Search Results (4,338)

Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application. Full article

Background/Objectives: The role of the endometrial microbiome in reproductive failure remains incompletely understood. This study aimed to describe the composition of the endometrial microbiome in women evaluated for infertility or recurrent miscarriage. Methods: In this single-center descriptive study, endometrial samples were collected from women evaluated for infertility or recurrent miscarriage. Microbiome profiling was performed using 16S rRNA gene next-generation sequencing. Samples were classified as Lactobacillus-dominant when Lactobacillus spp. accounted for ≥90% of the total bacterial community. Alpha diversity was assessed using the Shannon and Simpson indices, while beta diversity was evaluated using Bray–Curtis dissimilarity, principal coordinates analysis (PCoA), PERMANOVA, and PERMDISP. Results: Of the 60 samples, 20 (33.3%) were Lactobacillus-dominant and 40 (66.7%) were non-Lactobacillus-dominant. Across all samples, Firmicutes was the predominant phylum (76.6%). Non-Lactobacillus-dominant samples showed significantly higher alpha diversity than Lactobacillus-dominant samples for both the Shannon and Simpson indices (p = 1.19 × 10⁻⁶ and p = 1.51 × 10⁻⁶, respectively), as well as higher observed taxa richness (p = 0.000017). PCoA based on Bray–Curtis dissimilarity demonstrated clear separation between microbiome profiles, supported by PERMANOVA (pseudo-F = 13.87, R² = 0.193, p = 0.001). PERMDISP showed significantly greater dispersion among non-Lactobacillus-dominant samples (F = 566.94, p < 0.001). Non-Lactobacillus-dominant samples showed greater representation of Enterococcus and Prevotella. Conclusions: In this cohort non-Lactobacillus-dominant communities were more frequent with greater diversity, richness, and compositional heterogeneity than Lactobacillus-dominant communities. These findings highlight the need for larger, standardized studies with appropriate control populations to clarify their clinical significance. Full article

Microorganisms in sediments participate actively in biogeochemical cycling and are essential for maintaining the stability of marine ecosystems. To investigate the spatial impact of seaweed mariculture on sediment bacterial communities, three distinct zones were selected along the Zhanjiang coast, China: the Gracilaria salicornia aquaculture zone, a transition zone (adjacent to the aquaculture area), and a control zone (with no direct mariculture influence). In this study, 16S rRNA gene amplicon sequencing was employed to examine the composition, diversity, and potential functions of sediment bacterial communities across these three zones. The dominant microbial communities identified included Pseudomonadota, Thermodesulfobacteriota, Chloroflexota, and Acidobacteriota. Analyses of α-diversity, β-diversity, and molecular ecological network revealed that the bacterial community in the G. salicornia aquaculture zone exhibited significant differences in species composition, community structure, and interspecies interaction compared with those in the transition and control zones. Environmental factors such as pH, dissolved oxygen (DO) and nitrate (NO₃⁻) exerted significant influence on the bacterial community composition and structure. Predicted functional potential analyses indicated high abundances of pathways related to carbohydrate metabolism and amino acid metabolism. Overall, this study characterizes the spatial distribution patterns of microbial communities in a coastal seaweed mariculture ecosystem and provides important data to support further research on biogeochemical processes mediated by sediment bacteria and their response mechanisms to mariculture activities. Full article

To address the application bottlenecks of organic phase change materials characterized by low thermal conductivity and susceptibility to liquid leakage, this study utilized natural poplar wood as a raw material to construct a three-dimensional carbon/silver heterogeneous porous skeleton via delignification, gradient carbonization, and in situ electroless silver plating. Polyethylene glycol (PEG) was then vacuum-encapsulated within this structure to prepare form-stable composite phase change materials (CPCMs). The regulatory effects of carbonization temperature and metal interface modification on the microscopic morphology and thermophysical properties of the materials were systematically investigated. The results indicate that the skeleton carbonized at 800 °C achieves an optimal balance between pore distribution and skeleton rigidity, ensuring the uniform conformal growth of silver nanoparticles and endowing the material with excellent anti-leakage performance. The thermal conductivity of the optimal sample reaches as high as 0.683 W/(m·K), with the melting latent heat maintained at 133.9 J/g, while also demonstrating an agile and stable photothermal conversion response. Non-equilibrium molecular dynamics (NEMD) simulations further confirm that the silver nanoparticle modification layer smooths the phonon vibration frequency mismatch between the carbon substrate and organic segments, significantly reducing the interfacial thermal resistance. This research provides an important reference for the structural design and microscopic heat transfer mechanism analysis of high-performance phase change energy storage materials. Full article

Dryland soils of the Caspian region of western Kazakhstan are exposed to environmental stress, including drought, alkalinity, low soil organic matter content, and anthropogenic pressure. In this preliminary study, bacterial communities were investigated in 18 soil samples collected from six sampling groups across Makat (M1, M2), Isatay (I1, I2), and Beyneu (B1, B2) districts. Soil physicochemical properties were measured, and bacterial diversity was analyzed using 16S rRNA gene sequencing of the V3–V4 region. Community composition analysis indicated spatial heterogeneity among the sampled groups. M1 and I1 showed the highest taxon richness, whereas B2 contained the highest number of unique taxa. Genus-level profiles showed that B1 and M2 were mainly associated with Rubrobacter and related actinobacterial taxa; B2 contained higher proportions of Marinobacter, Tychonema, Qipengyuania, and Halomonas; and I2 was enriched with Antarcticibacterium, Salinimicrobium, Rhodococcus, Gillisia, Marinobacter, Dietzia, and Pontibacter. Correlation analysis showed that several bacterial taxa were associated with soil organic matter content, total nitrogen, total phosphorus, exchangeable cations, and pH, although the overall Mantel relationship between soil properties and community structure was not significant. FAPROTAX-based prediction indicated differences in putative heterotrophic, nitrogen-related, sulfur-related, and hydrocarbon-associated functional categories among sites. Because FAPROTAX predictions are based on taxonomic composition, these results should be interpreted only as putative functional potential and not as evidence of actual microbial metabolic activity. These findings suggest that the sampled Caspian dryland soils contain distinct bacterial assemblages and taxa with potential ecological relevance; however, their role in dryland soil resilience or bioremediation should be verified through future culture-based, metagenomic, and functional validation studies. Full article

Extracellular vesicles (EVs) are key mediators of intercellular communication across biological kingdoms, with central roles in immune regulation and disease processes. Despite shared structural features, EVs derived from bacteria, plants, and mammalian cells differ substantially in their biogenesis, molecular composition, and immunological functions. EV formation pathways generate vesicles with distinct cargo profiles, including pathogen-associated molecular patterns (PAMPs) in bacterial EVs, regulatory small RNAs in plant-derived vesicles, and cytokines, microRNAs, and antigen-presenting complexes in mammalian EVs. Differences in cargo result in divergent immune outcomes. Bacterial EVs predominantly activate innate immunity via pattern recognition receptors such as Toll-like receptors, whereas plant-derived EVs exhibit low immunogenicity and mediate cross-kingdom RNA interference. In contrast, mammalian EVs primarily regulate immune responses by modulating antigen presentation and cytokine signaling. These findings support a framework in which EV origin determines immunological function and therapeutic applicability. This perspective highlights the importance of selecting appropriate EV sources for vaccine development, regenerative medicine, and targeted delivery strategies, while addressing current challenges related to heterogeneity, standardization, and safety. Full article

To investigate the impact of underground multiple stress disturbances on the long-term stability of cemented tailings backfill (CTB), this study conducted experiments under different disturbance levels (20–80% of static strength) and frequencies (1–4 times). By comprehensively utilizing mechanical testing, wave velocity monitoring, digital image correlation (DIC), and scanning electron microscopy (SEM), the “heterogeneous” evolution mechanism of macro-micro damage was revealed. The results indicate that disturbance level and frequency exert distinctly different driving effects on the deterioration of CTB, rather than a simple linear superposition. Specifically, low-frequency disturbance produces a compaction strengthening effect, microscopically promoting the generation of Ca(OH)₂ and ettringite (increased Ca/Si ratio). In contrast, the combination of high disturbance and high frequency induces free water extrusion and inhibits hydration, leading to an advanced damage threshold based on energy evolution and the accelerated coalescence of microcracks, which favors the formation of C-S-H gel (decreased Ca/Si ratio). Within this heterogeneous mechanism, the disturbance level acts as the dominant controlling factor. This study clarifies the nonlinear mechanical and chemical evolution paths under composite disturbances, providing theoretical support for the dynamic stability control of backfill in deep multi-step mining. Full article

Background/Objectives: Foot and ankle presentations during Hajj occur in a dense mass-gathering environment where prolonged walking, heat exposure, crowding, variable footwear, and limited self-care can interact with chronic disease and wound vulnerability. Previous Hajj studies have described foot injuries and diabetes-related complications, but less is known about whether simple high-risk foot documentation flags identify presentation records with higher care-pathway intensity. The primary objective was to estimate the presentation-level burden of core high-risk foot profiles among pilgrims presenting with foot and ankle conditions during Hajj 2025. Secondary objectives were to evaluate associations with a surgery-coded care-intensity indicator, hospital referral, and component heterogeneity. Methods: This observational presentation-level analysis included 3957 foot and ankle presentation records. The unit of analysis was the presentation/case record, not a unique individual pilgrim. A core high-risk foot profile was defined as diabetes, neuropathy, diabetic foot ulcer, foot ulcer, complications of open wound, or osteomyelitis. The primary outcome was a surgery-coded care-intensity indicator, defined solely from treatment documentation containing “Surgery” and interpreted as a care-pathway proxy rather than confirmed operating-room surgery. Logistic regression estimated crude and adjusted odds ratios (ORs); exploratory risk-category analyses assessed heterogeneity within the composite profile. Results: Core high-risk foot profiles were identified in 1793/3957 presentations (45.3%). The primary outcome occurred in 239/1793 high-risk presentations (13.3%) and 201/2164 non-high-risk presentations (9.3%), an absolute difference of 4.0 percentage points. The crude OR was 1.50 (95% CI 1.23–1.83; p < 0.001). The association persisted in the primary adjusted model (adjusted OR 1.47; 95% CI 1.20–1.79; p < 0.001) and in the extended clinical sensitivity model (adjusted OR 1.47; 95% CI 1.20–1.80; p < 0.001). Care pathways and secondary outcomes are summarized was also more frequent in high-risk presentations (12.2% vs. 9.8%; crude OR 1.28; 95% CI 1.05–1.57; p = 0.017). Exploratory category analysis showed that chronic-risk-only presentations had a primary outcome rate similar to non-high-risk presentations (9.0% vs. 9.3%), whereas ulcer/wound/deep-infection presentations had a higher rate (17.3%; crude OR 2.04; 95% CI 1.63–2.55; p < 0.001). Model discrimination was modest (C-statistics 0.55–0.64). Conclusions: Core high-risk foot flags were common among Hajj foot and ankle presentation records and were associated with surgery-coded care-intensity and referral documentation. However, the composite was clinically heterogeneous, the outcome was not a validated surgery endpoint, and the models were not prediction tools. These findings support cautious use of high-risk foot flags as operational prompts for assessment and pathway planning rather than as standalone clinical risk estimates. Full article

Urban flood vulnerability is increasingly shaped by the interaction between climate change, urbanization, and spatial planning practices, particularly in Mediterranean metropolitan areas. This study develops an integrated GIS–AHP framework to assess the susceptibility component of flood vulnerability in the urban area of Thessaloniki, Greece. Using open-access geospatial data, ten indicators representing soil, hydrological, and environmental conditions are derived and spatially analyzed. The Analytic Hierarchy Process (AHP), based on expert judgment, is applied to estimate the relative importance of these indicators and to support their integration into a composite flood susceptibility index. The results reveal strong spatial heterogeneity, with high susceptibility concentrated in low-lying, densely urbanized areas and zones near drainage pathways. Among the examined factors, the Topographic Wetness Index emerges as the most influential, highlighting the persistent role of terrain-driven hydrological processes even in highly built environments. The proposed framework provides a transparent and transferable methodology for identifying flood-prone areas and supports evidence-based urban planning and climate resilience strategies. The findings contribute to the broader discussion on vulnerability and resilience in urban systems by linking spatial analysis with decision-support tools in a policy-relevant context. Full article

Reservoir effectiveness in marine shales is controlled not only by pore volume but also by pore-fluid occurrence, pore–throat connectivity, and mineral–organic matter coupling. In this study, the Permian Gufeng Formation shales from the Enshi area, western Hubei, South China, were investigated through an integrated analysis of total organic carbon (TOC), X-ray diffraction (XRD)-based mineral composition and lithofacies, low-field nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), micro-computed tomography (Micro-CT), and entropy-weighted technique for order preference by similarity to an ideal solution (TOPSIS) evaluation. The TOC content ranges from 1.60% to 21.38% and shows clear vertical differentiation, with moderate but variable enrichment in the lower interval, reduced organic matter abundance in the middle interval, and pronounced organic enrichment in the upper interval. Mineral compositions demonstrate an upward transition from a mixed siliceous–carbonate system to a dominantly siliceous shale system. NMR results reveal strong heterogeneity in porosity, NMR-derived permeability, T2cutoff, bound-fluid saturation, and free-fluid saturation. Based on saturated and centrifuged T2 spectra, four descriptive reservoir response types were identified: short-T2-dominated micropore-bound response, intermediate-T2-dominated movable-fluid response, long-T2-enriched but low-efficiency response, and NMR-inferred enhanced mobility composite response. SEM observations show diverse pore types, including organic-matter-related pores, dissolution pores, interparticle pores, mineral-edge pores, pyrite intercrystalline pores, and local microfracture-like pores. Micro-CT results indicate that micrometer-scale pore bodies are commonly isolated, demonstrating that pore abundance or pore size alone cannot determine reservoir effectiveness. TOC mainly controls pore generation potential, whereas siliceous minerals, pore–throat connectivity, movable fluid proportion, and local fractures exert stronger controls on effective reservoir development. The most favorable reservoir responses are concentrated in the upper high-organic siliceous shale interval from A33 to A42, with local enhanced responses in A16 and A21. These results provide an integrated framework for evaluating reservoir heterogeneity and favorable intervals in complex marine shale systems. Full article

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Human saliva is a heterogeneous bodily fluid with a complex composition, which contains antibodies, proteins, and viruses, making it applicable in clinical diagnosis. There are several advantages of the analysis of saliva samples over other biofluids, including a non-invasive and simple collection procedure for extraoral detection. Biomarker or pathogen detection in saliva can be performed with various methods: mass spectrometry, PCR, ELISA, electrochemical, and optical methods such as fluorescence, SPR, and SERS. The early detection of cancer and other disease biomarkers, as well as infectious agents, can be crucial for effective treatment and minimization of mortality from those diseases. The following paper reviews extraoral detection techniques to identify the most sensitive methods for diagnosing early and asymptomatic patients. The LODs collected and tabulated from 149 analytical papers, alongside the sensitivity, specificity, and sometimes the area under the curve (AUC) tabulated from 118 clinical studies, have all become parameters for the comparative quantitative analysis. Based on the limited but substantial number of analytical studies on the detection of cortisol in saliva (29), the electrochemical platforms demonstrated the highest sensitivity, with a geometric mean LOD of 11 pM. Within these methods, voltametric ones showed the best performance with 6 pM geometric mean LOD. Electrochemical techniques are then followed by immunoassay- and mass spectrometry-based platforms, with corresponding geometric average LOD values of 39.1 and 171 pM, respectively. However, clinical outcomes are at least as meaningful as LOD values. In terms of clinical analysis, ELISA and direct-SERS outperformed other methods, achieving balanced accuracy of approximately 87% and AUC values of 0.96 for direct SERS and 0.86 for ELISA. MS and PCR followed closely, with balanced accuracies around 84%. While the direct SERS is not yet widespread in clinical applications, its potential can be forged if the standardization issue is addressed. Full article

Heterogeneous hydrogels capable of complex, programmable deformation are highly desirable for soft actuators, yet general strategies that simultaneously impart structural anisotropy, rapid responsiveness, and mechanical robustness remain limited. Here, a gradient anisotropic natural rubber-poly(N-isopropylacrylamide) (NR-PNIPAM) composite hydrogel is developed through a simple one-pot polymerization strategy by coupling pH-regulated colloidal stability with gravity-directed redistribution of natural rubber latex particles. Under an optimized pH window, NR nanoparticles gradually migrate during gelation and are fixed as a continuous gradient within the PNIPAM network, generating built-in structural asymmetry for nonuniform deformation. Meanwhile, NR nanoparticles act as soft reinforcing domains to improve mechanical strength, while water-soluble graphene nanosheets provide efficient photothermal conversion for remotely-controlled near-infrared (NIR)-responsive actuation. Benefiting from this synergistic design, the hydrogel exhibits programmable bending and localized folding with high actuation rates of 129° s⁻¹ and 46° s⁻¹, respectively, along with a tensile strength of 0.32 MPa and an active lifting capability exceeding 70 times its own weight. The material further enables biomimetic gripping and lifting under NIR stimulation. This work establishes a general route to robust gradient hydrogels by integrating colloidal regulation, structural anisotropy, and photothermal actuation, offering a versatile platform for high-performance soft intelligent systems. Full article

Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail to address the underlying gut microbial imbalance, prompting growing interest in microbiota-based therapies. Probiotic supplementation has demonstrated potential to modulate the disease. However, its clinical application is limited by variability in formulations and strain composition. Debate persists regarding the relative benefits of single-strain probiotics (SSPs), which depend on strain specificity, versus multi-strain probiotics (MSPs), which may provide synergistic effects. The literature remains inconclusive, with some studies indicating that MSPs outperform SSPs, while others emphasize the importance of strain specificity. This review describes the mechanistic basis of both approaches and descriptively synthesizes their clinical efficacy in UC management based on the clinical studies published between 2018 and 2025. Several studies report that both SSPs and MSPs are associated with clinical improvements, including reduced disease activity, symptom alleviation, and enhanced endoscopic outcomes. Given the methodological heterogeneity across included studies, comparative findings should be interpreted with appropriate caution. A direct head-to-head trial could provide a better understanding to determine the optimal approach. Advancing toward personalized probiotic therapy may further enhance the clinical application of probiotics for disease management. Full article

The past few years has witnessed the rapid development of China’s logistics industry. However, the industry still faces problems such as uneven regional development, low-cost efficiency, insufficient technology application, and pressure for green transformation. To support more effective policy and strategic planning, this study used composite location entropy, spatial autocorrelation analysis, and kernel density estimation to analyze the spatiotemporal evolution of logistics industry agglomeration based on China’s city-level panel data from 2010 to 2023. Geographic detectors and geographically weighted regression were used to explore its driving mechanisms from multiple perspectives. The results indicated that (1) China’s logistics industry agglomeration exhibited a decreasing gradient from east to west and the regional disparities gradually narrowed down over time. (2) China’s logistics industry showed significantly positive spatial autocorrelation, characterized mainly by high-high and low-low clusters. Northeastern China experienced the most active and tortuous local spatial evolution of logistics agglomeration, while Eastern China exhibited high tortuosity but stable spatial structure. Western China showed a smooth evolution, and Central China followed a relatively independent evolutionary path. Spatially, China’s logistics industry presented a pattern of high concentration in the southeast and sparse distribution in the northwest, with high-value zones expanding toward the central and western regions. (3) Transportation accessibility was the primary factor influencing logistics industry agglomeration, and the interaction among factors was stronger than the effect of individual factors. Specifically, the degree of openness exhibited a driving pattern centered on coastal areas and decreasing towards inland regions; the level of commercial development showed a positive correlation in the west and a negative correlation in the east; the spatial pattern of transportation capacity shifted from a pronounced east–west polarization to a more fragmented multi-cluster distribution; and transportation accessibility demonstrated spatial heterogeneity, with positive correlation in the southeast coastal areas and negative correlation in the west. Full article