Search Results (208)

The operational failure of lithium-ion batteries under extreme temperatures (−40~60 °C) stems primarily from electrolyte limitations. While prior efforts improved either low-temperature or high-temperature performance independently, holistic electrolyte design with practical validation remains elusive. Herein, we develop an all-climate electrolyte (ACE) through synergistic coordination of solvent, Li salt, and additive, achieving low viscosity (<10 mPa·s at −40 °C) and high ionic conductivity (7.0 mS cm⁻¹ at −40 °C). Raman and NMR spectra reveal MA and EC co-occupying Li⁺ solvation sheath while EMC acts as a diluent, enabling rapid ion transport. Consequently, LiFePO₄ (LFP)|graphite (Gr) cell delivers unprecedented cyclability: zero capacity decay over 500 cycles at 0 °C, stable operation across −40~60 °C, and 94.1% retention after 100 cycles at 45 °C in Ah-level pouch cells. XPS and SEM analysis demonstrate lithium difluorophosphate (LiDFP) and lithium bis(fluorosulfonyl)imide (LiFSI) collaboratively remodel SEI/CEI interphases, enriching them with LiF, Li₃PO₄, and Li₂SO₄. This inorganic-dominant architecture enhances interfacial Li⁺ kinetics and all-climate stability compared to the baseline electrolyte. Our tripartite electrolyte strategy provides a material-agnostic solution for all-climate energy storage. Full article

Hydrogen production from water electrolysis can not only reduce greenhouse gas emissions, but also has abundant raw materials, which is one of the ideal ways to produce hydrogen from new energy. The hydrogen production power supply is the core component of the new energy electrolytic water hydrogen production device, and its characteristics have a significant impact on the efficiency and purity of hydrogen production and the service life of the electrolytic cell. In essence, the DC/DC converter provides the large current required for hydrogen production. For the converter, its input still needs the support of a DC power supply. Given the maturity and technical characteristics of new energy power generation, integrating energy storage into offshore energy systems enables stable power supply. This configuration not only mitigates energy fluctuations from renewable sources but also further reduces electrolysis costs, providing a feasible pathway for large-scale commercialization of green hydrogen production. First, this paper performs a simulation analysis on the wind–solar hybrid energy storage power generation system to demonstrate that the wind–solar–storage system can provide stable power support. It places particular emphasis on the significance of hydrogen production power supply design—this focus stems primarily from the fact that electrolyzers impose specific requirements on high operating current levels and low current ripple, which exert a direct impact on the electrolyzer’s service life, hydrogen production efficiency, and operational safety. To suppress the current ripple induced by high switching frequency and high output current, traditional approaches typically involve increasing the output inductor. However, this method substantially increases the volume and weight of the device, reduces the rate of current change, and ultimately results in a degradation of the system’s dynamic response performance. To this end, this paper focuses on developing a virtual impedance control technology, aiming to reduce the ripple amplitude while avoiding an increase in the filter inductor. Owing to constraints in current experimental conditions, this research temporarily relies on simulation data. Specifically, a programmable power supply is employed to simulate the voltage output of the wind–solar–storage hybrid system, thereby bringing the simulation as close as possible to the actual operating conditions of the wind–solar–storage hydrogen production system. The experimental results demonstrate that the proposed method can effectively suppress the ripple amplitude, maintain high operating efficiency, and ultimately meet the expected research objectives. That makes it particularly suitable as a high-quality power supply for offshore hydrogen production systems that have strict requirements on volume and weight. Full article

Bone marrow aspirate concentrate (BMAC) is increasingly recognized as a valuable orthobiologic, offering promising outcomes in reducing inflammation, alleviating pain for patients with osteoarthritis (OA) and various musculoskeletal conditions. However, BMAC contains a very low percentage of mesenchymal stem cells (MSCs), and multiple injections are often required with multiple harvests, which can lead to scarring at the extraction site and patient discomfort. This study aimed to determine whether freezing BMAC affects the function of MSCs in vitro and their capacity to repair articular cartilage in vivo using an OA rat model. BMAC was obtained from patients undergoing BMAC treatment. The in vitro results showed that the proliferation and multilineage differentiation of MSCs remained similar after being frozen for 4 weeks at −80 °C. In vivo, both fresh and frozen BMAC demonstrated significantly improved ICRS histology score of tibial plateau cartilage compared to the PBS control. No significant difference was found between fresh and frozen BMAC treatment groups. Our results suggest that the freezing process does not negatively affect the function of MSCs from BMAC for cartilage repair. These findings support the potential future applications of a single harvest with BMAC storage for multiple injections, thereby enhancing the tissue repair capabilities of BMAC. Full article

Background: Cryopreservation of hematopoietic stem cells (HSCs) at −80 °C using uncontrolled-rate freezing is frequently employed in resource-constrained settings, yet concerns remain regarding long-term viability and clinical efficacy. Reliable post-thaw assessment is essential to ensure graft quality and engraftment success. Methods: This single-center, retrospective study evaluated 72 cryopreserved stem cell products from 25 patients stored at −80 °C for a median of 868 days. Viability was assessed using both acridine orange (AO) staining and 7-AAD (7-aminoactinomycin D) flow cytometry at three time points: collection (T0), pre-infusion (T1), and delayed post-thaw evaluation (T2). Associations between viability loss, storage duration, and clinical engraftment outcomes were analyzed. Results: Median post-thaw viability remained high (94.8%) despite a moderate time-dependent decline (~1.02% per 100 days; R² = 0.283, p < 0.001). Mean viability loss at T2 was 9.2% (AO) and 6.6% (flow cytometry). AO demonstrated greater sensitivity to delayed degradation, with a significant difference between methods (p < 0.001). Engraftment kinetics were preserved in most patients, with neutrophil and platelet recovery primarily influenced by disease type rather than product integrity. Notably, storage duration and donor age were not significantly associated with engraftment outcomes or CD34⁺ cell dose. Conclusions: Long-term cryopreservation at −80 °C maintains HSC viability sufficient for durable engraftment, despite gradual decline. While transplant outcomes are primarily dictated by disease biology and remission status, AO staining provides enhanced sensitivity for detecting delayed cellular damage. Notably, our viability-loss model offers a practical framework for predicting product quality, potentially supporting graft selection and clinical decision-making in real-world, resource-constrained transplant settings. Full article

Wound healing in oral surgery is influenced by systemic conditions (aging, diabetes) and habits (smoking, alcoholism), which can hinder the natural regenerative capacity of the oral mucosa. The human amniotic membrane (hAM), long recognized for its wound-healing properties, has gained attention as a valuable biomaterial in regenerative dentistry. Its biological composition—including epithelial and mesenchymal stem cells, collagen, growth factors, cytokines, and proteins with anti-inflammatory and antimicrobial properties—supports anti-inflammatory, angiogenic, immunomodulatory, and pro-epithelializing effects. These elements work synergistically to enhance tissue repair, reduce scarring, and promote rapid healing. The hAM can be preserved through cryopreservation, dehydration, or freeze-drying, maintaining its structural and functional integrity for diverse clinical uses. In oral surgery, the hAM has been applied with significant success to surgical wound coverage, treatment of periodontal and bone defects, and implant site regeneration, as well as management of complex conditions like medication-related osteonecrosis of the jaw (MRONJ). Clinical studies and meta-analyses support its safety, efficacy, and adaptability. Despite its proven therapeutic benefits, the hAM remains underutilized in dentistry due to challenges related to its preparation and storage. This review aims to highlight its potential and encourage broader clinical adoption in regenerative oral surgical practices. Full article

This paper addresses the challenge of renewable energy curtailment, which stems from the inherent uncertainty and volatility of wind and photovoltaic (PV) generation, by developing a robust model predictive control (RMPC)-based scheduling strategy for an integrated wind–PV–hydrogen storage multi-energy flow system. By building a “wind–PV–hydrogen storage–fuel cell” collaborative system, the time and space complementarity of wind and PV is used to stabilize fluctuations, and the electrolyzer–hydrogen production–gas storage tank–fuel cell chain is used to absorb surplus power. A multi-time scale state-space model (SSM) including power balance equation, equipment constraints, and opportunity constraints is established. The RMPC scheduling framework is designed, taking the wind–PV joint probability scene generated by Copula and improved K-means and SSM state variables as inputs, and the improved genetic algorithm is used to solve the min–max robust optimization problem to achieve closed-loop control. Validation using real-world data from Xinjiang demonstrates a 57.83% reduction in grid power fluctuations under extreme conditions and a 58.41% decrease in renewable curtailment rates, markedly enhancing the local system’s capacity to utilize wind and solar energy. Full article

Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including negative pressure wound therapy, antibiotic-based infection control, and wound debridement, have been developed to treat skin wounds. However, these approaches primarily target local wound conditions and offer only short-term relief, not achieving sustained functional regeneration. Stem cell-based therapy has emerged as an alternative therapeutic method for skin wound treatment owing to its ability to suppress inflammation, stimulate angiogenesis, and promote cellular proliferation. However, the low post-transplantation survival rate of stem cells remains a major limitation. Exosomes, nanosized extracellular vesicles, transport proteins, lipids, mRNAs, and miRNAs and mediate regenerative functions, including anti-inflammatory effects, angiogenesis promotion, and extracellular matrix remodeling. Stem cell-derived exosomes (SC-Exos) offer several advantages over their parent cells, including greater stability, lower immunogenicity, absence of tumorigenic risks, and ease of storage and distribution. These attributes render SC-Exos particularly attractive for cell-free regenerative therapies. In this review, we introduce exosomes derived from various types of stem cells and explore their therapeutic applications in skin wound regeneration. Full article

Mesenchymal stem cells (MSCs) are a type of multipotent, non-hematopoietic cells of mesodermal origin. Due to their strong immunomodulatory, immunosuppressive, and regenerative potential, MSCs are used in cell therapy for inflammatory, immune-mediated, and degenerative diseases. Exosomes derived from MSCs have several advantages over MSC therapy, including non-immunogenicity, lack of infusion toxicity, ease of isolation, manipulation, and storage, cargo specificity, and the absence of tumor-forming potential and ethical concerns. We hypothesized that preconditioning human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with the proinflammatory cytokines interleukin 17 (IL-17), IL-22, and tumor necrosis factor alpha (TNF-α), the increased levels of which are typical in psoriasis patients, can significantly increase the therapeutic efficacy of both hUCB-MSCs and their exosomes (hUCB-MSC-Exo). Our aim was to compare the therapeutic effects of hUCB-MSCs preconditioned with various combinations of proinflammatory cytokines and their hUCB-MSC-Exo, in an in vivo imiquimod-induced psoriasis-like skin inflammation model in mice. Our results showed a significant attenuation of psoriasis symptoms (erythema, scaling, and skin thickness) in mice treated with intact hUCB-MSCs, hUCB-MSCs preconditioned with IL-22 and TNF-α, and hUCB-MSC-Exo preconditioned with IL-17, IL-22 and TNF-α (MSC-Exo 3C). However, the most pronounced therapeutic effect was observed with MSC-Exo 3C treatment. In summary, we demonstrated that MSC-Exo 3C transplantation has therapeutic potential for treating psoriasis-like skin lesions. Full article

Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance of discerning the role of different cellular proteins involved in VLDL biogenesis, transport, and secretion. Small VCP-Interacting Protein (SVIP) has been identified as a component of VLDL transport vesicles and VLDL secretion. This study evaluates the cellular effects stemming from the CRISPR-Cas9-mediated depletion of SVIP in rat hepatocytes. The SVIP-knockout (KO) cells display an increased VLDL retention with elevated intracellular levels of ApoB100 and neutral lipid staining. RNA sequencing studies reveal an impaired PPARα and Nrf2 signaling in the SVIP KO cells, implying a state of metabolic reprograming, with a shift from fatty acid uptake, synthesis, and oxidation to cells favoring the activation of glucose by impaired glycogen storage and increased glucose release. Additionally, SVIP KO cells exhibit a transcriptional profile indicative of acute phase response (APR) in hepatocytes. Many inflammatory markers and genes associated with APR are upregulated in the SVIP KO hepatocytes. In accordance with an APR-like response, the cells also demonstrate an increase in mRNA expression of genes associated with protein synthesis. Together, our data demonstrate that SVIP is critical in maintaining hepatic lipid homeostasis and metabolic balance by regulating key pathways such as PPARα, Nrf2, and APR. Full article

Energy storage plays an essential role in stabilizing fluctuations in renewable energy sources such as wind and solar, enabling surplus electricity retention, and delivering dynamic frequency regulation. However, relying solely on a single form of storage often proves insufficient due to constraints in performance, capacity, and cost-effectiveness. To tackle frequency regulation challenges in remote desert-based renewable energy hubs—where traditional power infrastructure is unavailable—this study introduces a planning framework for an electro-hydrogen energy storage system with grid-forming capabilities, designed to supply both inertia and frequency response. At the system design stage, a direct current (DC) transmission network is modeled, integrating battery and hydrogen storage technologies. Using this configuration, the capacity settings for both grid-forming batteries and hydrogen units are optimized. This study then explores how hydrogen systems—comprising electrolyzers, storage tanks, and fuel cells—and grid-forming batteries contribute to inertial support. Virtual inertia models are established for each technology, enabling precise estimation of the total synthetic inertia provided. At the operational level, this study addresses stability concerns stemming from renewable generation variability by introducing three security indices. A joint optimization is performed for virtual inertia constants, which define the virtual inertia provided by energy storage systems to assist in frequency regulation, and primary frequency response parameters within the proposed storage scheme are optimized in this model. This enhances the frequency modulation potential of both systems and confirms the robustness of the proposed approach. Lastly, a real-world case study involving a 13 GW renewable energy base in Northwest China, connected via a ±10 GW HVDC export corridor, demonstrates the practical effectiveness of the optimization strategy and system configuration. Full article

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder causing systemic skeletal dysplasia due to a deficiency of N-acetyl-galactosamine-6-sulfate sulfatase (GALNS) enzyme activity, leading to the impaired degradation and accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate. While treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available, they have significant limitations regarding efficacy in skeletal tissues and long-term safety, highlighting the need for more effective therapies. We evaluated a novel gene therapy approach using a dual Integrase-deficient lentiviral vector (IDLV) to deliver an expression cassette that includes human GALNS cDNA and Cas9 sgRNA, targeting the upstream region of the mouse Galns initial codon. This approach leverages the endogenous promoter to drive transgene expression. We assessed in vitro transduction, editing, and functional correction in NIH3T3 and MPS IVA mouse fibroblasts. In vivo efficacy was successfully evaluated via the facial vein injection in MPS IVA newborn mice. In vitro, this IDLV platform demonstrated supraphysiological GALNS activity in cell lysate, resulting in the normalization of KS levels. In vivo direct IDLV platform in newborn MPS IVA mice led to sustained plasma GALNS activity, reduced plasma KS, and favorable biodistribution. Partial correction of heart and bone pathology was observed, with no vector toxicity and minimal antibody responses. This dual IDLV-CRISPR/Cas9 approach effectively mediated targeted GALNS knock-in, yielding sustained enzyme activity, reduced KS storage, and partial pathological amelioration in MPS IVA mice. In conclusion, IDLVs represent an efficient, safe platform for delivering the CRISPR/Cas9 gene editing system for MPS IVA. Full article

Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as promising candidates in regenerative medicine due to their immunomodulatory, pro-regenerative, and paracrine properties. MSC-EVs have shown potential to modulate the microenvironment and favor tissue repair in bone-related disorders such as osteoarthritis and osteoporosis. Interestingly, MSC-EVs can be engineered to reach the bone and carry therapeutics, including ERT- and GT-related molecules, enabling targeted delivery to hard-to-reach bone regions. This review describes the main features of MSC-EVs and discusses the therapeutic potential of MSC-EVs as a potential cell-free strategy for bone-affected LSDs. Full article

This review presents information obtained over the past 10 years on the methods to control the widespread worldwide phytopathogen Pectobacterium carotovorum subsp. carotovorum (Pcc). This bacterium is among the ten most dangerous phytopathogens; it affects a wide range of cultivated plants: vegetables, ornamental and medicinal crops, both during vegetation and during the storage of fruits. Symptoms of Pcc damage include the wilting of plants, blackening of vessels on leaves, stems and petioles. At the flowering stage, the stem core gradually wilts and, starting from the root, the stem breaks and the plant dies. Pcc is a rod-shaped, non-capsule and endospore-forming facultative anaerobic Gram-negative bacterium with peritrichous flagellation. Pcc synthesizes bacteriocins—carocins. The main virulence factors of Pcc are the synthesis of N-acyl-homoserine lactone (AHL) and plant cell wall-degrading enzymes (PCWDEs) (pectinases, polygalacturonases, cellulases, and proteases). Diagnostic methods for this phytopathogen include polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), multilocus genotyping of strain-specific genes and detection of unique volatile organic compounds (VOCs). The main methods to control this microorganism include the use of various chemicals (acids, phenols, esters, salts, gases), plant extracts (from grasses, shrubs, trees, and algae), antagonistic bacteria (Bacillus, Pseudomonas, Streptomyces, and lactic acid bacteria), viruses (including a mixture of bacteriophages), and nanomaterials based on metals and chitosan. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Flexographic printing, traditionally used in the packaging industry, has emerged as a promising technology for microfluidic device fabrication due to enabling high resolution and being commercially available at a low cost compared to conventional techniques. This review explores the adaptation of a photopolymer flexographic printing plate mold (FMold) for microfluidics, examining its advantages, challenges, and applications. It offers a state-of-the-art view of the application of FMold for microfluidic systems, which offers a unique opportunity in terms of cost-effectiveness, scalability, and rapid prototyping. Applications are diverse: FMold has enabled the fabrication of microfluidic devices used in enhanced oil recovery to prepare rock-on-a-chip models, droplet generation and storage, suspension cell culture, monoclonal antibody production, complex cell differentiation pattern creation, phage screening, drug screening, cell detection, and cancer stem cell culture. Since its first appearance in 2018, FMold has been utilized in 50 publications in different laboratories around the world. Key advancements, current research trends, and future prospects are discussed to provide a comprehensive overview of this evolving tool. Full article