CRISPR-Based KCC2 Upregulation Attenuates Drug-Resistant Seizure in Mouse Models of Epilepsy.

OBJECTIVE: The precise intervention of K-Cl cotransporter isoform 2 (KCC2) as a promising target for drug-resistant epilepsy remains elusive. METHODS: Here, we used a CRISPRa system delivered by adeno-associated viruses to specifically upregulate KCC2 in the subiculum to confirm its therapeutic potential in various in vivo epilepsy models. Calcium fiber photometry was used to reveal the role of KCC2 in the restoration of impaired GABAergic inhibition. RESULTS: CRISPRa system effectively upregulated KCC2 expression both in in vitro cell culture and in vivo brain region. Delivery of CRISPRa with adeno-associated viruses resulted in upregulating the subicular KCC2 level, contributing to alleviating the severity of hippocampal seizure and facilitating the anti-seizure effect of diazepam in a hippocampal kindling model. In a kainic acid-induced epilepticus status model, KCC2 upregulation greatly increased the termination percentage of diazepam-resistant epilepticus status with the broadened therapeutic window. More importantly, KCC2 upregulation attenuated valproate-resistant spontaneous seizure in a kainic acid-induced chronic epilepsy model. Finally, calcium fiber photometry showed CRISPRa-mediated KCC2 upregulation partially restored the impaired GABAA -mediated inhibition in epilepsy. INTERPRETATION: These results showed the translational potential of adeno-associated viruses-mediated delivery of CRISPRa for treating neurological disorders by modulating abnormal gene expression that is directly associated with neuronal excitability, validating KCC2 as a promising therapeutic target for treating drug-resistant epilepsy. ANN NEUROL 2023;94:91-105.

A Ship Detection Model Based on Dynamic Convolution and an Adaptive Fusion Network for Complex Maritime Conditions.

Ship detection is vital for maritime safety and vessel monitoring, but challenges like false and missed detections persist, particularly in complex backgrounds, multiple scales, and adverse weather conditions. This paper presents YOLO-Vessel, a ship detection model built upon YOLOv7, which incorporates several innovations to improve its performance. First, we devised a novel backbone network structure called Efficient Layer Aggregation Networks and Omni-Dimensional Dynamic Convolution (ELAN-ODConv). This architecture effectively addresses the complex background interference commonly encountered in maritime ship images, thereby improving the model's feature extraction capabilities. Additionally, we introduce the space-to-depth structure in the head network, which can solve the problem of small ship targets in images that are difficult to detect. Furthermore, we introduced ASFFPredict, a predictive network structure addressing scale variation among ship types, bolstering multiscale ship target detection. Experimental results demonstrate YOLO-Vessel's effectiveness, achieving a 78.3% mean average precision (mAP), surpassing YOLOv7 by 2.3% and Faster R-CNN by 11.6%. It maintains real-time detection at 8.0 ms/frame, meeting real-time ship detection needs. Evaluation in adverse weather conditions confirms YOLO-Vessel's superiority in ship detection, offering a robust solution to maritime challenges and enhancing marine safety and vessel monitoring.

An Underwater Source Location Privacy Protection Scheme Based on Game Theory in a Multi-Attacker Cooperation Scenario.

Ensuring source location privacy is crucial for the security of underwater acoustic sensor networks amid the growing use of marine environmental monitoring. However, the traditional source location privacy scheme overlooks multi-attacker cooperation strategies and also has the problem of high communication overhead. This paper addresses the aforementioned limitations by proposing an underwater source location privacy protection scheme based on game theory under the scenario of multiple cooperating attackers (SLP-MACGT). First, a transformation method of a virtual coordinate system is proposed to conceal the real position of nodes to a certain extent. Second, through using the relay node selection strategy, the diversity of transmission paths is increased, passive attacks by adversaries are resisted, and the privacy of source nodes is protected. Additionally, a secure data transmission technique utilizing fountain codes is employed to resist active attacks by adversaries, ensuring data integrity and enhancing data transmission stability. Finally, Nash equilibrium could be achieved after the multi-round evolutionary game theory of source node and multiple attackers adopting their respective strategies. Simulation experiments and performance evaluation verify the effectiveness and reliability of SLP-MACGT regarding aspects of the packet forwarding success rate, security time, delay and energy consumption: the packet delivery rate average increases by 30%, security time is extended by at least 85%, and the delay is reduced by at least 90% compared with SSLP, PP-LSPP, and MRGSLP.

Diverse nature of interictal oscillations: EEG-based biomarkers in epilepsy.

Interictal electroencephalogram (EEG) patterns, including high-frequency oscillations (HFOs), interictal spikes (ISs), and slow wave activities (SWAs), are defined as specific oscillations between seizure events. These interictal oscillations reflect specific dynamic changes in network excitability and play various roles in epilepsy. In this review, we briefly describe the electrographic characteristics of HFOs, ISs, and SWAs in the interictal state, and discuss the underlying cellular and network mechanisms. We also summarize representative evidence from experimental and clinical epilepsy to address their critical roles in ictogenesis and epileptogenesis, indicating their potential as electrophysiological biomarkers of epilepsy. Importantly, we put forwards some perspectives for further research in the field.

Inflachromene attenuates seizure severity in mouse epilepsy models via inhibiting HMGB1 translocation.

Epilepsy is not well controlled by current anti-seizure drugs (ASDs). High mobility group box 1 (HMGB1) is a DNA-binding protein in the nucleus regulating transcriptional activity and maintaining chromatin structure and DNA repair. In epileptic brains, HMGB1 is released by activated glia and neurons, interacting with various receptors like Toll-like receptor 4 (TLR4) and downstream glutamatergic NMDA receptor, thus enhancing neural excitability. But there is a lack of small-molecule drugs targeting the HMGB1-related pathways. In this study we evaluated the therapeutic potential of inflachromene (ICM), an HMGB-targeting small-molecule inhibitor, in mouse epilepsy models. Pentylenetetrazol-, kainic acid- and kindling-induced epilepsy models were established in mice. The mice were pre-treated with ICM (3, 10 mg/kg, i.p.). We showed that ICM pretreatment significantly reduced the severity of epileptic seizures in all the three epilepsy models. ICM (10 mg/kg) exerted the most apparent anti-seizure effect in kainic acid-induced epileptic status (SE) model. By immunohistochemical analysis of brain sections from kainic acid-induced SE mice, we found that kainic acid greatly enhanced HMGB1 translocation in the hippocampus, which was attenuated by ICM pretreatment in subregion- and cell type-dependent manners. Notably, in CA1 region, the seizure focus, ICM pretreatment mainly inhibited HMGB1 translocation in microglia. Furthermore, the anti-seizure effect of ICM was related to HMGB1 targeting, as pre-injection of anti-HMGB1 monoclonal antibody (5 mg/kg, i.p.) blocked the seizure-suppressing effect of ICM in kainic acid-induced SE model. In addition, ICM pretreatment significantly alleviated pyramidal neuronal loss and granule cell dispersion in kainic acid-induced SE model. These results demonstrate that ICM is an HMGB-targeting small molecule with anti-seizure potential, which may help develop a potential drug for treating epilepsy.

Fluxonium: An Alternative Qubit Platform for High-Fidelity Operations.

Superconducting qubits provide a promising path toward building large-scale quantum computers. The simple and robust transmon qubit has been the leading platform, achieving multiple milestones. However, fault-tolerant quantum computing calls for qubit operations at error rates significantly lower than those exhibited in the state of the art. Consequently, alternative superconducting qubits with better error protection have attracted increasing interest. Among them, fluxonium is a particularly promising candidate, featuring large anharmonicity and long coherence times. Here, we engineer a fluxonium-based quantum processor that integrates high qubit coherence, fast frequency tunability, and individual-qubit addressability for reset, readout, and gates. With simple and fast gate schemes, we achieve an average single-qubit gate fidelity of 99.97% and a two-qubit gate fidelity of up to 99.72%. This performance is comparable to the highest values reported in the literature of superconducting circuits. Thus our work, within the realm of superconducting qubits, reveals an alternative qubit platform that is competitive with the transmon system.

Nanoscale strain engineering on the surface of a bulk TiO2 crystal.

Arrays of highly strained 5-25 nm-wide regions have been prepared on rutile TiO2(110) surface through a low energy Ar ion bombardment technique. Using scanning tunneling microscopy (STM) and an innovative STM tip-triggered nanoexplosion approach we show experimentally that the protrusions arise from subsurface Ar-filled pockets. Continuum mechanics modeling gives good estimates of the corresponding elastic deformation. Surface strain values of up to 4% have been deduced.

Carbon emission prediction models: A review.

Amidst growing concerns over the greenhouse effect, especially its consequential impacts, establishing effective Carbon Emission Prediction Models (CEPMs) to comprehend and predict CO2 emission trends is imperative for climate change mitigation. A review of 147 Carbon Emission Prediction Model (CEPM) studies revealed three predominant functions-prediction, optimization, and prediction factor selection. Statistical models, comprising 75 instances, were the most prevalent among prediction models, followed by neural network models at 21.8 %. The consistent rise in neural network model usage, particularly feedforward architectures, was observed from 2019 to 2022. A majority of CEPMs incorporated optimized approaches, with 94.4 % utilizing metaheuristic models. Parameter optimization was the primary focus, followed by structure optimization. Prediction factor selection models, employing Grey Relational Analysis (GRA) and Principal Component Analysis (PCA) for statistical and machine learning models, respectively, filtered factors effectively. Scrutinizing accuracy, pre-optimized CEPMs exhibited varied performance, Root Mean Square Error (RMSE) values spanned from 0.112 to 1635 Mt, while post-optimization led to a notable improvement, the minimum RMSE reached 0.0003 Mt, and the maximum was 95.14 Mt. Finally, we summarized the pros and cons of existing models, classified and counted the factors that influence carbon emissions, clarified the research objectives in CEPM and assessed the applied model evaluation methods and the spatial and temporal scales of existing research.

Upregulation of IDO gene expression reduces the immunogenicity of epidermal cells and strengthens the immune protection of epidermal cells during transplantation treatment of wounds.

BACKGROUND: Epidermal cell transplantation is a feasible treatment option for large wounds; however, sources of autologous epidermal cells are often limited. Allogeneic epidermal cells can be cultured conveniently; however, related immune rejection needs to be addressed. Herein, we hypothesized that the immunogenicity of epidermal cells with high indoleamine 2,3-dioxygenase (IDO) expression may be reduced by gene transfection. METHODS/RESULTS: To test this hypothesis, we obtained stable transfectants by transfecting epidermal stem cells with a lentiviral vector encoding the IDO gene and screening them for puromycin resistance (a marker for successful transfection). The phenotype tested using cell counting kit -8 and Transwell assays confirmed that IDO-transfected epidermal cells maintained their characteristics. Co-culture of IDO-transfected epidermal cells with allogeneic CD4+ T cells in vitro showed that the upregulation of IDO expression in epidermal cells inhibited the proliferation of CD4+ T cells (P < 0.001, P < 0.001, and P < 0.001, respectively) and promoted their apoptosis (P = 0.00028, P = 0.0006, and P = 0.00247, respectively) and transformation into functional regulatory T cells (Tregs) (P = 0.0051, P = 0.0132, and P = 0.0248, respectively) compared with Con, NC, and 1-MT groups. The increased proportion of Tregs may be related to the overexpression of IDO, which promoted the expression of transforming growth factor beta (TGF-ß) (P = 0.0001, P = 0.0013, and, P = 0.0009) and interleukin (IL) 10 (IL-10) (P = 0.0062, P = 0.0058, and P = 0.0119) while inhibited the expression of IL-2 (P = 0.0012, P = 0.0126, and P = 0.0066). We further verified these effects in vivo as transplanted IDO-transfected epidermal stem cells were effective in treating wounds in mice. On days 5 and 7, wounds treated with IDO cells healed faster than those in the other groups (day 5: P = 0.012 and P = 0.0136; day 7: P = 0.0242 and P = 0.0187, respectively), whereas this effect was significantly inhibited by 1-methyltryptophan (1-MT) (day 5: P = 0.0303; day 7: P = 0.0105). Immunofluorescence staining detected IDO and CD4+ Foxp3+ Tregs in the transplanted wounds, which may promote Foxp3+ Tregs in the wound tissue (day 5: P < 0.0001, P < 0.0001, and P < 0.0001; day 7: P < 0.0001, P < 0.0001, and P < 0.0001), respectively) and decrease CD4+ T cells (day 5: P < 0.0001, P < 0.0001, and P < 0.0001; day 7: P < 0.0001, P < 0.0001, and P < 0.0001). CONCLUSION: Our results suggest that the upregulation of IDO expression in epidermal stem cells can reduce their immunogenicity by promoting Tregs, thus inducing the immune protection of epidermal stem cells.

Geochemical Characteristics and Origin of Sinian-Cambrian Natural Gas in Penglai Gas Area, Sichuan Basin.

The Sichuan Basin in southern China is well-known for its large natural gas resource potential stored in Sinian-Cambrian systems. Recently, high-yield industrial gas flow has been discovered from the Dengying Formation (Sinian System) and Canglangpu Formation (Cambrian System) in the Penglai gas area, preluding the multilayer stereoscopic exploration in Sichuan Basin. However, the origin of the natural gas and its preserving mechanics is still debated, and thus, in this study the geochemical characteristics of the natural gas are systematically analyzed, based on the data from gas composition and hydrocarbon isotope of a series of local wells. On this basis, the geochemical characteristics of natural gas in different regions and layers are compared, and the reasons for these differences from the origin and influencing factors are analyzed. The results show the following: (1) The natural gas of the Penglai gas field is dry gas dominated by CH4, and the Sinian Dengying Formation gas has lower C2H6 content, larger dryness coefficient, heavier δ13C, and lighter δ2HCH4 than the Cambrian gas, which is associated with the high proportion of hydrocarbons from the high-maturity Dengying source rocks. (2) The natural gas from some wells in the lower part of the structure is characterized by high H2S content and low CH4 content, and heavy δ13C in the components, which seems to be affected by the thermochemical sulfate reduction (TSR) effect. (3) The natural gas from the Penglai gas area has a relatively low maturity, which appears to be attributed to the continuous sealing ability of the caprock, which can preserve both the early generated gas and the late thermal-cracked gas.

113Gb/s (10 x 11.3Gb/s) ultra-low power EAM driver array.

This paper presents an ultra-low power SiGe BiCMOS IC for driving a 10 channel electro-absorption modulator (EAM) array at 113Gb/s for wavelength division multiplexing passive optical network (WDM-PON) applications. With an output swing of 2.5V(pp), the EAM driver array consumes only 2.2W or 220mW per channel, 50% below the state of the art. Both the output swing and bias are configurable between 1.5 and 3.0V(pp) and 0.75-2.15V respectively.

Protocol for labeling epileptic-status-related neuronal ensembles in mouse hippocampal kindling model.

Epileptic networks are characterized by two states, seizures or more prolonged interictal periods. Here, we present the procedure for labeling seizure-activated and interictal-activated neuronal ensembles in mouse hippocampal kindling model using an enhanced-synaptic-activity-responsive element. We describe the seizure model establishment, tamoxifen induction, electrical stimulation, and calcium signal recording of labeled ensembles. This protocol has demonstrated dissociated calcium activities in the two ensembles during focal seizure dynamics and can be applied to other animal models of epilepsy. For complete details on the use and execution of this protocol, please refer to Lai et al. (2022).1.

Comparative analysis of the influence of Chinese urban and rural family cultures on household financial asset allocation.

Despite the national strategic priority to achieve common prosperity, there still exist prominent discrepancies in financial asset allocation between Chinese urban and rural families, which requires a deeper, more comprehensive investigation. To fill this gap, the present research adopted a cultural perspective to investigate relevant issues by addressing the cognitive differences of residents between urban and rural families. Under the analytical framework of Hofstede's cultural values, this paper discusses the cognitive differences between urban and rural families in terms of financial asset allocation in the cultural dimensions of collectivism, individualism and uncertainty avoidance; hypotheses are accordingly developed. In terms of research methods, the data of the China Family Panel Studies (CFPS) were used in the probit model to investigate the influence of urban and rural family cultural differences on household financial asset allocation. The results of this paper are as follows: (1) family cultural values have a positive impact on family financial asset allocation; (2) knowledge acquisition plays an intermediary role in family cultural values and family financial asset allocation; (3) and for rural families with high collectivism and uncertainty avoidance, the mediating effect is more prominent. This paper provides a new perspective for exploring the possibility of household asset allocation from the perspective of cultural psychology. The contribution of this paper have theoretical and practical reference significance to narrow the wealth gap between urban and rural areas and achieve common prosperity.

Path planning for mobile robots in complex environments based on improved ant colony algorithm.

Aiming at the problems of the basic ant colony algorithm in path planning, such as long convergence time, poor global path quality and not being suitable for dynamic environments and unknown environments, this paper proposes a path planning method for mobile robots in complex environments based on an improved ant colony (CBIACO) algorithm. First, a new probability transfer function is designed for an ant colony algorithm, the weights of each component in the function are adaptively adjusted to optimize the convergence speed of the algorithm, and the global path is re-optimized by using the detection and optimization mechanism of diagonal obstacles. Second, a new unknown environment path exploration strategy (UPES) is designed to solve the problem of poor path exploration ability of the ant colony algorithm in unknown environment. Finally, a collision classification model is proposed for a dynamic environment, and the corresponding dynamic obstacle avoidance strategy is given. The experimental results show that CBIACO algorithm can not only rapidly generate high-quality global paths in known environments but also enable mobile robots to reach the specified target points safely and quickly in a variety of unknown environments. The new dynamic obstacle avoidance strategy enables the mobile robot to avoid dynamic obstacles in different directions at a lower cost.

WITHDRAWN: Transdifferentiation of Human Neonatal Foreskin Fibroblasts into Keratinocyte-like Cells via Regulating the AKT/P53/WNT/LEF1 Axis

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal Current Stem Cell Research & Therapy.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham editorial policy on article withdrawal can be found at https://benthamscience.com/pages/editorial-policies-main BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Role and Mechanism of Endoplasmic Reticulum Stress in Mice Pancreatic Islet Dysfunction After Severe Burns.

This study attempted to investigate the role and mechanism of endoplasmic reticulum (ER) stress in the islet dysfunction in mice after severe burns. C57BL/6 mice were randomly divided into the sham group, burn group, and burn+4-phenylbutyric acid (4-PBA) group. Mice were burned with full thickness of 30% total surface area (TBSA), and 4-PBA solution was intraperitoneally injected into mice in burn+4-PBA group. Glucose-stimulated insulin secretion (GSIS), Fasting blood glucose (FBG) and glucose tolerance were detected 24 hours post severe burns. The ER stress-related pathway markers immunoglobulin binding protein (BIP), X-box binding protein 1 (XBP1), phosphorylation-PKR-like ER kinase (p-PERK), phosphorylation-eukaryotic translation initiation factor 2α (p-eIF2α), CHOP, activating transcription factor 6 (ATF6), apoptosis-related protein Cleaved-Caspase 3, and islet cell apoptosis were measured. Mice were characterized with elevated FBG, decreased glucose tolerance and GSIS levels post severe burns. The expression of BIP, XBP1, p-PERK, p-eIF2α, CHOP, ATF6, Cleaved-Caspase 3, and islet cell apoptosis were increased significantly after severe burns. 4-PBA treatment contributed to decreased FBG, improved glucose tolerance, increased GSIS, inhibited islet ER stress, and reduced pancreatic islet cell apoptosis in mice post severe burns. ER stress occurs in islets of severely burned mice, which leads to increased apoptosis of islet cells, thus resulting in islet dysfunction.

The Epidermal Barrier Structure and Function of Re-Harvested Skin from Non-Scalp Donor Sites.

AIM: The aim of this study was to explore the epidermal barrier structure and function of re-harvested skin from non-scalp donor sites. METHODS: Six patients with large-area deep burns who met the inclusion and exclusion criteria were subjected to split-thickness skin excision three times on the same healthy non-scalp donor sites, with an interval of 14 days. The donor skin thus harvested was labeled as primary skin (S1), secondary skin (S2), and tertiary skin (S3). The transepidermal water loss (TEWL) and stratum corneum water content (SCH) of donor skin were detected before each surgery, and the donor skin was harvested during the surgery. The donor skin was stained with hematoxylin and eosin (HE) and involucrin, loricrin, filaggrin, small molecule proline-rich protein 3 (SPRR3), ZO-3, JAM-A, and JAM-C, or observed by transmission electron microscopy. RESULTS: The epidermal barrier function of the re-harvested skin from the non-scalp donor sites became impaired. The histopathological structure of the re-harvested skin from non-scalp donor sites became abnormal. The barrier of the epidermal stratum corneum of the re-harvested skin from non-scalp donor sites was damaged. The epidermal tight junction barrier in the re-harvested skin from non-scalp donor sites was damaged. CONCLUSIONS: As the number of harvesting increases, the epidermal barrier function of the skin decreased, and the damage to the barrier structure increased. Hence, it is vitally important to restore the epidermal barrier function for re-harvesting in non-scalp donor sites.

On the determination of absolute vibrational excitation probabilities in molecule-surface scattering: case study of NO on Au(111).

We describe a method to obtain absolute vibrational excitation probabilities of molecules scattering from a surface based on measurements of the rotational state, scattering angle, and temporal distributions of the scattered molecules and apply this method to the vibrational excitation of NO scattering from Au(111). We report the absolute excitation probabilities to the v = 1 and v = 2 vibrational states, rotational excitation distributions, and final scattering angle distributions for a wide range of incidence energies and surface temperatures. In addition to demonstrating the methodology for obtaining absolute scattering probabilities, these results provide an excellent benchmark for theoretical calculations of molecule-surface scattering.

Prevalence of blindness and low vision: a study in the rural Heilongjiang Province of China.

BACKGROUND: The prevalence of blind individuals in the north of China is unknown. The study aimed to investigate the prevalence and causes of blindness and low vision in rural areas in Heilongjiang province of China in 2008-2009. DESIGN: Cross-sectional study. PARTICIPANTS OR SAMPLES: A cluster random sampling method was used to recruit participants of all ages in rural areas of Heilongjiang. METHODS: Trained professionals performed interviews and clinical examinations to measure visual acuity. The relationships between blindness or low vision and age, gender and education level were analysed. MAIN OUTCOME MEASURES: The main outcome measure was prevalence rates of bilateral blindness and bilateral low vision. RESULTS: Of the 11 787 subjects, 10 384 (88.1%) were surveyed. The overall age-adjusted prevalence rates were 0.7% (95% confidence interval: 0.5-0.8%) for bilateral blindness and 1.7% (95% confidence interval: 1.4-1.9%) for bilateral low vision. The prevalence rates of blindness and low vision were higher in the elderly and uneducated population (P < 0.05). The main causes for blindness and low vision were cataracts (44.1 and 46.0%, respectively) and refractive errors (17.7 and 42.5%, respectively). CONCLUSION: Blindness and low vision are highly prevalent among people with cataracts and refractive errors. Eye care planning must focus on treating the avoidable and curable forms of blindness.

Multiquantum vibrational excitation of NO scattered from Au(111): quantitative comparison of benchmark data to ab initio theories of nonadiabatic molecule-surface interactions.

Surface phenomena: measurements of absolute probabilities are reported for the vibrational excitation of NO(v=0→1,2) molecules scattered from a Au(111) surface. These measurements were quantitatively compared to calculations based on ab initio theoretical approaches to electronically nonadiabatic molecule-surface interactions. Good agreement was found between theory and experiment (see picture; T(s) =surface temperature, P=excitation probability, and E=incidence energy of translation).