Search Results (887)

Particulate matter (PM) is a complex mixture of airborne solid particles and liquid droplets originating from various environmental sources, and it has been implicated in the initiation, development, and progression of pulmonary inflammation and respiratory diseases. However, the underlying associated molecular mechanisms remain unclear. Adenophora divaricate Franch. & Sav. (AD) is a medicinal herb classified within the Campanulaceae family and genus Adenophora, with a broad geographic distribution across East Asia, including Korea, Asia, and Russia. In this study, we investigated the mechanisms underlying the effects of AD on PM-induced lung inflammation in both PM-stimulated RAW264.7 cells and PM-exposed mice. Considering that the reactive oxygen species (ROS)-mediated thioredoxin-interacting protein (TXNIP) and NOD-like receptor pyrin domain containing (NLRP3) inflammasome pathway plays a role in PM-induced inflammatory responses, we focused on determining whether AD exerts its anti-inflammatory effects through modulation of this signaling pathway. The anti-inflammatory properties of the methanolic extract of AD were evaluated using PM-stimulated RAW264.7 cells and PM-exposed mice. PM was administered intranasally to mice for 7 days, whereas AD or dexamethasone was orally administered for the same duration. AD treatment significantly attenuated pulmonary inflammation, as evidenced by reduced inflammatory cell counts and decreased cytokine levels in bronchoalveolar lavage fluid. In addition, AD decreased oxidative stress marker (ROS and thiobarbituric acid reactive substances) while increasing glutathione content, leading to suppression of TXNIP/NLRP3 inflammasome expression. Histopathological analysis revealed a marked alleviation of inflammatory responses in lung tissue, characterized by diminished inflammatory cell infiltration and reduced alveolar wall thickening. Collectively, these findings suggest ROS-mediated TXNIP serves as a key regulatory factor, and AD may serve as a potential therapeutic agent for pulmonary inflammation. Full article

The mechanical properties and in situ stress conditions of coal reservoirs critically control the effectiveness of hydraulic fracturing, yet the continuous acquisition of relevant parameters at the well scale is often limited by logging data availability and quality. To address this, an integrated workflow combining machine learning-based parameter inversion with a fracturing suitability evaluation framework was proposed for coalbed methane (CBM) reservoirs. A supervised neural network model was developed to establish nonlinear relationships between conventional logs and key parameters, including Young’s modulus, Poisson’s ratio, and horizontal principal stresses. Based on these inverted parameters, a dimensionless Fracturing Index (FI) was constructed to comprehensively characterize coal fracturability by integrating brittleness, fracture toughness, and stress conditions, with a density-based constraint introduced to ensure mechanical consistency. Point-scale FI values within coal seams were upscaled to the well scale for inter-well comparison and regional evaluation. Results showed that FI varied relatively little within individual wells but markedly between wells, reflecting systematic inter-well variations in mechanical and stress conditions, consistent with spatial patterns revealed by cross-well profiles. Correlation analysis from over ten wells with both FI and treatment data demonstrated positive relationships between FI and breakdown pressure, injected fluid volume, and proppant volume, confirming its engineering relevance. Consequently, a four-level FI-based classification scheme was established to identify favorable zones across the study area. This FI framework provides a practical, interpretable tool for early-stage CBM development, offering quantitative guidance for well prioritization, stimulation design, and regional planning in unfractured areas. Full article

Feline panleukopenia (FPL) is a serious viral disease caused by Feline panleukopenia virus (FPV) that causes leukopenia, lymphopenia, and neutropenia, particularly in young or unvaccinated cats. There is no specific antiviral treatment available for FPL, and treatment protocols generally consist of fluid therapy and supportive care. This study evaluated the clinical and hematological efficacy of filgrastim, a granulocyte colony-stimulating factor (G-CSF) that has shown successful results in treating FPL in various studies, and the paraimmune activator-inactivated Parapoxvirus ovis (iPPVO) in 49 cats naturally infected with FPV. Cats were randomly assigned to four groups: low-dose filgrastim (5 µg/kg, n = 13), high-dose filgrastim (20 µg/kg, n = 14), iPPVO (n = 12), and standard supportive treatment (n = 10). Clinical signs and complete blood counts were assessed on days 0 and 7. By day 7, high-dose filgrastim showed greater increases in white blood cell, lymphocyte, monocyte, and neutrophil counts compared with the other groups (p < 0.05), whereas moderate improvements were observed in the iPPVO group. Leukopenia and lymphopenia resolved faster in the high-dose filgrastim group than in the low-dose filgrastim and standard treatment groups. Clinical recovery, including reduction in vomiting and lethargy, was more pronounced in the high-dose filgrastim and iPPVO groups. Survival rates did not differ significantly among groups (p = 0.615), although the high-dose filgrastim group showed the lowest mortality (42.9%). These findings suggest that high-dose filgrastim may contribute to cytopenias and promote hematological recovery in FPL, while iPPVO may serve as a supportive immunomodulatory therapy. However, it should be noted that the efficacy of filgrastim and/or iPPVO treatments has not been definitively confirmed, likely due to the small sample size and the lack of well-controlled randomized studies. Full article

Curcumin exhibits potent anti-obesity and anti-inflammatory activities; however, its therapeutic application is limited by poor aqueous solubility and low oral bioavailability. A curcumin-loaded chewable gel was developed to transform into an in situ gastric gel upon contact with gastric fluid after mastication. Curcumin solid dispersions (CUR-SDs) were prepared with Eudragit^® EPO (1:1–1:7, w/w) using the solvent evaporation method. The optimized formulation (1:3) markedly enhanced solubility and dissolution in acidic medium (0.1 N HCl, pH 1.2) compared with crystalline curcumin and physical mixtures. The optimized CUR-SD was subsequently incorporated into chewable gels composed of sodium alginate and κ-carrageenan, with calcium carbonate as a gas-forming agent. The formulations formed buoyant matrices under acidic conditions, exhibiting floating lag times of 21–215 s and sustaining drug release for up to 8 h. Increasing polymer content improved mechanical strength and modulated release kinetics. Among the tested formulations, F7 achieved the optimal balance between texture properties, floating behavior, and controlled-release performance. In LPS-stimulated RAW264.7 macrophages, curcumin, CUR-SD, and F7 showed comparable and potent anti-inflammatory activity (IC₅₀ = 4.12–4.84 µg/mL), outperforming indomethacin. In 3T3-L1 adipocytes, F7 significantly reduced lipid accumulation (~47%) in a concentration-dependent manner. These findings demonstrate that this transformable chewable in situ gelling platform is a promising gastroretentive strategy for improving the oral therapeutic efficacy of poorly soluble bioactive compounds for anti-obesity applications. Full article

The perception that hormonal contraception causes weight gain is a general belief that frequently hinders the initiation and continuation of effective family planning. This narrative review analyses data from Cochrane systematic reviews and recent pharmacogenomic studies to separate patient perception from metabolic reality. Analysis of high-quality data, including Cochrane systematic reviews, indicates that the association between Combined Hormonal Contraceptives (CHCs)—including oral pills, the transdermal patch, and the vaginal ring—and weight gain is not supported by consistent high-quality evidence. Placebo-controlled trials demonstrate that these methods are weight-neutral on average. Perceived weight increases in CHC users are likely mediated in part by fluid retention linked to the estrogenic stimulation of the Renin–Angiotensin–Aldosterone System (RAAS), rather than adipose tissue accumulation. Conversely, Depot Medroxyprogesterone Acetate (DMPA) represents a verified clinical risk for weight gain, showing a demonstrated clinical association with significant fat mass accumulation. Hypothesized biological mechanisms for this increase include hypothalamic appetite stimulation and glucocorticoid-like activity. The etonogestrel implant occupies a complex middle ground. While population-level data suggests weight neutrality, recent exploratory pharmacogenomic research has identified a specific variant in the Estrogen Receptor 1 (ESR1) gene. For the minority of women carrying this variant, the implant may trigger clinically significant weight gain, suggesting a biological basis for their subjective experience despite statistical evidence. Ultimately, the persistence of the weight gain concern is fueled by the nocebo effect and the misattribution of natural age-related weight trajectories to contraceptive use. Full article

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article

Geothermal energy is a clean, renewable, and baseload-stable resource of strategic importance for carbon neutrality. Hot dry rock (HDR) reservoirs are characterized by high temperatures, great depths, and abundant reserves. However, their extremely low natural permeability requires artificial fracturing to establish effective heat exchange networks. Conventional hydraulic fracturing in enhanced geothermal systems (EGS) faces major challenges under HDR conditions, including excessive water consumption, strong water–rock interactions, and elevated induced seismicity risks, limiting its engineering applicability. Waterless or low-water fracturing technologies offer alternative stimulation pathways due to their distinctive physicochemical properties. Existing reviews have mainly addressed individual aspects, such as specific fracturing media or proppant transport, without systematically integrating recent advances in supercritical CO₂ fracturing, foam fracturing, liquid nitrogen fracturing, and hybrid-fluid fracturing technologies, or comprehensively evaluating their engineering implications. This review systematically analyzed the fracturing mechanisms, heat exchange performance, environmental risks, and HDR-specific engineering challenges of these technologies. Results indicate that waterless/low-water fracturing technologies enhance heat extraction efficiency by generating complex fracture networks while mitigating seismic and reservoir damage risks. However, large-scale application requires further advances in the high-temperature stability of fracturing media, material durability, multiphase flow control, and field validation. Full article

In vitro fertilisation (IVF) has significant hurdles due to individual differences in ovarian response during controlled ovarian stimulation. The Asn680Ser polymorphism of the follicle-stimulating hormone receptor (FSHR) is linked to varying ovarian sensitivity to FSH. However, its relationship with intrafollicular redox signalling remains unclear. Nitric oxide (NO) is a crucial compound that functions inside follicles and participates in angiogenesis, steroidogenesis, and oocyte competence. This prospective observational research classified women undergoing IVF into Asn allele carriers (Asn/Asn and Asn/Ser) and Ser/Ser homozygotes, according to the FSHR Asn680Ser polymorphism. The groups were assessed according to follicular fluid nitric oxide metabolites (NO₂-NO₃), fertilisation results, ovarian response indicators, and hormonal profiles. No substantial variation was seen between baseline and trigger-day hormone levels. In contrast, Ser/Ser individuals had a significantly higher total count of recovered oocytes, an elevated number of metaphase II oocytes, and enhanced fertilisation outcomes relative to carriers. The Ser/Ser group demonstrated increased intrafollicular NO₂-NO₃ concentrations. This difference was not statistically significant. These results link FSH receptor genetics to functional follicular competence, indicating that the FSHR Asn680Ser polymorphism is associated with differing ovarian responsiveness during IVF and may affect intrafollicular nitric oxide bioavailability. Full article

Vasodilatory shock, primarily driven by sepsis, remains a leading cause of mortality in intensive care units (ICU), with mortality rates exceeding 90% in refractory cases. While norepinephrine is the first-line vasopressor, prolonged exposure to high doses of catecholamines is linked to severe adverse effects, including myocardial toxicity, arrhythmias, and immunodepression. Consequently, the concept of decatecholaminization, utilizing non-adrenergic vasopressors to reduce catecholamine burden, has emerged as a critical therapeutic strategy. This comprehensive review aims to define the current role of vasopressin and its analogues, terlipressin and selepressin, in managing patients with circulatory shock, evaluating their physiological rationale, clinical benefits, and adverse event profiles. The vasopressin system provides a multimodal approach to hemodynamic stability independent of α-adrenergic stimulation. Arginine vasopressin (AVP) acts on V1a receptors to induce vasoconstriction and improve glomerular filtration, and on V2 receptors for water reabsorption. Clinical trials indicate that while AVP may not reduce overall mortality, it significantly reduces the need for renal replacement therapy (RRT) and offers survival benefits in the less severe shock subgroup. Synthetic analogues like terlipressin offer a longer half-life but carry an increased risk of peripheral ischemia. Conversely, selepressin, a pure V1a agonist, was designed to mitigate fluid retention and edema, though recent trials have not yet demonstrated superior clinical outcomes over placebo. Modulation of the vasopressin system is a cornerstone of decatecholaminization in distributive and cardiogenic shock. Although a universal mortality benefit has not been established, these agents are crucial for protecting renal function, reducing catecholamine toxicity, and lowering the incidence of arrhythmias. Future strategies should focus on precision medicine, utilizing biomarkers like copeptin and artificial intelligence to optimize the timing and selection of multimodal vasopressor therapy. Full article

Natural gas represents a pivotal transitional clean energy resource, and biogenic coalbed methane (CBM) is ubiquitously distributed in coal reservoirs worldwide. In the context of carbon neutrality targets and the growing demand for large-scale commercial CBM exploitation, innovative technological solutions are urgently required. CBM bioengineering aims to substantially enhance CBM production by stimulating biomethane generation, promoting gas desorption, and improving reservoir permeability, while simultaneously enabling effective CO₂ sequestration. The potential for biomethane generation is largely governed by the intrinsic physicochemical characteristics of coal, including aromatic structures, maceral composition, and pore–fracture architecture. In addition, hydrogeological conditions—such as geothermal gradients, pH variability, and redox potential—play critical roles in regulating microbial functional gene expression and metabolic enzyme synthesis. Core pretreatment strategies in coalbed gas bioengineering can be broadly classified into approaches that enhance coal bioconversion potential and those that optimize functional microbial consortia. Electric fields and conductive materials can influence microbial community structure by enriching electroactive microorganisms and facilitating interspecies electron transfer. In addition to engineered conductive interventions, reservoir environmental conditions also play an important role in shaping methanogenic community structure. Experimental observations under reservoir-relevant CO₂ pressure and temperature conditions indicate that deep coalbed environments are associated with shifts in methanogenic community composition, including an increased relative abundance of hydrogenotrophic methanogens. These observations suggest that physicochemical conditions in deep coal seams may favor hydrogen-dependent CO₂ reduction pathways, thereby supporting hydrogenotrophic methanogenesis and contributing to biomethane generation. The integration of supercritical CO₂ with microbially acclimated stimulation fluids as an innovative reservoir fracturing strategy offers multiple advantages, including effective reservoir stimulation, permanent carbon sequestration, and sustainable biomethane generation. Future research should focus on modulating coal matrix bioavailability, optimizing microbial consortia, enhancing interspecies metabolic synergies, and advancing carbon fixation bioprocesses to facilitate the large-scale implementation of coalbed gas bioengineering systems. This review synthesizes recent advances in microbially mediated CBM enhancement and CO₂ sequestration, with a particular focus on field-scale evidence and the key challenges that must be addressed for large-scale implementation. Full article

The straddle packer fracturing technique represents a core technology for reservoir stimulation in horizontal wells targeting deep shale gas formations. However, the fracturing string constrained by dual packers is highly susceptible to severe vibrations induced by high-pressure pulsating fluid flow, which subsequently leads to collisions between the string and the casing. These collisions may compromise the sealing integrity of the packers or cause fatigue damage to the string. The existing design of packer spacing primarily relies on static mechanical experience and lacks the support of nonlinear dynamics theory. As a result, it is difficult to maximize operational efficiency while ensuring safety. Therefore, this paper establishes a fluid–solid coupling fracturing string model that takes into account fluid pulsation, geometric nonlinearity and gap collision constraints. Using the Galerkin discretization and the fourth-order Runge–Kutta algorithm, the influence laws of packer spacing and flow rate on the system stability are systematically studied. Studies have shown that the spacing of packers non-monotonically controls the system stability. Both too short or too long packer spacings will induce chaotic instability. However, there exists a highly robust, stable contact window near the ratio. Within this interval, the fracturing string is locked onto a stable period-doubling orbit. Based on this proposed optimization criterion, compared with the traditional conservative design, the spacing of the packers can be extended by approximately 90%. This not only avoids the risk of chaos but also significantly improves the efficiency of the fracturing operation. Full article

Multi-stage multi-cluster hydraulic fracturing in conglomerate reservoirs is often characterized by strong cluster-to-cluster variability in fluid distribution, which can reduce stimulation efficiency. However, field-scale observations that constrain how injected fluid is partitioned among clusters remain limited, especially in strongly heterogeneous formations. In this study, wide-field electromagnetic (WFEM) monitoring was applied to a horizontal well completed in the Baikouquan Formation sandstone–conglomerate reservoir of the Mahu Sag, Junggar Basin. The monitored treatment consisted of 13 fracturing stages, each containing six perforation clusters. Time-lapse electromagnetic data acquired during pumping were inverted to reconstruct the spatiotemporal evolution of the effective conductive fluid-swept region. Based on the inversion results, we introduce a set of quantitative proxy indicators (swept area, swept length, cluster-specific sweep, and an asymmetric index) to support relative comparison of fluid distribution patterns at both stage and cluster scales. Results show pronounced non-uniformity within and between stages, even under similar pumping conditions. A limited number of clusters exhibit stronger and farther-reaching WFEM-inferred conductive-fluid responses, whereas other clusters show weaker or more localized responses. Asymmetric sweep patterns on opposite sides of the wellbore are also commonly observed. These patterns are consistent with the combined influences of reservoir heterogeneity, local structural/stress disturbances, and operational factors, although WFEM alone does not uniquely validate causal mechanisms of fracture growth. Overall, this study demonstrates that WFEM monitoring provides a field-scale proxy tool for delineating effective conductive fluid-swept regions and for evaluating cluster-to-cluster variability under consistent acquisition and inversion settings. The findings offer practical guidance for interpreting fluid distribution and optimizing multi-cluster fracturing in strongly heterogeneous unconventional reservoirs. Full article

Deep-seated coalbed methane (CBM) resources in the Daniudi Gas Field of the Ordos Basin are abundant; however, conventional laboratory-scale hydraulic fracturing experiments are unable to realistically reproduce fracture propagation behavior due to pronounced reservoir heterogeneity and the complex development of bedding and cleat structures. In this study, a self-developed 10,000-ton true triaxial hydraulic fracturing simulation platform was employed to conduct mine-scale experiments using large 2 m × 2 m × 1 m No. 8 coal-rock outcrop specimens. A full-scale steel-casing wellbore and an industrial fracturing fluid system were incorporated to replicate field conditions. Experiments were performed under varying pumping rates (0.2–0.4 m³/min) and fracturing fluid viscosities (10–50 mPa·s). The results indicate that post-failure fractures in deep coal formations primarily develop into complex fracture zones extending vertically from the wellbore. Their morphology is strongly governed by bedding planes and cleats, producing tortuous, banded, and mesh-like patterns. When the fracturing fluid viscosity is maintained between 18 and 27 mPa·s, longitudinal fracture diversion along the wellbore is effectively suppressed, while the increased static pressure promotes the activation of natural fractures. Increasing the pumping rate to 0.4 m³/min markedly enhances the stimulated reservoir volume (SRV), with an increase of approximately 1354%, and significantly increases fracture branch density. However, higher viscosities (>27 mPa·s), despite promoting fracture complexity, reduce proppant transport efficiency due to increased in-fracture tortuosity. This study quantitatively characterizes the coupled responses of fracture volume fraction, branch density, and fracture-surface roughness, and elucidates the interplay between displacement and viscosity in governing fracture network evolution. The findings provide an important experimental foundation for optimizing hydraulic fracturing parameters in the efficient development of deep-seated CBM reservoirs. Full article

Background: Endometriosis is associated with infertility and impaired assisted reproductive technology (ART) outcomes, potentially due to an altered follicular microenvironment characterized by chronic inflammation. This study investigates the systemic and local inflammatory profiles in women with endometriosis and assesses their impact on oocyte and embryo quality using both static and dynamic embryo evaluation. Methods: A prospective, monocentric observational study enrolled 47 women undergoing controlled ovarian stimulation for ART, including 29 with laparoscopically confirmed endometriosis and 18 controls with tubal or male-factor infertility. Serum and follicular fluid cytokines (TGF-β1, NF-κB, IL-10, HIF-1α) were quantified. A sub-study analyzed embryo quality and development in 36 patients subdivided into static morphological assessment and dynamic time-lapse monitoring cohorts. Results: Endometriosis patients exhibited significantly elevated pro-inflammatory cytokines (TGF-β1, NF-κB) and reduced anti-inflammatory IL-10 in serum, alongside decreased NF-κB in follicular fluid. These alterations correlated with diminished ovarian reserve, reduced oocyte yield, and lower fertilization rates. Embryos from endometriosis patients showed increased multinucleation and persistent fragmentation, features more sensitively detected via dynamic time-lapse imaging. Clinical pregnancy rates were significantly lower in the endometriosis group. Conclusions: Endometriosis induces a dysregulated inflammatory follicular milieu that adversely affects oocyte competence and embryo morphodynamics. Dynamic embryo assessment provides enhanced detection of subtle developmental abnormalities. Integration of immunomodulatory strategies and advanced embryo monitoring may improve ART success in this population. Full article

Due to reservoir heterogeneity and drilling/completion damage, the gas production distribution along the wellbore in low-permeability gas reservoirs generally exhibits significant unevenness, restricting the full utilization of single-well productivity. To address this issue, this paper constructs a novel multi-segment horizontal-well flow model considering the permeability differences along the wellbore. Our methodology developed the skin factor calculation method to quantitatively predict production after acid stimulation. Studies have shown that the heterogeneity of permeability along the wellbore significantly controls the gas production contribution and early production response of each well section, and the traditional homogeneity assumption is prone to leading to biases in production capacity evaluation. Compared with general acidizing, targeted acidizing combined with flow constraints can effectively reconstruct the gas production distribution, significantly enhance the contribution of low-yield sections, and improve overall production performance. Taking the P002-H3 well in the Sichuan Basin as an example, based on gas production profile identification and skin coefficient decomposition, drilling fluid invasion was identified as the dominant damage mechanism, and the acidizing scheme was optimized accordingly, verifying the engineering applicability of the proposed method in horizontal-well production capacity evaluation and stimulation optimization. Full article