Glycogen accumulation and phase separation drives liver tumor initiation.

Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.

Rad52 Restrains Resection at DNA Double-Strand Break Ends in Yeast.

Rad52 is a key factor for homologous recombination (HR) in yeast. Rad52 helps assemble Rad51-ssDNA nucleoprotein filaments that catalyze DNA strand exchange, and it mediates single-strand DNA annealing. We find that Rad52 has an even earlier function in HR in restricting DNA double-stranded break ends resection that generates 3' single-stranded DNA (ssDNA) tails. In fission yeast, Exo1 is the primary resection nuclease, with the helicase Rqh1 playing a minor role. We demonstrate that the choice of two extensive resection pathways is regulated by Rad52. In rad52 cells, the resection rate increases from ∼3-5 kb/h up to ∼10-20 kb/h in an Rqh1-dependent manner, while Exo1 becomes dispensable. Budding yeast Rad52 similarly inhibits Sgs1-dependent resection. Single-molecule analysis with purified budding yeast proteins shows that Rad52 competes with Sgs1 for DNA end binding and inhibits Sgs1 translocation along DNA. These results identify a role for Rad52 in limiting ssDNA generated by end resection.

EpiCarousel: memory- and time-efficient identification of metacells for atlas-level single-cell chromatin accessibility data.

SUMMARY: Recent technical advancements in single-cell chromatin accessibility sequencing (scCAS) have brought new insights to the characterization of epigenetic heterogeneity. As single-cell genomics experiments scale up to hundreds of thousands of cells, the demand for computational resources for downstream analysis grows intractably large and exceeds the capabilities of most researchers. Here, we propose EpiCarousel, a tailored Python package based on lazy loading, parallel processing, and community detection for memory- and time-efficient identification of metacells, i.e. the emergence of homogenous cells, in large-scale scCAS data. Through comprehensive experiments on five datasets of various protocols, sample sizes, dimensions, number of cell types, and degrees of cell-type imbalance, EpiCarousel outperformed baseline methods in systematic evaluation of memory usage, computational time, and multiple downstream analyses including cell type identification. Moreover, EpiCarousel executes preprocessing and downstream cell clustering on the atlas-level dataset with 707 043 cells and 1 154 611 peaks within 2 h consuming <75 GB of RAM and provides superior performance for characterizing cell heterogeneity than state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The EpiCarousel software is well-documented and freely available at https://github.com/biox-nku/epicarousel. It can be seamlessly interoperated with extensive scCAS analysis toolkits.

In Situ Polymerization of Hydrogel Electrolyte on Electrodes Enabling the Flexible All-Hydrogel Supercapacitors with Low-Temperature Adaptability.

All-hydrogel supercapacitors are emerging as promising power sources for next-generation wearable electronics due to their intrinsic mechanical flexibility, eco-friendliness, and enhanced safety. However, the insufficient interfacial adhesion between the electrode and electrolyte and the frozen hydrogel matrices at subzero temperatures largely limit the practical applications of all-hydrogel supercapacitors. Here, an all-hydrogel supercapacitor is reported with robust interfacial contact and anti-freezing property, fabricated by in situ polymerizing hydrogel electrolyte onto hydrogel electrodes. The robust interfacial adhesion is developed by the synergistic effect of a tough hydrogel matrix and topological entanglements. Meanwhile, the incorporation of zinc chloride (ZnCl2) in the hydrogel electrolyte prevents the freezing of water solvents and endows the all-hydrogel supercapacitor with mechanical flexibility and fatigue resistance across a wide temperature range of 20 °C to -60 °C. Such all-hydrogel supercapacitor demonstrates satisfactory low-temperature electrochemical performance, delivering a high energy density of 11 mWh cm-2 and excellent cycling stability with a capacitance retention of 90% over 10000 cycles at -40 °C. Notably, the fabricated all-hydrogel supercapacitor can endure dynamic deformations and operate well under 2000 tension cycles even at -40 °C, without experiencing delamination and electrochemical failure. This work offers a promising strategy for flexible energy storage devices with low-temperature adaptability.

Activating Inert Perovskite Oxides for CO2 Electroreduction via Slight Cu2+ Doping in B-Sites.

Perovskite oxides are proven as a striking platform for developing high-performance electrocatalysts. Nonetheless, a significant portion of them show CO2 electroreduction (CO2RR) inertness. Here a simple but effective strategy is reported to activate inert perovskite oxides (e.g., SrTiO3) for CO2RR through slight Cu2+ doping in B-sites. For the proof-of-concept catalysts of SrTi1-xCuxO3 (x = 0.025, 0.05, and 0.1), Cu2+ doping (even in trace amount, e.g., x = 0.025) can not only create active, stable CuO6 octahedra, increase electrochemical active surface area, and accelerate charge transfer, but also significantly regulate the electronic structure (e.g., up-shifted band center) to promote activation/adsorption of reaction intermediates. Benefiting from these merits, the stable SrTi1-xCuxO3 catalysts feature great improvements (at least an order of magnitude) in CO2RR activity and selectivity for high-order products (i.e., CH4 and C2+), compared to the SrTiO3 parent. This work provides a new avenue for the conversion of inert perovskite oxides into high-performance electrocatalysts toward CO2RR.

Operando Studies of Bismuth Nanoparticles Embedded in N, O-Doped Porous Carbon for High-Performance Potassium-Ion Hybrid Capacitor.

A highly viable alternative to lithium-ion batteries for stationary electrochemical energy-storage systems is the potassium dual-ion hybrid capacitor (PIHC), especially toward fast-charging capability. However, the sluggish reaction kinetics of negative electrode materials seriously impedes their practical implementation. In this paper, a new negative electrode Bi@RPC (Nano-bismuth confined in nitrogen- and oxygen-doped carbon with rationally designed pores, evidenced by advanced characterization) is developed, leading to a remarkable electrochemical performance. PIHCs building with the active carbon YP50F positive electrode result in a high operation voltage (0.1-4 V), and remarkably well-retained energy density at a high-power density (11107 W kg-1 at 98 Wh kg-1). After 5000 cycles the proposed PHICs still show a superior capacity retention of 92.6%. Moreover, a reversible mechanism of "absorption-alloying" of the Bi@RPC nanocomposite is revealed by operando synchrotron X-ray diffraction and Raman spectroscopy. With the synergistic potassium ions storage mechanism arising from the presence of well-structured pores and nano-sized bismuth, the Bi@RPC electrode exhibits an astonishingly rapid kinetics and high energy density. The results demonstrate that PIHCs with Bi@RPC-based negative electrode is the promising option for simultaneously high-capacity and fast-charging energy storage devices.

Efficacy and safety of intrathecal dexamethasone combined with isoniazid in the treatment of tuberculous meningitis: a meta-analysis.

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

Kinetic understanding of lithium metal electrodeposition for lithium anodes.

Lithium, a representative alkali metal, holds the coveted status of the "holy grail" in the realm of next-generation rechargeable batteries, owing to its remarkable theoretical specific capacity and low electrode potential. However, the inherent reactivity of Li metal inevitably results in the formation of the solid-electrolyte interphase (SEI) on its surface, adding complexity to the Li electrodeposition process compared to conventional metal electrodeposition. Attaining uniform Li deposition is crucial for ensuring stable, long-cycle performance and high Coulombic efficiency in Li metal batteries, which requires a comprehensive understanding of the underlying factors governing the electrodeposition process. This review delves into the intricate kinetics of Li electrodeposition, elucidating the multifaceted factors that influence charge and mass transfer kinetics. The intrinsic relationship between charge transfer kinetics and Li deposition is scrutinized, exploring how parameters such as current density and electrode potential impact Li nucleation and growth, as well as dendrite formation. Additionally, the applicability of classical mass-transfer-controlled electrodeposition models to Li anode systems is evaluated, considering the influence of ionic concentration and solvation structure on Li+ transport, SEI formation, and subsequent deposition kinetics. The pivotal role of SEI compositional structure and physicochemical properties in governing charge and mass transfer processes is underscored, with an emphasis on strategies for regulating Li deposition kinetics from both electrolyte and SEI perspectives. Finally, future directions in Li electrodeposition research are outlined, emphasizing the importance of ongoing exploration from a kinetic standpoint to fully unlock the potential of Li metal batteries.

Emodin ameliorates matrix degradation and apoptosis in nucleus pulposus cells and attenuates intervertebral disc degeneration through LRP1 in vitro and in vivo.

Low back pain (LBP) is the leading cause of disability worldwide, with a strong correlation to intervertebral disc degeneration (IDD). Inflammation-induced extracellular matrix (ECM) degradation plays a major role in IDD's progression. Emodin, known for its anti-inflammatory effects and ability to inhibit ECM degradation in osteoarthritis, but its role in IDD is unclear. Our study aimed to explore emodin's role and mechanisms on IDD both in vivo and in vitro. We discovered that emodin positively regulated anabolic markers (COL2A1, aggrecan) and negatively impacted catabolic markers (MMP3, MMP13) in nucleus pulposus cells, while also inhibiting cell apoptosis under inflammation environment. We revealed that emodin inhibits inflammation-induced NF-ĸB activation by suppressing the degradation of LRP1 via the proteasome pathway. Additionally, LRP1 was validated as essential to emodin's regulation of ECM metabolism and apoptosis, both in vitro and in vivo. Ultimately, we demonstrated that emodin effectively alleviates IDD in a rat model. Our findings uncover the novel pathway of emodin inhibiting ECM degradation and apoptosis through the inhibition of NF-κB via LRP1, thus alleviating IDD. This study not only broadens our understanding of emodin's role and mechanism in IDD treatment but also guides future therapeutic interventions.

Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells.

Cannabidiol (CBD), one of the major components extracted from the plant Cannabis sativa L., has been used as a prescription drug to treat seizures in many countries. CBD-induced male reproductive toxicity has been reported in animal models; however, the underlying mechanisms remain unclear. We previously reported that CBD induced apoptosis in primary human Leydig cells, which constitute the primary steroidogenic cell population in the testicular interstitium. In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlying CBD-induced cytotoxicity. mRNA-sequencing analysis of CBD-treated human and mouse Leydig cells over a 5-day time-course indicated similar responses in both cell types. Mitochondria and lysosome dysfunction, oxidative stress, and autophagy were the major enriched pathways in both cell types. Taken together, these findings demonstrate comparable toxic effects and underlying mechanisms in CBD-treated mouse and primary human Leydig cells.

Deviant peer affiliation, self-control, and aggression during early adolescence: within-person effects and between-person differences.

Abundant studies have explored the relations among deviant peer affiliation, self-control, and aggression without separating within-person from between-person effects. Moreover, it is unclear whether self-control mediates the associations between deviant peer affiliation and aggression during early adolescence. This longitudinal study used Random Intercept Cross-Lagged Panel Model to examine the dynamic relations among deviant peer affiliation, self-control, and aggression within individuals, including examining whether self-control mediated the relations between deviant peer affiliation and aggression. A total of 4078 early adolescents (54% boys, Mage = 9.91, SD = 0.73) completed questionnaires on four occasions across 2 years. Results indicated: (a) Deviant peer affiliation and aggression positively predicted each other; (b) Self-control and aggression negatively predicted each other but were unstable; (c) Deviant peer affiliation and self-control negatively predicted each other; and (d) Self-control mediated the path from aggression to deviant peer affiliation, but not vice versa. The results more precisely identify the relations among deviant peer affiliation, self-control, and aggression within individuals, providing valuable information for prevention and intervention programs targeted at alleviating early adolescent aggression.

Analysis of chaos and capsizing of a class of nonlinear ship rolling systems under excitation of random waves.

The action of wind and waves has a significant effect on the ship's roll, which can be a source of chaos and even capsize. The influence of random wave excitation is considered in order to investigate complex dynamic behavior by analytical and numerical methods. Chaotic rolling motions are theoretically studied in detail by means of the relevant Melnikov method with or without noise excitation. Numerical simulations are used to verify and analyze the appropriate parameter excitation and noise conditions. The results show that by changing the parameters of the excitation amplitude or the noise intensity, chaos can be induced or suppressed.

Graphene-Based Tunable Polarization Conversion Metasurface for Array Antenna Radar Cross-Section Reduction.

A graphene-based tunable polarization conversion metasurface (PCM) was designed and analyzed for the purpose of reducing the radar cross-section (RCS) of array antennas. The metasurface comprises periodic shuttle-shaped metal patches, square-patterned graphene, and inclined grating-patterned graphene. By adjusting the Fermi energy levels of the upper (µ1) and lower (µ2) graphene layers, different states were achieved. In State 1, with µ1 = 0 eV and µ2 = 0.5 eV, the polarization conversion ratio (PCR) exceeded 0.9 in the bandwidths of 1.65-2.19 THz and 2.29-2.45 THz. In State 2, with µ1 = µ2 = 0.5 eV, the PCR was greater than 0.9 in the 1.23-1.85 THz and 2.24-2.60 THz bands. In State 3, with µ1 = µ2 = 1 eV, the PCR exceeded 0.9 in the 2.56-2.75 THz and 3.73-4.05 THz bands. By integrating the PCM with the array antenna, tunable RCS reduction was obtained without affecting the basic radiation functionality of the antenna. In State 1, RCS reduction was greater than 10 dB in the 1.60-2.43 THz and 3.63-3.72 THz frequency ranges. In State 2, the RCS reduction exceeded 10 dB in the 2.07-2.53 THz, 2.78-2.98 THz, and 3.70-3.81 THz bands. In State 3, RCS reduction was greater than 10 dB in the 1.32-1.43 THz, 2.51-2.76 THz, and 3.76-4.13 THz frequency ranges. This polarization conversion metasurface shows significant potential for applications in switchable and tunable antenna RCS reduction.

Mechanism of action of anthocyanin on the detoxification of foodborne contaminants-A review of recent literature.

Foodborne contaminants refer to substances that are present in food and threaten food safety. Due to the progress in detection technology and the rising concerns regarding public health, there has been a surge in research focusing on the dangers posed by foodborne contaminants. These studies aim to explore and implement strategies that are both safe and efficient in mitigating the associated risks. Anthocyanins, a class of flavonoids, are abundantly present in various plant species, such as blueberries, grapes, purple sweet potatoes, cherries, mulberries, and others. Numerous epidemiological and nutritional intervention studies have provided evidence indicating that the consumption of anthocyanins through dietary intake offers a range of protective effects against the detrimental impact of foodborne contaminants. The present study aims to differentiate between two distinct subclasses of foodborne contaminants: those that are generated during the processing of food and those that originate from the surrounding environment. Furthermore, the impact of anthocyanins on foodborne contaminants was also summarized based on a review of articles published within the last 10 years. However, further investigation is warranted regarding the mechanism by which anthocyanins target foodborne contaminants, as well as the potential impact of individual variations in response. Additionally, it is important to note that there is currently a dearth of clinical research examining the efficacy of anthocyanins as an intervention for mitigating the effects of foodborne pollutants. Thus, by exploring the detoxification effect and mechanism of anthocyanins on foodborne pollutants, this review thereby provides evidence, supporting the utilization of anthocyanin-rich diets as a means to mitigate the detrimental effects of foodborne contaminants.

SARS-CoV-2 infection decreases cardiorespiratory fitness and time-trial performance even two months after returning to regular training - Insights from a longitudinal case series of well-trained kayak athletes.

Objective: The aims of this study were to examine the effect of SARS-CoV-2 infection on cardiorespiratory fitness (CRF) and time-trial performance in vaccinated well-trained young kayak athletes. Methods: This is a longitudinal observational study. Sixteen (7 male, 9 female) vaccinated kayakers underwent body composition assessment, maximal graded exercise test, and 1000-m time-trial tests 21.9 ± 1.7 days before and 66.0 ± 2.2 days after the SARS-CoV-2 infection. The perception of training load was quantified with Borg's CR-10 scale before and after the infection return to sport period. Results: There were significant decreases in peak oxygen uptake (-9.7 %; effect size [ES] = 1.38), peak oxygen pulse (-5.7 %; ES = 0.96), and peak heart rate (-1.9 %; ES = 0.61). Peak minute ventilation, and minute ventilation/carbon dioxide production slope were unchanged after infection compared to the pre-infection values. In the entire 1000-m, the impaired tendencies were found in completion time, mean power, and mean speed (-2.4 to 1.2 %; small ESs = -0.40 to 0.47) as well as significant changes in stroke rate and stroke length (-4.5 to 3.7 %; ESs = -0.60 to 0.73). Conclusion: SARS-CoV-2 infection decreased CRF and time-trial performance even two months after return to regular training in vaccinated athletes.

NeuroD1 administration ameliorated neuroinflammation and boosted neurogenesis in a mouse model of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with hippocampal neuroinflammation. Growing evidences have shown that astrocytes played a significant role in mediating neuroinflammation. Recently, in vivo reprogramming of astrocytes to neurons by NeuroD1 or PTBP1 administration has generated a lot of interests and controversies. While the debates centered on the source of neurogenesis, no attention has been paid to the changes of the astrocytes-mediated neuroinflammation and its impact on endogenous neurogenesis after NeuroD1 administration. METHODS: 80 adult male C57BL/6 mice were used in this study. SAH was established by pre-chiasmatic injection of 100 µl blood. AAV-NeuroD1-GFP virus was injected to the hippocampus 3 day post-SAH. Neurocognitive function, brain water content, in vivo electrophysiology, Golgi staining, western blot and immunofluorescent staining were assessed at day 14 post-virus injection. RESULTS: NeuroD1 administration markedly attenuated reactive astrocytes-mediated neuroinflammation by reversing neurotoxic A1 astrocytes transformation, decreasing the secretion of neuroinflammatory cytokines, and reducing the activation of harmful microglia. NeuroD1 treatment significantly reversed the brain-blood barrier impairment and promoted the release of neurotrophic factors pleiotrophin (PTN), all of which contributed to the improvement of cellular microenvironment and made it more suitable for neurogenesis. Interestingly, besides neurogenesis in the hippocampus from cells transfected with NeuroD1 at the early phase of SAH, NeuroD1 administration significantly boosted the endogenous neurogenesis at the late phase of SAH, which likely benefited from the improvement of the neuroinflammatory microenvironment. Functionally, NeuroD1 treatment significantly alleviated neurocognitive dysfunction impaired by SAH. CONCLUSIONS: NeuroD1 significantly promoted neurofunctional recovery by attenuating reactive astrocytes-mediated neuroinflammation and boosting neurogenesis decimated by SAH. Specifically, NeuroD1 efficiently converted transfected cells, most likely astrocytes, to neurons at the early phase of SAH, suppressed astrocytes-mediated neuroinflammation and boosted endogenous neurogenesis at the late phase of SAH.

Induction of apoptosis by cannabidiol and its main metabolites in human Leydig cells.

Cannabidiol (CBD) is one of the most prevalent and abundant cannabinoids extracted from the plant Cannabis sativa. CBD has been reported to induce male reproductive toxicity in animal models. In this study, we examined the effects of CBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD, on primary human Leydig cells, which play a crucial role in male reproductive health. Our results showed that CBD, at concentrations below the Bayesian benchmark dose (BMD)50, inhibited the growth of human Leydig cells by arresting the cell cycle at G1/S transition, disrupting cell cycle regulators, and decreasing DNA synthesis. Concentration-response transcriptomic profiling identified that apoptosis was one of the top biological processes significantly affected by treatment with CBD for 24 h. The occurrence of apoptosis was confirmed by increased activation of caspase-3/7 and an increased proportion of annexin V and propidium iodide (PI)-positive cells. Similar to CBD, both 7-carboxy-CBD and 7-hydroxy-CBD decreased cell viability and induced apoptosis after treatment for 24 h. 7-Hydroxy-CBD and 7-carboxy-CBD showed lower cytotoxicity than CBD, and 7-carboxy-CBD had the lowest cytotoxicity among the three compounds. Our findings revealed that CBD and its main metabolites can cause adverse effects on primary human Leydig cells.

Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays.

Propranolol is a widely used ß-blocker that can generate a nitrosated derivative, N-nitroso propranolol (NNP). NNP has been reported to be negative in the bacterial reverse mutation test (the Ames test) but genotoxic in other in vitro assays. In the current study, we systematically examined the in vitro mutagenicity and genotoxicity of NNP using several modifications of the Ames test known to affect the mutagenicity of nitrosamines, as well as a battery of genotoxicity tests using human cells. We found that NNP induced concentration-dependent mutations in the Ames test, both in two tester strains that detect base pair substitutions, TA1535 and TA100, as well as in the TA98 frameshift-detector strain. Although positive results were seen with rat liver S9, the hamster liver S9 fraction was more effective in bio-transforming NNP into a reactive mutagen. NNP also induced micronuclei and gene mutations in human lymphoblastoid TK6 cells in the presence of hamster liver S9. Using a panel of TK6 cell lines that each expresses a different human cytochrome P450 (CYP), CYP2C19 was identified as the most active enzyme in the bioactivation of NNP to a genotoxicant among those tested. NNP also induced concentration-dependent DNA strand breakage in metabolically competent 2-dimensional (2D) and 3D cultures of human HepaRG cells. This study indicates that NNP is genotoxic in a variety of bacterial and mammalian systems. Thus, NNP is a mutagenic and genotoxic nitrosamine and a potential human carcinogen.

Energy-Optimal Adaptive Control Based on Model Predictive Control.

Energy-optimal adaptive cruise control (EACC) is becoming increasingly popular due to its ability to save energy. Considering the negative impacts of system noise on the EACC, an improved modified model predictive control (MPC) is proposed, which combines the Sage-Husaadaptive Kalman filter (SHAKF), the cubature Kalman filter (CKF), and the back-propagation neural network (BPNN). The proposed MPC improves safety and tracking performance while further reducing energy consumption. The final simulation results show that the proposed algorithm has a stronger energy-saving capability compared to previous studies and always maintains an appropriate relative distance and relative speed to the vehicle in front, verifying the effectiveness of the proposed algorithm.

DPDH-CapNet: A Novel Lightweight Capsule Network with Non-routing for COVID-19 Diagnosis Using X-ray Images.

COVID-19 has claimed millions of lives since its outbreak in December 2019, and the damage continues, so it is urgent to develop new technologies to aid its diagnosis. However, the state-of-the-art deep learning methods often rely on large-scale labeled data, limiting their clinical application in COVID-19 identification. Recently, capsule networks have achieved highly competitive performance for COVID-19 detection, but they require expensive routing computation or traditional matrix multiplication to deal with the capsule dimensional entanglement. A more lightweight capsule network is developed to effectively address these problems, namely DPDH-CapNet, which aims to enhance the technology of automated diagnosis for COVID-19 chest X-ray images. It adopts depthwise convolution (D), point convolution (P), and dilated convolution (D) to construct a new feature extractor, thus successfully capturing the local and global dependencies of COVID-19 pathological features. Simultaneously, it constructs the classification layer by homogeneous (H) vector capsules with an adaptive, non-iterative, and non-routing mechanism. We conduct experiments on two publicly available combined datasets, including normal, pneumonia, and COVID-19 images. With a limited number of samples, the parameters of the proposed model are reduced by 9x compared to the state-of-the-art capsule network. Moreover, our model has faster convergence speed and better generalization, and its accuracy, precision, recall, and F-measure are improved to 97.99%, 98.05%, 98.02%, and 98.03%, respectively. In addition, experimental results demonstrate that, contrary to the transfer learning method, the proposed model does not require pre-training and a large number of training samples.