Search Results (1,166)

Stem cells, unspecialized cells with regenerative and differentiation capabilities, hold immense potential in regenerative medicine, exemplified by hematopoietic stem cell transplantation. However, their clinical application faces significant limitations, including their tumorigenic risk due to uncontrolled proliferation and cellular heterogeneity. This review explores how synthetic biology, an interdisciplinary approach combining engineering and biology, offers promising solutions to these challenges. It discusses the concepts, toolkit, and advantages of synthetic biology, focusing on the design and integration of genetic circuits to program stem cell differentiation and engineer safety mechanisms like inducible suicide switches. This review comprehensively examines recent advancements in synthetic biology applications for stem cell engineering, including programmable differentiation circuits, cell reprogramming strategies, and therapeutic cell engineering approaches. We highlight specific examples of genetic circuits that have been successfully implemented in various stem cell types, from embryonic stem cells to induced pluripotent stem cells, demonstrating their potential for clinical translation. Despite these advancements, the integration of synthetic biology with mammalian cells remains complex, necessitating further research, standardized datasets, open access repositories, and interdisciplinary collaborations to build a robust framework for predicting and managing this complexity. Full article

REG3A, a prominent member of the human regenerating islet-derived (REG) lectin family, plays a pivotal and multifaceted role in immune defense, inflammation, and cancer biology. Primarily expressed in gastrointestinal epithelial cells, REG3A reinforces barrier integrity, orchestrates mucosal immune responses, and regulates host–microbiota interactions. It also functions as a potent non-enzymatic antioxidant, protecting tissues from oxidative stress. REG3A expression is tightly regulated by inflammatory stimuli and is robustly induced during immune activation, where it limits microbial invasion, dampens tissue injury, and promotes epithelial repair. Beyond its antimicrobial and immunomodulatory properties, REG3A contributes to the resolution of inflammation and the maintenance of tissue homeostasis. However, its role in cancer is highly context-dependent. In some tumor types, REG3A fosters malignant progression by enhancing cell survival, proliferation, and invasiveness. In others, it acts as a tumor suppressor, inhibiting growth and metastatic potential. These opposing effects are likely dictated by a combination of factors, including the tissue of origin, the composition and dynamics of the tumor microenvironment, and the stage of disease progression. Additionally, the secreted nature of REG3A implies both local and systemic effects, further modulated by organ-specific physiology. Experimental variability may also reflect differences in methodologies, analytical tools, and model systems used. This review synthesizes current knowledge on the pleiotropic functions of REG3A, emphasizing its roles in epithelial defense, immune regulation, redox homeostasis, and oncogenesis. A deeper understanding of REG3A’s pleiotropic effects could open up new therapeutic avenues in both inflammatory disorders and cancer. Full article

Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article

Hyperekplexia (OMIM 149400), a sensorimotor syndrome of perinatal clinical relevance, causes newborns to display an energic startle reflex in response to certain trivial stimuli. This condition can be lethal due to apnea episodes. The disease is caused by a blockade of glycinergic neurotransmission. Glycinergic interneurons preserve their identity by the activity of the surface glycine transporter GlyT2, which supplies glycine to presynaptic terminals to maintain glycine content in synaptic vesicles. Loss-of-function mutations in the GlyT2 gene (SLC6A5) cause a presynaptic form of human hyperekplexia. Here, we describe a new GlyT2 variant found in an infantile patient diagnosed with hyperekplexia. A missense mutation in the open reading frame of the GlyT2 gene inherited in homozygosity caused the substitution G449E in a residue highly conserved across the phylogenetic scale. The sequences of the glycine receptor genes GLRA1 and GLRB did not show abnormalities. We expressed the recombinant GlyT2 variant in heterologous cells and analyzed its pathogenic mechanism. The transporter was totally inactive, behaving as a bona fide loss-of-function mutant. Furthermore, the mutation promoted the abnormal insertion of the protein into the membrane, leading to its large incorporation into lipid rafts. However, there was no apparent alteration of wild-type trafficking upon mutant coexpression, as the mutant was prematurely degraded from the endoplasmic reticulum. Rescue with chemical chaperones was not possible for this mutant. Proteomics demonstrated that the expression of the mutant induced the unfolded protein response and interfered with raft-dependent processes. Therefore, the new variant causes a loss of function regarding GlyT2 activity but a gain of function as a cell proteostasis disturber. Full article

Background/Objective: The Rs1 exon-1-del rat (Rs1KO) XLRS model shows normal retinal development until postnatal day 12 (P12) when small cystic spaces start to form in the inner nuclear layer. These enlarge rapidly, peak at P15, and then collapse by P19. These events overlap with eye opening at P12–P15. We investigated whether new light-driven retinal activity could contribute to the appearance and progression of schisis cavities in this rat model of XLRS disease. Methods: For dark rearing (D/D), mating pairs of Rs1KO strain were raised in total darkness in a special vivarium at UC Davis. When pups were born, they were maintained in total darkness, and eyes were collected at P12, P15, and P30 (n = 3/group) for each of the D/D and cyclic light-reared 12 h light–12 h dark (L/D) Rs1KO and wild-type (WT) littermates. Eyes were fixed, paraffin-embedded, and sectioned. Tissue morphology was examined by H&E and marker expression of retinoschisin1 (Rs1), rhodopsin (Rho), and postsynaptic protein 95 (Psd95) by fluorescent immunohistochemistry. H&E-stained images were analyzed with ImageJ version 1.54h to quantify cavity size using the “Analyze Particles” function. Results: Small intra-retinal schisis cavities begin to form by P12 in the inner retina of both D/D and L/D animals. Cavity formation was equivalent or more pronounced in D/D animals than in L/D animals. We compared Iba1 (activation marker of immune cells) distribution and found that by P12, when schisis appeared, Iba1⁺ cells had accumulated in regions of schisis. Iba1⁺ cells were more abundant in Rs1KO animals than WT animals and appeared slightly more prevalent in D/D- than L/D-reared Rs1KO animals. We compared photoreceptor development using Rho, Rs1, and Psd95 expression, and these were similar; however, the outer segments (OSs) of D/D animals with Rho labeling at P12 were longer than L/D animals. Conclusions: The results showed that cavities formed at the same time in D/D and L/D XLRS rat pups, indicating that the timing of schisis formation is not light stimulus-driven but rather appears to be a result of developmental events. Cavity size tended to be larger under dark-rearing conditions in D/D animals, which could be due to the decreased rate of phagocytosis by the RPE in the dark, allowing for continued growth of the OSs without the usual shedding of the distal tip, a key mechanism behind dark adaptation in the retina. These results highlight the complexity of XLRS pathology; however, we found no evidence that light-driven metabolic activity accounted for schisis cavity formation. Full article

It is projected that the world population will quadruple over the next century, and to meet future food demands, agricultural production will need to increase by 70%. Therefore, there has been a transition from traditional farming methods to autonomous modern agriculture. One such modern technique is aeroponic farming, in which plants are grown without soil under controlled and hygienic conditions. In aeroponic farming, plants are significantly less affected by climatic conditions, infectious diseases, and biotic and abiotic stresses, such as pest infestations. Additionally, this method can reduce water, nutrient, and pesticide usage by 98%, 60%, and 100%, respectively, while increasing the yield by 45–75% compared to traditional farming. In this study, a three-dimensional industrial design of an innovative aeroponic plant growth chamber was presented for use by individuals, researchers, and professional growers. The proposed chamber design is modular and open to further innovation. Unlike existing chambers, it includes load cells that enable real-time monitoring of the fresh weight of the plant. Furthermore, cameras were integrated into the chamber to track plant growth and changes over time and weight. Additionally, RGB power LEDs were placed on the inner ceiling of the chamber to provide an optimal lighting intensity and spectrum based on the cultivated plant species. A customizable chamber design was introduced, allowing users to determine the growing tray and nutrient nozzles according to the type and quantity of plants. Finally, system models were developed for temperature control of the chamber. Temperature control was implemented using a proportional-integral-derivative controller optimized with particle swarm optimization, radial movement optimization, differential evolution, and mayfly optimization algorithms for the gain parameters. The simulation results indicate that the temperatures of the growing and feeding chambers in the cabinet reached a steady state within 260 s, with an offset error of no more than 0.5 °C. This result demonstrates the accuracy of the derived model and the effectiveness of the optimized controllers. Full article

This study provides an in-depth numerical simulation to optimize the structure of InGaN-based p-i-n single homojunction solar cells using SCAPS-1D software. The cell comprised a p-type ${\mathrm{I}\mathrm{n}}_{0.6}{\mathrm{G}\mathrm{a}}_{0.4}\mathrm{N}$ layer, an intrinsic i-type ${\mathrm{I}\mathrm{n}}_{0.52}{\mathrm{G}\mathrm{a}}_{0.48}\mathrm{N}$ layer, and an n-type ${\mathrm{I}\mathrm{n}}_{0.48}{\mathrm{G}\mathrm{a}}_{0.52}\mathrm{N}$ layer. A systematic parametric optimization methodology was employed, involving a sequential investigation of doping concentrations, layer thicknesses, and indium composition to identify the optimal device configuration. Initial optimization of doping levels established optimal concentrations of ${\mathrm{N}}_{\mathrm{d}}=1\times {10}^{16} {\mathrm{c}\mathrm{m}}^{-3}$ for the p-layer and ${\mathrm{N}}_{\mathrm{a}}=8\times {10}^{17} {\mathrm{c}\mathrm{m}}^{-3}$ for the n-layer. Subsequently, structural parameters were optimized through systematic variation of layer thicknesses while maintaining optimal doping concentrations. The comprehensive optimization culminated in the identification of an optimal device architecture featuring a p-type layer thickness of 0.2 μm, an intrinsic layer thickness of 0.4 μm, an n-type layer thickness of 0.06 μm, and an indium composition of x = 0.59 in the intrinsic layer. This fully optimized configuration achieved a maximum conversion efficiency (η) of 21.40%, a short-circuit current density (${\mathrm{J}}_{\mathrm{s}\mathrm{c}}$) of 28.2 mA/cm², and an open-circuit voltage ($V_{oc}$) of 0.874 V. The systematic optimization approach demonstrates the critical importance of simultaneous parameter optimization in achieving superior photovoltaic performance, with the final device configuration representing a 30.01% efficiency improvement compared to the baseline structure. These findings provide critical insights for improving the design and performance of InGaN-based solar cells, serving as a valuable reference for future experimental research. Full article

Neural stem cells have shown great potential in the therapy of neurodegenerative diseases such as Parkinson’s disease (PD), because of their ability to differentiate into various types of neural cells and substitute for damaged neurons. Their clinical application is, however, impeded by limitations such as low survival rates following transplantation, low efficiency of differentiation, the potential for tumorigenesis, and the risk of immune rejection by the host. Adipose-derived stem cells (ADSCs) have become increasingly popular as an alternative tool in regenerative medicine due to their accessibility, multipotency, and low immunogenicity. The recent advance in inducing ADSCs into neural stem cell-like cells (iNSCs) opens up a new avenue for the treatment of PD by restoring dopaminergic neuron populations. Here, the biological characteristics, induction protocols, molecular mechanisms, and prospective applications of ADSCs in neural repair are summarized systematically. We also covered current technical challenges, such as differentiation protocol optimization and functional integration, and future perspectives, including biomaterial and gene editing applications to enhance ADSC-based therapies. With these challenges met, ADSCs hold excellent potential for advancing personalized and combination therapies for neurodegenerative diseases. Full article

The review compares the principles of organization of the brain and immune system, two important organs developed over 500 million years in multicellular organisms, including humans. It summarizes the latest results from research in neurosciences and immunology concerning intercellular communication. While in the brain, intercellular communication is primarily based on exchange of electrical signals, this is not the case in the immune system. The question, therefore, arises as to whether nature developed two entirely different systems of organization. It will be demonstrated that a few basic principles of brain and immune responses are organized in a different way. A majority of intercellular communications, however, such as the formation of synapses, are shown to have many similarities. Both systems are intimately interconnected to protect the body from the1 dangers of the outside and the inside world. During homeostasis, all systems are in regulatory balance. A new hypothesis states that the central systems surrounded by bone, namely the central nervous system (CNS) and the central immune system (CIS), are based on three types of stem cells and function in an open but autonomous way. T cell immune responses to antigens from blood and cerebrospinal fluid protect the system and maintain neuroimmune homeostasis. The newly discovered tunneling nanotubes and extracellular vesicles are postulated to play an important role in crosstalk with already known homeostasis regulators and help in cellular repair and the recycling of biologic material. Three examples are selected to illustrate dysfunctions of homeostasis, namely migraine, multiple sclerosis, and brain cancer. The focus on these different conditions provides deep insights into such neurological and/or immunological malfunctions. Technological advances in neurosciences and immunology can enable neuroimmunomodulation and the development of new treatment possibilities. Full article

Traditional PMUT ultrasonic ranging systems usually possess a large measurement blind area under the integrated transmit–receive mode, dramatically limiting its distance measurement in confined spaces, such as when determining the clearance of large bearing components. Here, a broadband PMUT rangefinder was designed by integrating six types of different cells with adjacent resonant frequencies into an array. Through overlapping and coupling of the bandwidths from the different cells, the proposed PMUTs showed a wide –6 dB fractional bandwidth of 108% in silicon oil. Due to the broadening of bandwidth, the device could obtain the maximum steady state with less excitation (5 cycles versus 14 cycles) and reduce its residual ring-down (ca. 6 μs versus 15 μs) compared with the traditional PMUT array with the same cells, resulting in a small blind area. The pulse–echo ranging experiments demonstrated that the blind area was effectively reduced to 4.4 mm in air or 12.8 mm in silicon oil, and the error was controlled within ±0.3 mm for distance measurements up to 250 mm. In addition, a specific ultrasound signal processing circuit with functions of transmitting, receiving, and processing ultrasonic waves was developed. Combining the processing circuit and PMUT device, the system was applied to determine the axial clearance of the main bearing in a tunneling machine. This work develops broadband PMUTs with a small blind area and high resolution for distance measurement in narrow and confined spaces, opening up a new path for ultrasonic ranging technology. Full article

Cell-free protein synthesis (CFPS) has transformed protein production capabilities by eliminating cellular constraints, enabling the rapid expression of difficult-to-produce proteins in an open, customizable environment. As CFPS applications expand from fundamental research to industrial production, therapeutic manufacturing, and point-of-care diagnostics, the diverse array of reactor formats has become increasingly important yet challenging to navigate. This review examines the evolution and characteristics of thirteen major CFPS reactor formats, from traditional batch systems to advanced platforms. The historical development of CFPS reactors from the 1960s to present day is presented. Additionally, for each format, operational principles, advantages, limitations, and notable applications are evaluated. The review concludes with a comparative assessment of reactor performance across critical parameters, including productivity, scalability, technical complexity, environmental stability, and application suitability. To our knowledge this structured analysis is the first to focus predominantly on the various reactor formats of cell-free systems and to provide a guide to assist researchers in choosing the reactor type that best fits their specific applications. Full article

Oncogenic viruses are infectious agents that can cause cancer in humans and animals. They are estimated to be responsible for approximately 12% of human cancers worldwide. These viruses trigger a series of mechanisms that allow them to insert their genetic material into host cells, disrupting normal cellular processes and leading to uncontrolled growth and tumor formation. This article reviews the literature on the main oncogenic viruses and reports on newly identified viruses potentially associated with cancer development, addressing the mechanisms of oncogenesis and the types of cancers associated. In addition, the article brings together the evidence for preventive strategies, such as vaccination, and therapeutic advances in combating oncogenic viral infections. This review discusses the role of early detection and treatment in managing virus-related cancers globally. This article reviews current prevention and treatment strategies, including HPV and HBV vaccines and antiviral therapies, and mentions future approaches like immunotherapies and CRISPR/Cas9. Therefore, this article underscores the importance of studying the dynamics of co-infection and the role of human microbiota in viral persistence and carcinogenesis, which opens new possibilities for combination therapies and microbiome-based interventions to slow the progression of viral-related tumors. Full article

Erythropoiesis, the process driving the differentiation of hematopoietic stem and progenitor cells to mature erythrocytes, unfolds through tightly orchestrated developmental stages, each defined by profound epigenetic remodeling. From the initial commitment of hematopoietic progenitors to the terminal enucleation of erythrocytes, dynamic changes in chromatin accessibility, transcription factor occupancy, and three-dimensional genome architecture govern lineage specification and stage-specific gene expression. Advances in our understanding of the regulatory genome have uncovered how non-coding elements, including enhancers, silencers, and insulators, shape the transcriptional landscape of erythroid cells. These elements work in concert with lineage-determining transcription factors to establish and maintain erythroid identity. Disruption of these epigenetic programs—whether by inherited mutations, somatic alterations, or environmental stress—can lead to a wide range of hematologic disorders. Importantly, this growing knowledge base has opened new therapeutic avenues, enabling the development of precision tools that target regulatory circuits to correct gene expression. These include epigenetic drugs, enhancer-targeted genome editing, and lineage-restricted gene therapies that leverage endogenous regulatory logic. As our understanding of erythroid epigenomics deepens, so too does our ability to design rational, cell-type-specific interventions for red blood cell disorders. Full article

It has been >35 years since the cells described as mesenchymal stem cells (MSCs) were reported to have multi-lineage potential, which opened the possibility that they could be used to repair injured or diseased musculoskeletal tissues. Since that time, similar cells have been isolated from many tissues, again raising expectations that they could be used to repair or regenerate many types of tissues. While some progress in using these cells, as well as induced pluripotent stem cells (iPSCs), to facilitate the repair of tissues has been achieved, an emerging body of literature would suggest that the cells in question facilitate repair via released extracellular vesicles (EVs) that contain a cargo of molecules which induce endogenous cells to do the actual repair. How the “stemness” of the cells is involved in such processes remains to be elucidated. While progress in the repair of compromised tissues has been obtained, from some perspectives, the progress has been challenging and successful translation to patients has been slow. In part, this has been due to considerable emphasis being placed on the cells or EVs, and not as much on the environments in which they are implanted. However, successful outcomes likely depend on both the development of optimized materials to be implanted and an environment that is conducive to success after implantation. This perspective article reviews some of the options regarding the implantable materials and the variables or factors that could impact the local environment’s suitability for success following implantation. In addition, attempts are made to reconcile the designation of endogenous cells labeled MSCs and their potential roles as regulators of tissue integrity in vivo. Full article

The SEPALLATA3 (SEP3)-like MADS-box genes play crucial roles in determining petal identity and development in the petunia and tomato of Solanaceae. Solanum nigrum is a self-pollinating plant in the Solanaceae family, and produces white flowers. However, the mechanisms controlling the transition from green to white petals during flower development remain poorly understood. In this study, we isolated a flower-specific SEP3-like gene, SnMADS37, from S. nigrum, and investigated its potential role in chlorophyll metabolism during petal development. Our results show that quantitative RT-PCR analysis demonstrates that SnMADS37 is exclusively expressed in petals and stamens during early floral bud development. Overexpression of SnMADS37 clearly enhanced the number of petals, promoting the formation of additional petal-like tissues in stamens and extra organs in some fruits. Moreover, fully opened transformed petals exhibited notable chlorophyll accumulation at their tips and veins, whereas silencing of Snmads37 clearly inhibited petal expansion and reduced green pigmentation in early flower buds. Additionally, the transformed green petals exhibited distinct conical epidermal cells in the green regions, similar to wild type (WT) petals. Our results demonstrate that SnMADS37 plays a critical role in regulating petal identity, expansion, and chlorophyll metabolism during petal development. These findings provide new insights into the functional diversification of SEP3-like MADS-box genes in angiosperms. Full article