Retrospective observational study. To comprehensively evaluate skeletal-muscle characteristics in patients with degenerative spondylolisthesis (DS), clarify the association between sarcopenia and DS, and determine the impact of sarcopenia on surgical outcomes. In lumbar spinal stenosis (LSS), factors such as spinal alignment, facet-joint orientation, and trunk muscle atrophy and fatty degeneration contribute to DS development. However, the role of sarcopenia in surgical outcomes in DS remains unclear. A cross-sectional analysis of 1,415 patients with LSS and L4-L5 stenosis (mean age 75.2±8.7 years; 703 males and 712 females) was performed to identify factors associated with Meyerding grade I or greater spondylolisthesis using sex-adjusted analysis of covariance and logistic regression. A longitudinal analysis of 373 patients who underwent surgery for LSS (mean age, 72.1±8.8 years; 200 males and 173 females) was conducted using the Asian Working Group for Sarcopenia algorithm to evaluate the effect of sarcopenia on 1-year postoperative outcomes. Logistic regression analysis identified female sex, greater lumbar lordosis, lower skeletal-muscle mass index, smaller lumbar-multifidus (LM) cross-sectional area, smaller facet-joint angle, disc degeneration, smaller L4-L5 dural-sac area, and low flavum-canal ratio as significant variables associated with DS. No significant differences in the surgical outcomes were observed in LSS patients with and without DS, and no significant intergroup differences were noted in limb skeletal-muscle mass. However, both LM and erector spinae exhibited significantly more postoperative decreases in the DS group than in the non-DS group. No significant differences in skeletal-muscle mass change or surgical outcomes were observed according to sarcopenia status among DS patients. Sarcopenia is associated with DS, trunk muscle atrophy, and fatty degeneration. However, surgical treatment of patients with DS and sarcopenia yields favorable clinical outcomes because adequate decompression and stabilization may mitigate the impact of reduced skeletal-muscle mass.
Long-term high-salt diets (HSD) are known to impair cognitive function, whereas the effects of low-salt diets (LSD) remain less well characterized. Here, we systematically compared the long-term effects of LSD and HSD on cognitive function and alterations along the gut-metabolite-brain axis under the same humanized microbiota background. We found that both long-term LSD and HSD induced cognitive impairment in humanized control (HC) mice, but were associated with distinct biological patterns. Both LSD and HSD impaired working and recognition memory and reduced hippocampal synaptic proteins. They also altered gut microbiota composition and decreased propionate and butyrate levels. Notably, HSD were additionally associated with increased pro-inflammatory microbial taxa, elevated circulating inflammatory cytokines, and broad lipid metabolic alterations. In contrast, cognitive impairment under LSD occurred in the absence of detectable systemic inflammation and was more specifically associated with reduced microbial metabolic output, including further decreases in acetate and isobutyrate. Our findings suggest that excessive salt restriction is not biologically equivalent to normal intake and may represent a distinct biological risk pattern for cognitive impairment, highlighting the importance of balanced dietary salt intake.
The incorporation of organic matter into loess can promote carbon sequestration while also significantly affecting the soil pore structure and strength properties. To investigate the effects of organic matter on the mechanical and physical properties of soil, as well as their interaction mechanisms, experimental studies were conducted on organic soils with different organic matter contents (0%-6%) and water contents (12%-24%). Meanwhile, the real-time evolution of resistivity during the mechanical tests was monitored. The results indicate that the addition of an appropriate amount of organic matter can improve the mechanical properties of loess, whereas the compressive strength decreases with increasing water content. As stress increased, the resistivity of the specimens decreased rapidly, and then remained relatively stable after the elastic stage until failure. Crack generation during the deformation process altered the conductive pathways within the organic soil and became an important factor influencing resistivity variation. These findings provide important theoretical support for soil remediation and land resource utilization in loess regions.
Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000 Hz, 95 dB SPL, 2 h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2 weeks post-exposure. ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1 day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1 day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.
Macrophages are the primary host cells for Leishmania, and their polarization into either M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes determines the course of the infection. This study aimed to investigate the effects of Leishmania tropica, the main agent of cutaneous leishmaniasis (CL) in Türkiye, on the polarization of primary human macrophages. Primary monocytes were isolated from human peripheral blood and differentiated into macrophages using GM-CSF. The cells were infected with L. tropica promastigotes, analyzed after 48 hours. Polarization was evaluated through morphological changes, flow cytometry for surface markers (CD80, CD163, CD206, CD209), and qPCR for gene expression of M1 (NOS2, IDO1, IRF4) and M2 (ARG1, CCL22, CCL1) markers. An infection rate of 56.5% was achieved, with infected macrophages shifting from a spindle-like morphology to a rounded and granular appearance. Flow cytometry revealed a significant decrease in the expression of M1 marker CD80 and M2 markers CD206 and CD209 (p<0.01), while CD163 expression showed a non-significant increase. qPCR analyses demonstrated a significant down regulation of M1-related genes and a significant upregulation of the M2-related gene ARG1 (p<0.05). The findings suggest that L. tropica infection induces a shift in macrophage polarization from an M1-like phenotype toward an M2-like phenotype, with partial resemblance to an M2c-like profile, though the concurrent decrease in CD206 and CD209 underscores the complexity of the phenotype and indicates that the activated state does not conform neatly to any single M2 subtype. This shift likely serves as an immune escape strategy, promoting parasite persistence and influencing the chronicity of CL. Further studies incorporating additional M2c subtype markers, multiple time points, and functional assays are needed.
Intradiscal condoliase injection is an established minimally invasive treatment for symptomatic lumbar disc herniation (LDH), but its effects on central neural processing remain poorly understood. This study investigated longitudinal alterations in resting-state functional connectivity (rsFC) following condoliase injection and their associations with pain improvement. Twenty-six patients with LDH who achieved clinically meaningful pain reduction (≥50% reduction on the Visual Analogue Scale) underwent longitudinal resting-state fMRI. Seed-to-voxel analyses identified rsFC alterations between pre-treatment and 3 months post-treatment, focusing on the salience network (SN). Associations between functional connectivity changes (ΔFC) and pain improvement rates were evaluated using Spearman's rank correlation coefficients with Benjamini-Hochberg false discovery rate (FDR) correction across identified regions of interest (ROIs). Condoliase treatment significantly altered SN-related cerebellar and temporoparietal pathways. Specifically, connectivity decreased between the anterior insula (AI) and a brainstem/Vermis X cluster, while it increased between the supramarginal gyrus (SMG) and temporal occipital fusiform cortex (TOFC). Pain improvement rates correlated with ΔFC in the AI-Vermis X (ρ = 0.47, p = 0.015) and SMG-TOFC (ρ = -0.48, p = 0.014) pathways. Both remained significant after FDR correction (q = 0.045). Pain improvement following condoliase injection is accompanied by longitudinal reorganization of SN-related functional connectivity, highlighting salience-cerebellar and salience-temporoparietal brain plasticity during recovery from LDH.
The primary mechanism and subcellular localisation of α-synuclein toxicity in Parkinson's disease pathogenesis remain unknown. We spatially and temporally resolved proteomic and transcriptomic changes in human iPSC-derived dopaminergic neurons with increasing burden of pathological α-synuclein. We found that misfolded α-synuclein proteoforms, signified by the formation of nanoscale intraneuronal puncta, are associated with impaired translocon function at the endoplasmic reticulum (ER). We show that α-synuclein interacts with Sec61A in iPSC-derived dopaminergic neurons and in post-mortem brain tissue from patients with Parkinson's disease. This interaction interferes with the co-translational translocation of ER-processed proteins including the vacuolar-type ATPase V0a1 subunit, glucocerebrosidase, and Cathepsin B, causing defective organelle function such as reduced lysosomal acidification, leading to increased extracellular vesicle release of α-synuclein. Defective ER-translocation was associated with increased ribosomal UFMylation and proteasomal recruitment but not activation of the unfolded protein response. Reduction of pathological α-synuclein by either CRISPRi to decrease α-synuclein expression or pharmacological activation of proteasomal degradation with repurposed drugs mitigates the ER defect. Our study offers a unifying mechanistic link between α-synuclein pathology and dysregulation of diverse organelle-associated proteins that are both Sec61A translocon substrates and genetic modifiers of Parkinson's disease risk. Our data also provide a therapeutic rationale for proteasomal activation in early Parkinson's disease.
Protein-polysaccharide conjugate systems have garnered significant attention due to their ability to remodel antioxidant and stability functions in food systems through conformational rearrangement and supramolecular assembly. This study constructed STP-polysaccharide conjugates using sheep testis protein hydrolysate (STP) as the substrate with polysaccharide in Cistanche (CIP), Astragalus (ASP), and Angelica (ANP), respectively, to systematically elucidate the relationship between structural variation, dominant interaction forces, and functional properties. Multispectral analysis revealed that the coupling effect significantly altered the structure, with functionally relevant hydrophobic groups and Tyr/Trp residues being either exposed or buried. Mechanistic analysis indicated that hydrophobic interactions, hydrogen bonds, and electrostatic interactions collectively drove the assembly and stabilization of the STP-polysaccharide system, with their contributions influenced by polysaccharide type. Functional evaluation indicates that, after conjugation, the DPPH free radical scavenging rate of STP-CIP increased to 89.39%. In vitro digestion and storage stability studies demonstrated that after polysaccharide conjugation, the digestibility index increased to over 75.18%, and the decrease of α-helix during storage was slowed, regulating the structural integrity of the system. These findings provide a basis for the structure-interaction-function oriented design of animal-derived protease hydrolysate-plant polysaccharide conjugate systems, offering references for developing multifunctional food ingredients with both antioxidant properties and stability.
Postharvest maturity critically influences the physicochemical properties and processing adaptability of kiwifruit. However, its specific impact on the behavior of radio-frequency vacuum drying (RFVD) remains poorly understood. The evolution of water state distribution, dielectric and thermal properties, drying behavior, and dried product quality of 'Xuxiang' kiwifruit at five postharvest maturity stages (S1-S5) was systematically investigated. Results showed that increasing maturity (S1-S5) induced a gradual transformation of bound and immobilized water toward free water, accompanied by cell wall relaxation and tissue degradation. Compared with S1, S2-S4 samples exhibited relatively higher dielectric loss factors under intermediate moisture contents, together with favorable specific heat capacity, which may contribute to improved radio frequency (RF) heating performance. Meanwhile, S2-S4 samples exhibited relatively shorter drying times (6.83-7.67 h) and lower total energy consumption (22.18-22.94 kW·h). Microstructural observations revealed that S4 developed a continuous and porous structure, which facilitated moisture migration (Deff = 9.80 × 10-10 ± 0.00 m2/s) and improved rehydration capacity (2.48 ± 0.03). Additionally, samples at S2-S4 exhibited lower volume shrinkage (73.37-74.63%), while higher maturity stages (S4-S5) significantly reduced hardness and chewiness (P < 0.05) and raised the sugar-acid ratio (7.70-8.96). Regarding product quality, total phenolics, flavonoids, vitamin C content, and antioxidant activity followed a decreasing-then-increasing trend with maturity. Overall, these findings elucidated the maturity-driven mechanisms underlying RFVD behavior in kiwifruit and provided a theoretical basis for optimizing maturity selection to achieve both drying efficiency and quality retention.
Lynch syndrome (LS) is a cancer susceptibility syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. Due to increased risk of colorectal cancer (CRC), enhanced colonoscopic surveillance is recommended for heterozygote MMR carriers. Using a registry of English patients with LS linked to digital National Health Service records, we aimed to assess adherence of MMR carriers to national surveillance guidelines and to determine the impact of surveillance on CRC incidence and mortality. We described the frequency of colonoscopies in 4732 MMR carriers and used logistic regression to determine predictors of surveillance adherence. For MMR carriers with a record of surveillance and those without, we estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks; assessed for stage shift by comparing CRC stage distributions and stage-specific AS-AIRs; and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox proportional hazards regression. Surveillance at a mean interval of ≤3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage shift was observed. Colonoscopic surveillance at a mean interval of ≤2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period, spectrum bias, or the impact of overdiagnosis. The observed reduction in all-cause mortality among regularly surveilled MMR carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study could also reflect the influence of selection bias.
Tezepelumab has demonstrated efficacy in patients with severe, uncontrolled asthma in randomized controlled trials (RCTs). Real-world studies assessing patient-reported outcomes are required to complement RCT findings. ASCENT is an ongoing, multi-country, single-arm, prospective, real-world study assessing asthma symptom control in participants (≥12 years old) with severe, uncontrolled asthma initiating tezepelumab as routine standard of care in Europe and Canada. This interim analysis assessed changes from baseline in Asthma Control Questionnaire-6 (ACQ-6) score, St George's Respiratory Questionnaire (SGRQ) total score, and pre-bronchodilator forced expiratory volume in 1 second (FEV1) at weeks 4, 12, and 24, and the annualized asthma exacerbation rate (AAER) in the 52-week baseline and 24-week follow-up periods. Overall, 211 participants were included in this analysis. ACQ-6 and SGRQ total scores improved from baseline to week 4 (least-squares mean [95% CI] change: -0.99 [-1.13, -0.84] and -13.2 [-15.6, -10.8], respectively) and further improved to week 24 (-1.28 [-1.44, -1.12] and -19.8 [-22.6, -17.0], respectively). AAER decreased by 65% (95% CI: 55, 73) between baseline (1.75) and follow-up (0.61) periods. Least-squares mean changes from baseline in pre-bronchodilator FEV1 at weeks 4 and 24 were 0.09 L (0.03, 0.14) and 0.12 L (0.06, 0.18), respectively. These changes were observed across asthma phenotypes and biomarker levels. Patients with severe, uncontrolled asthma treated with tezepelumab had clinically meaningful improvements in asthma control, health-related quality of life, lung function, and exacerbations as early as week 4 through to week 24, irrespective of asthma phenotype. NCT05677139.
Medium-high temperature Daqu is used as a starter culture for strong-aroma Baijiu. In this process, wheat starch not only serves as the primary carbon source for microbial growth but also contributes to ethanol production and aroma development during fermentation. However, how the physicochemical properties and fine structure of wheat starch change during medium-high temperature Daqu fermentation is not well understood. In this study, we examined the changes in starch molecular structure during fermentation using three wheat varieties as substrates. The total starch and amylopectin contents decreased in chuanmai 605 (CM605), zhongkemai 47 (ZK47), and mianmai 907 (MM907) after 25 days of fermentation. The amylose content slightly increased in zhongkemai 47 (ZK47) and mianmai 907 (MM907) but decreased in chuanmai 605 (CM605). The fermented starch exhibited higher solubility than native starch at 95 °C for all three varieties. Although fermentation did not alter the crystalline type pattern, but it increased the V-type starch content and slightly elevated the relative crystallinity. Fourier transform infrared analysis revealed that fermentation influenced absorption in the hydrogen-bond-related spectral region compared with native starch. In addition, fermentation reduced both the trough and final viscosity. These results provide scientific support for Daqu-optimized wheat breeding and establish practical criteria for baijiu producers in sourcing superior wheat.
Silk fibroin (SF) is widely investigated in bone tissue engineering owing to its biocompatibility, enzymatic biodegradability, and ability to promote osteoblast adhesion. However, native SF scaffolds lack sufficient calcium-binding sites for effective hydroxyapatite (HAp) nucleation and inadequate mechanical strength for load-bearing applications. To address both limitations, this study developed a strategy combining chemical phosphorylation and laccase-catalyzed cross-linking. Specifically, phosphorylation of primary amine and hydroxyl groups on SF chains introduced negative charges, thereby chelating calcium ions and promoting the in situ formation of HAp during the alternating biomimetic mineralization process, while enzymatic cross-linking improved the mechanical properties of the resulting SF scaffolds. Following the combined treatment, surface electronegativity decreased, and the molecular weight of SF increased, enabling rapid, uniform deposition of carbonate nanocrystalline HAp with a bone-like calcium-to‑phosphorus ratio. The compressive strength was noticeably increased from 8.67 kPa to 45.68 kPa. In vitro evaluations confirm the excellent cytocompatibility of the engineered scaffolds and accelerated osteogenic commitment compared to pristine SF. By bridging nano-level interfacial mineralization with macro-scale mechanical enhancement, this eco-friendly and sustainable strategy provides a highly translatable platform for clinically relevant bone regeneration.
Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6 months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p < 0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3 ± 8.6) min, much shorter than the early phase (89.5 ± 10.3) min (p < 0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p < 0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p > 0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.
Localized chemotherapy represents a promising strategy for enhancing tumor-targeted drug delivery while minimizing systemic toxicity. In this study, we investigated thermosensitive hydroxypropyl methylcellulose (HPMC)-based hydrogels for the prolonged localized delivery of 5-fluorouracil (5-FU). The sol-gel transition temperature of the formulations was modulated within the physiological range (32-37 °C) using Hofmeister salts. Rheological analysis revealed that 5-FU alone decreased the gelation temperature of HPMC from 47 ± 0.8 °C to 44 ± 0.7 °C due to the competitive disruption of polymer hydration shells. Salt addition further decreased sol-gel transition temperatures following the salting-out order PO43- > SO42- > Cl-. Synergistic effects in HPMC/salt/5-FU systems were observed. 5-FU increased the viscoelastic moduli and promoted a more compact, homogeneous microstructure exclusively in gels with K2SO4 content. FTIR spectroscopy confirmed the absence of covalent interactions between the gel components, indicating physical crosslinking In vitro release studies demonstrated that drug transport is governed by both the specific nature of the anions and the ionic strength. The HPMC/K2SO4_0.2M/5-FU formulation provided the most prolonged release profile, which correlated with superior mechanical strength and a homogeneous gel network structure. These findings highlight the potential of Hofmeister salt modulated HPMC hydrogels for tailored, long-acting localized drug delivery in cancer therapy.
Vibrio-associated foodborne diseases constitute a substantial global health burden, and aquatic products are frequently contaminated with antibiotic-resistant and potentially virulent Vibrio. This meta-analysis aimed to quantify the global prevalence, antibiotic resistance, and virulence genes of Vibrio in aquatic products. From 108 eligible studies, pooled prevalence of Vibrio reached 20.99% (95% CI: 18.04-24.09%), exhibiting a decreasing trend over time. Contamination rates were higher in shellfish (25.43%) than in shrimp (21.69%) and fish (17.63%), and in farm samples (26.31%) compared to retail samples (18.12%). Species and geographic analyses identified V. parahaemolyticus as the predominant species, with Asia and North America as principal hotspots. Among 47 antibiotics tested, resistance to penicillins was most prevalent (67.52%). Resistance to polymyxin B, erythromycin, vancomycin, and tetracycline demonstrated increasing trend over time, accompanied by high frequencies of key resistance genes (blaCTX, blaTEM, ermB, aadA, str, and GyrA associated mutations). Virulence analysis indicated high prevalence of adhesion factors (tcp), secretion systems (type VI secretion system and type III secretion system 1), and hemolysin-related genes (tlh and hlyA). Asian isolates possessed the broadest virulence gene spectrum. Notably, farm-derived isolates exhibited higher prevalence of adhesion- and toxin-related genes, whereas retail-derived isolates harbored more genomic islands and other virulence genes. These findings reveal a high prevalence of Vibrio in aquatic products worldwide, characterized by distinct spatiotemporal distribution patterns, severe antibiotic resistance and diverse virulence attributes. Our results underscore the necessity for integrated surveillance and targeted intervention strategies across the aquaculture-to-retail continuum.
The role of the Maillard reaction in shaping dried abalone quality during drying was investigated. During the drying process, a progressive increase in browning intensity and in the color parameters ΔE and BI was observed in abalone muscle. SDS-PAGE analysis revealed aggregation of proteins such as myosin heavy chain, while PAS staining confirmed the formation of glycoprotein polymers. CD spectroscopy analysis indicated that the reaction led to a reduction in α-helix content from 29.89% to 6.52%, alongside increases in β-sheet and random coil contents to 48.52% and 28.48%, respectively, accompanied by a marked decrease in intrinsic fluorescence intensity. Dynamic substrate analysis showed significant reductions in glucose and key amino acids, including Glu, Lys, and Phe, facilitating the generation and accumulation of 18 Amadori and Heyns compounds. Seven compounds of Fru-Tyr, Fru-Phe, Glu-Met, Fru-pGlu, Fru-Lys, Glu-Gln, and Fru-Val, were identified as characteristic biomarkers of dried abalone through principal component analysis. A predictive model based on near-infrared spectroscopy and partial least squares regression achieved high predictive accuracy for these seven markers, with determination coefficients exceeding 0.90 and root mean square errors of prediction below 0.20. These findings demonstrate that the Maillard reaction induces protein glycation in abalone muscle, accompanied by the accumulation of Amadori/Heyns compounds, providing a theoretical basis for quality precise control in dried abalone processing.
Enterotoxigenic Escherichia coli (ETEC) can cause diarrheal disease in both humans and young livestock, posing substantial challenges to intestinal health. This study investigated the protective effects and mechanisms of encapsulated tannic acid (ETA) against ETEC-induced intestinal injury. ETA was successfully prepared, and in vitro digestion experiments showed that the release rate of tannic acid was 10.27% in simulated gastric fluid, with a cumulative release rate of 78.97% in simulated intestinal fluid after 360 min, indicating its excellent controlled-release property. In vivo, 500 mg/kg ETA was selected as the optimal dose and alleviated ETEC-induced growth inhibition, reduced the spleen weight ratio, and mitigated intestinal inflammation. Histologically, ETA improved intestinal morphology by increasing villus height and decreasing crypt depth, and its efficacy was better than that of TA. ETA also attenuated inflammation by downregulating TNF-α, IL-1β, IL-8 and the TLR4/MYD88/TAK1 pathway, relieved oxidative stress by increasing SOD activity and decreasing MDA content, and restored intestinal barrier function. Additionally, In vitro, 0.6% ETA digestion supernatant alleviated ETEC-induced damage in IPEC-J2 cells. ETA also reshaped ETEC-induced cecal microbiota dysbiosis by reducing α-diversity, increasing the abundance of beneficial bacteria and decreasing pathogenic bacteria, and restored short-chain fatty acid levels. Mechanistically, antibiotic-induced gut microbiota depletion abolished the protective effects of ETA, while fecal microbiota transplantation from ETA-treated donors replicated these protective effects. These findings demonstrate that ETA attenuates ETEC-induced intestinal injury through gut microbiota modulation, providing a promising strategy for the prevention and treatment of bacterial enteritis.
This study evaluated the effects of sun drying (SD), heat pump drying (HPD), far-infrared drying (FIRD), and combined FIR with HPD (FIR-HPD) on drying kinetics and quality attributes of chili peppers, using metabolomics to profile changes in carotenoids and alkaloids. Mechanical drying accelerated the drying rate by 56.8-90.3% compared to SD. Color retention was superior in peppers dried at 45 °C and 55 °C, whereas SD caused color fading. Ascorbic acid was better preserved in SD and 45 °C-dried samples, while total phenolics, antioxidant capacity, and carotenoids decreased with rising temperature. Capsaicin was lowest in SD peppers. Among 44 identified carotenoids, degradation was more severe in SD than in FIR-HPD, with zeaxanthin, capsanthin, and capsorubin as key metabolites in the enriched carotenoid biosynthesis pathway. Additionally, 132 differential alkaloids were screened from 236 identified, mainly enriched in tryptophan metabolism. Overall, FIR-HPD improved drying efficiency and better preserved bioactive compounds in dried chili peppers.
The neurohypophysis (NH) is a specialized neuro-glial interface where neuronal, glial, and vascular elements coordinate neuroendocrine secretion and immune signalling. Its intrinsic plasticity supports adaptation to osmotic and inflammatory stress. Osmotic challenges, such as salt loading, induce structural and functional remodelling within the NH, engaging both microglia and pituicytes. To determine these adaptive processes, we examined the effects of 4 and 8 days of salt loading (2% NaCl) on cellular plasticity in the mouse NH. Pituicyte morpho-functional remodelling was assessed by immunohistochemistry using specific markers (GFAP, AQP4), while microglial activation and polarization were evaluated using Iba1 and CD206. These analyses were complemented by Western blot experiments, including the measurement of the pro-inflammatory cytokine IL-1β. Physiological parameters such as fluid intake, body weight, plasma osmolality and haematocrit were also evaluated. Immunohistochemical analysis revealed a marked morphological transformation of microglia from a ramified to an amoeboid phenotype following osmotic stimulation. Western blot analysis showed stable Iba1 expression, indicating that this activation occurred without microglial proliferation. After 8 days of salt loading, CD206 expression significantly increased, accompanied by a decrease in IL-1β, suggesting polarization of microglia toward an anti-inflammatory M2 profile. Additionally, GFAP expression decreased, whereas AQP4 expression increased, particularly in the perivascular region. Physiologically, salt loading increased fluid intake and haematocrit, reduced body weight, while plasma osmolality remained unchanged. Together, these findings indicate coordinated neuroimmune remodelling in the NH. The shift toward an anti-inflammatory glial profile and increased AQP4 expression likely represents an adaptive mechanism that supports tissue homeostasis during hyperosmotic stress.