A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction.

Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis upon metabolic demands. Detection of these contact sites at the nanometer scale over time in living cells is challenging. We developed a tool kit for detecting contact sites based on fluorogen-activated bimolecular complementation at CONtact sites, FABCON, using a reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic regulation.

Developing an explainable diagnosis system utilizing deep learning model: a case study of spontaneous pneumothorax.

OBJECTIVE: The trend in the medical field is towards intelligent detection-based medical diagnostic systems. However, these methods are often seen as "black boxes" due to their lack of interpretability. This situation presents challenges in identifying reasons for misdiagnoses and improving accuracy, which leads to potential risks of misdiagnosis and delayed treatment. Therefore, how to enhance the interpretability of diagnostic models is crucial for improving patient outcomes and reducing treatment delays. So far, only limited researches exist on deep learning-based prediction of spontaneous pneumothorax, a pulmonary disease that affects lung ventilation and venous return. Approach. This study develops an integrated medical image analysis system using explainable deep learning model for image recognition and visualization to achieve an interpretable automatic diagnosis process. Main results. The system achieves an impressive 95.56% accuracy in pneumothorax classification, which emphasizes the significance of the blood vessel penetration defect in clinical judgment. Significance. This would lead to improve model trustworthiness, reduce uncertainty, and accurate diagnosis of various lung diseases, which results in better medical outcomes for patients and better utilization of medical resources. Future research can focus on implementing new deep learning models to detect and diagnose other lung diseases that can enhance the generalizability of this system. .

Infrared and Visible Image Fusion Algorithm Based on Double-Domain Transform Filter and Contrast Transform Feature Extraction.

Current challenges in visible and infrared image fusion include color information distortion, texture detail loss, and target edge blur. To address these issues, a fusion algorithm based on double-domain transform filter and nonlinear contrast transform feature extraction (DDCTFuse) is proposed. First, for the problem of incomplete detail extraction that exists in the traditional transform domain image decomposition, an adaptive high-pass filter is proposed to decompose images into high-frequency and low-frequency portions. Second, in order to address the issue of fuzzy fusion target caused by contrast loss during the fusion process, a novel feature extraction algorithm is devised based on a novel nonlinear transform function. Finally, the fusion results are optimized and color-corrected by our proposed spatial-domain logical filter, in order to solve the color loss and edge blur generated in the fusion process. To validate the benefits of the proposed algorithm, nine classical algorithms are compared on the LLVIP, MSRS, INO, and Roadscene datasets. The results of these experiments indicate that the proposed fusion algorithm exhibits distinct targets, provides comprehensive scene information, and offers significant image contrast.

Fe-Doped g-C3N4/Bi2MoO6 Heterostructured Composition with Improved Visible Photocatalytic Activity for Rhodamine B Degradation.

The binary heterostructured semiconducting visible light photocatalyst of the iron-doped graphitic carbon nitride/bismuth molybdate (Fe-g-C3N4/Bi2MoO6) composite was prepared by coupling with Fe-doped g-C3N4 and Bi2MoO6 particles. In the present study, a comparison of structural characteristics, optical properties, and photocatalytic degradation efficiency and activity between Fe-doped g-C3N4 particles, Bi2MoO6 particles, and Fe-g-C3N4/Bi2MoO6 composite was investigated. The results of X-ray diffraction (XRD) examination indicate that the hydrothermal Bi2MoO6 particles have a single orthorhombic phase and Fourier transform infrared (FTIR) spectroscopy analysis confirms the formation of Fe-doped g-C3N4. The optical bandgaps of the Fe-doped g-C3N4 and Bi2MoO6 particles are 2.74 and 2.73 eV, respectively, as estimated from the Taut plots obtained from UV-Vis diffuse reflectance spectroscopy (DRS) spectra. This characteristic indicates that the two semiconductor materials are suitable for absorbing visible light. The transmission electron microscopy (TEM) micrograph reveals the formation of the heterojunction Fe-g-C3N4/Bi2MoO6 composite. The results of photocatalytic degradation revealed that the developed Fe-g-C3N4/Bi2MoO6 composite photocatalyst exhibited significantly better photodegradation performance than the other two single semiconductor photocatalysts. This property can be attributed to the heterostructured nanostructure, which could effectively prevent the recombination of photogenerated carriers (electron-hole pairs) and enhance photocatalytic activity. Furthermore, cycling test showed that the Fe-g-C3N4/Bi2MoO6 heterostructured photocatalyst exhibited good reproducibility and stability for organic dye photodegradation.

Photoacoustic method for measuring the elasticity of polydimethylsiloxane at various mixing ratios.

Measuring elasticity without physical contact is challenging, as current methods often require deconstruction of the test sample. This study addresses this challenge by proposing and testing a photoacoustic effect-based method for measuring the elasticity of polydimethylsiloxane (PDMS) at various mixing ratios, which may be applied on the wide range of applications such as biomedical and optical fields. A dual-light laser source of the photoacoustic (PA) system is designed, employing cross-correlation signal processing techniques. The platform systems and a mathematical model for performing PDMS elasticity measurements are constructed. During elasticity detection, photoacoustic signal features, influenced by hardness and shapes, are analyzed using cross-correlation calculations and phase difference detection. Results from phantom tests demonstrate the potential of predicting Young's modulus using the cross-correlation method, aligning with the American Society for Testing and Materials (ASTM) standard samples. However, accuracy may be affected by mixed materials and short tubes. Normalization or calibration of signals is suggested for aligning with Young's coefficient.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

SSVEP-DAN: Cross-Domain Data Alignment for SSVEP-Based Brain-Computer Interfaces.

Steady-state visual-evoked potential (SSVEP)-based brain-computer interfaces (BCIs) offer a non-invasive means of communication through high-speed speller systems. However, their efficiency is highly dependent on individual training data acquired during time-consuming calibration sessions. To address the challenge of data insufficiency in SSVEP-based BCIs, we introduce SSVEP-DAN, the first dedicated neural network model designed to align SSVEP data across different domains, encompassing various sessions, subjects, or devices. Our experimental results demonstrate the ability of SSVEP-DAN to transform existing source SSVEP data into supplementary calibration data. This results in a significant improvement in SSVEP decoding accuracy while reducing the calibration time. We envision SSVEP-DAN playing a crucial role in future applications of high-performance SSVEP-based BCIs. The source code for this work is available at: https://github.com/CECNL/SSVEP-DAN.

Noninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration.

Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain's visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Proline Isomerization and Molten Globular Property of TgPDCD5 Secreted from Toxoplasma gondii Confers Its Regulation of Heparin Sulfate Binding.

Toxoplasmosis, caused by Toxoplasma gondii, poses risks to vulnerable populations. TgPDCD5, a secreted protein of T. gondii, induces apoptosis through heparan sulfate-mediated endocytosis. The entry mechanism of TgPDCD5 has remained elusive. Here, we present the solution structure of TgPDCD5 as a helical bundle with an extended N-terminal helix, exhibiting molten globule characteristics. NMR perturbation studies reveal heparin/heparan sulfate binding involving the heparan sulfate/heparin proteoglycans-binding motif and the core region, influenced by proline isomerization of P107 residue. The heterogeneous proline recruits a cyclophilin TgCyp18, accelerating interconversion between conformers and regulating heparan/heparin binding. These atomic-level insights elucidate the binary switch's functionality, expose novel heparan sulfate-binding surfaces, and illuminate the unconventional cellular entry of pathogenic TgPDCD5.

Aibika Flower Flavonoid Extract Exhibits Antiulcer Activity in a Murine Model of Ethanol-Induced Acute Gastric Injury.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1ß, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

Unveiling novel LRP5 pathogenic variant in familial exudative vitreoretinopathy: Diverse phenotypic expressions in a mother-daughter duo.

PURPOSE: This report aims to delineate distinct phenotypes of Familial Exudative Vitreoretinopathy (FEVR) observed in a mother and her daughter, both harboring a novel LRP5 pathogenic variation. METHODS: The investigation involves a retrospective review of medical records accompanied by multimodal imaging. Molecular characterization was performed using whole exon sequencing, and the pathogenic variant was subsequently confirmed through Sanger sequencing. RESULT: A 6-year-old girl diagnosed with anisometropic amblyopia exhibited macular dragging and peripheral avascular retina in her right eye. Whole exon sequencing identified a previously unreported heterozygous missense LRP5 pathogenic variation, Glu528Lys. Simultaneously, her 43-year-old mother also carried the same mutation, manifesting peripheral exudations, avascular areas, and multiple microaneurysms. Notably, both cases presented distinctive phenotypes of FEVR. CONCLUSION: Our findings underscore the diversity in clinical presentations associated with FEVR, emphasizing the pivotal role of genetic evaluation. Despite variations in severity between the eyes of the same patient, it is crucial to remain vigilant for potential progression to a pathological status in the seemingly normal eye. Additionally, this study contributes to expanding the genetic spectrum of FEVR.

Geographic and psychosocial correlates of homelessness or unstable housing among US veterans in the Midwest.

The purpose of this study was to explore (1) the prevalence of physical and mental health conditions among veterans stratified by homelessness and unstable housing (HUH) in several Midwestern states, and (2) the correlation between HUH and sociodemographic, military, financial, risky behavior, health, and geographical characteristics. The study cohort consisted of 7260 HUH veterans and stably housed veterans in 2018-2022 in Veterans Integrated Service Network (VISN) 23. A multivariate logistic regression analysis was performed which revealed the strongest associations with HUH were any incarceration experience (adjusted odds ratio [AOR] = 0.21) and rural location (AOR = 0.33). Frontier and remote location scores (AOR = 1.23) were associated with increased risk of HUH among veterans. Our results suggest potential differences in risk for HUH among veterans living in rural versus frontier and remote locations, which may be important to consider to provide care to the many veterans in these areas.

Abietane Diterpenoids from the Bark of Cryptomeria japonica and Their Antifungal Activities against Wood Decay Fungi.

Phytochemical investigation of the bark of Cryptomeria japonica led to the isolation of five new abietane diterpenoids, 5-epi-12-hydroxy-6-nor-5,6-secoabieta-8,11,13-trien-7,5-olide (1), 12-hydroxy-6ß-methoxy-6,7-secoabieta-8,11,13-trien-7,6-olide (2), 6ß,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (4), 5,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (5), and 5α,8-epoxy-12-hydroxy-7,8-secoabieta-8,11,13-trien-7-al (6), together with one known abietane diterpenoid, obtuanhydride (3). Their structures were elucidated by analysis of spectroscopic data and comparison with the spectral data of known analogs. At the concentration of 100 µg/mL, compounds 4, 5, and 6 inhibited antifungal activities against wood decay fungi activity by 18.7, 37.2, and 46.7%, respectively.

Radiographic chest wall abnormalities in primary spontaneous pneumothorax identified by artificial intelligence.

Primary spontaneous pneumothorax (PSP) primarily affects slim and tall young males. Exploring the etiological link between chest wall structural characteristics and PSP is crucial for advancing treatment methods. In this case-control study, chest computed tomography (CT) images from patients undergoing thoracic surgery, with or without PSP, were analyzed using Artificial Intelligence. Convolutional Neural Network (CNN) model of EfficientNetB3 and InceptionV3 were used with transfer learning on the Imagenet to compare the images of both groups. A heatmap was created on the chest CT scans to enhance interoperability, and the scale-invariant feature transform (SIFT) was adopted to further compare the image level. A total of 2,312 CT images of 26 non-PSP patients and 1,122 CT images of 26 PSP patients were selected. Chest-wall apex pit (CAP) was found in 25 PSP and three non-PSP patients (p < 0.001). The CNN achieved a testing accuracy of 93.47 % in distinguishing PSP from non-PSP based on chest wall features by identifying the existence of CAP. Heatmap analysis demonstrated CNN's precision in targeting the upper chest wall, accurately identifying CAP without undue influence from similar structures, or inappropriately expanding or minimizing the test area. SIFT results indicated a 10.55 % higher mean similarity within the groups compared to between PSP and non-PSP (p < 0.001). In conclusion, distinctive radiographic chest wall configurations were observed in PSP patients, with CAP potentially serving as an etiological factor linked to PSP. This study accentuates the potential of AI-assisted analysis in refining diagnostic approaches and treatment strategies for PSP.

Necessary for seizure forecasting outcome metrics: seizure frequency and benchmark model.

Work is ongoing to advance seizure forecasting, but the performance metrics used to evaluate model effectiveness can sometimes lead to misleading outcomes. For example, some metrics improve when tested on patients with a particular range of seizure frequencies (SF). This study illustrates the connection between SF and metrics. Additionally, we compared benchmarks for testing performance: a moving average (MA) or the commonly used permutation benchmark. Three data sets were used for the evaluations: (1) Self-reported seizure diaries of 3,994 Seizure Tracker patients; (2) Automatically detected (and sometimes manually reported or edited) generalized tonic-clonic seizures from 2,350 Empatica Embrace 2 and Mate App seizure diary users, and (3) Simulated datasets with varying SFs. Metrics of calibration and discrimination were computed for each dataset, comparing MA and permutation performance across SF values. Most metrics were found to depend on SF. The MA model outperformed or matched the permutation model in all cases. The findings highlight SF's role in seizure forecasting accuracy and the MA model's suitability as a benchmark. This underscores the need for considering patient SF in forecasting studies and suggests the MA model may provide a better standard for evaluating future seizure forecasting models.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Intrinsically Stretchable Organic Thermoelectric Polymers Enabled by Incorporating Fused-Ring Conjugated Breakers.

While research on organic thermoelectric polymers is making significant progress in recent years, realization of a single polymer material possessing both thermoelectric properties and stretchability for the next generation of self-powered wearable electronics is a challenging task and remains an area yet to be explored. A new molecular engineering concept of "conjugated breaker" is employed to impart stretchability to a highly crystalline diketopyrrolepyrrole (DPP)-based polymer. A hexacyclic diindenothieno[2,3-b]thiophene (DITT) unit, with two 4-octyloxyphenyl groups substituted at the tetrahedral sp3-carbon bridges, is selected to function as the conjugated breaker that can sterically hinder intermolecular packing to reduce polymers' crystallinity. A series of donor-acceptor random copolymers is thus developed via polymerizing the crystalline DPP units with the DITT conjugated breakers. By controlling the monomeric DPP/DITT ratios, DITT30 reaches the optimal balance of crystalline/amorphous regions, exhibiting an exceptional power factor (PF) value up to 12.5 µW m-1 K-2 after FeCl3-doping; while, simultaneously displaying the capability to withstand strains exceeding 100%. More significantly, the doped DITT30 film possesses excellent mechanical endurance, retaining 80% of its initial PF value after 200 cycles of stretching/releasing at a strain of 50%. This research marks a pioneering achievement in creating intrinsically stretchable polymers with exceptional thermoelectric properties.

Large Language Model Performance on Practice Epilepsy Board Examinations.

This diagnostic study examines whether large language models are able to pass practice licensing examinations for epilepsy.

Subgroups of pelvic pain are differentially associated with endometriosis and inflammatory comorbidities: a latent class analysis.

ABSTRACT: Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence to Adulthood (A2A) cohort. Six participant characteristics were included in the LCA: severity, frequency, and impact on daily activities of both menstruation-associated (cyclic) and non-menstruation-associated (acyclic) pelvic pain. Three-step LCA quantified associations between LC subgroups, demographic and clinical variables, and 18 comorbidities (10 with prevalence ≥10%). Five subgroups were identified: none or minimal (23%), moderate cyclic only (28%), severe cyclic only (20%), moderate or severe acyclic plus moderate cyclic (9%), and severe acyclic plus severe cyclic (21%). Endometriosis prevalence within these 5 LCA-pelvic pain-defined subgroups ranged in size from 4% in "none or minimal pelvic pain" to 24%, 72%, 70%, and 94%, respectively, in the 4 pain subgroups, with statistically significant odds of membership only for the latter 3 subgroups. Migraines were associated with significant odds of membership in all 4 pelvic pain subgroups relative to those with no pelvic pain (adjusted odds ratios = 2.92-7.78), whereas back, joint, or leg pain each had significantly greater odds of membership in the latter 3 subgroups. Asthma or allergies had three times the odds of membership in the most severe pain group. Subgroups with elevated levels of cyclic or acyclic pain are associated with greater frequency of chronic overlapping pain conditions, suggesting an important role for central inflammatory and immunological mechanisms.