搜索结果：Decreases

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.

Since World War II, pesticide use has increased significantly. This study evaluated the effects of the biopesticide spinosad on the epididymis and sperm quality of Wistar rat exposed during the juvenile period. Male rats were divided into six groups (control, 0.2 and 2 mg/kg; immediate and delayed) and exposed between PND 25-65. On PND 66 and PND 131, the epididymides and spermatozoa were collected for immediate and delayed evaluations, respectively. The results indicate that sperm transit time showed an immediate increase, whereas a reduction was observed during the delayed period (0.2). Sperm motility showed an immediate reduction (2.0) and a decrease during the delayed period (0.2). Mitochondrial evaluation revealed reductions in both the immediate (0.2; 2.0) and delayed (2.0) periods, suggesting persistent impairment of mitochondrial function. Alterations in the antioxidant system indicate the involvement of oxidative stress. Therefore, results demonstrate that spinosad impairs epididymal function and sperm quality.

Ferroptosis caused by metabolic stress is a main contributor to pancreatic β-cell injury in type 2 diabetes. Orphan nuclear receptor NR4A1 can be activated by various stimuli and stressors, but its role remains unclear in pancreatic β-cell ferroptosis. This study focuses on how NR4A1 transcriptionally regulates pancreatic β-cell ferroptosis and reveals its underlying network. The Metabolic parameters, pancreatic morphological alterations and ferroptotic phenotypes were assessed in NR4A1 pancreatic-specific knockout (cKO) mice and flox mice under a high-fat diet. Ferroptosis markers, including ROS, Fe2+, MDA and GSH, were detected in MIN6 cells treated with Cytosporone B (CsnB) and NR4A1 overexpression cells (OV cells). PCR array was used to identify differentially expressed genes in OV cells. Our data showed that under high-fat diet feeding, cKO mice exhibited exacerbated weight gain, hyperglycemia, impaired glucose tolerance, and reduced insulin secretion, accompanied by compensatory islet hypertrophy, a decreased β-cell proportion, and a distinct pancreatic ferroptosis phenotype. In MIN6 cells, the ferroptosis inducer Erastin triggered ROS/Fe2+/MDA accumulation, GSH exhaustion, accompanied by downregulated expression of GPX4 and SLC7A11 (xCT), as well as upregulated levels of PTGS2 (COX2) and ACSL4. These effects were reversed by NR4A1 overexpression or treatment with CsnB in MIN6 cells. Notably, xCT and GPX4 transcript levels did not show a significant increase upon NR4A1 overexpression. Our findings demonstrate that NR4A1 negatively regulates pancreatic β-cell ferroptosis, suggesting its promise as a therapeutic target to safeguard β-cell survival in type 2 diabetes.

Distal necrosis remains a common postoperative complication of perforator flaps, largely due to insufficient perfusion and inadequate angiogenesis in ischemic flap tissue. Transient receptor potential vanilloid type 1 (TRPV1) has been implicated in vascular regulation through calcium-dependent signaling pathways; however, whether pharmacological blockade of TRPV1 affects angiogenesis in perforator flaps remains unclear. In this study, capsazepine was used to pharmacologically block TRPV1 in a rat perforator flap model. The results showed that capsazepine treatment significantly reduced flap survival compared with vehicle treatment (64.5 ± 1.2 % vs. 79.0 ± 1.7 %) and impaired angiogenesis, as indicated by reduced vascular density and decreased expression of VEGF-A, eNOS, and MMP2. Capsazepine also reduced the phosphorylation of CaMKII, CaMKKβ, and AMPK, together with decreased Beclin1 expression, a reduced LC3-II/I ratio, and induced pro-apoptotic changes, as evidenced by increased Bax and cleaved caspase-3 expression and decreased Bcl-2 expression. Notably, pharmacological enhancement of autophagy with rapamycin reduced Bax expression and increased MMP2 expression. Collectively, these findings indicate that capsazepine-mediated TRPV1 blockade impairs perforator flap survival and angiogenesis, at least in part, through reduced CaMKII/CaMKKβ/AMPK activation and attenuation of autophagy. The rapamycin rescue findings position autophagy as an important functional intermediary between TRPV1-associated signaling and the regulation of apoptosis and angiogenesis in perforator flaps.

Clostridium perfringens (C. perfringens) spores pose a persistent food safety risk owing to their high resistance, yet the mechanisms governing their germination and outgrowth remain poorly understood. This study utilized ε-polylysine (ε-PL) as a model antimicrobial to systematically investigate its inhibitory effects and underlying mechanisms during the spore-to-vegetative cell transition. The results indicate that ε-PL had the least effect on early germination events; over 60 min, no significant differences were observed between the treatment and control groups in terms of OD₆₀₀ reduction or DPA release. In contrast, ε-PL significantly prolonged the lag phase and inhibited growth rates during the growth phase, suggesting a phase-dependent inhibitory effect. Mechanistic analyses revealed that the spore coat and cortex act as critical physical barriers during early germination, limiting antimicrobial access. As these outer layers progressively degraded, the inner membrane (IM) became exposed as the primary target. ε-PL disrupted IM lipid organization, significantly decreasing membrane order (GP value declined from 0.56 to 0.42), inducing membrane depolarization, and increasing permeability. These impairments led to intracellular protein leakage, ATP depletion, inhibition of Na+/K+-ATPase activity, and abnormal accumulation of pyruvate (0.3 g/L). Furthermore, excessive generation of reactive oxygen species (ROS) and DNA interference collectively signaled a collapse of energy metabolism and cellular integrity. The efficacy of ε-PL was validated in a ham sausage model, where microbial proliferation was significantly delayed. This study provides critical mechanistic insights into spore control and supports the application of ε-PL in food preservation.

Salmonella remains a major foodborne zoonotic hazard, yet long-term data on the distribution of serovars in foods of animal origin in south-eastern Europe are limited. This study describes the temporal dynamics and food-category distribution of Salmonella enterica serovars isolated from foods of animal origin in Bulgaria between 2007 and 2023. A total of 1,906 confirmed Salmonella isolates submitted by public and private laboratories to the National Reference Laboratory were analysed by classical biochemical identification and serotyping according to the White-Kauffmann-Le Minor scheme. Salmonella was most frequently recovered from poultry meat (39.8%), poultry by-products (13.1%), meat preparations (16.9%), minced meat (11.7%) and pork meat (6.9%). Temporal serovar composition differed significantly (Monte Carlo &#x3c7;2 = 763.0, P < 0.0001; Cramer's V = 0.258). Binomial generalized linear models showed a significant annual increase in S. Infantis (OR/year = 1.095, 95% CI 1.056-1.136; FDR q < 0.001) and decrease in S. Typhimurium (OR/year = 0.929, 95% CI 0.873-0.989; q = 0.030), whereas S. Enteritidis showed no significant linear trend. Food category and major serovar were strongly associated (Monte Carlo &#x3c7;2 = 827.0, P < 0.0001; Cramer's V = 0.339). S. Infantis, S. Enteritidis and S. Kottbus were concentrated in poultry-derived products, whereas S. Typhimurium, its monophasic variant and S. Derby were associated with pork, minced meat and meat preparations. These findings support continuous serovar-level surveillance and targeted control measures in poultry and pork chains.

Breast cancer (BC) is the most common cancer and the leading cause of cancer death among women worldwide. Its treatment is often ineffective due to metastasis in all BC subtypes and resistance to targeted therapy in HER2-positive breast cancer (HER2+ BC). On the other hand, the lack of traditional cell surface markers for molecularly targeted therapy in triple-negative breast cancer (TNBC) limits its treatment to conventional chemotherapy. Therefore, there is an urgent need to identify new molecular targets for BC therapy. The endothelial barrier, maintained by several types of cell junctions, including tight junctions (TJs), is loosened by cancer cells during the metastasis-linked processes. Cancer cells disrupt TJs in the endothelial wall of blood vessels and new TJs are formed between endothelial cells and cancer cells, leading to metastasis. The level of a TJ protein, F11 platelet receptor aka junctional adhesion molecule-A (F11R/JAM-A), is abnormal in most types of cancer, particularly in BC. The idea of targeting the F11R/JAM-A protein for BC treatment arose from the discovery that overexpression of the miR-145 microRNA in BC cells reduced F11R/JAM-A level and decreased cell migration. This observation was confirmed by subsequent studies, which supported the importance of F11R/JAM-A in cancer progression, particularly in BC. In this review, F11R/JAM-A is characterized as a molecular target for BC therapy. Particular attention was paid to peptide antagonists of F11R/JAM-A, that appear to be promising candidates for anticancer drugs.

Imbalance in energy intake and energy expenditure due to changes in lifestyle and genetic issues results in obesity, which is a serious health problem. Appetite-inducing signals and satiety peptides in the enteroendocrine system have a definite role in the management of obesity. To regulate food intake and digestive signals, gut-derived satiety peptides act in a coordinated network to regulate appetite and metabolic homeostasis. Among these peptides, obestatin has garnered interest for its role in modulating food intake and obesity-associated lipid parameters, as demonstrated in mouse models. This study investigates the interaction among major satiety peptides in the enteroendocrine system on administration of obestatin and its fragment analog, Nt8U, for 30 days. Obestatin and Nt8U, along with a positive control, Orlistat, were administered to high-fat fed mice. Circulating Cholecystokinin-8 (CCK-8) levels increased in obestatin-treated mice but decreased with Nt8U, while Oxyntomodulin (OXM) levels increased by 20% in the obestatin group. In contrast, glucagon-like peptide-1 (GLP-1) levels were reduced following obestatin and orlistat treatment. These alterations were accompanied by significant changes in intestinal mRNA expression of the corresponding peptide precursors, suggesting altered gene expression. Long-term indicators of energy stores, including leptin and adiponectin, were reduced across all treatment groups, while insulin levels were significantly decreased in obestatin-treated mice. These hormonal changes were associated with reductions in body weight, plasma total cholesterol, and triglycerides. Collectively, these findings indicate that obestatin and Nt8U administration altered circulating satiety peptide concentrations and the intestinal expression of genes encoding gut-derived satiety hormones. These coordinated changes suggest modulation of metabolic hormone networks associated with energy balance in diet-induced obesity.

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&#x2009;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&#x2009;<&#x2009;0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3&#x2009;&#xb1;&#x2009;8.6) min, much shorter than the early phase (89.5&#x2009;&#xb1;&#x2009;10.3) min (p&#x2009;<&#x2009;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&#x2009;<&#x2009;0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p&#x2009;>&#x2009;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.

The relationship of the greater palatine canal (GPC) to dentoalveolar landmarks and how this relationship changes with demographic factors are of critical importance for surgical interventions. We aimed to evaluate the relationship between the GPC and maxillary molars using multiple dentoalveolar landmarks, and to investigate the influence of age, gender, and tooth type using cone-beam computed tomography (CBCT). A total of 1156 maxillary molars (649 first, 507 second) were analyzed. This CBCT-based cohort study included patients allocated to age groups: 18-35&#x2009;years, 36-65&#x2009;years, and >65&#x2009;years. Distances between the GPC and the occlusal plane (OP-GPC), cementoenamel junction (CEJ-GPC), and root apices were measured. The horizontal relationship between GPC and apices (superior, adjacent, and inferior positions), as well as canal morphology, was assessed. Linear mixed-effects models, generalized estimating equations, and Pearson's chi-square were used. Second molars demonstrated significantly shorter OP-GPC, CEJ-GPC, and apex-GPC distances compared to first molars (p<0.05). Females exhibited reduced vertical distances (p<0.05). CEJ-GPC distances increased with age, while OP-GPC decreased with age (p<0.05). The superior position was more common in older age groups (p<0.05). GPC morphology remained stable across age and gender (p>0.05). The spatial relationship between the GPC and maxillary molars is dynamic rather than fixed, and varies systematically with age and gender. Second molars present reduced anatomical safety margins. The CEJ-GPC distance tended to be greater in those over 35 than in those under 35. This study highlights the importance of individualized, CBCT-supported assessment based on demographic factors to ensure safe surgical procedures.

Post-infectious bronchiolitis obliterans (PIBO) may occur following childhood infections. Subsequent dysanaptic lung growth, with differential development of the alveolar compartment over the airways, remains elusive. We performed a morphological characterization of the whole airway tree in PIBO compared to bronchiolitis obliterans syndrome (BOS) after lung transplantation. Lungs from matched PIBO (n=5), BOS (n=5), and non-diseased donors (n=5) were evaluated using ex vivo high-resolution computed tomography (CT) scans followed by three-dimensional (3D)-airway segmentation. Matched lung tissue samples (n=4 locations/lung) were scanned with micro-CT (resolution: 5-10&#x2005;&#xb5;m) for 3D terminal bronchiole assessment and histology. No significant difference in the number of airways per generation (until generation 11) was observed between groups (p=0.86). Airway diameters in PIBO (generations 6-11) and BOS (generations 7-10) were increased compared to controls (overall p=0.018), without significant differences between PIBO and BOS. More obstructed airways were present in BOS versus PIBO (p=0.016), but airway obstructions were larger in PIBO versus BOS (p=0.032). There were significantly fewer terminal bronchioles in PIBO compared to BOS and controls (PIBO: median 2934 terminal bronchioles/lung (IQR:2247-4115), BOS 8424 terminal bronchioles/lung (IQR:6207-10480), controls 10&#x2009;903 terminal bronchioles/lung (IQR:7583-12&#x2009;820), p=0.0009), but terminal bronchiole diameters were not significantly different (p=0.37). Obstruction of pre-terminal bronchioles was segmental (i.e., focal with normal distal terminal bronchiole) in BOS, but partly non-focal (non-reopening bronchiole) in PIBO. PIBO lungs display an almost threefold decrease in terminal bronchioles compared to BOS, with morphological differences in the type and location of airway obstructions, providing structural evidence supporting dysanaptic lung growth.

In this study, we demonstrate for the first time that post-injury creatine supplementation (300mg/kg, p.o.) administered for two weeks attenuates blood-brain barrier disruption, cortical lesion volume (by ~60%), spatial memory deficits (reducing escape latency by ~50% in the Barnes maze), hippocampal theta/delta rhythm alterations, and epileptiform activity in 35-day-old male rats subjected to severe fluid percussion injury (FPI). In the hippocampus, the FPI protocol did not cause overt neuronal loss-particularly of parvalbumin-positive neurons in the CA1 and CA2 regions-but it significantly reduced creatine levels and induced marked mitochondrial dysfunction. These alterations were evidenced by impaired MTT reduction, disrupted mitochondrial membrane potential (&#x394;&#x3c8;), decreased SDH activity, inhibition of respiratory chain complexes I-III, COX, citrate synthase (CS), and CKm activity, together with increased mitochondrial oxidative stress (enhanced DCFH-DA oxidation, elevated 4-hydroxynonenal levels, depletion of free -SH groups, and reduced GSH levels). We propose a mechanistic cascade wherein mitochondrial dysfunction and elevated oxidative stress drive the inhibition of Na&#x207a;,K&#x207a;-ATPase, which in turn contributes to neuronal hyperexcitability and cognitive deficits. Creatine's ability to maintain mitochondrial integrity directly interrupts this cascade, protecting against dysfunctions in these essential ion-gradient systems. In conclusion, post-injury creatine supplementation preserves mitochondrial function, maintains Na&#x207a;,K&#x207a;-ATPase activity, and prevents epileptiform activity and cognitive deficits, highlighting creatine as a promising strategy to mitigate secondary injury. However, these findings must be interpreted in light of certain limitations, including the use of a male-only cohort, a single time-point assessment, and the correlational nature of the proposed mechanistic pathways, warranting further investigation.

The number of people who remain single for extended periods is steadily increasing around the world. While studies have described a decline in the mental well-being of singles, the underlying causes remain largely unexplored. This study seeks to address this gap by examining the relationship between attachment styles and mental well-being, focusing on the roles of intolerance of uncertainty and immature defense mechanisms. By examining these factors, the study aims to identify the contributors to the reduction of mental well-being among involuntary singles and to highlight individual differences within this population. Using a cross-sectional design, a total of 183 involuntary singles (average age = 27.66, age range = 25-40) participated in the study and filled out self-report questionnaires. Data were analyzed using Pearson correlations and structural equation modeling (SEM) with bootstrapping procedures to test indirect effects. The results showed a direct negative relationship between insecure attachment styles and mental well-being. Moreover, intolerance of uncertainty and immature defense mechanisms were found to mediate this relationship, suggesting that insecure attachment style among involuntary singles, can decrease mental well-being through the mediating role of ineffective coping mechanisms and intolerance of uncertainty.

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 (&#x2265;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.

Implant-supported rehabilitation following maxillary or mandibular reconstruction with vascularized osseous free flaps is frequently compromised by inadequate peri-implant soft tissues, vestibular obliteration, and scar contracture. This study describes a fully digital workflow for peri-implant soft tissue management based on a patient-specific CAD/CAM vestibuloplasty stent (PSVS) and reports its preliminary clinical use. Five consecutive patients who had previously undergone jaw reconstruction with vascularized osseous free flaps underwent subperiosteal vestibuloplasty followed by placement of the 3D-printed PSVS. The device was fixed to the reconstructed bone to guide soft-tissue maturation and stabilize a free gingival graft. Vestibular depth was measured at baseline, 2 months, and 6 months postoperatively. Vestibular reconstruction was successful in all patients. Mean vestibular depth decreased from 10.6 &#xb1; 3.1 mm at baseline to 9.0 &#xb1; 3.9 mm after 6 months (mean reduction: 1.5 &#xb1; 1.1 mm). All free gingival grafts survived, resulting in a measurable band of keratinized mucosa, while implant-supported cases showed favourable peri-implant clinical parameters. No implant loss, flap compromise, osteonecrosis, or major complications occurred. This pilot case series suggests that a patient-specific CAD/CAM vestibuloplasty stent is a feasible approach for vestibular reconstruction and peri-implant soft tissue augmentation following jaw reconstruction with vascularized osseous free flaps. Larger prospective comparative studies are required to confirm its long-term clinical value.

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&#x2011;phosphorus ratio. The compressive strength was noticeably increased from 8.67&#x202f;kPa to 45.68&#x202f;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.

Neuritin 1 (NRN1) is a neurotrophic factor known to protect neurons from damage and cell death; however, its role and mechanism in cervical spinal cord injury (CSCI) remain unclear. In this study, we investigated the function of NRN1 using oxygen-glucose deprivation (OGD)-treated PC12 cells and a rat model of CSCI established by anterior cervical screw compression. In vitro, NRN1 overexpression promoted neurite outgrowth, attenuated oxidative stress, and inhibited apoptosis in OGD&#x2011;exposed PC12 cells, while NRN1 knockdown showed opposite results. Mechanistically, co-immunoprecipitation and immunofluorescence confirmed that NRN1 interacts with FZD2. In OGD-treated PC12 cells, overexpression of FZD2 reversed the neuronal damage induced by NRN1 silencing, reducing oxidative stress and the number of apoptotic cells. Furthermore, NRN1&#x2011;mediated neuroprotection was dependent on activation of the GSK&#x2011;3&#x3b2;/Nrf2 pathway, since pharmacological inhibition of Nrf2 with ML385 abrogated the protective effects of NRN1. In vivo, decreased expression of NRN1 was observed at the site of spinal cord injury in rats. Notably, intramedullary delivery of adeno&#x2011;associated virus (AAV) encoding NRN1 restored NRN1 levels, significantly improved motor function, reduced neuronal apoptosis, and alleviated oxidative stress in spinal cord tissue. Collectively, our findings demonstrate that NRN1 exerts neuroprotective effects against CSCI by binding to FZD2 and activating the GSK&#x2011;3&#x3b2;/Nrf2 signaling pathway, suggesting that targeting NRN1 may represent a novel therapeutic strategy for promoting motor recovery in CSCI patients.

Osteoporosis is a prevalent metabolic bone disease characterized by heterogeneous molecular mechanisms. Emerging evidence implicates that natural killer cells and immunomodulator-related genes (NIRGs) were involved in its pathogenesis; however, systematic exploration of NIRGs remains limited. To explore the role of natural killer (NK) cells and immunomodulator-related differentially expressed genes (NIRDEGs) in osteoporosis. Two osteoporosis datasets (GSE56815 and GSE7429) were integrated after batch effect correction and normalization. Natural killer cell-related genes (NRGs) and immunomodulator-related genes (IRGs) were curated from GeneCards. And NIRDEGs were identified by intersecting co-differentially expressed genes (Co-DEGs) across datasets. Functional enrichment (GO, KEGG, GSEA, GSVA) and immune infiltration analyses were performed. Then, diagnostic models were developed using random forest, support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) regression, validated by receiver operating characteristic curves (ROC), and nomograms. Protein-Protein Interaction (PPI) networks and regulatory networks were generated using bioinformatic tools. Twelve NIRDEGs were identified, and they were enriched in regulation of inflammatory response, myeloid cell homeostasis, negative regulation of DNA-binding transcription factor activity, homeostasis of number of cells, and I-&#x3ba;B kinase/NF-&#x3ba;B signaling. A diagnostic model comprising seven genes (IDO1, PTMA, RAB11FIP1, MYH14, HAMP, HMOX1, and ESR1) exhibited moderate accuracy (0.7&#x202f;<&#x202f;AUC&#x202f;<&#x202f;0.9). The protein-level expression of the six candidate genes was further validated in osteoporosis medol rats. Specifically, the IDO1 and PTMA was obviously elevated in the osteoporosis rat model, while the RAB11FIP1, MYH14, HAMP, and HMOX1 was markedly decreased. Immune infiltration analysis revealed distinct patterns of 20 immune cell types between high and low BMD groups, especially monocytes, macrophages, and eosinophils. The PPI network indicated that five key genes were interconnected (IDO1, PTMA, HAMP, HMOX1, and ESR1) and that there were 20 functionally related proteins. Regulatory networks highlighted interactions with 26 transcription factors (TFs), 28 miRNAs, 26 RBPs and 32 therapeutic compounds. This study establishes NIRDEGs as critical players in osteoporosis pathogenesis and provides a clinically translatable seven-gene diagnostic model for early osteoporosis detection. The integration of multi-omic analyses uncovered key pathways, immune dynamics, and regulatory networks. These findings provide novel insights into immune-mediated mechanisms and therapeutic targets for osteoporosis management.

This study constructed a novel green freezing technology by coupling low-frequency pulsed ultrasound with transcritical CO&#x2082; refrigeration (UTCF). Pectin-sucrose-gelatin gel models (PSGMs) with different moisture contents and fresh fruits and vegetables (FVs) were used to evaluate its freezing characteristics and quality-preserving effects. Results showed that UTCF-40 outperformed RF-40 (traditional refrigerator freezing), it significantly shortened transition time and total freezing time by 18.46-21.79%, thus improving freezing efficiency and decreasing drip loss. Moreover, compared with RF-40, UTCF-40 also exhibited better texture, minimized microstructural damage, and improved moisture-holding capacity. This was mainly attributed to the modulation of ice crystal morphology and size during freezing, with UTCF-40 decreased the ice crystal area by 29.68-35.45% relative to RF-40. Finally, its efficacy was further validated in fresh FVs (blueberry, kiwifruit, citrus, radish). These observed benefits mainly stem from rapid heat transfer of transcritical CO&#x2082; (0 ODP and 1 GWP) and uniform small ice crystals induced by ultrasound. This study confirms that UTCF is a promising green technology for FVs processing.