Helical polymers for dissymmetric circularly polarized light imaging.

Control of the spin angular momentum (SAM) carried in a photon provides a technologically attractive element for next-generation quantum networks and spintronics1-5. However, the weak optical activity and inhomogeneity of thin films from chiral molecular crystals result in high noise and uncertainty in SAM detection. Brittleness of thin molecular crystals represents a further problem for device integration and practical realization of chiroptical quantum devices6-10. Despite considerable successes with highly dissymmetric optical materials based on chiral nanostructures11-13, the problem of integration of nanochiral materials with optical device platforms remains acute14-16. Here we report a simple yet powerful method to fabricate chiroptical flexible layers via supramolecular helical ordering of conjugated polymer chains. Their multiscale chirality and optical activity can be varied across the broad spectral range by chiral templating with volatile enantiomers. After template removal, chromophores remain stacked in one-dimensional helical nanofibrils producing a homogeneous chiroptical layer with drastically enhanced polarization-dependent absorbance, leading to well-resolved detection and visualization of SAM. This study provides a direct path to scalable realization of on-chip detection of the spin degree of freedom of photons necessary for encoded quantum information processing and high-resolution polarization imaging.

Systematic modeling-driven experiments identify distinct molecular clockworks underlying hierarchically organized pacemaker neurons.

In metazoan organisms, circadian (∼24 h) rhythms are regulated by pacemaker neurons organized in a master-slave hierarchy. Although it is widely accepted that master pacemakers and slave oscillators generate rhythms via an identical negative feedback loop of transcription factor CLOCK (CLK) and repressor PERIOD (PER), their different roles imply heterogeneity in their molecular clockworks. Indeed, in Drosophila, defective binding between CLK and PER disrupts molecular rhythms in the master pacemakers, small ventral lateral neurons (sLNvs), but not in the slave oscillator, posterior dorsal neuron 1s (DN1ps). Here, we develop a systematic and expandable approach that unbiasedly searches the source of the heterogeneity in molecular clockworks from time-series data. In combination with in vivo experiments, we find that sLNvs exhibit higher synthesis and turnover of PER and lower CLK levels than DN1ps. Importantly, light shift analysis reveals that due to such a distinct molecular clockwork, sLNvs can obtain paradoxical characteristics as the master pacemaker, generating strong rhythms that are also flexibly adjustable to environmental changes. Our results identify the different characteristics of molecular clockworks of pacemaker neurons that underlie hierarchical multi-oscillator structure to ensure the rhythmic fitness of the organism.

Identification of schizophrenia by applying interpretable radiomics modeling with structural magnetic resonance imaging of the cerebellum.

AIMS: The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum. METHODS: A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1-MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability. RESULTS: We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82-0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second-order size zone non-uniformity feature from the right lobule IX and first-order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia. CONCLUSION: The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease-defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker-based decision-making in clinical practice.

Factors Affecting Adherence to National Colorectal Cancer Screening: A 12-Year Longitudinal Study Using Multi-Institutional Pooled Data in Korea.

BACKGROUND: Consistent uptake of colorectal cancer (CRC) screening is important to reduce the incidence and mortality from advanced-stage CRC and increase the survival rate of the patients. We conducted a longitudinal study to determine the factors affecting CRC screening compliance in Korean adults using individual-level linked data from the Korean National Health and Nutrition Examination Survey, Korean National Health Insurance Service, and Korean Health Insurance Review and Assessment Service. METHODS: We selected 3,464 adults aged 50-79 years as the study population and followed them for 12 years (January 2007-December 2018). The outcome variable was the level of adherence to CRC screening, categorized as nonadherent, intermittently adherent, and consistently adherent. An ordinal logistic regression model was designed to determine the socioeconomic factors, family history of CRC, and medical conditions that could facilitate the consistent uptake of CRC screening. RESULTS: The results showed a significant and positive association between consistent uptake of CRC screening and the 100-150% income category (odds ratio [OR], 1.710; 95% confidence interval [CI], 1.401-2.088); clerical, sales and service job category (OR, 1.962; 95% CI, 1.582-2.433); residency at medium-sized cities (OR, 1.295; 95% CI, 1.094-1.532); high-school graduation (OR, 1.440; 95% CI, 1.210-1.713); married status (OR, 2.281; 95% CI, 1.946-2.674); use of employment-based national health insurance (OR, 1.820; 95% CI, 1.261-2.626); use of private insurance (OR, 2.259; 95% CI, 1.970-2.589); no disability (OR, 1.428; 95% CI, 1.175-1.737); family history of CRC (OR, 2.027; 95% CI, 1.514-2.714); and history of colorectal neoplasm (OR, 1.216; 95% CI; 1.039-1.422). CONCLUSION: The lack of regular participation in CRC screening programs in the Republic of Korea was found to be an issue that requires attention. Policies on CRC screening must place increased emphasis on strengthening educational and public relations initiatives.

Synergistic Anti-Inflammatory Activity of Lipid-Free Apolipoprotein (apo) A-I and CIGB-258 in Acute-Phase Zebrafish via Stabilization of the apoA-I Structure to Enhance Anti-Glycation and Antioxidant Activities.

CIGB-258, a 3 kDa peptide from heat shock protein 60, exhibits synergistic anti-inflammatory activity with apolipoprotein A-I (apoA-I) in reconstituted high-density lipoproteins (rHDLs) via stabilization of the rHDL structure. This study explored the interactions between CIGB-258 and apoA-I in the lipid-free state to assess their synergistic effects in the structural and functional enhancement of apoA-I and HDL. A co-treatment of lipid-free apoA-I and CIGB-258 inhibited the cupric ion-mediated oxidation of low-density lipoprotein (LDL) and a lowering of oxidized species in the dose-responsive manner of CIGB-258. The co-presence of CIGB-258 caused a blue shift in the wavelength of maximum fluorescence (WMF) of apoA-I with protection from proteolytic degradation. The addition of apoA-I:CIGB-258, with a molar ratio of 1:0.1, 1:0.5, and 1:1, to HDL2 and HDL3 remarkably enhanced the antioxidant ability against LDL oxidation up to two-fold higher than HDL alone. HDL-associated paraoxonase activities were elevated up to 28% by the co-addition of apoA-I and CIGB-258, which is linked to the suppression of Cu2+-mediated HDL oxidation with the slowest electromobility. Isothermal denaturation by a urea treatment showed that the co-presence of CIGB-258 attenuated the exposure of intrinsic tryptophan (Trp) and increased the mid-points of denaturation from 2.33 M for apoA-I alone to 2.57 M for an apoA-I:CIGB-258 mixture with a molar ratio of 1:0.5. The addition of CIGB-258 to apoA-I protected the carboxymethyllysine (CML)-facilitated glycation of apoA-I with the prevention of Trp exposure. A co-treatment of apoA-I and CIGB-258 synergistically safeguarded zebrafish embryos from acute death by CML-toxicity, suppressing oxidative stress and apoptosis. In adult zebrafish, the co-treatment of apoA-I+CIGB-258 exerted the highest anti-inflammatory activity with a higher recovery of swimming ability and survivability than apoA-I alone or CIGB-258 alone. A co-injection of apoA-I and CIGB-258 led to the lowest infiltration of neutrophils and interleukin (IL)-6 generation in hepatic tissue, with the lowest serum triglyceride, aspartate transaminase, and alanine transaminase levels in plasma. In conclusion, the co-presence of CIGB-258 ameliorated the beneficial functionalities of apoA-I, such as antioxidant and anti-glycation activities, by enhancing the structural stabilization and protection of apoA-I. The combination of apoA-I and CIGB-258 synergistically enforced the anti-inflammatory effect against CML toxicity in embryos and adult zebrafish.

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

Altered DNA Methylation of the Serotonin Transporter Gene Associated with Early Life Stress and White Matter Microalterations in Korean Patients with Panic Disorder.

INTRODUCTION: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. METHODS: The participants comprised 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five cytosine-phosphate-guanine (CpG) sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. RESULTS: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. In patients with PD, the DNA methylation levels at 5-HTTLPR 5 CpG sites showed significant negative association with the parental separation-related psychological distress, and positive correlations with the fractional anisotropy values of the superior longitudinal fasciculus (SLF) which might be related to trait anxiety. CONCLUSION: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased white matter integrity in the SLF region in PD. Decreased white matter connectivity in the SLF might be related to trait anxiety and is vital to the pathophysiology of PD.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

AIMS: We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. METHODS: Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. RESULTS: The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. CONCLUSION: Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Epigenetic Regulation of the Expression of T Cell Stimulatory and Inhibitory Factors by Histone H3 Lysine Modification Enzymes and Its Prognostic Roles in Glioblastoma.

BACKGROUND: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific co-stimulatory and co-inhibitory factors were investigated. METHODS: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed. Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. RESULTS: The mean follow-up duration was 27.5 months (range, 4.1-43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3-20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = -1.746) and those of PD-L1 and EZH1 (R2 linear = -2.118); these relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. CONCLUSION: These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.

Design, Synthesis, and Biological Evaluation of 3-Substituted-Indolin-2-One Derivatives as Potent Anti-Inflammatory Agents.

This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research.

Enhanced Intervertebral Disc Repair via Genetically Engineered Mesenchymal Stem Cells with Tetracycline Regulatory System.

The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific cytokines and proteins. This study aimed to investigate the therapeutic potential of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells (ToMSC-Tetoff-TGFß1-IGF1-BMP7) for treating intervertebral disc (IVD) degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene editing. Transgene expression was confirmed through immunofluorescence, western blots, and an enzyme-linked immunosorbent assay for transforming growth factor beta 1 (TGFß1) protein secretion, and the effect of MSC-TetOff-TGFß1-IGF1-BMP7 on disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFß1-IGF1-BMP7 treatment exhibited superior therapeutic effects compared to ToMSC-TGFß1, and ToMSC-SDF1α implantation groups, stimulating the regeneration of nucleus pulposus (NP) cells crucial for IVD. The treatment showed potential to restore the structural integrity of the extracellular matrix (ECM) by upregulating key molecules such as aggrecan and type II collagen. It also exhibited anti-inflammatory properties and reduced pain-inducing neuropeptides. ToMSC-Tetoff-TGFß1-IGF1-BMP7 holds promise as a novel treatment for IVD degeneration. It appears to promote NP cell regeneration, restore ECM structure, suppress inflammation, and reduce pain. However, more research and clinical trials are required to confirm its therapeutic potential.

Molecular origins of reduced activity and binding commitment of processive cellulases and associated carbohydrate-binding proteins to cellulose III.

Efficient enzymatic saccharification of cellulosic biomass into fermentable sugars can enable production of bioproducts like ethanol. Native crystalline cellulose, or cellulose I, is inefficiently processed via enzymatic hydrolysis but can be converted into the structurally distinct cellulose III allomorph that is processed via cellulase cocktails derived from Trichoderma reesei up to 20-fold faster. However, characterization of individual cellulases from T. reesei, like the processive exocellulase Cel7A, shows reduced binding and activity at low enzyme loadings toward cellulose III. To clarify this discrepancy, we monitored the single-molecule initial binding commitment and subsequent processive motility of Cel7A enzymes and associated carbohydrate-binding modules (CBMs) on cellulose using optical tweezers force spectroscopy. We confirmed a 48% lower initial binding commitment and 32% slower processive motility of Cel7A on cellulose III, which we hypothesized derives from reduced binding affinity of the Cel7A binding domain CBM1. Classical CBM-cellulose pull-down assays, depending on the adsorption model fitted, predicted between 1.2- and 7-fold reduction in CBM1 binding affinity for cellulose III. Force spectroscopy measurements of CBM1-cellulose interactions, along with molecular dynamics simulations, indicated that previous interpretations of classical binding assay results using multisite adsorption models may have complicated analysis, and instead suggest simpler single-site models should be used. These findings were corroborated by binding analysis of other type-A CBMs (CBM2a, CBM3a, CBM5, CBM10, and CBM64) on both cellulose allomorphs. Finally, we discuss how complementary analytical tools are critical to gain insight into the complex mechanisms of insoluble polysaccharides hydrolysis by cellulolytic enzymes and associated carbohydrate-binding proteins.

Impact of FtsZ Inhibition on the Localization of the Penicillin Binding Proteins in Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen of acute clinical importance. Combination treatment with an FtsZ inhibitor potentiates the activity of penicillin binding protein (PBP)-targeting ß-lactam antibiotics against MRSA. To explore the mechanism underlying this synergistic behavior, we examined the impact of treatment with the FtsZ inhibitor TXA707 on the spatial localization of the five PBP proteins expressed in MRSA. In the absence of drug treatment, PBP1, PBP2, PBP3, and PBP4 colocalize with FtsZ at the septum, contributing to new cell wall formation. In contrast, PBP2a localizes to distinct foci along the cell periphery. Upon treatment with TXA707, septum formation becomes disrupted, and FtsZ relocalizes away from midcell. PBP1 and PBP3 remain significantly colocalized with FtsZ, while PBP2, PBP4, and PBP2a localize away from FtsZ to specific sites along the periphery of the enlarged cells. We also examined the impact on PBP2a and PBP2 localization of treatment with ß-lactam antibiotic oxacillin alone and in synergistic combination with TXA707. Significantly, PBP2a localizes to the septum in approximately 15% of the oxacillin-treated cells, a behavior that likely contributes to the ß-lactam resistance of MRSA. Combination treatment with TXA707 causes both PBP2a and PBP2 to localize in malformed septum-like structures. Our collective results suggest that PBP2, PBP4, and PBP2a may function collaboratively in peripheral cell wall repair and maintenance in response to FtsZ inhibition by TXA707. Cotreatment with oxacillin appears to reduce the availability of PBP2a to assist in this repair, thereby rendering the MRSA cells more susceptible to the ß-lactam. IMPORTANCE MRSA is a multidrug-resistant bacterial pathogen of acute clinical importance, infecting many thousands of individuals globally each year. The essential cell division protein FtsZ has been identified as an appealing target for the development of new drugs to combat MRSA infections. Through synergistic actions, FtsZ-targeting agents can sensitize MRSA to antibiotics like the ß-lactams that would otherwise be ineffective. This study provides key insights into the mechanism underlying this synergistic behavior as well as MRSA resistance to ß-lactam drugs. The results of this work will help guide the identification and optimization of combination drug regimens that can effectively treat MRSA infections and reduce the potential for future resistance.

Quantitative Proteomic Approach for Discriminating Major Depressive Disorder and Bipolar Disorder by Multiple Reaction Monitoring-Mass Spectrometry.

Because major depressive disorder (MDD) and bipolar disorder (BD) manifest with similar symptoms, misdiagnosis is a persistent issue, necessitating their differentiation through objective methods. This study was aimed to differentiate between these disorders using a targeted proteomic approach. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was performed to quantify protein targets regarding the two disorders in plasma samples of 270 individuals (90 MDD, 90 BD, and 90 healthy controls (HCs)). In the training set (72 MDD and 72 BD), a generalizable model comprising nine proteins was developed. The model was evaluated in the test set (18 MDD and 18 BD). The model demonstrated a good performance (area under the curve (AUC) >0.8) in discriminating MDD from BD in the training (AUC = 0.84) and test sets (AUC = 0.81) and in distinguishing MDD from BD without current hypomanic/manic/mixed symptoms (90 MDD and 75 BD) (AUC = 0.83). Subsequently, the model demonstrated excellent performance for drug-free MDD versus BD (11 MDD and 10 BD) (AUC = 0.96) and good performance for MDD versus HC (AUC = 0.87) and BD versus HC (AUC = 0.86). Furthermore, the nine proteins were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions. This proof-of-concept study introduces a potential model for distinguishing between the two disorders.

Three-Dimensional Single-Molecule Localization Microscopy in Whole-Cell and Tissue Specimens.

Super-resolution microscopy techniques are versatile and powerful tools for visualizing organelle structures, interactions, and protein functions in biomedical research. However, whole-cell and tissue specimens challenge the achievable resolution and depth of nanoscopy methods. We focus on three-dimensional single-molecule localization microscopy and review some of the major roadblocks and developing solutions to resolving thick volumes of cells and tissues at the nanoscale in three dimensions. These challenges include background fluorescence, system- and sample-induced aberrations, and information carried by photons, as well as drift correction, volume reconstruction, and photobleaching mitigation. We also highlight examples of innovations that have demonstrated significant breakthroughs in addressing the abovementioned challenges together with their core concepts as well as their trade-offs.

Investigation of the Post-Synthetic Confinement of Fluorous Liquids Inside Mesoporous Silica Nanoparticles.

Perfluorocarbon (PFC) filled nanoparticles are increasingly being investigated for various biomedical applications. Common approaches for PFC liquid entrapment involve surfactant-based emulsification and Pickering emulsions. Alternatively, PFC liquids are capable of being entrapped inside hollow nanoparticles via a postsynthetic loading method (PSLM). While the methodology for the PSLM is straightforward, the effect each loading parameter has on the PFC entrapment has yet to be investigated. Previous work revealed incomplete filling of the hollow nanoparticles. Changing the loading parameters was expected to influence the ability of the PFC to fill the core of the nanoparticles. Hence, it would be possible to model the loading mechanism and determine the influence each factor has on PFC entrapment by tracking the change in loading yield and efficiency of PFC-filled nanoparticles. Herein, neat PFC liquid was loaded into silica nanoparticles and extracted into aqueous phases while varying the sonication time, concentration of nanoparticles, volume ratio between aqueous and fluorous phases, and pH of the extraction water. Loading yields and efficiency were determined via 19F nuclear magnetic resonance and N2 physisorption isotherms. Sonication time was indicated to have the strongest correlation to loading yield and efficiency; however, method validation revealed that the current model does not fully explain the loading capabilities of the PSLM. Confounding variables and more finely controlled parameters need to be considered to better predict the behavior and loading capacity by the PSLM and warrants further study.

Association of Carotid Artery Endothelial Signal Intensity Gradient with Unilateral Large Artery Ischemic Stroke.

BACKGROUND: Common carotid artery (CCA) and internal carotid artery (ICA) are aligned linearly, but their hemodynamic role in ischemic stroke has not been studied in depth. OBJECTIVES: We aimed to investigate whether CCA and ICA endothelial shear stress (ESS) could be associated with the ischemic stroke of large artery atherosclerosis (LAA). METHODS: We enrolled consecutive patients with unilateral ischemic stroke of LAA and healthy controls aged >60 years in the stroke center of Jeonbuk National University Hospital. All patients and controls were examined with carotid artery time-of-flight magnetic resonance angiography, and their endothelial signal intensity gradients (SIGs) were determined, as a measure of ESS. The effect of right or left unilateral stroke on the association between carotid artery endothelial SIG and ischemic stroke of LAA was assessed. RESULTS: In total, the results from 132 patients with ischemic stroke of LAA and 121 controls were analyzed. ICA endothelial SIG showed significant and independent associations with the same-sided unilateral ischemic stroke of LAA, even after adjusting for the potential confounders including carotid stenosis, whereas CCA endothelial SIG showed a significant association with the presence of the ischemic stroke of LAA. CONCLUSION: Although CCA and ICA are located with continuity, the hemodynamics and their roles in large artery ischemic stroke should be considered separately. Further studies are needed to delineate the pathophysiologic roles of ESS in CCA and ICA for large artery ischemic stroke.

Early Trauma Is Associated With Suicidal Ideation in Patients With Panic Disorder.

ABSTRACT: There are several predictors of suicidality in patients with panic disorder (PD). Being a woman, younger age, low education level, unmarried status, and symptom severity have been suggested. This study aimed to examine whether early trauma is associated with suicidal ideation in patients with PD. Our study included 267 patients with PD and 105 controls. Data on sociodemographic variables and data from the Early Trauma Inventory Self Report-Short Form, Beck Depression Inventory, Panic Disorder Severity Scale, Anxiety Sensitivity Inventory-Revised, Coping Scales, and Scale for Suicide Ideation were collected, and correlation and regression analyses were performed. This study suggests that clinicians should consider early trauma when assessing suicidal ideation in patients with PD. Clinicians could consider alternative treatments, such as trauma-focused cognitive-behavioral therapy, eye movement desensitization, reprocessing approaches, and classical pharmacological and psychological treatments for patients with PD who have a history of early trauma and are expected to be at high risk for suicide.

Cognitive Behavioral Therapy and Mindfulness-Based Cognitive Therapy for Depressive Disorders.

Recently, the importance of cognitive behavioral therapy (CBT) in the treatment of depression is gradually emerging. Particularly, mindfulness meditation has various approaches related to dialectical behavioral therapy (DBT), acceptance and commitment therapy (ACT), mindfulness-based stress reduction (MBSR), and mindfulness-based cognitive therapy (MBCT), and evidence has been provided that they alleviate depressive symptoms. In particular, as MBCT increases the level of evidence in the treatment of repetitive depressive disorders, guidelines are being recommended to prevent recurrence. Mindfulness may also contribute to improving the patient's symptoms as well as improving the therapeutic relationship with the therapist. For both mindful patients and therapists, positive awareness of internal experiences can be a good way to enrich the mind and overcome depressive disorders.

Fluorescent paper strip immunoassay with carbon nanodots@silica for determination of human serum amyloid A1.

A fluorescent paper strip immunoassay in conjunction with carbon nanodots@silica (CND@SiO2) as a label was developed for the quantitative measurements of human serum amyloid A1 (hSAA1) in serum at clinically significant concentrations for lung cancer diagnosis. Monodispersed CND@SiO2 was prepared by cohydrolysis between silane-crosslinked carbon nanodots and silica precursors via the Ströber method and further attached covalently to anti-hSAA1 (14F8) monoclonal antibody [anti-hSAA1(14F8)] specific to the hSAA1 target. The hSAA1 concentrations were then determined by quantifying the blue fluorescence intensity upon 365 nm excitation of the captured hSAA1 with anti-hSAA1(14F8)-CND@SiO2 conjugates in the test line on a paper strip where anti-hSAA1 (10G1) monoclonal antibody was physisorbed. The developed fluorescent paper strip with CND@SiO2 can detect hSAA1 at concentrations ranging from 0.1 to 5 nM (R2 = 0.995), with a limit of detection of  0.258 nM in 10 mM phosphate buffer pH 7.4 containing human serum albumin. The performance of  recovery (90.98-109.17%) and repeatability (coefficients of variation < 8.46%) obtained was also acceptable for quantitative determinations. The platform was employed for direct determination of hSAA1 concentrations in undiluted serum samples from lung cancer patients (relative standard deviation (RSD) < 7.46%) and healthy humans (RSD < 3.96%). The results were compared with those obtained using a commercially available enzyme-linked immunosorbent assay alongside liquid chromatography with tandem mass spectrometry measurements.