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We assessed the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2014 and December 2022.Considering the MACE safety profile, enzalutamide may be a better choice for prostate cancer. This needs to be further confirmed by larger prospective studies and longer follow-up periods. Background: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to newgeneration ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. Results: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide. Conclusion: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further. [ABSTRACT FROM AUTHOR]

• Residential energy vulnerability is assessed from social, built, and energy aspects. • Bayesian spatial mapping is proposed for occupancy and building integration. • Occupancy schedules in energy models are customized for various demographic groups. • Results reveal spatial-temporal disparities in energy vulnerability. With global trends in electrification, communities highly dependent on electricity are facing increasing challenges, particularly due to more frequent weather events, which lead to significant surges in electricity demand or result in blackouts. However, the impact is disproportionate across space and time, which raises an urgent need to comprehensively assess residential energy vulnerabilities to ensure energy security for households. Existing methodologies, whether large-scale regional assessments or community-based surveys, predominantly rely on static data. This reliance significantly limits their ability to capture the spatial and temporal dynamics of energy vulnerability, which is particularly important in the face of climate change. This study analyses residential energy vulnerability in the dimensions of social vulnerability, building resilience, and energy burden by innovatively linking occupancy patterns with the built environment through a Bayesian-based spatial mapping methodology. We applied this method through a case study in a Philadelphia census tract area identified for its high vulnerability based on FEMA's National Risk Index. By mapping occupancy with residential buildings, we simulated the energy consumption patterns of approximately 900 residential buildings. The simulations utilized DOE single-family energy prototypes, tailored to account for empirical occupancy and building features, to predict hourly energy consumption and assess indoor thermal comfort during power outages on days with extreme temperatures. The findings reveal disparities across different dimensions of energy vulnerability and illustrate the dynamic nature of energy vulnerability that fluctuates with daily activities. The study also highlights areas with low thermal resilience, suggesting a need for retrofitting older buildings to improve energy efficiency. The implications of this research extend beyond the built environment to the socioeconomic aspects of energy use, advocating for adaptive community planning and the development of resilient energy infrastructures. The results serve as a foundation for stakeholders to implement targeted interventions, prioritize retrofitting efforts, and support equitable access to energy resources, thereby enhancing urban sustainability and resilience. [ABSTRACT FROM AUTHOR]

Kefir is an acidic-alcoholic fermented milk that can provide probiotic benefits, such as intestinal microecological balance regulation, antibacterial activity, and anti-inflammatory activity. In this study, Lactobacillus fermentum grx08 isolated from longevous people was used to further improve the health properties of kefir. L. fermentum grx08 and kefir grains obtained from Xinjiang, People’s Republic of China, were mixed at ratios of 1:1, 5:1, and 25:1 as starters. The six gram-positive and gram-negative foodborne pathogens were able to grow in the supernatant of kefir but not in the supernatant of kefir with L. fermentum grx08. With increasing amounts of inoculated L. fermentum grx08, the antibacterial activity of the mixed fermented kefir gradually increased. The contents of lactic acid, fumaric acid, and malic acid in the mixed fermented milk were significantly increased by adding L. fermentum grx08 (P < 0.05), while the content of acetic acid decreased with the increase of L. fermentum grx08 and the content of citric acid was unaffected. This study suggests that the addition of L. fermentum grx08 shortened the fermentation time, improved the acidity, and retained the quality of fermented milk. Moreover, the antibacterial properties of kefir is enhanced by increasing the production of certain acids. [ABSTRACT FROM AUTHOR]

• A contact multi-body dynamics model of an RV reducer is presented. • Vibration properties of RV reducer under excitation of faulty NBRs are studied. • The accuracy of the dynamic model has been confirmed by experimental tests. • Defect excitation has a unique periodic effect on the RV reducer's vibration. • The condition monitoring of RV reducer is supported by simulation and test data. The rotate vector (RV) reducer's needle roller bearings (NRBs) are vulnerable to wear and flaws such as fatigue spalling of the raceway material. Studying the vibration mechanism and the excitation laws of NRB failures is essential to enhancing the RV reducer's performance and comprehending its operating state. This paper presents a dynamic model of the RV reducer based on the theory of contact multibody dynamics. It integrates internal and external raceway defects and takes into account the synchronous contact interaction between NRB groups and the crankshaft and cycloidal gears, as well as the time-varying mesh stiffness in the planetary gear transmission and cycloidal pin transmission. The study demonstrates that the rolling of bearings and the meshing of internal transmission components are the primary causes of vibration in a healthy RV reducer through experimental verification and dynamic simulation analysis of the system with and without NRB failures. Both the crankshaft rotation frequency and the cycloidal gear rotation frequency affect the vibration excitation source's characteristic frequency. The vibration amplitude of the RV reducer is influenced by bearing flaws on a periodic basis. The impact of internal raceway defects is greater than that of external raceway faults, resulting in a notable rise in vibration amplitude. [ABSTRACT FROM AUTHOR]

The cuticle is the outmost layer of the eggshell and may affect the hatchability by modulating eggshell conductance. Three different solutions using acetic acid (AA), vinegar (V), and citric acid (CA) for cuticle removal by egg washing were developed, and the effects of cuticle removal on hatching performance of quail hatching eggs were evaluated. A total of 5,238 fresh quail hatching eggs were randomly divided into 9 treatments as follows: unwashed control, nondipped (CND); washed control, water dipped (CWD); standard control, 0.13% sodium hyperchlorite (CSH); 2% AA (AA2); 4% AA (AA4); 44.4% V (V2); 88.8% V (V4); 2% CA (CA2); and 4% CA (CA4). Overall, AA4, V4, and CA4 treatments significantly improved the hatchability of fertile eggs (95.42%, 94.16% and 95.66%, respectively) (P < 0.05) and the hatchability of CND, CWD, CSH, AA2, V2 and CA2 treatments were 90.98%, 93.00%, 92.27%, 79.44%, 90.37%, and 90.59%, respectively. The eggshell thickness and cuticle quality results showed that all AA, V, and CA solutions can effectively remove the quail eggshell cuticle, and AA4, V4 and CA4 significantly decreased eggshell thickness (P < 0.05). Microbial activity on the eggshell surface in all acid treatments was reduced significantly at day 0 of incubation (P < 0.05) and that significantly decreased than controlled treatments over the incubation period except AA2 treatment.Egg weight loss was lower for all acid treatments than that of the CND treatment (P < 0.05). There was no clear effect of treatments on chick quality. Hatch time in AA4, V4, and CA4 treatments slightly improved compared with controlled treatments (P > 0.05). There were no significant differences between treatments for chick livability and live weight at the first 21 D of life. Results of the present study indicate that cuticle removal with AA4, V4, or CA4 could effectively decrease the microbial activity on the eggshell surface during the incubation period and improve hatchability of quail hatching eggs without negative effects on hatch time and performance of quail chicks. [ABSTRACT FROM AUTHOR]

Cefotaxime is commonly used in treating bacterial infections in neonates. To characterize the pharmacokinetic process in neonates and evaluate different recommended dosing schedules of cefotaxime, a physiologically-based pharmacokinetic (PBPK) model of cefotaxime was established in adults and scaled to neonates. A whole-body PBPK model was built in PK-SIM® software. Three elimination pathways are composed of enzymatic metabolism in the liver, passive filtration through glomerulus, and active tubular secretion mediated by renal transporters. The ontogeny information was applied to account for age-related changes in cefotaxime pharmacokinetics. The established models were verified with realistic clinical data in adults and pediatric populations. Simulations in neonates were conducted and 100 % of the dosing interval where the unbound concentration in plasma was above the minimum inhibitory concentration (f T >MIC) was selected as the target index for dosing regimen evaluation. The developed PBPK models successfully described the pharmacokinetic process of cefotaxime in adults and were scaled to the pediatric population. Good verification results were achieved in both adults' and neonates' PBPK models, indicating a good predictive performance. The optimal dosage regimen of cefotaxime was proposed according to the postnatal age (PNA) and gestational age (GA) of neonates. For preterm neonates (GA < 36 weeks), dosages of 25 mg/kg every 8 h in PNA 0–6 days and 25 mg/kg every 6 h in PNA 7–28 days were suggested. For term neonates (GA ≥ 36 weeks), dosages of 33 mg/kg every 8 h in PNA 0–6 days and 33 mg/kg every 6 h in PNA 7–28 days were recommended. Our study may provide useful experience in practicing PBPK model-informed precision dosing in the pediatric population. [ABSTRACT FROM AUTHOR]

[Display omitted] • Brain-target glucose-modified liposome EGCG-Glu-Lip was prepared and characterized. • EGCG-Glu-Lip possessed better ability to cross blood–brain barrier than EGCG. • EGCG-Glu-Lip protected neuronal cell from oxidative damage more than EGCG. • EGCG-Glu-Lip is an efficient nano delivery pathway of EGCG to brain tissue. (-)-Epigallocatechin-3-gallate (EGCG) possesses potent antioxidant and neuroprotective properties. In this study, a novel glucose-modified EGCG encapsulated liposome (EGCG-Glu-Lip) was developed and characterized. EGCG-Glu-Lip liposome's cytotoxicity, brain targeting ability, and its antioxidative neuroprotection were examined via bEnd.3 and PC12 cells testing. EGCG-Glu-Lip liposome particle mean size was 158.7 nm, with encapsulation efficiency 73.05 % under EGCG/lipid mass ratio 1:22 and soybean phospholipids (SPC) to cholesterol (Chol) mass ratio 3.84:1. EGCG-Glu-Lip exhibited less cytotoxicity, stronger protection to PC12 cells from H 2 O 2 induced oxidative damage, keeping reactive oxygen species (ROS) level. Glucose modified liposome (Glu-Lip) cellular uptake in bEnd.3 and PC12 cells were 1.5-fold and 1.3-fold higher than that of Lip, supporting EGCG-Glu-Lip possessing enhanced blood–brain barrier (BBB) permeability mediated via glucose transporter protein 1 (GLUT1) and neuronal cell uptake for brain targeting. EGCG-Glu-Lip could provide an efficient nano delivery pathway to deliver sufficient EGCG to brain tissue exerting its antioxidative neuroprotection more efficiently. [ABSTRACT FROM AUTHOR]

Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H 2 O 2 -induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H 2 O 2 -induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy. Image 1 • Exosomes can suppress the H 2 O 2 -induced nucleus pulposus cell inflammation. • Damaged mitochondria can be restored with exosomes treatment. • Exosomes can slow the progression of intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Abstract In this paper, seismic response of a subway station structure was analyzed using a fault-structure system, which was performed in a two-step process. First, the strong ground motions induced by the specific active fault were synthesized using the revised empirical Green's function (EGF) method at a geologic-length scale. Then, the synthesized seismic waves were used as the input seismic excitations for the dynamic response analysis of a subway station structure at an engineering-length scale. The maximum story drift deformation was calculated by finite element methods. The calculated results indicate that the maximum story drift angles of the subway station have a linear correlation with the peak ground displacements, which are different from the surface structures. Correlation between maximum story drift angles and the flexibility ratio were discussed at last. The results show that subway stations with smaller flexibility ratio suffer smaller story drift deformation. For underground structures with small flexibility ratio, the decreasing of frictional coefficients of the interfaces between the underground structure and the surrounding soil would decrease the maximum story drift deformation. [ABSTRACT FROM AUTHOR]

Highlights • A deep autoencoder-based reconstruction model is proposed for 3D saliency estimation. • Integrating depth in the initial stage exhibits more decisive results on perception. • Enhancing the learning of background is effective to reduce the false positive rate. • Reconstruction residual is coherent with the cognitive gap to reflect saliency. • Our model shows inspiring results on fixation prediction and proto-object extraction. Abstract Studies have implied that depth is one of the important cues guiding visual attention. However, depth information has not been well explored in existing saliency estimation models. In this paper, we propose a model inspired by the observations in three-dimensional environment to better present the influence of depth. Firstly, we use depth to estimate each region's probability of being background. Afterward, we sample pairs of surrounding and central patches from the possible background of each image to train an autoencoder-based network. As a network learned from background, it tends to describe the center-surround reconstruction pattern in background rather than foreground. Therefore, the detection of saliency can be formulated by measuring the reconstruction residual of the network. With emphasis on sampling from background, the proposed method can decrease the false positive rate in stereoscopic saliency estimation significantly. Experimental results demonstrate that the proposed method can outperform the state-of-the-art fixation prediction algorithms on several public data sets for stereoscopic saliency estimation. Additionally, it is efficiently used for proto-object extraction. [ABSTRACT FROM AUTHOR]

The comprehension of the community vulnerability levels is pivotal for understanding how communities respond to diverse hazard events and supporting community resilience management. Existing assessment approaches often treat social vulnerability as static by assuming that residents stay within their home community, which ignored the influence of human mobilities on the vulnerability distribution. To overcome these limitations, in this study, we developed a spatial-temporal community vulnerability assessment framework that integrates human mobility with demographic characteristics. Specifically, we integrated geographic data, e.g., mobile phone data, and human activity trajectory data, e.g., activity survey data, to (1) map demographic-dependent varying human trajectory, (2) identify the dynamic distributions of social vulnerable groups, and (3) based on this to more comprehensively evaluate community vulnerability. We selected Philadelphia County of Pennsylvania as a case study to validate this method. The simulation results demonstrate that the spatial-temporal distribution of some vulnerable populations undergoes significant changes over time due to individual mobility. Furthermore, we also find that different vulnerable groups within the same community show various mobility patterns. Our results highlight the importance of integrating demographic-based human mobility into community vulnerability assessment and complementing current static vulnerability with a more comprehensive understanding to support emergency management, which could enhance the effectiveness and efficiency of timely emergency planning and responses to disasters. [ABSTRACT FROM AUTHOR]

The uses of thermal and chemical treatments were evaluated with respect to the inactivation of the Lactobacillus virulent bacteriophage P2. Thermal treatments consisted of heating the phage at 63, 72, and 90°C in three broth media: de Man Rogosa Sharpe broth, reconstituted skim milk, and Tris magnesium gelatin buffer. Chemical treatments evaluated were ethanol, isopropanol, sodium hypochlorite, and peracetic acid at various concentrations. Phage P2 was completely inactivated in 20 and 5 min at 72 and 90°C, respectively. Reconstituted skim milk and de Man Rogosa Sharpe broth provided optimum and minimum heat protection, respectively. Only sodium hypochlorite at 400 and 800 ppm completely inactivated the phage in 50 and 30 min, respectively. Treatment with 100% ethanol and isopropanol resulted in only a ca. 5.1-log reduction. Peracetic acid at the highest concentration used (0.45%) resulted in only a 1.40-log reduction of the phage within 60 min. These results provide additional data for establishing effective methods of controlling phage contamination in dairy and laboratory environments. [ABSTRACT FROM AUTHOR]