Search Results (193)

Addressing climate change necessitates coordinated efforts across multiple sectors, with agriculture representing a significant source of greenhouse gas (GHG) emissions. This requires sophisticated mitigation strategies at the farm level. Digital decision support tools (DSTs) tailored for this purpose play a crucial role in accelerating farm-level decarbonization. Ensuring the reliability and accuracy of these DSTs mandates thorough model robustness validation. This study validates a farm-level GHG accounting and decarbonization DST using Sobol and Morris global sensitivity analyses to evaluate output robustness and to identify key input parameters critical for reliable mitigation planning. Both sensitivity analysis methods provide a comprehensive assessment of the tool’s robustness and highlight parameters most influencing farm-level GHG emission outcomes. Results show consistent outcomes across sensitivity approaches, reinforcing confidence in the tool’s application for emission reduction planning. The sensitivity analysis results indicate that the tool delivers reliable outcomes across various sensitivity analysis methods, thereby enhancing confidence in its suitability for decarbonization planning. Furthermore, the findings of this study provide a methodological foundation for future advancements and expanded use within the agriculture sector. This supports the DST’s effectiveness in prioritizing mitigation strategies and planning emission reduction pathways at the farm scale, while providing a transparent template to guide future tool improvements and broader agricultural applications. Full article

Background/Objectives: Unpredictable chronic mild stress exposure is a primary driver of cognitive decline, largely mediated by hypothalamic–pituitary–adrenal (HPA) axis dysregulation and subsequent oxidative neurotoxicity. In traditional Thai medicine, the AYW-KK-04 formulation—a complex polyherbal remedy—has long been utilized as a “Ya Aayu-Wattana” to restore vitality and elemental balance, yet its neurobiological mechanisms remain poorly understood. This study aimed to evaluate the adaptogenic and neuroprotective potential of AYW-KK-04 against cognitive impairment. Methods: Unpredictable Chronic Mild Stress (UCMS)-induced cognitive impairment in a ICR mouse model. Total phenolic and flavonoid contents and antioxidant capacity (ABTS assay) of AYW-KK-04 were determined. Behavioral assessments using Y-maze test, novel object recognition test (NORT), and Morris Water Maze (MWM) test. BDNF, CREB, Nrf and Keap1 mRNA gene expression, SOD and CAT enzymatic activity and lipid peroxidation assay were investigated to clarify the mechanisms of action. Moreover, HPLC chromatography was studied to quantify the active compounds of the AYW-KK-04 formulation. Results: It demonstrated that oral administration of AYW-KK-04 significantly reversed UCMS-induced memory deficits. At the molecular level, AYW-KK-04 effectively upregulated BDNF and CREB mRNA expression in the frontal cortex and hippocampus, suggesting a restoration of synaptic plasticity. Simultaneously, the formulation activated the Nrf2/Keap1 signaling pathway, leading to enhanced SOD and CAT enzymatic activities and a marked reduction in MDA-mediated lipid peroxidation. HPLC analysis confirmed the presence and consistency of key bioactive constituents. Conclusions: These findings suggest that the adaptogenic properties of AYW-KK-04 arise from its dual capacity to reinforce neurotrophic support and bolster the endogenous antioxidant shield, providing a mechanistic support for the traditional use of AYW-KK-04 as an adaptogenic formulation and highlighting its potential as a multi-target intervention for stress-related cognitive dysfunction. Full article

Background: After imipenem was introduced in clinical practice, neurologic adverse effects led to recommendations against its use in patients with neurologic conditions. However, these conclusions were drawn without considering pharmacokinetic variations in such patients. Furthermore, animal studies lack the use of clinically relevant doses and supporting morphological studies in both naïve and disease models. Objectives: We aim to study the effects of imipenem in the hippocampus of naïve animals, evaluating potential behavioral and morphological alterations. Methods: Naïve Wistar rats received a 10-day course of intraperitoneal imipenem (40 mg/kg) while controls received a saline injection. After that, they were put through the Morris water maze, elevated plus maze, open-field test, and then euthanized. We analyzed neurogenesis (using doublecortin immunoreactivity), astrogliosis, and the γ-Aminobutyric acid (GABA)ergic system (using parvalbumin (PV), calretinin (CR) and calbindin (CB) immunoreactive (IR) neurons) in the hippocampus. Results: Interestingly, our results showed no significant alterations in both short and long-term memory, nor in anxiety. There were also no significant changes in the neuronal density of doublecortin-immunoreactive (IR) neurons nor in astrogliosis. Furthermore, the areal density of PV- and CR-IR was preserved in all hippocampal subfields. The density of CB-IR neurons also showed no changes in the dentate gyrus, CA3, and subiculum; however, a significant increase was found in the CA1 region. Conclusions: Our results indicate that in naïve individuals, a clinically relevant dose of imipenem does not seem to cause overt behavioral deficits or widespread morphological alterations in the hippocampus. However, a specific increase in the CB-IR neuronal population in the CA1 region highlights a localized cellular alteration/plasticity induced by the imipenem. Hence, pharmacokinetic factors seem to be the potential contributors of imipenem side effects. Further studies should focus on this as a possible cause and focus on individuals with brain diseases. Full article

Social factors profoundly shape the bereavement process for individuals who have lost someone to a drug-related death. In this study, we integrate qualitative (n = 19), quantitative (n = 5), and mixed-methods (n = 2) results from a large research project on drug-related bereavement and utilise Bronfenbrenner and Morris’s bioecological model as an analytical framework. The results of the project demonstrate that bereavement following a drug-related death is deeply rooted in social context, and they highlight that the process of grieving a drug-related death requires the navigation of complex personal, familial, and societal challenges. Sociocultural understandings of addiction and societal stigma must be addressed to create a more supportive environment for bereaved individuals. A more cohesive and responsive support system can be developed by understanding and acting at all levels of Bronfenbrenner and Morris’s model, encompassing individual competencies, organisational structures, broader social environments, and systemic policies. Focusing on a family and compassionate community approach, our research promotes an inclusive and empathetic societal response to these multifaceted losses. Furthermore, the importance of enhanced professional competencies, interdisciplinary collaboration, and the implementation of organisational change is emphasised in order to meet the needs of those affected by a drug-related death. Ultimately, social work can play a pivotal role in this context. Full article

Background/Objectives: The effect of proanthocyanidins (PAs) on neuroinflammation through the modulation of colonic microflora and their metabolites was investigated in obese mice fed a high-fat diet (HFD). Methods: Thirty healthy male C57BL/6J mice of similar body weight were randomly divided into control (CON), high-fat diet (HFD), and proanthocyanidin (PA_HFD) groups. HFD and PA_HFD groups were fed an HFD, whereas the CON group was fed a basic diet for 8 weeks. Subsequently, the CON and HFD groups were administered equal doses of saline, and the PA_HFD group was administered PA (100 mg/kg/day) daily. We evaluated microbial changes through gut microbiota richness and probiotic relative abundance, analyzed metabolite variations via non-targeted metabolomics and pathway enrichment, assessed neuroinflammation via related gene expression, and measured cognitive function using platform crossing frequency and target quadrant time in the Morris water maze, where longer duration and more crossings indicate better cognition. Results: Body weight was significantly lower in the PA_HFD group than in the HFD group. In the PA_HFD group, fewer inflammatory and hepatic fat cells were observed, and hepatocellular edema was alleviated. PA significantly decreased total cholesterol, low-density lipoprotein, IL-1β, TNF-α, lipopolysaccharide, and Lc3 expression and increased Sirt1 and FGF21 expression in hippocampal tissue (p < 0.01). PA significantly altered the abundance of colonic microbiota (p < 0.01), including phyla Patescibacteria and Bacteroidota and genera Lactobacillus and Akkermansia. KEGG analysis revealed that differences in metabolite profiles between CON and HFD groups were reflected in glycerophospholipid metabolism, while those between HFD and PA_HFD groups were in steroid hormone biosynthesis and tryptophan metabolism. Metabolomic analysis demonstrated that changes in metabolites and microbiota were significantly correlated with neuroinflammation. Conclusions: In conclusion, PAs play a role in modulating neuroinflammation, colonic microflora, and colonic metabolites in mice and have a mitigating effect on cognitive decline in HFD-induced obese mice. Full article

Background: The incidence of dementia, especially Alzheimer’s disease (AD), is rising, with over 55 million affected globally. Therefore, this disease, for which there is no adequate treatment, is more frequent and prevalent in women. Royal jelly, a bee secretion, is known for its health benefits and contains proteins, carbohydrates, lipids, minerals, polyphenols, enzymes, and B vitamins, as well as anti-inflammatory and antioxidant properties relevant to AD. Thus, we aimed to investigate the chemical compounds in royal jelly extract and their effect on neurobehavioral changes in an AD female model. Methods: In vitro studies were used to investigate the chemical and physicochemical properties of the royal jelly extract. In vivo studies, we divided female mice into five groups (n = 25): Control (C), Alzheimer (ALZ), ALZ standard (ALZ-STD, rivastigmine 1 mg/Kg), ALZ-D1 (royal jelly 150 mg/kg), and ALZ-D2 (royal jelly 300 mg/kg). The mice received the treatments orally at 45 days. We induced the AD model by orally administering aluminum chloride at 100 mg/kg and intraperitoneally injecting D-galactose at 120 mg/kg for 45 consecutive days, after which we subjected the animals to the radial arm maze, Morris water maze, elevated plus maze, and forced swim tests. Results: Analyses showed moderate acidity and a rich bioactive profile, with flavonoids being more prevalent. Antioxidant activity tests indicated moderate efficacy, while FTIR-ATR analysis revealed the chemical complexity of royal jelly. The royal jelly extract used in the study did not induce toxicity in vivo. Notably, royal jelly improved cognitive deficits, neurodegeneration, and reduced anxiety in AD. Conclusions: The study suggests that royal jelly extract has promising neuroprotective properties and could be a viable natural therapeutic option for AD. Full article

Background: Alzheimer’s disease (AD) features progressive cognitive decline and amyloid-beta (Aβ) accumulation. Insulin resistance in type 2 diabetes mellitus (T2DM) is increasingly recognised as a mechanistic link between metabolic dysfunction and neurodegeneration. Although sodium–glucose cotransporter-2 inhibitors (SGLT2is) have established glycaemic and cardioprotective benefits, their neuroprotective role remains less well defined. Objectives: This systematic review examines animal studies on the neuroprotective effects of SGLT2i in T2DM and AD models. Methods: A literature search was conducted across the Web of Science, Scopus, and PubMed databases, covering January 2014 to November 2024. Heterogeneity was assessed with I², and data were pooled using fixed-effects models, reported as standardised mean differences with 95% confidence intervals. We focus on spatial memory performance as measured by the Morris Water Maze (MWM) test, including escape latency and time spent in the target quadrant, as the primary endpoints. The secondary endpoints of Aβ accumulation, oxidative stress, and inflammatory markers were also analysed and summarised. Results: Twelve studies met the inclusion criteria for this review. A meta-analysis showed that SGLT2i treatment significantly improved spatial memory by reducing the escape latency in both T2DM and AD models. In addition, SGLT2i yielded a significant improvement in spatial memory, as indicated by an increased target quadrant time for both T2DM and AD. Furthermore, SGLT2i reduced Aβ accumulation in the hippocampus and cortex, which met the secondary endpoint; the treatment also lessened oxidative stress and inflammatory markers in animal brains. Conclusions: Our findings indicate that SGLT2is confer consistent neuroprotective benefits in experimental T2DM and AD models. Full article

River ice is a common natural phenomenon in cold regions during winter, and it is also one of the key factors that must be considered in the development and utilization of water resources in these areas. In this paper, based on a two-dimensional hydrodynamic model and ice dynamics model coupled with a linear thermodynamic process, this study simulates and validates the formation, decay, transport, and accumulation of river ice at the Toudaoguai reach of the Yellow River in Inner Mongolia during the winters of 2019–2020 and 2020–2021. The influence of different parameters on backwater level variations caused by ice jams is further investigated using a modified Morris sensitivity analysis method. The results show that (1) the coupled thermal-dynamic model can accurately simulate the formation, transport, and accumulation process of river ice in natural river, as well as the freeze-up patterns and corresponding hydraulic characteristics. (2) Due to the influence of river topography, flow rate, and flow density, the freeze-up form is slightly different in different years, and the low discharge process favor a more stable freeze-up. (3) According to the modified Morris screening method, discharge (Q) and ice concentration (N) are the most sensitive to the change in the backwater water level after the ice jam, and the sensitivity is more than 50%. The next most sensitive factor is the ice-cover roughness (n_i), whereas ice porosity (e_f) exhibits a negative sensitivity to the water level after ice jam. Thus, this study provides effective tools to reproduce the process of river ice transport and accumulation in the reach of the Yellow River (Inner Mongolia section) and offers technical support and insights for ice-flood prevention and mitigation in this section. Full article

STEM education increasingly relies on technology-enhanced environments that utilize data-driven strategies, digital tools, and adaptable learning models. To support the evaluation of contemporary STEM teaching methods, this study proposes a multi-criteria analytical framework based on expert assessment. Semi-structured interviews were conducted with 41 experienced teachers from Bulgarian schools (N = 41), who evaluated six key indicators (m = 6) of STEM integration: Effectiveness, Engagement, Applicability, Flexibility, Validity, and Accessibility. The qualitative data were transformed into numerical values and analyzed using the Target Parameter Ranking method. The degree of expert agreement was assessed through the Morris–Kendall coefficient, yielding a statistically significant moderate agreement (w_k = 0.137; χ² = 28.085, df = 5, p = 3.50 × 10⁻⁵ (p < 0.001)). The results indicate that Engagement (W_j = 0.206), Flexibility (W_j = 0.188), and Effectiveness (W_j = 0.186) are the most highly weighted criteria, reflecting teachers’ prioritization of active participation, learning outcomes, and adaptability in technology-rich STEM environments. In comparison, Applicability and Accessibility show higher variability, highlighting their dependence on contextual factors such as infrastructure and resource availability. The proposed framework provides a structured, data-driven basis for evaluating and refining STEM teaching practices and can be integrated into educational decision-support systems. Full article

Background: Alzheimer’s disease (AD), a progressive brain disorder, is the most common form of dementia and necessitates the development of effective intervention strategies. Ginseng-Natto composite fermentation products (GN) have demonstrated beneficial bioactivities in mouse models of AD; however, the underlying mechanism of action through which GN ameliorates AD requires further elucidation. Methods: Mice received daily intragastric administration of low- or high-dose GN for 4 weeks, followed by intraperitoneal injection of scopolamine to induce the AD model. The pharmacological effects of GN were systematically evaluated using the Morris water maze test, ELISA, and H&E staining. To further investigate the underlying mechanisms, 16S rRNA gene sequencing and metabolomics were employed to analyze the regulatory effects of GN on the gut–brain axis. Additionally, Western blotting was performed to assess the impact of GN on blood–brain barrier (BBB) integrity. Results: GN intervention significantly ameliorated cognitive deficits and attenuated neuropathological injury in AD mice, restoring the brain levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) to normal ranges. GN reshaped the gut microbiota by promoting beneficial bacteria and inhibiting pro-inflammatory strains. It also regulated key metabolic pathways related to amino acid and unsaturated fatty acid metabolism. This metabolic remodeling restored the compromised BBB integrity by upregulating tight junction proteins (ZO-1, Occludin and Claudin-1). Conclusions: Our findings demonstrate that GN ameliorates AD through a gut-to-brain pathway, mediated by reshaping the microbiota-metabolite axis and repairing the BBB. Thus, GN may represent a promising intervention candidate for AD. Full article

Background/Objective: The purpose of this study was to determine whether the effects of pain education combined with physiotherapy could be explained by changes in psychological well-being and self-efficacy in individuals with chronic low back pain (LBP). Methods: This study includes a secondary analysis (mediation analysis) of a randomized controlled trial (RCT) that compares the effect of physiotherapy and pain education with physiotherapy alone. The Roland-Morris Disability Questionnaire, assessed at six weeks, was used as a primary outcome in this study, with pain intensity as a secondary outcome. The World Health Organization Five Well-Being Index (WHO-5) and the General Self-Efficacy Scale were evaluated as potential mediators. Causal mediation analysis based on a counterfactual framework was employed to estimate both direct and indirect effects. Results: The analyses comprised 46 participants (mean age = 42.2 years; 54.3% female) who received pain education along with physiotherapy. In the mediation models, improvements in emotional well-being (assessed by WHO-5) explained approximately one quarter of the effect of the intervention on disability (average causal mediation effect = −1.66, 95% CI [−2.8, −0.72], p < 0.001). By contrast, self-efficacy did not significantly mediate disability, and neither factor accounted for changes in pain intensity. Sensitivity analyses suggested that the indirect effect on psychological well-being was reasonably robust against potential unmeasured confounding factors. Conclusions: Enhancements in psychological well-being were associated with reductions in disability following pain education, whereas self-efficacy did not emerge as a significant mediator. These findings may support the value of incorporating mental well-being strategies within rehabilitation programs for chronic LBP. Full article

Background/Objectives: Postoperative cognitive dysfunction (POCD) is a serious complication of anaesthesia/surgery. The present study investigated the effects of nicardipine—a calcium channel blocker—on neuroinflammation and POCD in rats. Methods: Following ethical approval, 30 Wistar albino rats were divided into three groups: control (Group C), surgery (Group S), and surgery and nicardipine (a single intraperitoneal dose of 5 mg/kg nicardipine) (Group N). Cognitive function was assessed 48 h postoperatively using the MWM test. The rats were sacrificed on the 5th day, and hippocampi were isolated and frozen at −80 °C on the same d ay. Hippocampal tissues were homogenised; ELISA and Western blot tests were performed to assess IL-1, IL-6, TNF-α, and caspase-3. Results: All groups showed a significant decrease in the time required to locate the hidden platform from day 1 to day 4. In the probe trial of the Morris water maze test, Group C spent more time in the target quadrant compared with Group S, indicating surgery-related cognitive impairment. The ELISA and Western blot analyses demonstrated that the hippocampal levels of IL-1, IL-6, TNF-α, and caspase-3 were significantly elevated in both Groups S and N compared with the controls. No statistically significant differences were observed between Groups S and N, indicating that the measured cognitive performance and hippocampal inflammatory responses were comparable between these groups. Conclusions: This study showed that a single intraperitoneal dose of 5 mg/kg of nicardipine did not measurably improve early postoperative cognitive performance or reduce hippocampal inflammation. In particular, nicardipine did not have a detectable effect on early postoperative neuroinflammation or cognition at the tested dose and timing in this rat model. Further studies exploring different doses and timing or repeated administration would help to clarify its potential role. Full article

Background/Objectives: Adult spinal deformity (ASD) is increasingly prevalent due to an ageing population and is associated with significant pain, disability, and reduced quality of life. While surgery is often considered for severe deformities, many patients are either unsuitable for major corrective procedures or prefer conservative care. This narrative review synthesizes the current evidence on nonoperative management strategies for ASD. Methods: A literature search on the PubMed and Cochrane databases identified relevant studies published up to 25 October 2025. Medical Subject Headings and keywords related to nonsurgical ASD management were used. Eligible studies included nonsurgical series with a minimum of 12 months’ follow-up, while case reports were excluded. Results: Seven studies met our inclusion criteria: three on bracing, three on physiotherapy and combined physical and cognitive rehabilitation programmes, and one on transforaminal epidural steroid injections (ESIs). Bracing was effective in slowing the curve progression rate. One study showed that the progression rate decreased from 1.47°/year to 0.24° for degenerative scoliosis (p < 0.0001) and from 0.70°/year to 0.24° for idiopathic scoliosis (p = 0.03). Another study showed that there was no statistically significant difference in the Cobb angle or anticipated worsening when comparing the initial measurement with the final control after treatment (p = 0.973). Finally, a third study reported reduced back pain, with Roland–Morris scores improving from 3.3 to 2.0 (p < 0.001) at 18 months. Physiotherapy and multidisciplinary rehabilitation programmes appeared to be effective in significantly reducing pain and disability levels. One study found that Oswestry Disability Index (ODI) scores improved from 39.5 to 31.8 (p < 0.001), while back pain, measured using the Numeric Pain Rating Scale (NPRS), improved from 58.4 to 42.1 (p < 0.001), with 51% achieving minimal clinically important change (MCIC). Another study reported ODI reductions from 38 to 17.6 and pain scores from 6.5 to 2.2 (p < 0.001), while in a third study, the “Koshimagari Exercise” programme yielded MCIDs in the ODI for 42% of patients. Finally, ESIs provided significant pain relief for at least a month in over half of the patients with degenerative scoliosis and radiculopathy, with diminishing effects throughout the first 2 years. More specifically, 37.2% of patients had a successful outcome at one year post-injection and 27.3% at 2 years (p < 0.01). Conclusions: Our study suggests that bracing, physiotherapy, and multidisciplinary rehabilitation programmes, as well as ESIs, can serve as effective short term alternatives for patients with ASD who are either unsuitable for surgery or do not wish to pursue it. As such, this review provides valuable evidence-based insights that can guide clinicians in developing a treatment plan and lay the foundations for establishing a novel pathway for this specific subgroup of patients with ASD. Full article

Background/Objective: Alzheimer’s disease (AD) is a neurodegenerative condition characterized by oxidative stress, neuroinflammation, amyloidogenesis, and tau-related pathology. This study investigated the macronutrient and phytochemical composition of strawberry (S), lemon (L), and lemon juice-assisted strawberry (S/L) extracts and evaluated their neuroprotective efficacy relative to selenium (Se) in an aluminum chloride (AlCl₃)-induced rat model of AD. Methods: Macronutrients and phenolics were quantified in S, L, and S/L, and the extracts were profiled using high-performance liquid chromatography and electrospray ionization tandem mass-spectrometry. Male Sprague–Dawley rats received AlCl₃ with or without S, L, S/L, or Se, and their cognitive performance was assessed using the Morris water maze, Y-maze, and conditioned avoidance tests. Markers of oxidative status, inflammation, cholinergic function, apoptotic signaling, and Wnt3/β-catenin pathway activity were quantified in the brain tissue, and cortico-hippocampal morphology was examined. Results: The S/L extract showed the highest carbohydrate, protein, and lipid content. The total phenolic content was highest in S/L (60.46 mg gallic acid equivalents/g), followed by L (55.08) and S (44.75), with S/L also being the richest in gallic, ellagic, and chlorogenic acids. S/L attenuated AlCl₃-induced cognitive deficits, restored antioxidant status, suppressed neuroinflammation, improved cholinergic indices, modulated apoptotic signaling, and downregulated amyloidogenic and NLRP3 inflammasome markers, consistent with histological evidence of neuronal preservation. Conclusions: Lemon juice-assisted extraction enhanced the macronutrient and phenolic richness and multitarget neuroprotection of strawberries. S/L co-extracts represent promising functional food–derived adjuvants for AD management and support integrative compositional–mechanistic profiling to optimize natural product–based interventions. Full article

Background/Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder with a high incidence but limited agents. Herein, PZ-2891 was discovered as a novel anti-AD candidate. Both in vivo and in vitro pharmacodynamic (PD) studies and pharmacokinetic (PK) properties were investigated and illustrated in this research. Methods: A computer-generated random number table was used to divide mice into various groups randomly. Injecting Aβ into the mice hippocampus to mimic AD-like pathologies, neurobehavioral tests, including the Morris maze, Y maze, open field test (OFT) and novel object recognition (NOR), were operated to evaluate the cognitive improvement in PZ-2891. D-galactose (D-gal), okadaic acid (OA) and lipopolysaccharide (LPS) were employed to trigger neural injuries in vitro. A reliable analytic method was developed to profile PZ-2891’s PK properties in SD rats through a triple quadrupole liquid chromatography–mass spectrometry (LC–MS/MS) instrument. Results: PZ-2891 markedly alleviated cognitive impairment in the Aβ-induced model mice. It also protected nerve cells from oxidative stress and inflammatory injuries and significantly reduced AD-typical pathological biomarkers. The PK results showed that PZ-2891 was exposed rapidly in both plasma and brain, with a brain-to-blood ratio of around 0.59, C_max of around 454.50 ± 151.35 ng/mL, T_max of around 0.49 ± 0.15 h and oral bioavailability of around 19.74 ± 6.78%. Conclusions: These findings suggest that PZ-2891, an agonist of PANK2, is a novel and potential candidate agent for AD with excellent efficacy and PK properties. Full article