bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Abelmoschus manihot (L.) and its combination with irbesartan in the treatment of diabetic nephropathy via the gut–kidney axis
Authors: Yu Hongmei , Tang Haitao , Saxu Rengui , Song Yuhui , Cui Xu , Xu Jingjing , Li Nan , Cui Siyuan , Ge Haitao , Tang Wei , Gu Harvest F. 
Published: October 2024

BackgroundClinical observations have recently shown that Abelmoschus manihot (L.) in the form of Huangkui capsule (HKC) and in combination with irbesartan (EB) is an effective therapy for diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). The present study aims to explore the mechanisms underlying the therapeutic efficacies of HKC and its combination with EB in DN via the gut-kidney axis.MethodsHKC, EB, and their combination or vehicle were administered in db/db mice, which is an animal model for the study of T2D and DN. Comparative analyses of the gut microbiota, serum metabolites, and kidney transcriptomics before and after drug administration were performed.ResultsAfter treatment with HKC, EB, and their combination for 4 weeks, the urinary albumin-to-creatinine ratios decreased significantly in the db/db mice with DN. In terms of the gut microbiota, the abundances of Faecalitalea, Blautia, and Streptococcus increased but those of Bacteroidetes, Firmicutes, Enterobacteriaceae, and Desulfovibrio decreased. Parallelly, serum metabolites, mainly including quercetin 3′-glucuronide and L-dopa, were elevated while cortisol and cytochalasin B were reduced. Furthermore, the S100a8, S100a9, Trem1, and Mmp7 genes in the kidneys were downregulated. These altered elements were associated with proteinuria/albuminuria reduction. However, EB had no effects on the changes in blood pressure and specific differentially expressed genes in the kidneys.ConclusionThe present study provides experimental evidence that HKC regulates the gut microbiota, circulating metabolites, and renal gene activities, which are useful for better understanding of the action mechanisms of A. manihot in the treatment of DN through the gut-kidney axis.
Modulation of Notch signaling pathway in activated hepatic stellate cells does not ameliorate the outcome of liver fibrosis in carbon tetrachloride and DDC-feeding models
Authors: Šisl Dino , Planinić Pavao , Novak Sanja , Filipović Maša , Flegar Darja , Šućur Alan , Turčić Petra , Kovačić Nataša , Kalajzić Ivo , Grčević Danka , Kelava Tomislav 
Published: October 2024

BackgroundRecent research suggests a possible role of Notch signaling pathway in development of liver fibrosis, but exact cellular and molecular mechanisms are still not well defined. Methods: We modulated Notch signaling in activated hepatic stellate cells/myofibroblasts using the model of inducible activation or inhibition of Notch signaling selective for αSMA positive cells in murine models of toxic fibrosis induced by CCl4 and cholestatic fibrosis induced by DDC supplemented feeding.ResultsOur results confirm that Notch signaling pathway is activated in both CCL4 and DDC model of liver fibrosis and that αSMA positive myofibroblasts are of activated hepatic stellate cells origin. However, neither the inhibition of canonical Notch signaling (in tamoxifen treated αSMACreER/RBP-Jfl/fl mice) nor its overactivation (in tamoxifen treated αSMACreER/NICD1 mice) changed the degree of liver fibrosis in comparison to the control groups in either of the investigated models. Furthermore, after the withdrawal of the fibrogenic treatment the degree of resolution of fibrosis was similar between the animals with Notch overactivation and controls. In addition to genetic manipulation, we investigated the effect of antibodies against NOTCH1 and NOTCH2 on the development of liver fibrosis. Treatment with antibodies had effects on thymus and spleen respectively, but failed to ameliorate liver fibrosis. In conclusion, our data demonstrate that modulation of Notch activity in activated HSC is not sufficient to change the outcome of liver fibrosis. The results obtained with inhibitory antibodies further demonstrate limitations of targeting Notch 1 and 2 receptors as antifibrotic therapy. Notch pathway remains a potential target for the treatment of liver fibrosis, but future studies should be directed to Notch 3 signaling and/or targeting different populations of cells.
Therapeutic targets for lung cancer: genome-wide Mendelian randomization and colocalization analyses
Authors: Luan Yi , Xian Desheng , Zhao Changwen , Qing Xin , He Hanlin , Zheng Kaixuan , Song Wenjun , Jiang Taijiao , Wang Wenjian , Duan Chaohui 
Published: October 2024

BackgroundLung cancer, categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), remains a significant global health challenge. The development of drug resistance and the heterogeneity of the disease necessitate the identification of novel therapeutic targets to improve patient outcomes.MethodsWe conducted a genome-wide Mendelian randomization (MR) and colocalization analysis using a comprehensive dataset of 4,302 druggable genes and cis-expressed quantitative trait loci (cis-eQTLs) from 31,884 blood samples. The study integrated genomic analysis with eQTL data to identify key genes associated with lung cancer risk.ResultsThe analysis revealed five actionable therapeutic targets for NSCLC, including LTB4R, LTBP4, MPI, PSMA4, and TCN2. Notably, PSMA4 demonstrated a strong association with both NSCLC and SCLC risks, with odds ratios of 3.168 and 3.183, respectively. Colocalization analysis indicated a shared genetic etiology between these gene expressions and lung cancer risk.ConclusionOur findings contribute to precision medicine by identifying druggable targets that may be exploited for subtype-specific lung cancer therapies.
Effects of fermented Arctium lappa L. root by Lactobacillus casei on hyperlipidemic mice
Authors: Chen MingJu , Wu Yuxiao , Yang Hongxuan , Liu Tianfeng , Han Tongkun , Dai Wangqiang , Cen Junyue , Ouyang Fan , Chen Jingjing , Liu Jianxin , Zhou Lin , Hu Xuguang 
Published: October 2024

IntroductionThis study aimed to establish a fermentation system based on Lactobacillus casei (LC) and Arctium lappa L. root (AR) to investigate its effects. The objectives included comparing metabolite profiles pre- and post-fermentation using untargeted metabolomics and evaluating the impact of LC-AR in high-fat diet-induced hyperlipidemic mice.MethodsUntargeted metabolomics was used to analyze differences in metabolites before and after fermentation. In vitro antioxidant activity, liver injury, lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA expression were assessed. 16S rRNA sequencing was conducted to evaluate changes in gut microbiota composition.ResultsLC-AR exhibited stronger antioxidant activity and higher metabolite levels than AR. It also improved liver injury as well as better regulation of lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA. 16S rRNA analysis revealed that LC-AR decreased the Firmicutes/Bacteroidetes ratio, which correlated negatively with triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels.DiscussionThese findings suggest that LC-AR may serve as a promising functional food and drug raw material for improving hyperlipidemia, particularly through its beneficial effects on gut microbiota and lipid regulation.
Effect of microplastics on the allelopathic effects of native and invasive plants on co-occurring invaders
Authors: Yuan Ling , Zhou Li , Li Junmin 
Published: October 2024

IntroductionMicroplastic pollution has emerged as a significant global change factor, with the potential to alter the biological, physicochemical properties of soil and to subsequently affect plant growth. Despite growing recognition of the impacts of microplastic pollution, the mechanisms by which microplastics modify plant leaf chemistry and influence allelopathic interactions among co-existing plant species remain unclear.MethodsWe used the native perennial forb Achyranthes bidentata and the invasive annual forb Amaranthus spinosus as focal species. We grew the two species with and without competition with each other. This setup was further combined with a treatment involving the addition of polyethylene (PE). We then testd the effects of aqueous extract on seed germination and seedling growth for five invasive and five native species. Subsequently, metabolomic analysis was conducted on the aqueous extracts, in which significant allelopathic effects were observed on test species.Results and discussionThe presence of PE microplastics enhanced the biomass of both Achyranthes and Amaranthus under competitive and non-competitive growth conditions. Furthermore, PE microplastics were found to induce a negative allelopathic effect for the native plant Achyranthes on co-occurring plants, which appeared to be mediated through changes in leaf chemistry. Bisdemethoxycurcumin, ethylparaben, salicin 6’-sulfate and 5-hydroxy-3’,4’,7-trimethoxyflavone glucoside were proven important compounds for allelopathic enhancement. Overall, these results suggest that microplastic pollution has the capability to influence the co-existence of invasive and native plants by altering their allelopathic potential. This insight into the interactions between microplastics and plant allelopathy provides a novel perspective on how microplastic pollution could modify plant species interactions and ecosystem dynamics. Future studies could aim to answer how microplastics might affect plant root exudates and whether this process would mediate biological invasion.
Loneliness and low fruit and vegetable consumption among adults in Japan
Authors: Stickley Andrew , Shirama Aya , Sumiyoshi Tomiki 
Published: October 2024

BackgroundLoneliness is the distressing feeling that arises when a person's network of social relations is perceived as being inadequate in some way. Research has linked loneliness to a number of detrimental health outcomes. There is also some evidence that lonely individuals are more likely to engage in poorer health behaviors. However, as yet, there has been comparatively little attention paid to the relation between loneliness and dietary behavior. In particular, there has been little focus on the association between loneliness and fruit and vegetable intake.ObjectiveThe aim of this cross-sectional study was to examine the association between loneliness and low fruit and vegetable consumption in the Japanese general population.MethodsData were analyzed from 3,410 Japanese adults collected in an online survey in early 2023. Information was obtained on past-week fruit and vegetable consumption with a single-item measure, while loneliness was assessed with the Three-Item Loneliness Scale. Information was also collected on sociodemographic characteristics, physical health status, health-risk behaviors and depressive symptoms. Logistic regression was used to assess associations.ResultsOne in twenty (5.3%) adults reported low fruit and vegetable consumption. In a fully adjusted analysis loneliness was associated with higher odds for low fruit and vegetable consumption (OR: 1.14, 95%CI: 1.04–1.26). In sex- and age-stratified analyses loneliness was significantly associated with low fruit and vegetable consumption in both women and middle-aged adults, although confidence intervals overlapped for this association across all of the sex and age groups in the fully adjusted analyses.ConclusionsLoneliness is associated with low fruit and vegetable consumption among adults in Japan. As loneliness and inadequate fruit and vegetable intake have both been linked to poorer health outcomes, the results of this study underscore the potential importance and public health benefits of reducing loneliness in Japan.
A cross-sectional study on health behavior changes during COVID-19 among adults in Malaysia
Authors: Ithnain Norbaidurah , Kassim Rosnani , Amirudin Nadia , Aimanan Siti Nurhanim Mohamed , Krishnan Manimaran , Panting Albeny Joslyn 
Published: October 2024

IntroductionCOVID-19 has triggered significant disruptions globally, necessitating swift adaptations in individuals’ health behaviors.MethodsThis cross-sectional study was conducted during Phase Four of Malaysia’s National Recovery Plan and examines how the pandemic has affected health behaviors among adult Malaysians. The study gathered data online using convenience sampling with 1,004 respondents aged 18 and above. The research focused on diverse health domains, including eating habits, physical activity, smoking, alcohol consumption, and sleep patterns. The Wilcoxon Signed Rank test and descriptive statistics were employed to compare health behaviors before and after COVID-19.ResultsFindings indicate noteworthy shifts in eating behaviors, with increased water and fruit consumption (p &lt; .001). The frequency of home-cooked meals stayed relatively stable despite declining dinner preference and increasing daily snacks. Physical activity declined, marked by increased sedentary behavior and screen time (p &lt; .001). There were differences in the patterns of smoking and alcohol consumption; some had started these behaviors during the pandemic. Notably, intentions to quit smoking among respondents were more prominent than attempts to stop drinking. Respondents’ sleep patterns also changed, with more sleeping fewer than seven hours daily (p &lt; .001).ConclusionThe study emphasizes the need for focused interventions to address new challenges by highlighting the impact on health behaviors. As Malaysia navigates the post-pandemic landscape, understanding and mitigating the persisting effects on health behaviors are crucial for promoting overall well-being.
Key Soil Abiotic Factors Driving Soil Sickness in Lycium barbarum L. Under Long-Term Monocropping
Authors: Liu Ziyu , Qi Chang , Song Yanfang , Peng Tong , Zhang Chuanji , Li Kaile , Pu Meiyun , Sun Hao , Li Junjie , He Xiaoqi , Cheng Zhenyu , Fei Panshuai , Wang Xiaomin , Bi Yurong , Na Xiaofan 
Published: October 2024

Sustainable cultivation of Lycium barbarum L. (L. barbarum) in northwest China faces challenges due to soil sickness. While previous studies have explored variations in L. barbarum’s root-associated microbiota, the impact of soil properties on its growth performance and plant–soil feedback remains unclear. This study investigated changes in soil properties across topsoil (0–20 cm) and subsoil (20–40 cm) in primary L. barbarum cultivation regions of northwest China, evaluating seedling growth and plant–soil feedback through pot experiments. Results revealed significantly higher fresh shoot weights in seedlings cultivated in topsoil compared to subsoil, with plant–soil feedback showing an inverse trend. Redundancy analysis indicated positive correlations between both fresh weight and plant–soil feedback with electrical conductivity and dissolved nitrogen content, while negative correlations were observed with soil pH at both depths. Notably, dissolved organic carbon content negatively correlated with fresh weight and plant–soil feedback in topsoil, suggesting a potential relationship between continuous single-species plant litter input and soil sickness under monocropping conditions. These findings indicate that long-term input of a single plant litter type, rather than chemical fertilization, may primarily contribute to L. barbarum soil sickness in northwest China, providing valuable insights for developing sustainable cultivation practices for growing L. barbarum.
Novel Fosfomycin Resistance Mechanism in Pseudomonas entomophila Due to Atypical Pho Regulon Control of GlpT
Authors: Sánchez-Maroto Laura , Gella Pablo , Couce Alejandro 
Published: October 2024

Background/Objectives: Pseudomonas entomophila is a ubiquitous bacterium capable of killing insects of different orders and has become a model for host–pathogen studies and a promising tool for biological pest control. In the human pathogen Pseudomonas aeruginosa, spontaneous resistance to fosfomycin arises almost exclusively from mutations in the glycerol-3-phosphate transporter (GlpT), the drug’s sole entry route in this species. Here, we investigated whether this specificity is conserved in P. entomophila, as it could provide a valuable marker system for studying mutation rates and spectra and for selection in genetic engineering. Methods: We isolated 16 independent spontaneous fosfomycin-resistant mutants in P. entomophila, and studied the genetic basis of the resistance using a combination of sequencing, phenotyping and computational approaches. Results: We only found two mutants without alterations in glpT or any of its known regulatory elements. Whole-genome sequencing revealed unique inactivating mutations in phoU, a key regulator of the phosphate starvation (Pho) regulon. Computational analyses identified a PhoB binding site in the glpT promoter, and experiments showed that phoU inactivation reduced glpT expression nearly 20-fold. While placing a sugar-phosphate transporter under the Pho regulon may seem advantageous, bioinformatic analysis shows this configuration is atypical among pseudomonads. Conclusions: This atypical Pho regulon control of GlpT probably reflects the peculiarities of P. entomophila’s habitat and lifestyle; highlighting how readily regulatory evolution can lead to the rapid divergence of resistance mechanisms, even among closely related species.
Vertical Electric-Field-Induced Switching from Strong to Asymmetric Strong–Weak Confinement in GaAs Cone-Shell Quantum Dots Using Transparent Al-Doped ZnO Gates
Authors: Alshaikh Ahmed , Peng Jun , Zierold Robert , Blick Robert H. , Heyn Christian 
Published: October 2024

The first part of this work evaluates Al-doped ZnO (AZO) as an optically transparent top-gate material for studies on semiconductor quantum dots. In comparison with conventional Ti gates, samples with AZO gates demonstrate a more than three times higher intensity in the quantum dot emission under comparable excitation conditions. On the other hand, charges inside a process-induced oxide layer at the interface to the semiconductor cause artifacts at gate voltages above U≈ 1 V. The second part describes an optical and simulation study of a vertical electric-field (F)-induced switching from a strong to an asymmetric strong–weak confinement in GaAs cone-shell quantum dots (CSQDs), where the charge carrier probability densities are localized on the surface of a cone. These experiments are performed at low U and show no indications of an influence of interface charges. For a large F, the measured radiative lifetimes are substantially shorter compared with simulation results. We attribute this discrepancy to an F-induced transformation of the shape of the hole probability density. In detail, an increasing F pushes the hole into the wing part of a CSQD, where it forms a quantum ring. Accordingly, the confinement of the hole is changed from strong, which is assumed in the simulations, to weak, where the local radius is larger than the bulk exciton Bohr radius. In contrast to the hole, an increasing F pushes the electron into the CSQD tip, where it remains in a strong confinement. This means the radiative lifetime for large F is given by an asymmetric confinement with a strongly confined electron and a hole in a weak confinement. To our knowledge, this asymmetric strong–weak confinement represents a novel kind of quantum mechanical confinement and has not been observed so far. Furthermore, the observed weak confinement for the hole represents a confirmation of the theoretically predicted transformation of the hole probability density from a quantum dot into a quantum ring. For such quantum rings, application as storage for photo-excited charge carriers is predicted, which can be interesting for future quantum photonic integrated circuits.
Clinical and laboratory evaluation of the effectiveness of children's toothpastes containing 1000 ppm fluoride
Authors: Tokmakova S. I. , Bondarenko O. V. , Kirienkova E. A. , Gurevich Yu. Yu. , Mokrenko E. V. , Kolyshkina S. V. , Melnik А. P. , Yarovaya A. O. , Savitskaya N. V. 
Published: October 2024

Relevance. This article presents the findings from studies evaluating the effectiveness of toothpastes containing 1000 ppm fluoride in clinical settings. The data demonstrates the cumulative benefits of these toothpastes on oral hygiene, the reduction of inflammatory oral manifestations, and their anticaries effects.Purpose. To assess the effectiveness of fluoride-containing toothpastes through laboratory tests and clinical trials.Materials and methods. The study evaluated the effectiveness of toothpastes containing 1000 ppm fluoride using the following parameters: Greene-Vermillion hygiene index, periodontal indices (PMA and SBI), enamel mineralization and resistance, presence and number of carious lesions at the white spot stage, enamel hypersensitivity, and antimicrobial activity against Streptococcus spp.Results. The analysis of hygiene indices demonstrated that the tested toothpastes were highly effective in cleaning, with a positive cumulative effect on participants' oral hygiene. The use of these toothpastes significantly reduced inflammatory manifestations, decreased gum bleeding, and improved periodontal tissue health. A reduction in the number of participants with early-stage carious lesions, as well as a decrease in the overall number of lesions, was observed. The toothpastes also enhanced enamel resistance to acid exposure, contributing to their anticaries benefits. Enamel hypersensitivity was reduced, and a dose-dependent antibacterial effect against Streptococcus mutans, Streptococcus gordonii, and Streptococcus sobrinus was observed.Conclusion. Toothpastes containing 1000 ppm fluoride demonstrated strong cleaning and refreshing effects, along with a positive cumulative impact on oral hygiene and a significant reduction in inflammation. Their anticaries benefits were confirmed, and they also reduced enamel hypersensitivity. The tested toothpastes were well-tolerated, with no reports of allergic reactions or irritation.
Lyme disease in UK primary care: a knowledge, attitude and practice survey
Authors: Delaney Lucy , Semper Amanda , French Neil , Tulloch John SP 
Published: October 2024

BackgroundLyme disease (LD) cases in the UK most commonly present within the primary care setting. Despite an upward trend of incidence, little is known regarding general practitioner (GP) experience with diagnosis and treatment.AimThis study aims to describe baseline primary care clinician Knowledge, Attitude and Practice (KAP) in Scotland and England.Design & settingOnline KAP survey on Lyme disease for UK based practising GPs.MethodAn online KAP questionnaire was developed for use in UK primary care. The survey was distributed through UK based research networks, professional societies and via social media.Results191 complete responses were analysed (Englandn=130, Scotlandn=61). The Scotland-based respondent group had more relevant consultations in the previous 3 years. Respondents from Scotland demonstrated a greater awareness that erythema migrans (EM) is pathognomonic for Lyme disease and that serological testing of this patient group is not indicated. Less common cardiac and neurological symptoms were not as well associated with Lyme disease by both respondent groups for the former and England-based respondents for the latter. Prescribing according to the National institute for Health and Care Excellence (NICE) guidance was identified in 70% of Scotland and 42% of England-based GP responses.ConclusionTargeted resources may improve clinician confidence on exposure risk, symptom recognition, testing limitations and treatment dose and duration. Scotland-based respondents’ better survey performance potentially reflects greater clinical exposure and public awareness of the disease, due to high endemicity within the nation.