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As cyberspace technologies advance rapidly, cyberspace security risks derived from new applications and technologies are becoming more complex and hidden. Establishing a unique cyberspace security model is a common practice to deal with complex security threats in China and abroad. However, existing cyberspace security models have problems such as unclear development directions, insufficient ability to analyze risks derived from new technologies, and lack of security capabilities required for cyberspace security defense assessment. This study evaluates existing cyberspace security models from the perspectives of technology, discipline, and industry, sorts out the characteristics and development context of the cyberspace security technology system, and clarifies the urgent problems existing in cybersecurity applications. Focusing on the perspective of cyberspace security technology, this study proposes a cyberspace security model system framework based on technical elements, using existing security technologies and emerging technologies to verify the security analysis capabilities of the system framework. This study further proposes the following development suggestions: (1) improving the core framework of the cyberspace security technology system, (2) promoting the industryuniversity-research integration in the field of cyberspace security, (3) promoting the formulation of core technology standards regarding cyberspace security, and (4) addressing AI security threats, thus to effectively deal with cyberspace security threats and enhance the cyberspace security capabilities of China.

Objective To systematiclly evaluate the relationship between assisted reproductive technology（ART） and autism spectrum disorders（ASD） in their offspring. Methods Systematic searches of PubMed, Web of Science, CBM, VIP, and CNKI databases were conducted to collect the cohort studies on ASD in ART progeny published from database establishment to April 1, 2022. After four independent reviewers screened the literature, extracted the data and assessed their quality with Newcastle-Ottawa scale（NOS）, a Meta-analysis was performed using Stata 15.1 software. Results Finally, 8 articles were included to assess the risk of ASD in 335507 offspring after ART（ART group） and 14233258 offspring of natural conception（NC group）. After excluding one study with greater heterogeneity by sensitivity analysis,the incidence of child with ASD in ART group was significantly higher than that in NC group（RR=1.06, 95%CI1.01-1.11, P

Objective: We aimed to develop consensus for diagnosis/management of SCN8A‐related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A‐related disorders. Methods: A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty‐eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%–79% fully/partially agree, <10% disagree. Results: Early diagnosis is important for long‐term clinical outcomes in SCN8A‐related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self‐limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first‐line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first‐line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First‐line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. Significance: This is the first‐ever global consensus for the diagnosis and treatment of SCN8A‐related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence‐based care and empowers SCN8A families to advocate for their children. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A‐related disorders. Methods: A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified‐Delphi process. Twenty‐eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified‐Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%–79% fully or partially agree, <10% disagree. Results: Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non‐seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep‐related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE. Significance: Significant comorbidities are present in most phenotypes of SCN8A‐related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long‐term management for patients with these comorbidities and provide the basis for future evidence‐based studies on optimal treatments of SCN8A‐related disorders. Identifying the prognosis of patients with SCN8A‐related disorders will also improve care and quality‐of‐life for patients and their caregivers. [ABSTRACT FROM AUTHOR]

Space cameras play a pivotal role in various fields, such as astronomical exploration. When operating in orbit, these cameras encounter the relative motion between the target and the camera during the exposure, resulting in image motion, which affects the imaging quality. Therefore, it is necessary to compensate for this image motion. This paper investigates the in-orbit image motion compensation (IMC) method for space cameras with a long integration time based on a two-axis pointing platform. Firstly, the mechanical design of the camera is introduced. Secondly, the in-orbit IMC model for the camera is analyzed, and the angular motion needed for compensating for the image motion by the two-axis pointing platform are derived. Factors influencing the compensation accuracy are also analyzed. The effectiveness of the IMC model is verified through simulations. Finally, the in-orbit experimental results indicate that the energy concentration of the target star images obtained exceeded 70%, demonstrating excellent performance in space cameras and effectively enhancing imaging quality using IMC technology. [ABSTRACT FROM AUTHOR]

This study investigates the influence of humidity on the dissolution behavior and microstructure of drugs in crystalline solid dispersions (CSDs). Using Bifonazole (BFZ) as a model drug, CSDs were prepared through spray drying with carriers such as Poloxamer 188 (P188), Poloxamer 407 (P407), and polyethylene glycol 8000 (PEG8000). The solubilization effect and mechanism were initially evaluated, followed by an examination of the impact of humidity (RH10%) on the dissolution behavior of CSDs. Furthermore, the influence of humidity on the microstructure of CSDs was investigated, and factors affecting the humidity stability of CSDs were summarized. Significant enhancements in the intrinsic dissolution rate (IDR) of BFZ in CSDs were observed due to changes in crystalline size and crystallinity, with the CSD-P188 system exhibiting the best performance. Following humidity treatment, the CSD-P407 system demonstrated the least change in the IDR of BFZ, indicating superior stability. The CSD-P407 system was followed by the CSD-P188 system, with the CSD-PEG8000 system exhibiting the least stability. Further analysis of the microstructure revealed that while humidity had negligible effects on the crystalline size and crystallinity of BFZ in CSDs, it had a significant impact on the distribution of BFZ on the CSD surface. This can be attributed to the water's potent plasticizing effect, which significantly alters the molecular mobility of BFZ. Additionally, the compatibility of the three polymers with BFZ differs, with CSD-P407 > CSD-P188 > CSD-PEG8000. Under the continuous influence of water, stronger compatibility leads to lower molecular mobility and more uniform drug distribution on the CSD surface. Enhancing the compatibility of drugs with polymers can effectively reduce the mobility of BFZ in CSDs, thereby mitigating changes caused by water and ultimately stabilizing the surface composition and dissolution behavior of drugs in CSDs. [ABSTRACT FROM AUTHOR]

Crystalline solid dispersions (CSDs) represent a thermodynamically stable system capable of effectively reducing the crystallite size of drugs, thereby enhancing their solubility and bioavailability. This study uses flavonoid drugs with the same core structures but varying numbers of hydroxyl groups as model drugs and poloxamer 188 as a carrier to explore the intrinsic relationships between drug–polymer interactions, crystallite size, and in vitro dissolution behavior in CSDs. Initially, we investigate the interactions between flavonoid drugs and P188 by calculating Hansen solubility parameters, determination of Flory–Huggins interaction parameters, and other methods. Subsequently, we explore the crystallization kinetics of flavonoid drugs and P188 in CSD systems using polarized optical microscopy and powder X-ray diffraction. We monitor the domain size and crystallite size of flavonoids in CSDs through powder X-ray diffraction and a laser-particle-size analyzer. Finally, we validate the relationship between crystallite size and in vitro dissolution behavior through powder dissolution. The results demonstrate that, as the number of hydroxyl groups increases, the interactions between drugs and polymers become stronger, making drug crystallization in the CSD system less likely. Consequently, reductions in crystalline domain size and crystallite size become more pronounced, leading to a more significant enhancement in drug dissolution. [ABSTRACT FROM AUTHOR]

Oudemansiella raphanipes, considered as a well-known culinary edible mushroom with a high content of natural bioactive substances, is widely cultivated in China with the commercial name Changgengu. However, due to the lack of genomic data, molecular and genetic study on O. raphanipes is rare. To obtain a comprehensive overview of genetic characteristics and enhance the value of O. raphanipes, two mating-compatible monokaryons isolated from the dikaryon were applied for de novo genome sequencing and assembly using Nanopore and /or Illumina sequencing platforms. One of the monokaryons, O. raphanipes CGG-A-s1, was annotated with 21,308 protein-coding genes, of which 56 were predicted to be involved in the biosynthesis of secondary metabolites such as terpene, type I PKS, NRPS, and siderophore. Phylogenetic and comparative analysis of multiple fungi genomes revealed a close evolutionary relationship between O. raphanipes and Mucidula mucid based on single-copy orthologous protein genes. Significant collinearity was detected between O. raphanipes and Flammulina velutipes on the synteny of inter-species genomes. 664 CAZyme genes in CGG-A-s1 were identified with GHs and AAs families significantly elevated when compared with the other 25 sequenced fungi, indicating a strong wood degradation ability. Furthermore, the mating type locus analysis revealed that CGG-A-s1 and CGG-A-s2 were conserved in the gene organization of the mating A locus but various in that of the mating B locus. The genome resource of O. raphanipes will provide new insights into its development of genetic studies and commercial production of high-quality varieties. [ABSTRACT FROM AUTHOR]

(1) Background: The Hypsizygus marmoreus is a popular edible mushroom in East Asian markets. In a previous study, we reported the proteomic analyses of different developmental stages of H. marmoreus, from primordium to mature fruiting body. However, the growth and protein expression changes from scratching to primordium are unclear. (2) Methods: A label-free LC-MS/MS quantitative proteomic analysis technique was adopted to obtain the protein expression profiles of three groups of samples collected in different growth stages from scratching to the tenth day after scratching. The Pearson's correlation coefficient analysis and principal component analysis were performed to reveal the correlation among samples. The differentially expressed proteins (DEPs) were organized. Gene Ontology (GO) analysis was performed to divide the DEPs into different metabolic processes and pathways. (3) Results: From the 3rd day to the 10th day after scratching, mycelium recovered gradually and formed primordia. Compared with the Rec stage, 218 highly expressed proteins were identified in the Knot stage. Compared with the Pri stage, 217 highly expressed proteins were identified in the Rec stage. Compared with the Pri stage, 53 highly expressed proteins were identified in the Knot stage. A variety of the same highly expressed proteins were identified in these three developmental stages, including: glutathione S-transferase, acetyltransferase, importin, dehydrogenase, heat-shock proteins, ribosomal proteins, methyltransferase, etc. The key pathways in the development of H. marmoreus are metabolic process, catabolic process, oxidoreductase activity and hydrolase activity. DEPs in the Knot or Pri stages compared with the Rec stage were significantly decreased in the metabolic-, catabolic- and carbohydrate-related process; and the oxidoreductase, peptidase, and hydrolase activity, which can serve as targets for selectable molecular breeding in H. marmoreus. A total of 2000 proteins were classified into eight different modules by WGCNA, wherein 490 proteins were classified into the turquoise module. (4) Conclusions: Generally, from the 3rd day to the 10th day after scratching, mycelium recovered gradually and formed primordia. Importin, dehydrogenase, heat-shock proteins, ribosomal proteins, transferases were all highly expressed in these three developmental stages. DEPs in the Rec stage compared with the Knot or Pri stages were significantly enriched in the metabolic-, catabolic- and carbohydrate-related process; and in oxidoreductase, peptidase and hydrolase activities. This research contributes to the understanding of the mechanisms of the development changes before primordium of H. marmoreus. [ABSTRACT FROM AUTHOR]

Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, it was found that the ABZ-BA group had 2.7-fold greater than that of Albenda after 1 month of oral administration. The relative bioavailability of ABZ-BA is significantly better than ABZ due to the transformation of the physical state from a crystalline state to an amorphous state. Furthermore, sodium-dependent bile acid transporter (ASBT) expressed in the apical small intestine has a synergistic effect through the effective transport of bile acids. Therefore, we concluded that the NC formulation could potentially be developed to improve anti-AE drug therapy. Author summary: Alveolar echinococcosis (AE) is a neglected zoonotic parasitic disease caused by Echinococcus multilocularis (E. multilocularis). This parasitic infection can cause severe damage to the liver, lungs, and other human or animal organs, which can be fatal if left untreated. The 10-year mortality rate for patients with untreated or improperly treated AE is greater than 90%. Therefore, AE is also called as "worm cancer". Benzimidazoles, including the first-line drug ABZ, are considered the only effective drug against AE. However, ABZ has a low and erratic oral bioavailability due to its low solubility,which has partially led to unsatisfactory clinical efficacy of this oral drug. In this study, albendazole bile acid derivatives were prepared to improve the anti-Echinococcus multilocularis effect. The synergistic effect of steric hindrance and transmembrane transport increased the equilibrium solubility of ABZ-BA in vitro by nearly 4-fold and the bioavailability in vivo by about 90-fold. The in vivo study demonstrated that the pharmacokinetic behavior of the ABZ-BA was superior to that of Albenda. In the pharmacodynamics study, it was also found that the ABZ-BA group had a significant therapeutic effect after 1 month of oral administration. This albendazole bile acid derivative provides an effective and translatable novel approach to oral drug therapy for chronic, fatal, and neglected parasitic infectious alveolar echinococcosis. [ABSTRACT FROM AUTHOR]

The radiation-induced inflammatory response is involved in radiation damage to the cochlea and causes sensorineural hearing loss (SNHL). NF-κB, as the master switch of the inflammatory response, regulates the expression of many inflammation-related genes and thus the inflammatory response. Therefore, in this study we used a mouse model to determine whether radiation-induced NF-κB activation is involved in damage to the cochlea and to investigate the underlying mechanism. Eventually, we found that NF-κB was activated after radiation of the cochleae and the activation reached a maximum at 2–6 h after radiation. And morphological analysis showed severe damage to the cochleae after radiation, but this damage was significantly ameliorated by JSH-23 (an inhibitor of NF-κB) pretreatment. Along with these morphological changes, the expression levels of proinflammatory molecules (including proinflammatory cytokines IL-6, TNF-α, COX-2 and inflammation-related proteins VCAM-1, MIP-1β) in the cochlear tissues were significantly increased after radiation, but were significantly decreased by JSH-23 pretreatment compared to radiation alone. Therefore, these results indicated that radiation-induced NF-κB activation was involved in damage to the cochleae and resultant SNHL via its promotion of the inflammatory response mediated by overexpression of some proinflammatory molecules in cochlear tissues, and inhibition of radiation-induced NF-κB was conducive to preventing such damage. [ABSTRACT FROM AUTHOR]

Objective Approximately 65 million people have epilepsy around the world. Recognition of epilepsy types is the basis to determine the treatment method and predict the prognosis in epilepsy patients. Childhood benign epilepsy with centrotemporal spikes (BECTS) or benign Rolandic epilepsy is the most common focal epilepsy in children, accounting for 15–20% of childhood epilepsies. These EEG patterns of individuals usually predict good treatment responses and prognosis. Until now, the interpretation of EEG still depends entirely on experienced neurologists, which may be a lengthy and tedious task. Method In this article, we proposed a novel machine learning model that efficiently distinguished Rolandic seizures from normal EEG signals. The proposed machine learning model processes the identification procedure in the following order (1) creating preliminary EEG features using signal empirical mode decomposition, (2) applying weighted overlook graph (WOG) to represent the decomposed EMD of IMF, and (3) classifying the results through a two Dimensional Convolutional Neural Network (2DCNN). The performance of our classification model is compared with other representative machine learning models. Results The model offered in this article gains an accuracy performance exceeding 97.6% in the Rolandic dataset, which is higher than other classification models. The effect of the model on the Bonn public dataset is also comparable to existing methods and even performs better in some subsets. Conclusion The purpose of this study is to introduce the most common childhood benign epilepsy type and propose a model that meets the real clinical needs to distinguish this Rolandic EEG pattern from normal signals accurately. Significance Future research will optimize the model to categorize other types of epilepsies beyond BECTS and finally implement them in the hospital system. [ABSTRACT FROM AUTHOR]

During resonance in resonant cavities, such as those used in laser or cavity ring-down spectroscopes (CRDS), resonant coupling between higher-order transverse modes and fundamental modes can seriously affect the quality of the beam and introduce measurement errors. Several coupling models, such as thermal deformation coupling and scattering coupling, have been established according to existing coupling theory and specific application scenarios; however, these coupling models have not been attributed to a unified theory. In this paper, we reveal that the same resonant coupling excitation factors exist under different types of environmental perturbation. The conditions and range of resonant coupling in a CRDS ring-down cavity are systematically analyzed, and a preferential coupling model of the middle-order modes is proposed. The time-domain characteristics of the CRDS are used in experiments to analyze the resonant coupling between the modes in a weak energy system. The order and coupling range of the middle-order modes involved in resonant coupling are verified using the modal filtering characteristics of the triangular cavity; this paper presents a unified explanation for various types of resonant coupling and also provides a new approach to resonant coupling experiments performed in high-finesse resonant cavities. [ABSTRACT FROM AUTHOR]

Glycyrrhetinic acid (GA) is an anti-inflammatory drug with potential for development. However, the poor solubility of GA in water leads to extremely low bioavailability, which limits its clinical applications. Solid dispersions have become some of the most effective strategies for improving the solubility of poorly soluble drugs. Soluplus®, a non-cytotoxic amphiphilic solubilizer, significantly improves the solubility of BCS II drugs and improves the bioavailability of insoluble drugs. l-arginine (L-Arg) can be used as a small molecular weight excipient to assist in improving the solubility of insoluble drugs. In this study, we developed a new formulation for oral administration by reacting GA and L-Arg to form salts by co-solvent evaporation and then adding the polymer-solvent Soluplus® with an amphiphilic chemical structure to prepare a solid dispersion GA-SD. The chemical and physical properties of GA-SD were characterized by DLS, TEM, XRD, FT-IR and TG. The anti-inflammatory activity of GA-SD was verified by LPS stimulation of RAW 267.5 cells simulating a cellular inflammation model, TPA-induced ear edema model in mice, and ethanol-induced gastric ulcer model. The results showed that the amide bond and salt formation of GA-SD greatly improved GA solubility. GA-SD effectively improved the anti-inflammatory effect of free GA in vivo and in vitro, and GA-SD had no significant effect on liver and kidney function, no significant tissue toxicity, and good biosafety. In conclusion, GA-SD with L-Arg and Soluplus® is an effective method to improve the solubility and bioavailability of GA. As a safe and effective solid dispersion, it is a promising anti-inflammatory oral formulation and provides some references for other oral drug candidates with low bioavailability. [ABSTRACT FROM AUTHOR]

Traditional lung-protective ventilation strategies (LPVS) are currently used to reduce the incidence of postoperative pulmonary complications (PPCs), including low tidal volume (VT), positive end-expiratory pressure (PEEP), low inspiratory plateau pressure (Pplat), permissive hypercapnia, and recruitment maneuver (RM). However, a meta-analysis showed that high driving pressure was closely associated with the incidence of PPCs, but not with PEEP or VT, which led to the driving pressure-guided ventilation strategy. Some studies have proved that the driving pressure-guided ventilation strategy is superior to the traditional LPVS in reducing the incidence of PPCs. The purpose of this review is to present the current research progress and application of driving pressure-guided ventilation strategy. [ABSTRACT FROM AUTHOR]