Different Components of Sexual Narcissism Are Differentially Associated With Specific Sexual Aggression Strategies: An Exploratory Study Among Male and Female College Students.

Objectives: This study investigated whether components of sexual narcissism are associated with different types of sexual aggression (e.g., verbal pressure or force) among students because this is a prevalent problem on college campuses. Methods: College students (N = 508) were recruited for a cross-sectional online study. Results: Results showed that components of sexual narcissism were related to different strategies of sexual aggression, with sexual entitlement being associated with not providing the victim an opportunity to object and exploiting intoxication. Gender moderated some of the associations, with women showing a stronger relationship than men. Conclusions: These findings suggest that sexual narcissism represents a risk factor for sexual aggression in men and women and highlight the need for gender-inclusive and tailored interventions to prevent sexual aggression.

Prediction of Acute Hepatotoxicity With Human Pluripotent Stem Cell-Derived Hepatic Organoids.

Recent development of hepatic organoids (HOs) derived from human pluripotent stem cells (hPSCs) provides an alternative in vitro model that can mimic the human liver detoxification pathway for drug safety assessment. By recapitulating the high level of maturity and drug-metabolizing capacity of the liver in a three-dimensional organoid culture, HOs may allow researchers to assess drug toxicity and metabolism more accurately than animal models or hepatocellular carcinoma cells. Although this promising potential has contributed to the development of various protocols, only a few protocols are available to generate functional HOs with guaranteed CYP450 enzymatic activity, the key feature driving toxic responses during drug metabolism. Based on previously published protocols, we describe an optimized culture method that can substantially increase the expression and activity of CYP450s, in particular CYP3A4, CYP2C9, and CYP2C19, in HOs. To generate mass-produced and highly reproducible HOs required as models for toxicity evaluation, we first generated hepatic endodermal organoids (HEOs) from hPSCs capable of in vitro proliferation and cryopreservation. The stepwise protocol includes generating HEOs as well as efficient methods to enhance CYP450 expression and activity in terminally differentiated HOs. Furthermore, we present a simple protocol for the assessment of HO cytotoxicity, one of the hallmarks of drug-induced acute hepatotoxicity. The protocols are relatively straightforward and can be successfully used by laboratories with basic experience in culturing hPSCs. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of hepatic endodermal organoids from human pluripotent stem cells Basic Protocol 2: Expansion and cryopreservation of hepatic endodermal organoids Basic Protocol 3: Differentiation of hepatic organoids from hepatic endodermal organoids Basic Protocol 4: Evaluation of hepatotoxicity using hepatic organoids Support Protocol: Human pluripotent stem cell culture.

Effect of memory therapy on enhancing postoperative cognitive function recovery and alleviating mood disturbances in brain glioma patients.

OBJECTIVE: To assess the impact of memory therapy on enhancing recovery of postoperative cognitive function and alleviating mood disturbances in brain glioma patients. METHODS: This retrospective study included 160 brain glioma patients who met the inclusion criteria from August 2019 to July 2022. They were divided into a control group and an observation group according to according to different treatment method, with 80 cases in each group. The control group was given routine rehabilitation, while the observation group received additional memory therapy. The study compared complications between the two groups, focusing on the changes in cognitive function [using the Neurobehavioral Cognitive Status Check Scale (NCSE), Clinical Dementia Score (CDR)], mood disturbances [measured by the State Anxiety Scale (S-AI), Trait Anxiety Scale (T-AI), and Hospital Stress Scale score], health-promoting behaviors [evaluated with the Chinese Version of Health Promotion Lifestyle Scale-II (HPLP-II)], coping styles [assessed through the Medical Response Questionnaire (MCQM)], and cancer-related fatigue [using the Cancer-Related Fatigue Scale (CFS)] before and after intervention were observed. A total of 160 glioma cases were classified into either a good or poor prognosis category, based on their prognosis 12 months post-surgery. Baseline data from both groups were compared, and multivariate logistic regression was employed to analyze the factors influencing outcomes in glioma patients. RESULTS: After intervention, the observation group exhibited higher scores of NCSE, HPLP-II, and CFS, but lower scores on the CDR, S-AI, T-AI and hospital stress scale compared to the control group (all P<0.05). Additionally, within the MCQM, the observation group showed reduced avoidance and yield scores, and an increased facing score, compared to the control group (all P<0.05). No significant difference was observed between the complication rates of the control (8.75%) and observation groups (3.75%) (P>0.05). However, the incidence of adverse prognosis was significantly lower in the observation group compared to the control group (8.75% vs 22.50%) (P<0.05). There were no significant differences in age, maximum tumor diameter, preoperative Karnofsky Performance Status score, gender or lesion location between the poor prognosis group and the good prognosis group (all P>0.05). The poor prognosis group had a higher proportion of patients in clinical stages III-IV and a lower proportion receiving recall therapy compared to good prognosis group (P<0.05). Multivariate logistic regression analysis identified clinical stage (III-IV stage) [OR=3.562 (95% CI: 1.476-8.600)] as a risk factor for poor prognosis after brain glioma surgery (P<0.05), while undergoing memory therapy [ß=0.330 (95% CI: 0.99-0.842)] acted as a protective factor against poor prognosis (P<0.05). CONCLUSION: Memory therapy has been shown to promote postoperative cognitive function recovery in glioma patients, reduce anxiety and stress response, bolster coping mechanisms and health-promoting behavior, diminish cancer-related fatigue, and improve patient prognosis.

Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

An evaluation of the effectiveness of 'ULTRACOL 200' in enhancing nasolabial fold wrinkles through cutaneous repair.

BACKGROUND: Injectable filler, a nonsurgical beauty method, has gained popularity in rejuvenating sagging skin. In this study, polydioxanone (PDO) was utilized as the main component of the ULTRACOL200 filler that helps stimulate collagenesis and provide skin radiant effects. The study aimed to evaluate and compare the effectiveness of ULTRACOL200 with other commercialized products in visually improving dermatological problems. METHODS: Herein, 31 participants aged between 20 and 59 years were enrolled in the study. 1 mL of the testing product, as well as the quantity for the compared groups was injected into each participants face side individually. Subsequently, skin texture and sunken volume of skin were measured using ANTERA 3D CS imaging technology at three periods: before the application, 4 weeks after the initial application, and 4 weeks after the 2nd application of ULTRACOL200. RESULTS: The final results of skin texture and wrinkle volume evaluation consistently demonstrated significant enhancement. Consequently, subjective questionnaires were provided to the participants to evaluate the efficacy of the testing product, illustrating satisfactory responses after the twice applications. CONCLUSION: The investigation has contributed substantially to the comprehension of a PDO-based filler (ULTRACOL200) for skin enhancement and provided profound insight for future clinical trials.

The senescence-associated secretory phenotype and its physiological and pathological implications.

Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. In this Review, we discuss the composition, dynamics and heterogeneity of the SASP as well as the mechanisms underlying its induction and regulation. We describe the various biological properties of the SASP, its beneficial and detrimental effects in different physiological and pathological settings, and its impact on overall health span. Finally, we discuss the use of the SASP as a biomarker and of SASP inhibitors as senomorphic interventions to treat cancer and other age-related conditions.

Experimental and numerical investigation on the reinforced concrete boundary beam-wall system subjected to axial compression.

This paper proposes a reinforced concrete (RC) boundary beam-wall system that requires less construction material and a smaller floor height compared to the conventional RC transfer girder system. The structural performance of this system subjected to axial compression was evaluated by performing a structural test on four specimens of 1/2 scale. In addition, three-dimensional nonlinear finite element analysis was also performed to verify the effectiveness of the boundary beam-wall system. Three test parameters such as the lower wall length-to-upper wall length ratio, lower wall thickness, and stirrup details of the lower wall were considered. The load-displacement curve was plotted for each specimen and its failure mode was identified. The test results showed that decrease in the lower wall length-to-upper wall length ratio significantly reduced the peak strength of the boundary beam-wall system and difference in upper and lower wall thicknesses resulted in lateral bending caused by eccentricity in the out-of-plane direction. Additionally, incorporating cross-ties and reducing stirrup spacing in the lower wall significantly improved initial stiffness and peak strength, effectively minimizing stress concentration.

The antidiabetic drug ipragliflozin induces vasorelaxation of rabbit femoral artery by activating a Kv channel, the SERCA pump, and the PKA signaling pathway.

We explored the vasorelaxant effects of ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, on rabbit femoral arterial rings. Ipragliflozin relaxed phenylephrine-induced pre-contracted rings in a dose-dependent manner. Pre-treatment with the ATP-sensitive K+ channel inhibitor glibenclamide (10 µM), the inwardly rectifying K+ channel inhibitor Ba2+ (50 µM), or the Ca2+-sensitive K+ channel inhibitor paxilline (10 µM) did not influence the vasorelaxant effect. However, the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (3 mM) reduced the vasorelaxant effect. Specifically, the vasorelaxant response to ipragliflozin was significantly attenuated by pretreatment with the Kv7.X channel inhibitors linopirdine (10 µM) and XE991 (10 µM), the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin (1 µM) and cyclopiazonic acid (10 µM), and the cAMP/protein kinase A (PKA)-associated signaling pathway inhibitors SQ22536 (50 µM) and KT5720 (1 µM). Neither the cGMP/protein kinase G (PKG)-associated signaling pathway nor the endothelium was involved in ipragliflozin-induced vasorelaxation. We conclude that ipragliflozin induced vasorelaxation of rabbit femoral arteries by activating Kv channels (principally the Kv7.X channel), the SERCA pump, and the cAMP/PKA-associated signaling pathway independent of other K+ (ATP-sensitive K+, inwardly rectifying K+, and Ca2+-sensitive K+) channels, cGMP/PKG-associated signaling, and the endothelium.

The Interplay Between Endoplasmic Reticulum Stress and Oxidative Stress in Chondrocyte Catabolism.

OBJECTIVE: Oxidative stress and endoplasmic reticulum (ER) stress play pivotal roles in disrupting the homeostasis of chondrocytes by producing catalytic proteases and enhancing chondrocyte senescence, consequently contributing to the progression of osteoarthritis (OA). Despite their close interaction, the underlying molecular mechanisms remain poorly understood. Here, we show that ER stress and oxidative stress reciprocally modulate each other to promote cartilage degradation. METHODS: Primary chondrocytes were obtained from the articular cartilage of 5-day-old C57BL/6J mice by excising distal femur and proximal tibia. Tunicamycin was applied to induce ER stress in primary chondrocytes. Surgical OA was induced in 12-week-old male C57BL/6J mice by destabilizing the medial meniscus (DMM). RESULTS: Tunicamycin-induced ER stress led to an increase in the production of reactive oxygen species (ROS) and catalytic proteases, including MMP13 and Adamts5, in primary chondrocytes, and it was primarily dependent on the NADPH oxidase (NOX) system. ER stress directly increased the expression of NOX2, NOX3, NOX4, and p22phox. Specifically, the protein kinase RNA-like ER kinase (PERK) pathway is involved in the expression of NOX4 and p22phox, the inositol-requiring enzyme 1 alpha (IRE1α) pathway in NOX2 and NOX3 expression, and the activating transcription factor 6 (ATF6) pathway influences NOX3 expression in chondrocytes. Conversely, inhibiting NOX function significantly reduced both ER stress sensor-related signaling and chondrocyte catabolism, thereby decelerating the progression of surgically induced OA in vivo. CONCLUSIONS: Our findings highlight the positive feedback loop between ER stress and oxidative stress in OA pathogenesis, suggesting that targeting NOX isoforms is a promising therapeutic strategy for OA.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Cyclic stretch induced epigenetic activation of periodontal ligament cells.

Periodontal ligament (PDL) cells play a crucial role in maintaining periodontal integrity and function by providing cell sources for ligament regeneration. While biophysical stimulation is known to regulate cell behaviors and functions, its impact on epigenetics of PDL cells has not yet been elucidated. Here, we aimed to investigate the cytoskeletal changes, epigenetic modifications, and lineage commitment of PDL cells following the application of stretch stimuli to PDL. PDL cells were subjected to stretching (0.1 Hz, 10 %). Subsequently, changes in focal adhesion, tubulin, and histone modification were observed. The survival ability in inflammatory conditions was also evaluated. Furthermore, using a rat hypo-occlusion model, we verified whether these phenomena are observed in vivo. Stretched PDL cells showed maximal histone 3 acetylation (H3Ace) at 2 h, aligning perpendicularly to the stretch direction. RNA sequencing revealed stretching altered gene sets related to mechanotransduction, histone modification, reactive oxygen species (ROS) metabolism, and differentiation. We further found that anchorage, cell elongation, and actin/microtubule acetylation were highly upregulated with mechanosensitive chromatin remodelers such as H3Ace and histone H3 trimethyl lysine 9 (H3K9me3) adopting euchromatin status. Inhibitor studies showed mechanotransduction-mediated chromatin modification alters PDL cells behaviors. Stretched PDL cells displayed enhanced survival against bacterial toxin (C12-HSL) or ROS (H2O2) attack. Furthermore, cyclic stretch priming enhanced the osteoclast and osteoblast differentiation potential of PDL cells, as evidenced by upregulation of lineage-specific genes. In vivo, PDL cells from normally loaded teeth displayed an elongated morphology and higher levels of H3Ace compared to PDL cells with hypo-occlusion, where mechanical stimulus is removed. Overall, these data strongly link external physical forces to subsequent mechanotransduction and epigenetic changes, impacting gene expression and multiple cellular behaviors, providing important implications in cell biology and tissue regeneration.

Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma.

BACKGROUND: The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. METHODS: Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. RESULTS: The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. CONCLUSION: Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

In Situ Construction of Inorganics-Rich Cathode-Electrolyte Interface toward Long-Life Prussian White Cathode.

Prussian white (PW) is one of the most promising candidates as a cathode for sodium-ion batteries (SIBs) because of its high theoretical capacity, excellent rate performance, and low production cost. However, PW materials suffer severe capacity decay during long-term cycling. In this work, a robust cathode electrolyte interface (CEI) is designed on the PW cathode by employing cresyl diphenyl phosphate (CDP) and adiponitrile (ADN) as electrolyte additives. CDP and ADN possess higher highest occupied molecular orbital energy levels (HOMO) than other solvents, leading to the preferential decomposition of CDP and ADN to construct an inorganics-rich CEI layer in situ on the PW cathode. Benefiting from this CEI layer, the degradation of PW is effectively inhibited during the long cycling. The Na||PW cell achieves an excellent cycling performance with a capacity retention of 85.62% after 1400 cycles. This work presented here provides a feasible strategy for improving the cycling performance of PW by electrolyte modification.

Characterization of an exopolysaccharide synthesized by Lacticaseibacillus rhamnosus B6 and its immunomodulatory activity in vitro.

An exopolysaccharide, designated F1, was purified from the fermented milk by Lacticaseibacillus rhamnosus strain B6 (CGMCC No. 13310). F1, with the weight average molecular weight of 1.577 × 106 Da, is consisted of rhamnose, glucose and galactose in a molar ratio of 3.7:1.5: 1. The backbone included 1,3-linked Rha, 1,2,3-linked Rha, 1,2-linked Glc and 1,3-linked Glc residues, with the branching point located at O2 position of 1,2,3-linked Rha residue, and the branch chain composed of terminal linked galactose residue with a pyruvate substituent. F1 could significantly stimulate the phagocytic activity and TNF-α expression in RAW 264.7 macrophages in a dose-dependent manner, and the release of NO at 200 µg/mL as well. F1 at 200 µg/mL could stimulate the expression of the pro-inflammatory cytokine encoding genes including TNF-α and iNOS, but with a negligible upregulating effect on the mRNA expression of IL-10. F1 could up-regulate the expression of NF-κBp65 and skew macrophage polarization towards M1 phenotype. These results suggest F1 elicit an immunomodulatory effect through the NF-κB signaling pathway.

Drug Repositioning via Graph Neural Networks: Identifying Novel JAK2 Inhibitors from FDA-Approved Drugs through Molecular Docking and Biological Validation.

The increasing utilization of artificial intelligence algorithms in drug development has proven to be highly efficient and effective. One area where deep learning-based approaches have made significant contributions is in drug repositioning, enabling the identification of new therapeutic applications for existing drugs. In the present study, a trained deep-learning model was employed to screen a library of FDA-approved drugs to discover novel inhibitors targeting JAK2. To accomplish this, reference datasets containing active and decoy compounds specific to JAK2 were obtained from the DUD-E database. RDKit, a cheminformatic toolkit, was utilized to extract molecular features from the compounds. The DeepChem framework's GraphConvMol, based on graph convolutional network models, was applied to build a predictive model using the DUD-E datasets. Subsequently, the trained deep-learning model was used to predict the JAK2 inhibitory potential of FDA-approved drugs. Based on these predictions, ribociclib, topiroxostat, amodiaquine, and gefitinib were identified as potential JAK2 inhibitors. Notably, several known JAK2 inhibitors demonstrated high potential according to the prediction results, validating the reliability of our prediction model. To further validate these findings and confirm their JAK2 inhibitory activity, molecular docking experiments were conducted using tofacitinib-an FDA-approved drug for JAK2 inhibition. Experimental validation successfully confirmed our computational analysis results by demonstrating that these novel drugs exhibited comparable inhibitory activity against JAK2 compared to tofacitinib. In conclusion, our study highlights how deep learning models can significantly enhance virtual screening efforts in drug discovery by efficiently identifying potential candidates for specific targets such as JAK2. These newly discovered drugs hold promises as novel JAK2 inhibitors deserving further exploration and investigation.

Air-Stable Prussian White Cathode Materials for Sodium-Ion Batteries Enabled by ZnO Surface Modification.

Iron-based Prussian white (PW) is one of the promising cathodes for sodium-ion batteries, owing to its high capacity and low cost. However, the practical application of PW is hindered by its poor air stability. The metal-oxide coating has been proven to be an effective way to improve the air stability of electrode materials. Whereas, the target electrode materials conventionally need to be dissolved in the aqueous solution to obtain precursor composites and subsequently calcined at a high temperature during the metal-oxide coating process, which could destroy the phase structure of PW as a result of the sodium leaching into the water and thermal decomposition at the high temperature. In this work, we propose a facile method to construct a ZnO surface layer on PW by utilizing ethanol as a solvent and a mild post-treatment temperature. The ZnO coating layer effectively enhances the air stability of PW and induces the formation of the stable interface on PW. The PW-5 wt % ZnO-E (exposed in 60% humidity air after 30 days) cathode demonstrates a much higher capacity retention (94.1%) at 1 C after 200 cycles than that of PW-E (54%). This work lays a solid foundation for further application of PW.

Psychophysiological and emotional effects of human-Dog interactions by activity type: An electroencephalogram study.

Animal-assisted interventions are being increasingly used in studies that support various health effects. This study compared the psychophysiological and emotional responses during diverse activities with a dog to understand the impact of activity type. This study included 30 healthy adults (average age: 27.9 ± 8.4 years). Participants performed eight different activities with a dog for 3 minutes each. These activities included meeting, playing, feeding, massaging, grooming, photographing, hugging, and walking. Brain waves in the prefrontal, frontal, parietal, and occipital lobes were measured during the activities. Subjective evaluation of their emotions was recorded after each activity via the Profile of Mood States, Semantic Differential Method, and Stress Numeric Rating Scale. The alpha (relative, relative slow, relative fast) power spectra indicated that the brain's relaxation and resting state significantly increased when playing with and walking a dog. The beta (relative, relative low, and relative mid) power spectra significantly increased during dog massage, grooming, and playing activities, indicating improved concentration without stress. Notably, playing with a dog positively affected both relaxation and concentration. The Profile of Mood States outcome showed that activities such as feeding, massaging, and hugging the dog decreased the total mood disorder score, which indicated a positive effect on participants' moods. The Semantic Differential Method revealed that participants felt comfortable and natural while walking with a dog and relaxed when massaging it. Participants showed significantly lower stress moods in all the activities. This study demonstrated that specific dog activities could activate stronger relaxation, emotional stability, attention, concentration, and creativity by facilitating increased brain activity. In addition, interactions with dogs could decrease stress and induce positive emotional responses. These results provide data that forms the basis for the composition of the AAI program and may be applicable as a reference to determine the most effective activities for specific applications.