Search Results (23,844)

Three-dimensional (3D) bioprinting is increasingly explored as a strategy for myocardial repair and regenerative medicine. Conventional 3D casting often yields heterogeneous cellularization, slow electromechanical maturation, and inadequate vascularization; by contrast, bioprinting places cells and biomaterials in predefined architectures to program alignment, stiffness, vascular pathways, and electrical coupling that better recapitulate native myocardium. This review focuses on cardiac-specific advances in 3D bioprinting. We compare major platforms (jetting, light-based, extrusion, and volumetric) and their trade-offs for cardiac applications; distill bioink design principles trending toward natural–synthetic hybrids, including conductive and shape-morphing components; and outline practical characterization readouts spanning rheology, print fidelity, swelling/degradation, and cardiac function. We also summarize cell sources and co-culture strategies. Applications surveyed include cardiac patches, engineered tissues, chambered constructs, and organoids. Finally, we discuss current limitations and potential future directions for 3D bioprinting cardiac tissues. Collectively, recent advances position 3D bioprinting to accelerate the realization of in vivo-like engineered heart tissues. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance, progressive β-cell dysfunction, and persistent hyperglycemia. While GLP-1 receptor agonists have revolutionized the management of T2D by improving glycemic control and reducing body weight, their insulinotropic effects increase the workload on pancreatic β-cells, which may hasten β-cell decline in certain individuals. Peptide YY (PYY), a gut-derived hormone secreted alongside glucagon-like peptide-1 (GLP-1) from L-cells, presents a unique and complementary therapeutic approach. In contrast to GLP-1, PYY does not directly induce insulin release but confers metabolic advantages by suppressing appetite through Y2 receptor pathways, enhancing insulin sensitivity via peripheral Y1/Y4 receptors, and slowing gastric emptying to minimize postprandial glucose surges. Notably, recent research suggests PYY supports the preservation and restoration of pancreatic islets by improving their structure and function without increasing the secretory demand. PYY levels are substantially increased after bariatric surgery, where it plays a pivotal role in weight-loss-independent improvements in glycemic regulation and islet hormone dynamics. These attributes position PYY as a strong candidate for use in combination with GLP-1 analogs, especially in individuals with advanced β-cell impairment or those who respond inadequately to GLP-1 monotherapy. This review discusses PYY’s physiological functions, mechanistic actions, and therapeutic opportunities in T2D, highlighting its potential as a valuable adjunct or alternative in gut-hormone-oriented treatment strategies. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have achieved striking clinical efficacy in the subset of CRCs with mismatch repair deficiency/high microsatellite instability (dMMR/MSI-H), the vast majority of patients—those with proficient mismatch repair/microsatellite-stable (pMMR/MSS) tumors—derive little benefit from current immunotherapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lethal accumulation of lipid peroxides, has emerged as a promising antitumor mechanism that can interact with and modulate antitumor immunity. Concurrently, the gut microbiota exerts powerful control over host metabolism and immune tone through microbial community structure and metabolite production; accumulating evidence indicates that microbiota-derived factors can either sensitize tumors to ferroptosis (for example, via short-chain fatty acids) or confer resistance (for example, indole-3-acrylic acid produced by Peptostreptococcus anaerobius acting through the AHR→ALDH1A3→FSP1/CoQ axis). In this review we synthesize mechanistic data linking microbial ecology, iron and lipid metabolism, and immune regulation to ferroptotic vulnerability in CRC. We discuss translational strategies to exploit this “microbiota–ferroptosis” axis—including precision microbiome modulation, dietary interventions, pharmacologic ferroptosis inducers, and tumor-targeted delivery systems—and we outline biomarker frameworks and trial designs to evaluate combinations with ICIs. We also highlight major challenges, such as interindividual microbiome variability, potential collateral harm to ferroptosis-sensitive immune cells, adaptive antioxidant compensation (e.g., NRF2/FSP1 activation), and safety/regulatory issues for live biotherapeutics. In summary, this review highlights that targeting the microbiota-ferroptosis axis may represent a rational and potentially transformative approach to reprogramming the tumor microenvironment and overcoming immune checkpoint resistance in pMMR/MSS colorectal cancer; however, further research is essential to validate this concept and address existing challenges. Full article

Coeliac disease (CeD) is a gastrointestinal enteropathy triggered by the consumption of gluten in predisposed individuals. A recent study showed that individuals were at more than 10% risk of having CeD if a first-degree relative also had the disease. However, only around 50% of CeD genetic heritability is attributable to specific loci, with the majority of this heritable risk attributed to the HLA loci, while the remaining 50% of disease risk is currently unidentified. We investigated the butyrophilin family of immunomodulators as novel CeD risk loci. We sequenced the butyrophilin loci of 48 CeD and 46 control patients and carried out gene-based burden testing on the captured single-nucleotide polymorphisms (SNPs). We found a significantly increased BTN2A1 gene burden in CeD patients. To validate these results, the SNP data of 3094 CeD patients and 29,762 control participants from the UK Biobank database were subjected to single-variant analyses. Fourteen BTN2A1, ten BTN3A1, and thirteen BTN3A2 SNPs were significantly associated with CeD status. These results are interesting, as BTN2A1 and BTN3A2 have not been associated with CeD risk previously but are known to modulate the activation of Vγ9+ γδ T cells and NK cells. Twenty of the 37 SNPs above were associated with CeD status independent of the risk-associated HLA genotypes. All twenty of these SNPs, alongside a novel SNP not included in the above SNPs, were associated with CeD in HLA-DQ2.5-matched case-control groups. We reaffirm the association of the BTN3A2 locus with CeD risk and identify BTN2A1 and BTN3A1 as putative novel CeD risk loci. Full article

c-Jun N-terminal kinase (JNK) activation has been shown to play a crucial role in the development of various types of cancer. IQ-1S is a JNK inhibitor based on the 11H-indeno[1,2-b]quinoxalin-11-one scaffold. The aim of this study was to investigate the antiproliferative effect of IQ-1S on MCF7 breast cancer cells in both two-dimensional (2D) monolayer and 3D multicellular spheroid test-systems. Non-adherent, non-tethered 3D objects were generated from single MCF7 breast cancer cells in a hydrogel array. IQ-1S was added directly to the cells seeded in the hydrogel array. MCF7 spheroids were grown for 7 days. Spheroid size, growth rate, and morphology were assessed at single-object resolution. The study revealed significant differences in the size, morphology and some vital characteristics of breast cancer 3D objects when treated with the JNK inhibitor compared to vehicle (dimethyl sulfoxide)-treated controls. Spheroids treated with IQ-1S (20 μM) after 7 days are significantly smaller than the control objects. This difference was not attributable to variations in the initial number of cells seeding for the spheroid formation. Morphological examinations showed that 3D multicellular objects grown from IQ-1S-treated cells lose their regular, round morphology, in contrast to control spheroids. Furthermore, cell proliferation measured using a label-free impedance monitoring platform was reduced in monolayer (2D) culture of MCF7 cells in the presence of 10 and 20 μM IQ-1S. MCF7 cells in 2D culture treated with IQ-1S (20 μM) for 72 and 153 h showed a significant increase in apoptosis as assessed by flow cytometry with annexin V/propidium iodide staining. An in silico evaluation showed that compound IQ-1S has generally satisfactory ADME (absorption, distribution, metabolism, and excretion) properties and high bioavailability. We conclude that IQ-1S effectively inhibits the growth of 3D spheroids and MCF7 cells in 2D culture and has a high potential for use in preclinical tumor growth models. Full article

The rapid adoption of hydrogen fuel cell vehicles (HFCVs) in the Beijing–Tianjin–Hebei (BTH) hub accentuates the mismatch between renewable-based hydrogen supply in Hebei and concentrated demand in Beijing and Tianjin. We develop a mixed-integer linear model that co-configures a hydrogen pipeline network and optimizes hourly flow schedules to minimize annualized cost and CO₂ emissions simultaneously. For 15,000 HFCVs expected in 2025 (137 t d⁻¹ demand), the Pareto-optimal design consists of 13 production plants, 43 pipelines and 38 refueling stations, delivering 50 767 t yr⁻¹ at 68% pipeline utilization. Hebei provides 88% of the hydrogen, 70% of which is consumed in the two megacities. Hourly profiles reveal that 65% of electrolytic output coincides with local wind–solar peaks, whereas refueling surges arise during morning and evening rush hours; the proposed schedule offsets the 4–6 h mismatch without additional storage. Transport distances are 40% < 50 km, 35% 50–200 km, and 25% > 200 km. Raising the green hydrogen share from 10% to 70% increases total system cost from USD 1.56 bn to USD 2.73 bn but cuts annual CO₂ emissions from 142 kt to 51 kt, demonstrating the trade-off between cost and decarbonization. The model quantifies the value of sub-day pipeline scheduling in resolving spatial–temporal imbalances for large-scale low-carbon hydrogen supply. Full article

This study reports the solvent-free mechanochemical synthesis of a novel series of 2-hydrazone-bridged benzothiazole derivatives 19–52 via the reaction of 2-hydrazinylbenzothiazole derivatives 4–6 with O-alkylated benzaldehydes 7–18. The stereostructure of the E-isomers was confirmed by 2D NOESY spectroscopy. The antiproliferative potential of these newly prepared 2-hydrazone derivatives of benzothiazole 19–52 was evaluated in vitro against eight human cancer cell lines. Several compounds demonstrated low micromolar IC₅₀ values, with some outperforming the reference drug etoposide. Among the most potent compounds, the 6-chloro-2-hydrazone(3-fluorophenyl)benzothiazole derivative 38 exhibited remarkable activity against pancreatic adenocarcinoma (Capan-1, IC₅₀ = 0.6 µM) and non-small cell lung cancer (NCI-H460, IC₅₀ = 0.9 µM). Structure–activity relationship analysis revealed that derivatives 45–52, featuring a methoxy group at position 6 of the benzothiazole ring and either a methoxy or fluorine substituent at position 3 of the phenyl ring, showed consistently strong antiproliferative effects across all tested cell lines (IC₅₀ = 1.3–12.8 µM). Furthermore, compounds bearing N,N-diethylamino or N,N-dimethylamino groups at position 4 of the phenyl ring generally exhibited superior activity compared to those with morpholine or piperidine moieties. However, as this study represents an initial screening, further mechanistic investigations are required to confirm specific anticancer pathways and therapeutic relevance. In addition to their in vitro anticancer properties, the antibacterial activity of the compounds was assessed against both Gram-positive and Gram-negative bacteria. Notably, compound 37 demonstrated selective antibacterial activity against Pseudomonas aeruginosa (MIC = 4 µg/mL). Overall, this work highlights the efficiency of a green, mechanochemical approach for synthesizing E-isomer hydrazone-bridged benzothiazoles and underscores their potential as promising scaffolds for the development of potent antiproliferative agents. Full article

With the growing interest in fabricating nanofiltration membranes using novel materials and techniques, there is an increasing need to evaluate the practical viability of innovative membranes at the early stages of development. In many materials research laboratories, access to professionally manufactured membrane-evaluation systems may be limited. Here we present a pressure-driven filtration system for evaluation of nanofiltration membranes, which can be constructed from 3D-printed parts and widely available off-the-shelf components at a cost of approximately 60 €. The system uses a stirred cross-flow design capable of circulating the feed solution in the filter cell and maintaining a stable solute concentration during extended filtration experiments—as in conventional cross-flow cells. It is suitable for the filtration of aqueous solutions containing dyes, inorganic salts, and dilute acids. Validation was performed by filtering a 2000 mg L⁻¹ MgSO₄ solution through a Veolia RL membrane at 7.6 bar, achieving a 96.5% rejection rate and a permeance of 7.5 L m⁻² h⁻¹ bar⁻¹ after 24 h of continuous operation. Full article

Scorpion venom is a rich source of diverse bioactive molecules with medicinal importance. While the venoms of many Buthidae scorpions have been extensively studied for their toxicity and therapeutic potential, Hottentotta judaicus scorpion venom (HjSV) remains poorly explored. In this study, using LC-ESI-MS, we show that HjSV has a complex composition. We find that HjSV has no significant cytotoxic effects on three human cancer cell lines, even at concentrations of up to 1000 µg/mL. However, it exerts a dose-dependent insecticidal effect against Drosophila melanogaster, a well-established genetic model organism, and two medically relevant mosquito species, Aedes albopictus and Culex pipiens. These findings highlight the venom’s selective activity and reveal a species-dependent susceptibility in insects, with mosquitoes being more sensitive than Drosophila. Furthermore, we show that at sub-lethal doses, HjSV alters D. melanogaster behavioral patterns, significantly reducing locomotor activity and increasing sleep duration. Altogether, our results provide new insights into the dual role of HjSV as both an insecticidal agent and behavioral modulator, shedding light on its ecological function in prey subduing and its potential application in pest control strategies. Full article

The number of endoprosthetic implants is constantly increasing. Successful osseointegration of the inserted material into the bone is essential for a prosthesis to remain in the bone as long as possible. In the clinical setting, a roughened titanium surface of implants is used as standard to enable the best possible osseointegration. Vitamin K2 and vitamin D3 play a decisive role in dynamic bone metabolism and therefore also influence osseointegration. For the first time, we carried out in vitro investigations with clinically relevant cells, primary healthy human osteoblasts (hOBs). We qualitatively compared the adhesion behaviour of hOBs on a plastic surface, a smooth, regular titanium surface structure and a roughened, irregular titanium surface structure by scanning electron microscopy and fluorescence microscopy. The osteogenic behaviour and the osteogenic differentiation capacity were quantitatively investigated by analysing the activity of alkaline phosphatase and the alizarin red S assay under the influence of vitamin K2, vitamin D3 and the combination of both vitamins. It was shown that more adhesion points formed between the cells and the titanium on the rough surface structure. In addition, a solid cell network developed more quickly on this side, with cell runners forming in three-dimensional space, which means the interactions between the cells across different cell layers. On the other hand, a structured cell network also appeared on the regular smooth surface structure, which means that the network seems to be formed and built up along a defined structure. The addition of vitamins further increased the osteogenic differentiation capacity on the rough titanium surface structure. In particular, the isolated addition of vitamin K2 showed an improved osteogenic differentiation in the long-term observation, whereas the combined addition of both vitamins promoted the initial osteogenic differentiation. Vitamin K2, therefore, plays a greater role in osseointegration than previously assumed. This opens up new possibilities for the use of vitamin K2 during and after the surgical insertion of an implant. The use of vitamin K2 should be reconsidered for clinical applications in implant care and further investigated clinically. Full article

The hydrogen energy industry is rapidly developing, positioning hydrogen refueling stations (HRSs) as critical infrastructure for hydrogen fuel cell vehicles. Within these stations, hydrogen compressors serve as the core equipment, whose performance and reliability directly determine the overall system’s economy and safety. This article systematically reviews the working principles, structural features, and application status of mechanical hydrogen compressors with a focus on three prominent types based on reciprocating motion principles: the diaphragm compressor, the hydraulically driven piston compressor, and the ionic liquid compressor. The study provides a detailed analysis of performance bottlenecks, material challenges, thermal management issues, and volumetric efficiency loss mechanisms for each compressor type. Furthermore, it summarizes recent technical optimizations and innovations. Finally, the paper identifies current research gaps, particularly in reliability, hydrogen embrittlement, and intelligent control under high-temperature and high-pressure conditions. It also proposes future technology development pathways and standardization recommendations, aiming to serve as a reference for further R&D and the industrialization of hydrogen compression technology. Full article

In the environment, the coexistence of microplastics (MPs) with other pollutants may either enhance or reduce the toxicity of MPs themselves or the co-occurring pollutants toward microalgae. This phenomenon is particularly notable when MPs interact with emerging pollutants, such as ultraviolet absorbers. This study investigates the single and combined exposure effects of ultraviolet absorber (Butyl methoxydibenzoylmethane, BMDM, 50 μg/L) and MPs (Polystyrene, PS, 10 mg/L, d = 1 μm) on Chlorella sp. with a stress duration of 7 days. The results showed that cell density, chlorophyll a (Chla) concentration, and physical properties of cell surface integrity were higher in the combined stress group compared to the BMDM single stress group. Furthermore, transcriptome sequencing analysis revealed that the number of differentially expressed genes (DEGs) in the combined exposure group (885 DEGs) was lower than in the single exposure groups (BMDM: 1870 DEGs and PS: 9109 DEGs). Transcriptomic profiling indicated that individual stressors of BMDM and PS disrupted 113 and 123 pathways, respectively, predominantly associated with protein synthesis and energy metabolism. Conversely, combined exposure significantly enriched 86 pathways, including ribosome function and oxidative phosphorylation, thereby manifesting an antagonistic effect. This study provides new insights into the effects of BMDM and PS on Chlorella sp. and offers valuable information for the risk assessment of multiple pollutants. Full article

Esophageal cancer (EC) continues to pose a major global health burden, ranking as the ninth most common malignancy and sixth leading cause of cancer mortality, with over 600,000 new cases and 500,000 deaths annually as of 2025. While esophagectomy has long been the standard for curative intent in resectable disease, organ preservation strategies have advanced significantly, offering viable alternatives for patients with locally advanced esophageal squamous cell carcinoma (ESCC) or those unsuitable for surgery due to comorbidities. These approaches encompass definitive chemoradiotherapy (dCRT), neoadjuvant chemoradiotherapy (nCRT) followed by active surveillance (“watch-and-wait”), and innovative integrations of immunotherapy and targeted therapies. This narrative review synthesizes evidence from recent clinical trials, systematic reviews, and international guidelines up to 2025, demonstrating that organ-sparing protocols can achieve comparable overall survival (OS) rates—often exceeding 50% at 5 years in selected cohorts-while substantially enhancing quality of life (QoL) by preserving esophageal function. For instance, the SANO trial (2025) confirmed non-inferiority of active surveillance post-nCRT, with 2-year OS of 74% versus 71% for standard surgery. Key challenges include imprecise response assessment, locoregional recurrences (20–30%), and treatment-related toxicities such as esophageal strictures. Emerging trials like ESOSTRATE and PALACE3 are evaluating immunotherapy-enhanced regimens, potentially expanding organ preservation to esophageal adenocarcinoma (EAC). With genomic biomarkers and novel modalities like proton therapy, personalized organ preservation promises to broaden applicability, reduce morbidity, and improve outcomes across histological subtypes. Additionally, recent studies emphasize the role of liquid biopsies, such as circulating tumor DNA (ctDNA), in monitoring treatment response and guiding surveillance, potentially reducing the need for invasive procedures and improving detection of minimal residual disease. The aim of this review is not only to summarize recent trials but to synthesize them into an operational framework that clinicians and researchers can apply: a decision algorithm for selecting organ preservation candidates. This is the novel element that distinguishes this work from prior narrative reviews. Full article

Studies examining IgG subclasses within circulating immune complexes (CICs) in patients with IgG4-related disease remain scarce. A Japanese man in his 50s with a history of diabetes mellitus and chronic pancreatitis was referred to our department because of an increase in serum creatinine levels. Serum IgG and IgG4 levels were markedly high, accompanied by eosinophilia and elevated serum IgE levels. C3 hypocomplementemia and an increase in CICs were also noted, and imaging revealed swollen mediastinal lymph nodes. Renal biopsy revealed extensive tubulointerstitial nephritis with numerous IgG4-positive plasma cells and dense interstitial fibrosis. The patient was diagnosed with IgG4-related disease, and glucocorticoid therapy was initiated; renal function, serological abnormalities, and swelling of the mediastinal lymph nodes improved. Subsequent analyses revealed that the patient’s CICs mainly comprised IgG4 and that there was tubular deposition of complement components C1q, C4d, C3, and C5b-9 in the renal biopsy tissue, suggesting that immune complexes containing IgG4 activated the complement pathway in circulation and locally in the kidneys. Hypocomplementemia and CICs are observed in a subset of patients with IgG4-related diseases; however, the underlying mechanisms remain unclear. Further accumulation of IgG4-related disease cases is required to evaluate the possibility of IgG4-mediated complement activation. Full article

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs—including spheroids, organoids, cardiac microtissues, and engineered heart tissues (EHTs)—for disease modeling, mechanistic research, and drug discovery. While 2D culture of iPSC-CMs reproduces hallmark proteotoxic phenotypes such as sarcomeric disorganization, oxidative stress, and apoptosis in ACM, 3D models provide enhanced physiological relevance through incorporating multicellularity, extracellular matrix interactions, and mechanical load-related features. Genome editing with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 further broadens the scope of iPSC-based models, enabling isogenic comparisons and the dissection of mutation-specific effects, particularly in transthyretin-related amyloidosis (ATTR). Despite limitations such as cellular immaturity and challenges in recapitulating aging-associated phenotypes, ongoing refinements in differentiation, maturation, and dynamic training of iPSC-cardiac models hold great promise for overcoming these barriers. Together, these advances position iPSC-based systems as powerful human-relevant platforms for modeling and elucidating disease mechanisms and accelerating therapeutic development to prevent ACM. Full article