Enhancing procedural decision making with cone beam CT in renal artery embolization.

Cone-beam computed tomography (CBCT) has proven to be a safe and effective adjunctive imaging tool for interventional radiology. Nevertheless, limited studies have examined the application of CBCT in renal artery embolization (RAE). The objective of this study is to evaluate the role of CBCT in intra-procedural decision-making for RAE. This multicenter retrospective study included 40 consecutive patients (age: 55.9 ± 16.5 years; male, 55%) who underwent CBCT during RAE from January 2019 to January 2023. The additional information provided by CBCT was classified into Category 1 (no additional information), Category 2 (more information without changing the treatment plan), and Category 3 (valuable information that led to a change in the treatment plan). CBCT did not add unique information for four patients (10%) classified as Category 1. CBCT clarified ambiguous angiographic findings and confirmed the existing treatment plan for 19 patients (47.5%) graded as Category 2; complex vascular anatomy was explained (n = 13), and a correlation between vascular territory and target lesion was established (n = 6). CBCT offered valuable information that was not visible on digital subtraction angiography and changed the treatment plan for 17 patients categorized as Category 3; a mismatch between the vascular territory and the target lesion led to the identification of alternative (n = 3) and additional feeders (n = 8); and the extent of embolization was reduced by using automatic feeder detection software (n = 6). CBCT is an efficient tool that aids in the decision-making process during the embolization procedure by providing supplementary imaging information. This additional information enables the confident identification of target vessels, facilitates superselective embolization, prevents non-target embolization, and helps locate missing feeders.

Correction: Ahn et al. Enzyme-Treated Zizania latifolia Ethanol Extract Improves Liver-Related Outcomes and Fatigability. Foods 2024, 13, 1725.

In the original publication [...].

Hybrid CMOS-Memristor synapse circuits for implementing Ca ion-based plasticity model.

Neuromorphic computing research is being actively pursued to address the challenges posed by the need for energy-efficient processing of big data. One of the promising approaches to tackle the challenges is the hardware implementation of spiking neural networks (SNNs) with bio-plausible learning rules. Numerous research works have been done to implement the SNN hardware with different synaptic plasticity rules to emulate human brain operations. While a standard spike-timing-dependent-plasticity (STDP) rule is emulated in many SNN hardware, the various STDP rules found in the biological brain have rarely been implemented in hardware. This study proposes a CMOS-memristor hybrid synapse circuit for the hardware implementation of a Ca ion-based plasticity model to emulate the various STDP curves. The memristor was adopted as a memory device in the CMOS synapse circuit because memristors have been identified as promising candidates for analog non-volatile memory devices in terms of energy efficiency and scalability. The circuit design was divided into four sub-blocks based on biological behavior, exploiting the non-volatile and analog state properties of memristors. The circuit was designed to vary weights using an H-bridge circuit structure and PWM modulation. The various STDP curves have been emulated in one CMOS-memristor hybrid circuit, and furthermore a simple neural network operation was demonstrated for associative learning such as Pavlovian conditioning. The proposed circuit is expected to facilitate large-scale operations for neuromorphic computing through its scale-up.

Recurrent fever of unknown origin and unexplained bacteremia in a patient with a novel 4.5 Mb microdeletion in Xp11.23-p11.22.

Fever of unknown origin (FUO) remains a formidable diagnostic challenge in the field of medicine. Numerous studies suggest an association between FUO and genetic factors, including chromosomal abnormalities. Here, we report a female patient with a 4.5 Mb Xp microdeletion, who presented with recurrent FUO, bacteremia, colitis, and hematochezia. To elucidate the underlying pathogenic mechanism, we employed a comprehensive approach involving single cell RNA sequencing, T cell receptor sequencing, and flow cytometry to evaluate CD4 T cells. Analysis of peripheral blood mononuclear cells revealed augmented Th1, Th2, and Th17 cell populations, and elevated levels of proinflammatory cytokines in serum. Notably, the patient exhibited impaired Treg cell function, possibly related to deletion of genes encoding FOPX3 and WAS. Single cell analysis revealed specific expansion of cytotoxic CD4 T lymphocytes, characterized by upregulation of various signature genes associated with cytotoxicity. Moreover, interferon-stimulated genes were upregulated in the CD4 T effector memory cluster. Further genetic analysis confirmed maternal inheritance of the Xp microdeletion. The patient and her mother exhibited X chromosome-skewed inactivation, a potential protective mechanism against extensive X chromosome deletions; however, the mother exhibited complete skewing and the patient exhibited incomplete skewing (85:15), which may have contributed to emergence of immunological symptoms. In summary, this case report describes an exceptional instance of FUO stemming from an incompletely inactivated X chromosome microdeletion, thereby increasing our understanding of the genetics underpinning FUO.

Bilateral Hemorrhagic Occlusive Retinal Vasculitis Induced by Osimertinib in a Patient with Non-Small Cell Lung Cancer.

PURPOSE: To report a case of bilateral retinal vasculitis in a patient with non-small cell lung cancer undergoing treatment with osimertinib. CASE REPORT: A 58-year-old woman with lung adenocarcinoma (T4N3M1a stage IV) presented with blurry vision in both eyes (OU). Eighteen months before symptom onset, the treatment was changed from afatinib (20 mg/day) to osimertinib (80 mg/day) because of tumor progression. The visual acuity was 20/30 and 20/25 in the right and left eyes, respectively. Clinical examination revealed few anterior chamber cells, 2+ vitreous cells, haze, and multiple retinal hemorrhages in the peripheral retinas (OU). Fluorescein angiography revealed retinal vasculitis with a severely non-perfused area in the periphery. These findings indicated hemorrhagic occlusive retinal vasculitis (HORV). Osimertinib was reduced to 40 mg/day, and oral prednisolone was started at 30 mg/day. This improved retinal vasculitis; however, the ischemic area did not improve. Pan-retinal photocoagulation was performed while tapering the oral prednisolone to 10 mg/day. Although macular edema (ME) occasionally occurred (OU), systemic and local treatment with steroid-stabilized HORV and ME helped increase the dose of osimertinib to 80 mg/day without cancer progression for 18 months. Her visual acuity remained 10/20 (OU). CONCLUSION: Osimertinib, a third-generation tyrosine kinase inhibitor, can be used to treat advanced non-small cell lung cancer with epidermal growth factor receptor mutation-induced bilateral HORV. This adverse effect can be managed with systemic and local steroid treatment and continued osimertinib administration.

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

BACKGROUND: This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). METHODS: Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). RESULTS: Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. CONCLUSIONS: Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

Ustekinumab was well-tolerated and safe for Koran patients with Crohn's disease with no new safety signal as induction and maintenance therapy. Biologic-naïve patients exhibited better effectiveness outcomes, whereas combination therapy with immunomodulators was not superior to ustekinumab monotherapy.

Detection and position evaluation of chest percutaneous drainage catheter on chest radiographs using deep learning.

PURPOSE: This study aimed to develop an algorithm for the automatic detecting chest percutaneous catheter drainage (PCD) and evaluating catheter positions on chest radiographs using deep learning. METHODS: This retrospective study included 1,217 chest radiographs (proper positioned: 937; malpositioned: 280) from a total of 960 patients underwent chest PCD from October 2017 to February 2023. The tip location of the chest PCD was annotated using bounding boxes and classified as proper positioned and malpositioned. The radiographs were randomly allocated into the training, validation sets (total: 1,094 radiographs; proper positioned: 853 radiographs; malpositioned: 241 radiographs), and test datasets (total: 123 radiographs; proper positioned: 84 radiographs; malpositioned: 39 radiographs). The selected AI model was used to detect the catheter tip of chest PCD and evaluate the catheter's position using the test dataset to distinguish between properly positioned and malpositioned cases. Its performance in detecting the catheter and assessing its position on chest radiographs was evaluated by per radiographs and per instances. The association between the position and function of the catheter during chest PCD was evaluated. RESULTS: In per chest radiographs, the selected model's accuracy was 0.88. The sensitivity and specificity were 0.86 and 0.92, respectively. In per instance, the selected model's the mean Average Precision 50 (mAP50) was 0.86. The precision and recall were 0.90 and 0.79 respectively. Regarding the association between the position and function of the catheter during chest PCD, its sensitivity and specificity were 0.93 and 0.95, respectively. CONCLUSION: The artificial intelligence model for the automatic detection and evaluation of catheter position during chest PCD on chest radiographs demonstrated acceptable diagnostic performance and could assist radiologists and clinicians in the early detection of catheter malposition and malfunction during chest percutaneous catheter drainage.

Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Impact of Hepatic Portal Venous Gas on the Prognosis of Traumatic Out-of-Hospital Cardiac Arrest: A Reason to Consider Terminating Cardiopulmonary Resuscitation.

Background: We evaluated the prognosis of traumatic out-of-hospital cardiac arrest (OHCA) by assessing the presence of hepatic portal vein gas (HPVG) observed in ultrasound (US) or point-of-care ultrasonography (POCUS) performed during CPR. Furthermore, we aimed to understand the role of HPVG in decision-making regarding CPR discontinuation or withholding in traumatic OHCA. Methods: The retrospective study was conducted at the level 1 trauma center of urban academic medical centers in South Korea. We included adult trauma OHCA patients who underwent CPR between January 1, 2020, and June 30, 2022. Data on traumatic OHCA patients who presented to the level I trauma center during this period were extracted from the hospital's electronic medical record system. The arrest data were separately managed through the hospital's electronic medical record system for quality control, specifically the arrest registry. US images or clips of the hepatic portal vasculature (HPV) during CPR were used to assess the presence of HPVG. These images were independently reviewed by two emergency medicine physicians with several years of US examination experience who were blinded to all clinical details and outcomes. We evaluated the prognosis of traumatic OHCA by assessing the presence of HPVG using the US. In addition, we analyzed the general characteristics and assessed the impact on the ROSC in traumatic OHCA. Results: Among the 383 cardiac arrest patients, 318 traumatic OHCA patients were included. The mean age was 54.9 ± 19.4 years, and most patients were male. The initial rhythm was mainly asystole, and falls were the most frequent cause of injury. The overall ROSC rate was 18.8%, with a survival rate of 7.2% at hospital discharge. Among the 50 patients who underwent a US examination of HPV, 40 showed HPVG. The HPVG group had a significantly lower ROSC rate and survival rate at ED discharge and hospital discharge compared to the group without HPVG. Conclusion: Traumatic OHCA with HPVG presents a significantly worse prognosis. This suggests that early consideration of termination or withholding of CPR may be appropriate in such cases.

The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial.

BACKGROUND: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. METHODS: Using a modified Dixon's up-and-down allocation approach, we sequentially enrolled male and female patients aged 19-60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer's Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. RESULTS: We included 22 male and 22 female patients. Based on Dixon's up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18-0.20) mg/kg in the male group and 0.29 (0.29-0.30) mg/kg in the female group. CONCLUSIONS: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. TRIAL REGISTRATION: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022).

Exposure to per- and polyfluoroalkyl substances and age-related macular degeneration in U.S. middle-aged and older adults.

Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005-2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend = 0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.

Improving prediction of linear regression models by integrating external information from heterogeneous populations: James-Stein estimators.

We consider the setting where (1) an internal study builds a linear regression model for prediction based on individual-level data, (2) some external studies have fitted similar linear regression models that use only subsets of the covariates and provide coefficient estimates for the reduced models without individual-level data, and (3) there is heterogeneity across these study populations. The goal is to integrate the external model summary information into fitting the internal model to improve prediction accuracy. We adapt the James-Stein shrinkage method to propose estimators that are no worse and are oftentimes better in the prediction mean squared error after information integration, regardless of the degree of study population heterogeneity. We conduct comprehensive simulation studies to investigate the numerical performance of the proposed estimators. We also apply the method to enhance a prediction model for patella bone lead level in terms of blood lead level and other covariates by integrating summary information from published literature.

Machine learning-assisted label-free colorectal cancer diagnosis using plasmonic needle-endoscopy system.

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future.

Real-Time Tunable Gas Sensing Platform Based on SnO2 Nanoparticles Activated by Blue Micro-Light-Emitting Diodes.

Micro-light-emitting diodes (µLEDs) have gained significant interest as an activation source for gas sensors owing to their advantages, including room temperature operation and low power consumption. However, despite these benefits, challenges still exist such as a limited range of detectable gases and slow response. In this study, we present a blue µLED-integrated light-activated gas sensor array based on SnO2 nanoparticles (NPs) that exhibit excellent sensitivity, tunable selectivity, and rapid detection with micro-watt level power consumption. The optimal power for µLED is observed at the highest gas response, supported by finite-difference time-domain simulation. Additionally, we first report the visible light-activated selective detection of reducing gases using noble metal-decorated SnO2 NPs. The noble metals induce catalytic interaction with reducing gases, clearly distinguishing NH3, H2, and C2H5OH. Real-time gas monitoring based on a fully hardware-implemented light-activated sensing array was demonstrated, opening up new avenues for advancements in light-activated electronic nose technologies.

Host cell-specific metabolism of linoleic acid controls Toxoplasma gondii growth in cell culture.

The obligate intracellular parasite Toxoplasma gondii can infect and replicate in any warm-blooded cell tested to date, but much of our knowledge about T. gondii cell biology comes from just one host cell type: human foreskin fibroblasts (HFFs). To expand our knowledge of host-parasite lipid interactions, we studied T. gondii in intestinal epithelial cells, the first site of host-parasite contact following oral infection and the exclusive site of parasite sexual development in feline hosts. We found that highly metabolic Caco-2 cells are permissive to T. gondii growth even when treated with high levels of linoleic acid (LA), a polyunsaturated fatty acid (PUFA) that kills parasites in HFFs. Caco-2 cells appear to sequester LA away from the parasite, preventing membrane disruptions and lipotoxicity that characterize LA-induced parasite death in HFFs. Our work is an important step toward understanding host-parasite interactions in feline intestinal epithelial cells, an understudied but important cell type in the T. gondii life cycle.

IL-28A/IL-10Rß axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression.

INTRODUCTION: Angiogenesis plays a significant role in the development of tumor progression and inflammatory diseases. The role of IL-28A in angiogenesis and its precise regulatory mechanisms remain rarely elucidated. OBJECTIVES: We report the novel regulatory role of IL-28A in physiological angiogenesis. The study aimed to elucidate the regulatory mechanisms involved in IL-28A-mediated angiogenesis and identify key genes associated with IL-28A-induced angiogenic responses. METHODS: To know the effect of IL-28A on angiogenesis, HUVECs were applied to perform proliferation, migration, invasion, tube formation, immunoblot, and EMSA. Gene expression changes in HUVECs following IL-28A treatment were analyzed by NGS. The functional role of HSP70-1 and IL-10Rß in IL-28A-induced angiogenic responses was evaluated using PCR and siRNA knockdown. Animal studies were conducted by aortic ring ex vivo assays, Matrigel plug in vivo assays, and immunochemistry using HSP70-1 knockout and transgenic mice models. The efficacy of IL-28A in angiogenesis was confirmed in a hind-limb ischemia model. RESULTS: Autocrine/paracrine actions in HUVECs regulated IL-28A protein expression. Exogenous IL-28A increased the proliferation of HUVECs via eNOS/AKT and ERK1/2 signaling. IL-28A treatment promoted migration, invasion, and capillary tube formation of HUVECs through induction of the AP-1/NF-κB/MMP-2 network, which was associated with eNOS/AKT and ERK1/2 signaling. The efficacy of IL-28A-induced angiogenic potential was confirmed by aortic ring and Matrigel plug assay. HSP70-1 was identified as an IL-28A-mediated angiogenic effector gene using bioinformatics. Knockdown of HSP70-1 abolished angiogenic responses and eNOS/AKT signaling in IL-28A-treated HUVECs. IL-28A-induced microvessel sprouting formation was testified in HSP70-1-deficient and HSP70-1 transgenic mice. Flow recovery in hind-limb ischemia mice was accelerated by IL-28A injection. Finally, ablation of the IL-10Rß gene impeded the angiogenic responses and eNOS/AKT signaling stimulated by IL-28A in HUVECs. CONCLUSION: HSP70-1 drives the progression of angiogenesis by the IL-28A/IL-10Rß axis via eNOS/AKT signaling and the AP-1/NF-κB/MMP-2 network.

TF-EPI: an interpretable enhancer-promoter interaction detection method based on Transformer.

The detection of enhancer-promoter interactions (EPIs) is crucial for understanding gene expression regulation, disease mechanisms, and more. In this study, we developed TF-EPI, a deep learning model based on Transformer designed to detect these interactions solely from DNA sequences. The performance of TF-EPI surpassed that of other state-of-the-art methods on multiple benchmark datasets. Importantly, by utilizing the attention mechanism of the Transformer, we identified distinct cell type-specific motifs and sequences in enhancers and promoters, which were validated against databases such as JASPAR and UniBind, highlighting the potential of our method in discovering new biological insights. Moreover, our analysis of the transcription factors (TFs) corresponding to these motifs and short sequence pairs revealed the heterogeneity and commonality of gene regulatory mechanisms and demonstrated the ability to identify TFs relevant to the source information of the cell line. Finally, the introduction of transfer learning can mitigate the challenges posed by cell type-specific gene regulation, yielding enhanced accuracy in cross-cell line EPI detection. Overall, our work unveils important sequence information for the investigation of enhancer-promoter pairs based on the attention mechanism of the Transformer, providing an important milestone in the investigation of cis-regulatory grammar.

Microbial Dynamics and Metabolite Profiles in Different Types of Salted Seafood (Jeotgal) During Fermentation.

Salted and fermented seafood (jeotgal) is known for its long shelf life and unique flavor. Despite the existence of various types of salted seafood, the factors influencing this quality have yet to be identified. These factors are essential for improving the quality of salted seafood, optimizing the fermentation process, and advancing the industrialization of fermented foods. Therefore, in this study, we explored microbial dynamics and changes in quality characteristics in three salted seafood items - salted anchovies (MJ), salted cutlass offal (GJ), and salted croakers (HJ), over a 24-month fermentation period. Distinct microbial community profiles, dominated by Tetragenococcus halophilus, Halanaerobium fermentans, and Chromohalobacter canadensis in MJ, GJ, and HJ, respectively, affect the metabolic pathways and the corresponding flavor profiles. The pH of all samples ranged from 5.7-6.0. The titratable acidity was highest in MJ at 1.4% and lowest in HJ at approximately 0.7%. Salinity was below 25% in all samples but slightly lower in MJ. Significant differences were observed in the amino acid, nucleotide, and overall metabolite profiles. MJ exhibited the highest amino acid and nitrogen-related factor levels, such as glutamic acid and hypoxanthine, enhancing flavor complexity. Correlation analysis revealed significant associations among the types, metabolites, and microbial communities. Microbial survival mechanisms in high-salt environments result in the production of unique metabolites, including umami and aroma components as well as precursors of biogenic amines, which can affect the overall quality of the final product. These differences were primarily influenced by the fish type rather than the fermentation time. Our findings provide foundational insights for enhancing fermentation strategies, improving product consistency, and advancing the industrial application of microbial management in seafood fermentation. This study not only fills a significant gap in the current understanding of fermented seafood but also outlines practical approaches for industry applications for the optimization of product quality.

The Extract of Humulus japonicus Inhibits Lipogenesis and Promotes Lipolysis via PKA/p38 Signaling.

INTRODUCTION: Previous research has shown that an aqueous extract of Humulus japonicus (EH) can ameliorate hypertension, nonalcoholic fatty liver disease, and oxidative stress in adipocytes by activating the thermogenic pathway. However, the effects of an ethanol (30%) extract of EH on obesity are unknown. METHODS: Various protein expression levels in fully differentiated 3T3-L1 adipocytes were assessed by Western blotting. Lipid deposition in 3T3-L1 adipocytes was examined by oil red O staining. The MTT assay was used to evaluate adipocyte viability. Caspase 3 activity and glycerol release were determined using commercial assay kits. RESULTS: In this study, we discovered that EH treatment inhibited lipogenesis and promoted lipolysis in both differentiated 3T3-L1 adipocytes and adipose tissue of mice fed a high-fat diet. EH treatment also increased phosphorylated protein kinase A (PKA) levels while reducing p38 phosphorylation. When H89, a PKA inhibitor, was used, the effects of EH on lipogenic lipid accumulation and lipolysis in 3T3-L1 adipocytes were eliminated. Treatment with luteolin 7-O-ß-d-glucoside (LU), the major active compound in EH, also suppressed lipid deposition and p38 phosphorylation but enhanced lipolysis in 3T3-L1 adipocytes. These changes were abrogated by H89. CONCLUSION: These findings indicate that EH containing LU reduces lipogenesis and stimulates lipolysis via the PKA/p38 signaling pathway, leading to an improvement in obesity in mice. Therefore, our study suggested that EH could be a promising therapeutic agent for treating obesity.

Diagnostic accuracy and predictors of alpha-synuclein accumulation in the gastrointestinal tract of Parkinson's disease.

The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.