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Introduction: In this longitudinal study, we examine the potential costs and benefits of humility for well-being and civic trust among immigrants in a pluralistic democracy. Methods: With data from 14,864 immigrant participants from a nationwide random sample in New Zealand, we used multilevel modeling to examine the associations of general humility (i.e., honesty-humility modesty) with well-being (life satisfaction and meaning) and civic trust (trust in police) over time in contexts with varying levels of ethnic deprivation and perceived religious discrimination. We hypothesized that (a) humility would correlate positively with well-being and civic trust (Hypothesis 1), (b) these associations would be attenuated in the contexts where perceptions of ethnic deprivation and religious discrimination are high (Hypothesis 2), and (c) these interaction effects would become more pronounced when cultural identities are salient (Hypothesis 3). Results: Multilevel modeling revealed partial support for these hypotheses. Although humility correlated positively with well-being and trust in police over time, the two-way and three-way interactions did not yield substantial support for Hypotheses 2 and 3, respectively. The context of religious discrimination did, however, marginally attenuate the positive association between humility and trust in police. Discussion: Collectively, these results demonstrate that humility is associated with multiple benefits to well-being and civic trust and has few-if any-potential drawbacks.
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Cannabis (Cannabis sativa) is a versatile crop belonging to the Cannabaceae family, and is dioecious, typically with separate male and female plants. The flowers of female plants, especially the trichomes, accumulate relatively higher contents of cannabinoids compared with those of male plants. For this reason, to obtain seeds that are genetically female, it is desirable to induce the development of male flowers on a female plant that produces genetically female haploid gametes. Silver thiosulfate (STS) is a highly effective chemical for male flower induction. We investigated male flower induction in three commercial cultivars of female cannabis (Spectrum303, SuperwomanS1, and CBGambit) regarding the treatment frequency, stage of application, and concentration of STS applied as a foliar spray. All three cultivars showed adequate induction of male flowers in response to 1.5 mM STS applied at the early reproductive stage. In particular, SuperwomanS1 was most highly responsive to induction of male flowers, even when treated with 0.3 mM STS at the early reproductive stage. Treatment with three applications of STS was more effective compared with a single application, but a single application of 1.5 mM STS at the early reproductive stage was sufficient for male flower induction. A single STS application during the middle stage of reproductive growth was inadequate for induction of male flowers. However, 6 weeks after three applications of STS, CBGambit exhibited approximately 54% male flower induction at 0.3 mM STS, Spectrum303 showed approximately 56% induction at 3 mM STS, and SuperwomanS1 yielded approximately 26% induction at 1.5 mM (expressed as percentage of total number of individuals with the induced male flowers). Pollen stainability tests using KI-I2 solution and Alexander's staining showed high pollen viability with over 65% at different single STS concentrations, indicating that pollen grains induced by STS have sufficient viability for the self-pollination. This study demonstrated that different cultivars of cannabis respond diversely to different STS concentrations and highlighted the potential benefits of three STS applications during the middle reproductive stage for cannabis breeding.
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BACKGROUND: Androgenetic alopecia (AGA) is a common form of hair loss. Androgens, such as testosterone and dihydrotestosterone, are the main causes of AGA. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can reduce AGA. However, preparing therapeutic doses of MSCs for clinical use is challenging. Induced pluripotent stem cell-derived MSCs (iMSCs) are homogenous and easily expandable, enabling scalable production of EVs. Hyaluronic acid (HA) can exert various functions including free radical scavenging, immune regulation, and cell migration. Herein, we examined whether hyaluronic acid (HA) stimulation of iMSCs could produce EVs with enhanced therapeutic outcomes for AGA. METHODS: EVs were collected from iMSCs primed with HA (HA-iMSC-EVs) or without HA (iMSC-EVs). The characteristics of EVs were examined using dynamic light scattering, cryo-transmission electron microscopy, immunoblotting, flow cytometry, and proteomic analysis. In vitro, we compared the potential of EVs in stimulating the survival of hair follicle dermal papilla cells undergoing testosterone-mediated AGA. Additionally, the expression of androgen receptor (AR) and relevant growth factors as well as key proteins of Wnt/ß-catenin signaling pathway (ß-catenin and phosphorylated GSK3ß) was analyzed. Subsequently, AGA was induced in male C57/BL6 mice by testosterone administration, followed by repeated injections of iMSC-EVs, HA-iMSC-EVs, finasteride, or vehicle. Several parameters including hair growth, anagen phase ratio, reactivation of Wnt/ß-catenin pathway, and AR expression was examined using qPCR, immunoblotting, and immunofluorescence analysis. RESULTS: Both types of EVs showed typical characteristics for EVs, such as size distribution, markers, and surface protein expression. In hair follicle dermal papilla cells, the mRNA levels of AR, TGF-ß, and IL-6 increased by testosterone was blocked by HA-iMSC-EVs, which also contributed to the augmented expression of trophic genes related to hair regrowth. However, no notable changes were observed in the iMSC-EVs. Re-activation of Wnt/ß-catenin was observed in HA-iMSC-EVs but not in iMSC-EVs, as shown by ß-catenin stabilization and an increase in phosphorylated GSK3ß. Restoration of hair growth was more significant in HA-iMSC-EVs than in iMSC-EVs, and was comparable to that in mice treated with finasteride. Consistently, the decreased anagen ratio induced by testosterone was reversed by HA-iMSC-EVs, but not by iMSC-EVs. An increased expression of hair follicular ß-catenin protein, as well as the reduction of AR was observed in the skin tissue of AGA mice receiving HA-iMSC-EVs, but not in those treated with iMSC-EVs. CONCLUSIONS: Our results suggest that HA-iMSC-EVs have potential to improve AGA by regulating growth factors/cytokines and stimulating AR-related Wnt/ß-catenin signaling.
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Alopecia , Vesículas Extracelulares , Folículo Piloso , Ácido Hialurónico , Células Madre Mesenquimatosas , Vesículas Extracelulares/metabolismo , Alopecia/terapia , Alopecia/metabolismo , Alopecia/tratamiento farmacológico , Ácido Hialurónico/farmacología , Ácido Hialurónico/metabolismo , Animales , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Humanos , Vía de Señalización Wnt/efectos de los fármacos , Masculino , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Testosterona/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones Endogámicos C57BLRESUMEN
In this study, we demonstrated that both the expression of most ribosomal protein genes and the amount of ribosomes were decreased in the Δaa 3 mutant of Mycobacterium smegmatis, in which the major terminal oxidase (aa 3 cytochrome c oxidase) of the respiratory electron transport chain (ETC) is inactivated, compared to those in the wild-type strain. Deletion of the rel gene encoding the major (p)ppGpp synthetase in the background of the Δaa 3 mutant restored the reduced expression of ribosomal protein genes, suggesting that inhibition of the respiratory ETC leads to the Rel-dependent stringent response (SR) in this bacterium. Both a decrease in the expression of ribosomal protein genes by overexpression of rel and the increased expression of rel in the Δaa 3 mutant relative to the wild-type strain support the Rel-dependent induction of SR in the Δaa 3 mutant. We also demonstrated that the expression of ribosomal protein genes was decreased in M. smegmatis exposed to respiration-inhibitory conditions, such as KCN and bedaquiline treatment, null mutation of the cytochrome bcc 1 complex, and hypoxia. The MprBA-SigE-SigB regulatory pathway was implicated in both the increased expression of rel and the decreased expression of ribosomal protein genes in the Δaa 3 mutant of M. smegmatis.
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To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.
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Rapeseed (Brassica napus L.) holds significant commercial value as one of the leading oil crops, with its agronomic features and oil quality being crucial determinants. In this investigation, 73,226 single nucleotide polymorphisms (SNPs) across 95 rapeseed mutant lines induced by gamma rays, alongside the original cultivar ('Tamra'), using genotyping-by-sequencing (GBS) analysis were examined. This study encompassed gene ontology (GO) analysis and a genomewide association study (GWAS), thereby concentrating on agronomic traits (e.g., plant height, ear length, thousand-seed weight, and seed yield) and oil traits (including fatty acid composition and crude fat content). The GO analysis unveiled a multitude of genes with SNP variations associated with cellular processes, intracellular anatomical structures, and organic cyclic compound binding. Through GWAS, we detected 320 significant SNPs linked to both agronomic (104 SNPs) and oil traits (216 SNPs). Notably, two novel candidate genes, Bna.A05p02350D (SFGH) and Bna.C02p22490D (MDN1), are implicated in thousand-seed weight regulation. Additionally, Bna.C03p14350D (EXO70) and Bna.A09p05630D (PI4Kα1) emerged as novel candidate genes associated with erucic acid and crude fat content, respectively. These findings carry implications for identifying superior genotypes for the development of new cultivars. Association studies offer a cost-effective means of screening mutants and selecting elite rapeseed breeding lines, thereby enhancing the commercial viability of this pivotal oil crop.
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BACKGROUND: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence. METHODS: Transcriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD+ and NADH levels, ATP production rate by Seahorse analyzer, and intracellular ATP content. Mitochondrial fitness was estimated by measurements of mitochondrial membrane potential, ROS, and calcium accumulation by flow cytometry, and morphology was visualized by TEM. Bioinformatic analysis, real-time qPCR, western blotting, chemical reaction prediction, and molecular docking were utilized to identify the drug target. The immunogenic potential was assessed by high mobility group box (HMGB)1 ELISA assay, luciferase-based extracellular ATP assay, ectopic calreticulin expression by flow cytometry, and validated by phagocytosis assay, and in vivo vaccination assay using syngeneic C57BL/6 mice. RESULTS: Transcriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients' stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities. CONCLUSIONS: Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.
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Stroke survivors face participation restrictions, yet little is known regarding how social support affects the association between an individual's abilities and participation. Through a Person-Environment-Occupation-Performance (PEOP) model lens, social support was examined as a potential mediator between ability and participation in cognitively and mobility-demanding activities for stroke survivors with aphasia (persons with aphasia [PWA]) and without aphasia (persons without aphasia [PWOA]). A cross-sectional design, including PWA (n = 50) and PWOA (n = 59) examined associations among person factors (physical impairment, cognition), an environmental factor (social support), and occupational participation through cognitively- and mobility-demanding activity subscales of the Activity Card Sort. Cognition was associated with participation in cognitively demanding activities for both groups, though social support was a mediator only for PWA. Physical impairment was associated with participation in mobility-demanding activities for PWOA, though social support did not mediate that relationship. Social support is key to PWA participating in cognitively demanding activities post-stroke.
Social Support's Role in Tasks that Require Cognition or Mobility for Stroke Survivors with and without AphasiaAfter a stroke, people can face difficulties doing the things they need and want to do in their daily life. Sometimes a stroke can cause aphasia, a disorder that can make it hard for someone to communicate. Social support occurs when one person helps someone do the things they need and want to do. Certain tasks may require different skills, like cognition (being able to think) or mobility (being able to move). Results showed that cognition is important to do tasks that require a lot of thinking for people who experience a stroke and social support is essential for people with aphasia to do tasks that require a lot of thinking. In addition, mobility is important to do tasks that require walking or movement for people without aphasia.
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Afasia , Apoyo Social , Rehabilitación de Accidente Cerebrovascular , Humanos , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Anciano , Rehabilitación de Accidente Cerebrovascular/psicología , Afasia/psicología , Afasia/etiología , Accidente Cerebrovascular/psicología , Accidente Cerebrovascular/complicaciones , Cognición , Participación Social/psicología , Actividades CotidianasRESUMEN
BACKGROUND: Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip. RESULTS: The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression. CONCLUSIONS: The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment.
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Membrane distillation (MD) is a process driven by the vapor pressure difference dependent on temperature variation, utilizing a hydrophobic porous membrane. MD operates at low pressure and temperature, exhibiting resilience to osmotic pressure. However, a challenge arises as the membrane performance diminishes due to temperature polarization (TP) occurring on the membrane surface. The vacuum MD process leverages the application of a vacuum to generate a higher vapor pressure difference, enhancing the flux and mitigating TP issues. Nevertheless, membrane fouling leads to decreased performance, causing membrane wetting and reducing the ion removal efficiency. This study investigates membrane fouling phenomena induced by various silica nanoparticle sizes (400, 900, and 1300 nm). The patterns of membrane fouling, as indicated by the flux reduction, vary depending on the particle size. Distinct MD performances are observed with changes in the feed water temperature and flow rate. When examining the membrane fouling mechanism for particles with a porosity resembling actual particulate materials, a fouling form similar to the solid type is noted. Therefore, this study elucidates the impact of particulate matter on membrane fouling under diverse conditions.
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Efficient extraction of natural pigments is a key focus in enhancing the utilization of by-products for applications in the food industry. In this study, an enzymatic extraction method using Pectinex Ultra SP-L, Pectinex XXL, Novoshape, and Celluclast was used to investigate natural pigment production from the pomace of aronia, a commercially important plant. The method's performance was monitored using high-performance liquid chromatography with diode-array detection by measuring total and individual anthocyanin levels. Pectinex XXL (0.5%) yielded the highest total anthocyanin extraction (2082.41 ± 85.69 mg/100 g) in the single enzyme treatment, followed by Pectinex Ultra SP-L (0.05%), Celluclast (0.01%), and Novoshape (0.1%). Combining Pectinex XXL (0.25%) with Celluclast (0.01%) increased the extraction ratio of total anthocyanins (2 323.04 ± 61.32 mg/100 g) by â¼50.7% compared with that obtained using the solvent extraction method. This study demonstrated an effective enzymatic extraction method for application in the food industry.
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Antocianinas , Técnicas de Química Analítica , Enzimas , Industria de Alimentos , Antocianinas/análisis , Antocianinas/aislamiento & purificación , Técnicas de Química Analítica/métodos , Enzimas/metabolismo , Colorantes de Alimentos/aislamiento & purificación , Industria de Alimentos/métodos , Photinia/química , Temperatura , TiempoRESUMEN
Previous studies have stated that both objective and subjective cognitive abilities and mental health symptoms are associated with community participation poststroke. However, there is a need to understand the direct and indirect associations among these variables in persons with stroke. The objective of this study was to investigate whether mental health symptoms mediate the associations of subjective and objective cognitive abilities with community participation poststroke. We built regression-based mediation models with 74 participants with mild to moderate stroke. Independent variables were objective and subjective cognitive abilities. The dependent variable was community participation. Mediators were mental health symptoms including depression, apathy, and anxiety. The results indicated that depression (b = .093), apathy (b = .134), and anxiety (b = .116) fully mediated the association between subjective cognitive ability (p < .05), but not objective cognitive ability (p > .05), and community participation poststroke. Our findings suggest that poor subjective cognitive ability combined with mental health symptoms should be addressed together to promote community participation poststroke.
Mental Health Mediators for Subjective, Not Objective, Cognition, and Community Participation PoststrokeResearchers and clinicians have used both objective and subjective tools to evaluate cognitive abilities including memory, attention, and thinking. Objective cognitive ability indicates the level of cognitive ability measured using an objective tool such as pen and paper tests while subjective cognitive ability refers to self-perceived cognitive ability indicated via self-report questionnaires. Previous studies have shown that both objective and subjective cognitive abilities and mental health symptoms (depression, anxiety, and apathy) are associated with community participation in persons with stroke. However, there is a need to understand the direct and indirect associations among objective and subjective cognitive abilities, mental health symptoms, and community participation. In this context, we investigated if mental health symptoms mediated the associations of subjective and objective cognitive ability with community participation poststroke. Our results suggest that mental health symptoms fully mediated the associations between subjective cognitive ability and community participation but not the associations between objective cognitive ability and community participation poststroke. Our findings propose that rehabilitation and occupational therapy professionals should carefully monitor subjective cognitive problems with special attention to persons with poststroke depression, apathy, and anxiety to increase community participation poststroke.
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Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer.NEW & NOTEWORTHY The utility of cancer therapeutics targeting the proteolytic activities of MMPs is limited because MMPs are widely distributed throughout the body and involved in many different aspects of cell functions. This work specifically targets the activation of MMP-7 through its interaction with syndecan-2. Notably, everolimus, a known mTOR inhibitor, blocked this interaction, demonstrating a novel role for everolimus in inhibiting mTOR signaling and impairing the interaction of MMP-7 with syndecan-2 in colon cancer.
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Neoplasias del Colon , Everolimus , Humanos , Everolimus/farmacología , Sindecano-2/genética , Sindecano-2/metabolismo , Metaloproteinasa 7 de la Matriz/genética , Metaloproteinasa 7 de la Matriz/metabolismo , Gelatina , Sirolimus/farmacología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Serina-Treonina Quinasas TORRESUMEN
Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.
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Fertilizers are widely used to improve the quality of fruits and vegetables. However, the overuse of fertilizers has become an issue because it causes environmental problems and negatively affects productivity and fruit quality. In this study, we examined the effects of nitrogen, phosphorus, and potassium (NPK) fertilizer levels on the metabolism of cucumber fruit in low- and high-nutrient soils using mass-spectrometry-based metabolomics approaches. Cucumber metabolite content was notably different depending on the initial soil nutrient status. Most amino acids and phenylpropanoids were abundant in the cucumbers raised in low-nutrient soil, whereas organic acids, some amino acids (aspartate, glutamate, and ornithine), and carbohydrates were comparatively higher in fruits from high-nutrient soil. The fertilizer supply resulted in an alteration in the metabolite profile, while no change in fruit yield was observed in either low- or high-nutrient soils. Fertilizer treatment perturbed the metabolite contents in cucumbers from low-nutrient soil. In contrast, treatment with higher concentrations of fertilizer in high-nutrient soil increased phenylpropanoid content in the cucumbers, while most metabolites decreased. In conclusion, fertilization levels should be carefully determined, considering culture conditions such as the original soil status, to increase product yield and fruit quality and avoid environmental problems.
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Rice, feeding a significant portion of the world, poses unique proteomic challenges critical to agricultural research and global food security. The complexity of the rice proteome, influenced by various genetic and environmental factors, demands specialized analytical approaches for effective study. The central challenges in rice proteomics lie in developing custom methods suited to the unique aspects of rice biology. These include data preprocessing, method selection, and result validation, all of which are essential for advancing rice research. Our aim is to decode these proteomic intricacies to facilitate breakthroughs in strain improvement, disease resistance, and yield optimization, all vital for combating global food insecurity. To achieve this, we have created the RiceProteomeDB (RPDB), a React + Django database, offering a streamlined and comprehensive platform for the analysis of rice proteomics data. RiceProteomeDB (RPDB) simplifies proteomics data management and analysis. It offers features for data organization, preprocessing, method selection, result validation, and data sharing. Researchers can access processed rice proteomics data, conduct analyses, and explore experimental conditions. The user-friendly web interface enhances navigation and interaction. RPDB fosters collaboration by enabling data sharing and proper acknowledgment of sources, contributing to proteomics research and knowledge dissemination. Availability and implementation: Web application: http://riceproteome.plantprofile.net/ . The web application's source code, user's manual, and sample data: https://github.com/dongu7610/Riceproteome .
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Oryza , Proteómica , Proteómica/métodos , Manejo de Datos , Programas Informáticos , Bases de Datos Factuales , Almacenamiento y Recuperación de la InformaciónRESUMEN
Faces and bodies both provide cues to age and cuteness, but little work has explored their interaction in cuteness perception. This study examines the interplay of facial and bodily cues in the perception of cuteness, particularly when these cues convey conflicting age information. Participants rated the cuteness of face-body composites that combined either a child or adult face with an age-congruent or incongruent body alongside manipulations of the head-to-body height ratio (HBR). The findings from two experiments indicated that child-like facial features enhanced the perceived cuteness of adult bodies, while child-like bodily features generally had negative impacts. Furthermore, the results showed that an increased head size significantly boosted the perceived cuteness for child faces more than for adult faces. Lastly, the influence of the HBR was more pronounced when the outline of a body's silhouette was the only available information compared to when detailed facial and bodily features were presented. This study suggests that body proportion information, derived from the body's outline, and facial and bodily features, derived from the interior surface, are integrated to form a unitary representation of a whole person in cuteness perception. Our findings highlight the dominance of facial features over bodily information in cuteness perception, with facial attributes serving as key references for evaluating face-body relationships and body proportions. This research offers significant insights into social cognition and character design, particularly in how people perceive entities with mixed features of different social categories, underlining the importance of congruency in perceptual elements.
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Kenaf (Hibiscus cannabinus L.), in the Malvaceae family, is an important crop for not only fiber production, but also various other industrial materials. We performed phylogenetic analysis and a genome-wide association study (GWAS) of seven agronomic traits: days to flowering, plant height, fresh weight, dry weight, flower color, stem color, and leaf shape, using 96 kenaf genotypes, including gamma-irradiation-derived mutant lines. Genotypes were determined by genotyping-by-sequencing (GBS) and a total of 49,241 single-nucleotide polymorphisms (SNPs) were used in the analysis. Days to flowering, plant height, fresh weight, and dry weight were positively correlated with each other, and stem color was also correlated with fresh weight and dry weight. The phylogenetic analysis divided the 96 lines into nine related groups within two independent groups, and the GWAS analysis detected a total of 49 SNPs for days to flowering, plant height, fresh weight, dry weight, flower color, stem color, and leaf shape with -log10(P) ≥ 4, of which 22 were located in genic regions. The detected SNPs were located in genes with homology ranging from 45% to 96% to plants of the Malvaceae and Betulaceae, and these genes were found to be involved in plant growth and development via various pathways. Our identification of SNP markers related to agronomic traits is expected to help improve the quality of selective breeding programs for kenaf.
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Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax and cardiac glycoside (CG) combination in AML. Despite preclinical evidence, the repurposing of cardiac glycosides (CGs) in cancer therapy remained unsuccessful due to a lack of predictive biomarkers. We report that the ex vivo response of AML patient blasts and the in vitro sensitivity of established cell lines to the hemi-synthetic CG UNBS1450 correlates with the ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1)/BCL2 like 1 (BCL2L1) expression ratio. Publicly available AML datasets identify myelomonocytic/monocytic differentiation as the most robust prognostic feature, along with core-binding factor subunit beta (CBFB), lysine methyltransferase 2A (KMT2A) rearrangements, and missense Fms-related receptor tyrosine kinase 3 (FLT3) mutations. Mechanistically, BCL2L1 protects from cell death commitment induced by the CG-mediated stepwise triggering of ionic perturbation, protein synthesis inhibition, and MCL1 downregulation. In vivo, CGs showed an overall tolerable profile while impacting tumor growth with an effect ranging from tumor growth inhibition to regression. These findings suggest a predictive marker for CG repurposing in specific AML subtypes.