Search Results (959)

Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article

The regio- and stereoselective adjacent bifunctionalization of olefins with amine and halogen groups can be effectively accomplished through catalytic haloamination methods. Stereoselective haloamination has emerged as a pivotal methodology for the introduction of halogen functional groups into chiral amines, demonstrating substantial applications in medicinal chemistry and organic synthesis. Since 1999, significant advancements have been achieved in this field, driven by innovations in catalytic systems and methodologies. The stereoselective haloamination of both functionalized and nonfunctionalized alkenes employing chiral catalysts has emerged as a prominent area of research. This review provides a comprehensive overview of the research progress in stereoselective haloamination reactions from 1999 to 2023. It examines the innovations in catalyst design that have facilitated more efficient and selective transformations. The review also analyzes the optimization of reaction conditions, which has been crucial in improving the overall performance and applicability of these reactions. Furthermore, it explores the diverse range of haloamination reactions that have been developed, emphasizing their potential for the synthesis of complex and valuable chemical structures. Additionally, this review offers insightful perspectives on future research directions in stereoselective haloamination reactions. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

This comprehensive review explores the expansive design space of network architectures and their significant impact on the mechanical and viscoelastic properties of hydrogel systems. By examining the intricate relationships between molecular structure, network connectivity, and resulting bulk properties, we provide critical insights into rational design strategies for tailoring hydrogel mechanics for specific applications. Recent advances in sequence-defined crosslinkers, dynamic covalent chemistries, and biomimetic approaches have significantly expanded the toolbox for creating hydrogels with precisely controlled viscoelasticity, stiffness, and stress relaxation behavior—properties that are crucial for biomedical applications, particularly in tissue engineering and regenerative medicine. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Background/Objectives: The demand for accessible and reliable digital health services has increased significantly in recent years, particularly in regions facing physician shortages. HomeDOCtor, a conversational AI platform developed in Slovenia, addresses this need with a nationally adapted architecture that combines retrieval-augmented generation (RAG) and a Redis-based vector database of curated medical guidelines. The objective of this study was to assess the performance and impact of HomeDOCtor in providing AI-powered healthcare assistance. Methods: HomeDOCtor is designed for human-centered communication and clinical relevance, supporting multilingual and multimedia citizen inputs while being available 24/7. It was tested using a set of 100 international clinical vignettes and 150 internal medicine exam questions from the University of Ljubljana to validate its clinical performance. Results: During its six-month nationwide deployment, HomeDOCtor received overwhelmingly positive user feedback with minimal criticism, and exceeded initial expectations, especially in light of widespread media narratives warning about the risks of AI. HomeDOCtor autonomously delivered localized, evidence-based guidance, including self-care instructions and referral suggestions, with average response times under three seconds. On international benchmarks, the system achieved ≥95% Top-1 diagnostic accuracy, comparable to leading medical AI platforms, and significantly outperformed stand-alone ChatGPT-4o in the national context (90.7% vs. 80.7%, p = 0.0135). Conclusions: Practically, HomeDOCtor eases the burden on healthcare professionals by providing citizens with 24/7 autonomous, personalized triage and self-care guidance for less complex medical issues, ensuring that these cases are self-managed efficiently. The system also identifies more serious cases that might otherwise be neglected, directing them to professionals for appropriate care. Theoretically, HomeDOCtor demonstrates that domain-specific, nationally adapted large language models can outperform general-purpose models. Methodologically, it offers a framework for integrating GDPR-compliant AI solutions in healthcare. These findings emphasize the value of localization in conversational AI and telemedicine solutions across diverse national contexts. Full article

Research results suggest the potential of topical adenosine as a hair-promoting agent. The aim of this study was to examine the available clinical evidence of the efficacy of topical adenosine products in hair loss. This systematic review was conducted in accordance with PRISMA and PICO guidelines and included articles indexed in PubMed, Scopus, and Web of Science. The strength of evidence was assessed according to the GRADE system. Wherever feasible, data were extracted for a meta-analysis. Among 8625 articles returned by the query, 7 clinical trials were identified of topical adenosine (lotion, shampoo) in hair loss. They unanimously reported on a reduction in hair loss and increase in hair density (strength of evidence very low to moderate). A meta-analysis of three eligible trials showed a tendency to increased hair density (OR = 1.03, 95% CI: 0.89–1.20, p = 0.68), an increase in thick hair (OR = 1.4, 95% CI: 0.82–2.38, p = 0.21) and a decrease in thin hairs (OR = 0.93, 95% CI: 0.61–1.43, p = 0.75) after 6 months of alopecia treatment with a 0.75% adenosine lotion. The results from clinical trials published until now suggest that topical adenosine increases hair thickness, reduces excessive hair loss, stimulates hair regrowth, and increases hair density. The overall strength of evidence remains low due to flawed design and small sample sizes in most trials. Nevertheless, topical adenosine products seem worth trying, especially in the case of contraindications or adverse effects to approved medicinal products for hair loss. Further, better designed trials of adenosine in hair loss are warranted. Full article

Parkinson’s disease (PD), a progressive neurodegenerative disorder, imposes growing clinical and socioeconomic burdens worldwide. Despite landmark discoveries in dopamine biology and α-synuclein pathology, translating mechanistic insights into effective, personalized interventions remains elusive. Recent advances in molecular profiling, neuroimaging, and computational modeling have broadened the understanding of PD as a multifactorial systems disorder rather than a purely dopaminergic condition. However, critical gaps persist in diagnostic precision, biomarker standardization, and the translation of bench side findings into clinically meaningful therapies. This review critically examines the current landscape of PD research, identifying conceptual blind spots and methodological shortfalls across pathophysiology, clinical evaluation, trial design, and translational readiness. By synthesizing evidence from molecular neuroscience, data science, and global health, the review proposes strategic directions to recalibrate the research agenda toward precision neurology. Here I highlight the urgent need for interdisciplinary, globally inclusive, and biomarker-driven frameworks to overcome the fragmented progression of PD research. Grounded in the Accelerating Medicines Partnership-Parkinson’s Disease (AMP-PD) and the Parkinson’s Progression Markers Initiative (PPMI), this review maps shared biomarkers, open data, and patient-driven tools to faster personalized treatment. In doing so, it offers actionable insights for researchers, clinicians, and policymakers working at the intersection of biology, technology, and healthcare delivery. As the field pivots from symptomatic relief to disease modification, the road forward must be cohesive, collaborative, and rigorously translational, ensuring that laboratory discoveries systematically progress to clinical application. Full article

The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against clinically significant pathogens, including both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) species (MIC = 31.25 mg/mL), achieving significant reduction in bacterial viability within 24 h. Through integrated multi-omics analysis combining scanning electron microscopy and RNA sequencing, we reveal SME’s unprecedented tripartite mechanism of action: (1) direct membrane disruption causing cell envelope collapse, (2) metabolic paralysis through coordinated suppression of TCA cycle and fatty acid degradation pathways, and (3) inhibition of DNA repair systems (SOS response and recombination downregulation). Despite its potent activity, SME shows low cytotoxicity toward mammalian cells (>90% viability) and can penetrate Gram-negative outer membranes. These features highlight SME’s potential to address drug-resistant infections through synthetic lethality across stress response, energy metabolism, and DNA integrity pathways. While advocating for synthetic alternatives to endangered animal products, this study establishes SME as a polypharmacological template for resistance-resilient antimicrobial design, demonstrating how traditional knowledge and modern systems biology can converge to guide sustainable anti-infective development. Full article

Nitrogen (N) availability often limits primary productivity in terrestrial ecosystems, and arbuscular mycorrhizal fungi (AMF) can enhance plant N acquisition. This study investigated the interactive effects of N fertilization and AMF inoculation on N uptake, plant performance and phenolic acid content in Hyssopus officinalis L., with the aim of promoting sustainable N management in H. officinalis cultivation. A factorial randomized complete block design was employed to evaluate four AMF inoculation strategies (no inoculation, root inoculation, soil inoculation and combined root–soil inoculation) across three N application rates (0, 0.5 and 1,1 g N pot⁻¹ (7 L)) in a controlled greenhouse environment. Combined root and soil AMF inoculation alongside moderate N fertilization (0.5 mg N pot⁻¹) optimized N use efficiency, maximizing plant biomass and bioactive compound production. Compared to non-inoculated controls, this treatment combination increased N uptake by 30%, phosphorus uptake by 24% and potassium uptake by 22%. AMF colonization increased chlorophyll content and total phenolic compounds under moderate N supply. However, excessive N application (1 g N pot⁻¹) reduced AMF effectiveness and secondary metabolite accumulation. Notably, AMF inoculation without N fertilization yielded the highest levels of anthocyanin and salicylic acid, indicating differential N-dependent regulation of specific biosynthetic pathways. The interaction between AMF and N demonstrated that moderate N fertilization (0.5 g N pot⁻¹) combined with dual inoculation strategies can reduce total N input requirements by 50%, while maintaining optimal plant performance. These findings provide practical insights for developing N-efficient cultivation protocols in medicinal plant production systems, contributing to sustainable agricultural practices that minimize environmental N losses. Full article

Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article

Medical education is the paradigm of 21st century education and the current changes involve the adoption of integrative and comprehensive patient-centered teaching and learning approaches. Thus, curricular developers from George Emil Palade University of Medicine, Pharmacy, Sciences, and Technology of Targu Mures (G.E. Palade UMPhST of Targu Mures) have recently designed and implemented an innovative medical curriculum, as well as two valuable assessment tools for both theoretical knowledge and practical skills. Thus, during the first three preclinical years, the students will benefit from an organ- and system-centered block teaching approach, while the clinical years will focus on enabling students to achieve the most important practical skills in clinical practice, based on a patient bedside teaching system. In terms of theoretical knowledge assessment, the UNiX center at G.E. Palade UMPhST of Targu Mures, a recently designed center endowed with the latest next-generation technology, enables individualized, secured multiple-choice question-based assessments of the student’s learning outcomes. Moreover, an intelligent assessment tool for practical skills was also recently implemented in our branch in Hamburg, the Objective Structured Clinical Examination (O.S.C.E). This system uses direct observations for testing the student’s practical skills regarding anamnesis, clinical exams, procedures/maneuvers, the interpretation of laboratory tests and paraclinical investigations, differential diagnosis, management plans, communication, and medical counselling. The integrative, comprehensive, patient-centered curriculum and the intelligent assessment system, implemented in G.E Palade UMPhST of Targu Mures, help define innovation in education and enable the students to benefit from a high-quality medical education. Full article

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9)-mediated genome editing has emerged as a transformative tool in medicine, offering significant potential for cancer therapy because of its capacity to precisely target and alter the genetic modifications associated with the disease. However, a major challenge for its clinical translation is the safe and efficient in vivo delivery of CRISPR/Cas9 components to target cells. Nanotechnology is a promising solution to this problem. Nanocarriers, owing to their tunable physicochemical properties, can encapsulate and protect CRISPR/Cas9 components, enabling targeted delivery and enhanced cellular uptake. This review provides a comprehensive examination of the synergistic potential of CRISPR/Cas9 and nanotechnology in cancer therapy and explores their integrated therapeutic applications in gene editing and immunotherapy. A critical aspect of in vivo CRISPR/Cas9 application is to achieve effective localization at the tumor site while minimizing off-target effects. Nanocarriers can be engineered to overcome biological barriers, thereby augmenting tumor-specific delivery and facilitating intracellular uptake. Furthermore, their design allows for controlled release of the therapeutic payload, ensuring sustained efficacy and reduced systemic toxicity. The optimization of nanocarrier attributes, including size, shape, surface charge, and composition, is crucial for improving the cellular internalization, endosomal escape, and nuclear localization of CRISPR/Cas9. Moreover, surface functionalization with targeting ligands can enhance the specificity of cancer cells, leading to improved gene-editing accuracy. This review thoroughly discusses the challenges associated with in vivo CRISPR/Cas9 delivery and the innovative nanotechnological strategies employed to overcome them, highlighting their combined potential for advancing cancer treatment for clinical application. Full article

Mandelic acid (MA), as an important chiral aromatic hydroxy acid, is widely used in medicine, the chemical industry, and agriculture. With the continuous growth of market demand, traditional chemical synthesis methods are increasingly inadequate to meet the requirements of green and sustainable development due to issues such as complex processes, poor stereoselectivity, numerous byproducts, and serious environmental pollution. MA synthesis strategies based on biocatalytic technology have become a research hotspot due to their high efficiency, environmental friendliness, and excellent stereoselectivity. Significant progress has been made in enzyme engineering modifications, metabolic pathway design, and process optimization. Importantly, biomechanical research provides a transformative perspective for this field. By analyzing the mechanical response characteristics of microbial cells in bioreactors, biomechanics facilitates the regulation of relevant environmental factors during the fermentation process, thereby improving synthesis efficiency. Molecular dynamics simulations are also employed to uncover stability differences in enzyme–substrate complexes, providing a structural mechanics basis for the rational design of highly catalytically active enzyme variants. These biomechanic-driven approaches lay the foundation for the future development of intelligent, responsive biosynthesis systems. The deep integration of biomechanics and synthetic biology is reshaping the process paradigm of green MA manufacturing. This review will provide a comprehensive summary of the applications of MA and recent advances in its biosynthesis, with a particular focus on the pivotal role of biomechanical characteristics. Full article

Background/Objectives: Electronic medical record systems play a crucial role in the operation of modern healthcare institutions, enabling the foundational data necessary for advancements in personalized medicine. Despite their importance, the software supporting these systems frequently experiences data availability and integrity issues, particularly concerning patients’ personal information. This study aims to present a decentralized architecture that integrates both clinical and personal patient data, with a provenance mechanism to enable data tracing and auditing, ultimately supporting more precise and personalized healthcare decisions. Methods: A system implementation based on the solution was developed, and a feasibility study was conducted with synthetic medical records data. Results: The system was able to correctly receive data of 190 instances of the entities designed, which included different types of medical records, and generate 573 provenance entries that captured in detail the context of the associated medical information. Conclusions: For the first cycle of the research, the system developed served to validate the main features of the solution, and through that, it was possible to infer the feasibility of a decentralized EHR and PHR health system with formal provenance data tracking. Such a system lays a robust foundation for secure and reliable data management, which is essential for the effective implementation and future development of personalized medicine initiatives. Full article