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Muscimol injection into the ventral posterolateral nucleus of the thalamus impairs tactile reward-seeking behavior but preserves affective vocalization in male rats
Ultrasonic vocalizations (USVs) are a useful tool for evaluating emotion and motivation in rodents. Rhythmic stroking in rats induces positive affective 50-kHz USVs and reward-seeking behavior. This response involves the dorsal column tract as the ascending pathway; however, supraspinal mechanisms remain unknown. We hypothesized that the ventral posterolateral nucleus of the thalamus (VPL), which receives somatosensory inputs from the spinal cord via the dorsal column–medial lemniscus pathway, might be involved in positive 50-kHz USV production and motivated tactile reward-induced behavior. To test the hypothesis, we used young adult male rats before and after inactivation of the VPL with bilateral infusion of muscimol, a potent γ-aminobutyric acid (GABA)-A type receptor agonist. We measured 50-kHz USVs, approach latency, and spontaneous behaviors pre- and post-muscimol injection, focusing on two emotional (during rhythmic stroking and receiving reward) and motivational (after rhythmic stroking and reward-seeking) conditions. Increased GABAergic inhibition in the VPL completely impaired approach behavior without causing obvious sensory and motor dysfunctions, but only slightly affected 50-kHz USVs. The present data indicate that the GABAergic system in the VPL is substantially involved in execution of reward-seeking behavior but not in the 50-kHz USVs induced by tactile rewards.
Associations of CYP2B6, CYP2C19, and CYP2D6 isoforms and phenoconversion with sertraline pharmacokinetics
Interindividual variability in sertraline exposure is substantial and may be influenced by genetic variation in drug-metabolizing enzymes as well as by concomitant medications that modify enzyme activity. This study explored the association between genetic variability in the cytochrome P450 isoforms CYP2B6, CYP2C19, and CYP2D6 and sertraline pharmacokinetics in a real-world clinical setting, accounting for medication-related phenotype modification. We conducted an observational case-series analysis including seven hospitalized patients with available pharmacogenetic data and sixteen therapeutic drug monitoring measurements of sertraline. Pharmacokinetic parameters were descriptively compared across genotype-predicted metabolic phenotypes and after adjustment for concomitant medications with potential inhibitory or inducing effects, as informed by available interaction data. Before accounting for medication-related phenotype modification within a descriptive framework, variability in sertraline exposure appeared to follow patterns consistent with genotype-predicted phenotypes related to CYP2B6, whereas limited or inconsistent patterns were observed for CYP2C19 and CYP2D6. After incorporating co-medication effects, patterns across sertraline serum concentrations, concentration-to-dose ratios, and apparent clearance were more consistent for adjusted CYP2B6 phenotypes. Adjusted CYP2C19 phenotypes showed additional variability patterns in dose-normalized exposure and clearance, while no consistent associations were observed for CYP2D6 after adjustment. The metabolite-to-parent compound ratio showed no clear relationship with either genetic or adjusted phenotypes. These findings suggest that interpretation of pharmacogenetic information for sertraline may benefit from integrating CYP2B6 and CYP2C19 genotype data with concomitant medication use. In this exploratory case series, accounting for medication-related phenotype modification revealed variability patterns that were less evident when genetic information was considered alone. Current guidelines consider CYP2B6 and CYP2C19 actionable for sertraline; our findings suggest that integrating co-medication–informed interpretation with pharmacogenetic testing and therapeutic drug monitoring may further refine individualized assessment of sertraline exposure in complex clinical settings.
The impact of physical therapy direct access policy on opioid shipments and opioid-related deaths: A difference-in-differences analysis
Background We exploit state-level policy changes for physical therapy direct access to estimate the effect of enacting direct access physical therapy policy on per-capita opioid pill volume (PCPV) and opioid-related deaths (ORD) compared to states without direct access to physical therapy. Methods We used a staggered difference-in-differences analysis to assess changes in PCPV and ORD for states that did (treatment states) and did not enact (control states) direct access physical therapy policies between 2006–2014. Various sensitivity analyses including synthetic control methods were used to check the robustness of our results. Results Treatment states had higher baseline PCPV (29.9 vs. 27.3) and ORD (27.2 vs. 16.9) compared to the control states. Pre-trends in PCPV and ORD were parallel between treatment and control states. After direct access physical therapy policies were enacted, PCPV was significantly reduced by −4.6 (95% confidence interval: −6.2 to −3.0) percentage points, a 15.4% relative reduction. There was no significant difference in ORDs (−2.3 [95% confidence interval: −7.2 to 2.6]). Conclusion Direct access physical therapy policies significantly reduced PCPV but not ORDs. Our results suggest that administrative barriers to physical therapy may lead to greater opioid reliance and reduced population health.
Gender and residential differences in sleep quality among Chinese adolescents aged 13–18 years
Background Good sleep is essential for healthy adolescent development, yet declining sleep quality among Chinese adolescents has become a nationwide public health concern. Residential setting and sex are key determinants of sleep quality; however, systematic evaluations of sleep quality across regions and between sexes among Chinese adolescents remain limited. Methods Data were collected on Pittsburgh Sleep Quality Index (PSQI), body mass index (BMI), Physical Fitness Index (PFI), sedentary time, screen time, and mental health from 5,713 adolescents (mean age, 15.11 ± 1.70 years). Logistic regression models were applied to examine the effects of these factors on adolescent sleep quality, including interactions with residence and gender. Results Overall, 33.71% of Chinese adolescents exhibited poor sleep quality. The prevalence of poor sleep quality was 35.78% among rural adolescents, which was significantly higher than that among urban adolescents (p < 0.001). Among females, 38.40% were classified as having poor sleep quality, a proportion significantly higher than that among males (p < 0.001). BMI, PFI, moderate-to-vigorous physical activity (MVPA), sedentary time, screen time, and mental health scores were significantly effects on the PSQI global score and its component scores (p < 0.05). Residence and gender significantly moderated the linear associations between sleep quality and BMI, PFI, MVPA, sedentary time, and mental health scores (p < 0.05). Conclusions Chinese adolescents living in rural areas and female adolescents experience a greater burden of poor sleep quality. Mental health and PFI appear to be protective factors for sleep quality, whereas BMI, sedentary time, and screen time are risk factors among Chinese adolescents. Moreover, these associations are moderated by residence and gender.
Cost analysis of a nationwide typhoid conjugate vaccine campaign in Burkina Faso
Background In Burkina Faso, typhoid fever remains a major public health concern, particularly among children under 15. In January 2025, a nationwide campaign introduced the typhoid conjugate vaccine targeting children aged 9 months to 14 years. This study aimed to estimate the cost of typhoid conjugate vaccine delivery during the national campaign and to identify the main cost drivers across different administrative levels. Methods We conducted a retrospective cross-sectional costing study using a microcosting approach from the perspective of the Ministry of Health. We collected data from fifty health facilities, eight health districts, five health regions, and the national level. Financial and economic costs were estimated for each level, excluding vaccine and syringe costs. All costs were converted to 2024 USD using the official exchange rate. Parameter uncertainty was explored through one-way sensitivity analysis on key assumptions. Findings Vaccinators administered a total of 10.5 million typhoid conjugate vaccine doses. The average financial cost per dose was $0.47 (95% CI: $0.39–$0.51), and the economic cost was $2.16 (95% CI: $1.71–$2.56). Human resources and per diem payments were the main contributors to costs. Costs varied by geography, delivery strategy, and security context, with higher costs observed in rural and conflict-affected areas. The mobile–temporary posts strategy had the highest economic cost per dose ($2.02; 95% CI: $1.64–$2.40), while the fixed strategy had the highest financial cost per dose ($0.41; 95% CI: ($0.32–$0.49). Sensitivity analyses indicated robust cost estimates, with volunteer time valuation having the greatest influence. Conclusion The financial cost per dose remained within Gavi’s operational support range. The observed cost variations highlight the need for targeted funding and enhanced logistical support to ensure equitable access, particularly in rural and insecure areas. This study provides evidence to inform future vaccination campaigns and supports decision-making for typhoid conjugate vaccine introduction in other countries in the region.
Extracellular flux analyses indicate low ATP yield and require refinement for accurate determination of maximal oxygen consumption rate
Intraperitoneal blue LED irradiation as a potential approach to suppress gastric cancer peritoneal dissemination in a murine model
Risk of obstructive sleep apnea among healthcare workers: a systematic review and meta-analysis
Time-frequency joint imaging algorithm for borehole radar logging
Abstract In borehole radar logging identification technology, there are two key issues: target detection range and spatial resolution. Existing imaging algorithms face limitations in imaging distant targets, tracking moving targets, and identifying low-scattering cross-section features. To address the contradiction between detection range and resolution, we propose a novel time-frequency joint imaging algorithm based on direct-wave referenced processing. The algorithm implements three core strategies: (1) Amplitude normalization and time-base synchronization using the direct wave as a stable benchmark to suppress source jitter; (2) Hybrid-domain digital filtering combining wavelet transform and Fourier bandpass filtering to mitigate out-of-band noise; and (3) Adaptive time-varying amplification to compensate for spherical spreading and medium attenuation. Experimental results indicate that, compared to conventional high-resolution logging methods (e.g., acoustic/resistivity logging) limited to < 3 m, the proposed framework demonstrates a detection range extension to 8.5–10 m while simultaneously improving spatial resolution to the centimeter level (5–10 cm). This work presents a viable framework for long-range, high-resolution borehole radar imaging in complex formations, subject to further validation in diverse geological settings.
Coherent Cancellation in Oscillatory Structural Forces Enables Surface Recognition in Colloidal Assembly
A randomized replication trial of physical rehabilitation versus no physical rehabilitation (DRAW2)
From Schreier graphs to secure s-boxes using a group-theoretic design framework
Distance and near vision impairment and its impact on work productivity among garment industry workers in Hyderabad, Telangana, India
K acquisition from vermiculite by sweet potato also improves K nutrition in neighboring plants
Abstract Intensive agriculture requires substantial external potassium (K) application to meet crop K requirements. Recent research has revealed that sweet potato ( Ipomoea batatas ), a crop with high K requirements, could acquire sufficient K from a mixture of Andosol and vermiculite without the need for additional fertilization. However, the specific K component in growth medium being utilized is still unclear. We evaluated K acquisition by sweet potato grown in either Andosol or vermiculite, comparing it with soybean, barley and water spinach ( Ipomoea aquatica ). Additionally, soybeans were grown in vermiculite together with sweet potato to assess the rhizosphere effect of sweet potato. Changes in K component in growth medium after plant growth were examined to identify the specific fraction responsible for these changes. Only sweet potato and water spinach, both from the genus Ipomoea , exhibited normal growth in vermiculite-only medium without K application by promoting the release of K from slowly available (fixed interlayer K) pools, which is unavailable to other crop species. K mapping image analysis confirmed that sweet potato roots accumulated more K than other species, even during 7 days of growth. In the mixed-culture system, the presence of sweet potato enhanced K availability in vermiculite to soybean ( Glycine max ), enhancing K and biomass accumulation of soybean. Our results reveal that sweet potato and water spinach exhibit efficient K acquisition from vermiculite, especially from slowly available K pool. Besides, sweet potato enhances K availability to neighboring plants through rhizosphere acidification.
Controlled delivery of nilotinib using LDH/Fe2O3-modified chitosan nanocomposite hydrogel beads for the treatment of chronic myeloid leukemia
Abstract Chronic myeloid leukemia remains a significant challenge in cancer treatment because conventional drug delivery systems often fail to provide sustained release and targeted therapeutic effects. To address these limitations, this study a chitosan-based nanocomposite hydrogel system for the controlled delivery of nilotinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia. Fe 2 O 3 -containing layered double hydroxide nanocomposites into were incorporated chitosan hydrogels under controlled synthesis conditions (70 ± 2 °C, stirring speed at 800 rpm) to fabricate chitosan nanocomposite hydrogel beads based on LDH and Fe 2 O 3 nanoparticles. Structural characterization using scanning electron microscopy and X-ray diffraction confirmed successful nanoparticle incorporation and the formation of a porous hydrogel network. Nilotinib was incorporated into the hydrogel beads using both in situ and post-synthetic approaches, and drug release was quantified by high-performance liquid chromatography. Among the formulations investigated, the Post-synthetic incorporation of nilotinib into dried hydrogel beads at a concentration of 20% yielded the highest cumulative nilotinib release after six hours (72.895 ± 0.004 µg/mL). Cytotoxicity studies revealed a concentration-dependent inhibition of chronic myeloid leukemia cell lines (BV173, EM-2, CML-T1, and JOSK-M) and indicated acceptable biocompatibility with human umbilical vein endothelial cells. In addition, the nanocomposite hydrogel demonstrated notable antioxidant activity in the DPPH assay. Overall, the developed LDH/Fe 2 O 3 -modified chitosan hydrogel system represents a promising platform for the controlled delivery of hydrophobic anticancer agents such as nilotinib.
Evaluating and optimizing public service facilities within the 15-min community life circle—evidence from Nanchang, China
Anticancer activity and molecular docking of active ingredients from ethanolic extract of grapefruit peels against HepG2 cell
Abstract Natural products are vital sources for drug discovery, offering greater structural diversity than synthetic chemicals. They have historically contributed to the identification of bioactive molecules and continue to play a crucial role in the discovery of new therapeutics. Citrus species, members of the Rutaceae family, represent one of the most economically important fruit tree crops worldwide, with a global yield of approximately 123 million tons in 2010. grapefruit peels were collected, dried and their active ingredients were extracted with 70% ethanol. The resulting extracts underwent phytochemical screening. The anticancer activity of the extracts was evaluated using the MTT assay, with cell viability assessed and IC₅₀ values determined. Promising fractions were further analyzed using high-performance liquid chromatography (HPLC). Results Phytochemical screening revealed high phenolic and flavonoid content, with naringenin being the most abundant compound, followed by chlorogenic acid and ferulic acid. The extract exhibited significant anticancer activity against HepG2 cells, with an IC 50 of 230.63 ± 1.61 µg/ml. Molecular docking analysis of sixteen phytochemicals against the AFP protein (PDB ID: 7YIM) identified several compounds with strong binding affinities toward the predicted active site. Ellagic acid showed the highest binding affinity (-8.9 kcal/mol), followed by rutin (-8.8 kcal/mol), quercetin (-8.5 kcal/mol), and naringenin (-8.4 kcal/mol). Interaction analysis revealed multiple hydrogen bonding and π-interactions with key AFP residues, including LYS228, CYS224, PHE172, GLU489, and MET490. These findings highlight polyphenolic compounds, particularly ellagic acid and rutin, as promising lead molecules for AFP-targeted anti-hepatocellular carcinoma therapy. Grapefruit peel extract exhibits promising antioxidant and anticancer activities, demonstrating concentration-dependent cytotoxicity against HepG2 cells. Despite its lower potency compared to doxorubicin, it represents a valuable natural source of bioactive compounds. Further studies are required to elucidate its mechanisms, safety, and potential application in hepatocellular carcinoma therapy.
Knowledge-guided multimodal reasoning framework for intelligent power grid maintenance
Structural and stratigraphic controls on reservoir distribution in the Ptah oil field, Shushan Basin, North Western Desert, Egypt
Abstract The Ptah Oil Field, located along the northwestern margin of the Shushan Basin in Egypt’s Western Desert, hosts structurally complex clastic reservoirs whose hydrocarbon distribution is strongly fault controlled. This study applies an integrated seismic–petrophysical–petrographic workflow to characterize reservoir architecture and trapping mechanisms within the Bahariya, Lower Cretaceous Alam El Bueib (AEB-3D/3E) and Paleozoic Shiffah B sandstone intervals. Interpretation of 20 two-dimensional (2D) seismic lines extracted from 3D seismic cube, calibrated with well logs and core from six wells, reveals an extensional fault framework dominated by NW–SE and E–W normal faults forming horst–graben geometries and three-way dip closures that govern reservoir preservation and compartmentalization. Petrophysical analysis indicates moderate reservoir quality with significant lateral variability in reservoir properties. The net pay thickness varies across the study area and reached to 13, 38 and 129 ft. for Bahariya, Alam El Bueib and Paleozoic Shiffah B Sandstone reservoirs. Effective porosity derived from well logs ranges approximately between 7–12%, while core measurements indicate porosity values reaching 21%. Permeability values obtained from core analysis vary widely between 0.02 and 839 mD, reflecting heterogeneous pore systems within the sandstone reservoirs. Structural mapping identifies several fault-bounded closures with aerial extents ranging from approximately 273 to 4500 acres across the studied stratigraphic intervals, these structural configurations may represent promising exploration targets, particularly where fault sealing and reservoir quality are favorable. Petrographic observations confirm that diagenetic clay distribution further controls pore structure and permeability. Integrated results demonstrate that hydrocarbon accumulation is primarily dictated by the interaction of fault architecture, stratigraphic preservation, and diagenetic modification rather than reservoir properties alone. This framework refines reservoir delineation, reduces exploration uncertainty, and identifies structurally favorable targets, providing a transferable methodology for evaluating fault-controlled clastic reservoirs in extensional basin settings.