Search Results (599)

Ketosis is a prevalent metabolic disorder in early-lactation dairy cows, significantly affecting animal health, milk production, and farm profitability. Developing accurate and non-invasive methods for early risk detection is therefore of critical importance. In this study, a hybrid optimization framework integrating an Improved Whale Migration Algorithm (IWMA) with a Light Gradient Boosting Machine (LightGBM) is proposed to predict ketosis risk based on the milk fat-to-protein ratio (F/P) using Dairy Herd Improvement (DHI) records. The proposed IWMA enhances optimization performance through cubic chaotic initialization, elite opposition-based learning, and a Cauchy–Gaussian hybrid mutation strategy, enabling improved global exploration and convergence stability. A dataset comprising 25,155 DHI records collected from multiple commercial dairy farms over seven months was used for model development and evaluation. Experimental results demonstrate that the IWMA–LightGBM model achieves a classification accuracy of 0.8997 and a mean squared error of 0.289, consistently outperforming six benchmark optimization methods. Feature analysis identifies Herd Within Index (WHI), Energy Corrected Milk (ECM), Days in Milk (DIM), Milk Urea Nitrogen, and Foremilk as key predictors associated with metabolic risk. Overall, the proposed approach provides a robust and effective non-invasive solution for early-stage metabolic risk screening at the herd level, offering practical value for precision dairy management. It should be noted that the model is intended for risk assessment rather than clinical diagnosis of ketosis. Full article

Poor vascularization is one of the basic obstacles to the regeneration of functioning tissues because an oxygen diffusion process and elimination of wastes are essential in preserving the grafts. Recently, biomaterials have allowed the invention of bioinspired polymer scaffolds and replicated the natural extracellular matrix (ECM) due to the mechanical tunability of the synthetic polymers with the biological signals of natural macromolecules. The review uses a mechanistic analysis of the strategies to improve angiogenesis by using surface topography modification, bioactive peptide incorporation and pre-vascularization. Another way to achieve complex, perfusable topologies is by using more sophisticated methods of fabrication, such as electrospinning, 3D/4D bioprinting, or microfluidics. Based on in vitro and in vivo results, we determine angiogenic effectiveness by using cellular assays and animal transfers, pointing towards the translational advances in patents and clinical uses of bone, cardiac, nervous, and skin tissues. In spite of the substantial improvements, large-scale production and high demands of the regulations still exist. The future directions include the incorporation of bioinspired designs and intelligent materials, nanotechnology, and AI-based optimization into developing patient-specific and adaptive scaffolds. The following innovations herald the advent of highly effective constructs that can be used to regenerate tissue and overcome the limitations of present tissue engineering therapies through the introduction of highly effective, vascularized constructs. Full article

This study investigates the short-term and long-term impacts of gross domestic product (GDP), inflation, foreign capital flows, trade balance and interest rate on stock market performance in Saudi Arabia for the period 1990–2023. The autoregressive distributed lag (ARDL) approach and error correction model (ECM) are employed to empirically examine the short-run and long-run relationships. The ARDL-ECM technique is effective for analyzing cointegration and assessing adjustment processes. Additionally, impulse response function (IRF) analysis based on the vector autoregression (VAR) model, estimated using these macroeconomic indicators, is applied in this paper. This study provides novel insights and addresses emerging gaps in the literature concerning Saudi Arabia as a developing economy. The long-term relationship in the bounds test results confirms its existence. In the long run, inflation and interest rate exert a statistically significant negative effect on stock market performance, while the trade balance has a significant positive impact. GDP and foreign capital inflows do not exhibit statistically significant long-run effects. Short-run dynamics indicate persistence in stock market performance along with significant effects from inflation and interest rate changes, while GDP and foreign capital inflows remain statistically insignificant in the long-run scenario. Forecast error variance decomposition (FEVD) results show that approximately 68.5% of the variation in market performance is explained by its own shocks, followed by foreign capital flows (16.3%) and inflation (8.4%). While foreign capital flow does not exhibit statistical significance in the ARDL long-run estimates, its contribution in variance decomposition highlights its role as an important source of external shocks. These findings are relevant to various stakeholders, including investors and policymakers. Additionally, policy emphasis should be placed on controlling inflation and maintaining stable interest rates while improving trade balance conditions. Although foreign capital flow does not show a direct long-run effect, its role in influencing market variability suggests the need for a stable and well-regulated investment environment. Full article

This paper presents an energy performance assessment and the development of an energy consumption baseline model for a quarry located in Gauteng Province, South Africa. Using 24 months of historical electricity consumption and production data, the energy use intensity (EUI) was calculated to benchmark the quarry against similar international operations. The results show that the quarry performs competitively, ranking third among seven comparable sites despite having no energy conservation measures (ECMs) in place. A linear regression model was developed to predict energy consumption based on tons produced, yielding a strong correlation (R² = 0.92) and statistically significant parameters. Model validation metrics—including a CVRMSE of 9%, Durbin–Watson value of 2.818, and negligible Net Determination Bias—indicate a reliable and accurate baseline suitable for future energy savings verification. The study highlights opportunities to further improve performance through energy management programmes and operational changes. Full article

Intervertebral disc degeneration (IDD) is a fundamental pathological basis of low back pain, yet its pathogenic mechanisms remain incompletely understood. Infection by low-virulence anaerobic bacteria has recently been recognized as a potential etiological factor. In this study, Cutibacterium acnes (C. acnes) was detected in 13.7% of degenerated intervertebral disc (IVD) tissues, and its presence was significantly associated with younger patients and Modic changes. In vitro experiments demonstrated that C. acnes supernatant induces oxidative stress, apoptosis, and extracellular matrix (ECM) degradation in nucleus pulposus (NP) cells in a dose-dependent manner. RNA sequencing and functional validation further indicated that these pathological effects are mediated through activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 with the specific inhibitor BIRB-796 effectively reversed the observed cellular damage. Wogonin exhibited negligible cytotoxicity toward NP cells and significantly attenuated C. acnes supernatant-induced oxidative stress, apoptosis, and ECM metabolic imbalance by inhibiting the phosphorylation of p38, JNK, and ERK1/2 within the MAPK pathway. Furthermore, in vivo experiments confirmed that Wogonin alleviated disc height loss, reduced T2-weighted signal attenuation, and mitigated histological damage induced by C. acnes in rat models, thereby restoring the balance between ECM synthesis and degradation. Collectively, this study demonstrates for the first time that C. acnes supernatant exacerbates IDD through activation of the p38 MAPK signaling pathway. It further shows that Wogonin can specifically inhibit this pathway and effectively ameliorate C. acnes-mediated IDD damage in both in vitro and in vivo models. These findings expand the theoretical framework of infection-related mechanisms underlying IDD and identify potential therapeutic targets and candidate agents for the treatment of IDD associated with C. acnes infection. Low back pain is a common health issue affecting populations worldwide, with intervertebral disc degeneration as its core etiology. However, the pathogenic causes in some patients, especially young individuals, remain incompletely understood. This study found that Cutibacterium acnes, a low-virulence bacterium commonly colonizing human skin and mucous membranes, produces metabolic products that can induce damage to the core cells of the intervertebral disc, exacerbate disc degeneration, and this process is associated with the abnormal activation of specific cellular signaling pathways. Through clinical sample detection, cell experiments, and animal model validation, we confirmed that infection with this bacterium is closely related to young patients and specific spinal imaging changes. Meanwhile, we identified Wogonin, a natural compound extracted from Scutellaria baicalensis, which can effectively inhibit the aforementioned abnormal signaling pathways, alleviate cell damage caused by bacterial metabolic products, and improve the pathological state of intervertebral disc degeneration. This study not only reveals the role of low-virulence bacterial infection in intervertebral disc degeneration and provides a new explanation for the pathogenic mechanism in young patients but also offers a natural antibiotic-free candidate for addressing bacterial resistance. It holds significant reference value for the clinical diagnosis and treatment of spinal diseases as well as the development of related drugs. Full article

Demineralized bone matrices (DBMs) are widely used in bone replacement therapy. Bone tissue of either cancellous or cortical origin is decellularized, demineralized, and sterilized during processing, while retaining portions of native organic extracellular matrix (ECM) proteins that regulate cell–matrix interactions during bone repair. The ECM largely accounts for the distinct functions of cortical and cancellous bone. Differences in three-dimensional architecture and matrix density between cancellous and cortical bone may therefore affect ECM proteome signatures and the resulting cellular microenvironment. In this study, ECM proteins were extracted from processed cancellous and cortical allografts at multiple processing steps and analyzed by quantitative mass spectrometry. We identified distinct extractable proteome signatures associated with bone metabolic functions. Cancellous grafts were relatively enriched in proteins associated with inflammatory, coagulative, and immune-related processes, whereas cortical grafts showed higher abundance of structural and matrix-organization-associated proteins. More extensively processed product formats showed fewer significant protein differences between the cortical and cancellous bone type. Within the limitations of pooled donor material and absent functional validation, these findings provide a proteomic framework for future characterization and evaluation of DBM-based allograft products. Full article

Copy number variations (CNVs) are a major source of structural genomic diversity that influences adaptation, reproduction, and production traits in livestock. The Black Bengal goat, an economically important Indian breed known for its high fecundity, superior skin quality, and resilience to humid tropical climates, was studied to uncover its structural genomic landscape. We performed whole-genome CNV analysis using high-depth (10×) sequencing data from eight individuals. A total of 31,816 copy number variants (CNVs) were identified, predominantly duplications, with an average length of approximately 45 kb. These CNVs were combined into 8910 copy number variation regions (CNVRs) covering approximately 0.15 Gb (about 5.3% of the autosomal genome). CNVR hotspots were mainly located on chromosome 1. Gene annotation showed that regions overlapping with CNVs and CNVRs contained more than 1987 protein-coding genes involved in pathways related to immunity, reproduction, metabolism, and extracellular matrix (ECM) organization. The presence of CNVs involving genes such as GDF9 and BMPR1B on chromosomes 7 & 6, respectively, is important because it indicates that the breed has a high reproductive capacity due to dosage-sensitive duplications. Changes in the extracellular matrix and increased dermal strength have been linked to duplications of genes such as COL6A1, LAMC2, LAMB3, FMN1, and CLDN1. This helps explain the superior hide quality of the breed. This research offers a comprehensive map of CNVs and CNVRs within the genome of the Black Bengal goat. It demonstrates how these duplications lead to structural changes that enhance both reproductive performance and skin resilience. These findings provide a valuable genomic resource for future marker-assisted selection, comparative genomics, and conservation breeding programs aimed at preserving indigenous goat populations. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive extracellular matrix (ECM) deposition. Current FDA-approved therapies, such as pirfenidone and nintedanib, offer limited efficacy in halting disease progression. Lysyl oxidase-like 2 (LOXL2) is a key enzyme involved in ECM remodeling and fibrosis. This study investigates Compound #765, a novel indolizine derivative, as a potential LOXL2 inhibitor for IPF treatment. Methods: Compound #765 was synthesized and characterized using spectroscopic methods. Its inhibitory effect on LOXL2 activity was evaluated using LOXL2 enzymatic assays, in vitro fibrosis models with human lung fibroblasts, and in vivo models of pulmonary fibrosis, including bleomycin-treated and TGF-β1-overexpressing transgenic mice. In silico docking studies predicted the binding affinity of Compound #765 to LOXL2. Results: Compound #765 targeted LOXL2 activity and reduced collagen production in lung fibroblasts. In both bleomycin-induced pulmonary fibrosis and TGF-β1-overexpressing murine models, Compound #765 significantly alleviated fibrosis, as indicated by reduced collagen accumulation and inflammatory cell infiltration. The in silico docking studies predicted favorable binding affinity to LOXL2, which was confirmed through in vitro experiments. Importantly, Compound #765 suppressed fibrosis-associated markers in fibroblasts derived from IPF patients, suggesting translational potential. Conclusions: These results demonstrate that Compound #765 functions as a LOXL2 inhibitor with significant anti-fibrotic effects in vitro and in vivo, offering a promising therapeutic approach for IPF and other fibrotic lung diseases. Full article

The modulation of the tumour microenvironment represents a pivotal step in tumorigenesis and metastasis and results from direct and paracrine cellular interactions. The innate immune Toll-like receptor 4 (TLR4) controls immune and inflammatory signalling in the tumour microenvironment. A growing body of evidence shows that TLR4 activation in cancer, immune and stromal cells upregulate gelatinase expression and activity, linking innate immune responses to extracellular matrix (ECM) remodelling. Gelatinases, or matrix metalloproteinases (MMP2) and (MMP9) play a pivotal role in tumour matrix degradation, thereby facilitating invasion, angiogenesis and metastasis. Interestingly, although TLR4 signalling in cancer cells and tumour-associated macrophages leads to different activation outputs, they can both induce gelatinases through NF-κB, MAPK, and Akt pathways. Evidence from clinical tumour tissues, co-culture models, in vivo and in vitro studies supports the crucial interplay between TLR4 signalling and gelatinases production in tumour growth and metastasis. An in-depth understanding of this crosstalk may reveal new therapeutic opportunities in targeted strategies. Full article

The production of cultivated meat relies on in vitro animal cell growth and requires the use of scaffolds that structurally resemble key features of the extracellular matrix (ECM), providing mechanical support and biochemical cues for cell adhesion, proliferation, and differentiation. Electrospinning has emerged as a promising technique for manufacturing three-dimensional edible scaffolds because it is robust, versatile, and capable of producing nanofibers with a high surface area-to-volume ratio, tunable porosity, and ECM-like fibrous architectures. Natural biopolymers are promising candidates for the fabrication of electrospun scaffolds, combining biocompatibility, biodegradability, and processing compatibility with food-grade requirements. However, the absence of fully food-grade electrospinning systems, coupled with limited scalable green-processing strategies, remains a critical barrier to industrial translation. In this context, this review presents recent advances in the food-grade electrospinning of natural biopolymers focused on cultivated meat production. Furthermore, scientific gaps in the development of fully edible scaffolds are discussed, along with the need for alternatives to animal-derived materials and synthetic carrier polymers, considering sustainability, consumer acceptance, and the translation from laboratory-scale studies to industrial systems. Finally, this review outlines a strategic roadmap to accelerate the transition from proof-of-concept studies toward scalable, regulatory-compliant, and industrially viable electrospinning technologies for cultivated meat production. Full article

Regenerative medicine aims to restore the structure and function for improved tissue health; reduced tissue health can arise from causes such as aging, which results in the ongoing degradation of the extracellular matrix (ECM) of the skin. Replacement of a single biological component is not sufficient for an esthetic treatment to be described as regenerative; it is the relative amounts, ratios, types and organization of stimulated components that are important in a treatment’s regenerative potential. Regenerative aesthetics aims to recapture the youthful structure and function of tissue by exploiting the body’s own systems. Poly-L-lactic acid (PLLA-SCA; Sculptra^®), an injectable, biodegradable, non-permanent biostimulator, induces a combination of mechanotransductional/mechanical stimulation and foreign body reaction response and promotes ECM remodeling via the production of collagen through the upregulation of cytokines interleukin-1b and CXCL6, elastin, proteoglycans and multiadhesive glycoproteins. In addition, PLLA-SCA stimulates adipocyte rejuvenation/adipogenesis and increases the thickness of the dermis and adipose layers. Hence, PLLA-SCA stimulates endogenous pathways, and the array of biostimulatory effects should not be considered individually but as interlinked with the overall goal of improvement in skin health. These effects manifest clinically as long-term improvements in the mechanical properties of the skin, the restoration of volume and elasticity, improvements in skin quality and thickness, and dermal remodeling. Full article

Longevity is a key determinant of economic efficiency and sustainability in dairy cattle production. The study evaluated longevity and lifetime productivity traits in red breed (RB) and Holstein breed (HB) dairy cows in Latvia and assessed the effects of birth year, age at first calving (AFC), and farm size. Data from 279,818 culled and living cows born between 2010 and 2019 were analyzed. The aim of the study was to investigate biological and farm-level factors affecting dairy cow longevity in RB and HB populations. RB and HB cows born between 2010 and 2013 had significantly longer (p < 0.05) total lifespan (LS) and productive life (PL) than cows born in later years; however, they showed lower life day (MPD) and productive life day (MPPD) milk productivity. AFC significantly affected MPD and MPPD. The highest life day productivity in RB cows was observed at AFC of 22.1–24 months, while in HB cows it was observed at <24 months. Significantly longer LS and PL were recorded on farms with fewer than 20 cows, whereas the highest MPD was observed on farms with 101–500 cows in RB and 101–200 cows in HB. Full article

Background: Osteosarcoma (OS) is an aggressive bone tumor. The lack of physiologically relevant three-dimensional models that recapitulate the native tumor microenvironment hampers drug development and mechanistic studies. The study aimed to develop bone-mimetic microspheres for the construction of an OS model. Materials and Methods: We employed droplet microfluidics to fabricate bone-mimetic microspheres (named MSHA) from a composite of gelatin methacryloyl, polyethylene glycol diacrylate, and nano-hydroxyapatite (nHA). MNNG/HOS cells were cultured on MSHA microspheres and subsequently evaluated for their bioactivity and capabilities of stemness, migration, and invasion. Results: The microfluidic platform enabled efficient and scalable production of highly uniform MSHA microspheres with controlled sizes. MNNG/HOS cells cultured on MSHA maintained high viability and spontaneously formed compact tumor spheroids after 7 days. Compared with two-dimensional cultures, cells cultured on these microsphere-based platforms exhibited enhanced migration and invasion capacities, along with increased expression of relevant biomarkers. RNA sequencing further revealed the activation of cancer-related pathways. Notably, the incorporation of nHA into microspheres amplified these malignant phenotypes, potentially through the activation of ECM–receptor interaction and calcium signaling pathways. Conclusions: The microfluidics-fabricated MSHA microspheres, as biomimetic three-dimensional culture scaffolds, offer a promising platform for applications in mechanistic studies of osteosarcoma progression and drug screening. Full article

In a previous study, we demonstrated that a novel surface treatment applied to laser-melted Ti6Al4V substrates supports osteoblast-like cell adhesion, proliferation, and the activation of early osteogenic pathways. Building on these preliminary findings, the present work aimed to further investigate the ability of the same surface to promote extracellular matrix (ECM) deposition, organization, and osteogenic maturation, which are critical events for the establishment of a stable bone–implant interface in subperiosteal dental implants. Human osteoblast-like MG-63 cells were cultured on Ti6Al4V discs subjected to different surface treatments, including a proprietary surface modification (ATcs) specifically designed for subperiosteal applications. ECM formation and maturation were evaluated through scanning electron microscopy coupled with energy-dispersive spectroscopy, immunofluorescence, and semiquantitative analyses of osteogenic markers type I collagen (COL1A1), secreted protein acidic and rich in cysteine (SPARC), and dentin matrix protein 1 (DMP1) through Western blotting. The results showed that, while all tested surfaces supported cell adhesion, the ATcs surface promoted a distinct osteogenic profile characterized by enhanced DMP1 expression, organized collagen deposition, and the formation of calcium–phosphate–rich mineralized structures. Compared to surfaces that primarily stimulated cell proliferation or early matrix production, ATcs appeared to favour progression toward late-stage osteogenic maturation and matrix mineralization. Taken together, these findings extend our previous observations and indicate that this novel surface treatment not only supports osteoblast viability and early differentiation but also promotes extracellular matrix maturation, a key prerequisite for effective osseointegration. Although further in vivo studies are required, the present data provide additional biological rationale for the use of ATcs-treated Ti6Al4V surfaces in next-generation custom-made subperiosteal implant designs. Full article

Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up. Full article