Sphingosine-1-Phosphate-Cathelicidin Axis Plays a Pivotal Role in the Development of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer caused by mutagenesis resulting from excess UVR or other types of oxidative stress. These stressors also upregulate the production of a cutaneous innate immune element, cathelicidin antimicrobial peptide (CAMP), through endoplasmic reticulum stress-initiated, sphingosine-1-phosphate (S1P) signaling pathway. Although CAMP has beneficial antimicrobial activities, it also can be proinflammatory and procarcinogenic. We addressed whether and how S1P-induced CAMP production leads to cSCC development. Our study demonstrated that (i) CAMP expression is increased in cSCC cells and skin from patients with cSCC; (ii) S1P levels are elevated in cSCC cells, whereas inhibition of S1P production attenuates CAMP-stimulated cSCC growth; (iii) exogenous CAMP stimulates cSCC but not normal human keratinocyte growth; (iv) blockade of FPRL1 protein, a CAMP receptor, attenuates cSCC growth as well as the growth and invasion of cSCC cells mediated by CAMP into an extracellular matrix-containing fibroblast substrate; (v) FOXP3+ regulatory T-cell (which decreases antitumor immunity) levels increase in cSCC skin; and (vi) CAMP induces endoplasmic reticulum stress in cSCC cells. Together, the endoplasmic reticulum stress-S1P-CAMP axis forms a vicious circle, creating a favorable environment for cSCC development, that is, cSCC growth and invasion impede anticancer immunity.

Distorted time perception in patients with neurocognitive impairment.

Background: Time perception is known to be distorted in patients with neuropsychiatric disorders. Therefore, this study aims to investigate the correlation between cognitive decline and time distortion by examining time perception in participants with neurocognitive impairment (Alzheimer's disease [AD], vascular dementia [VD], and Parkinson's disease dementia [PDD]) compared to those with subjective cognitive impairment (SCI). Methods: Overall, 569 participants with cognitive decline complaints between 2013 and 2022 were investigated. Participants were subjected to a verbal estimation task, time production task, time comparison task, and neuropsychological assessments. Results: Time perception abilities were distorted in patients with neurocognitive impairment compared to those with SCI. Despite similar educational backgrounds, the vascular cognitive impairment (VCI)/VD group demonstrated the lowest MMSE scores (22.4 ± 4.2, p-value <0.001) and larger time-estimation errors. Patients with VCI/VD significantly underestimated time in the 35-s (19.6 ± 12.6s) and 60-s (28.7 ± 19.9s) tasks. In the time production task, patients with VCI/VD produced shorter times in their 15-s (12.7 ± 4.3; p-value = 0.001), 30-s (23.6 ± 8.3; p value < 0.001), and 60-s (43.8 ± 18.9; p-value <0.001) trials. In the time comparison task, the VCI/VD group had significantly fewer correct answers than that in the SCI groups (6.0 ± 1.3 vs. 7.1 ± 0.9, p-value <0.001). Correlation analysis revealed that multiple cognitive functions are involved in the time perception tasks. Conclusions: Patients with VCI/VD had the poorest time perception. These findings may provide a modest contribution to understanding the underlying pathophysiology and psychological connections related to temporal abilities in time perception.

Exploring the Interfacial Dynamics of Unilamellar and Multilamellar Cationic Liposomes on SiO2 and Their Interactions with Membrane-Active Peptide.

Understanding the interplay between lipid assemblies and solid supports is crucial for advancing model membrane systems and biomedical applications. This study investigates the interfacial behaviors of unilamellar and multilamellar cationic liposomes on silicon dioxide and their interactions with a membrane-active AH peptide. Using QCM-D monitoring, unilamellar liposomes were found to rapidly form SLBs through one-step adsorption kinetics, whereas multilamellar liposomes exhibited slower adsorption. Further addition of liposomes caused fusogenic interactions with SLBs, where multilamellar liposomes formed more rigid lipid membranes. Upon AH peptide exposure, unilamellar-based lipid membranes showed higher susceptibility to structural transformations, achieving complete SLB formation, while multilamellar-based lipid membranes displayed reduced sensitivity and retained residual viscoelastic components, indicative of incomplete SLB formation. These findings underscore the significant influence of liposome lamellarity on their interfacial dynamics and peptide interactions, crucial for designing effective lipid-based delivery and sensing systems.

Rescue therapy of early neurological deterioration in lacunar stroke.

BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Predicting neuroticism with open-ended response using natural language processing.

Introduction: With rapid advancements in natural language processing (NLP), predicting personality using this technology has become a significant research interest. In personality prediction, exploring appropriate questions that elicit natural language is particularly important because questions determine the context of responses. This study aimed to predict levels of neuroticism-a core psychological trait known to predict various psychological outcomes-using responses to a series of open-ended questions developed based on the five-factor model of personality. This study examined the model's accuracy and explored the influence of item content in predicting neuroticism. Methods: A total of 425 Korean adults were recruited and responded to 18 open-ended questions about their personalities, along with the measurement of the Five-Factor Model traits. In total, 30,576 Korean sentences were collected. To develop the prediction models, the pre-trained language model KoBERT was used. Accuracy, F1 Score, Precision, and Recall were calculated as evaluation metrics. Results: The results showed that items inquiring about social comparison, unintended harm, and negative feelings performed better in predicting neuroticism than other items. For predicting depressivity, items related to negative feelings, social comparison, and emotions showed superior performance. For dependency, items related to unintended harm, social dominance, and negative feelings were the most predictive. Discussion: We identified items that performed better at neuroticism prediction than others. Prediction models developed based on open-ended questions that theoretically aligned with neuroticism exhibited superior predictive performance.

Isolation and characterization of NGFFYamide neuropeptide from Patiria pectinifera pyloric caeca extract.

Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (Patiria pectinifera) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an in vitro bioassay to screen for fractions and peptides with relaxing effects on P. pectinifera apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from P. pectinifera through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. In vitro pharmacological studies on muscle preparations from P. pectinifera and Asterias amurensis revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in P. pectinifera cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on P. pectinifera cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in P. pectinifera apical muscle but not in A. amurensis, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in P. pectinifera, consistent with findings in Asterias rubens.

Stroke Measures Analysis of pRognostic Testing-Mortality nomogram predicts long-term mortality after ischemic stroke.

BACKGROUND: Predicting long-term mortality is essential for understanding prognosis and guiding treatment decisions in patients with ischemic stroke. Therefore, this study aimed to develop and validate the method for predicting 1- and 5-year mortality after ischemic stroke. METHODS: We used data from the linked dataset comprising the administrative claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data for patients with acute stroke within 7 days of onset. The outcome was all-cause mortality following ischemic stroke. Clinical variables linked to long-term mortality following ischemic stroke were determined. A nomogram was constructed based on the Cox's regression analysis. The performance of the risk prediction model was evaluated using the Harrell's C-index. RESULTS: This study included 42,207 ischemic stroke patients, with a mean age of 66.6 years and 59.2% being male. The patients were randomly divided into training (n = 29,916) and validation (n = 12,291) groups. Variables correlated with long-term mortality in patients with ischemic stroke, including age, sex, body mass index, stroke severity, stroke mechanisms, onset-to-door time, pre-stroke dependency, history of stroke, diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cancer, smoking, fasting glucose level, previous statin therapy, thrombolytic therapy, such as intravenous thrombolysis and endovascular recanalization therapy, medications, and discharge modified Rankin Scale were identified as predictors. We developed a predictive system named Stroke Measures Analysis of pRognostic Testing-Mortality (SMART-M) by constructing a nomogram using the identified features. The C-statistics of the nomogram in the developing and validation groups were 0.806 (95% confidence interval (CI), 0.802-0.812) and 0.803 (95% CI, 0.795-0.811), respectively. CONCLUSION: The SMART-M method demonstrated good performance in predicting long-term mortality in ischemic stroke patients. This method may help physicians and family members understand the long-term outcomes and guide the appropriate decision-making process.

Impact of Systolic Blood Viscosity on Deep White Matter Hyperintensities in Patients With Acute Ischemic Stroke.

BACKGROUND: Elevated blood viscosity (BV), a critical determinant in blood rheology, is a contributing factor in cerebrovascular diseases. The specific influence of BV on small vessel disease burden remains unexplored. This study aims to examine the relationship between BV and regional white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. METHODS AND RESULTS: We enrolled a cohort of 302 patients with acute ischemic stroke or transient ischemic attack who were admitted to a hospital within 7 days of symptom onset in this study. We measured whole BV using a scanning capillary-tube viscometer and categorized systolic blood viscosity into 3 groups based on established references. We quantified and normalized WMH volumes using automated localization and segmentation software by NEUROPHET Inc. We performed multivariable logistic regression analysis to assess the correlation between systolic BV and WMH. The mean subject age was 66.7±13.4 years, and 38.7% (n=117) of the participants were female. Among a total of 302 patients, patients with higher deep WMH volume (T3) were typically older and had an atrial fibrillation, strokes of cardioembolic or undetermined cause, elevated levels of C-reactive protein, diastolic blood viscosity and systolic BV. A multivariable adjustment revealed a significant association between high systolic BV and increased deep-WMH volume (odds ratio [OR], 2.636 [95% CI, 1.225-5.673]). CONCLUSIONS: Elevated systolic BV is more likely to be associated with deep WMH volume in patients with acute ischemic stroke or transient ischemic attack. These findings reveal novel therapeutic strategies focusing on blood rheology to enhance cerebral microcirculation in stroke management.

Screening and purification of antimicrobial materials from coelomic fluid of sea urchin, Heliocidaris crassispina.

Marine organisms, such as sea urchins like Heliocidaris crassispina, produce bioactive substances with antimicrobial activity to protect themselves from the high density of microorganisms in their habitats. One such substance, Echinochrome A (Ech A), has been isolated from various sea urchins' shells and spines using strong acidic solutions and organic solvents. Ech A, however, has not been reported from the coelomic fluid of H. crassispina. In this study, we report the antimicrobial activity of H. crassispina coelomic fluid extract against various microbes, evaluating its potential for purifying potent antimicrobial materials. Upon confirming the extract as a promising source of antimicrobial materials, we isolated antimicrobial compounds from the extract. A series of HPLC steps were taken to purify antimicrobial materials from the H. crassispina coelomic fluid extract, resulting in the isolation of two single absorbance peaks showing antimicrobial activity against Staphylococcus aureus. One peak consisted of a single antimicrobial compound with a molecular weight (MW) corresponding to Ech A, while the other peak comprised five MWs inferred to be those of Ech A and its oxidative products. The elution of Ech A in two separate peaks may be attributable to the presence of Ech A's isomer, as reported in several previous studies. The use of the environmentally friendly extraction method in procurement of Ech A from the coelomic fluid would contribute to the implementation of risk-reducing extraction method for researchers studying Ech A from sea urchins.

Assessing the Impact of Nutritional Support Teams on Clinical Outcomes: Compliance and Feasibility of Micronutrient Supplementation.

Background: Micronutrient (MN) supplementation has a positive impact on clinical outcomes. However, the evidence for the impact of MN supplementation remains controversial. Therefore, our study aims to assess the impact on nutritional outcomes according to exploring the implementation of MN support with multidisciplinary collaboration. Methods: This retrospective cohort study was conducted at a university hospital in Incheon, Korea. All patients referred to a nutrition support team (NST) between July and November 2022 were included. The NST reviews the MN protocol, which includes multivitamins and trace elements, based on international nutrient guidelines. All patients who were on nothing per oral and did not meet ≥70% of their nutritional requirements within 1 week were recommended MN supplements. Compliance with the MN protocol was evaluated, alterations in nutritional status based on the Nutrition Risk Screening 2002 (NRS 2002) scoring system and clinical outcomes were assessed after 7 day and at discharge. Multiple logistic regression analysis was used to identify factors associated with high nutritional risk in discharged patients. In addition, a sub-analysis was performed on changes in the nutritional of patients on the ward and in the ICU. Results: A total of 255 patients were eligible for analysis, with many patients requiring an MN supply of nothing per oral. The rate of implementation of MN supplementation was 50.2%. The findings indicate a significant decrease in the NRS 2002 score in the good compliance group with MN supplementation. No significant differences in protocol compliance were observed in terms of mortality, hospital stay, or length of stay in the intensive care unit. However, bad compliance with MN supplementation was correlated with risk factors for malnutrition at discharge. In subgroup analysis, nutritional status in the ICU and wards improved, with a significant difference between the two groups. Conclusions: The implementation of a MN supplementation protocol by a multidisciplinary NST is a feasible approach for improving the nutritional status of inpatients. Ensuring high compliance with this protocol is crucial, as poor compliance has been identified as a risk factor for malnutrition at discharge. Active intervention by the NST is essential to achieve optimal nutritional outcomes.

Diesel Particulate Matter Permeation into Normal Human Skin and Intervention Using a Topical Ceramide Formulation.

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

Treatment resistant late-life depression: A narrative review of psychosocial risk factors, non-pharmacological interventions, and the role of clinical phenotyping.

BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. LIMITATIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.

Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection.

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.

Complementary Therapeutic Effect of Fecal Microbiota Transplantation in Ulcerative Colitis after the Response to Anti-Tumor Necrosis Factor Alpha Agent Was Lost: A Case Report.

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

Elucidating Structural Configuration of Lipid Assemblies for mRNA Delivery Systems.

The development of mRNA delivery systems utilizing lipid-based assemblies holds immense potential for precise control of gene expression and targeted therapeutic interventions. Despite advancements in lipid-based gene delivery systems, a critical knowledge gap remains in understanding how the biophysical characteristics of lipid assemblies and mRNA complexes influence these systems. Herein, we investigate the biophysical properties of cationic liposomes and their role in shaping mRNA lipoplexes by comparing various fabrication methods. Notably, an innovative fabrication technique called the liposome under cryo-assembly (LUCA) cycle, involving a precisely controlled freeze-thaw-vortex process, produces distinctive onion-like concentric multilamellar structures in cationic DOTAP/DOPE liposomes, in contrast to a conventional extrusion method that yields unilamellar liposomes. The inclusion of short-chain DHPC lipids further modulates the structure of cationic liposomes, transforming them from multilamellar to unilamellar structures during the LUCA cycle. Furthermore, the biophysical and biological evaluations of mRNA lipoplexes unveil that the optimal N/P charge ratio in the lipoplex can vary depending on the structure of initial cationic liposomes. Cryo-EM structural analysis demonstrates that multilamellar cationic liposomes induce two distinct interlamellar spacings in cationic lipoplexes, emphasizing the significant impact of the liposome structures on the final structure of mRNA lipoplexes. Taken together, our results provide an intriguing insight into the relationship between lipid assembly structures and the biophysical characteristics of the resulting lipoplexes. These relationships may open the door for advancing lipid-based mRNA delivery systems through more streamlined manufacturing processes.

SPATA20 deficiency enhances the metastatic and angiogenic potential of cancer cells by promoting HIF-1α synthesis.

Hypoxia-inducible factors (HIFs) regulate cellular oxygen balance and play a central role in cancer metastasis and angiogenesis. Despite extensive research on HIFs, successful therapeutic strategies remain limited due to the intricate nature of their regulation. In this study, we identified SPATA20, a relatively understudied protein with a thioredoxin-like domain, as an upstream regulator of HIF-1α. Depleting SPATA20 induced HIF-1α expression, suggesting a tumor-suppressive role for SPATA20 in cancer cells. SPATA20 depletion increased HIF-1α protein levels and transcriptional activity without affecting its degradation. It appears that SPATA20 inhibits the de novo synthesis of HIF-1α, possibly by repressing the cap-dependent translation process involving AKT phosphorylation. Additionally, depletion of SPATA20 promoted cancer cell migration and invasion, which can be reversed by pharmacological inhibition of HIF-1α. Clinical data analysis revealed an inverse correlation between SPATA20 expression and colorectal cancer progression, providing evidence of its role as a potential biomarker. Utilizing SPATA20 as an indicator for HIF-1α-targeting therapy may be an attractive strategy for treating patients with hypoxia-driven cancers. In conclusion, this study demonstrates that SPATA20 deficiency promotes cancer progression by activating the HIF-1α signaling pathway.

COVID-19, Influenza, and RSV in Children and Adults: A Clinical Comparative Study of 12,000 Cases.

(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5-2.4] in children and 21.4 times [2.4-189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs.

Daily vitality fluctuations in older adults with depressive symptoms: A multilevel location-scale model.

BACKGROUND: Examining the daily experiences of older adults with depression facilitates the development and application of personalized effective treatments for them. In previous clinical research on depression, traditional mean-based approaches have mainly been employed. However, the within-person residual variance as a random effect provides greater insight into the heterogeneity of daily experiences among geriatric samples. OBJECTIVE: This study aimed to examine the relationship between depression and daily vitality in older adults. Specifically, it focused on the mean and residual variance of daily vitality measured by the Ecological Momentary Assessment (EMA). METHODS: Data from 64 older adults aged 65 years or more, who participated in community welfare centers or retirees' associations, were used. Daily vitality was examined using EMA surveys for seven consecutive days (four random surveys per day). The data were analyzed using a location-scale model. RESULTS: The intraclass correlation computed from the empty model for the EMA data was 0.488, indicating significant variances in daily vitality across time between individuals. Older adults with higher levels of depressive symptoms showed low mean levels of daily vitality and a large log-residual variance of daily vitality. CONCLUSIONS: The findings from the current study suggest that individuals experiencing depression not only exhibit low vitality in their daily lives but also struggle to maintain stable levels of vitality in their lives. These insights could contribute to the facilitation and advancement of personalized interventions tailored for older adults.

The impact of statin treatment duration on the risk of new-onset diabetes mellitus and recurrent vascular events in ischemic stroke patients: a linked data analysis.

INTRODUCTION: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. METHODS: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). RESULTS: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes. CONCLUSION: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Skin-whitening effects of Spergularia marina by suppressing MITF translocation.

Spergularia marina is a plant that grows in salty regions along the coastline and exerts radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of S. marina extract (SME) in B16F10 melanoma cells. SME was found to exert radical-scavenging effects. It suppressed α-melanocyte-stimulating hormone-induced melanogenesis and tyrosinase activity. We also assessed the melanin production signaling pathway to identify the inhibitory action mechanism of SME on melanogenesis. SME decreased the protein expression levels of tyrosinase-related protein (TRP)-1, TRP-2, and tyrosinase, which play important roles in melanogenesis. Furthermore, western blotting revealed that SME inhibited the nuclear translocation of melanocyte inducing transcription factor (MITF), which is a transcription factor for TRP-1, TRP-2, and tyrosinase, suggesting that SME exerts its skin-whitening effect by inhibiting MITF nuclear translocation. Therefore, SME may potentially be used in skin-whitening medicines and cosmetics.