Development of an Integrated Disposable Device for SARS-CoV-2 Nucleic Acid Extraction and Detection.

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).

Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

Itga5-PTEN signaling regulates striatal synaptic strength and motor coordination in Parkinson's disease.

Background: Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and cognitive dysfunctions. The molecular mechanisms underlying synaptic alterations in PD remain elusive, with a focus on the role of Itga5 in synaptic integrity and motor coordination and TAT-Itga5 was designed to suppress PTEN activity in this investigation. Methods: This study utilized MPTP-induced PD animal models to investigate the expression and role of Itga5 in the striatum. Techniques included quantitative PCR, Western blotting, immunostaining, CRISPR-CasRx-mediated knockdown, electrophysiological assays, behavioral tests, and mass spectrometry. Results: Itga5 expression was significantly reduced in MPTP-induced PD models. In these models, a marked decrease in dendritic spine density and a shift towards thinner spines in striatal GABA neurons were observed, suggesting impaired synaptic integration. Knockdown of Itga5 resulted in reduced dendritic branching, decreased mushroom spines, and increased thin spines, altering synaptic architecture. Electrophysiological analyses revealed changes in action potential and spontaneous excitatory postsynaptic currents, indicating altered synaptic transmission. Motor behavior assessments showed that Itga5 deficiency led to impairments in fine motor control and coordination. Furthermore, Itga5 was found to interact with PTEN, affecting AKT signaling crucial for synaptic development and motor coordination. Conclusion: The study demonstrates that Itga5 plays a critical role in maintaining synaptic integrity and motor coordination in PD. The Itga5-PTEN-AKT pathway represents a potential therapeutic target for addressing synaptic and motor dysfunctions in PD.

Factors Associated with Intention to Use Telerehabilitation for Children with Special Needs: A Cross-Sectional Study.

Background: Children with special health care needs (CSHCN) require long-term and ongoing rehabilitation interventions supporting their development. Telerehabilitation can provide continuous rehabilitation services for CSHCN. However, few studies have explored the intention of CSHCN and their caregivers to use telerehabilitation and its impact on them. Objective: The objective of this study was to identify factors that influence the intention to use telerehabilitation among CSHCN and their caregivers. Methods: This study was a cross-sectional study. Based on the unified theory of acceptance and use of technology, extended with additional predictors (trust and perceived risk [PR]), this study developed a research model and proposed 10 hypotheses. A structured questionnaire was distributed to 176 caregivers. Data were analyzed and research hypotheses were tested using partial least squares structural equation modeling to better understand the factors influencing the use of telerehabilitation. Results: A total of 164 valid questionnaires were collected. CSHCN and their caregivers were overall satisfied with this telerehabilitation medical service. The results of the structural model analysis indicated that social influence (SI), facilitating conditions (FC), and trust had significant effects on behavioral intention (BI) to use telerehabilitation, while the paths between performance expectancy (PE), effort expectancy (EE), and PR and BI were not significant. PE, EE, and SI had a significant effect on trust. Moreover, EE and SI had indirect effects on BI, with trust as the mediator. Conclusions: The results indicated that SI, FC, and trust are significant factors influencing CSHCN and their caregivers' use of telerehabilitation. Trust is also an important mediator for the intention and highly influenced by PE, EE, and SI.

Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a major risk factor for chronic gastritis, affecting approximately half of the global population. H. pylori eradication is a popular treatment method for H. pylori-positive chronic gastritis, but its mechanism remains unclear. Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment. However, no clinical study has been conducted on urinary metabolomics of chronic gastritis. AIM: To elucidate the urinary metabolic profiles during H. pylori eradication in patients with chronic gastritis. METHODS: We applied LC-MS-based metabolomics and network pharmacology to investigate the relationships between urinary metabolites and H. pylori-positive chronic gastritis via a clinical follow-up study. RESULTS: Our study revealed the different urinary metabolic profiles of H. pylori-positive chronic gastritis before and after H. pylori eradication. The metabolites regulated by H. pylori eradication therapy include cis-aconitic acid, isocitric acid, citric acid, L-tyrosine, L-phenylalanine, L-tryptophan, and hippuric acid, which were involved in four metabolic pathways: (1) Phenylalanine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; (3) citrate cycle; and (4) glyoxylate and dicarboxylate metabolism. Integrated metabolomics and network pharmacology revealed that MPO, COMT, TPO, TH, EPX, CMA1, DDC, TPH1, and LPO were the key proteins involved in the biological progress of H. pylori eradication in chronic gastritis. CONCLUSION: Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H. pylori-positive chronic gastritis patients.

Eudesmane sesquiterpenoids with inhibitory effects on NO production from Artemisia princeps.

Five undescribed eudesmane methyl esters (1-5), three undescribed eudesmane-12,6-olides (6-8), and 21 known analogues (9-29) were isolated from the aerial part of Artemisia princeps Pamp. Their structures were established by detailed analysis of the NMR and HRESIMS data. The absolute configurations of 1-8 were determined based on single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory effects on LPS-induced NO production in BV-2 microglial cells of all the isolated compounds were assessed. Except for compounds 2, 4, 10, and 11, the others showed significant inhibitory activities, with IC50 values of 0.73-18.66 µM, wherein the potential structure-activity relationship was also discussed.

Hysterolides A-I, dimeric or monomeric sesquiterpene lactones from Parthenium hysterophorus L.

Nine undescribed sesquiterpene lactones, including two pseudoguaianolide dimers (1 and 2), a pseudoguaiac dilactone (3), and six pseudoguaianolides (4-9), along with 13 known analogues (10-22) were isolated from Parthenium hysterophorus. Among them, hysterolide A (1) possesses an unusual carbon skeleton with a unique cyclobutane ring connecting two pseudoguaianolides. Hysterolide C (3) is a sesquiterpene dilactone incorporating a bicyclo[5.1.0]octane core. Spectroscopic analyses, 13C NMR and ECD calculations, and X-ray diffraction elucidated their structures and absolute configurations. Moreover, all the isolates were assayed for their anti-inflammatory activities by inhibiting LPS-induced nitric oxide production in BV-2 microglia cells, wherein, nine compounds displayed significant inhibitory activities with IC50 of 0.52-6.32 µM. Furthermore, the preliminary structure-activity relationship was also established.

[Gonadoblastoma: Clinicopathological study and literature review of 3 cases].

OBJECTIVE: To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma. METHODS: Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed. RESULT: Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence. CONCLUSION: Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.