Potassium‐ion batteries (PIBs) have emerged as a compelling complement to existing lithium‐ion batteries for large‐scale energy storage applications, due to the resource‐abundance of potassium, the ...low standard redox potential and high conductivity of K+‐based electrolytes. Rapid progress has been made in identifying suitable carbon anode materials to address the sluggish kinetics and huge volume variation problems caused by large‐size K+. However, most research into carbon materials has focused on structural design and performance optimization of one or several parameters, rather than considering the holistic performance especially for realistic applications. This perspective examines recent efforts to enhance the carbon anode performance in terms of initial Coulombic efficiency, capacity, rate capability, and cycle life. The balancing of the intercalation and surface‐driven capacitive mechanisms while designing carbon structures is emphasized, after which the compatibility with electrolyte and the cell assembly technologies should be considered under practical conditions. It is anticipated that this work will engender further intensive research that can be better aligned toward practical implementation of carbon materials for K+ storage.
For developing advanced carbon anode materials in potassium‐ion batteries, it is vital to well balance the diffusion‐controlled intercalation and surface‐driven capacitive mechanisms. Consequently, comprehensive optimization of initial Coulombic efficiency, capacity, rate capability, cycle life, and low‐potential plateau discharge/charge curves could be realized to be better aligned toward practical implementation of carbon materials for K+ storage.
Vocalizations in animals, particularly birds, are critically important behaviors that influence their reproductive fitness. While recordings of bioacoustic data have been captured and stored in ...collections for decades, the automated extraction of data from these recordings has only recently been facilitated by artificial intelligence methods. These have yet to be evaluated with respect to accuracy of different automation strategies and features. Here, we use a recently published machine learning framework to extract syllables from ten bird species ranging in their phylogenetic relatedness from 1 to 85 million years, to compare how phylogenetic relatedness influences accuracy. We also evaluate the utility of applying trained models to novel species. Our results indicate that model performance is best on conspecifics, with accuracy progressively decreasing as phylogenetic distance increases between taxa. However, we also find that the application of models trained on multiple distantly related species can improve the overall accuracy to levels near that of training and analyzing a model on the same species. When planning big-data bioacoustics studies, care must be taken in sample design to maximize sample size and minimize human labor without sacrificing accuracy.
Vocalizations in animals, particularly birds, are critically important behaviors that influence their reproductive fitness. While recordings of bioacoustic data have been captured and stored in ...collections for decades, the automated extraction of data from these recordings has only recently been facilitated by artificial intelligence methods. These have yet to be evaluated with respect to accuracy of different automation strategies and features. Here, we use a recently published machine learning framework to extract syllables from ten bird species ranging in their phylogenetic relatedness from 1 to 85 million years, to compare how phylogenetic relatedness influences accuracy. We also evaluate the utility of applying trained models to novel species. Our results indicate that model performance is best on conspecifics, with accuracy progressively decreasing as phylogenetic distance increases between taxa. However, we also find that the application of models trained on multiple distantly related species can improve the overall accuracy to levels near that of training and analyzing a model on the same species. When planning big-data bioacoustics studies, care must be taken in sample design to maximize sample size and minimize human labor without sacrificing accuracy.
Seamless phase 2/3 design has become increasingly popular in clinical trials with a single endpoint. Trials that define success based on the achievement of all co-primary endpoints (CPEs) encounter ...the challenge of inflated type 2 error rates, often leading to an overly large sample size. To tackle this challenge, we introduced a seamless phase 2/3 design strategy that employs Bayesian predictive power (BPP) for futility monitoring and sample size re-estimation at interim analysis. The correlations among multiple CPEs are incorporated using a Dirichlet-multinomial distribution. An alternative approach based on conditional power (CP) was also discussed for comparison. A seamless phase 2/3 vaccine trial employing four binary endpoints under the non-inferior hypothesis serves as an example. Our results spotlight that, in scenarios with relatively small phase 2 sample sizes (e.g., 50 or 100 subjects), the BPP approach either outperforms or matches the CP approach in terms of overall power. Particularly, with n
= 50 and ρ = 0, BPP showcases an overall power advantage over CP by as much as 8.54%. Furthermore, when the phase 2 stage enrolled more subjects (e.g., 150 or 200), especially with a phase 2 sample size of 200 and ρ = 0, the BPP approach evidences a peak difference of 5.76% in early stop probability over the CP approach, emphasizing its better efficiency in terminating futile trials. It's noteworthy that both BPP and CP methodologies maintained type 1 error rates under 2.5%. In conclusion, the integration of the Dirichlet-Multinominal model with the BPP approach offers improvement in certain scenarios over the CP approach for seamless phase 2/3 trials with multiple CPEs.
B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein involved in apoptosis and autophagy by communication with ER and mitochondria. BAP31 is cleaved by ...caspase-8 and generates a proapoptotic fragment, p20BAP31, which has shown to induce ER stress and apoptosis through multiple pathways. In this study, we found that p20BAP31 significantly increased the agglomeration of LC3 puncta, suggesting the occurrence of autophagy. Therefore, it is meaningful to explore the mechanism of p20BAP31-induced autophagy, and further analyze the relationships among p20BAP31-induced autophagy, ER stress and apoptosis. The data showed that p20BAP31 induced autophagy by inhibition of the PI3K/AKT/mTOR signaling in colorectal cells. ER stress inhibitor 4-PBA and PERK siRNA alleviated p20BAP31-induced autophagy; in turn, autophagy inhibitors 3-MA and CQ did not affect p20BAP31-induced ER stress, suggesting that p20BAP31-induced ER stress is the upstream of autophagy. We also discovered that ROS inhibitor NAC inhibited p20BAP31-induced autophagy. Furthermore, inhibition of autophagy by CQ suppressed p20BAP31-induced apoptosis and ameliorated cell proliferation. Importantly, p20BAP31 markedly reduced the tumor size in vivo, and significantly enhanced the autophagy levels in the tumor tissues. Collectively, p20BAP31 initiates autophagy by inhibiting the PI3K/AKT/mTOR signaling and activating the PERK-mediated ROS accumulation, further promotes p20BAP31-induced apoptosis and ultimately results in cell death. This study comprehensively reveals the potential mechanism of p20BAP31-induced cell death, which may provide new strategies for antitumor therapy.
Post-stroke fatigue is a typical complication following stroke. However, existing research primarily focused on its underlying mechanisms, and its impact on rehabilitation outcomes has yet to be ...uncovered.
This study aims to explore the impact of post-stroke fatigue on rehabilitation outcomes during hospitalization.
This was a prospective multicenter observational study including 46 stroke patients receiving comprehensive rehabilitation treatment. Patients' basic information was recorded upon admission and patients' functional independence was assessed with Functional Independence Measure (FIM) both upon admission and discharge. One week after rehabilitation treatment, fatigue, positivity in daily activity, attention, and memory were assessed. Serum biochemical indicators and levels of C-reactive protein (CRP) were assessed weekly following admission. The pain scores were assessed during the first week of hospitalization to calculate the average. Correlation analysis, linear regression and propensity score matching (PSM) were used to analyze the impact of fatigue on FIM scores at discharge and length of hospital stay.
The proportion of patients with low fatigue was 39.13% and significant improvement was revealed in FIM scores upon admissions and discharge (50.67±18.61) vs. (75.13±21.04), P<0.05. Positivity in daily activity, attention, and age are factors that influence post-stroke fatigue. After PSM, low-fatigue group (Fatigue score< 3) showed significant higher motor function independence at discharge (54.39 ± 15.42) vs. (41.89 ± 14.90), P<0.05 and shorter hospital stay (28.54±9.13)d vs. (37.32 ± 9.81)d, P<0.05 than high-fatigue group. There was a significant difference (P<0.05) in level of CRP between the first inpatient week and the third week, with declining trend.
Post-stroke fatigue can affect the rehabilitation outcomes regarding motor function independence and length of hospital stay.
Neuroblastoma (NB) is one of the highly vascularized childhood solid tumors, and understanding the molecular mechanisms underlying angiogenesis in NB is crucial for developing effective therapeutic ...strategies. B-cell receptor-associated protein 31 (BAP31) has been implicated in tumor progression, but its role in angiogenesis remains unexplored. This study investigated BAP31 modulation of pro-angiogenic factors in SH-SY5Y NB cells. Through protein overexpression, knockdown, antibody blocking, and quantification experiments, we demonstrated that overexpression of BAP31 led to increased levels of vascular endothelial growth factor A (VEGFA) and Galectin-3 (GAL-3), which are known to promote angiogenesis. Conditioned medium derived from BAP31-overexpressing neuroblastoma cells stimulated migration and tube formation in endothelial cells, indicating its pro-angiogenic properties. Also, we demonstrated that BAP31 enhances capillary tube formation by regulating hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream target, GAL-3. Furthermore, GAL-3 downstream proteins, Jagged 1 and VEGF receptor 2 (VEGFR2), were up-regulated, and blocking GAL-3 partially inhibited the BAP31-induced tube formation. These findings suggest that BAP31 promotes angiogenesis in NB by modulating GAL-3 and VEGF signaling, thereby shaping the tumor microenvironment. This study provides novel insights into the pro-angiogenic role of BAP31 in NB.
Arenobufagin (ArBu) is a natural anticancer drug with good anti-tumor effects, but its clinical applications and drug development potential are limited due to its toxicity. The purpose of this study ...is to reduce the toxic side effects of ArBu and improve the efficacy of tumor treatment by incorporating it into poly(ethylene glycol)-b-poly (lactide) co-polymer (PEG-PLA). ArBu@PEG-PLA micelles were prepared by a thin film hydration method. The optimized micelles were characterized by size, stability, drug loading, encapsulation rate, and drug release. The tumor-inhibition efficacy of the micelles was evaluated on A549 cells and tumor-bearing mice. The ArBu@PEG-PLA micelles have good drug-loading capacity, release performance, and stability. They can accumulate at the tumor site through the EPR effect. The micelles induce apoptosis through a mitochondrial apoptosis pathway. Compared with the free ArBu, the ArBu@PEG-PLA micelles had lower toxicity and higher safety in the acute toxicity evaluation experiment. The in vivo anti-tumor experiment with tumor-bearing mice showed that the tumor-inhibition rate of ArBu@PEG-PLA micelles was 72.9%, which was 1.28-fold higher than that of free ArBu (57.1%), thus showing a good tumor treatment effect. This study indicates that ArBu@PEG-PLA polymeric micelles can significantly improve the toxicity and therapeutic efficacy of ArBu. These can lead to a new therapeutic strategy to reduce the toxicity of ArBu and enhance tumor treatment.
The recent rise in the frequency of influenza A(H5N6) infections in China has raised serious concerns about whether the risk for human infection has increased. We surveyed epidemiologic, clinical, ...and genetic data of human infections with A(H5N6) viruses. Severe disease occurred in 93.8% of cases, and the fatality rate was 55.4%. Median patient age was 51 years. Most H5N6 hemagglutinin (HA) genes in human isolates in 2021 originated from subclade 2.3.4.4b; we estimated the time to most recent common ancestor as June 16, 2020. A total of 13 genotypes with HA genes from multiple subclades in clade 2.3.4.4 were identified in human isolates. Of note, 4 new genotypes detected in 2021 were the major causes of increased H5N6 virus infections. Mammalian-adapted mutations were found in HA and internal genes. Although we found no evidence of human-to-human transmission, continuous evolution of H5N6 viruses may increase the risk for human infections.
The expression of B-cell receptor associated protein 31 (BAP31) is increased in many tumor types, and it is reported to participate in proliferation, migration, and apoptosis. However, the ...relationship between BAP31 and chemoresistance is uncertain. This study investigated the role of BAP31 in regulating the doxorubicin (Dox) resistance of hepatocellular carcinoma (HCC). The expression of proteins was assessed by Western blotting. The correlation between BAP31 expression and Dox resistance was examined by MTT and colony formation assays. Apoptosis was analyzed by flow cytometry and TdT-mediated dUTP nick end labeling assays. Western blot and immunofluorescence analyses were performed in the knockdown cell lines to explore the possible mechanisms. In this study, BAP31 was strongly expressed, and knockdown of BAP31 increased Dox chemosensitivity in cancer cells. Furthermore, the expression of BAP31 was higher in the Dox-resistant HCC cells than that in their parental cells; knockdown of BAP31 reduced the half maximal inhibitory concentration value and overcame Dox resistance in Dox-resistant HCC cells. In HCC cells, knockdown of BAP31 increased Dox-induced apoptosis and enhanced Dox chemosensitivity in vitro and in vivo. The potential mechanism by which BAP31 increased Dox-induced apoptosis is that BAP31 inhibited survivin expression by promoting FoxO1 nucleus-cytoplasm translocation. Knockdown of BAP31 and survivin had a synergistic effect on Dox chemosensitivity by enhancing the apoptosis of HCC cells. These findings reveal that BAP31 knockdown enhances Dox chemosensitivity through the downregulation of survivin, suggesting that BAP31 is a potential therapeutic target for improving the treatment response of HCC with resistance to Dox.
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