Spike structures, receptor binding, and immune escape of recently circulating SARS-CoV-2 Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants.

The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.

EnRDeA U-Net Deep Learning of Semantic Segmentation on Intricate Noise Roads.

Road segmentation is beneficial to build a vision-controllable mission-oriented self-driving bot, e.g., the Self-Driving Sweeping Bot, or SDSB, for working in restricted areas. Using road segmentation, the bot itself and physical facilities may be protected and the sweeping efficiency of the SDSB promoted. However, roads in the real world are generally exposed to intricate noise conditions as a result of changing weather and climate effects; these include sunshine spots, shadowing caused by trees or physical facilities, traffic obstacles and signs, and cracks or sealing signs resulting from long-term road usage, as well as different types of road materials, such as cement or asphalt; all of these factors greatly influence the effectiveness of road segmentation. In this work, we investigate the extension of Primordial U-Net by the proposed EnRDeA U-Net, which uses an input channel applying a Residual U-Net block as an encoder and an attention gate in the output channel as a decoder, to validate a dataset of intricate road noises. In addition, we carry out a detailed analysis of the nets' features and segmentation performance to validate the intricate noises dataset on three U-Net extensions, i.e., the Primordial U-Net, Residual U-Net, and EnRDeA U-Net. Finally, the nets' structures, parameters, training losses, performance indexes, etc., are presented and discussed in the experimental results.

Three-Fluid Nozzle Spray Drying Strategy for Efficient Fabrication of Functional Colloidosomes.

Colloidosomes as Pickering emulsion microcapsules are expected to serve various applications, including encapsulation of drugs and loading of functional materials. Normally, when using colloidosomes for drug encapsulation, the latex particles as shell materials need to be mixed with drugs before the assembly process. However, this procedure may cause aggregation of latex particles, thereby resulting in disordered assembled shells or a low loading efficiency. Herein, we propose a three-fluid nozzle spray drying process to efficiently assemble latex particles of P(styrene (St)-co-butyl acrylate (BA)) into colloidosomes. The three-fluid nozzle spray drying equipment allows for the preparation for drug encapsulation without advance mixing of drug and shell materials. This strategy enables the construction of colloidosomes with uniform and controllable pores and the loading of functional materials. The effects of the compressed air flow rate, inlet temperature, feed rate, and solid content were explored, revealing the formation mechanism of colloidosomes during the spray drying process. Doxycycline hydrochloride (DH) was encapsulated in colloidosomes for controllable release, and the sustained release time is up to 100 h. The release rate can be adjusted by varying the glass transition temperature (Tg) and size of latex particles. Furthermore, Fe3O4 nanoparticle (NP)-loaded colloidosomes were constructed by this strategy. The magnetic response intensity of colloidosomes can be modulated by varying the amount of Fe3O4 NPs. The anticancer drug encapsulation and loading of other functional particles were also explored to expand applications.

Intermittent hypoxia conditioning as a potential prevention and treatment strategy for ischemic stroke: Current evidence and future directions.

Ischemic stroke (IS) is the leading cause of disability and death worldwide. Owing to the aging population and unhealthy lifestyles, the incidence of cerebrovascular disease is high. Vascular risk factors include hypertension, diabetes, dyslipidemia, and obesity. Therefore, in addition to timely and effective reperfusion therapy for IS, it is crucial to actively control these risk factors to reduce the incidence and recurrence rates of IS. Evidence from human and animal studies suggests that moderate intermittent hypoxia (IH) exposure is a promising therapeutic strategy to ameliorate common vascular risk factors and comorbidities. Given the complex pathophysiological mechanisms underlying IS, effective treatment must focus on reducing injury in the acute phase and promoting repair in the recovery phase. Therefore, this review discusses the preclinical perspectives on IH conditioning as a potential treatment for neurovascular injury and highlights IH pre and postconditioning strategies for IS. Hypoxia conditioning reduces brain injury by increasing resistance to acute ischemic and hypoxic stress, exerting neuroprotective effects, and promoting post-injury repair and regeneration. However, whether IH produces beneficial effects depends not only on the hypoxic regimen but also on inter-subject differences. Therefore, we discuss the factors that may influence the effectiveness of IH treatment, including age, sex, comorbidities, and circadian rhythm, which can be used to help identify the optimal intervention population and treatment protocols for more accurate, individualized clinical translation. In conclusion, IH conditioning as a non-invasive, non-pharmacological, systemic, and multi-targeted intervention can not only reduce brain damage after stroke but can also be applied to the prevention and functional recovery of IS, providing brain protection at different stages of the disease. It represents a promising therapeutic strategy. For patients with IS and high-risk groups, IH conditioning is expected to develop as an adjunctive clinical treatment option to reduce the incidence, recurrence, disability, and mortality of IS and to reduce disease burden.

Cerebral edema after ischemic stroke: Pathophysiology and underlying mechanisms.

Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in prevention and treatment strategies as well as drug development. This review discusses the classification and pathological characteristics of cerebral edema, the possible relationship of the development of cerebral edema after ischemic stroke with aquaporin 4, the SUR1-TRPM4 channel, matrix metalloproteinase 9, microRNA, cerebral venous reflux, inflammatory reactions, and cerebral ischemia/reperfusion injury. It also summarizes research on new therapeutic drugs for post-stroke cerebral edema. Thus, this review provides a reference for further studies and for clinical treatment of cerebral edema after ischemic stroke.

Photocatalyst-free Light-driven Dehydrogenation of Alcohols into Carbonyl Compounds under Mild Conditions.

Herein, we reported a photocatalyst-free, facile and eco-friendly method for conducting dehydrogenation of alcohols to corresponding aldehydes or ketones with high selectivity under mild conditions. The methodology exhibited outstanding tolerance with electron-donating and electron-withdrawing groups and afforded series of aldehydes or ketones in considerable yields. Furthermore, the plausible mechanism was investigated by control experiments and DFT calculations. The advantages of readily accessible, atomic economy and green reaction conditions for the present method will endow it with prospective application in chemical synthesis.

Correlation Between Sialidase NEU1 mRNA Expression Changes in Autism Spectrum Disorder.

Abnormal alterations in enzymes functioned in sialic acid modifications may be associated with ASD. In order to study the differences in peripheral blood sialidase (neuraminidase 1; NEU1) mRNA expression between autism spectrum disorder (ASD) children and healthy control, and to examine the correlation between NEU1 mRNA expression and the main behavioral phenotypes in children with ASD, we performed RT-qPCR to measure NEU1 mRNA expression in peripheral blood of 42 children with ASD and 42 healthy controls. In addition, we used the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) to measure and evaluate the behavioral phenotypes of children with ASD. Our results showed that NEU1 mRNA in the ASD group was significantly higher than in the control group (P < 0.0001). In addition, the ADOS-2 diagnostic scores of 42 children with ASD were correlated with their NEU1 mRNA expression results (R = 0.344, P = 0.0257). Moreover, in general, NEU1 mRNA expression was also positively correlated with the Social Affect (SA) of ADOS-2 (R = 0.3598, P = 0.0193) but not with the Restricted and Repetitive Behavior (RRB) (R = 0.15, P = 0.3432). Our results indicated that sialidase NEU1 mRNA was significantly increased in children with ASD, and its expression was correlated with the SA of children with ASD, which suggested that sialidase NEU1 may affect the SA of ASD. Our data highlighted the potential of NEU1 expression change may play an important role in ASD disease and lay the foundation for further studies on the relationship between NEU1 and ASD.

Clinical Characteristics, Radiological Features and Gene Mutation in 10 Chinese Families with Spinocerebellar Ataxias.

BACKGROUND: Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs. METHODS: In this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed. RESULTS: We found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset. CONCLUSIONS: Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.