Search Results (66)

Intrabody cage augmentation has emerged as a minimally invasive technique for anterior column reconstruction in Kümmell disease and osteoporotic burst fractures. These osteoporotic conditions lead to progressive vertebral collapse, kyphosis, and instability. While cement augmentation provides rapid pain relief, it often fails to reliably restore sagittal balance or ensure biological integration in advanced stages of collapse. Although conventional anterior corpectomy with long-segment posterior fusion can achieve satisfactory deformity correction, these procedures are associated with substantial surgical morbidity. In contrast, screw fixation alone often fails to withstand anterior loading, resulting in loss of correction or hardware failure. By adapting standard interbody devices for off-label intravertebral use, this technique utilizes the intravertebral cleft as a natural cavity to restore vertebral height and sagittal alignment while preserving adjacent intervertebral discs and reducing stress on posterior instrumentation. The surgical technique involves transpedicular access, meticulous curettage of necrotic tissue, and insertion of a cage packed with osteoinductive material. This approach minimizes surgical trauma and operative time compared with conventional corpectomy procedures. Reported outcomes from retrospective series suggest promising pain relief, maintenance of correction, and low complication rates. Collectively, current evidence suggests that intrabody cage augmentation may serve as a potential, less invasive surgical option, acting as an intermediate approach between cement augmentation and corpectomy. However, as the existing evidence remains preliminary, high-quality prospective comparative studies are required to establish definitive indications and long-term efficacy. Full article

Body area networks (BANs) require secure intra-body communication, yet sensor nodes are too resource-constrained for conventional public-key cryptography, and pre-shared key schemes conflict with plug-and-play clinical workflows. This paper introduces PhysioKey, a TinyML-based key agreement framework that derives symmetric session keys from physiological signals without pre-shared secrets or trusted third parties. A lightweight 1D-CNN (6320 parameters, INT8-quantized, 31.2 KB flash) extracts embeddings from ECG and PPG windows on ARM Cortex-M4 class devices, which are reconciled through fuzzy commitment with BCH error-correcting codes. Patient-level 5-fold cross-validation on PTB-XL (500 patients, dual-ECG) achieves EER of $7.8\%\pm 0.8\%$ with ROC AUC $0.978\pm 0.004$; on BIDMC (53 patients, ECG + PPG), a dual-encoder architecture reduces cross-modal EER to $30.6\%\pm 1.2\%$. Since standalone PhysioKey yields only 7–24 effective key bits, the recommended deployment mode is a hybrid PhysioKey + ECDH protocol providing 128-bit security while PhysioKey adds physical on-body authentication; standalone operation suits energy-constrained scenarios with its $27\times$ advantage over ECDH. HKDF-SHA-256 post-processing yields session keys passing all six NIST SP 800-22 tests (≥96% at the 1024-bit level). Full article

Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). Yet the molecular mechanisms underlying its contribution to AD remain to be fully elucidated. Here, we developed and characterized a set of apoE-specific single-domain antibodies (nanobodies) as a molecular toolbox to investigate intracellular apoE4. The nanobodies bind human apoE with nanomolar to sub-nanomolar affinity and recognize both apoE3 and apoE4. Domain-level epitope mapping revealed nanobodies that selectively bind either an N-terminal (residues 1–173) or C-terminal (residues 170–299) apoE4 fragment. Several nanobodies were validated as endoplasmic reticulum-targeted intrabodies that bind apoE4 intracellularly and promote its intracellular retention. These nanobodies constitute a versatile toolbox for probing and manipulating apoE4 in cellular models. As an exploratory application of this nanobody toolbox, we examined cytosolic apoE4, motivated by previous studies suggesting that cytosolic apoE4 fragments may influence AD-related cellular processes. Cytosolic expression of apoE4 resulted in perinuclear protein assemblies and the appearance of a ~25 kDa apoE4 fragment. Using a nanobody-based nuclear relocalization assay, we showed that cytosolic apoE4 remains accessible for nanobody binding but was not relocated to the nucleus by a nuclear localization signal-equipped nanobody. Altogether, this study introduces a nanobody-based toolbox to investigate apoE4 in distinct intracellular contexts, which can be relevant to AD. Full article

Implantable intrabody communication (IBC) is a method that enables low-power, high-security communication between implanted in-body devices that could track biomedical signals and an on-body receiver by using the human body as a communication medium. As the human body consists of various tissues that each have different conductivity, this paper explores the effects of the conductivity of the communication medium on the channel gain over a wide frequency range from 10 MHz up to 300 MHz through the measurements and two models: an electrical circuit model and a FEM simulation model. Measurements are conducted using a liquid phantom with varying conductivity values from 0 S/m up to 1 S/m, covering most human tissues in the frequency range of interest. The circuit and FEM models are designed to mimic the measurement setup in order to verify the measurement results. Results show that the circuit model predicts the communication channel characteristics well at lower frequencies but cannot account for the influence of the measurement setup at higher frequencies. The influence of wire inductances, which can cause a resonant behavior when measuring at frequencies above 100 MHz, was observed using the FEM model. The results also show that the higher the conductivity of the tissue in which the device is implanted, the lower the gain of the signal, with the difference in gain being more prominent when capacitive termination with a high-impedance load is used instead of low-impedance termination. These findings provide valuable insight for selecting the appropriate interface (low-impedance vs. high-impedance termination) across specific frequency ranges for in-body to on-body (IB2OB) communication devices, while illustrating the effect of tissue conductivity on an IBC channel, thereby supporting the optimized design and implementation of reliable IB2OB communication systems. Full article

Implantable technologies targeting the cerebral cortex and deeper brain structures are increasingly utilised in human–machine interfacing, advanced neuroprosthetics, and clinical interventions for neurological conditions. These systems require highly efficient and low-power methods for exchanging information between the implant and external electronics. Traditional approaches often rely on inductively coupled data transfer (ic-DT), where the same coils used for wireless power are modulated for communication. Other designs use high-frequency antenna-based radio systems, typically operating in the 401–406 MHz MedRadio band or the 2.4 GHz ISM band. A promising alternative is intrabody communication (IBC), which leverages the bioelectrical characteristics of body tissue to enable signal propagation. This work presents a theoretical investigation into two schemes—inductive coupling and galvanically coupled IBC (gc-IBC)—as applied to cortical data links, considering frequencies from 1 to 10 MHz and implant depths of up to 7 cm. We propose a hybrid solution where gc-IBC supports data transmission and inductive coupling facilitates wireless power delivery. Our findings indicate that gc-IBC can accommodate wider bandwidths than ic-DT and offers significantly reduced path loss, approximately 20 dB lower than those of conventional RF-based antenna systems. Full article

Optical intrabody wireless nanosensor networks (OiWNSNs) enable groundbreaking biomedical applications via optical nanocommunication within biological tissues. Synchronization is critical for accurate data recovery in these energy- and size-constrained nanonetworks. In this study, we investigate timing synchronization in a highly dispersive and noisy intravascular optical channel, particularly under an on–off keying preamble comprising Gaussian optical pulses. We proposed a synchronization scheme based on the repetitive transmission of a preamble and noncoherent detection using continuous-time moving average filters with multiple integrator windows. The simulation results reveal that increasing the communication distance degrades the synchronization performance. To counter this degradation, we can increase the number of preamble repetitions, which markedly improves the system reliability and timing accuracy due to the averaging gain, although the performance saturates due to the dispersion floor inherent in the blood channel. Moreover, we found that low-resolution nanoreceivers with fewer integrators outperform high-resolution designs in dispersive environments, as they mitigate the energy-splitting problem due to pulse broadening. This tradeoff between temporal resolution and robustness highlights the importance of channel-aware receiver design. Overall, this study provides key insights into the physical layer design of OiWNSNs and offers practical guidelines for achieving robust synchronization under realistic biological conditions. Full article

Murine double minute 2 (MDM2) is involved in various cancers and is an attractive target. The RING domain of MDM2 has been discussed as an alternative target to stabilize p53. Designing drugs to target the RING domain of MDM2 is an alternative approach to preventing MDM2-mediated deactivation of p53. In this study, we obtained a human VH single-domain antibody and revealed its regulatory effects and mechanisms. The RING domain of MDM2 was synthesized using a chemical synthesis method, and antibodies against the MDM2 RING domain were screened from a human VH single-domain antibody library and expressed intracellularly. A nuclear localization sequence was designed to ensure intrabody efficiency. The binding activity of the individually cloned antibodies was detected using ELISA. MTT and flow cytometry assays were used to detect the reactions related to intrabody in vitro. The combination and its influence on MDM2 were detected using immunoprecipitation assays, confocal microscopy, and Western blotting. The effects on apoptosis-related mitochondrial pathways downstream of p53 were examined using Western blotting. The influence on cell cycle distribution and cyclin-related proteins was detected using flow cytometry and Western blotting. A549 cell xenografts were constructed to assess the effect of intrabodies on growth in vivo. The molecular mechanisms of MDM2 and p53 were studied using Western blotting. Eight individual cloned antibodies were positive compared to the signals on the BSA-coated plates, especially intrabodies VH-HT3. In A549 and MCF-7 cell lines, VH-HT3 exhibited significant inhibitory effects on cell proliferation and apoptosis. VH-HT3 co-localized with MDM2 in the nucleus and cytoplasm. The specific combination of VH-HT3 triggered no significant effect on MDM2 activity for p53 degradation but upregulated the levels of factors downstream of p53, especially those in the mitochondrial apoptosis pathway. Moreover, VH-HT3 induced cell cycle arrest, and the expression of cyclin-related proteins was consistent with this observation. VH-HT3 also retarded the growth of A549 xenografts in vivo. Further tests suggested that VH-HT3 inhibited MDM2 function by increasing HIPK2 levels and activating p53 at the Ser46 site. VH-HT3, prepared from a human VH single-domain antibody library, inhibited p53 activity and produced a tumor-suppressive effect. The intrabody VH-HT3 is a candidate for the development of novel MDM2 inhibitors. Full article

Intrabody communication (IBC) establishes a wireless connection between devices in a Wireless Body Area Network (WBAN) by utilizing the human body as a transmission medium. The characteristics of the IBC channel are significantly influenced by the geometric and biological features of the human body and tissues. This paper analyzes a dataset with experimental real subjects’ data on signal loss in a galvanic IBC channel, models IBC identification using the K-Nearest Neighbors (KNN) algorithm, and proposes a novel IBC WBAN architecture incorporating an identification function. The analysis of the dataset revealed that the IBC channel gain exhibits a wide range of variations depending on individual human body characteristics such as height, weight, body mass index, and body composition. Consequently, biometric identification can be leveraged within the IBC WBAN paradigm. Through modeling IBC identification on cleaned and labeled data, we demonstrated an identification accuracy of 99.9% based on the results of our modeling. The proposed IBC WBAN architecture with an integrated identification function is anticipated to enhance the application scope and accelerate the development of IBC WBANs. Full article

The P2X7 receptor is involved in innate immune responses, with its intracellular C-terminal domain capable of interacting with signaling molecules to regulate immune cell activation; however, the mechanisms underlying the signaling complexes remain unclear. To elucidate the function of the P2X7 C-terminal domain, we established bone marrow-derived macrophage (BMDM) cell lines from transgenic (Tg) mice overexpressing the C-terminal domain of P2X7 or anti-P2X7 C-terminal domain single-chain variable fragment (scFv) intrabody. In contrast to wild-type mouse BMDMs, the Tg BMDMs showed impairment of inflammatory responses induced by lipopolysaccharide (LPS) stimulation, such as NF-κB activation and subsequent TNF-α, IL-1β, and IL-6 expression. Furthermore, P2X7 was specifically associated with myeloid differentiation primary response gene 88 (MyD88) in wild-type BMDMs; its specific interaction was strongly interfered with by overexpression of the P2X7 C-terminal domain or anti-P2X7 C-terminal domain scFv in Tg BMDMs. These observations strongly suggest that P2X7 may have pivotal roles in LPS signaling cascades and could modulate macrophage inflammatory responses through its C-terminal domain. Full article

Recombinant antibodies and, more recently, T cell receptor (TCR)-engineered T cell therapies represent two immunological strategies that have come to the forefront of clinical interest for targeting intracellular neoantigens in benign and malignant diseases. T cell-based therapies targeting neoantigens use T cells expressing a recombinant complete TCR (TCR-T cell), a chimeric antigen receptor (CAR) with the variable domains of a neoepitope-reactive TCR as a binding domain (TCR-CAR-T cell) or a TCR-like antibody as a binding domain (TCR-like CAR-T cell). Furthermore, the synthetic T cell receptor and antigen receptor (STAR) and heterodimeric TCR-like CAR (T-CAR) are designed as a double-chain TCRαβ-based receptor with variable regions of immunoglobulin heavy and light chains (VH and VL) fused to TCR-Cα and TCR-Cβ, respectively, resulting in TCR signaling. In contrast to the use of recombinant T cells, anti-neopeptide MHC (pMHC) antibodies and intrabodies neutralizing intracellular neoantigens can be more easily applied to cancer patients. However, different limitations should be considered, such as the loss of neoantigens, the modification of antigen peptide presentation, tumor heterogenicity, and the immunosuppressive activity of the tumor environment. The simultaneous application of immune checkpoint blocking antibodies and of CRISPR/Cas9-based genome editing tools to engineer different recombinant T cells with enhanced therapeutic functions could make T cell therapies more efficient and could pave the way for its routine clinical application. Full article

Single-domain antibodies, including variable domains of the heavy chains of heavy chain-only antibodies (VHHs) from camelids and variable domains of immunoglobulin new antigen receptors (VNARs) from cartilaginous fish, show the therapeutic potential of targeting antigens in a cytosol reducing environment. A large proportion of single-domain antibodies contain non-canonical cysteines and corresponding non-canonical disulfide bonds situated on the protein surface, rendering them vulnerable to environmental factors. Research on non-canonical disulfide bonds has been limited, with a focus solely on VHHs and utilizing only cysteine mutations rather than the reducing agent treatment. In this study, we examined an anti-lysozyme VNAR and an anti-BC2-tag VHH, including their non-canonical disulfide bond reduced counterparts and non-canonical cysteine mutants. Both the affinity and stability of the VNARs and VHHs decreased in the non-canonical cysteine mutants, whereas the reduced-state samples exhibited decreased thermal stability, with their affinity remaining almost unchanged regardless of the presence of reducing agents. Molecular dynamics simulations suggested that the decrease in affinity of the mutants resulted from increased flexibility of the CDRs, the disappearance of non-canonical cysteine–antigen interactions, and the perturbation of other antigen-interacting residues caused by mutations. These findings highlight the significance of non-canonical cysteines for the affinity of single-domain antibodies and demonstrate that the mutation of non-canonical cysteines is not equivalent to the disruption of non-canonical disulfide bonds with a reducing agent when assessing the function of non-canonical disulfide bonds. Full article

Glioblastoma is the most prevalent and fatal form of primary brain tumors. New targeted therapeutic strategies for this type of tumor are imperative given the dire prognosis for glioblastoma patients and the poor results of current multimodal therapy. Previously reported drawbacks of antibody-based therapeutics include the inability to translocate across the blood–brain barrier and reach intracellular targets due to their molecular weight. These disadvantages translate into poor target neutralization and cancer maintenance. Unlike conventional antibodies, vNARs can permeate tissues and recognize conformational or cryptic epitopes due to their stability, CDR3 amino acid sequence, and smaller molecular weight. Thus, vNARs represent a potential antibody format to use as intrabodies or soluble immunocarriers. This review comprehensively summarizes key intracellular pathways in glioblastoma cells that induce proliferation, progression, and cancer survival to determine a new potential targeted glioblastoma therapy based on previously reported vNARs. The results seek to support the next application of vNARs as single-domain antibody drug-conjugated therapies, which could overcome the disadvantages of conventional monoclonal antibodies and provide an innovative approach for glioblastoma treatment. Full article

Fluctuation-induced forces are a hallmark of the interplay between fluctuations and geometry. We recently proved the existence of a multi-parametric family of exact representations of Casimir and Casimir–Polder interactions between bodies of arbitrary shape and material composition, admitting a multiple scattering expansion (MSE) as a sequence of inter-body and intra-body multiple wave scatterings. The approach requires no knowledge of the scattering amplitude (T-matrix) of the bodies. In this paper, we investigate the convergence properties of the MSE for the Casimir–Polder interaction of a polarizable particle with a macroscopic body. We consider representative materials from different classes, such as insulators, conductors, and semiconductors. Using a sphere and a cylinder as benchmarks, we demonstrate that the MSE can be used to efficiently and accurately compute the Casimir–Polder interaction for bodies with smooth surfaces. Full article

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) remains a deadly cancer worldwide with a need for new therapeutic approaches. A dysregulation in the equilibrium between pro- and anti-inflammatory responses with a predominant immunosuppressive inflammatory reaction in advanced stage tumors seem to contribute to tumor growth and metastasis. The current therapies do not include strategies against pro-tumorigenic inflammation in cancer patients. We have shown that the upregulated cell surface expression of Toll-like Receptor (TLR) 2 and of TLR9 inside PDAC cells maintain chronic inflammatory responses, support chemotherapeutic resistance, and mediate tumor progression in human pancreatic cancer. We further demonstrated intracellular TLR2 and TLR9 targeting using specific intrabodies, which resulted in downregulated inflammatory signaling. In this study, we tested, for the first time, an intrabody-mediated TLR blockade in human TLR2- and TLR9-expressing pancreatic cancer cells for its effects on inflammatory signaling-mediated tumor growth. Newly designed anti-TLR2- and anti-TLR9-specific intrabodies inhibited PDAC growth. Co-expression analysis of the intrabodies and corresponding human TLRs showed efficient retention and accumulation of both intrabodies within the endoplasmic reticulum (ER), while co-immunoprecipitation studies indicated both intrabodies interacting with their cognate TLR antigen within the pancreatic cancer cells. Cancer cells with attenuated proliferation expressing accumulated TLR2 and TRL9 intrabodies demonstrated reduced STAT3 phosphorylation signaling, while apoptotic markers Caspases 3 and 8 were upregulated. To conclude, our results demonstrate the TLR2 and TLR9-specific intrabody-mediated signaling pathway inhibition of autoregulatory inflammation inside cancer cells and their proliferation, resulting in the suppression of pancreatic tumor cell growth. These findings underscore the potential of specific intrabody-mediated TLR inhibition in the ER relevant for tumor growth inhibition and open up a new therapeutic intervention strategy for the treatment of pancreatic cancer. Full article

Signal propagation models play a fundamental role in radio frequency communication research. However, emerging communication methods, such as body-coupled communication (BCC), require the creation of new models. In this paper, we introduce mathematical models that approximate the human body as an electrical circuit, as well as linear regression- and random forest-based predictive models that infer the expected signal loss from its frequency, measurement point locations, and body parameters. The results demonstrate a close correspondence between the amplitude-frequency response (AFR) predicted by the electrical circuit models and the experimental data gathered from volunteers. The accuracy of our predictive models was assessed by using their root mean square errors (RMSE), ranging from 1.5 to 7 dB depending on the signal frequency within the 0.05 to 20 MHz range. These results allow researchers and engineers to simulate and forecast the expected signal loss within BCC systems during their design phase. Full article