Search Results (1,883)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, which has recently been found to be closely associated with neuroinflammation. As an anti-inflammatory drug, triptolide (TP), a natural diterpenoid from Tripterygium wilfordii, was selected in the current study for treating PS19 (tau^P301S transgenic) mice, tauopathy AD mice. In addition, we have previously found that TP had the ability to reduce the level of cholesterol. However, the roles and mechanisms of TP in the above processes are not clear. To this end, we found that elevated cholesterol in serum and brain tissues upregulated the expression of apolipoprotein E (APOE) and sialic acid-binding Ig-like lectin 3 (CD33), leading to the activation of SH2-containing protein tyrosine phosphatase 1 (SHP-1). The activation of SHP-1 inhibits the signaling pathways of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6), which results in inhibition of the M2 polarization of microglia, which exacerbates neuroinflammation and cognitive decline in high-cholesterol diet (HCD)-fed mice. Conversely, TP treatment significantly inhibited the hepatic sterol regulatory element-binding protein 2 (SREBP2)/3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) pathway, which reduced the cholesterol levels in the serum and brain. By depressing the levels of cholesterol, the axis of CD33 and SHP-1 was suppressed, which resulted in restoration of the activity of JAK1 and STAT6 pathways, leading to the transition of microglia from the M1 to the M2 phenotype. Of note, these observations demonstrate that TP alleviates the cognitive impairment of PS19 mice via depressing neuroinflammation. Altogether, our results revealed the mechanisms of TP in treating AD via CD33/SHP-1/JAK1/STAT6 pathways in a cholesterol-dependent manner. Full article

This study aimed to investigate the regulatory effect and cryoprotective mechanism of melatonin (MT) on the physiological functions of Lactobacillus plantarum FQR during freezing and freeze-drying. Results indicated that the addition of 5 mg/mL MT as a cryoprotectant maximized the freeze-drying survival rate to 32.04 ± 2.14%. MT effectively alleviated low-temperature and freeze-drying stress by reducing extracellular alkaline phosphatase activity, enhancing intracellular lactate dehydrogenase activity, and decreasing extracellular β-galactosidase activity without significant differences. Higher survival rates in defining medium further suggested that MT reduced damage to cell wall and membrane structures during lyophilisation, decreased membrane permeability, and preserved cellular physiological functions. In addition, MT supported cellular energy metabolism and protein synthesis, enhanced transmembrane potential to facilitate ATP transport, and helped maintain intracellular and extracellular pH balance. The prepared freeze-drying protectant containing 69.80 mg/mL exopolysaccharides (EPS) and 4.25 mg/mL MT showed better protective effects than the control group. MT also increased bound water content, lowered the freezing point of the solution, and inhibited ice crystal formation. Transcriptomic analysis revealed that amino acid biosynthesis, amino acid metabolism, and ABC transport systems were the primary pathways affected by MT treatment. These findings demonstrate that MT improves freeze-drying tolerance by maintaining membrane integrity, regulating cellular metabolism, and enhancing oxidative stress resistance. Given its natural biosynthetic origin, generally recognized as safe (GRAS) status, and absence of residual solvents or allergenic proteins, MT can be safely considered for incorporation into food and nutraceutical products. This study underscores the practical relevance of MT as a functional component in compound cryoprotectants, providing a feasible strategy to enhance the viability, stability, and industrial applicability of Lactobacillus plantarum during freeze-drying and storage. Full article

Excessive glucocorticoids induced by stress trigger hepatic lipid metabolism disorder and oxidative stress in poultry, impairing growth performance and welfare. At the same time, resveratrol (RSV) has antioxidant and lipid-regulating properties, but the protective mechanisms in corticosterone (CORT)-challenged broilers remain unclear. This study investigated RSV’s effects on CORT-induced hepatic damage in AA broilers, with 240 one-day-old broilers randomized into three groups: control (basal diet), CORT (basal diet + 4 mg/kg BW CORT intraperitoneal injection), and RSV (400 mg/kg RSV-supplemented diet + CORT injection). Growth performance, hepatic redox status, serum biochemistry, liver histopathology, and gene/protein expression related to antioxidant/lipid metabolism were determined. The growth performance of AA broilers injected with CORT was significantly affected, showing reduced body weight gain (p < 0.05), increased abdominal fat content (p < 0.05), and hepatomegaly (p < 0.05). The addition of RSV in the diet significantly reduced abdominal fat accumulation and hepatomegaly (p < 0.05), improving the growth performance of broilers; Effects of RSV on liver function and lipid metabolism of CORT-treated AA broilers: After CORT injection, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity and total bile acid (TBA) content significantly increased (p < 0.05). Hepatic total cholesterol (TC) and triglycerides (TG) increased after CORT injection (p < 0.05), causing severe liver damage. RSV supplementation could reverse the increases in serum ALP, ALT, and AST activity (p < 0.05) and reduce TBA content in stressed broilers (p < 0.05). TC and TG levels in the liver decreased under the alleviation of RSV (p < 0.05), and serum TG levels declined (p < 0.05). Microscopic and ultrastructural observations showed that after CORT injection, hepatic tissue cells were swollen, scattered fat vacuoles were present, pores were enlarged, and intracellular lipid droplets appeared. The RSV group significantly alleviated hepatocyte damage, reduced vacuolation, showed uniform chromatin, and decreased lipid droplets. RSV significantly mitigated the CORT-induced increase in SREBP-1 mRNA and protein expression and the decrease in PPARα protein expression; CORT caused a decline in the antioxidant function of AA broiler livers, with significant decreases in SOD and GSH-PX (p < 0.05), and the expression of Nrf2 and its downstream genes also showed a decreasing trend. Compared to the CORT group, the RSV group exhibited significant increases in liver CAT, SOD, and GSH-PX (p < 0.05), and Nrf2 protein expression was elevated (p < 0.05). In summary, resveratrol can alleviate the decline in growth performance, liver steatosis, and hepatic oxidative stress in AA broilers induced by CORT, downregulate lipogenic genes such as SREBP-1c, regulate liver lipid metabolism, and mitigate CORT-induced hepatic oxidative stress in broilers by upregulating the Nrf2 pathway. Full article

Bone grafting remains limited, and the strategies to design even more structurally complex scaffolds—able to reproduce the hierarchical architecture of bone extracellular matrix—are rapidly growing. In this study, we report the fabrication of a hierarchically structured scaffold produced by layering poly(ε-caprolactone)/gelatin (PCL/Gt) or poly(lactic acid)/gelatin (PLA/Gt) electrospun nanofibers via coaxial electrospinning onto 3D-printed poly(lactic acid) (PLA) scaffolds via fused deposition modeling (FDM). After the printing process, PLA disks (10 × 1 mm, 20% infill, ~80% porosity, pore size ~1.57 mm) were coated with core/shell (PCL/Gt, PLA/Gt) fibers to investigate the in vitro interfacial response of osteoblasts in comparison with monocomponent fibrous coatings (PCL, PLA, Gt). SEM and TEM confirmed that core/shell fibers exhibited bead-free morphologies, with a significant reduction in fiber diameter (≈287–316 nm) and higher interfibrillar porosity compared to monocomponent fibers. FTIR and thermogravimetric analyses indicated the presence of hydrogen bonding between the polyester and gelatin, and the absence of residual solvent after deposition. At the same time, water contact angle measurements confirmed an increase in hydrophilic properties from 80–86° to 120° ascribable to the presence of gelatin. Accordingly, in vitro response of human fetal osteoblasts (hFOB 1.19) exhibited an evident improvement in the case of Gt-based fibrous coatings (i.e., PCL/Gt and PLA/Gt) in terms of early adhesion (4–24 h) and metabolic activity from 3 to 21 days, cell spreading into star-shaped morphologies, formation of extracellular matrix, and mineral phase deposition. In more detail, a remarkable increase in alkaline phosphatase activity was observed in Gt-based coaxial coatings from day 7 onward, with the highest values recorded for PLA/Gt. Overall, we demonstrated that the Gt-based coaxial fibrous coating provided a mix of topological and biochemical cues that synergistically promoted key osteoblast activities at the interface, supporting the regeneration of new bone tissue in highly tailored 3D-printed scaffolds, thus suggesting a promising strategy for personalized regenerative medicine. Full article

Sarcoidosis is a multisystemic inflammatory disease defined by non-caseating granuloma formation in involved organs. The liver is the third most implicated organ after the lungs and lymph nodes. Due to its frequently asymptomatic presentation, the true prevalence of hepatic sarcoidosis may be understated. Increased levels of alkaline phosphatase and gamma-glutamyl transferase are the most frequent biochemical abnormalities. The liver biopsy is still the gold standard and reveals non-caseating granulomas in almost all cases. The use of corticosteroids and ursodeoxycholic acid results in a significant decrease in biochemical parameters. However, the clinical course of hepatic sarcoidosis is diverse and requires individualized management strategies, especially to prevent hepatic complications. This review aims to synthesize the current evidence on epidemiology, pathogenesis, diagnostic approaches, and therapeutic strategies for this disease. Full article

Phenolics in Sphagnum can inhibit its microbial decomposition. Climate warming and drainage have driven vascular plants, such as Ericaceae, to expand into Sphagnum-dominated peatland. However, the impact of fine root invasion by Rhododendron auriculatum Hemsl. on Sphagnum decomposition and changes in phenolic compounds remains unclear. This study compared Sphagnum decomposition in a Sphagnum palustre L.-dominated peatland and an R. auriculatum (Sapling)–S. palustre peatland by examining the microscopic structure of S. palustre and microbial community composition. Decomposition was higher in the R. auriculatum–S. palustre peatland. On this site, bacterial metabolic types such as aerobic chemoheterotrophy and chemoheterotrophy had higher relative abundances, as did fungal trophic modes, including those with combined ectomycorrhizal, ericoid mycorrhizal, and saprotrophic functions. Acid phosphatase, laccase, total nitrogen (TN), C/N ratio (C:N), and pH differed significantly across decomposition stages. Microbial communities are affected by physicochemical factors and enzyme activities. Untargeted metabolomics revealed more downregulated than upregulated phenolics, cinnamic acids, and tannins, indicating loss of phenolic compounds. In summary, R. auriculatum fine root invasion altered enzyme activities and physicochemical properties, driving the restructuring of bacterial and fungal trophic modes and accelerating S. palustre cell wall and hyaline cell decomposition. Full article

Intensive aquaculture of rice field eel (Monopterus albus) is constrained by oxidative stress induced by high-density culture resulting in growth inhibition, while prophylactic antibiotics pose escalating risks of drug resistance and food safety hazards. This study addresses the critical need for developing efficient, environmentally friendly functional feed additives as sustainable growth promoters in intensive aquaculture. To investigate the dietary berberine (BBR) effect on promoting growth performance, hepatic antioxidant capacity and metabolism in M. albus, four experimental groups were established: control (CON, 0 mg/kg) and berberine-supplemented groups (BBR25, 25 mg/kg; BBR50, 50 mg/kg; BBR100, 100 mg/kg). Growth performance, serum biochemical parameters, hepatic antioxidant capacity, and liver metabolomics (LC-MS) were evaluated after the 8-week feeding trial. BBR50 and BBR100 had significantly increased final weight, weight gain rate (WG), and survival rate (SR), while reducing feed conversion ratio (FCR) (p < 0.05). Serum glucose (Glc), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased (p < 0.05), while high-density lipoprotein cholesterol (HDL-C) and phosphofructokinase (PFK) activity were increased (p < 0.05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly reduced (p < 0.05). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were upregulated (p < 0.05), whereas malondialdehyde (MDA) was downregulated (p < 0.05). Metabolomics identified 98 differential metabolites, with significant enrichment of metabolites associated with arachidonic acid metabolism, histidine metabolism, arginine/proline metabolism, tryptophan metabolism, and pathways related to mTOR signaling. Overall, dietary supplementation with 50 mg/kg BBR emerged as a practically favorable dose among the tested concentrations for promoting growth performance and feed utilization efficiency, whereas 100 mg/kg BBR was associated with lipid and amino acid metabolic alterations suggestive of metabolic reprogramming and antioxidant-related shifts, without conferring additional growth benefits. Full article

Cardio-renal metabolic (CRM) syndrome, characterized by insulin resistance and dyslipidemia, disrupts renal insulin signaling, enhances oxidative stress, and activates inflammasome pathways, ultimately promoting renal fibrosis and kidney dysfunction. Aberrant renal gluconeogenesis has emerged as a critical contributor to tubular injury under cardiometabolic stress; however, its mechanistic linkage to inflammatory and fibrotic remodeling remains incompletely defined. In this study, ApoE^−/− mice subjected to streptozotocin administration and a high-fat diet developed pronounced cardiometabolic dysfunction, accompanied by elevated blood urea nitrogen, creatinine, uric acid, and glycated hemoglobin levels, as well as severe renal histopathological alterations. N-Acetylcysteine (NAC) supplementation significantly improved metabolic abnormalities and attenuated tubular dilation, glomerular hypertrophy, and mesangial expansion. Mechanistically, NAC suppressed renal gluconeogenesis by downregulating glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression and mitigated epithelial–mesenchymal transition by restoring E-cadherin and reducing vimentin expression, thereby limiting fibrotic remodeling. Consistent with in vivo findings, NAC reduced reactive oxygen species production, restored PI3K/Akt-dependent insulin signaling, and inhibited inflammasome activation in NRK-52E renal tubular cells exposed to high glucose and oleic acid, resulting in attenuation of inflammatory signaling and gluconeogenic activity. Collectively, these results demonstrate that NAC mitigates cardiometabolic stress-induced renal injury by modulating inflammasome activation and gluconeogenic reprogramming, highlighting its potential as a mechanistic modulator of renal fibrosis under CRM conditions. Full article

Surgical intervention is a primary treatment for osteosarcoma, often resulting in a tumorous bone defect with an irregular shape. Postoperative management is essential to minimize tumor recurrence risks and promote bone regeneration. To address these issues, we developed a multifunctional injectable, rapidly photo-curable hydrogel composed of gelatin methacryloyl/carboxymethyl chitosan/hyaluronic acid (GelMA/CMCS/HA), modified with vanadium-doped mesoporous bioactive glass (VMBG). The exceptional injectability enables seamless adaptation to irregular bone defects, offering a significant advantage over preformed implants, while the rapid photocurability of the hydrogel ensures stable fixation within minutes, thereby reducing potential risks during surgery. Furthermore, this platform exhibits dual therapeutic efficacy, characterized by antitumor activity and osteogenic induction. In vitro assessments demonstrated that V(V)/V(IV) valence cycling-driven ROS generation mediated its potent antitumor efficacy. Additionally, concurrent enhancement of alkaline phosphatase activity and osteogenic marker expression validated its osteogenic potential. The CMCS incorporation promoted healing at the defect site, while the HA addition created binding sites for cell adhesion and growth, thereby improving scaffold bioactivity. Collectively, this study presents the development and validation of a multifunctional GelMA/CMCS/HA hydrogel, highlighting its dual capability for bone regeneration and tumor suppression within tumor-associated bone microenvironments. Full article

Maize (Zea mays L.), a typical thermophilic crop originating from tropical regions, exhibits an inherent sensitivity to low-temperature stress. Cold stress severely restricts maize seed germination, seedling growth, the physiological metabolism, and the final grain yield, which greatly limits its geographical cultivation range and sustainable industrial development. Elucidating the molecular regulatory mechanisms underlying maize cold tolerance and excavating cold-resistant functional genes are essential for the molecular breeding of cold-tolerant maize varieties and expanding maize planting areas in high-latitude and low-temperature-prone regions. In this study, using the strongly cold-tolerant maize inbred line B144 as the experimental material, we cloned the ZmMAPKKKA gene (NCBI accession: LOC103651289) and systematically screened and verified its cold-stress-specific interacting proteins via multiple molecular biological assays. The full-length coding sequence (CDS) of ZmMAPKKKA is 1134 bp, encoding a 377-amino-acid protein with a predicted molecular weight of 40.37 kDa. The quantitative real-time PCR (qRT-PCR) results demonstrated that the ZmMAPKKKA expression was significantly upregulated by 16.56-fold in maize roots after 12 h of low-temperature treatment, indicating a tissue-specific and robust cold response in root tissues. A total of 25 interacting proteins were identified through yeast two-hybrid screening, among which three stress-responsive proteins, including a protein kinase (LOC100286253), a protein phosphatase 2C (PP2C) (LOC542176), and a NAC transcription factor (LOC118474710), were selected for subsequent verification. The Pull-Down, Co-immunoprecipitation (Co-IP), and bimolecular fluorescence complementation (BiFC) assays consistently confirmed that ZmMAPKKKA specifically interacts with these three proteins both in vitro and in vivo under cold stress conditions. This study is the first to construct a ZmMAPKKKA-centered protein interaction module in the maize mitogen-activated protein kinase (MAPK) cascade under cold stress, establishing a novel kinase–phosphatase–transcription factor regulatory cascade that improves the current understanding of cold signal transduction mechanisms in maize. Homologous genes of ZmMAPKKKA in gramineous crops including rice (Oryza sativa) and sorghum (Sorghum bicolor) have been proven to participate in diverse abiotic stress responses, suggesting the conserved functional roles of MAPKKK family genes across gramineous species. Collectively, our findings provide comprehensive insights into the molecular mechanism of the maize MAPK signaling pathway mediating cold stress adaptation and supply valuable functional gene resources for cold-tolerant maize germplasm innovation and molecular breeding. Full article

Morchella sextelata a species of high nutritional and economic value, is widely cultivated. To investigate how different cultivation environments affect the soil physicochemical properties and microbial communities associated with common morel, this study established cultivation plots under three distinct settings: apple orchard canopies, dry upland fields, and paddy fields. The objective was to compare the differential impacts of common morel cultivation on soil environmental conditions across these habitats. The results indicate that cultivating common morel effectively enhances soil fertility. Across all environments, soil hydrolyzable nitrogen (HN), available potassium (AK), and organic matter content were higher than in the control. In apple orchard and dryland soils, total phosphorus (TP), total potassium (TK), available phosphorus (AP), and pH values were also elevated compared to the control, with most differences reaching significant levels. Solid Sucrase (S-SC) activity increased in all environments compared to the control, with values of 17.52 mg/d/g in PG, 17.39 mg/d/g in HD, and 21.68 mg/d/g in DT soils. Soil Amylase (S-AL) activity was higher in PG (451.28 μg/h/g) and HD (475.38 μg/h/g) soils. In contrast, Soil-acid phosphatase (S-ACP) activity was significantly elevated in DT soil (2922.08 nmol/h/g). PG soil exhibited significantly higher activities of Solid-Catalase (S-CAT), Solid polyphenol oxidase (S-PPO), and Solid Urease (S-UE), with S-CAT reaching 952.5 μmol/h/g. Following common morel cultivation, bacterial richness and diversity decreased across all conditions, while fungal richness increased but diversity declined. At the phylum level, Proteobacteria remained the dominant bacterial group, accounting for 26.78% in PG, 28.27% in HD, and 20.05% in DT soils. Ascomycota was the predominant fungal phylum, comprising 68.03% in PG, 72.16% in HD, and 68.94% in DT soils. Predicted bacterial functional pathways were primarily associated with metabolism, genetic information processing, environmental information processing, and cellular processes. Key metabolic pathways included carbohydrate metabolism, amino acid metabolism, and metabolism of cofactors and vitamins. fungal functional guilds were mainly classified as pathotrophic, pathotrophic–saprotrophic, pathotrophic–saprotrophic–symbiotrophic, and saprotrophic. Among these, saprotrophic and pathotrophic guilds showed higher abundance compared to the control. This shift is characterized by a reduction in both the diversity and abundance of beneficial microorganisms, alongside an increase in the richness of harmful microbial taxa. The combined effect of these factors disrupts the soil microbial equilibrium. The findings of this study provide a theoretical foundation for the cultivation of common morel and the management of associated soils. Full article

Soil acidity is a major constraint in many agricultural regions, where increased aluminum (Al³⁺) solubility at low pH severely affects plant health by inhibiting root elongation, disrupting nutrient uptake, and inducing oxidative stress. Recent studies have highlighted melatonin, a widely occurring indoleamine with strong antioxidant and stress-modulating properties, which alleviates Al-induced damage in crops. This review synthesizes current physiological, biochemical, and agronomic evidence demonstrating that exogenous melatonin enhances plant tolerance to aluminum toxicity. Across multiple model and crop species, melatonin application has been shown to improve root elongation by 20–45%, reduce lipid peroxidation by 30–60%, and enhance key antioxidant enzymes such as SOD, POD, and CAT by 25–70% under Al stress. Case studies in soybean, wheat, maize, and rice further indicate that melatonin protects root meristems from oxidative damage, stabilizes photosynthetic machinery, and improves nutrient acquisition. In acidic soils (pH 4.5), melatonin-treated soybean exhibited 28% greater biomass and 15–22% higher N and P uptake, while wheat plants demonstrated 10–18% higher grain filling under field-simulated Al stress. Emerging long-term studies show that melatonin also benefits soil health. Multi season experiments reveal that melatonin enhances root exudates that support beneficial rhizosphere microbes, increases soil enzymatic activities (urease, phosphatase) by 20–35%, and lowers exchangeable Al by 12–18%. These improvements contribute to cumulative yield gains of 10–18% over successive cropping cycles. Additionally, genetic approaches aimed at increasing endogenous melatonin levels in plants have demonstrated 12–30% yield improvement in acid soil conditions. This review highlights the need for multi-year, multi-location studies to further clarify how melatonin can support sustainable agricultural practices, enhance soil fertility, and mitigate aluminum toxicity in acid-affected regions. Full article

In containerized finished plant production, the effects of biostimulants in nursery practice are often judged primarily on the basis of visual condition, while a more precise interpretation of treatment response requires leaf-level physiological and rhizosphere-level indicators. The aim of our study was to determine how the humic- and fulvic acid-based BiStep biostimulant influences the physiological functioning and, in part, the rhizosphere enzyme activity of three deciduous ornamental shrub taxa widely used both in nursery finished plant production and in urban green space plantings, namely, Forsythia × intermedia ‘Beatrix Farrand’, Weigela florida ‘Eva Rathke’, and Viburnum opulus ‘Roseum’, under commercial container conditions. In the experiment, control and biostimulant treatments were compared. Treatment effects were evaluated on the basis of net photosynthesis (Pn); transpiration (E); chlorophyll content; stomatal density; stomatal length; and acid phosphatase (ACP), alkaline phosphatase (ALP), and β-glucosidase (GLUC) activities. For Pn, a significant taxon × treatment interaction was observed (p = 0.002). Pn showed taxon-dependent numerical changes under BiStep: values were 22.212 µmol CO₂ m⁻² s⁻¹ in F. intermedia, 4.182 µmol CO₂ m⁻² s⁻¹ in W. florida, and 3.370 µmol CO₂ m⁻² s⁻¹ in V. opulus, but pairwise differences from the control were not statistically significant. Transpiration also showed a significant taxon × treatment interaction (p < 0.001), although BiStep–control differences were not significant within taxa. Stomatal density increased significantly in F. intermedia and W. florida, while the BiStep–control difference was not significant in V. opulus. Chlorophyll content increased only in W. florida (from 699.6 to 924.4 µg g⁻¹ fresh weight), but this change was not statistically significant. ACP activity showed significant treatment and interaction effects (p = 0.0107; p = 0.00546), whereas ALP and GLUC did not show a consistent treatment response. Based on the results, the effect of BiStep was clearly taxon-dependent and functionally selective. Therefore, in nursery finished plant production and subsequent urban plant use, it should not be considered a universally effective input, but rather a biostimulant whose relevance depends on the specific physiological and rhizosphere-level response of the taxon. Full article

Excessive bone resorption by osteoclasts causes pathological bone loss in diseases such as osteoporosis. 7-Deacetoxy-7-oxogedunin (CG-1), a limonoid isolated from Carapa guianensis (Meliaceae), exhibits various biological activities. Here, we examined the anti-osteoclastogenic effect of CG-1 and its underlying mechanism in receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells. CG-1 inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and decreased the expression of osteoclastogenesis-related genes. When CG-1 was added to the culture during the first 3 days of the 5-day-osteoclastogenesis period, the expression levels of the osteoclastogenesis-related genes (Nfatc1, Acp5, Src, Ctsk, and Mmp9) were decreased, as was observed when CG-1 was added continuously for 5 days. Furthermore, CG-1 lowered RANKL-induced Akt phosphorylation, which is similar to the results seen with the PI3K inhibitor, LY294002. Moreover, CG-1 and LY294002 suppressed the RANKL-induced expression of NFATc1, the master transcription factor for regulating terminal differentiation into osteoclasts. These results suggest that CG-1 attenuated RANKL-induced osteoclastogenesis by inhibiting the PI3K/Akt-NFATc1 axis during the early stage of osteoclast differentiation. Thus, CG-1 has the potential to suppress osteoclast-mediated bone resorption. Full article

The objective of this study was to analyze the patterns of extracellular enzyme activity in the soil of shade-grown coffee orchards (SCOs) and their association with soil physicochemical properties and selected microbial taxa in Tropical Montane Cloud Forest (TMCF) landscapes at 38 sites in the Sierra Norte de Puebla, Mexico. Correlation analyses and a redundancy analysis (RDA) were used to examine the relationships between edaphic variables, enzymatic activities, and the presence of culturable microorganisms. Protease activity was positively associated with nitrate concentration, whereas acid phosphatase activity showed no clear relationship with available phosphorus. A negative association between protease and acid phosphatase activities represented the strongest relationship observed, indicating contrasting patterns of enzyme activities across sites. Multivariate analysis indicated that soil variables, including pH, available phosphorus, electrical conductivity, nitrate concentration, and soil moisture, were associated with variations in enzyme activity patterns and selected microbial taxa. In addition, the abundance of genera such as Bacillus, Cladosporium, and Pseudomonas was associated with soil variability, suggesting ecological associations between microbial indicators and soil conditions. Overall, the results indicate that soil physicochemical variability is associated with differences in enzyme activity patterns and selected microbial taxa in SCO systems. These findings are broadly consistent with patterns described in ecoenzymatic framework, although interpreted here as associative relationships. Full article