born under the abuse of antibiotics have further escalated the status quo. Nowadays, at the crossroads of multiple disciplines such as chemistry, nanoscience and biomedicine, nanozymes, as enzyme-mimicking nanomaterials, not only possess excellent bactericidal ability but also reduce the possibility of inducing resistance. Thus, nanozymes are promising to serve as an alternative to traditional antibiotics. Nanozymes that mimic peroxidase (POD) activity are also known as POD nanozymes. In recent years, POD nanozymes have become one of the most frequently reported and effective nanozymes due to their broad-spectrum bactericidal properties and unique sterilization mechanism. In this review, we introduce the mechanism as well as the classification of POD nanozymes. More importantly, to further improve the antibacterial efficacy of POD nanozymes, we elaborate on three aspects: (1) improving the physicochemical properties; (2) regulating the catalytic microenvironment; and (3) designing multimodel POD nanozymes. In addition, we review the nanosafety of POD nanozymes for discussing their potential toxicity. Finally, the remaining challenges of POD nanozymes and possible future directions are discussed. This work provides a systematic summary of POD nanozymes and hopefully contributes to the early clinical translation.

Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3.

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).

Fundus Tessellated Density of Pathologic Myopia.

PURPOSE: The study aimed to quantitatively evaluate the fundus tessellated density (FTD) in different categories of pathologic myopia (PM) using fundus photographs with the application of artificial intelligence. METHODS: A retrospective review of 407 PM (META-PM, Category 2-Category 4) eyes was conducted, employing a biomimetic mechanism of human vision and integrated image processing technologies for FTD extraction and calculation. Different regions of interest were analyzed, including circle O4.5 (optic disc centered, diameter of 4.5 mm) and circle M1.0, M3.0, M6.0 (macular centered, diameter of 1.0, 3.0, and 6.0 mm), using 2 partitioning methods ("X" and "+"). The density of patchy (Category 3) or macular atrophy (Category 4) areas was quantified. Univariate and multivariate linear regression analyses were performed to assess the association with FTD. RESULTS: The mean FTD of total PM eyes was 0.283, ranging from 0.002 to 0.500, and demonstrating a negative correlation with the PM category. In multivariate analysis, age was found to be significantly associated with FTD ( P <0.05), while axial length did not show a significant association. Fundus tessellation of circle O4.5 and circle M6.0 displayed associations with the FTD across different PM categories. The "X" partitioning method better fit the circle M6.0 region, while both methods were suitable for the circle O4.5 region. After excluding the patchy and macular atrophic areas, the mean FTD values were 0.346 in Category 2, 0.261 in Category 3, and 0.186 in Category 4. CONCLUSIONS: The study revealed a decreasing trend in FTD values across different categories of PM, regardless of the presence or absence of patchy or macular atrophic areas. Quantifying FTD in PM could be a valuable tool for improving the existing PM classification system and gaining insights into the origin of posterior staphyloma and visual field defects in high myopia.

MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed.

While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. To understand the function of miRNAs during the AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activated essential neuronal genes to initiate the reprogramming process but also induced miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and were also upregulated by NeuroD1. We further showed that manipulating the miR-375 level regulated nELAVLs' expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs were also induced by the reprogramming factors Neurog2 and ASCL1 in HA, suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improved NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA and did not appear to compromise the maturation of the reprogrammed neurons. Lastly, overexpression of miR-375-refractory ELAVL4 induced apoptosis and reversed the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrated a neuroprotective role of miR-375 during NeuroD1-mediated AtN reprogramming.

Heterogeneous treatment effects of coronary artery bypass grafting in ischemic cardiomyopathy: A machine learning causal forest analysis.

OBJECTIVES: We aim to evaluate the heterogeneous treatment effects of coronary artery bypass grafting in patients with ischemic cardiomyopathy and to identify a group of patients to have greater benefits from coronary artery bypass grafting compared with medical therapy alone. METHODS: Machine learning causal forest modeling was performed to identify the heterogeneous treatment effects of coronary artery bypass grafting in patients with ischemic cardiomyopathy from the Surgical Treatment for Ischemic Heart Failure trial. The risks of death from any cause and death from cardiovascular causes between coronary artery bypass grafting and medical therapy alone were assessed in the identified subgroups. RESULTS: Among 1212 patients enrolled in the Surgical Treatment for Ischemic Heart Failure trial, left ventricular end-systolic volume index, serum creatinine, and age were identified by the machine learning algorithm to distinguish patients with heterogeneous treatment effects. Among patients with left ventricular end-systolic volume index greater than 84 mL/m2 and age 60.27 years or less, coronary artery bypass grafting was associated with a significantly lower risk of death from any cause (adjusted hazard ratio, 0.61; 95% CI, 0.45-0.84) and death from cardiovascular causes (adjusted hazard ratio, 0.63; 95% CI, 0.45-0.89). By contrast, the survival benefits of coronary artery bypass grafting no longer exist in patients with left ventricular end-systolic volume index 84 mL/m2 or less and serum creatinine 1.04 mg/dL or less, or patients with left ventricular end-systolic volume index greater than 84 mL/m2 and age more than 60.27 years. CONCLUSIONS: The current post hoc analysis of the Surgical Treatment for Ischemic Heart Failure trial identified heterogeneous treatment effects of coronary artery bypass grafting in patients with ischemic cardiomyopathy. Younger patients with severe left ventricular enlargement were more likely to derive greater survival benefits from coronary artery bypass grafting.