Search

Objective: This study aims to explore the perspectives and experiences of Australian caregivers and community pharmacists about pediatric melatonin use. Methods: A convenience sample of caregivers with children (aged 11–16 years) using melatonin as a sleep aid and community pharmacists (including pharmacist interns) were recruited. Participants first completed an online survey followed by an online semi-structured interview. Interviews were guided by a schedule of questions for the respective participant groups, broadly exploring their beliefs about melatonin, experiences in using/supplying melatonin, and perceived facilitators/barriers for melatonin use. Interviews were digitally recorded, transcribed verbatim, and analyzed using the Framework Approach. Results: Fourteen caregivers of predominantly neurodiverse adolescents and 24 community pharmacists were interviewed. While melatonin was perceived by caregivers of both typically developing and neurodiverse dependants as safer than pharmacological sleep aids, treatment was only initiated after trialling non-pharmacological strategies first. Pharmacists expressed concerns around the ambiguities in practice and the limited scope of existing resources for guiding pediatric melatonin use. Caregivers frequently deferred to the information available online to procure products or self-adjust doses and dosing schedules. Both pharmacists and caregivers emphasized the need for more affordable and age-appropriate proprietary formulations that are readily accessible. Conclusion: Melatonin is administered predominantly by caregivers of neurodiverse adolescents to address their sleep disturbances. The findings underscore the need for reliable, evidence-based information to guide safe and appropriate use of melatonin in pediatric populations. Patient education is also warranted to address maladaptive medication-administration practices. Lastly, there is a need for stronger regulatory oversight of melatonin products to ensure their quality and safety of use. [ABSTRACT FROM AUTHOR]

Injury to the peripheral nervous system disconnects targets to the central nervous system, disrupts signal transmission, and results in functional disability. Although surgical and therapeutic treatments improve nerve regeneration, it is generally hard to achieve fully functional recovery after severe peripheral nerve injury. A better understanding of pathological changes after peripheral nerve injury helps the development of promising treatments for nerve regeneration. Single-cell analyses of the peripheral nervous system under physiological and injury conditions define the diversity of cells in peripheral nerves and reveal cellspecific injury responses. Herein, we review recent findings on the single-cell transcriptome status in the dorsal root ganglia and peripheral nerves following peripheral nerve injury, identify the cell heterogeneity of peripheral nerves, and delineate changes in injured peripheral nerves, especially molecular changes in neurons, glial cells, and immune cells. Cell-cell interactions in peripheral nerves are also characterized based on ligand-receptor pairs from coordinated gene expressions. The understanding of cellular changes following peripheral nerve injury at a single-cell resolution offers a comprehensive and insightful view for the peripheral nerve repair process, provides an important basis for the exploration of the key regulators of neuronal growth and microenvironment reconstruction, and benefits the development of novel therapeutic drugs for the treatment of peripheral nerve injury. [ABSTRACT FROM AUTHOR]

β-nicotinamide mononucleotide (NMN) is a naturally occurring biologically active nucleotide widely present in organisms and an inherent substance in the human body. As a critical intermediate in synthesizing coenzyme I (NAD+), it widely participates in multiple biochemical reactions in the human body and is closely related to immunity, metabolism, and other factors. In recent years, NMN has rapidly developed and made significant progress in medicine, food, and healthcare. However, there is currently a lack of comprehensive reports on the research progress of NMN, as well as exploration and analysis of the current research achievements and progress of NMN. Therefore, this review is based on retrieving relevant research on NMN from multiple databases at home and abroad, with the retrieval time from database establishment to 20 May 2024. Subsequently, literature search, reading, key information extraction, organization, and summarization were conducted with the aim of providing a comprehensive and in-depth analysis of the characteristics, metabolic pathways, pharmacological effects, progress in human clinical trials, and wide applications of NMN in drug development and food applications. Furthermore, it offers personal insights into NMN's potential future developments and advancements to present the current development state and existing challenges comprehensively. Ultimately, this review aims to provide guidance and serve as a reference for the future application, innovation, and progression of NMN research. [ABSTRACT FROM AUTHOR]

Purpose: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles. Methods: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep. Results: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001). Conclusion: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk. [ABSTRACT FROM AUTHOR]

Currently, despite advancements in diagnostic and therapeutic modalities, osteomyelitis and prosthetic joint infection (PJI) continue to pose significant challenges for orthopaedic surgeons. These challenges are primarily attributed to the high degree of heterogeneity exhibited by these disorders, which are influenced by a combination of environmental and host factors. Recent research efforts have delved into the pathogenesis of osteomyelitis and PJI by investigating single nucleotide polymorphisms (SNPs). This review comprehensively summarizes the current evidence regarding the associations between SNPs and the predisposition to osteomyelitis and PJI across diverse populations. The findings suggest potential linkages between SNPs in genes such as IL-1, IL-6, IFN-γ, TNF-α, VDR, tPA, CTSG, COX-2, MMP1, SLC11A1, Bax, NOS2, and NLRP3 with the development of osteomyelitis. Furthermore, SNPs in genes like IL-1, IL-6, TNF-α, MBL, OPG, RANK, and GCSFR are implicated in susceptibility to PJI. However, it is noted that most of these studies are single-center reports, lacking in-depth mechanistic research. To gain a more profound understanding of the roles played by various SNPs in the development of osteomyelitis and PJI, future multi-center studies and fundamental investigations are deemed necessary. [ABSTRACT FROM AUTHOR]

The rapid growth of large-scale spatial gene expression data demands efficient and reliable computational tools to extract major trends of gene expression in their native spatial context. Here, we used stability-driven unsupervised learning (i.e., staNMF) to identify principal patterns (PPs) of 3D gene expression profiles and understand spatial gene distribution and anatomical localization at the whole mouse brain level. Our subsequent spatial correlation analysis systematically compared the PPs to known anatomical regions and ontology from the Allen Mouse Brain Atlas using spatial neighborhoods. We demonstrate that our stable and spatially coherent PPs, whose linear combinations accurately approximate the spatial gene data, are highly correlated with combinations of expert-annotated brain regions. These PPs yield a brain ontology based purely on spatial gene expression. Our PP identification approach outperforms principal component analysis and typical clustering algorithms on the same task. Moreover, we show that the stable PPs reveal marked regional imbalance of brainwide genetic architecture, leading to region-specific marker genes and gene coexpression networks. Our findings highlight the advantages of stability-driven machine learning for plausible biological discovery from dense spatial gene expression data, streamlining tasks that are infeasible by conventional manual approaches. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis is the pathogen that causes Glässer's disease in pigs, which is characterized by fibrinous polyserositis, arthritis and meningitis. Research on ribosomal protein L32 in microorganisms has mainly focused on regulating gene transcription and translation, but its effect on bacterial virulence is unclear. The role of L32 gene in G. parasuis is not clear, and in order to study the function of L32 gene, a suicide plasmid-mediated natural transformation method was used to construct a L32 gene deletion mutant. We found that although L32 was shown to be non-essential for cell proliferation, the growth curve of ΔL32 is clearly different compared with that of ZJ1208. ΔL32 produced more outer membrane vesicles (OMVs) with a variety of irregular shapes, but produced similar biofilm to the parental strain. ΔL32 is more sensitive to osmotic pressure, oxidation pressure and heat shock stress. Meanwhile, ΔL32 is significantly more susceptible to antimicrobials such as spectinomycin, apramycin, sulfafurazole, but not to other antibiotics used in this study. In the mouse challenge experiment, the mortality of mice infected with the mutant strain decreased by 40% compared to those infected with the wild-type strain, indicating that L32 is a virulence-associated factor which contributes to bacterial fitness in host environments. The above results show that L32 is important for the growth, stress resistance and virulence of G. parasuis, and this study also confirms for the first time that L32 plays an important role in antibiotic resistance against aminoglycosides and sulfonamides. [ABSTRACT FROM AUTHOR]

Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution. [ABSTRACT FROM AUTHOR]

Nerve injuries significantly impact the quality of life for patients, with severe cases posing life-threatening risks. A comprehensive understanding of the pathophysiological mechanisms underlying nerve injury is crucial to the development of effective strategies to promote nerve regeneration. Circular RNAs (circRNAs), a recently characterized class of RNAs distinguished by their covalently closed-loop structures, have been shown to play an important role in various biological processes. Numerous studies have highlighted the pivotal role of circRNAs in nerve regeneration, identifying them as potential therapeutic targets. This review aims to succinctly outline the latest advances in the role of circRNAs related to nerve injury repair and the underlying mechanisms, including peripheral nerve injury, traumatic brain injury, spinal cord injury, and neuropathic pain. Finally, we discuss the potential applications of circRNAs in drug development and consider the potential directions for future research in this field to provide insights into circRNAs in nerve injury repair. [ABSTRACT FROM AUTHOR]

Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China. Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020. Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according totime and region. Over time, the incidence of Gram-positive andGramnegative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillinresistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenemandcefoperazone-sulbactamwerethemostactiveagentsagainstGramnegative aerobes. Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Under the policy background and advocacy of carbon capture, utilization, and storage (CCUS), CO2-EOR has become a promising direction in the shale oil reservoir industry. The multi-scale pore structure distribution and fracture structure lead to complex multiphase flow, comprehensively considering multiple mechanisms is crucial for development and CO2 storage in fractured shale reservoirs. In this paper, a multi-mechanism coupled model is developed by MATLAB. Compared to the traditional Eclipse 300 and MATLAB Reservoir Simulation Toolbox (MRST), this model considers the impact of pore structure on fluid phase behavior by the modified PengeRobinson equation of state (PR-EOS), and the effect simultaneously radiate to MaxwelleStefan (MeS) diffusion, stress sensitivity, the nano-confinement (NC) effect. Moreover, a modified embedded discrete fracture model (EDFM) is used to model the complex fractures, which optimizes connection types and half-transmissibility calculation approaches between non-neighboring connections (NNCs). The full implicit equation adopts the finite volume method (FVM) and NewtoneRaphson iteration for discretization and solution. The model verification with the Eclipse 300 and MRST is satisfactory. The results show that the interaction between the mechanisms significantly affects the production performance and storage characteristics. The effect of molecular diffusion may be overestimated in oil-dominated (liquid-dominated) shale reservoirs. The well spacing and injection gas rate are the most crucial factors affecting the production by sensitivity analysis. Moreover, the potential gas invasion risk is mentioned. This model provides a reliable theoretical basis for CO2-EOR and sequestration in shale oil reservoirs. [ABSTRACT FROM AUTHOR]

Adiponectin is a pleiotropic cytokine predominantly derived from adipose tissue. In addition to its role in regulating energy metabolism, adiponectin may also be related to estrogen-dependent diseases, and many studies have confirmed its involvement in mediating diverse biological processes, including apoptosis, autophagy, inflammation, angiogenesis, and fibrosis, all of which are related to the pathogenesis of endometriosis. Although many researchers have reported low levels of adiponectin in patients with endometriosis and suggested that it may serve as a protective factor against the development of the disease. Therefore, the purpose of this review was to provide an up-to-date summary of the roles of adiponectin and its downstream cytokines and signaling pathways in the aforementioned biological processes. Further systematic studies on the molecular and cellular mechanisms of action of adiponectin may provide novel insights into the pathophysiology of endometriosis as well as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) can cause loss of sensory and motor function below the level of injury, posing a serious threat to human health and quality of life. One significant characteristic feature of pathological changes following injury in the nervous system is demyelination, which partially contributes to the long-term deficits in neural function after injury. The remyelination in the central nervous system (CNS) is mainly mediated by oligodendrocyte progenitor cells (OPCs). Numerous complex intracellular signaling and transcriptional factors regulate the differentiation process from OPCs to mature oligodendrocytes (OLs) and myelination. Studies have shown the importance of microRNA (miRNA) in regulating OPC functions. In this review, we focus on the demyelination and remyelination after SCI, and summarize the progress of miRNAs on OPC functions and remyelination, which might provide a potential therapeutic target for SCI treatments. [ABSTRACT FROM AUTHOR]

Approximately 80% of all malignant brain tumors are gliomas, which are primary brain tumors. The most prevalent subtype of glioma, glioblastoma multiforme (GBM), is also the most deadly. Chemotherapy, immunotherapy, surgery, and conventional pharmacotherapy are currently available therapeutic options for GBM; unfortunately, these approaches only prolong the patient's life by 5 years at most. Despite numerous intensive therapeutic options, GBM is considered incurable. Accumulating preclinical data indicate that overt antitumoral effects can be induced by pharmacologically activating endocannabinoid receptors on glioma cells by modifying important intracellular signaling cascades. The complex mechanism underlying the endocannabinoid receptor-evoked antitumoral activity in experimental models of glioma may inhibit the ability of cancer cells to invade, proliferate, and exhibit stem cell-like characteristics, along with altering other aspects of the complex tumor microenvironment. The exact biological function of the endocannabinoid system in the development and spread of gliomas, however, is remains unclear and appears to rely heavily on context. Previous studies have revealed that endocannabinoid receptors are present in the tumor microenvironment, suggesting that these receptors could be novel targets for the treatment of GBM. Additionally, endocannabinoids have demonstrated anticancer effects through signaling pathways linked to the classic features of cancer. Thus, the pharmacology of endocannabinoids in the glioblastoma microenvironment is the main topic of this review, which may promote the development of future GBM therapies. [ABSTRACT FROM AUTHOR]

With the proposal of the "biological-psychological-social" model, clinical decision-makers and researchers have paid more attention to the bidirectional interactive effects between psychological factors and diseases. The brain-gut-microbiota axis, as an important pathway for communication between the brain and the gut, plays an important role in the occurrence and development of inflammatory bowel disease. This article reviews the mechanism by which psychological disorders mediate inflammatory bowel disease by affecting the brain-gut-microbiota axis. Research progress on inflammatory bowel disease causing "comorbidities of mind and body" through the microbiota-gut-brain axis is also described. In addition, to meet the needs of individualized treatment, this article describes some nontraditional and easily overlooked treatment strategies that have led to new ideas for "psychosomatic treatment". [ABSTRACT FROM AUTHOR]

Introduction: The brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective inmanaging this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence. Methods: In this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH. Results: YHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Yresponsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings. Discussion: These findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties. [ABSTRACT FROM AUTHOR]

The planar-chiral ligands have been widely applied as a class of unique and significant ligands in asymmetric catalysis. Among them, chiral [2.2]paracycyclophane has emerged as a privileged type of planar-chiral framework and has been utilized as an important toolbox due to their structural stability. Herein, we design and synthesize [2.2]paracyclophane-derived oxazole-pyrimidine ligands (abberviated as PYMCOX). These N,N-ligands with stable properties, rigid structure and large steric hindrance performed successfully in nickel-catalyzed asymmetric 1,2-reduction of a,ß-unsaturated ketones, affording the chiral allylic alcohols with up to 99% yield and 99% ee. Meanwhile, this reduction reaction could be conducted on gram-scale without loss of activity and enantioselectivity, and the chiral ligand could be conveniently recovered with high yield. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the efficacy of immune checkpoint inhibitors (ICIs) combined with concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. Materials and methods: This retrospective cohort study included patients diagnosed with locally advanced esophageal squamous cell carcinoma who received either CCRT alone or CCRT combined with ICIs from April 2019 to February 2023. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS). Results: A total of 101 patients were enrolled, with 58 undergoing CCRT alone and 43 receiving CCRT+ICI. The CCRT+ICI group demonstrated a higher complete response rate compared to the CCRT alone group (11.6% vs. 1.7%, P = 0.037). However, no significant difference was observed in 1-year PFS (58.9% vs. 55.2%; hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 0.70-2.26; P = 0.445) or 1-year OS (70.8% vs. 75.9%; HR = 1.21, 95% CI: 0.58-2.53; P = 0.613) between CCRT+ICI and CCRT alone groups. The CCRT alone group experienced a higher incidence of leukopenia of any grade (93.1% vs. 76.7%, P = 0.039) but a lower incidence of pneumonitis of any grade (36.2% vs. 65.1%, P = 0.008). Conclusion: CCRT+ICI may not lead to improved survival outcomes compared to CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. These findings indicate the need for further investigation into this treatment approach. [ABSTRACT FROM AUTHOR]

Virus-induced gene silencing (VIGS) is a powerful technology for molecular characterization of gene functions in plants and has the potential to prevent and control plant diseases. Unfortunately, VIGS in many woody perennials such as citrus are severely hindered because they have a long juvenile period and are recalcitrant to infection compared to herbaceous plants. Here, we report the development of a simple and effective VIGS system based on citrus leaf blotch virus (CLBV), a virus endemic in most citrus-producing countries but showing no symptoms in most citrus varieties. By Agrobacterium-mediated vacuum-infiltration (AVI), pCLBV201-su245 and pCLBV201-pds391 triggered efficient gene silencing (85%) and silencing phenotypes began to appear at 30 days post infiltration/inoculation (dpi), a similar period for achieving that on herbaceous plants. Moreover, the silencing phenotypes could still be observed four years post inoculation. Further, pCLBV201-lob369 was constructed to silence the gene lateral organ boundaries1 (lob1), encoding a key factor for susceptibility to citrus canker that caused by Xanthomonas citri ssp. citri (Xcc). The resistance evaluation results showed that the lesion area, disease index, and bacterial content in the pCLBV201-lob369 treatment group were decreased by 64%, 14%, and 67%, respectively. This work provides a simple and effective VIGS system for citrus which has the potential to be used for diseases control. [ABSTRACT FROM AUTHOR]

The electrocatalytic nitrogen reduction reaction (eNRR) under ambient conditions is deemed a promising alternative for NH3 synthesis. In this paper, an FeP–Fe3O4 nanocomposite electrocatalyst was prepared by phosphating annealing using Fe2O3 as a precursor, and the resulting FeP–Fe3O4 exhibited excellent N2-to-NH3-producing activity over a wide potential window. The highest faradaic efficiency of FeP–Fe3O4 is 11.02% at −0.1 V vs. reversible hydrogen electrode (RHE), and the maximum NH3 yield reaches 12.73 μg h−1 mgcat−1, comparable to or exceeding the reported values in this field. Furthermore, the FeP–Fe3O4 nanocomposite electrocatalyst presents high electrochemical stability, selectivity, and durability. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. Methods: Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30 s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). Results: In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56 ± 11 years, BMI 29.8 ± 5.3 kg/m2, and treatment duration was 4.0 ± 3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, − 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, − 0.4 ± 1.5, p = 0.01; LF, − 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (β(SE) = − 2.21 (0.01), t = − 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. Conclusion: The study findings suggest that successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability. [ABSTRACT FROM AUTHOR]

In this study, we employed a network pharmacology-molecular docking-based strategy to investigate the mechanism of Mie-you decoction (MYT) in treating chronic atrophic gastritis (CAG) and gastric ulcer (GU) based on the theory of "homotherapy for heteropathy". First, we searched for the bioactive ingredients of MYT using the TCMSP and BATMAN-TCM databases. Then, we identified the corresponding protein targets for CAG and GU by searching the GeneCards, OMIM, DisGeNET, and DrugBank databases. Using Cytoscape 3.9.1, we constructed a "drug-ingredients-target-pathway-disease" network. The protein-protein interaction (PPI) network was generated using the STRING network platform. To further analyze the core targets, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the DAVID online tool. AutoDock4 was utilized to assess the binding affinity between ingredients and core targets, and the molecule-protein interactions were visualized using PyMOL 2.2. Our findings revealed a total of 73 bioactive ingredients with 101 potential targets for MYT. Among them, 54 potential targets were identified for both CAG and GU. Ultimately, 37 proteins were determined to be the core targets of MYT in combating CAG and GU. Molecular docking analysis demonstrated high affinity between five proteins, including tumor suppressor protein p53 (TP53) and interleukin-6 (IL-6), and bioactive ingredients, such as luteolin, acacetin, naringenin, baicalein, and wogonin. KEGG pathway enrichment analysis revealed 152 signaling pathways that might play crucial roles in the effectiveness of MYT against CAG and GU. The characteristics of MYT, including its multi-component, multi-target, and multi-pathway effects, aligned with the concept of "homotherapy for heteropathy" in both CAG and GU. By effectively modulating various signaling pathways, including those related to cancer, lipid metabolism, atherosclerosis, and others, MYT achieved its therapeutic objectives. These findings provided modern medical evidence supporting traditional Chinese medicine theory and offered directions for future drug development and experimental design. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases. Methods: The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination. Results: The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy. Discussion: While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

The unbalanced distribution of parking demand is a primary source of parking problems. The autonomous driving system and parking assist system of fully autonomous vehicles provide a possibility to alleviate the uneven distribution of parking demand in the city. Exploring the parking behavior of autonomous vehicle (AV) users is necessary for assessing parking pricing policies. In turn, the distribution of parking demand and people's preference for parking lots may be impacted by the change in the AV parking lot's parking charge. Thus, this paper aims to provide an effective optimization method for AV parking lot price strategy, based on the analysis of the parking behavior of AV users. A stated choice experiment is designed to understand AV users' parking behavior. To estimate the impact of attributes and social-demographic factors, the multinomial logit model is adopted. From the results, we find a farther but cheaper parking lot is more attractive than a closer but more expensive parking lot to AVusers. Based on the estimated results, a bilayer optimization model based on parking behavior is built to optimize AV parking lot prices. The Lagrangian relaxation method is employed to solve the model. By empirical testing, the AV parking price optimization model based on parking behavior is proven to be feasible and effective. According to the case study's findings, the parking lot pricing optimization model and algorithm proposed in this paper can not only meet the benefits of parking lots and the utility of autonomous vehicle users, but also alleviate the demand for parking concentrated in the city center, which means the parking difficulties caused by the distribution of parking demand can be alleviated through the optimization of AV parking lots' parking price. [ABSTRACT FROM AUTHOR]

The arc ignition system based on charring polymers has advantages of simple structure, low ignition power consumption and multiple ignitions, which bringing it broadly application prospect in hybrid propulsion system of micro/nano satellite. However, charring polymers alone need a relatively high input voltage to achieve pyrolysis and ignition, which increases the burden and cost of the power system of micro/nano satellite in practical application. Adding conductive substance into charring polymers can effectively decrease the conducting voltage which can realize low voltage and low power consumption repeated ignition of arc ignition system. In this paper, a charring conductive polymer ignition grain with a cavity geometry in precombustion chamber, which is composed of PLA and multiwall carbon nanotubes (MWCNT) was proposed. The detailed ignition processes were analyzed and two different ignition mechanisms in the cavity of charring conductive polymers were revealed. The ignition characteristics of charring conductive polymers were also investigated at different input voltages, ignition grain structures, ignition locations and injection schemes in a visual ignition combustor. The results demonstrated that the ignition delay and external energy required for ignition were inversely correlated with the voltages applied to ignition grain. Moreover, the incremental depth of cavity shortened the ignition delay and external energy required for ignition while accelerated the propagation of flame. As the depth of cavity increased from 2 to 6 mm (at 50 V), the time of flame propagating out of ignition grain changed from 235.6 to 108 ms, and values of mean ignition delay time and mean external energy required for ignition decreased from 462.8 to 320 ms and 16.2 to 10.75 J, respectively. The rear side of the cavity was the ideal ignition position which had a shorter ignition delay and a faster flame propagation speed in comparison to other ignition positions. Compared to direct injection scheme, swirling injection provided a more favorable flow field environment in the cavity, which was beneficial to ignition and initial flame propagation, but the ignition position needed to be away from the outlet of swirling injector. At last, the repeated ignition characteristic of charring conductive polymers was also investigated. The ignition delay time and external energy required for ignition decreased with repeated ignition times but the variation was decreasing gradually. [ABSTRACT FROM AUTHOR]

The insect mitogenome is typically a compact circular molecule with highly conserved gene contents. Nonetheless, mitogenome structural variations have been reported in specific taxa, and gene rearrangements, usually the tRNAs, occur in different lineages. Because synapomorphies of mitogenome organizations can provide information for phylogenetic inferences, comparative analyses of mitogenomes have been given increasing attention. However, most studies use a very few species to represent the whole genus, tribe, family, or even order, overlooking potential variations at lower taxonomic levels, which might lead to some incorrect inferences. To provide new insights into mitogenome organizations and their implications for phylogenetic inference, this study conducted comparative analyses for mitogenomes of three social bee tribes (Meliponini, Bombini, and Apini) based on the phylogenetic framework with denser taxonomic sampling at the species and population levels. Comparative analyses revealed that mitogenomes of Apini and Bombini are the typical type, while those of Meliponini show diverse variations in mitogenome sizes and organizations. Large inverted repeats (IRs) cause significant gene rearrangements of protein coding genes (PCGs) and rRNAs in Indo-Malay/Australian stingless bee species. Molecular evolution analyses showed that the lineage with IRs have lower dN/dS ratios for PCGs than lineages without IRs, indicating potential effects of IRs on the evolution of mitochondrial genes. The finding of IRs and different patterns of gene rearrangements suggested that Meliponini is a hotspot in mitogenome evolution. Unlike conserved PCGs and rRNAs whose rearrangements were found only in the mentioned lineages within Meliponini, tRNA rearrangements are common across all three tribes of social bees, and are significant even at the species level, indicating that comprehensive sampling is needed to fully understand the patterns of tRNA rearrangements, and their implications for phylogenetic inference. [ABSTRACT FROM AUTHOR]

Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood. Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein. Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116- 5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU. Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance. [ABSTRACT FROM AUTHOR]

Interactions between rice plants (Oryza sativa L.) and brown planthoppers (Nilaparvata lugens Stål, BPHs) are used as a model system to study the molecular mechanisms underlying plant-insect interactions. Small RNAs (sRNAs) regulate growth, development, immunity, and environmental responses in eukaryotic organisms, including plants and insects. Recent research suggests that sRNAs play significant roles in rice-BPH interactions by mediating post-transcriptional gene silencing. The focus of this review is to explore the roles of sRNAs in rice-BPH interactions and to highlight recent research progress in unraveling the mechanism of cross-kingdom RNA interference (ckRNAi) between host plants and insects and the application of ckRNAi in pest management of crops including rice. The research summarized here will aid in the development of safe and effective BPH control strategies. [ABSTRACT FROM AUTHOR]

This study proposes two novel tests for security analyst herding based on binomial correlation and forecast error volatility scaling, and applies it to investigate herding patterns in analyst target prices in 2008–2020 in the UK. Analysts robustly herd in their valuations, with results consistent across years, sectors, in terms of panel fixed effect, quantile, instrumental variable regressions, and when controlled for optimism and conservatism. Herding becomes prominent for stocks followed by at least five analysts and towards the long sides of Fama-French sorts, reinforcing its non-spurious and behavioral nature. [ABSTRACT FROM AUTHOR]

An essential technology of carbon capture, utilization and storage-enhanced oil recovery (CCUS-EOR) for tight oil reservoirs is CO2 huff-puff followed by associated produced gas reinjection. In this paper, the effects of multi-component gas on the properties and components of tight oil are studied. First, the core displacement experiments using the CH4/CO2 multi-component gas are conducted to determine the oil displacement efficiency under different CO2 and CH4 ratios. Then, a viscometer and a liquid density balance are used to investigate the change characteristics of oil viscosity and density after multi-component gas displacement with different CO2 and CH4 ratios. In addition, a laboratory scale numerical model is established to validate the experimental results. Finally, a composition model of multi-stage fractured horizontal well in tight oil reservoir considering nano-confinement effects is established to investigate the effects of multi-component gas on the components of produced dead oil and formation crude oil. The experimental results show that the oil displacement efficiency of multi-component gas displacement is greater than that of single-component gas displacement. The CH4 decreases the viscosity and density of light oil, while CO2 decreases the viscosity but increases the density. And the numerical simulation results show that CO2 extracts more heavy components from the liquid phase into the vapor phase, while CH4 extracts more light components from the liquid phase into the vapor phase during cyclic gas injection. The multi-component gas can extract both the light components and the heavy components from oil, and the balanced production of each component can be achieved by using multi-component gas huff-puff. [ABSTRACT FROM AUTHOR]

This article explores the development of a single-transistor core processor for neuromorphic computing. The researchers propose a compact neuron that can emulate essential neuronal behaviors and process complex spatiotemporal information. The core processor has the potential for practical applications, such as human speech separation, and aims to advance hardware development for brain-inspired computing. The text also discusses the concept of self-recovery in neural transistors, the use of feedforward inhibition in multisensory integration, and presents an application of the neural transistor in improving neural network performance. Overall, this research offers a biorealistic approach to hardware implementation for post-von Neumann computing and machine perception. [Extracted from the article]

Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, p < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, p < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy via multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification. [ABSTRACT FROM AUTHOR]

Background. Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target. Methods. Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis. Results. Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs. Conclusions. This study demonstrated that daidzein alleviates OVX-induced os-teoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason. [ABSTRACT FROM AUTHOR]

The finite difference time domain (FDTD) method was used to solve the Maxwell's equation to obtain the reverse time migration (RTM) of ground penetrating radar (GPR) signals, namely, the FDTD-RTM. In order to ensure that the correct numerical solution of iterative calculation was achieved, it was necessary to obtain high-resolution signals, which greatly limits the applicability of FDTD-RTM in engineering. Based on the characteristics of wavelet multi-resolution analysis, this study proposed a super-resolution signal reconstruction method to improve signal resolution, with the view to completely solving the problem of FDTD-RTM limitation caused by insufficient signal sampling using GPR. The results of electromagnetic simulation showed that the signals reconstructed by the above method were highly similar to the signals sampled with the same resolution. On this basis, reverse time migration electromagnetic simulation and physical model tests were designed. The results of both experiments showed that the under-sampled GPR signals could achieve FDTD-RTM following super-resolution reconstruction, and that the migration imaging results of the target were basically consistent with the design scheme. The signal super-resolution reconstruction method based on the wavelet theory was thus shown to successfully achieve the overall application of FDTD-RTM in GPR signal analysis. [ABSTRACT FROM AUTHOR]

Begonia kayinensis, a new species from Kayin State, Myanmar is described and illustrated. This new species is identified as a member of Begonia section Monophyllon A.DC. in its morphological characteristics including the upright stem with tuber, inflorescences arising from the top of the stem, and 2-loculed ovary. A description, photographs, illustration, and comparison with allied species in sect. Monophyllon and provisional assessment of the conservation status are provided. [ABSTRACT FROM AUTHOR]

Background: In Australia, prescription melatonin became a 'Pharmacist Only Medicine' for people over 55 with insomnia from June 2021. However, little is known about pharmacists' views on melatonin down-scheduling and perceived impacts on practice. Aim: To explore Australian community pharmacists' views on and attitudes towards the down-scheduling of melatonin. Method: A convenience sample of community pharmacists and pharmacy interns were recruited. Participants completed a survey capturing demographic and professional practice details, and rated their knowledge, beliefs and attitudes towards melatonin. This was followed by an online semi-structured interview. Interviews were guided by a schedule of questions developed using the Theoretical Domains Framework and explored the perceived role of melatonin, preparation/response to down-scheduling, practice changes and patient interactions. Interviews continued until data saturation and were digitally recorded, transcribed verbatim and analysed using the Framework Approach. Results: Twenty-four interviews were conducted with community pharmacists (n = 19) and intern pharmacists (n = 5), all practicing in metropolitan areas. Pharmacists/intern pharmacists welcomed the increased accessibility of melatonin for patients. However, pharmacists perceived a disconnect between the guidelines, supply protocols and pack sizes with practice, making it difficult to monitor patient use of melatonin. The miscommunication of eligibility also contributed to patient-pharmacist tension when supply was denied. Importantly, most participants indicated their interest in upskilling their knowledge in melatonin use in sleep, specifically formulation differences and dosage titration. Conclusion: While pharmacists welcomed the down-scheduling of melatonin, several challenges were noted, contributing to pharmacist-patient tensions in practice. Findings highlight the need to refine and unify melatonin supply protocols and amend pack sizes to reflect guideline recommendations as well as better educating the public about the risk-benefits of melatonin. [ABSTRACT FROM AUTHOR]