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Background Patients with acute ischemic stroke (AIS) and cancer are at exceptionally high risk for recurrent thromboembolism (RTE), which includes venous thromboembolism (VTE) and arterial thromboembolism (ATE). Yet contemporary data from Chinese patients remain scarce. Methods In this retrospective, observational study conducted at Tianjin First Central Hospital (June 2023-December 2024), consecutive adults with AIS and cancer were enrolled. The primary outcomes during 6 months follow-up were recurrent VTE།composite VTE (symptomatic and incidental VTE requiring treatment), recurrent stroke [cerebral infarction, transient ischemic attack (TIA), and systemic embolism (SE)], and bleeding (major bleeding and clinically significant non-major bleeding). Multivariable logistic regression was used to identify independent predictors of each endpoint. Results Among 218 eligible patients, 49 (22.5%) had baseline VTE, of whom 45 (91.8%) were asymptomatic. Baseline VTE was independently predicted by cryptogenic stroke subtype (OR 2.70; 95% CI 1.101–6.621; P  = 0.030) and D-dimer > 1.2 µg/mL (OR 3.619; 95% CI 1.505–8.703; P  = 0.004). During follow-up, 25 patients (11.5%) experienced composite VTE, 71 patients (32.6%) experienced recurrent stroke, and 21 patients (9.6%) experienced bleeding. Multivariable analysis revealed that D-dimer > 1.2 µg/mL independently predicted recurrent VTE (OR 3.501; 95% CI 1.012–12.112; P  = 0.048), whereas cancer metastasis portended recurrent stroke (OR 3.155; 95% CI 1.423–6.995; P  = 0.005), and anticoagulant therapy was associated with an increased bleeding risk (OR 9.458; 95% CI 1.158–77.267; P  = 0.036). Conclusions In this Chinese cohort of patients with acute ischemic stroke (AIS) and cancer, routine screening revealed venous thromboembolism (VTE) in roughly one-fifth of participants at baseline, most of whom were asymptomatic. Exploratory multivariable analyses indicated that cryptogenic stroke subtype and D-dimer > 1.2 µg/mL were associated with prevalent VTE, while D-dimer > 1.2 µg/mL also predicted recurrent VTE. These findings suggested that D-dimer guided VTE screening might be considered at the time of stroke presentation, even in the absence of symptoms. Cancer metastasis showed an association with recurrent stroke, whereas anticoagulant therapy was linked to a higher bleeding risk.

Background/Objectives: This study investigates the therapeutic potential of camel milk-derived extracellular vesicles (CM-EVs) for treating colonic damage caused by high-altitude hypoxia, supporting the WHO’s “Food as Medicine” initiative. Methods: Using a 5500 m mouse model, researchers induced colonic injury and treated it with oral CM-EVs for 15 days, comparing results to whole camel milk. Results: CM-EVs outperformed whole milk, significantly improving colon health by restoring barrier integrity and reducing disease activity index (DAI) (p < 0.01). They boosted beneficial bacteria like Lactobacillus and Bifidobacterium and decreased Enterobacteriaceae (p < 0.01). Metabolic analysis showed restored bile acid balance and amino acid modulation via the FXR/NF-κB pathway, reducing TLR4/MyD88-mediated inflammation and oxidative stress (p < 0.01). Fecal microbiota transplantation in the CM-EVs group notably decreased DAI and increased colon length (p < 0.05). Conclusions: CM-EVs repair mucosal damage, balance microbiota, and regulate metabolism to combat hypoxia-induced colonic damage, suggesting their potential as nutraceuticals and altitude-adaptive foods. This showcases nanotechnology’s role in enhancing traditional dietary benefits via precision nutrition.

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1 ) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases. Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Here, the authors show that Sortilin in adipose tissues facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation, which controls adipose tissue fatty acid oxidation and substrate fuel selection during beige fat activation.

In Escherichia coli , RNase E, a central enzyme in RNA processing and mRNA degradation, contains a catalytic N-terminal domain, a membrane-targeting sequence (MTS), and a C-terminal domain (CTD). We investigated how MTS and CTD influence RNase E localization, diffusion, and function. Super-resolution microscopy revealed that ~93% of RNase E localizes to the inner membrane and exhibits slow diffusion similar to polysomes. Comparing the native amphipathic MTS with a transmembrane motif showed that the MTS confers slower diffusion and stronger membrane binding. The CTD further slows diffusion by increasing mass but unexpectedly weakens membrane association. RNase E mutants with partial cytoplasmic localization displayed enhanced co-transcriptional degradation of lacZ mRNA. These findings indicate that variations in the MTS and the presence of the CTD shape the spatiotemporal organization of RNA processing in bacterial cells, providing mechanistic insight into how RNase E domain architecture influences its cellular function.

This study aimed to examine the effects and the efficacy of a combination of interventional embolization and endocrine hormone therapy for Pelvic congestion syndrome (PCS). We retrospectively analyzed 132 patients diagnosed with PCS, and divided them into three groups based on their therapeutic schedule. The visual analog scale (VAS), pelvic venous blood flow parameters, and serum hormone levels of the three groups were compared before and after treatment. Moreover, the clinical efficacy and long-term changes in ovarian reserve functions were analyzed. For the comparison of measurement data before and after treatment within the group, paired - sample - test was used for analysis. For the comparison between groups, one - way analysis of variance was applied. A P - value less than 0.05 indicated a statistically significant difference. Patients in the study group had significantly lower pain degrees than in the control group I and the control group II at 24 h and the first month after the operation ( < 0.05). The degree of pain in patients in the study group was significantly lower than that in the control group I at the third and 6 months following the treatment ( < 0.05). The parameters of venous blood flow and ovarian reserve in patients treated with the combined endocrine hormone therapy were significantly better than those in patients not treated with endocrine hormone therapy ( < 0.05). The total effective rate of the study group was significantly higher than that of the control groups ( < 0.05). A combination of precise interventional embolization and endocrine hormone therapy can rapidly and effectively relieve pain in patients with PCS. Compared with free coil embolization, this combination can effectively increase vascular tension, reduce congestion, inhibit ovarian function, reduce pelvic congestion, and relieve symptoms.

Beige adipose tissue protects against obesity and related metabolic diseases by catabolizing stored energy to generate heat. While iron is essential for this process due to its role in mitochondrial function, the specific signaling mechanisms involved remain unclear. Here, we report that diet-induced obese mice exhibit a local iron deficiency in subcutaneous adipose tissue. Crucially, through integrated multi-omics approaches (RNA-seq and ATAC-seq), we identify that iron downregulates Paraspeckle component 1(PSPC1), which interacts with SMAD family member 3 (SMAD3) to promote its phosphorylation. The iron-induced reduction of PSPC1 alleviates the repressive signaling of SMAD3 on thermogenic gene expression, thereby inducing the beiging of white adipocytes. Furthermore, overexpression of Pspc1 in subcutaneous adipose tissue counteracted the iron-induced suppression of SMAD3 phosphorylation, effectively reversing iron-induced beiging of white adipocytes and its associated metabolic benefits. Collectively, our findings demonstrate that iron promotes the beiging of white adipocytes within subcutaneous adipose tissue and exerts anti-obesity effect by inhibiting PSPC1-SMAD3 axis, which may provide a potential therapeutic target for obesity and its related metabolic diseases. Graphical Abstract Iron protects against diet-induced obesity by promoting the beiging of adipocytes in white adipose tissue. This study identifies a novel regulatory mechanism where iron downregulates the expression of PSPC1. The reduction in PSPC1, which interacts with SMAD3, leads to decreased SMAD3 phosphorylation, thereby relieving its inhibition on thermogenic genes.

This study aims to investigate the synergistic and attenuation mechanism of Xihuang pill in the treatment of cholangiocarcinoma (CCA), thereby providing a reliable scientific basis for the selection of postoperative treatment strategies in cholangiocarcinoma patients. In total, 120 patients with advanced CCA who underwent stent implantation were divided into control group I (n = 40), control group II (n = 40), and observation group (n = 40). The patients in control group I were only treated with a tumor immunosuppressant (tislelizumab injection), the patients in control group II were administered tumor double immunotherapy (tislelizumab injection + thymalfasin injection), and the patients in the observation group were treated with Xihuang pill combined with tumor double immunotherapy. The therapeutic effect, side effects, coagulation function, tumor markers, and immune function were compared among the three groups. Compared to the patients in control groups I and II, those in the observation group showed significantly longer activated partial thromboplastin time (APPT) and prothrombin time (PT), and lower fibrinogen (FIB) levels and platelet count (PLT) after treatment (P < 0.05). In the observation group, the levels of CD3+, CD4+, and CD4+/CD8+ increased, but the level of CD8+ decreased. The levels of CEA, CA125, CA19-9, CA242, and CA50 in serum decreased. The adverse reactions in the observation group were lower, while the objective remission rate (ORR) was significantly higher than their corresponding values in control groups I and II (42.5%vs17.5%, 27.5%) (P < 0.05). The 1-year overall survival rates of the control group I, control group II and observation group were 42.5%, 50% and 60%, and the difference was not statistically significant (P > 0.05). Xihuang Pill combined with dual immunotherapy can synergistically enhance anti-tumor efficacy and reduce treatment-related toxicity in patients with advanced CCA by regulating coagulation function and immune mechanisms.

Static charges on optical anti-counterfeiting membranes may lead to materials structural changes, dust stain aggravation, and misreading of optical information. Incorporating conductive particles is a common way to transfer accumulative charges, but the key issue is how to achieve high dispersion and effective distribution of particles. According to the strategy of assembly-induced structural colors, cellulose nanocrystals (CNCs) were employed as a solid emulsifier to stabilize hydrophobic carbon nanoparticles (CNPs) in aqueous media; subsequently, by solvent-evaporation-modulated co-assembly under a condition of 30 °C and 20 RH%, the binary suspensions containing 2 wt% CNC and CNPs with the equivalent concentration relative to CNC ranged from 1:40 to 1:10 were used to prepare antistatic composite membranes. Surface chemistry regulation of CNCs was applied to optimize the dispersibility of CNPs and the orientation of assembled CNC arrays, and the hydrophilic CNCs were more favorable for dispersion and assembly of binary suspension systems. Meanwhile, one-dimension carbon nanotube (CNT) and zero-dimension carbon black (CB) were found to show better dispersibility than two-dimension graphene, which was verified by a semiquantitative theoretical study. Moreover, the stable binary systems of CNT/CNC and CB/CNC were chosen for co-assembly as membranes, and the uniaxial orientation could be optimized as the full-width of 9.8° at half-maximum deviation angle while the surface resistivity could also drop down to 3.42 × 102 Ω·cm·cm−1. The structural color character of such paper-homology and antistatic-integrated membranes contributes to optical information hiding-and-reading, and shows great potential as optical mark recognition materials for electrostatic discharge protective packaging and anti-counterfeiting applications.

The preservation and transportation of raw camel milk are essential for the maintenance of its molecular biological activity. Prolonged storage periods and improper storage temperatures can diminish both the nutritional value and biological functionality of its constituent molecules. This study examines the effects of storage conditions on commercially sourced Bactrian camel milk from Delingha City, Qinghai Province, China. Results indicate that the levels of protein, amino acids, fats, and fatty acids in camel milk stored in a 4°C milk tanker truck decrease progressively over a period of 0 to 7 days. Microbial analysis indicates a shift in microbial composition over time, characterized by a notable rise in Psychrobacter and a marked decline in Kocuria . These alterations in microbial populations result in the degradation of various components. Drawing on previous research, this study underscores the unsuitability of transporting camel milk over long distances in 4°C milk tankers to preserve the quality and nutritional integrity of the product.

BackgroundWe previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia.MethodWe carried out a case–control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500–3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.ResultsAverage cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72–4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99–27.75), long gestational age (AOR = 3.18, 95% CI: 1.74–5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34–3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31–11.69) significantly increased the risk of macrosomia.ConclusionsLower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.