Search Results (781)

In the Kelameili volcanic gas reservoir, primary hydraulic fracturing treatments in some wells take place on a limited scale, resulting in a rapid decline in production post stimulation and necessitating re-fracturing operations. However, prolonged production has led to a significant evolution in the in situ stress field, which complicates the design of re-fracturing parameters. To address this, this study adopts an integrated geology–engineering approach to develop a formation-specific geomechanical model, using rock mechanical test results and well-log inversion to reconstruct the reservoir’s initial stress field. The dynamic stress field simulations and re-fracturing parameter optimization were performed for Block Dixi-14. The results show that stress superposition effects induced by multiple fracturing stages and injection–production cycles have significantly altered the current in situ stress distribution. For Well K6, the optimized re-fracturing parameters comprised a pump rate of 12 m³/min, total fluid volume of 1200 m³, prepad fluid ratio of 50–60%, and proppant volume of 75 m³, and the daily gas production increased by 56% correspondingly, demonstrating the effectiveness of the optimized re-fracturing design. This study not only provides a more realistic simulation framework for fracturing volcanic rock gas reservoirs but also offers a scientific basis for fracture design optimization and enhanced gas recovery. The geology–engineering integrated methodology enables the accurate prediction and assessment of dynamic stress field evolution during fracturing, thereby guiding field operations. Full article

The effects of changes in China’s final demand structure on its forestry sector and associated supply chains have not been thoroughly examined. This study aims to provide a detailed analysis of the quantitative relationships and underlying mechanisms between these interactive changes. Using China’s 153-sector input–output tables from the National Bureau of Statistics and applying a Leontief-based input–output model, we conducted scenario simulations through three distinct schemes, generating both quantitative and qualitative results. Our findings indicate that (1) For China’s forestry sector and its entire value chain to thrive, policymakers should boost consumer demand. This can better stimulate the development of forestry and the “agriculture-forestry-animal husbandry-fishery services” sector and related service industries; (2) Increased investment demand effectively stimulates the development of tertiary industries and secondary industries within the forestry supply chain and boosts the demand and production of intermediate products; (3) Changes in net exports have a significant impact on forestry and the forestry industry chain. To reduce dependence on foreign timber resources, China should strategically expand commercial plantation development; (4) Regarding intermediate product production, investment has a more pronounced effect on increasing total volume compared to consumption. Additionally, the Sino–US tariff disputes negatively impact the forestry industries of both countries. China needs to accelerate import substitution strategies for timber products, adjust international trade markets, and expand domestic consumption and investment to ensure the healthy and stable development of its forestry sector. Full article

Semen collection is an important component of conservation and animal husbandry. Semen quality is generally improved using voluntary collection methods, particularly artificial vaginas (AVs). Most commercially available AVs are tube-shaped with few species-specific design augmentations. As genitalia are highly variable across taxa, incorporating species-specific genital morphologies into AV designs may enhance collected semen quality. We compared dolphin semen quality using: (1) silicone bioinspired artificial vaginas (BAVs) that reflect the internal shape of dolphin vaginas, and (2) manual stimulation. Sperm motility and kinematic parameters of five bottlenose dolphins (Tursiops sp.) were assessed using computer-aided sperm analysis (CASA). Sperm collected using BAVs showed non-significant increases in median progressive and rapid motility, and increases in median and mean linear motility, supporting a sexual selection functional hypothesis for the biodiverse vaginal folds unique to whales, dolphins, and porpoises. Sperm concentration decreased with BAV collection, while no consistent trends were detected in volume, pH, velocity, or plasma membrane integrity. Modifications to AVs for other species that incorporate genital morphologies may also optimize collected semen quality for application to artificial insemination. Full article

This study addresses the challenge of non-uniform fracture propagation in multi-cluster staged fracturing of horizontal wells by proposing a three-dimensional dynamic simulation method for temporary plugging fracturing, grounded in a fully coupled fluid–solid damage theory framework. A Tubing-CZM (cohesive zone model) coupling model was developed to enable real-time interaction computation of flow distribution and fracture propagation. Focusing on the Xinjiang X Block reservoir, this research systematically investigates the influence mechanisms of reservoir properties, engineering parameters (fracture spacing, number of perforation clusters, perforation friction), and temporary plugging parameters on fracture propagation morphology and fluid allocation. Our key findings include the following. (1) Increasing fracture spacing from 10 m to 20 m enhances intermediate fracture length by 38.2% and improves fracture width uniformity by 21.5%; (2) temporary plugging reduces the fluid intake heterogeneity coefficient by 76% and increases stimulated reservoir volume (SRV) by 32%; (3) high perforation friction (7.5 MPa) significantly optimizes fracture uniformity compared to low-friction (2.5 MPa) scenarios, balancing flow allocation ratios between edge and central fractures. The proposed dynamic flow diversion control criteria and quantified temporary plugging design standards provide critical theoretical foundations and operational guidelines for optimizing unconventional reservoir fracturing. Full article

Nerve tissue damage is an unsolved problem in modern neurology and neurosurgery, which prompts the need to search for approaches to stimulate neuroprotection and regeneration of neural tissue. Earlier we have shown that the secretome of human mesenchymal stromal cells (MSCs) stimulates rat survival, reduces the severity of neurological deficits, and decreases the volume of brain damage in a hemorrhagic stroke model. A significant disadvantage of using the MSC secretome is the need to concentrate it (at least 5–10 fold) to achieve appreciable pharmacological activity. This increases the cost of obtaining clinically applicable amounts of secretome and slows down the clinical translation of this technology. Here, we created a number of genetically modified human MSC cultures, including immortalized MSCs and those with hyperexpression of brain-derived neurotrophic factor (BDNF) and urokinase-type plasminogen activator (uPA) and with suppressed expression of Von Hippel–Lindau tumor suppressor (VHL), and we evaluated the pharmacological activity of their secretomes in a model of intracerebral hemorrhage (ICH) in rats. The secretome of MSCs immortalized by hyperexpression of the catalytic subunit of human telomerase (hTERT) revealed neuroprotective activity indistinguishable from that of primary MSC cultures, yet it still required 10-fold concentration to achieve neuroprotective efficacy. The secretome of MSC culture with combined hyperexpression of BDNF and uPA and suppressed expression of Von Hippel–Lindau tumor suppressor even without additional concentration reduced the severity of neurological disorders and decreased brain lesion volume in the ICH model. The secretomes of MSCs with separate overexpression of BDNF and uPA or suppression of VHL had no such effect or, on the contrary, revealed a toxic effect in the ICH model. Presumably, this may be due to an imbalance in the representation of individual growth factors in the secretome of genetically modified MSCs, which individually may lead to undesirable effects in damaged nervous tissue, such as increased permeability of the blood–brain barrier (under the influence of pro-angiogenic factors) or neural cell apoptosis (due to an excess of neurotrophic factors). The obtained data show that genetic modification of MSC cultures can enhance or alter the therapeutic activity of their secretomes, which can be used in the creation of promising sources of biopharmaceutical substances. Full article

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and fewer long-term side effects. Dendritic cell (DC) vaccines have been shown to induce tumor specific cytotoxic T-cell (CTL) responses both in vitro and in vivo; however, due to the nature of the disease, resistance to immunotherapy is often developed. Various modifications, such as the implementation of viral vectors, tumor RNA, or even tumor-specific peptides (neoantigens), have been studied as a means to avoid resistance and enhance the effectiveness of the vaccines. In this review, we aim to assess the effects of neoantigen-loaded DC vaccines (naDCVs) on the immune response against gastric cancer cells. Materials and methods: A thorough literature search was conducted on PubMed and clinicaltrials.gov for studies assessing the efficacy of naDCVs against gastric cancer both in vivo and in vitro. The studies were assessed for eligibility by two independent reviewers based on predetermined inclusion and exclusion criteria. The search was completed following the PRISMA guidelines. Results: Eleven studies were included in our systematic review. In five of the studies, the effects of the naDCVs were tested in vitro; in two and in four they were examined both in vitro and in vivo. The in vitro studies showed that the naDCVs resulted in a more robust immune response against the cancer cells in the study groups compared to the control groups. The in vivo studies conducted on mice showed that tumor volume was reduced in the groups treated with the naDCV compared to the untreated groups. What is more, the cytotoxic effect of CTLs against tumor cells was also increased in the vaccine groups. One of the studies was conducted on humans as a phase I study. The results show increased CTL proliferation and cytokine production in the vaccinated group compared to the control, but no difference regarding the tumor size was observed. Conclusions: Neoantigen-loaded DC vaccines can stimulate a strong immune response against specific gastric cancer cell peptides and enhance tumor cell lysis, therefore hindering or even reversing disease progression, offering great potential for the treatment of patients with gastric cancer. Full article

This study investigated the effects of local fibroblast growth factor (FGF)-2 application on periodontal healing in an osteoporotic model, both in vivo and in vitro. Wistar rats were divided into the ovariectomy (OVX) and Control groups. Periodontal defects were created 8 weeks post-OVX and treated with hydroxypropylcellulose (HPC) or FGF-2 + HPC. Healing was evaluated through micro-computed tomography and histological analyses at 2 and 4 weeks. In vitro, bone marrow mesenchymal stromal cells (BMSCs) were cultured with/without FGF-2 and assessed for cell morphology, viability/proliferation, and osteoblastic marker expression. Alkaline phosphatase (ALP) staining was also performed. FGF-2-treated defects in both groups showed significantly greater bone volume fraction, trabecular number, and thickness compared to HPC only. Histologically, FGF-2 enhanced new bone formation, with the greatest levels in the Control group. In vitro, OVX BMSCs showed reduced actin staining versus controls. FGF-2 increased cell viability/proliferation and protrusions in both groups while downregulating Alpl and Bglap expression levels and reducing ALP-positive cells. FGF-2 increased new bone formation in the OVX group, stimulated proliferation of OVX BMSCs, and modulated their differentiation. FGF-2 could enhance periodontal healing even under osteoporotic conditions, albeit to a lesser extent. Full article

Micro-fracturing technology is a key approach to enhancing the flow capacity of oil sands reservoirs and improving Steam-Assisted Gravity Drainage (SAGD) performance, whereas heterogeneity in reservoir physical properties significantly impacts stimulation effectiveness. This study systematically investigates the coupling mechanisms of asphaltene content, clay content, and heavy oil viscosity on micro-fracturing stimulation effectiveness, based on the oil sands reservoir in Block Zhong-18 of the Fengcheng Oilfield. By establishing an extended Drucker–Prager constitutive model, Kozeny–Poiseuille permeability model, and hydro-mechanical coupling numerical simulation, this study quantitatively reveals the controlling effects of reservoir properties on key rock parameters (e.g., elastic modulus, Poisson’s ratio, and permeability), integrating experimental data with literature review. The results demonstrate that increasing clay content significantly reduces reservoir permeability and stimulated volume, whereas elevated asphaltene content inhibits stimulation efficiency by weakening rock strength. Additionally, the thermal sensitivity of heavy oil viscosity indirectly affects geomechanical responses, with low-viscosity fluids under high-temperature conditions being more conducive to effective stimulation. Based on the quantitative relationship between cumulative injection volume and stimulation parameters, a classification-based optimization model for oil sands reservoir operations was developed, predicting over 70% reduction in preheating duration. This study provides both theoretical foundations and practical guidelines for micro-fracturing parameter design in complex oil sands reservoirs. Full article

Reservoir heterogeneity, fluid property variations, and permeability contrasts across different geological layers result in significant disparities in water absorption capacities during oilfield development, often leading to premature water breakthrough, uneven sweep efficiency, and suboptimal waterflooding outcomes. The accurate determination of layer-specific water injection volumes is critical to addressing these challenges. This study focuses on a study area in China, employing comprehensive on-site investigations to evaluate the current state of layered water injection practices. The injection allocation strategy was optimized using a hybrid approach combining the splitting coefficient method and grey correlation analysis. Key challenges identified in the study area include severe reservoir heterogeneity, poor injection–production correspondence, rapid water cut escalation, and low recovery rates. Seven dominant influencing factors—the sedimentary microfacies coefficient, effective thickness, stimulation factor, well spacing, permeability, connectivity, and permeability range coefficient—were identified through grey correlation analysis. Field application of the proposed method across fourteen wells demonstrated significant improvements: a monthly oil production increase of 40 tons, a water production reduction of 399.24 m³/month, and a 2.45% decline in the water cut. The obtained results substantiate the method’s capability in resolving interlayer conflicts, optimizing oil recovery performance, and effectively controlling water channeling problems. Full article

Poly-L-lactic acid (PLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. Subcutaneous adipose tissue (SAT) contains precursors that differentiate into mature adipocytes that secrete adiponectin, which modulates SAT function and increases adipogenesis. During aging, adiponectin and precursor cell functions decrease, reducing adipogenesis and facial volume. Adiponectin also increases collagen synthesis by stimulating fibroblasts. After hydrogen peroxide treatment to induce senescent adipocytes (3T3-L1) and aged skin, follow-up PLLA treatment increased adipogenesis by stimulating the nuclear factor erythroid-2-related factor 2 (NRF2)/peroxisome proliferator-activated receptor gamma (PPARγ)/CCAAT/enhancer binding protein alpha (C/EBPα) pathway. This resulted in increased adiponectin secretion, which promoted collagen synthesis and mitigated the loss of SAT volume. In the senescent adipocyte, PLLA increased NRF2/PPARγ/C/EBPα, adipogenesis factors (fatty acid binding protein 4, lipoprotein lipase, and cluster of differentiation 36), lipogenesis factors (ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase), adiponectin, and lipid droplet size. Treatment of senescent fibroblasts with conditioned medium from PLLA-treated adipocytes increased collagen1 and 3 and decreased matrix metalloproteinase1 and 3 expressions. Similarly, PLLA increased NRF2/PPARγ/C/EBPα, adipogenesis, and lipogenesis factors in aged mouse SAT. Also, PLLA increased adiponectin and adipocyte numbers without hypertrophy and increased collagen accumulation and dermal thickness. In summary, PLLA increased adipogenesis and adiponectin, which increased the volume of SAT and collagen synthesis, thereby rejuvenating aged skin. Full article

The advanced glycation end product (AGE)–RAGE axis has been implicated in the pathophysiology of diabetic bladder dysfunction (DBD). However, no previous studies have explored the effects of RAGE blockade on this condition. Here, we explored the effects of the selective RAGE inhibitor TTP488 (azeliragon) at the functional and molecular levels of bladder dysfunction in ob/ob leptin-deficient mice. Female B6.V-Lep ob/JUnib (ob/ob) and wild-type (WT) C57BL/6 mice were used as lean controls. Treatment with TTP488 in ob/ob mice resulted in no changes in body weight, fasting glucose, or insulin resistance; however, it reduced total AGE and MG-H1 levels without altering RAGE levels in bladder tissues. TTP488 normalized glyoxalase-1, glutathione reductase, glutathione peroxidase, and superoxide dismutase activities in bladder tissues. Marked increases in collagen intensity were also observed in ob/ob mice, an effect fully reversed by TTP488 treatment. TTP488 reduced total void volume, volume per void, and ex vivo bladder contractility in response to electrical-field stimulation and carbachol. Our finding that TTP488 mitigates DBD in ob/ob mice supports the proposal that RAGE blockade could serve as a promising therapeutic strategy for managing DBD. Full article

Natural gas hydrates (NGHs) are promising energy resources, although their marine exploitation is limited by low reservoir permeability and hydrate decomposition efficiency. Multi-cluster fracturing technology can enhance reservoir permeability, yet complex properties of hydrate sediments render the prediction of fracture behavior challenging. Therefore, we developed a three-dimensional (3D) fluid–solid coupling model for hydraulic fracturing in NGH reservoirs based on cohesive elements to analyze the effects of sediment plasticity, hydrate saturation, fracturing fluid viscosity, and injection rate, as well as the stress interference mechanisms in multi-cluster simultaneous fracturing under different cluster spacings. Results show that selecting low-plastic reservoirs with high hydrate saturation (S_H > 50%) and adopting an optimal combination of fracturing fluid viscosity and injection rate can achieve the co-optimization of stimulated reservoir volume (SRV) and cross-layer risk. In multi-cluster fracturing, inter-fracture stress interference promotes the propagation of fractures along the fracture plane while suppressing it in the normal direction of the fracture plane, and this effect diminishes significantly till 9 m cluster spacing. This study provides valuable insights for the selection of optimal multi-cluster fracturing parameters for marine NGH reservoirs. Full article

Endometriosis is a chronic, hormone-dependent disease that affects women of reproductive age. It leads to numerous adverse clinical symptoms, which significantly impact women’s quality of life. The chronic nature of the disease and its recurrence are the main reasons for the search for new, non-hormonal drugs and drug candidates, either as adjunct treatment options or alternative therapies. The catechin found in green tea, epigallocatechin gallate (EGCG), has been shown to exhibit a wide array of biological activities, which may also contribute to its potential effectiveness in treating endometriosis. The poor physicochemical stability and relatively low bioavailability of EGCG have stimulated the development of a peracetylated prodrug (pro-EGCG) and other solutions, based on nanotechnology, that would eliminate the problems with EGCG. In this review article, we summarize the studies on the effects of EGCG, pro-EGCG, and EGCG-based nanoparticles on the course of endometriosis published in the GoogleScholar and PubMed databases. Of note is the fact that the results of in vitro and animal model studies have suggested that EGCG and pro-EGCG can reduce the number of endometriosis foci and their size and volume, and they can prevent fibrosis by affecting multiple molecular factors and signaling pathways. The promising results provide a basis for using green herbal extracts for endometriosis treatment in a clinical trial. Nevertheless, it should be emphasized that the number of studies on the topic is currently very limited; further expansion in the coming years is necessary. Broad, well-designed clinical trials are also essential to validate the true potential of EGCG and related compounds in the fight against endometriosis. Full article

This study systematically investigates the pore–fracture architecture of deep coal seams in the JiaTan (JT) block of the Ordos Basin using an integrated suite of advanced techniques, including nuclear magnetic resonance (NMR), high-pressure mercury intrusion, low-temperature nitrogen adsorption, low-pressure carbon dioxide adsorption, and micro-computed tomography (micro-CT). These complementary methods enable a quantitative assessment of pore structures spanning nano- to microscale dimensions. The results reveal a pore system overwhelmingly dominated by micropores—accounting for more than 98% of the total pore volume—which play a central role in coalbed methane (CBM) storage. Microfractures, although limited in volumetric proportion, markedly enhance permeability by forming critical flow pathways. Together, these features establish a dual-porosity system that governs methane transport and recovery in deep coal reservoirs. The multiscale characterization employed here proves essential for resolving reservoir heterogeneity and designing effective stimulation strategies. Notably, enhancing methane desorption in micropore-rich matrices and improving fracture connectivity are identified as key levers for optimizing deep CBM extraction. These insights offer a valuable foundation for the development of deep coalbed methane (DCBM) resources in the Ordos Basin and similar geological settings. Full article

Facial aging is a multifactorial and stratified biological process characterized by progressive morphological and biochemical alterations affecting both cutaneous (Layer I) and subcutaneous (Layer II) tissues. These age-related changes manifest clinically as volume depletion, tissue ptosis, and a decline in overall skin quality. In response to these phenomena, thread lifting techniques have evolved significantly—from simple mechanical suspension methods to sophisticated bioactive platforms. Contemporary threads now incorporate biocompatible polymers and hyaluronic acid (HA), aiming not only to reposition soft tissues but also to promote dermal regeneration. This review provides a comprehensive classification and critical assessment of thread lifting materials, focusing on their chemical composition, mechanical performance, degradation kinetics, and biostimulatory potential. Particular emphasis has been given to the surface integration of HA into monofilament threads, especially with the emergence of advanced delivery systems such as NAMICA, which facilitate sustained HA release. Advanced thread materials, especially those fabricated from poly(L-lactide-co-ε-caprolactone) [P(LA/CL)], demonstrate both tensile support and regenerative efficacy. Emerging HA-covered threads exhibit synergistic bioactivity, stimulating skin remodeling. NAMICA technology represents an advancement in the field, in which HA is encapsulated within biodegradable polymer fibers to enable gradual release and enhanced dermal integration. Nonetheless, well-designed human studies are still needed to substantiate its therapeutic efficacy. Consequently, the paradigm of thread lifting is shifting from purely mechanical interventions toward biologically active systems that promote comprehensive ECM regeneration. The integration of HA into resorbable threads, especially when combined with sustained-release technologies, represents a meaningful innovation in aesthetic dermatology, meriting further preclinical and clinical evaluation. Full article