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Background: Learning engagement is a crucial predictor of academic achievement. It is essential to understand the factors influencing learning engagement among nursing students, especially from the learner's perspective, which is notably scarce but vital for designing effective educational interventions., Objectives: This study aims to investigate the mediating effect of self-efficacy on the relationship between professional identity and learning engagement for nursing students in higher vocational colleges., Design: A cross-sectional electronic survey was conducted., Setting: The study was conducted in four higher vocational colleges located in Guangdong Province, China., Participants: A total of 944 first- and second-year nursing students participated in the study between October and November 2022., Methods: Data were collected with questionnaires on general information, professional identity, self-efficacy, and learning engagement and analyzed with SPSS 26.0 and PROCESS v4.1 (Model 4), exploring relationships among professional identity, self-efficacy, and learning engagement through Pearson correlations, multivariate regression, and mediation analysis with 5000 bootstrap samples., Results: The participants exhibited moderate levels of professional identity (85.37 ± 13.52), self-efficacy (25.58 ± 5.74), and learning engagement (71.26 ± 16.17), which were all significantly correlated with each other (P < 0.01). In the model of the mediating effect, professional identity directly (β = 0.811, t = 27.484, P < 0.001) and indirectly [β = 0.112,95%CI (0.074-0.154)] significantly predicts college students' learning engagement; professional identity has a significant positive predictive effect on self-efficacy (β = 0.182, t = 14.459, P < 0.001) and self-efficacy significantly predicts learning engagement (β = 0.614, t = 8.292, P < 0.001). Furthermore, the direct effect of professional identity on learning engagement (0.699) and its mediating effect (0.112) account for 86.19 % and 13.81 % of the total effect (0.811), respectively., Conclusion: Participants exhibited moderate levels of professional identity, self-efficacy, and learning engagement. Professional identity and self-efficacy are interconnected and positively correlated, influencing learning engagement among nursing students, which highlights the need to foster these qualities to enhance education and future practice., Competing Interests: Declaration of competing interest No conflicts of interest have been declared by the authors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The antidepressant properties of Hypericum species are known. Hyperibone J, a principal component found in the flowers of Hypericum bellum, exhibited in vitro anti-inflammatory effects. However, the antidepressant effects and mechanisms of Hyperibone J remain to be elucidated. Adenosine kinase (ADK) is upregulated in epilepsy and depression and has been implicated in promoting neuroinflammation., Objectives: This study aimed to explore the impact of Hyperibone J on neuroinflammation-mediated depression and the mechanism underlying this impact., Methods: This study employed acute and chronic in vivo depression models and an in vitro LPS-induced depression model using BV-2 microglia. The in vivo antidepressant efficacy of Hyperibone J was assessed through behavioral assays. Techniques such as RNA-seq, western blot, qPCR and ELISA were utilized to elucidate the direct target and mechanism of action of Hyperibone J., Results: Compared with the model group, depression-like behaviors were significantly alleviated in the Hyperibone J group. Furthermore, Hyperibone J mitigated hippocampal neuroinflammation and neuronal damage. RNA-seq suggested that Hyperibone J predominantly influenced inflammation-related pathways. In vitro experiments revealed that Hyperibone J reversed the LPS-induced overexpression and release of inflammatory factors. Network pharmacology and various molecular biology experiments revealed that the potential binding of Hyperibone J at the ASN-312 site of ADK diminished the stability and protein expression of ADK. Mechanistic studies revealed that Hyperibone J attenuated the ADK/ATP/P2X7R/Caspase-1-mediated maturation and release of IL-1β. The study also revealed a significant correlation between Tlr4 expression and depression-like behaviors in mice. Hyperibone J downregulated ADK, inhibiting Tlr4 transcription, which in turn reduced the phosphorylation of NF-κB and the subsequent transcription of Nlrp3, Il-1b, Tnf, and Il-6., Conclusion: Hyperibone J exerted antineuroinflammatory and antidepressant effects by binding to ADK in microglia, reducing its expression and thereby inhibiting the ATP/P2X7R/Caspase-1 and TLR4/NF-κB pathways. This study provides experimental evidence for the therapeutic potential of Hypericum bellum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

This study was designed to explore the role of RIP3 in DOX-induced cardiotoxicity and its underlying molecular mechanisms. Our results demonstrate that RIP3 exacerbates DOX-induced cardiotoxicity through promoting oxidative stress and pyroptosis by regulating the AKT/Nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway. Inhibition of RIP3 using GSK-872 attenuated DOX-induced cardiac remodeling and contractile dysfunction. Moreover, using GSK-872 in vivo, the results revealed that inhibition of RIP3 alleviated DOX-induced cardiotoxicity by the resulting inhibition of oxidative stress and pyroptosis. In addition, inhibition of RIP3 increased the protein levels of AKT and Nrf2 in DOX-treated mouse hearts. Furthermore, the AKT inhibitor LY294002 lessened RIP3 reduction-offered protection against DOX-induced H9c2 cell injury by moderating oxidative stress and pyroptosis. Taken together, these data demonstrate that RIP3 activation orchestrates DOX-induced cardiotoxicity through elevated oxidative stress and pyroptosis in an AKT/Nrf2-dependent manner. Those findings highlight the clinical relevance and therapeutic potential of targeting RIP3 for the treatment of DOX-induced cardiotoxicity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury in vitro. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity., Methods: A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO 2 ) and the carbon dioxide ventilation equivalent slope (VE/VCO 2 slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters., Results: The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO 2 and VE/VCO 2 slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO 2 slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO 2  ≤ 15 mL/kg/min and a VE/VCO 2 slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters., Conclusions: TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance., (© 2024. The Author(s).)

Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer. We demonstrate that a simple protocol enriches prostatic proteins in urine. Secreted and EV proteins arise from different subcellular compartments. Urinary EVs are faithful surrogates of tissue proteomes, but secreted proteins in urine or cell line EVs are not. The urinary proteome is longitudinally stable over several years. It can accurately and non-invasively distinguish malignant from benign prostatic lesions and can risk-stratify prostate tumors. This resource quantifies the complexity of the urinary proteome and reveals the synergistic value of secreted and EV proteomes for translational and biomarker studies., (© 2024. The Author(s).)

Background: Studies have shown that oxidative stress and its resistance plays important roles in the process of tumor metastasis, and mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is an important molecular event in oxidative stress. In lung cancer, the normal fibroblasts (NFs) are activated as cancer-associated fibroblasts (CAFs), and act in the realms of the tumor microenvironment (TME) with consequences for tumor growth and metastasis. However, its activation mechanism and whether it participates in tumor metastasis through antioxidative stress remain unclear., Methods: The role and signaling pathways of tumor cell derived extracellular vesicles (EVs) activating NFs and the characteristic of induced CAFs (iCAFs) were measured by the transmission electron microscopy, nanoparticle tracking analysis, immunofluorescence, collagen contraction assay, quantitative PCR, immunoblotting, luciferase reporter assay and mitochondrial membrane potential detection. Mitochondrial genome and single nucleotide polymorphism sequencing were used to investigate the transport of mtDNA from iCAFs to ρ 0 cells, which were tumor cells with mitochondrial dysfunction caused by depletion of mtDNA. Further, the effects of iCAFs on mitochondrial function, growth and metastasis of tumor cells were analysed in co-culture models both in vitro and in vivo, using succinate dehydrogenase, glutathione and oxygen consumption rate measurements, CCK-8 assay, transwell assay, xenotransplantation and metastasis experiments as well as in situ hybridization and immunohistochemistry., Results: Our findings revealed that EVs derived from high-metastatic lung cancer cells packaged miR-1290 that directly targets MT1G, leading to activation of AKT signaling in NFs and inducing NFs conversion to CAFs. The iCAFs exhibit higher levels of autophagy and mitophagy and more mtDNA release, and reactive oxygen species (ROS) could further promote this process. After cocultured with the conditioned medium (CM) of iCAFs, the ρ 0 cells may restore its mitochondrial function by acquisition of mtDNA from CAFs, and further promotes tumor metastasis., Conclusions: These results elucidate a novel mechanism that CAFs activated by tumor-derived EVs can promote metastasis by transferring mtDNA and restoring mitochondrial function of tumor cells which result in resistance of oxidative stress, and provide a new therapeutic target for lung cancer metastasis., (© 2024. The Author(s).)

Background: Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low-intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters., Methods: This study is a single-center, prospective study, including 105 PAH patients who underwent regular follow-up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography-based three-strata risk model was assessed using Kaplan-Meier curves and COX regression analysis., Results: A total of 98 PAH patients were ultimately included in this study. The median follow-up duration was 26 months (range 7-28 months). The echocardiography-based three-strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography-based three-strata model had higher diagnostic value (C-index = .76) compared to the 2022 ESC/ERS three-strata model and four-strata model (C-index = .66 and C-index = .61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR = 15.1, 95%CI:4.4-51.9, p < .001)., Conclusion: The echocardiography-based three-strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low-intermediate risk PAH patients under targeted treatment., (© 2024 Wiley Periodicals LLC.)

Anesthetic-induced brain activity study is crucial in avian cognitive-, consciousness-, and sleep-related research. However, the neurobiological mechanisms underlying the generation of brain rhythms and specific connectivity of birds during anesthesia are poorly understood. Although different kinds of anesthetics can be used to induce an anesthesia state, a comparison study of these drugs focusing on the neural pattern evolution during anesthesia is lacking. Here, we recorded local field potentials (LFPs) using a multi-channel micro-electrode array inserted into the nidopallium caudolateral (NCL) of adult pigeons (Columba livia) anesthetized with chloral hydrate, pelltobarbitalum natricum or urethane. Power spectral density (PSD) and functional connectivity analyses were used to measure the dynamic temporal neural patterns in NCL during anesthesia. Neural decoding analysis was adopted to calculate the probability of the pigeon's brain state and the kind of injected anesthetic. In the NCL during anesthesia, we found elevated power activity and functional connectivity at low-frequency bands and depressed power activity and connectivity at high-frequency bands. Decoding results based on the spectral and functional connectivity features indicated that the pigeon's brain states during anesthesia and the injected anesthetics can be effectively decoded. These findings provide an important foundation for future investigations on how different anesthetics induce the generation of specific neural patterns., (© 2024. International Federation for Medical and Biological Engineering.)

The accurate detection of biogenic amines (BAs) is an important means of ensuring the quality and safety of cephalopod seafood products. In this study, the pre-column derivatization of high-performance liquid chromatography (HPLC) was optimized using dansyl chloride (Dns-Cl) to detect BAs in octopus, cuttlefish, and squid. The reasons for the formation of BAs were investigated by assessing their decarboxylase activity and the rates of decomposition. The findings demonstrated that using Dns-Cl to optimize pre-column derivatization enabled the separation of nine different BAs. The detection limits ranged from 0.07 to 0.25 mg/L, and the results exhibited a high level of linearity (R 2  ≥ 0.997). The decarboxylase activity and biodegradation rate positively correlated with the formation of BAs at temperatures below 0°C. Notably, the decarboxylase activity of octopus, cuttlefish, and squid exhibited a significant increase with prolonged storage time, and formyltransferase and carbamate kinase may be the key decarboxylase in cephalopod products. These findings serve as a valuable reference for further investigations into the mechanisms behind BAs production and the development of control technologies for BAs in cephalopod products. This study has successfully demonstrated the effectiveness of the Dns-Cl pre-column derivatization-HPLC method in accurately and efficiently detecting BAs in octopus, cuttlefish, and squid. Moreover, it highlights the influence of decarboxylase content and biodegradation rate on the formation of BAs. Importantly, this method can serve as a reference for detecting BAs in various seafood products., (© 2024 Institute of Food Technologists.)

Background: Exploring the neural encoding mechanism and decoding of motion state switching during flight can advance our knowledge of avian behavior control and contribute to the development of avian robots. However, limited acquisition equipment and neural signal quality have posed challenges, thus we understand little about the neural mechanisms of avian flight., Methods: We used chronically implanted micro-electrode arrays to record the local field potentials (LFPs) in the formation reticularis medialis mesencephali (FRM) of pigeons during various motion states in their natural outdoor flight. Subsequently, coherence-based functional connectivity networks under different bands were constructed and the topological features were extracted. Finally, we used a support vector machine model to decode different flight states., Results: Our findings indicate that the gamma band (80-150 Hz) in the FRM exhibits significant power for identifying different states in pigeons. Specifically, the avian brain transmitted flight related information more efficiently during the accelerated take-off or decelerated landing states, compared with the uniform flight and baseline states. Finally, we achieved a best average accuracy of 0.86 using the connectivity features in the 80-150 Hz band and 0.89 using the fused features for state decoding., Conclusions: Our results open up possibilities for further research into the neural mechanism of avian flight and contribute to the understanding of flight behavior control in birds., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Photocatalytic selective oxidation of alcohols into aldehydes and H 2 is a green strategy for obtaining both value-added chemicals and clean energy. Herein, a dual-purpose ZnIn 2 S 4 @CdS photocatalyst was designed and constructed for efficient catalyzing benzyl alcohol (BA) into benzaldehyde (BAD) with coupled H 2 evolution. To address the deep-rooted problems of pure CdS, such as high recombination of photogenerated carriers and severe photo-corrosion, while also preserving its superiority in H 2 production, ZnIn 2 S 4 with a suitable band structure and adequate oxidizing capability was chosen to match CdS by constructing a coupled reaction. As designed, the photoexcited holes (electrons) in the CdS (ZnIn 2 S 4 ) were spatially separated and transferred to the ZnIn 2 S 4 (CdS) by electrostatic pull from the built-in electric field, leading to expected BAD production (12.1 mmol g -1 h -1 ) at the ZnIn 2 S 4 site and H 2 generation (12.2 mmol g -1  h -1 ) at the CdS site. This composite photocatalyst also exhibited high photostability due to the reasonable hole transfer from CdS to ZnIn 2 S 4 . The experimental results suggest that the photocatalytic transform of BA into BAD on ZnIn 2 S 4 @CdS is via a carbon-centered radical mechanism. This work may extend the design of advanced photocatalysts for more chemicals by replacing H 2 evolution with N 2 fixation or CO 2 reduction in the coupled reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abnormal microglial activation has been suggested as "driven force" promoting brain aging. Lipid droplets accumulating microglia (LDAM), identified as a novel inflammatory phenotype, elevate neuroinflammation and exaggerate neuronal injuries in aging and multiple neurodegenerative diseases. Since chronic HIV (human immunodeficiency virus) (+) individuals show an accelerated brain aging and higher incidence of neurological symptoms compared to age-matched HIV (-) population, we hypothesize that LDAM are also involved in such phenomenon. For validating the hypothesis, we employed HIV transgenic (HIV-Tg) and wilt type (WT) rats to check lipid droplets (LDs) accumulation in the brains at mature (6 months) and middle age (12 months). Our results showed that HIV-Tg rats possess higher levels of LDs formation in the hippocampus (HP) and prefrontal cortex (PFc) than controls at middle age. Increased LDs are mainly presented in microglia in the HP but largely co-localized with astrocytes in the PFc. Interestingly, increased LDs are associated with upregulation on Iba1 but not with GFAP levels. HIV-Tg rats reveal an accelerated LDs accumulation during normal aging. Purified microglia from HIV-Tg rats (12 month) show higher expression of neuroimmune signaling than microglia from controls. HIV-Tg rats showed dysregulation on cholesterol synthesis in the brain HP as well as deficiency on locomotion coordination compared to controls. Overall, our results demonstrate substantial LDs accumulation in the brains of HIV-Tg rats which is associated with abnormal microglial activation and accelerated decline on locomotion coordination during aging. Dysregulation on lipid metabolism might underlie accelerated brain aging in the context of chronic HIV infection.

Background: The main clinical manifestations of patients with Pierre Robin sequence (PRS) include micrognathia, the glossoptosis and dyspnoea. The difficulty of tracheal intubation (TI) in such patients is increased. Objective: The purpose of the study was to evaluate the reliability and efficacy of the PRS simulator. Methods: A PRS simulator was developed by using 3-dimensional (3D) printing technology under computer-aided design. A total of 12 anaesthesiologists each trained 5 times for TI on the PRS Training Simulator-1 and recorded the simulation time. After the training, they were randomly divided into three groups with a total of 12 nontrained anaesthesiologists, and the simulation was completed on PRS Simulator-2, 3 and 4. The simulation time was recorded, and the performance was evaluated by three chief anaesthesiologists. Then, all 24 anaesthesiologists completed the questionnaire. Results: A PRS simulator developed by 3D printing was used to simulate the important aspects of TI. The average number of years worked was 6.3 ± 3.1 years, and 66.7% were female. The time for the 12 anaesthesiologists to complete the training gradually decreased ( p < 0.01). Compared with the trained anaesthesiologists, the simulation time of TI in the nontrained anaesthesiologists was much longer (all p < 0.01). In addition, the simulation performance of the trained anaesthesiologists was relatively better (all p < 0.01). Conclusion: The reliability and efficacy of the PRS simulator is herein preliminarily validated, and it has potential to become a teaching and training tool for anaesthesiologists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mao, Liu, Zhong, Qin, Ma, Zuo, Zhang and Yang.)

Research in reinforcement learning indicates that animals respond differently to positive and negative reward prediction errors, which can be calculated by assuming learning rate bias. Many studies have shown that humans and other animals have learning rate bias during learning, but it is unclear whether and how the bias changes throughout the entire learning process. Here, we recorded the behavior data and the local field potentials (LFPs) in the striatum of five pigeons performing a probabilistic learning task. Reinforcement learning models with and without learning rate biases were used to dynamically fit the pigeons' choice behavior and estimate the option values. Furthemore, the correlation between the striatal LFPs power and the model-estimated option values was explored. We found that the pigeons' learning rate bias shifted from negative to positive during the learning process, and the striatal Gamma (31 to 80 Hz) power correlated with the option values modulated by dynamic learning rate bias. In conclusion, our results support the hypothesis that pigeons employ a dynamic learning strategy in the learning process from both behavioral and neural aspects, providing valuable insights into reinforcement learning mechanisms of non-human animals.

Navigation is a complex task in which the hippocampus (Hp), which plays an important role, may be involved in interactions between different frequency bands. However, little is known whether this cross-frequency interaction exists in the Hp of birds during navigation. Therefore, we examined the electrophysiological characteristics of hippocampal cross-frequency interactions of domestic pigeons ( Columba livia domestica ) during navigation. Two goal-directed navigation tasks with different locomotor modes were designed, and the local field potentials (LFPs) were recorded for analysis. We found that the amplitudes of high-frequency oscillations in Hp were dynamically modulated by the phase of co-occurring theta-band oscillations both during ground-based maze and outdoor flight navigation. The high-frequency amplitude sub-frequency bands modulated by the hippocampal theta phase were different at different tasks, and this process was independent of the navigation path and goal. These results suggest that phase-amplitude coupling (PAC) in the avian Hp may be more associated with the ongoing cognitive demands of navigational processes. Our findings contribute to the understanding of potential mechanisms of hippocampal PAC on multi-frequency informational interactions in avian navigation and provide valuable insights into cross-species evolution.

Model-based decision-making guides organism behavior by the representation of the relationships between different states. Previous studies have shown that the mammalian hippocampus (Hp) plays a key role in learning the structure of relationships among experiences. However, the hippocampal neural mechanisms of birds for model-based learning have rarely been reported. Here, we trained six pigeons to perform a two-step task and explore whether their Hp contributes to model-based learning. Behavioral performance and hippocampal multi-channel local field potentials (LFPs) were recorded during the task. We estimated the subjective values using a reinforcement learning model dynamically fitted to the pigeon's choice of behavior. The results show that the model-based learner can capture the behavioral choices of pigeons well throughout the learning process. Neural analysis indicated that high-frequency (12-100 Hz) power in Hp represented the temporal context states. Moreover, dynamic correlation and decoding results provided further support for the high-frequency dependence of model-based valuations. In addition, we observed a significant increase in hippocampal neural similarity at the low-frequency band (1-12 Hz) for common temporal context states after learning. Overall, our findings suggest that pigeons use model-based inferences to learn multi-step tasks, and multiple LFP frequency bands collaboratively contribute to model-based learning. Specifically, the high-frequency (12-100 Hz) oscillations represent model-based valuations, while the low-frequency (1-12 Hz) neural similarity is influenced by the relationship between temporal context states. These results contribute to our understanding of the neural mechanisms underlying model-based learning and broaden the scope of hippocampal contributions to avian behavior.

Prostate cancer is a significant health problem in the United States. It is remarkably heterogenous, ranging from slow growing disease amenable to active surveillance to highly aggressive forms requiring active treatments. Therefore, being able to precisely determine the nature of disease and appropriately match patients to available and/or novel therapeutics is crucial to improve patients' overall outcome and quality of life. Recently small extracellular vesicles (sEVs), a subset of nanoscale membranous vesicles secreted by various cells, have emerged as important analytes for liquid biopsy and promising vehicles for drug delivery. sEVs contain various biomolecules such as genetic material, proteins, and lipids that recapitulate the characteristics and state of their donor cells. The application of existing and newly developed technologies has resulted in an increased depth of knowledge about biophysical structures, biogenesis, and functions of sEVs. In prostate cancer patients, tumor-derived sEVs can be isolated from biofluids, commonly urine and blood. They mediate intercellular signaling within the tumor microenvironment and distal organ-specific sites, supporting cancer initiation, progression, and metastasis. A mounting body of evidence suggests that sEV components can be potent biomarkers for prostate cancer diagnosis, prognosis, and prediction of disease progression and treatment response. Due to enhanced circulation stability and bio-barrier permeability, sEVs can be also used as effective drug delivery carriers to improve the efficacy and specificity of anti-tumor therapies. This review discusses recent studies on sEVs in prostate cancer and is focused on their role as biomarkers and drug delivery vehicles in the clinical management of prostate cancer., (Copyright © 2024. Published by Elsevier Inc.)

Diabetic cardiomyopathy (DCM) is a chronic microvascular complication of diabetes that is generally defined as ventricular dysfunction occurring in patients with diabetes and unrelated to known causes. Several mechanisms have been proposed to contribute to the occurrence and persistence of DCM, in which oxidative stress and autophagy play a non-negligible role. Diabetic cardiomyopathy is involved in a variety of physiological and pathological processes. The 5' adenosine monophosphate-activated protein kinase/nuclear factor-erythroid 2-related factor 2 (AMPK/Nrf2) are expressed in the heart, and studies have shown that asiaticoside (ASI) and activated AMPK/Nrf2 have a protective effect on the myocardium. However, the roles of ASI and AMPK/Nrf2 in DCM are unknown. The intraperitoneal injection of streptozotocin (STZ) and high-fat feed were used to establish the DCM models in 100 C57/BL mice. Asiaticoside and inhibitors of AMPK/Nrf2 were used for intervention. Cardiac function, oxidative stress, and autophagy were measured in mice. DCM mice displayed increased levels of oxidative stress while autophagy levels declined. In addition, AMPK/Nrf2 was activated in DCM mice with ASI intervention. Further, we discovered that AMPK/Nrf2 inhibition blocked the protective effect of ASI by compound C and treatment with ML-385. The present study demonstrates that ASI exerts a protective effect against DCM via the potential activation of the AMPK/Nrf2 pathway. Asiaticoside is a potential therapeutic target for DCM., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Atherosclerosis (AS) is a chronic inflammatory vascular disease. Myocardial ischemia originated from AS is the main cause of cardiovascular diseases, one of the major factors contributing to the global disease burden. AS is typically quiescent until occurrence of plaque rupture and thrombosis, leading to acute coronary syndrome and sudden death. Currently, clinical diagnostic techniques suffer from major pitfalls including lack of accuracy and specificity, which makes it rather difficult for drugs to directly target plaques to achieve therapeutic effect. Therefore, how to accurately diagnose and effectively intervene vulnerable AS plaques to achieve accurate delivery of drugs has become an urgent and evolving clinical problem. With the rapid development of nanomedicine and nanomaterials, nanotechnology has shown unique advantages in monitoring vulnerable plaques and thrombus and improving drug efficacy. Recent studies have shown that application of nanoparticle drug delivery system can booster the safety and effectiveness of drug therapy, and molecular imaging technology and nanomedicine also exhibit high clinical application potentials in disease diagnosis. Therefore, nanotechnology provides another promising avenue for diagnosis and treatment of AS and thrombosis, and has shown excellent performance in the development of targeted drug therapy and biomaterials. In this review, the research progress, challenges and prospects of nanotechnology in AS and thrombosis are discussed, expecting to provide new ideas for the prevention, diagnosis and treatment of AS and thrombosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Photocatalytic water splitting has been identified as a promising solution to tackle the current environmental and energy crisis in the world. However, the challenge of this green technology is the inefficient separation and utilization of photogenerated electron-hole pairs in photocatalysts. To overcome this challenge in one system, a ternary ZnO/Zn 3 In 2 S 6 /Pt material was prepared as a photocatalyst using a stepwise hydrothermal process and in-situ photoreduction deposition. The integrated S-scheme/Schottky heterojunction in the constructed ZnO/Zn 3 In 2 S 6 /Pt photocatalyst enabled it to exhibit efficient photoexcited charge separation/transfer. The evolved H 2 reached up to 3.5 mmol g -1 h - 1 . Meanwhile, the ternary composite possessed a high cyclic stability against photo-corrosion under irradiation. Practically, the ZnO/Zn 3 In 2 S 6 /Pt photocatalyst also showed great potential for H 2 evolution while simultaneously degrading organic contaminants like bisphenol A. It is hoped in this work that the incorporation of Schottky junctions and S-scheme heterostructures in the construction of photocatalysts would lead to accelerated electron transfer and high photoinduced electron-hole pair separation, respectively, to synergistically enhance the performance of photocatalysts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Spike sorting is the basis for analyzing spike firing patterns encoded in high-dimensional information spaces. With the fact that high-density microelectrode arrays record multiple neurons simultaneously, the data collected often suffers from two problems: a few overlapping spikes and different neuronal firing rates, which both belong to the multi-class imbalance problem. Since deep reinforcement learning (DRL) assign targeted attention to categories through reward functions, we propose ImbSorter to implement spike sorting under multi-class imbalance. We describe spike sorting as a Markov sequence decision and construct a dynamic reward function (DRF) to improve the sensitivity of the agent to minor classes based on the inter-class imbalance ratios. The agent is eventually guided by the optimal strategy to classify spikes. We consider the Wave&#95;Clus dataset, which contains overlapping spikes and diverse noise levels, and the macaque dataset, which has a multi-scale imbalance. ImbSorter is compared with classical DRL architectures, traditional machine learning algorithms, and advanced overlapping spike sorting techniques on these two above datasets. ImbSorter obtained improved results on the Macro&#95;F1. The results show ImbSorter has a promising ability to resist overlapping and noise interference. It has high stability and promising performance in processing spikes with different degrees of skewed distribution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Copper (Cu) homeostasis is gaining increasing attention in human health as both Cu overload and deficiency evokes pathological changes including cardiovascular diseases (CVDs). Cu supplementation, nanocarriers, and chelators have all exhibited therapeutic promise in some human diseases, although how Cu dyshomeostasis and cuproptosis, a novel form of regulated cell death, contribute to CVD pathology remains elusive. Here, we discuss Cu dyshomeostasis and the potential role of cuproptosis in various CVDs. We evaluate underlying cellular mechanisms, aiming to provide some insights regarding the utility of targeting Cu dyshomeostasis and cuproptosis as a novel strategy in the management of CVDs., Competing Interests: Declaration of interests The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Multiple studies have shown that E2 conjugating enzyme family are dysregulated in various cancers and associated with tumor progression and poor prognosis. In present study, we screened and confirmed that UBE2S is one of the E2 conjugating enzymes highly expressed in non-small cell lung cancer (NSCLC), and it plays an oncogenic role by enhancing cell proliferation, migration and stemness in vitro. Using immunoprecipitation technology combined with mass spectrometry assay, we identified ribosomal protein RPL26 as the substrate protein of UBE2S in NSCLC. At the molecular level, overexpression of UBE2S accelerated the ubiquitination and degradation of RPL26, thus upregulating c-Myc to enhance the progression of NSCLC. In addition, the results of a xenograft experiment showed that inhibiting UBE2S could suppress RPL26-c-Myc mediated NSCLC tumor growth in vivo. Our data provided mechanistic evidence supporting the existence of a novel UBE2S-RPL26-c-Myc axis and its critical contribution to progression of NSCLC., Competing Interests: None., (AJCR Copyright © 2023.)

Echocardiography, a simple and noninvasive tool, is the first choice for screening pulmonary hypertension (PH). However, accurate assessment of PH, incorporating both the pulmonary artery pressures and additional signs for PH remained unsatisfied. Thus, this study aimed to develop a machine learning (ML) model that can automatically evaluate the probability of PH. This cohort included data from 346 (275 for training set and internal validation set and 71 for external validation set) patients with suspected PH patients and receiving right heart catheterization. Echocardiographic images on parasternal short axis-papillary muscle level (PSAX-PML) view from all patients were collected, labeled, and preprocessed. Local features from each image were extracted and subsequently integrated to build a ML model. By adjusting the parameters of the model, the model with the best prediction effect is finally constructed. We used receiver-operating characteristic analysis to evaluate model performance and compared the ML model with the traditional methods. The accuracy of the ML model for diagnosis of PH was significantly higher than the traditional method (0.945 vs. 0.892, p  = 0.027 [area under the curve [AUC]]). Similar findings were observed in subgroup analysis and validated in the external validation set (AUC = 0.950 [95% CI: 0.897-1.000]). In summary, ML methods could automatically extract features from traditional PSAX-PML view and automatically assess the probability of PH, which were found to outperform traditional echocardiographic assessments., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

In Brief: Bacterial infection can induce testicular inflammation and damage male fertility. This paper reveals the role of nuclear receptor subfamily 2 group C member 2 (NR2C2) in macrophage cells in orchitis caused by bacterial endotoxin lipopolysaccharide (LPS) infection., Abstract: Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of NR2C2 in testicular inflammatory injury induced by infection with the bacterial endotoxin LPS. We found that NR2C2 was highly expressed in the testes and the expression of NR2C2 was upregulated in testicular macrophages in the LPS-induced mouse orchitis model in vivo. In primary testicular macrophages and RAW264.7 cells in vitro, RNA interference with the Nr2c2 gene downregulated the expression of inflammatory factors such as IL-1β and IL-6. In addition, the knockdown of NR2C2 in macrophages alleviated the inhibitory effect of the inflammatory supernatant secreted by the macrophages on the proliferation of spermatogonia GC-1 SPG cells. Mechanistically, NR2C2 activated NF-κB signaling by binding with DR elements in the promotor of the Nfκb gene and promoted the development of inflammation. These data are the first to confirm that during LPS-induced bacterial infection, NR2C2 plays a proinflammatory role by activating IL-1β and IL-6 via the NF-κB pathway in macrophages, consequently inhibiting the proliferation of spermatogonia and damaging the quality of sperm. Our findings reveal the important role of NR2C2 in testicular inflammatory injury induced via LPS and provide a new potential target and a molecular basis for the treatment of male infertility caused by bacterial infection.

Multiagent systems face numerous challenges due to environmental uncertainty, with scalability being a critical issue. To address this, we propose a novel multi-agent cooperative model based on a graph attention network. Our approach considers the relationship between agents and continuous action spaces, utilizing graph convolution and recurrent neural networks to define these relationships. Graph convolution is used to define the relationship between agents, while recurrent neural networks define continuous action spaces. We optimize and model the multiagent system by encoding the interaction weights among agents using the graph neural network and the weights between continuous action spaces using the recurrent neural network. We evaluate the performance of our proposed model by conducting experimental simulations using a 3D wargame engine that involves several unmanned air vehicles (UAVs) acting as attackers and radar stations acting as defenders, where both sides have the ability to detect each other. The results demonstrate that our proposed model outperforms the current state-of-the-art methods in terms of scalability, robustness, and learning efficiency., Competing Interests: XW and WC were employed by Beijing SmartChip Microelectronics Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Cui, Huang, Yang, Tao and Wang.)

Studies have shown that acetylation modification plays an important role in tumor proliferation and metastasis. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is downregulated in certain tumors, as a tumor suppressor role. However, the regulation of LHPP expression and its function in nasopharyngeal carcinoma (NPC) remain unclear. In the present study, we found that LHPP was downregulated in NPC, and overexpression of LHPP inhibited the proliferation and invasion of NPC cells. Mechanistically, HDAC4 deacetylated LHPP at K6 and promoted the degradation of LHPP through TRIM21 mediated K48-linked ubiquitination. HDAC4 was confirmed to be highly expressed in NPC cells and promoted the proliferation and invasion of NPC cells through LHPP. Further research found that LHPP could inhibit the phosphorylation of tyrosine kinase TYK2, thereby inhibiting the activity of STAT1. In vivo, knockdown of HDAC4 or treatment with small molecule inhibitor Tasquinimod targeting HDAC4 could significantly inhibit the proliferation and metastasis of NPC by upregulating LHPP. In conclusion, our finding demonstrated that HDAC4/LHPP signal axis promotes the proliferation and metastasis of NPC through upregulating TYK2-STAT1 phosphorylation activation. This research will provide novel evidence and intervention targets for NPC metastasis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Enhanced recovery after surgery (ERAS) is currently the recommended surgical strategy, the main content of which is to reduce perioperative stress response and postoperative complications through perioperative multimodal analgesia and intensive surgery. Since ERAS was introduced, many rehabilitation medicine teams have been deeply involved, including physical therapy, occupational therapy, nutrition therapy and psychological counseling. However, ERAS lacks several powerful means to address perioperative prognostic issues. Therefore, how to further improve the effects of ERAS, reduce perioperative complications and protect vital organ functions has become an urgent problem. With the continuous development of traditional Chinese medicine, electroacupuncture (EA) has been widely used in various clinical applications, and its efficacy and safety have been fully proved. Recent studies have shown that the application of EA in ERAS has had an important impact on rehabilitation researches. In terms of reducing complications, the therapeutic effects of EA treatment mainly include: reducing pain and the use of analgesics; Improvement of postoperative nausea and vomiting; Postoperative immune function treatment; Relieve anxiety and depression. In addition, EA also protects the recovery of physiological functions, including cardiovascular function, cerebrovascular function and gastrointestinal function, etc. To sum up, the complementary strengths of EA and ERAS will allow them to develop and combine. This review discusses the potential value and feasibility of EA in ERAS from the aspects of improving perioperative efficacy and protecting organ functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mao and Yang.)

Peroxynitrite (ONOO - ), as a strong oxidizing reactive nitrogen substance (RNS), is generated endogenously by cells. Its visualization research is crucial to understand relevant disease processes. Herein, we reported a long-wavelength mitochondria-targeted fluorescence "turn on" probe TL. The probe TL could react with ONOO - by using 4-(Bromomethyl)benzeneboronic as a reactive site, which exhibited outstanding characteristics for detection of ONOO - , thus improving response time (about 50 s), sensitivity (DL, 10.1 nM), and emission wavelength (667 nm). Besides, TL displayed well mitochondria targeting and biological visualizing of exogenous and endogenous ONOO - in biological systems. Finally, TL was used to monitor high concentration of dexamethasone-induced an up-regulation of ONOO - . This indicated that TL has excellent potential to study the fluctuation of ONOO - in the physiological and pathological system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The cognitive processes of goal-directed navigation are believed to be organized around and serve the identification and selection of goals. Differences in LFP signals in avian nidopallium caudolaterale (NCL) under different goal location/distance information in the goal-directed behavior have been studied. However, for goals that are multifarious constructs that include various information, the modulation of goal time information on the LFP of NCL during goal-directed behavior remains unclear. In this study, we recorded the LFP activity from the NCL of eight pigeons as they performed two goal-directed decision-making tasks in a plus-maze. During the two tasks with different goal time information, spectral analysis revealed significant LFP power selectively enhanced in the slow gamma band (40-60 Hz), while the slow gamma band of LFP which could effectively decode the behavioral goal of the pigeons existed in different time periods. These findings suggest that the LFP activity in the gamma band correlates with the goal-time information, and help to shed light on the contribution of the gamma rhythm recorded from the NCL in goal-directed behavior., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Exercise capacity is an important component of risk assessment for pulmonary arterial hypertension (PAH). We investigated the association of the Duke Activity Status Index (DASI) with peak oxygen consumption (peakVO 2 ) and explored whether the DASI can discriminate the high-risk individuals in patients with PAH, according to peakVO 2 < 11 mL/min/kg. A total of 89 patients were evaluated using cardiopulmonary exercise testing (CPET) and DASI. The correlation between the DASI and peakVO 2 was measured by univariate analysis, and a receiver operating characteristic (ROC) curve analysis was conducted. The DASI was correlated with peakVO 2 in the univariate analysis. The ROC curve analysis revealed that the DASI had a discriminative value for identifying the individuals with a high risk in PAH patients ( p < 0.001), with an area under ROC curve (AUC) of 0.79 (95% CI: 0.67-0.92). Similar results were observed in patients with PAH associated with congenital heart disease (CHD-PAH), ( p = 0.001), with an AUC of 0.80 (95% CI: 0.658-0.947). Therefore, DASI reflects exercise capacity in patients with PAH and has good ability to discriminate patients with a low risk and a high risk, and it may be included in the risk assessment of PAH.

Metastasis is a critical stage of tumor progression, a crucial challenge of clinical therapy, and a major cause of tumor patient death. Numerous studies have confirmed that distant tumor metastasis is dependent on the formation of pre-metastatic niche (PMN). Recent studies have shown that extracellular vesicles (EVs) play an important role in PMN formation. The non-coding RNAs (ncRNAs) derived from EVs mediate PMN formation and tumor-distant metastasis by promoting an inflammatory environment, inhibiting anti-tumor immune response, inducing angiogenesis and permeability, and by microenvironmental reprogramming. Given the stability and high abundance of ncRNAs carried by EVs in body fluids, they have great potential for application in tumor diagnosis as well as targeted interventions. This review focuses on the mechanism of ncRNAs derived from EVs promoting tumor PMN formation and distant metastasis to provide a theoretical reference for strategies to control tumor metastasis.

Glioblastoma (GBM) is the most common malignant glioma, with a high recurrence rate and a poor prognosis. However, the molecular mechanism behind the malignant progression of GBM is still unclear. In the present study, through the tandem mass tag (TMT)-based quantitative proteomic analysis of clinical primary and recurrent glioma samples, we identified that aberrant E3 ligase MAEA was expressed in recurrent samples. The results of bioinformatics analysis showed that the high expression of MAEA was related to the recurrence and poor prognosis of glioma and GBM. Functional studies showed that MAEA could promote proliferation, invasion, stemness and temozolomide (TMZ) resistance. Mechanistically, the data indicated that MAEA targeted prolyl hydroxylase domain 3 (PHD3) K159 to promote its K48-linked polyubiquitination and degradation, thus enhancing the stability of HIF-1α, thereby promoting the stemness and TMZ resistance of GBM cells through upregulating CD133. The in vivo experiments further confirmed that knocking down MAEA could inhibit the growth of GBM xenograft tumors. In summary, MAEA enhances the expression of HIF-1α/CD133 through the degradation of PHD3 and promotes the malignant progression of GBM., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To investigate the mechanisms of antidepressant action of active fraction of Polyrhachis vicina Rogers (AFPR) through network pharmacology, molecular docking and experimental validation., Methods: GC-MS was used to predict chemical compounds, corresponding databases were used to predict chemical compound targets and depression targets, Cytoscape software was used to construct and analyze the protein interaction network map, DAVID database was used to analyze gene ontology (GO) and KEGG signaling pathway, and AGFR software was used to perform molecular docking. Subsequently, the underlying action mechanisms of AFPR on depression predicted by network pharmacology analyses were experimentally validated in a CORT-induced depression model in vitro and in vivo., Results: A total of 52 potential targets of AFPR on antidepressant were obtained. GO is mainly related to chemical synaptic transmission, signal transduction and others. KEGG signaling pathways are mainly related to cAMP signaling pathway and C-type lectin receptor signaling pathway. The experiment results showed that AFPR significantly increased the expression of PRKACA, CREB and BDNF in mouse brain tissue and PC12 cells. Furthermore, after interfered of cAMP in PC12 cells, the decreased expression of PRKACA, CREB and BDNF was reversed by AFPR., Conclusion: AFPR may exert antidepressant effects through multiple components, targets and pathways. Furthermore, it could improve neuroplasticity via the cAMP signaling pathway to improve depression-like symptoms., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 He et al.)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although a cadre of therapeutic strategies have been made available for CVDs in the clinical setting, predominantly through medication and surgery, these do not fully address the clinical needs of patients with CVD. As a new technique for CVD treatment, nanocarriers are employed to modify and package medications to ease the targeting of tissues, cells and molecules within the cardiovascular system. Nanocarriers are made of biomaterials, metals, or a combination of these materials, with sizes similar to bioactive molecules such as proteins and DNA. Cardiovascular nanomedicine (CVN) has only surfaced in recent years and is still in its infancy. Ample studies have displayed promise for the clinical utility of nanomedicine techniques, courtesy of continued perfection in nanocarrier design to optimize drug delivery and treatment outcomes. Here in this review, we will summarize the research advances in the literature on nanoparticles in the management of CVDs, including ischemic and coronary heart disease (e.g., atherosclerosis, angina pectoris and myocardial infarction), myocardial ischemia-reperfusion injury, aortic aneurysm, myocarditis, hypertension, and pulmonary artery hypertension and thrombosis.

Glioblastoma (GBM) is the most frequent and aggressive malignant glioma. Due to patients' poor prognosis, it is of great clinical significance to determine new targets that may improve GBM treatment. In the present study, we showed that ubiquitin (Ub)-conjugating enzyme E2T (UBE2T) was significantly overexpressed in GBM and could promote proliferation, invasion, and inhibit apoptosis of GBM cells. Mechanistically, UBE2T functioned as the Ub enzyme of ribosomal protein L6 (RPL6) and induced the ubiquitination and degradation of RPL6 in an E3 ligase-independent manner through direct modification by K48-linked polyubiquitination, thus contributing to the malignant progression of GBM cells. Furthermore, inhibiting the expression of RPL6 by UBE2T could not only reduce the expression of wild-type p53, but also enhance the gain-of-function of mutant p53. Moreover, knockdown of UBE2T in LN229 cells obviously suppressed tumor growth in LN229 xenograft mouse models. Collectively, our study demonstrated that UBE2T promotes GBM malignancy through ubiquitination-mediated degradation of RPL6 regardless of the p53 mutation status. It will provide new candidates for molecular biomarkers and therapeutic targets for clinical application in GBM., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Medicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies of medicinal plants have been performed to identify molecular markers of species and functional genes controlling key biological traits, as well as to understand biosynthetic pathways of bioactive metabolites and the regulatory mechanisms of environmental responses. Omics technologies have been widely applied to medicinal plants, including as taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics and mutagenomics. However, because of the complex biological regulation network, single omics usually fail to explain the specific biological phenomena. In recent years, reports of integrated multi-omics studies of medicinal plants have increased. Until now, there have few assessments of recent developments and upcoming trends in omics studies of medicinal plants. We highlight recent developments in omics research of medicinal plants, summarise the typical bioinformatics resources available for analysing omics datasets, and discuss related future directions and challenges. This information facilitates further studies of medicinal plants, refinement of current approaches and leads to new ideas., (© The Author(s) 2022. Published by Oxford University Press.)

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFR wt kinase (IC 50  ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFR wt tyrosine kinase with IC 50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC 50 ) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Rhinacanthin C (RC) is a naphthoquinone ester with an anti-inflammatory activity extracted from Rhinacanthus nasutus (L.) Kurz (Rn). It has been proven to improve hyperglycemia and hyperlipidemia, but the prevention and mechanism of RC in nonalcoholic fatty liver disease (NAFLD) are not clear. In the current study, we first extracted RC from Rn using ethyl acetate and identified it by HPLC, MS, and NMR. At the same time, molecular docking analysis of RC with AMPK and SREBP-1c was performed using AutoDock software. In addition, the mouse model of NAFLD was induced by a high-fat diet in vivo, and low, medium, and high concentrations of RC were used for intervention. The results showed that RC significantly reduced the body mass and liver body coefficient of NAFLD mice, inhibited liver inflammation and fat accumulation, and improved insulin resistance. Further studies showed that RC significantly reduced the levels of serum leptin and resistin, upregulated the expression levels of adiponectin and adiponectin receptor in the liver, and inhibited the expression levels of MCP-1, TNF- α, and IL-6. In terms of mechanism, RC upregulates the expression of p-AMPK and SIRT1 and downregulates the expression of p-p65, SREBP-1c, Fas, Acc- α , PPAR- γ , and SCD1. These studies suggest that RC improves insulin resistance and lipid accumulation in NAFLD by activating the AMPK/SIRT1 and SREBP-1c/Fas/ACC pathways, respectively., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Zhiqiang Gong et al.)

A Gram-stain-positive, rod-shaped, facultatively anaerobic, motile and spore-forming bacterium with multiple flagella designated GXH0341 T was isolated from the soil associated with decayed pine tree samples collected from Weizhou Island, Beihai, Guangxi, China. Growth occurred at 4-37 °C (optimum 30 °C), at pH 5.0-11.0 (optimum 8.0) and in the presence of 0-7% (w/v) NaCl (optimum 2%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain GXH0341 T was most closely related to Bacillus mesophilus DSM 101000  T (98.9%), followed by Bacillus salitolerans KC1 T (96.95%) and Margalitia shackletonii DSM 18435  T (96.67%). Phylogenetic analysis revealed that strain GXH0341 T represented a separate lineage within the genus Bacillus. Peroxidase is positive. The predominant quinone was MK-7 and the cell-wall diagnostic diamino acid was meso-diaminopimelic acid. The predominant polar lipids are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, and two unidentified phospholipids. The major fatty acids are iso-C 14:0 , iso-C 15:0 , anteiso-C 15:0 and iso-C 16:0 . The genome of GXH0341 T comprises the biosynthetic gene cluster for T3PKS, terpene, lassopeptide and RRE-containing element as secondary metabolites. The average nucleotide identity values and the digital DNA-DNA hybridization values between GXH0341 T and B. mesophilus DSM 101000  T were 78.22% and 21.00%, respectively, which were in the range of the recommended level for interspecies identity. The results of phenotypic, chemotaxonomic and genotypic analyses clearly indicated strain GXH0341 T represents a novel species of the genus Bacillus, for which the name Bacillus pinisoli sp. nov. is proposed. The type strain is GXH0341 T (= MCCC 1K07157 T  = JCM 35212  T )., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chromodomain helicase DNA-binding domain 2 (CHD2) is a chromatin remodeling factor involved in many developmental processes. However, its role in male germ cell development has not been elucidated. Here, we confirm that CHD2 expression is enriched in the male germline. In a heterozygous knockout mouse model of Chd2 ( Chd2 +/- ), we demonstrated that Chd2 haploinsufficiency resulted in testicular developmental delay, an increased rate of abnormal sperm, and impaired fertility in mice. In vitro experiments in mouse spermatogonia showed that CHD2 knockdown inhibits spermatogonial self-renewal. Mechanistically, CHD2 maintains the enrichment of H3K4me3 in the Ccnb1 and Ccnd2 promotors, consequently promoting the transcription of Ccnb1 and Ccnd2 . In addition, CHD2 interacts with the cleavage stimulation factor CSTF3 and upregulates the expression of OCT4 and PLZF by improving mRNA stability. This is the first study to reveal the role and mechanism of CHD2 in maintaining spermatogonial self-renewal., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Ionic liquids (ILs), with their wide electrochemical stable potential window, are promising electrolytes for supercapacitors (SCs). The suitable matching of the ion size and shape of the ILs to the pore size and structure of porous carbon (PC) electrode materials can realize the enhanced capacitive performance of the SCs. Here we report an interesting result: The capacitance of PC-based SCs shows a quasi-sinusoidal relationship with the composition (mass fraction) of the binary IL mixture as the electrolyte. This relationship is also interpreted based on the matching between the pore sizes of the PC materials and the size/shape of various ions of the IL mixture electrolyte. This can provide a new strategy to improve the performance of SCs by formulating a suitable mixture of different ILs to match the carbon-based electrode materials with a special pore size distribution.

Glioblastoma (GBM) is the most frequently observed and aggressive type of high-grade malignant glioma. Temozolomide (TMZ) is the primary agent for GBM treatment. However, TMZ resistance remains a major challenge. In this study, we report that MDK is overexpressed in GBM, which leads to enhanced proliferation, apoptosis inhibition, increased invasion and TMZ resistance in GBM cells. It was also determined that MDK could significantly improve the stem-like properties of GBM cells. Mechanistically, MDK enhanced p-JNK through Notch1 and subsequently increased the expression of stemness markers, such as CD133 and Nanog, thereby promoting TMZ resistance. Finally, xenograft experiments and clinical sample analysis also demonstrated that MDK knockdown could significantly inhibit tumor growth in vivo , and the expression of MDK was positively correlated with Notch1, p-JNK and CD133. This study revealed that MDK induces TMZ resistance by improving the stem-like properties of GBM by upregulating the Notch1/p-JNK signaling pathway, which provides a possible target for therapeutic intervention of GBM, especially in TMZ-resistant GBM with high MDK expression., Competing Interests: None., (AJCR Copyright © 2022.)

Resuscitation-promoting factor B (RpfB) is one of the five members of Rpf-like family in Mycobacteriales , which have the resuscitation-promoting activity. Most strains of Rhodococcus also have RpfB gene, but the study of rpfB gene in Rhodococcus is not thorough. Here, we amplified the rpfB gene of intact Rhodococcus sp. (GX12401) and cloned it into pET30a (+) expression vector. Then a recombinant form of soluble RpfB was expressed in Escherichia coli BL21. The soluble recombinant RpfB was purified by Ni-Sepharose affinity chromatography and molecular weight of the protein was 55 kDa, determined by 12% SDS-PAGE stained with Coomassie brilliant blue R-250. When 4-methylumbelliferyl-β-D-N,N',N″-triacetylchitoside was used as enzyme substrate to test lysozyme activity, the recombinant protein RpfB had good stability and enzyme activity, and the lysozyme activity was low (4.74 U), among which Mg 2+ , Na + , Al 3+ and DMSO could significantly increase the activity of RpfB. The purified recombinant protein was added to Rhodococcus VBNC cells, and the VBNC cells were resuscitated at the concentration of 1 picomolar concentrations, which increased by 18% compared with the control, while the cell resuscitation was inhibited at the concentration of 1,000 picomolar concentrations. Therefore, RpfB can improve the survival ability of Rhodococcus in extreme or harsh environment and enhance the corresponding biological activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gong, Lu, Wu, Zhou, Yang, Wang, Shen and Jiang.)