Search Results (2,777)

Self-regulated learning (SRL) is a fundamental competence for academic transition and success in higher education, especially in health sciences, where autonomy and learning management are essential. This systematic review analyzed the relationship between SRL, academic performance, and student well-being among undergraduate health sciences students. Following the PRISMA protocol, 39 articles published between 2015 and 2025 on Web of Science, Scopus, and PubMed databases were selected. The consolidated sample consisted of 24,835 participants. The methodological quality of the selected studies was assessed using the Newcastle–Ottawa scale (NOS). A predominantly positive association was found between high levels of SRL and academic performance (GPA) (with correlation coefficients ranging from r = 0.11 to r = 0.55 in the primary studies). Furthermore, evidence from standardized self-report questionnaires in the reviewed literature indicates that several studies report female students showed higher levels of organization and planning, but these findings were not consistently observed across all studies. SRL acts as a key protective factor against stress, anxiety, and academic burnout. However, a “stagnation paradox” was identified: SRL skills do not always evolve linearly, often showing regression or stagnation in advanced clinical years due to the high cognitive load and insufficient support structure in those environments. Regarding sociodemographic variables, female students reported higher levels of planning and responsibility. SRL does not develop spontaneously with academic progress. Therefore, higher-education institutions must implement systematic and intentional pedagogical strategies from the early years of training to foster student well-being and the development of resilient professionals. Full article

Background/Objectives: Mandarin orange peel (MOP) is rich in bioactive polymethoxyflavones, including hesperidin and nobiletin, which have shown neuroprotective effects in rodent models. However, comprehensive safety data in dogs are required to support its development as a therapeutic intervention for canine cognitive dysfunction syndrome. In this study, the safety profile of a standardized MOP formulation was evaluated in four healthy Beagle dogs. Methods: Initially, compositional analysis was performed, and 202 pesticide residues and psoralens were screened to ensure compliance with Japanese pet food safety standards. Subsequently, a dose-escalation study was conducted in which dogs received oral MOP at 2, 6, and 10 g/head/day for 3–4 weeks at each dose level. Clinical signs, hematology, and serum biochemistry were monitored throughout the study period. Results: The MOP powder composition and residue levels remained within regulatory safety limits. In the dose-escalation study, no significant dose-dependent abnormalities were observed in physical or clinicopathological parameters. One dog exhibited transient loose stools at higher doses and a temporary elevation in alkaline phosphatase levels at 2 g/head/day; however, these symptoms resolved spontaneously despite continued administration. Conclusions: MOP was safe and well tolerated in dogs even at 10 g/head/day (787–952 mg/kg/day), which is approximately five times the anticipated clinical dose. The observed fluctuations in active ingredient concentrations remained within the acceptable range for natural products and did not affect overall safety. Combined with comprehensive screening for residues, these results indicate that MOP is a high-quality and safe dietary intervention for older dogs. Full article

Autoantibodies (AAbs) play an important role in the development of autoimmune diseases. While many AAbs induce apoptosis of target cells, a distinct subgroup, termed functional autoantibodies (fAAbs) against G protein–coupled receptors (GPCRs), can modulate physiological receptor signaling without inducing cell death. The functional activity of GPCR-fAAbs may be influenced by various cofactors, including inflammation (e.g., inflammatory cytokine, ciliary neurotrophic factor (CNTF)) and ischemia. As ischemia triggers a substantial release of arachidonic acid (AA) from membrane phospholipids, the present study aimed to examine exploratively the influence of AA, eicosapentaenoic acid (EPA), and CNTF on the responses of spontaneously beating neonatal rat cardiomyocytes to GPCR agonists and GPCR-fAAbs. AA and EPA differentially influenced responses in cardiomyocytes induced by GPCR-fAAbs: AA altered the functional responses associated with adrenergic β₂-fAAb, adrenergic α₁-fAAb, angiotensin II (AT1)-fAAb, endothelin A (ETA)-fAAb and angiotensin 1–7 MAS-fAAbs. However, muscarinergic M₂-fAAb responses remained largely unaffected. In contrast, EPA attenuated the responses to β₂-fAAb, α₁-fAAb, AT1-fAAb, and ETA-fAAb, while MAS-fAAb and M₂-fAAb responses were not markedly altered. CNTF acted as a time-dependent modulator of cardiomyocyte chronotropic responses and influenced the magnitude of GPCR-mediated signaling on a cardiomyocyte bioassay. Together, these findings might suggest that lipid mediators such as AA and EPA or CNTF may modulate functional responses of cardiomyocytes associated with GPCR-fAAbs. Full article

Background/Objectives: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is linked to poorer overall survival and a higher risk of brain metastases compared to HER2-negative breast cancer. Current preclinical studies lack robust HER2+ metastatic syngeneic mouse models for investigating targeted and immunomodulatory therapies. This study aims to develop effective HER2+ mouse models to investigate response dynamics to HER2-targeted therapy and immunotherapy. Methods: The human HER2 gene (WT or mutant p.A775_G776insYVMA, GFP-tagged at the C-terminus) was introduced into triple-negative breast cancer (TNBC) mouse mammary carcinoma cells with known metastatic potential (4T1 and EO771) via lentiviral transduction. HER2 expression and phosphorylation were analyzed using Western blotting and immunohistochemistry. Tumors were treated with HER2-targeted therapy (trastuzumab and tucatinib), immune checkpoint blockade (anti-PD-1 and anti-CTLA-4), and anti-HER2 antibody–drug conjugate (ADC) to evaluate treatment efficacy. Metastatic potential was assessed with brain fluorescence imaging. Statistical analysis included ANOVA and Kaplan–Meier tests. Results: Newly established lines demonstrated expression of HER2+, with HER2^YVMA lines showing higher phosphorylation than HER2^WT lines. Cells were tumorigenic, demonstrating in vivo tumor take rates at 100% for 4T1-HER2 and 15–30% for EO771-HER2. HER2 overexpression led to a 30% increase in spontaneous brain metastasis in the 4T1-HER2 models. Trastuzumab alone did not reduce primary tumor size but significantly reduced brain GFP signal by 17% ± 8% and 26% ± 7% in the 4T1-HER2^WT and 4T1-HER2^YVMA models, respectively. Combinational therapies with anti-HER2 therapy and immune checkpoint blockade effectively suppressed primary tumor growth and prolonged survival in EO771-HER2^YVMA model. T-Dxd, but not T-DM1, demonstrated partial treatment response in the EO771-HER2^WT model. Conclusions: HER2+ syngeneic tumor models were developed that spontaneously metastasize to the brain and demonstrate variable responses to immunotherapies and ADCs. These models are valuable for advancing molecular imaging modalities for HER2+ brain metastasis, studying blood–brain barrier penetration of HER2-targeted drugs, and exploring the combination of therapies, including immunotherapy. Full article

The human cerebral cortex is organized into distinct area-specific regions along the rostral–caudal axis, yet current human brain organoid models incompletely recapitulate this regional diversity. Here, we establish an area-specific brain organoid platform by leveraging transcription factors (TFs) identified through re-analysis of in vivo human cortical transcriptomic datasets. Publicly available single-cell RNA sequencing datasets from human developing cortex were re-analyzed to identify differentially expressed genes associated with rostral and caudal cortical identities. From this analysis, we identified SP9 (rostral-enriched) and DMRTA2 (caudal-enriched) as candidate TFs governing regional specification. To model cortical area identity, these TFs were overexpressed in an inducible manner during human cerebral organoid (hCO) generation. Overexpression of SP9 resulted in hCOs exhibiting rostral cortical characteristics, whereas DMRTA2 overexpression promoted caudal cortical features. The resulting hCOs showed distinct regional identities, reflected by differential expression of area-specific markers. In addition, these regional identities were accompanied by distinct functional phenotypes, as calcium imaging revealed divergent patterns of spontaneous neural activity between rostral and caudal hCOs. Altogether, our findings demonstrate that overexpression of TFs enables the controlled generation of area-specific hCOs. This approach provides a scalable and reproducible platform for studying human cortical regionalization and offers a framework for investigating region-specific mechanisms underlying neurodevelopmental and neurological disorders. Full article

Inflammation is widely viewed as a driver of hepatocellular carcinoma (HCC), yet inflammatory signaling also reshapes hepatic xenobiotic metabolism. Here, we established transgenic (Tg) IKKβ^Δhep mice (Tg-IKKβ^Δhep), which combine hepatocyte-specific IKKβ deletion with liver expression of a nuclear, kinase-inactive IKKβ mutant (NLS-IKKβKN). Tg-IKKβ^Δhep mice developed spontaneous chronic hepatitis and progressive fibrosis but were strikingly resistant to diethylnitrosamine (DEN)-induced hepatocarcinogenesis, with markedly reduced tumor multiplicity and total tumor burden. Despite persistent inflammatory injury, DEN-triggered oxidative DNA damage and p53 activation were markedly attenuated, compatible with reduced tumor initiation. Transcriptomic and biochemical analyses revealed broad repression of xenobiotic-metabolizing cytochrome P450 genes, including the pericentral enzyme CYP2E1, accompanied by reduced CYP2E1 protein abundance. This was associated with impaired HNF4α–PXR–CAR transcriptional output and reduced HNF4α occupancy at target promoters. Acute TNFα or IL-1β exposure recapitulated this repression, in part through reduced PGC-1α expression and decreased RNA polymerase II recruitment to target promoters. In parallel, pericentral xenobiotic metabolism was blunted, a change that could plausibly diminish DEN bioactivation and genotoxic stress. Together, these findings support a “metabolic gatekeeping” model in which chronic inflammation can constrain chemical hepatocarcinogenesis by attenuating carcinogen-metabolizing capacity. Full article

The origin of life is, to the best of our knowledge, impossible to imagine without the formation of complex prebiotic biomolecules such as RNA, DNA, proteins and lipids. Lipids play a crucial role in the spontaneous formation of cell membranes, which are responsible for cell integrity, compartmentalization, selective permeability, and providing a microenvironment for biochemical reactions. The goal of the current work is to summarize the current state of the art regarding the abiotic formation of membrane building blocks, such as glycerol, fatty acids, and their phosphorylated version as phospholipid precursors. We describe the necessity of a systems chemistry approach for the complexification and expansion of the prebiotic network, enabling the formation of several membranogenic precursors. We also discuss prebiotic pathways for phosphorylation and acylation that could lead to phospholipid availability in hydrothermal environments and on the early Earth surface. We conclude with the possible spontaneous vesiculation of these molecules as a primitive version of the cell membrane. Thus, we present a comprehensive perspective on prebiotic vesicle formation, starting from simple molecules and developing until the self-assembly of vesicles. Full article

Textile wastewater pollution is a global issue that requires attention due to its potential negative environmental impacts. Therefore, in the present investigation, Inga feuilleei seed (IFS) powder was used as a potential adsorbent of Direct Red 80 (DR80) dye in synthetic water. The results showed that the highest removal efficiency was achieved at pH = 2 and an IFS powder particle size of 150 μm. ART-FTIR analysis of IFS dust showed the presence of -OH, C=C, and C-H groups. The kinetic study revealed a better fit of the experimental adsorption data to the pseudo-second-order kinetics, suggesting that the mechanism governing the adsorption process is chemisorption. The maximum adsorption capacity of DR80 on IFS powder was 133.11, 146.78, 152.78, and 183.51 mg/g at 20, 30, 40, and 50 °C, respectively. According to the thermodynamic study, the process is endothermic and spontaneous. Finally, the use of IFS powder is a cost-effective alternative since the project approach for the development of the production process of this adsorbent is feasible and profitable. In conclusion, IFS powder is a cost-effective adsorbent for removing DR80 in water, and the process could be scaled up in removal studies on textile wastewater. Full article

To address the challenges of rapid water loss and insufficient long-term inhibition efficiency of conventional inhibitors in the high-temperature environments of deep goafs, a novel, environmentally friendly Deep Eutectic Inhibitor (DEI) was synthesized. This DEI utilizes citric acid (Ca) and proline (Pr) as the hydrogen bond donor and acceptor, respectively, with ascorbic acid (VC) and propyl gallate (PG) serving as antioxidants. A moisture retention evaluation model based on Fick’s law of diffusion was established to systematically investigate the liquid-domain stability of the DEI across a temperature range of 30 °C to 120 °C. The results demonstrate that the DEI exhibits superior moisture retention capabilities under high-temperature conditions, with the relative moisture retention peaking in the 80–110 °C range. Mechanistically, the formation of a robust hydrogen bond network effectively counteracts moisture evaporation driven by thermal kinetic energy. Furthermore, the DEI demonstrated significant inhibition effects on four coal samples with varying degrees of metamorphism. Tests on oxidative heat release characteristics revealed that DEI treatment delayed the initial oxidation temperature of the coal. Kinetic analysis further indicated that during the critical oxidation stage (200–300 °C), the apparent activation energy of the treated coal samples increased by 10.28–18.9 kJ/mol, effectively suppressing the spontaneous combustion process. This study contributes to the development of high-efficiency and eco-friendly fire prevention materials for coal mines. Full article

Reverse osmosis concentrate (ROC) contains relatively high levels of refractory organic pollutants, posing significant challenges due to its difficult treatment and high environmental risks. Therefore, efficient and convenient removal strategies are essential. In this study, a self-developed iron-modified activated carbon fiber (Fe-ACF) was employed as an adsorbent to remove organic pollutants from ROC. Additionally, response surface methodology (RSM) was applied to model the adsorption process, identify and evaluate key influencing parameters, and optimize operational conditions. The adsorption mechanisms and regeneration stability of Fe-ACF were also investigated. Kinetic analysis revealed that the adsorption process is predominantly governed by chemisorption, with intraparticle diffusion identified as the primary rate-limiting step. Isothermal adsorption studies demonstrated that the Langmuir–Freundlich model best describes the adsorption behavior, yielding a theoretical maximum adsorption capacity of 12.21 ± 0.80 mg/g. Thermodynamic analysis confirmed that the adsorption process is spontaneous, endothermic, and driven by an increase in entropy. The RSM optimization identified pH as the dominant factor. The optimal adsorption conditions were a pH of 4.18, a temperature of 34.63 °C, a stirring speed of 547.91 rpm, and an adsorbent dosage of 1.55 g/L. The adsorption mechanism involves hydrogen bonding, π–π interactions, surface complexation, and electrostatic forces. Fe-ACF exhibits competitive regeneration stability and structural integrity. In summary, Fe-ACF demonstrates significant potential as a treatment material for ROC. Full article

Pregnancy (HP), defined as the coexistence of intrauterine and ectopic gestations, is a rare condition, especially in spontaneous conception, but it is a life-threatening obstetric emergency when rupture occurs, with a reported maternal mortality rate of 0.03%. Diagnosis is often delayed because confirmation of an intrauterine pregnancy can mask clinical signs of a concurrent ectopic gestation. Early recognition and prompt surgical intervention are therefore critical to maternal safety and preservation of intrauterine viability. This case highlights the diagnostic challenges and successful management of a spontaneous ruptured heterotopic pregnancy. Case presentation: A 34-year-old Middle Eastern woman, gravida 4, with a spontaneous conception, presented with sudden severe lower abdominal pain and signs of acute hemoperitoneum (hypotension, tachycardia, and marked peritoneal signs). Transvaginal ultrasound demonstrated a viable intrauterine pregnancy at 9 weeks 4 days gestation, together with a ruptured left tubal ectopic pregnancy of similar gestational age. The patient underwent urgent laparoscopic left salpingectomy with evacuation of approximately 1200 mL of intraperitoneal blood and clots. Postoperatively, she developed significant anemia (hemoglobin drop from 11.2 g/dL on admission to 6.5 g/dL) requiring transfusion of four units of packed red blood cells. Serial ultrasonographic follow-up confirmed ongoing viability of the intrauterine pregnancy, which ultimately resulted in a live birth at term. Progressive resolution of the postoperative pelvic hematoma was also noted. Conclusions: Ruptured heterotopic pregnancy remains a diagnostic and therapeutic challenge. This case, along with a synthesis of the contemporary literature, demonstrates that a high clinical index of suspicion, timely ultrasound diagnosis, and immediate minimally invasive surgical management are paramount. Furthermore, rigorous postoperative monitoring and resuscitation, including targeted transfusion, are essential to achieve maternal stabilization while allowing continuation of a viable intrauterine pregnancy, with reported live birth rates exceeding 70% following timely intervention. Full article

Background/Objectives: Kidney transplantation is the standard of care for the majority of patients with end-stage kidney disease. Neurological complications are common, and among them, tremor is very frequent and usually attributed to immunosuppressive drug toxicity. Methods: In this retrospective study, we investigate the incidence and characteristics of tremor in kidney transplant patients and analyze its occurrence with respect to a multitude of demographic and clinical parameters, thereby aiming to confirm the role of calcineurin inhibitor-induced neurotoxicity and to identify other putative predictive factors. Furthermore, we characterize post-transplant tremor with the goal of identifying its clinical features and determining the impact on quality of life. Results: A total of 129 kidney transplant recipients were screened; six patients were excluded due to a history of movement disorders prior to kidney transplantation. In total, 123 patients were included in the final analysis—69 male (56%) and 54 female patients (44%), with a median age of 50. A total of 36% (46 patients) developed tremor in the post-transplant period. Using both univariable and multivariable analyses, we found that female sex and tacrolimus use were independently associated with the development of post-transplant tremor. In addition, multivariable analysis identified an association between younger age and post-transplant tremor. Furthermore, we observed a trend in the duration of symptoms in relation to the calcineurin inhibitor choice. Conclusions: Despite a relatively high prevalence (36%), post-transplant tremor does not significantly impact the QoL and spontaneously resolves within 1 year in adult kidney transplant recipients. Female sex and tacrolimus were identified as independent predictors of post-transplant tremor in renal transplant recipients. Full article

Endoscopic retrograde cholangiopancreatography (ERCP) is the cornerstone in the management of choledocholithiasis. Despite continuous advancements in technique and safety, ERCP carries a risk of significant complications, underscoring the importance of avoiding unnecessary procedures. The principal contributor to potentially avoidable ERCPs in patients with known choledocholithiasis is the spontaneous passage of common bile duct stones. Small stone size and a long interval between diagnosis and the procedure have increasingly been found to favor this event. Moreover, despite the development of well-defined risk stratification scores for patients with suspected choledocholithiasis, the incidence of negative ERCPs within this patient population remains considerable, even when a high suspicion of choledocholithiasis is evident. This review summarizes current evidence on the incidence and predictors of avoidable ERCPs in these contexts, with particular emphasis on spontaneous stone passage. It also discusses the role of endoscopic ultrasound (EUS) as a diagnostic tool to reduce unnecessary procedures when initial imaging fails to confirm the presence of stones despite persistent high clinical suspicion. By integrating and critically appraising recent findings, we provide practical guidance for clinicians on decision-making regarding ERCP, particularly in situations where spontaneous stone passage is likely or imaging results are inconclusive. Full article

The wine ecosystem constitutes a highly selective ecological niche characterized by low pH, high ethanol levels, sulfur dioxide, polyphenols, and nutrient limitation. During malolactic fermentation, this environment becomes dominated by specialized lactic acid bacteria (LAB), particularly Lactiplantibacillus plantarum and Oenococcus oeni, whose persistence under such stressors suggests the presence of adaptive traits relevant to probiotic development. In this study, twenty-three LAB isolates obtained from the spontaneous wine ecosystem were systematically evaluated through a multi-stage screening strategy. Primary single-factor assays revealed pronounced inter- and intraspecies variability in tolerance to acid, lysozyme, and bile salts. As a result, all O. oeni isolates and eight L. plantarum strains were excluded from further consideration. The four selected L. plantarum isolates (M-1, SY-2, XJA2, and XJ14) were subsequently subjected to simulated gastrointestinal challenges. Strains M-1 and XJ14 maintained high viability across both gastric and intestinal phases. In contrast, SY-2 and XJA2 exhibited pronounced gastric sensitivity but demonstrated strong survival in the intestinal phase. Functional characterization further distinguished the isolates: M-1 and XJ14 displayed balanced probiotic profiles, whereas XJA2 exhibited exceptional auto-aggregation and efficient metabolic capacity, suggesting specific colonization potential despite its gastric vulnerability. Comprehensive safety assessments confirmed the absence of hemolytic activity, biogenic amine production, and acquired antibiotic resistance in the tested isolates. Collectively, these findings identify M-1 and XJ14 as promising candidates for direct probiotic application, and XJA2 as a promising functional strain for encapsulation-based delivery. This study highlights the wine ecosystem as a valuable reservoir for novel probiotic development. Full article

Enrofloxacin (ENR), as a widely used antimicrobial agent in aquaculture, poses potential risks to ecosystems and human health due to its environmental persistence. Therefore, it is of great significance to explore efficient methods for removing ENR from aquaculture wastewater. In this study, a series of shrimp shell-derived aerogel (MBC300–MBC700) were fabricated from Litopenaeus vannamei shells through chemical modification followed by pyrolysis at 300–700 °C, and their adsorption performance and mechanisms toward ENR were systematically investigated. The modified porous materials exhibited a well-developed micro–mesoporous structure, high specific surface area, and abundant surface functional groups. Meanwhile, MBC400 demonstrated the highest adsorption capacity for ENR, reaching 14.56 mg/g, with a corresponding specific surface area of 77.71 m²/g. The adsorption kinetics followed the pseudo-second-order model, and the isothermal data were better fitted by the Freundlich model, indicating a chemisorption-dominated, heterogeneous multilayer adsorption process. Thermodynamic analysis revealed that the adsorption was spontaneous (ΔG < 0) and endothermic (ΔH > 0). In regeneration experiments, 30% ethanol solution achieved the best desorption efficiency for MBC400, with adsorption efficiency remaining above 75% after three cycles. Based on the characterization and adsorption results, adsorption mechanism of ENR on MBC400 was elucidated as a synergistic effect of hydrogen bonding, π–π stacking, electrostatic interaction, and surface complexation. This study provides a novel strategy and theoretical basis for the high-value utilization of shrimp shell waste and for the efficient removal of fluoroquinolone antibiotics from aquaculture effluents. Full article