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Views of aging, encompassing conceptions about older adults, old age, and aging, are related to health and well-being via related behaviors. However, little is known about how different views of aging predict behaviors. Descriptive views of aging (DVoA) describe how older adults allegedly are (e.g., unfit or lonely). Prescriptive views of active aging (PVoA) entail beliefs about how older adults should behave (e.g., exercise or engage socially). Two alternatives for the relations between DVoA and PVoA with behaviors are possible-PVoA mirror DVoA as they entail normative expectations that older adults should compensate for deficits expressed via negative DVoA (e.g., older adults are lonely, so they should become socially engaged), indicating that behaviors can be predicted by one or the other. However, PVoA could be more strongly related to behaviors than DVoA, as they directly prescribe age-appropriate behaviors. Focusing on the health and social domains, we tested these predictions in three preregistered studies (total N = 1,141, 60-90 years). All studies showed that higher endorsement of PVoA (e.g., older adults should stay fit) and more positive DVoA (e.g., older adults do a lot for their fitness) were related to more self-reported health-related, prosocial, and socializing behaviors. PVoA was more closely related to self-reported behaviors than DVoA. Our findings underline the importance of PVoA and DVoA for understanding how views of aging could become embodied in older adults' self-reported behaviors. Moreover, interventions aiming at changing older adults' behaviors via views of aging should also target PVoA, not just DVoA. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
The Salmonella inner membrane is not just a selectively permeable barrier. It is also a working platform where transport, energy metabolism, protein export, signal transduction, envelope biogenesis, and host adaptation are brought together. In this review, inner membrane proteins are therefore not discussed only as isolated structural units. We use representative transporters, respiratory enzymes, secretion systems, sensor kinases, envelope assembly factors, and phospholipids to show how these modules can work with one another under infection-related stress. Protein secretion covers Sec/Tat translocation as well as type III secretion systems (T3SSs), because these routes together link protein export with envelope assembly, motility, invasion, and intracellular survival. ATP-binding cassette (ABC) importers and secondary transporters help Salmonella take up nutrients, metals, ions, and osmoprotectants, whereas efflux systems and lipid transporters help Salmonella cope with antibiotics, bile, antimicrobial peptides, and small molecules from the host. Respiratory complexes and F₀F₁-ATPase translate changing oxygen and electron-acceptor conditions into proton motive force and ATP, which then feed back into transport, secretion, and stress tolerance. At the same time, lipid A/lipopolysaccharide (LPS), phospholipids, peptidoglycan, and cell division pathways shape envelope integrity, immune recognition, antimicrobial peptide resistance, and intracellular survival. These effects are often condition-dependent, so drug resistance and virulence phenotypes need to be read in the context of host niche, stress conditions, growth state, strain background, and compensatory regulation. Viewed in this way, the Salmonella inner membrane is a coordinated adaptive network, and this view can help identify antibacterial targets that weaken bacterial adaptation rather than simply blocking one isolated protein.
The US opioid crisis is currently driven by illicitly manufactured fentanyl combined with an evolving mix of stimulants and adulterants, such as the veterinary sedative xylazine, which further complicate clinical and public health responses. Using urine drug testing (UDT) to understand changes in the geographic spread and relative concentration of xylazine over time may provide clarity on the changing dose of exposure for xylazine and future emerging adulterants. To differentiate spatiotemporal trends in xylazine detection and relative concentration in UDT specimens from 2023 to 2025. This retrospective cross-sectional study analyzed UDT specimens collected from US patients (1 specimen per patient) aged 18 years or older from March 2023 and September 2025. Tests were ordered by behavioral health, primary care, or substance use treatment practitioners. If more than 1 specimen was provided by a patient during the study period, only the first specimen collected was included. Data were analyzed from June to September 2025. UDT specimens were analyzed for fentanyl and xylazine (primary exposure) using liquid chromatography with tandem mass spectrometry. Specimens were included in the study if fentanyl was detected. Differences in xylazine positivity by patient and practitioner characteristics, copositivity for other substances, and fentanyl concentration were assessed using logistic regression. Spatiotemporal trends in monthly percentages of xylazine positivity and concentration in UDT, stratified by East and West Census regions, are described. A total of 42 307 specimens (24 339 [57.52%] from male patients; 15 583 [36.83%] from patients aged 26-35 years) were analyzed. In both regions, xylazine detection increased between the first and last months (East: 8.52 percentage points [from 11.11% to 19.63%]; West 13.46 percentage points [from 0.0% to 13.46%]) while concentration decreased (East: -37.76 ng xylazine per 1 mg creatinine [from 61.77 to 24.00 ng xylazine per 1 mg creatinine]; West: -7.98 ng xylazine per 1 mg creatinine [from 28.62 to 20.64 ng xylazine per 1 mg creatinine]). Odds of xylazine detection were 79% lower in the West (AOR vs East, 0.21 [95% CI, 0.19 to 0.22]; P < .001), and 120% higher in samples with heroin positivity (AOR vs heroin negativity, 2.20 [95% CI, 2.07 to 2.35]; P < .001) or with higher fentanyl concentrations (AOR per 10-fold increase, 1.55 [95% CI, 1.53 to 1.57]; P < .001). In this cross-sectional study of xylazine-fentanyl in UDT specimens, xylazine detection increased but concentration decreased over time. These findings suggest UDT complements existing drug surveillance and provides unique insights into emerging fentanyl adulterants.
L-type amino acid transporter 1 (LAT1) is a heterodimeric membrane protein that primarily facilitates the transport of phenylalanine, along with other amino acids such as valine, leucine, isoleucine, tryptophan, and tyrosine across the cell membrane. It is predominantly expressed at the blood-brain barrier. While LAT1 has been extensively studied in the context of drug delivery, its specific transport pathway for phenylalanine and the related conformational dynamics remains largely unexplored. Investigation of the transport pathway of phenylalanine via LAT1 is also very important, as excessive amounts of phenylalanine can cause phenylketonuria (PKU). Inhibiting LAT1's transport could reduce phenylalanine's entry into the brain, aiding in the management of its levels and alleviating the adverse effects of PKU. To investigate the phenylalanine transport mechanism and the conformational dynamics of LAT1, microsecond-long molecular dynamics (MD) as well as steered molecular dynamics (SMD) and targeted molecular dynamics (TMD) simulations were performed. The results of this study identify essential structural motifs that enable the isomerization of LAT1 among outward-facing, inward-facing, and occluded states. A significant conclusion drawn from this research is the identification of seven critical transmembrane helices that play central roles along the transport pathway, namely, TM1, TM4, TM6, TM7, TM8, TM9, and TM12. Root-mean-square deviation (RMSD) analyses across the structural models further indicate that TM1 and TM6 are consistently engaged during both extracellular and intracellular phenylalanine transitions, whereas TM9 and TM12 contribute more specifically to the outward and inward opening events, respectively. The observed conformational changes offer fresh insights into the alternating-access mechanism of LAT1 during phenylalanine transport, contrasting with conclusions from structural models based on other substrates transport through LAT1. By elucidating this transport mechanism, the study will contribute to developing LAT1 inhibitors that can selectively regulate brain phenylalanine levels without disrupting the transport of other essential amino acids.
The acute hepatic venous pressure gradient (HVPG)-response to i.v. propranolol predicts outcomes in patients with advanced chronic liver disease (ACLD) and clinically significant portal hypertension (CSPH). While non-invasive tests (NIT) to monitor non-selective beta-blocker (NSBB)-induced HVPG changes are lacking, spleen stiffness measurement (SSM) has shown promising results as a surrogate for HVPG. This study aimed to assess the correlation between changes in SSM at 100 Hz and HVPG upon acute i.v. propranolol. ACLD patients with CSPH undergoing paired HVPG and SSM-100 Hz assessments pre- and post-i.v. propranolol (0.15 mg/kg) at three expert centres between 2019 and 2024 were included. HVPG-response was defined as a ≥ 10% decrease in HVPG. Ninety-four patients (63.8% males, median age 57.5 [Q1-Q3: 50.0-65.0] years, BMI 26.6 [22.8-31.1] kg/m2) were included. Most had alcohol-related liver disease (ALD)/metabolic-associated liver disease (59.6%) or metabolic-associated steatotic liver disease (11.7%). The median HVPG decreased from 17 (Q1-Q3: 15-20) mmHg to 16 (Q1-Q3: 12-19) mmHg post-NSBB (p < 0.001), with 45.7% achieving an acute HVPG-response. SSM decreased by -8.7 ([Q1-Q3: -19.2; -0.2] kPa, p < 0.001). HVPG-responders had a significant SSM decrease (-12.4 [Q1-Q3: -26.3; -5.6] kPa, p < 0.001), while non-responders showed no change. A moderate correlation between relative changes in SSM and HVPG was observed (Spearman's ρ: 0.387; p < 0.001). Relative change in SSM achieved an area under the receiver operating characteristic curve (AUROC) of 0.717 (95% CI: 0.614-0.820, p < 0.001) for diagnosing HVPG-response. SSM-100 Hz dynamics are associated with HVPG changes upon i.v. propranolol administration. Although the discriminative ability of changes in SSM was insufficient for clinical use, they may serve as a surrogate of efficacy in clinical trials investigating medical therapies for portal hypertension. In advanced chronic liver disease, the hepatic venous pressure gradient (HVPG) response is a key determinant of treatment efficacy, but its assessment currently requires an invasive procedure. Spleen stiffness measurement is a promising non‐invasive alternative and was shown in this study to be associated with changes in portal pressure and treatment response. However, its accuracy is insufficient to replace HVPG measurement in routine clinical practice, although it may still be useful in clinical trials or under standardised conditions.
The immune response against cancer is influenced by the tumor stroma. Carcinoma-associated fibroblasts (CAFs), a significant part of the stroma, are important modulators of the tumour microenvironment (TME). The current study examined the immunomodulatory properties of CAFs isolated from a stage II mouse model of mammary invasive ductal cancer. Based on the expression of surface markers, we described Stage II CAFs and assessed their effects on cytokine release, nitric oxide (NO) generation, and splenocyte proliferation in direct co-culture systems. Class II MHC molecules (I-Ad/I-Ed), FAP-1, CD29, CD90, and CD105 were all expressed by isolated CAFs, indicating the possibility of direct immunological contact. In direct co-culture, CAFs demonstrated two distinct functions: their conditioned medium (CM) had immunosuppressive effects, whereas direct cell interactions promoted splenocyte growth. Additionally, CAFs changed the cytokine milieu, particularly by secreting high levels of TGF-β and PGE₂, and dramatically reduced splenocyte NO generation. COX-2, IDO, and MMP2 were significantly upregulated in CAFs, according to gene expression data. Our results emphasize the potential of Stage II CAFs as a therapeutic target in breast cancer by demonstrating their complex immunomodulatory character, which includes the ability to both stimulate and repress immune responses through cellular contact and soluble factors.
To evaluate the feasibility and safety as well as potential effects of percutaneous sacral nerve stimulation (SNS) via acupuncture needles in patients with active rheumatoid arthritis (RA). Twenty-one patients with active RA were allocated to receive either active SNS (n = 11) or sham stimulation (n = 10) for 60 min daily over 14 days. Primary outcomes were changes in disease activity, assessed by the Disease Activity Score in 28 joints (DAS-28), tender joint count (TJC), swollen joint count (SJC), pain intensity on a visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Secondary outcomes included the following: (1) patient-reported outcomes for joint function, fatigue, anxiety, and depression; (2) serum levels of inflammatory cytokines; and (3) heart rate variability (HRV) parameters as a measure of autonomic function. In this pilot study, the SNS group showed significant within-group improvements in TJC, VAS, DAS28-ESR, and DAS28-CRP. However, an analysis of covariance (ANCOVA) adjusting for baseline values revealed no significant between-group differences in clinical and inflammatory parameters. The SNS group showed a significant increase in rMSSD (parasympathetic marker), with the between-group difference sustained after baseline adjustment. No significant differences were observed in functional and psychological scores or serum cytokine levels between the two groups. This first-in-human study indicates that percutaneous SNS is feasible and safe, with a possible modulatory effect on autonomic function in active RA. Further large‑scale, adequately powered trials are warranted to confirm the clinical efficacy and mechanisms of SNS in RA. This study was registered at ClinicalTrials.gov on March 25, 2021 under the identifier NCT04821050 (Protocol ID: 202002053). Key Points • First-in-human pilot study of percutaneous sacral nerve stimulation (SNS) in active RA. • SNS was associated with significant within-group improvements in tender joint count, pain VAS, and DAS28, but between-group differences did not reach statistical significance after baseline adjustment. • SNS significantly enhances parasympathetic activity (rMSSD) compared with sham stimulation, an effect that remained significant after adjusting for baseline differences. • Percutaneous SNS was safe and well-tolerated, with no serious adverse events reported.
The management of geriatric patients with urological cancers is becoming increasingly important due to rising life expectancy and the growing incidence of such diseases. However, treatment decisions are often based primarily on chronological age or clinical guidelines, whilst insufficient consideration is given to the functional reserve of older patients. Geriatric patients exhibit specific physiological changes such as impaired renal or liver function, sarcopenia, multimorbidity, polypharmacy, malnutrition and cognitive impairments, which increase the risk of postoperative complications, functional decline, delirium, falls and the need for care. Standard therapies can therefore lead to significant functional limitations despite their oncological benefits. The aim of modern uro-oncological treatment is not only to prolong life but, in particular, to preserve autonomy, mobility and quality of life. For the purpose of individualised treatment planning, current guidelines recommend a stepwise geriatric assessment. This begins with screening using the G8 and mini-COG©, followed by a simplified geriatric assessment or a comprehensive geriatric assessment (CGA) if any abnormalities are detected. Classifying patients as fit, vulnerable or frail enables risk-adapted treatment decisions and targeted geriatric interventions. This can improve functional reserves, reduce complications and potentially avoid the need for long-term care. Die uroonkologische Versorgung geriatrischer Patienten gewinnt durch die steigende Lebenserwartung und zunehmende Inzidenz uroonkologischer Erkrankungen zunehmend an Bedeutung. Therapeutische Entscheidungen orientieren sich jedoch häufig primär am chronologischen Alter oder an Leitlinien, während die funktionelle Reserve älterer Patienten unzureichend berücksichtigt wird. Geriatrische Patienten weisen spezifische physiologische Veränderungen wie Einschränkungen der Niere- und Leberfunktion, Sarkopenie, Multimorbidität, Polypharmazie, Malnutrition und kognitive Einschränkungen auf, die das Risiko für postoperative Komplikationen, funktionellen Abbau, Delirien, Stürze und Pflegebedürftigkeit erhöhen. Standardtherapien können daher trotz onkologischen Nutzens zu relevanten funktionellen Einschränkungen führen. Ziel moderner uroonkologischer Therapie ist neben der Lebensverlängerung insbesondere der Erhalt von Autonomie, Mobilität und Lebensqualität. Zur individualisierten Therapieplanung empfehlen aktuelle Leitlinien ein stufenbasiertes geriatrisches Assessment. Hierbei erfolgen zunächst Screeningverfahren mittels G8 und Mini-Cog©, gefolgt von einem vereinfachten geriatrischen Assessment beziehungsweise einem umfassenden geriatrischen Assessment (CGA) bei auffälligen Befunden. Die Einteilung in fitte, vulnerable und gebrechliche Patienten ermöglicht eine risikoadaptierte Therapieentscheidung sowie gezielte geriatrische Interventionen. Dadurch können funktionelle Reserven verbessert, Komplikationen reduziert und langfristige Pflegebedürftigkeit potenziell vermieden werden.
Molecular dynamics (MD) simulations are widely used in computational and structural biology to study the time-dependent behavior of biological macromolecules at atomic resolution. Over the years, they have become an indispensable tool in the study of biomolecular systems and have been applied to investigate protein folding, conformational change, ligand interaction, protein structure determination, and refinement of X-ray crystallographic models. This chapter presents a practical, end-to-end protocol for performing MD simulations on large biomolecules, using a full-length antibody as a case study. It also introduces foundational software tools commonly used in molecular modeling and MD simulations, including PyMOL, visual molecular dynamics (VMD), nanoscale molecular dynamics (NAMD), MDAnalysis, and others. Additionally, the protocol covers the modeling of antibody-excipient interactions and identifying binding sites from MD trajectories. Together, this accessible and reproducible framework aims to equip researchers with the computational tools and foundational knowledge needed to study the dynamic behavior of complex biomolecular systems and integrate MD simulations into their own biological research.
The binuclear zinc(II) complex, Na2[Zn2(dipic)2(µ-adipic)] (1) (where dipic is dipicolinic acid and adipic is adipic acid), was synthesized and characterized by elemental analysis (EA), FT-IR, 1H NMR, mass spectrometry, and UV-Vis spectroscopy. The complex geometry was optimized using DFT calculations. In-vitro interaction of DNA/HSA with complex (1) was explored using different experimental methods. Both experimental and theoretical results support confirmed effective interaction with these macromolecules. The observed data display that the complex interacts with CT-DNA predominantly via a groove binding mode through hydrogen bonding and van der Waals forces. Fluorescence data suggest a static quenching mechanism for both DNA and HSA systems. Binding constant analysis showed that the complex has a higher affinity for DNA compared to HSA. Also, this study investigated the antioxidant activity of (1) by measuring its ability to scavenge the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, and the results were comparable to those of Vitamin C.
Postmenopausal women face increased risks of vascular dysfunction, loss of lean muscle mass, and reduced physical performance due to age-related hormonal and metabolic changes. These factors contribute to heightened cardiovascular risk and physical frailty. L-citrulline, a non-essential amino acid and precursor to nitric oxide (NO), has emerged as a potential therapeutic agent for improving vascular and muscular health. When combined with structured exercise, L-citrulline may enhance NO bioavailability, improve endothelial function, increase muscle perfusion, and potentiate exercise-induced adaptations. This review synthesizes current evidence on the combined impact of L-citrulline supplementation and exercise on endothelial function, arterial stiffness, leg muscle function, lean mass, and strength in postmenopausal women. Findings from preclinical and clinical studies suggest that this combined intervention can reduce arterial stiffness, enhance leg muscle strength, increase lean body mass, and improve overall physical function, potentially via NO-mediated vasodilation, the mechanistic target of rapamycin signaling, improved mitochondrial function, and reduced oxidative stress. These effects are especially relevant in postmenopausal populations at risk for cardiovascular disease and sarcopenia. While early results are promising, further high-quality randomized controlled trials are needed to confirm these benefits, establish optimal dosing strategies, and determine long-term clinical relevance.
Recent research has established that it is feasible to assess executive function (EF) skills in infancy and toddlerhood via parental report using the Early Executive Functions Questionnaire (EEFQ; Hendry & Holmboe, 2021). However, little is known about the predictiveness of early-emerging regulatory and cognitive aspects of parent-reported EFs to later EF outcomes. We collected longitudinal EEFQ data from 178 U.K. children (85% White) with predominantly highly educated parents at ages 10, 16, 24, and 30 months. Moreover, 92% of respondents were mothers. Parent-reported EF outcomes were assessed using the Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P; Gioia et al., 2000) at 36 months. Age-related improvements were observed for EEFQ-Cognitive Executive Function scores (quadratic effect; most rapid changes at 10-24 months). EEFQ-Regulation scores decreased between 10 and 30 months (quadratic effect; most rapid change at 10-16 months). Individual differences in EEFQ-Cognitive Executive Function and EEFQ-Regulation scores showed moderate stability over a 6-month period, small but significant stability across a 20-month interval, and predictive associations to 36-month BRIEF-P scores from 10 months. EEFQ-Cognitive Executive Function scores were primarily associated with cognitively focused BRIEF-P scales (working memory, plan/organize), and most associations emerged from 16 months onward, whereas EEFQ-Regulation scores were predictive of all BRIEF-P scales from 10 months. Our findings provide characterization of age-related change in early parent-reported EFs, evidence for stability in parent-reported EFs across the infancy-to-preschool period, and novel insights into dissociable patterns of development in the regulatory and cognitive aspects of EFs. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
This study assesses climatic and bioclimatic variability on Kolguev Island (Barents Sea) using meteorological observations from the Kolguev Severny station for 1941-2024 and expedition measurements conducted in June-July 2023 and 2025. Trends in air temperature, precipitation, frost-free and growing seasons were analyzed, while bioclimatic conditions were evaluated using the Universal Thermal Climate Index (UTCI). A statistically significant increase in air temperature was identified in all seasons, with a pronounced intensification after 2000. Mean annual temperature increased by 0.27 °C per decade during 1941-2024 and by 0.89 °C per decade during 2000-2024. The spring transition of air temperature across 0 °C shifted to earlier dates, while the autumn transition shifted later, resulting in an increase in the frost-free period from 146 days (1961-1990) to 157 days in the 1991-2020. The duration of the growing season increased by about one month, and the sum of positive temperatures rose by 117 °C. During the second decade of the 21st century, a tendency toward decreasing moisture availability on the island has also been observed. Bioclimatic conditions on Kolguev Island are dominated by cold stress of varying intensity according to the UTCI classification, ranging from extreme to slight cold stress. The frequency of extreme cold stress decreased from 18% of days in the 1970s to 9% in the 2010s, while the proportion of days without thermal stress in summer increased from 4% to 7%. Expedition observations showed prevailing strong and moderate cold stress conditions, although rapid changes from very strong to moderate cold stress may occur within hours due to weakening winds. The observed climatic changes contribute to Arctic "greening," increasing vegetation productivity and potentially affecting tundra ecosystems, reindeer herding, and biodiversity.
This study contributes to research on the patterns of change in, and parent-child relationship correlates of, sibling relationships in Latino/a children in middle childhood and early adolescence. Specifically, the study goals were to (a) chart age-related trajectories of sibling intimacy and conflict between 6 and 12 years of age using a cohort-sequential accelerated longitudinal design and (b) examine between-person and within-person associations with parent-child warmth and conflict. Data were collected from a three-cohort study of 285 Latino sibling pairs and their caregivers, who participated at three time points over an 18-month period in a randomized clinical trial. Results of multilevel longitudinal growth models revealed a quadratic effect of sibling intimacy, with moderation by child sex, and a linear effect of sibling conflict, moderated by mother nativity. Findings of multilevel models further revealed that mother-child (but not father-child) warmth was linked to sibling intimacy, suggesting that higher maternal warmth was related to greater sibling intimacy, on average, across time (between-person effect). Regarding conflict, there was a significant between-person effect of father-child conflict on sibling conflict, with higher average father-child conflict associated with higher sibling conflict over time. A within-person effect of mother-child conflict on sibling conflict revealed that on occasions when mothers reported greater conflict with their children than usual, children reported more sibling conflict. The discussion considers age-related changes in sibling relationships and the interplay of family dynamics in Latino families during middle childhood and the transition to adolescence. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
To examine the relationship between posterior vitreous changes and retinal detachment (RD) associated with acute retinal necrosis (ARN). Retrospective, consecutive case study. This study evaluated the clinical findings for 32 eyes of 29 patients (12 women, 17 men) diagnosed with ARN, with the posterior vitreous condition monitored by swept-source optical coherence tomography (SS-OCT). The causative virus, incidence of RD, and relationship between the development of RD and final visual acuity were investigated. Patients were checked for posterior vitreous detachment (PVD) from the initial visit to the last SS-OCT observation. Varicella-zoster virus caused 67% of the ARN cases, with RD developing in 66% of the cases, and proliferative vitreoretinopathy (PVR) in 90% at onset or at recurrence. Silicone oil could not be removed in 38% of the cases with RD. Final best-corrected visual acuity was significantly worse in the RD (+) group than in the RD (-) group (median logMAR 1.02 vs. 0.16, p = 0.04). PVD occurred in 20 of 21 eyes without PVD at the initial examination, with 18 of these 20 eyes developing RD (90%). PVD occurred at an average of 45.8 ± 32.1 days after the initial examination, with 85% of the cases developing PVD within 3 months. The visual prognosis of ARN complicated by RD is poor. PVD is involved in the development of RD and is often associated with PVR, which itself is refractory.
Streptococcus pneumoniae is a major cause of pneumonia and other diseases. First-line antibiotics work for infections; however, drug-resistant strains complicate their control. Traditional Chinese medicine (TCM) may help treat drug-resistant infections, although the underlying mechanism is unclear. This study explored the efficacy and mechanism of action of Yinhuapinggan Granules (YHPG) in infected mice, focusing on the PI3K/AKT and RAS/MAPK pathways. A mouse model of Streptococcus pneumoniae infection was established using an intranasal instillation approach. Different doses of Yinhuapinggan granules were then continuously administered for six days after infection. Hematoxylin-eosin (HE) staining, immunohistochemical staining, quantitative polymerase chain reaction (qPCR) analysis and western blotting were used to assess the effects of Yinhuapinggan Granules on the histopathological changes in the lungs, the levels of inflammatory factors and the expression of relevant signaling pathway proteins in mice. YHPG reduces lung damage, inflammation and neutrophil infiltration in mice. These findings suggest that the anti-inflammatory and immunomodulatory effects of YHPG are associated with the observed phenomena. YHPG inhibited the upregulation of streptococcus pneumoniae-induced pathway-associated signaling proteins (IκBα, JNK, P38 and ERK), which may be related to the regulation of the PI3K/AKT and RAS/MAPK signaling pathways. The findings of this study provide experimental evidence for the efficacy and anti-inflammatory mechanism of YHPG against pneumonia caused by Streptococcus pneumoniae infection. The present study confirms that YHPG particles can exhibit therapeutic effects in Streptococcus pneumoniae-infected mice by modulating the PI3K/AKT and Ras/MAPK pathways.
The tide is turning against a major idea in social psychology: that implicit evaluations reflect mental content that lies beyond conscious awareness. This view is being reconsidered in light of mounting evidence that people can predict their own implicit evaluations with high accuracy. However, there are reasons to question whether such predictive accuracy reflects introspective access. First, prior studies have relied almost exclusively on familiar targets (e.g., racial groups), allowing predictions to be informed by background knowledge (e.g., knowing that a group is stigmatized) rather than introspection. Second, implicit and explicit evaluations have been highly correlated in prior work, enabling accurate predictions simply by assuming that implicit evaluations mirror explicit ones. Here, we report eight experiments (five pre-registered; N = 6,794) designed to minimize these nonintrospective routes to predictive accuracy. We introduced participants to novel targets and shifted implicit and explicit evaluations of these targets in opposite directions, rendering explicit evaluations an unreliable cue. Under these conditions, predictive accuracy ranged from low to nonexistent; participants frequently anticipated shifts in their implicit evaluations in the opposite direction of the actual change. These results generalized across two learning paradigms (impression formation and attribute conditioning), two implicit evaluation measures (Implicit Association Test and evaluative priming task), and between-participant and within-participant designs. We consider multiple interpretations of these findings, including the possibility that implicit evaluations reflect mental content that is largely or even entirely inaccessible to conscious awareness. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Feed efficiency, usually assessed by residual feed intake (RFI) and residual intake and gain (RIG), is a key trait for enhancing the profitability and sustainability of livestock systems. Although several genes linked to feed efficiency have been identified, the molecular mechanisms underlying this trait are not well understood. This study identified potential biomarkers and molecular mechanisms for feed efficiency in Texel ewes using a proteome approach. Thirty-nine ewes were evaluated in a feedlot to calculate RFI and RIG. Blood samples of a subset of 12 animals at the extremes of the feed efficiency range (six low-efficiency and six high-efficiency) were used for proteomic analysis. Differentially abundant proteins between the groups (absolute fold change ≥ 2; p < 0.05) were used for protein-protein interaction (PPI) network analysis using the STRING tool and functional enrichment analysis using the DAVID tool. Proteomics analysis detected 2,580 proteins; of these, 35 were differentially abundant between the high- and low-efficiency groups. PPI analyses revealed proteins encoded by the AHSG, PLG, CP, AFM, KNG1, LTF, ITIH2, and ITIH3 genes to be important nodes based on their centrality and interactions. Functional enrichment analysis identified ferroptosis, iron transport, copper binding, phospholipid metabolism, ATP binding, and endopeptidase inhibitor activities as significant terms, which may potentially contribute to feed efficiency. The findings provide new insights into the molecular mechanisms underlying feed efficiency in sheep and contribute to identifying potential biomarkers that may support future genomic selection strategies aimed at improving the efficiency and sustainability of sheep production.
This chapter describes a fluorescence anisotropy-based method for quantifying the binding affinity between a nucleic acid aptamer and its protein target, using the thrombin-binding aptamer (TBA)-thrombin interaction as an example. Fluorescence anisotropy is a rapid and sensitive technique that monitors changes in a molecule's rotational speed upon binding. By fluorescently labeling an aptamer and titrating it with increasing concentrations of its target protein, users can generate a binding isotherm and determine the dissociation constant (KD) with accuracy. The protocol includes detailed instructions for reagent preparation, plate setup, data acquisition, and analysis, with emphasis on minimizing experimental variability. Although demonstrated for the thrombin aptamer system, the approach is broadly applicable to other protein-nucleic acid interactions.