Progress on deep learning in genomics.

With the rapid growth of data driven by high-throughput sequencing technologies, genomics has entered an era characterized by big data, which presents significant challenges for traditional bioinformatics methods in handling complex data patterns. At this critical juncture of technological progress, deep learning-an advanced artificial intelligence technology-offers powerful capabilities for data analysis and pattern recognition, revitalizing genomic research. In this review, we focus on four major deep learning models: Convolutional Neural Network(CNN), Recurrent Neural Network(RNN), Long Short-Term Memory(LSTM), and Generative Adversarial Network(GAN). We outline their core principles and provide a comprehensive review of their applications in DNA, RNA, and protein research over the past five years. Additionally, we also explore the use of deep learning in livestock genomics, highlighting its potential benefits and challenges in genetic trait analysis, disease prevention, and genetic enhancement. By delivering a thorough analysis, we aim to enhance precision and efficiency in genomic research through deep learning and offer a framework for developing and applying livestock genomic strategies, thereby advancing precision livestock farming and genetic breeding technologies.

Selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids.

A novel selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids was reported. Two types of leucosceptrane derivatives with different valence states of selenium atoms (Se2+ and Se4+) were obtained. The mechanisms of these two processes were proposed, and the selenium-containing derivates may serve as intermediates of Riley oxidation that could be trapped with appropriate substrates. Immunosuppressive activity screening revealed that 10 and 11 had obvious inhibitory effects on IFN-γ production, with IC50 values of 5.29 and 17.60 µM, respectively, which were more active than their precursor leucosceptroid A.

[Role and mechanism of ginsenoside Rg1 in ameliorating sepsis-induced acute lung injury based on PERK/eIF2α/ATF4/CHOP-induced alveolar epithelial cell apoptosis].

The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.

Surface Cladding Engineering via Oxygen Sulfur Distribution for Stable Electrocatalytic Oxygen Evolution Reaction.

Inevitable leaching and corrosion under anodic oxidative environment greatly restrict the lifespan of most catalysts with excellent primitive activity for oxygen production. Here, based on Fick' s Law, we present a surface cladding strategy to mitigate Ni dissolution and stabilize lattice oxygen triggering by directional flow of interfacial electrons and strong electronic interactions via constructing elaborately cladding-type NiO/NiS heterostructure with controlled surface thickness. Multiple in-situ characterization technologies indicated that this strategy can effectively prevent the irreversible Ni ions leaching and inhibit lattice oxygen from participating in anodic reaction. Combined with density functional theory calculations, we reveal that the stable interfacial O-Ni-S arrangement can facilitate the accumulation of electrons on surficial NiO side and weaken its Ni-O covalency. This would suppress the overoxidation of Ni and simultaneously fixing the lattice oxygen, thus enabling catalysts with boosted corrosion resistance without sacrificing its activity. Consequently, this cladding-type NiO/NiS heterostructure exhibits excellent performance with a low overpotential of 256 mV after 500 h. Based on Fick's law, this work demonstrates the positive effect of surface modification through precisely adjusting of the oxygen-sulfur exchange process, which has paved an innovative and effective way to solve the instability problem of anodic oxidation.

Erratum: Corrigendum: Liu W-B, Wang C-Y, Tang Y-N, Wang Y, Pei W-X, Yan C-C (2024) Six new species of Cryptochironomus Kieffer (Diptera, Chironomidae) from the Nearctic region. ZooKeys 1200: 275-302. doi: 10.3897/zookeys.1200.119225.

[This corrects the article DOI: 10.3897/zookeys.1200.119225.].

Leucosceptrane sesterterpenoids from Tibetan Leucosceptrum canum and their immunosuppressive activity.

Phytochemical investigation on the leaves of Tibetan Leucosceptrum canum, a Chinese medicinal herb, led to the isolation of seven new leucosceptrane sesterterpenoids (1-7) and five known analogs (8-12). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRMS), quantum chemistry computations, and single crystal X-ray crystallographic analysis were applied to elucidate their structures. Compounds 1-3 and 6 were the first examples of the leucosceptrane sesterterpenoids with rare C-2 oxidation. Compound 2 exhibited immunosuppressive activities via suppressing the secretion of cytokines IL-6 and TNF-α in LPS-induced macrophages RAW264.7 with IC50 values of 13.39 and 19.34 µM, respectively.

Stimulating Electron Delocalization of Lanthanide Elements through High-Entropy Confinement to Promote Electrocatalytic Water Splitting.

High-entropy alloys (HEAs) have aroused extensive attention in the field of catalysis. However, due to the integration of multiple active sites in HEA, it exhibits excessive adsorption behavior resulting in difficult desorption of active species from the catalyst surfaces, which hinders the catalytic efficiency. Therefore, adjusting the adsorption strength of the active site in HEA to enhance the catalytic activity is of great importance. By introducing rare-earth (RE) elements into the high-entropy alloy, the delocalization of 4f electrons can be achieved through the interaction between the multimetal active site and RE, which benefits to regulate the adsorption strength of the HEA surface. Herein, the RE Ce-modified hexagonal-close-packed PtRuFeCoNiZn-Ce/C HEAs are synthesized and showed an excellent electrocatalytic activity for hydrogen evolution reaction and oxygen evolution reaction with ultralow overpotentials of 4, 7 and 156, 132 mV, respectively, to reach 10 mA cm-2 in 0.5 M H2SO4 and 1.0 M KOH solutions, and the assembled water electrolysis cell only requires a voltage of 1.43 V to reach 10 mA cm-2, which is much better than the performance of PtRuFeCoNiZn/C. Combined with the results of in situ attenuated total reflection infrared spectroscopy and density functional theory (DFT), the fundamental reasons for the improvement of catalyst activity come from two aspects: (i) local lattice distortion of HEA caused by the introduction of RE with large atomic radius induces 4f orbital electron delocalization of RE elements and enhances electron exchange between RE and active sites. (ii) The electronegativity difference between the RE element and the active site forms a surface dipole in HEA, which optimizes the adsorption of the active intermediate by the HEA surface site. This study provides an insightful idea for the rational design of high-performance HEA- and RE-based electrocatalysts.

Leverage Effective Deep Learning Searching Method for Forensic Age Estimation.

Dental age estimation is extensively employed in forensic medicine practice. However, the accuracy of conventional methods fails to satisfy the need for precision, particularly when estimating the age of adults. Herein, we propose an approach for age estimation utilizing orthopantomograms (OPGs). We propose a new dental dataset comprising OPGs of 27,957 individuals (16,383 females and 11,574 males), covering an age range from newborn to 93 years. The age annotations were meticulously verified using ID card details. Considering the distinct nature of dental data, we analyzed various neural network components to accurately estimate age, such as optimal network depth, convolution kernel size, multi-branch architecture, and early layer feature reuse. Building upon the exploration of distinctive characteristics, we further employed the widely recognized method to identify models for dental age prediction. Consequently, we discovered two sets of models: one exhibiting superior performance, and the other being lightweight. The proposed approaches, namely AGENet and AGE-SPOS, demonstrated remarkable superiority and effectiveness in our experimental results. The proposed models, AGENet and AGE-SPOS, showed exceptional effectiveness in our experiments. AGENet outperformed other CNN models significantly by achieving outstanding results. Compared to Inception-v4, with the mean absolute error (MAE) of 1.70 and 20.46 B FLOPs, our AGENet reduced the FLOPs by 2.7×. The lightweight model, AGE-SPOS, achieved an MAE of 1.80 years with only 0.95 B FLOPs, surpassing MobileNetV2 by 0.18 years while utilizing fewer computational operations. In summary, we employed an effective DNN searching method for forensic age estimation, and our methodology and findings hold significant implications for age estimation with oral imaging.

Catalytic properties of trivalent rare-earth oxides with intrinsic surface oxygen vacancy.

Oxygen vacancy (Ov) is an anionic defect widely existed in metal oxide lattice, as exemplified by CeO2, TiO2, and ZnO. As Ov can modify the band structure of solid, it improves the physicochemical properties such as the semiconducting performance and catalytic behaviours. We report here a new type of Ov as an intrinsic part of a perfect crystalline surface. Such non-defect Ov stems from the irregular hexagonal sawtooth-shaped structure in the (111) plane of trivalent rare earth oxides (RE2O3). The materials with such intrinsic Ov structure exhibit excellent performance in ammonia decomposition reaction with surface Ru active sites. Extremely high H2 formation rate has been achieved at ~1 wt% of Ru loading over Sm2O3, Y2O3 and Gd2O3 surface, which is 1.5-20 times higher than reported values in the literature. The discovery of intrinsic Ov suggests great potentials of applying RE oxides in heterogeneous catalysis and surface chemistry.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision.

BACKGROUND: Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM: To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS: A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS: Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION: The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

Association between different obesity patterns and the risk of NAFLD detected by transient elastography: a cross-sectional study.

BACKGROUND: Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. METHODS: Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. RESULTS: A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74-12.70], 2.84 [2.38-3.39], 3.02 [2.02-4.51], and 9.53 [7.79-11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42-1.53; P < 0.001). WC also demonstrated strong discriminatory ability for NAFLD in Receiver Operating Characteristic (ROC) analysis, achieving an Area Under the Curve (AUC) of 0.802. CONCLUSIONS: Different patterns of obesity are risk factors for NAFLD. An increase in WC significantly increased NAFLD risk. More attention should be paid to preventing different patterns of obesity among adults.

Exogenous autoinducer-2 alleviates intestinal damage in necrotizing enterocolitis via PAR2/MMP3 signaling pathway.

BACKGROUND: Imbalanced intestinal microbiota and damage to the intestinal barrier contribute to the development of necrotizing enterocolitis (NEC). Autoinducer-2 (AI-2) plays a crucial role in repairing intestinal damage and reducing inflammation. OBJECTIVE: This study aimed to investigate the impact of AI-2 on the expression of intestinal zonula occludens-1 (ZO-1) and occludin proteins in NEC. We evaluated its effects in vivo using NEC mice and in vitro using lipopolysaccharide (LPS)-stimulated intestinal cells. METHODS: Pathological changes in the intestines of neonatal mice were assessed using histological staining and scoring. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to determine the optimal conditions for LPS and AI-2 interventions. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA levels of matrix metalloproteinase-3 (MMP3), protease activated receptor-2 (PAR2), interleukin-1ß (IL-1ß), and IL-6. Protein levels of MMP3, PAR2, ZO-1, and occludin were evaluated using western blot, immunohistochemistry, or immunofluorescence. RESULTS: AI-2 alleviated NEC-induced intestinal damage (P < 0.05) and enhanced the proliferation of damaged IEC-6 cells (P < 0.05). AI-2 intervention reduced the mRNA and protein expressions of MMP3 and PAR2 in intestinal tissue and cells (P < 0.05). Additionally, it increased the protein levels of ZO-1 and occludin (P < 0.05), while reducing IL-1ß and IL-6 mRNA expression (P < 0.05). CONCLUSION: AI-2 intervention enhances the expression of tight junction proteins (ZO-1 and occludin), mitigates intestinal damage in NEC neonatal mice and IEC-6 cells, potentially by modulating PAR2 and MMP3 signaling. AI-2 holds promise as a protective intervention for NEC. AI-2 plays a crucial role in repairing intestinal damage and reducing inflammation.

Microbial life-history strategies and particulate organic carbon mediate formation of microbial necromass carbon and stabilization in response to biochar addition.

Microbial necromass carbon (MNC) contributes significantly to the formation of soil organic carbon (SOC). However, the microbial carbon sequestration effect of biochar is often underestimated and influenced by nutrient availability. The mechanisms associated with the formation and stabilization of MNC remain unclear, especially under the combined application of biochar and nitrogen (N) fertilizer. Thus, in a long-term field experiment (11 years) based on biochar application, we utilized bacterial 16S rRNA gene sequencing, fungal ITS amplicon sequencing, metagenomics, and microbial biomarkers to examine the interactions between MNC accumulation and microbial metabolic strategies under combined treatment with biochar and N fertilizer. We aimed to identify the critical microbial modules and species involved, and to analyze the sites where MNC was immobilized from various components. Biochar application increased the MNC content by 13.9 %. Among the MNC components, fungal necromass contributed more to MNC, but bacteria were more readily enriched after biochar application. The microbial life-history strategies that affected MNC formation under the application of various amounts biochar were linked to the N application level. Under N added at 226.5 kg ha-1, communities such as Actinobacteria and Bacteroidetes with high-growth yield strategies were prevalent and contributed to MNC production. By contrast, under N added at 113.25 kg ha-1 with high biochar application, Proteobacteria with strong resource acquisition strategies were dominant and MNC accumulation was lower. The mineral-associated organic carbon pool was rapidly saturated with the addition of biochar, so the contribution of fungal necromass carbon may have been reduced by reutilization, thereby resulting in the more rapid preservation of bacterial necromass carbon in the particulate organic carbon pool. Overall, our findings indicate that microbial life history traits are crucial for linking microbial metabolic processes to the accumulation and stabilization of MNC, thereby highlighting the their importance for SOC accumulation in farmland soils, and the need to tailor appropriate biochar and N fertilizer application strategies for agricultural soils.

MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1.

BACKGROUND: TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1. The aim of this study was to determine whether MARCH1 regulates the mTOR signaling pathway by targeting TBK1. METHODS: The co-immunoprecipitation (Co-IP) assay was used to verify the interaction between MARCH1 with STING or TBK1. The ubiquitination of STING or TBK1 was analyzed using denatured co-immunoprecipitation. The level of proteins detected in the co-immunoprecipitation or denatured co-immunoprecipitation samples were determined by Western blotting. Stable knocked-down cells were constructed by infecting lentivirus bearing the related shRNA sequences. Scratch wound healing and clonogenic cell survival assays were used to detect the migration and proliferation of breast cancer cells. RESULTS: We showed that MARCH1 played an important role in growth factor-induced the TBK1- mTOR signaling pathway. MARCH1 overexpression attenuated the growth factor-induced activation of mTOR signaling pathway, whereas its deficiency resulted in the opposite effect. Mechanistically, MARCH1 interacted with and promoted the K63-linked ubiquitination of TBK1. This ubiquitination of TBK1 then attenuated its interaction with mTOR, thereby inhibiting the growth factor-induced mTOR signaling pathway. Importantly, faster proliferation induced by MARCH1 deficiency was weakened by mTOR, STING, or TBK1 inhibition. CONCLUSION: MARCH1 suppressed growth factors mediated the mTOR signaling pathway by targeting the STING-TBK1-mTOR axis.

Impact of Pulmonary Ventilation Dysfunction on Prognosis of Patients with Coronary Artery Disease: A Single-Center, Observational Study.

Background: Patients with coronary artery disease (CAD) often experience pulmonary ventilation dysfunction following their initial event. However, there is insufficient research exploring the relationship between this dysfunction and CAD prognosis. Methods: To address this gap, a retrospective observational study was conducted involving 3800 CAD patients without prior pulmonary ventilation disease who underwent cardiopulmonary exercise testing (CPET) during hospitalization between November 2015 and September 2021. The primary endpoint was a composite of major adverse cardiovascular events (MACE), such as death, myocardial infarction (MI), repeat revascularization, and stroke. Propensity score matching (PSM) was used to minimize selection bias between the two groups, with a subgroup analysis stratified by smoking status. Results: The results showed that patients were divided into normal (n = 2159) and abnormal (n = 1641) groups based on their pulmonary ventilation function detected by CPET, with 1469 smokers and 2331 non-smokers. The median follow-up duration was 1237 (25-75% interquartile range 695-1596) days. The primary endpoint occurred in 390 patients (10.26%). 1472 patients in each of the two groups were enrolled in the current analysis after PSM, respectively. However, pulmonary function was not associated with MACE before (hazard ratio (HR) 1.20, 95% confidence interval (95% CI) 0.99-1.47; Log-rank p = 0.069) or after PSM (HR 1.07, 95% CI 0.86-1.34; Log-rank p = 0.545) among the entire population. Nonetheless, pulmonary ventilation dysfunction was significantly associated with an increased risk of MACE in smoking patients (HR 1.65, 95% CI 1.25-2.18; p < 0.001) but not in non-smoking patients (HR 0.81, 95% CI 0.60-1.09; p = 0.159). In addition, there was a significant interaction between current smoking status and pulmonary ventilation dysfunction on MACE (p for interaction < 0.001). Conclusions: Pulmonary ventilation dysfunction identified through CPET was independently associated with long-term poor prognosis in smoking patients with CAD but not in the overall population.

Immunosuppressive leucosesterterpane and penta-nor-leucosesterterpane sesterterpenoids from Leucosceptrum canum.

Five undescribed leucosesterterpane sesterterpenoids, leucosceptrines A-E, two undescribed penta-nor-leucosesterterpane (C20) sesterterpenoids, nor-leucosceptrines A and B, and three known analogues, were obtained from the aerial parts of Leucosceptrum canum of Chinese origin. Leucosceptrines A-C are the first examples of leucosesterterpane-type sesterterpenoids with unclosed dihydropyran rings and reverse configurations at chiral centers C-4 and/or C-12. Nor-leucosceptrines A and B possesses an unusual penta-nor-leucosesterterpane skeleton. Their structures were unambiguously elucidated through comprehensive spectroscopic analyses and single-crystal X-ray diffraction. A plausible biogenetic pathway for these sesterterpenoids was proposed. The immunosuppressive effects of these isolates on the secretion of the cytokine IFN-γ by T cells stimulated with anti-CD3/CD28 monoclonal antibodies were observed with different potencies.

Ceria-Optimized Oxygen-Species Exchange in Hierarchical Bimetallic Hydroxide for Electrocatalytic Water Oxidation.

The utilization of rare earth elements to regulate the interaction between catalysts and oxygen-containing species holds promising prospects in the field of oxygen electrocatalysis. Through structural engineering and adsorption regulation, it is possible to achieve high-performance catalytic sites with a broken activity-stability tradeoff. Herein, this work fabricates a hierarchical CeO2/NiCo hydroxide for electrocatalytic oxygen evolution reaction (OER). This material exhibits superior overpotentials and enhanced stability. Multiple potential-dependent experiments reveal that CeO2 promotes oxygen-species exchange, especially OH- ions, between catalyst and environment, thereby optimizing the redox transformation of hydroxide and the adsorption of oxygen-containing intermediates during OER. This is attributed to the reduction in the adsorption energy barrier of Ni to *OH facilitated by CeO2, particularly the near-interfacial Ni sites. The less-damaging adsorbate evolution mechanism and the CeO2 hierarchical shell significantly enhance the structural robustness, leading to exceptional stability. Additionally, the observed "self-healing" phenomenon provides further substantiation for the accelerated oxygen exchange. This work provides a neat strategy for the synthesis of ceria-based complex hollow electrocatalysts, as well as an in-depth insight into the co-catalytic role of CeO2 in terms of oxygen transfer.

Evaluation of plasma-derived extracellular vesicles miRNAs and their connection with hippocampal mRNAs in alcohol use disorder.

Alcohol use disorder (AUD) is a common mental illness with high morbidity and disability. The discovery of laboratory biomarkers has progressed slowly, resulting in suboptimal diagnosis and treatment of AUD. This study aimed to identify promising biomarkers, as well as the potential miRNA-mRNA networks associated with AUD pathogenesis. RNA sequencing was performed on plasma-derived small extracellular vesicles (sEVs) from AUD patients and healthy controls (HCs) to harvest miRNAs expression profiles. Machine learning (ML) models were built to screen characteristic miRNAs, whose target mRNAs were analyzed using TargetScan, miRanda and miRDB databases. Gene Expression Omnibus (GEO) datasets (GSE181804 and GSE180722) providing postmortem hippocampal gene expression profiles of AUD subjects were mined. A total of 247 differentially expressed (DE) plasma-derived sEVs miRNAs and 122 DE hippocampal mRNAs were obtained. Then, 22 overlapping sEVs miRNAs with high importance scores were gained by intersecting 5 ML models. As a result, we established a putative sEVs miRNA-hippocampal mRNA network that can effectively distinguish AUD patients from HCs. In conclusion, we proposed 5 AUD-representative sEVs miRNAs (hsa-miR-144-5p, hsa-miR-182-5p, hsa-miR-142-5p, hsa-miR-7-5p, and hsa-miR-15b-5p) that may participate in the pathogenesis of AUD by modulating downstream target hippocampal genes. These findings may provide novel insights into the diagnosis and treatment of AUD.

Coronary CTA-based Vascular Radiomics Predicts Atherosclerosis Development Proximal to LAD Myocardial Bridging.

BACKGROUND: Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD). OBJECTIVE: To assess coronary CT angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB. METHODS: Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as development set. They were divided into training and internal testing in an 8:2 ratio. Patients from 4 other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centerline (MB CL), proximal MB CL (pMB CL), MB cross section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). RESULTS: 295 patients were included in the development (n=192; median age, 54±11 years; 137 men) and external validation sets (n=103; median age, 57±9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC=0.78, 0.75, 0.75) than the clinical and anatomical model (all p<0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (p=0.002), along with enhanced NRI (0.76 [0.37-1.14], p<0.001) and IDI (0.17 [0.07-0.26], p<0.001) in the external validation set. CONCLUSION: The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB.

Six new species of Cryptochironomus Kieffer (Diptera, Chironomidae) from the Nearctic region.

Six new species of Cryptochironomus Kieffer, 1918, C.absum Liu, sp. nov., C.beardi Liu, sp. nov., C.dentatus Liu, sp. nov., C.ferringtoni Liu, sp. nov., C.parallelus Liu, sp. nov. and C.taylorensis Liu, sp. nov., are described and illustrated based on adult males. The specimens were collected from various water systems in the United States and preserved by Dr. Leonard Charles Ferrington Jr. An updated key to adult males of all known Cryptochironomus species in the Nearctic region is also provided.