Multiplicity of Positive Solutions for a Singular Second-Order Three-Point Boundary Value Problem with a Parameter

This paper is concerned with the following second-order three-point boundary value problem u″t+β2ut+λqtft,ut=0, t∈0 , 1, u0=0, u(1)=δu(η), where β∈(0,π/2), δ>0, η∈(0,1), and λ is a positive parameter. First, Green’s function for the associated linear boundary value problem is constructed, and then some useful properties of Green’s function are obtained. Finally, existence, multiplicity, and nonexistence results for positive solutions are derived in terms of different values of λ by means of the fixed point index theory

The Analysis and Calculation Method of Urban Rail Transit Carrying Capacity Based on Express-Slow Mode

Urban railway transport that connects suburbs and city areas is characterized by uneven temporal and spatial distribution in terms of passenger flow and underutilized carrying capacity. This paper aims to develop methodologies to measure the carrying capacity of the urban railway by introducing a concept of the express-slow mode. We first explore factors influencing the carrying capacity under the express-slow mode and the interactive relationships among these factors. Then we establish seven different scenarios to measure the carrying capacity by considering the ratio of the number of the express trains and the slow trains, the station where overtaking takes place, and the number of overtaking maneuvers. Taking Shanghai Metro Line 16 as an empirical study, the proposed methods to measure the carrying capacity under different express-slow mode are proved to be valid. This paper contributes to the literature by remodifying the traditional methods to measure the carrying capacity when different express-slow modes are applied to improve the carrying capacity of the suburban railway

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear.Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment.Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA’s roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP’s main bioactives, underscoring their therapeutic potential.Conclusion: This research delineates UR-AP’s pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP’s potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies

New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease

Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of “LB-like aggregates,” by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson’s pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials

Cluster-Like Headache Secondary to Anamnesis of Sphenoid Ridge Meningioma: A Case Report and Literature Review

Cluster headache is generally considered to be a primary headache; secondary cluster-like headache is quite rare, while cluster-like headache secondary to meningioma is even rarer. Here, we describe an unusual case with cluster-like headache 2.5 years after sphenoid ridge meningioma surgery. The cluster-like headache and meningioma were on the same side, and even at the same position. Furthermore, the cluster-like headache lasted for 6 months. In addition, the patient did not respond well to conventional treatments for cluster headache, such as oxygen inhalation, carbamazepine, and tramadol. Brain magnetic resonance imaging demonstrated a softening lesion, glial hyperplasia, and localized thickening and enhancement of the dura in the left frontal-temporal lobe. However, positron-emission computed tomography showed reduced metabolism in the left frontal-temporal lobe. Although the possibility of a primary headache cannot be completely eliminated, the association between cluster-like headache and probable tumor recurrence or postoperative changes should be considered

Efficacy and pharmacoeconomic advantages of Fufang Huangbai Fluid hydropathic compress in diabetic foot infections: a comparative clinical study with antimicrobial calcium alginate wound dressing

Objective: To compare the intervention effects and pharmacoeconomic advantages of Fufang Huangbai Fluid (FFHB) hydropathic compress versus Antimicrobial Calcium Alginate Wound Dressing (ACAWD) in the treatment of diabetic foot infections (DFI).Methods: Patients with DF who were hospitalized in the peripheral vascular Department of Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2020 to February 2022 and met the inclusion and excluding criteria were allocated into the experimental group and control group through minimization randomization. The experimental group was treated with FFHB hydropathic compress for 2 weeks, while the control group was treated with ACAWD for the same duration. The wound healing of both groups was monitored for 1 month post-discharge. Clinical data from all eligible patients were collected, and differences in various indices between cohorts were analyzed.Results: 22 in the experimental group (including two fell off) and 20 in the control group. After the treatment, the negative rate of wound culture in the experimental group was 30% and that in the control group was 10%, There was no significant difference in the negative rate of wound culture and change trend of minimum inhibitory concentration (MIC) value of drug sensitivity (p > 0.05). The infection control rate of the experimental group was 60%, and that of the control group was 25%. The difference between the two groups was statistically significant (χ2 = 5.013, p = 0.025). The median wound healing rate of the experimental group was 34.4% and that of the control group was 33.3%. There was no significant difference between the two groups (p > 0.05). During the follow-up 1 month later, the wound healing rate in the experimental group was higher, and the difference was statistically significant (p = 0.047). Pharmacoeconomic evaluations indicated that the experimental group had greater cost-effectiveness compared to the control group.Conclusion: In the preliminary study, FFHB demonstrated comparable pathogenic and clinical efficacy to ACAWD in the treatment of mild DF infection, and exhibited superior pharmacoeconomic advantages. With the aid of infection control, the wound healing rate in the FFHB group showed notable improvement. Nevertheless, due to the limited sample size, larger-scale studies are warranted to further validate these findings.Clinical Trial Registration: (https://www.chictr.org.cn/showproj.aspx?proj=66175), identifier (ChiCTR2000041443)

Genome-wide analysis of WRKY gene family in Cucumis sativus

<p>Abstract</p> <p>Background</p> <p>WRKY proteins are a large family of transcriptional regulators in higher plant. They are involved in many biological processes, such as plant development, metabolism, and responses to biotic and abiotic stresses. Prior to the present study, only one full-length cucumber WRKY protein had been reported. The recent publication of the draft genome sequence of cucumber allowed us to conduct a genome-wide search for cucumber WRKY proteins, and to compare these positively identified proteins with their homologs in model plants, such as <it>Arabidopsis</it>.</p> <p>Results</p> <p>We identified a total of 55 WRKY genes in the cucumber genome. According to structural features of their encoded proteins, the cucumber WRKY (<it>CsWRKY</it>) genes were classified into three groups (group 1-3). Analysis of expression profiles of <it>CsWRKY </it>genes indicated that 48 WRKY genes display differential expression either in their transcript abundance or in their expression patterns under normal growth conditions, and 23 WRKY genes were differentially expressed in response to at least one abiotic stresses (cold, drought or salinity). The expression profile of stress-inducible <it>CsWRKY </it>genes were correlated with those of their putative <it>Arabidopsis WRKY (AtWRKY) </it>orthologs, except for the group 3 WRKY genes. Interestingly, duplicated group 3 <it>AtWRKY </it>genes appear to have been under positive selection pressure during evolution. In contrast, there was no evidence of recent gene duplication or positive selection pressure among <it>CsWRKY </it>group 3 genes, which may have led to the expressional divergence of group 3 orthologs.</p> <p>Conclusions</p> <p>Fifty-five WRKY genes were identified in cucumber and the structure of their encoded proteins, their expression, and their evolution were examined. Considering that there has been extensive expansion of group 3 WRKY genes in angiosperms, the occurrence of different evolutionary events could explain the functional divergence of these genes.</p

Mapping the path towards novel treatment strategies: a bibliometric analysis of Hashimoto’s thyroiditis research from 1990 to 2023

BackgroundHashimoto’s thyroiditis (HT), a common form of thyroid autoimmunity, is strongly associated with deteriorating clinical status and impaired quality of life. The escalating global prevalence, coupled with the complexity of disease mechanisms, necessitates a comprehensive, bibliometric analysis to elucidate the trajectory, hotspots, and future trends in HT research.ObjectiveThis study aims to illuminate the development, hotspots, and future directions in HT research through systematic analysis of publications, institutions, authors, journals, references, and keywords. Particular emphasis is placed on novel treatment strategies for HT and its complications, highlighting the potential role of genetic profiling and immunomodulatory therapies.MethodsWe retrieved 8,726 relevant documents from the Web of Science Core Collection database spanning from 1 January 1990 to 7 March 2023. Following the selection of document type, 7,624 articles were included for bibliometric analysis using CiteSpace, VOSviewer, and R software.ResultsThe temporal evolution of HT research is categorized into three distinct phases: exploration (1990-1999), rapid development (1999-2000), and steady growth (2000-present). Notably, the United States, China, Italy, and Japan collectively contributed over half (54.77%) of global publications. Among the top 10 research institutions, four were from Italy (4/10), followed by China (2/10) and the United States (2/10). Recent hotspots, such as the roles of gut microbiota, genetic profiling, and nutritional factors in HT management, the diagnostic dilemmas between HT and Grave’s disease, as well as the challenges in managing HT complicated by papillary thyroid carcinoma and type 1 diabetes mellitus, are discussed.ConclusionAlthough North America and Europe have a considerable academic impact, institutions from emerging countries like China are demonstrating promising potential in HT research. Future studies are anticipated to delve deeper into the differential diagnosis of HT and Grave’s disease, the intricate relationship between gut microbiota and HT pathogenesis, clinical management of HT with papillary thyroid carcinoma or type 1 diabetes, and the beneficial effects of dietary modifications and micronutrients supplementation in HT. Furthermore, the advent of genetic profiling and advanced immunotherapies for managing HT offers promising avenues for future research