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From the microscopic electroporation to the irregular distribution of cell populations, the inactivation efficacy of pulsed electric fields (PEFs) from in vitro experiments has lacked a unified physical model due to its cross-scale complexity. Inspired by a coarse-grained approach from the percolation theory, the inactivation process is simulated from a simple yet robust lattice model, where the spatiotemporal heterogeneity of the collective structure and the stochastic PEF strike are portrayed as random matrices, while also accounting for the rules of single-cell electroporation and subsequent death. Beyond successfully simulating the inactivation of monolayer adherent cells and suspended cells, which are in good agreement with in vitro results, our model reveals that (1) macroscopically three-staged inactivation pattern originates from the "accelerate–uniform–decelerate" transition of inactivation velocity, and (2) the inactivation patterns obey a universal scaling law under varied field strength, which is not satisfied under varied pulsed widths. The simulation not only sheds light on the PEF inactivation of the macroscopic cell collectives but also provides a simple and generalized numerical method for predicting PEF efficacy in experiments or engineering. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in “active surveillance (AS)” candidates refusing standard treatment options. Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Conclusions: Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach. [ABSTRACT FROM AUTHOR]

This article explores the genetic characteristics of malignant melanoma in adults with congenital nevi, a topic that has been primarily studied in children. The researchers analyzed a group of 76 patients and identified seven adults with melanoma arising from a congenital nevus. The study found that adult CMN melanomas had different genetic features compared to pediatric CMN melanomas, including the presence of certain mutations and deletions. The findings suggest potential therapeutic targets but also indicate resistance to immune checkpoint inhibitor treatment. Further research is needed to gain a better understanding of the genomic characteristics of CMN melanomas in adults. [Extracted from the article]

Objectives: The aim of the IRECAP study was to evaluate the rate of locally advanced pancreas cancer patients (LAPC) who could undergo R0 or R1 surgery after irreversible electroporation (IRE). Materials and methods: IRECAP study is a phase II, single-center, open-label, prospective, non-randomized trial registered at clinicaltrials.gov (NCT03105921). Patients with LAPC were first treated by 3-month neo-adjuvant chemotherapy in order to avoid inclusion of either patients with LAPC having become resectable after chemotherapy or patients with rapid disease progression. In cases of stable disease, IRE was performed percutaneously under CT guidance. Surgery was planned between 28 and 90 days after IRE. Tumor specimens were studied to evaluate the resection margins (R0/R1/R2). Results: Six men and 11 women were included (median age 61 years, range 37–77 years). No IRE-related death was observed. Ten patients (58%, 10/17) experienced 25 serious adverse events related to IRE. Four patients progressed between IRE and surgery and were excluded from surgery. Thirteen patients were finally operated, six withheld for pancreas resection, three for diffuse peritoneal carcinosis, two for massive vascular entrapment, and one for hepato-cellular carcinoma not diagnosed before surgery. Rate of R1-R0 was 35% (n = 6/17). Median overall survival was 31 months (95% CI; 4–undefined) for the six patients with R0/R1 resection and 21 months (95% CI; 4–25) for the 11 patients without resection or R2 resection (logrank p = 0.044). Conclusion: After neoadjuvant chemotherapy, IRE could provide R0 or R1 resection in 35% of LAPC, which seems to be associated with higher OS. Clinical relevance statement: After induction chemotherapy, stable locally advanced pancreatic cancers can be treated by irreversible electroporation, which could lead to a secondary 35% rate of R0 or R1 surgical resection which may be associated with a significantly higher overall survival. Key Points: • In cases of unresectable LAPC (locally advanced pancreatic cancer), percutaneous irreversible electroporation (pIRE) is feasible (100% success rate of the procedure), but is associated with a 58% rate of grade 3–4 adverse events. • In patients with unresectable LAPC, pIRE could lead 35% of patients to R0-R1 surgical resection. • From IRE, median overall survival was 31 months (95% CI; 4–undefined) for the patients with R0/R1 resection and 21 months (95% CI; 4–25) for the patients without resection or R2 resection (logrank p = 0.044). [ABSTRACT FROM AUTHOR]

Background: Pulsed‐field ablation (PFA) is a cutting‐edge technique that employs non‐thermal energy to cause cell death by inducing irreversible electroporation of cell membranes. This systematic review evaluates the PFA effectiveness as a potential alternative to radiofrequency and cryo‐ablation for treating ventricular tachycardia. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched using keywords related to ventricular tachycardia and pulsed‐field ablation. Eligible Studies evaluating this therapeutic approach for ventricular tachycardia were included in the final analysis. Results: We included six studies (five case reports and one case series) in our systematic review. Eight (88.8%) of procedures were successful with 100% long‐term efficacy. No procedural complications or ventricular tachycardia (VT) recurrence were observed in the cases. Conclusion: The absence of complications, high effectiveness, and long‐term success rate make PFAs a good VT treatment option. However, PFA safety and efficacy studies for VT treatment are scarce. Thus, larger investigations on this topic are urgently needed. [ABSTRACT FROM AUTHOR]

In the irreversible electroporation (IRE) therapy, the absorbed energy is normally characterized as the applied dose and assumed to be distributed in the homogeneous dielectric. By employing statistical analyses, we have studied the absorbed energy distribution in the porous multicellular dielectric, with the geometric patterns randomly generated from the following statistical quantities: system size, cell size, cell concentration, and cell flattening ratio. Parametric formulas regarding the mean and standard deviation of the absorbed energy are obtained through numerical simulations and iterative fitting. Our statistical results reveal that the mean value of absorbed energy with cell concentration exhibits a "conductance" to "resistance" transition, similar to the percolation of two-phase materials, and the direction of the transition flips as cell diameter increases. The standard deviation of energy, however, follows a bell-shaped curve under varied concentration, indicating a shift in energy distribution from an "aggregation" to a "dispersion" state. Based on the parametric formulation, we quantitatively explore the critical threshold of the transition, as well as the general scaling laws of the geometric variables on the mean and standard deviation of the absorbed energy. Our work could help to quantitatively explain the lethality variation in IRE ablation targeting monolayer cell collectives with different geometrical characteristics. [ABSTRACT FROM AUTHOR]

Background In patients with non-valvular atrial fibrillation (AF), at high stroke risk, and who are ineligible for long-term oral anticoagulation, the left atrial appendage closure (LAAC) could be an alternative to anticoagulation. Pulsed field ablation (PFA) is a new non-thermal method for cardiac ablation modality based on high-voltage electrical energy for irreversible electroporation. We first report a case of a concomitant PFA pulmonary vein isolation (PVI) and LAAC. Case summary A 74-year-old female patient was referred to our department for PVI for persistent AF (CHA2DS2-VASc score 5). A concomitant percutaneous LAAC was proposed because of a history of previous cerebellar transient ischaemic attack despite continuous oral anticoagulation therapy. Pulmonary vein isolation was achieved with a pentaspline PFA catheter, and LAAC was performed with a WATCHMAN FLX™ device (Boston Scientific, Plymouth, MN, USA). After PVI, a swelling of the left atrial ridge was observed, yet a 27 mm LAAC device was successfully implanted. The follow-up transesophageal echo (TEE) after 6 weeks showed complete resolution of the oedema, no device-related thrombus, but a slight proximal tilting of the LAAC device without leakage could be observed. The 6-month follow-up demonstrated a stable sinus rhythm, no stroke, or bleeding events were recorded. Discussion In this case of synchronous PFA-PVI procedure in AF and WATCHMAN FLX™ device implantation, the electroporation created an acute oedema at the ridge level which at the TEE follow-up after 6 weeks was resolved. This resulted in a slightly tilted WATCHMAN device position which was nevertheless stable and showed no leakage. [ABSTRACT FROM AUTHOR]

Introduction: Radiation Therapy and IRreversible Electroporation for Intermediate Risk Prostate Cancer (RTIRE) is a phase II clinical trial testing combination of radiation therapy and irreversible electroporation for intermediate risk prostate cancer Background: PCa is the most common non-cutaneous cancer in men and the second leading cause of cancer death in men. PCa treatment is associated with long term side effects including urinary, sexual, and bowel dysfunction. Management of PCa is based on risk stratification to prevent its overtreatment and associated treatment-related toxicity. There is increasing interest in novel treatment strategies, such as focal therapy, to minimize treatment associated morbidity. Focal therapy alone has yet to be included in mainstream guidelines, given ongoing concerns with potentially higher risk of recurrence. We hypothesize combining focal therapy with whole gland, reduced dose radiotherapy will provide acceptable oncologic efficacy with minimal treatment associated morbidity. RTIRE is a phase II single institution, investigator-initiated study combining a local ablative technique though local irreversible electroporation (IRE) with MR guided RT (MRgRT) to treat the entire prostate. The goal is to provide excellent oncologic outcomes and minimize treatment related side effects through leveraging benefits of locally ablative therapy with established radiation treatment techniques. Methods: A total of 42 men with intermediate risk PCa per NCCN guidelines and focal grade group (GG) 2 or 3, Gleason Score (GS) 3 + 4 or GS 4 + 3, cancer in an MRI target will be enrolled. Patients with MRI visible foci of GG2/GG3 will undergo focal therapy with IRE of this lesion. Following successful focal therapy, patients will then undergo a course of reduced dose, whole gland MRgRT with either 32.5 Gy in 5 Fractions or 22 Gy in 2 fractions. The primary objective of the study is to determine safety. Secondary outcomes include evaluation of oncologic efficacy (as measured by the proportion of patients free of clinically significant cancer as defined as > Grade Group 1 at 1-year follow-up biopsy), imaging characteristics of patients pre and post RTIRE, impact on quality of life (QoL), and PSA kinetics. Discussion: Combining IRE with a reduced dose radiotherapy may offer a new treatment paradigm for PCa by both reducing treatment effects of full dose radiotherapy and minimizing the risk of recurrence observed with focal therapy. Trial Registration: Clinicaltrials.gov identifier: NCT05345444. Date of registration: April 25, 2022. Protocol Version: 6.0, July 7, 2023. [ABSTRACT FROM AUTHOR]

Duodenal mucosa ablation (DMA) is a novel approach to treat diabetes, consisting of endoscopic ablation of dysfunctional diabetic duodenal mucosa, which, following the healing response, is replaced by normally functioning mucosa. Two techniques, duodenal mucosal resurfacing (DMR) and recellularization via electroporation therapy (ReCET), recently showed promise in type 2 diabetes mellitus (T2DM) patients. [ABSTRACT FROM AUTHOR]

Introduction: Pulsed Field Ablation (PFA) is a novel non-thermal method for cardiac ablation, relying on irreversible electroporation induced by high-energy pulsed electric fields (PEFs) to create localized lesions in the heart atria. A significant challenge in optimizing PFA treatments is determining the lethal electric field threshold (EFT), which governs ablation volume and varies with PEF waveform parameters. However, the proprietary nature of device developer’s waveform characteristics and the lack of standardized nonclinical testing methods have left optimal EFTs for cardiac ablation uncertain. Methods: To address this gap, we introduced a laboratory protocol employing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in monolayer format to evaluate the impact of a range of clinically relevant biphasic pulse parameters on lethal EFT and adiabatic heating (AH). Cell death areas were assessed using fluorescent dyes and confocal microscopy, while lethal EFTs were quantified through comparison with electric field numerical simulations. Results and conclusion: Our study confirmed a strong correlation between cell death in hiPSC-CMs and the number and duration of pulses in each train, with pulse repetition frequency exerting a comparatively weaker influence. Fitting of these results through machine learning algorithms were used to develop an open-source online calculator. By estimating lethal EFT and associated temperature increases for diverse pulse parameter combinations, this tool, once validated, has the potential to significantly reduce reliance on animal models during early-stage device de-risking and performance assessment. This tool also offers a promising avenue for advancing PFA technology for cardiac ablation medical devices to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Transcatheter arterial embolization has been used clinically for the treatment of intermediate to advanced unresectable tumors, which is a complex procedure and may pose other risks. In order to achieve an efficient and simple therapeutic diagnostic method for tumors, this paper is based on the fact that the fluorescence properties of AIE fluorescent molecules are similar to those of pH-responsive polyamino acid materials undergoing a "sol–gel" phase transition in a tumor micro-acid environment, and two polyamino acid materials, PGTTC and PGCLTGCL, were linked with TPA derivatives of AIE fluorescent molecules to obtain catheter-free embolic agents, PGTTC-DCDPP-2TPA and PGCLTGCL-DCDPP-2TPA. In tumor fluorescence imaging experiments in tumor-bearing mice, both were enriched at the tumor 72 h after injection and that of the PGCLTGCL-DCDPP-2TPA was stronger, moreover, the tumor cells were suppressed and necrotic after 25 days. Therefore, this pH-responsive noninterventional embolization combination therapeutic diagnostic system has good prospects for application in the field of combined therapeutic diagnostic multifunctional platforms. [ABSTRACT FROM AUTHOR]

[Display omitted] Triple-negative breast cancer (TNBC) is insensitive to conventional therapy due to its highly invasive nature resulting in poor therapeutic outcomes. Recent studies have shown multiple genes associated with ferroptosis in TNBC, suggesting an opportunity for ferroptosis-based treatment of TNBC. However, the efficiency of present ferroptosis agents for cancer is greatly restricted due to lack of specificity and low intracellular levels of H 2 O 2 in cancer cells. Herein, we report a nano-theranostic platform consisting of gold (Au)-iron oxide (Fe 3 O 4) Janus nanoparticles (GION@RGD) that effectively enhances the tumor-specific Fenton reaction through utilization of near-infrared (NIR) lasers, resulting in the generation of substantial quantities of toxic hydroxyl radicals (•OH). Specifically, Au nanoparticles (NPs) converted NIR light energy into thermal energy, inducing generation of abundant intracellular H 2 O 2 , thereby enhancing the iron-induced Fenton reaction. The generated •OH not only lead to apoptosis of malignant tumor cells but also induce the accumulation of lipid peroxides, causing ferroptosis of tumor cells. After functionalizing with the activity-targeting ligand RGD (Arg-Gly-Asp), precise synergistic treatment of TNBC was achieved in vivo under the guidance of Fe 3 O 4 enhanced T 2 -weighted magnetic resonance imaging (MRI). This synergistic treatment strategy of NIR-enhanced ferroptosis holds promise for the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the use of super‐resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular‐disrupting agent (VDA). Methods: A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA‐MB‐231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein. Following baseline ultrasound imaging, VDA drug (combretastatin A4 phosphate, CA4P, Sigma Aldrich) or control saline was injected via the placed catheter. After 4 or 24 hours, repeat ultrasound imaging along the same tumor cross‐section occurred. Direct intratumoral pressure measurements were obtained using a calibrated sensor. All raw ultrasound data were saved for offline processing and SRUS image reconstruction using custom MATLAB software (MathWorks Inc). From a region encompassing the tumor space and the entire postprocessed ultrasound image sequence, time MB count (TMC) curves were generated in addition to traditional SRUS maps reflecting MB enumeration at each pixel location. Peak enhancement (PE) and wash‐in rate (WIR) were extracted from these TMC curves. At termination, intratumoral microvessel density (MVD) was quantified using tomato lectin labeling of patent blood vessels. Results: SRUS images exhibited a clear difference between control and treated tumors. While there was no difference in any group parameters at baseline (0 hour, P >.09), both SRUS‐derived PE and WIR measurements in tumors treated with VDA exhibited significant decreases by 4 (P =.03 and P =.05, respectively) and 24 hours (P =.02 and P =.01, respectively), but not in control group tumors (P >.22). Similarly, SRUS derived microvascular maps were not different at baseline (P =.81), but measures of vessel density were lower in treated tumors at both 4 and 24 hours (P <.04). An inverse relationship between intratumoral pressure and both PE and WIR parameters were found in control tumors (R2 >.09, P <.03). Conclusion: SRUS imaging is a new modality for assessing tumor response to treatment using a VDA. [ABSTRACT FROM AUTHOR]

The article discusses the long-term oncologic outcomes of image-guided irreversible electroporation for localized prostate cancer. The study followed 30 men with low- to intermediate-risk prostate cancer who underwent focal MRI–transrectal US fusion–guided IRE treatment. The 5-year oncologic outcomes showed a failure-free survival rate of 63% at 5 years, with 100% metastasis-free survival, prostate cancer–specific survival, and overall survival. The study suggests that focal IRE may be a safe and effective minimally-invasive treatment option for selected patients. [Extracted from the article]

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Triply Enhanced Immunotherapy via Dual Glycan Reforming Integrated with Perforation" published in the journal Advanced Science. The correction addresses misuses of images in Figures 2, 4, and 5, as well as in the Supporting Information. The corrected figures are presented in the notice. The correction does not affect the results and conclusions of the published article. The article discusses the triple functions of SLO-Gal and SLO-NEU on 4T1 cells, the characterization and degradation of TEID, and the triply enhanced immunotherapy with TEID on tumor-bearing mice. [Extracted from the article]

The build-up of lactate in solid tumors stands as a crucial and early occurrence in malignancy development, and the concentration of lactate in the tumor microenvironment may be a more sensitive indicator for analyzing primary tumors. In this study, we designed a self-powered lactate sensor for the rapid analysis of tumor samples, utilizing the coupling between the piezoelectric effect and enzymatic reaction. This lactate sensor is fabricated using a ZnO nanowire array modified with lactate oxidase (LOx). The sensing process does not require an external power source or batteries. The device can directly output electric signals containing lactate concentration information when subjected to external forces. The lactate concentration detection upper limit of the sensor is at least 27 mM, with a limit of detection (LOD) of approximately 1.3 mM and a response time of around 10 s. This study innovatively applied self-powered technology to the in situ detection of the tumor microenvironment and used the results to estimate the growth period of the primary tumor. The availability of this application has been confirmed through biological experiments. Furthermore, the sensor data generated by the device offer valuable insights for evaluating the likelihood of remote tumor metastasis. This study may expand the research scope of self-powered technology in the field of medical diagnosis and offer a novel perspective on cancer diagnosis. [ABSTRACT FROM AUTHOR]

In this research work, we investigate the influence of heat source and chemical reaction on electro-magneto-hydrodynamic (EMHD) blood flow through bifurcated arteries with external tilted magnetic field for treating tumor. The potential electric field applied along the bifurcated arterial wall, accurately described the Poisson-Boltzmann equation. We modeled the EMHD blood flow to obtain the non-dimensionalized form of the equations. We converted the modeled equations to ordinary differential equations by the use of suitable variables. Exact solutions of the converted equations are calculated by the method of undetermined coefficients and the results obtained with the aid of Mathcad software were simulated and presented graphically. From the graphical representation of results, we observed that increase in Joule heating and Eckert number, increases the temperature distribution in the affected tumor cells which prevent high thermal radiation exposure from killing the healthy cells within the tumor region. The curves of the wall shear stress seem to be greater in the converging region in comparison to the diverging region, but when the strength of magnetic field and thermal radiation parameters increase the wall shear stress decreases at the bifurcated wall where blockage may likely occur due to the development of boundary layers on the inner walls of the bifurcated region. By increasing the heat radiation parameter, we observed that the curves representing both velocity and temperature profiles increase rapidly from the origin and the velocity of blood flow varies directly for the converging, diverging and the tumor regions of the bifurcated arteries. Thus, thermal radiation effect is a result of the higher rate of heat transfer at the vessel walls. Further, combining the electromagnetic field and the heat radiation together gives new insights of the physical properties of blood flow in the body system network which is essential for health practitioners and clinicians. [ABSTRACT FROM AUTHOR]

Platinum supramolecular complexes based on photosensitizers have garnered great interest in photodynamic therapy (PDT) due to Pt (II) centers as chemotherapeutic agents to eliminate tumor cells completely, which greatly improve the antitumor efficacy of PDT. However, in comparison to precursor photosensitizer ligand, the formed platinum supramolecular complexes typically exhibit inferior outcomes in terms of reactive oxygen species (ROS) generation. How to boost ROS generation in the formed platinum supramolecular complexes for enhanced PDT is an enticing yet highly challenging task. Here we report a Pt‐coordination‐based dimeric photosensitizer complex (Cz−BTZ−Py)2Pt(OTf)2. It is found that comparing with photosensitizer ligand Cz−BTZ−Py, the formed supramolecular complex exhibit redshifts of absorption wavelength as well as enhanced ROS generation efficiency. Moreover, type‐I ROS generation (O2⋅−) is produced in the formed platinum supramolecular complexes mainly due to a reduced energy gap ΔEST resulting from exciton coupling between two photosensitizer ligands. And type‐I ROS (O2⋅−) generation significantly amplifies the photodynamic therapy (PDT) outcomes. In vitro evaluation shows excellent photochemotherapy performance of (Cz−BTZ−Py)2Pt(OTf)2 nanoparticles. We anticipate this work would provide a novel approach to design type‐I photosensitizers for efficient PDT. [ABSTRACT FROM AUTHOR]

Rotating magnetic fields enable biomedical microrobots to overcome physiological barriers and promote extravasation and accumulation in tumors. Nevertheless, targeting deeply situated tumors requires suppression of off-target actuation in healthy tissue. Here, we investigate a control strategy for applying spatially selective torque density to microrobots by combining rotating fields with magnetostatic selection fields. Taking magnetotactic bacteria as diffuse torque-based actuators, we numerically model off-target torque suppression, indicating the feasibility of centimeter to millimeter resolution for human applications. We study focal torque application in vitro, observing off-target suppression of actuation-dependent effects such as colonization of bacteria in tumor spheroids. We then design and construct a mouse-scale torque-focusing apparatus capable of maneuvering the focal point. Applying this system to a mouse tumor model increased accumulation of intravenously injected bacteria within tumors receiving focused actuation compared to non-actuated or globally actuated groups. This control scheme combines the advantages of torque-based actuation with spatial targeting. The delivery of therapeutic payloads and living vectors to tumors remains a clinical challenge. Here the authors explore a spatially targeted control strategy applying torque density to magnetotactic bacteria, demonstrating feasibility in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials. [ABSTRACT FROM AUTHOR]

Background: Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high‐frequency irreversible electroporation (H‐FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound‐guided percutaneous H‐FIRE using four electrode needles in porcine livers. Methods: Twelve experimental pigs underwent percutaneous H‐FIRE ablation using a compound steep‐pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast‐enhanced ultrasound (CEUS), contrast‐enhanced magnetic resonance imaging (MRI), and hematoxylin–eosin staining were performed to evaluate the ablation performance. Results: Ultrasound‐guided percutaneous H‐FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H‐FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. Conclusions: This study demonstrated the feasibility and safety of ultrasound‐guided percutaneous H‐FIRE ablation in porcine livers in vivo, and proposed a four‐needle method to optimize its clinical application. [ABSTRACT FROM AUTHOR]

In this study, we introduced a mathematical model mimicking as much as possible the evolutions and interactions between glioma and lactate in the brain, in order to test different therapies and administration protocols. We simulated both glioma cell density evolution and lactate concentration, and considered two therapies: chemotherapy and a treatment targeting lactate production. Three different protocols for administrating the therapies were tested. We compared the efficiency of the combined therapies, depending on the administration protocols and the dosage of the drugs, in order to evaluate the importance of controlling lactate production. Results show that the use of an agent to reduce lactate concentration permits one to significantly reduce the dose of the chemotherapeutic drug. [ABSTRACT FROM AUTHOR]

Featured Application: This review explores an innovative approach to combating resistance to breast cancer through the application of nanotechnology. Breast cancer (BC) ranks among the most diagnosed solid tumors worldwide. For decades, significant research efforts have been dedicated to finding selective treatments for these solid tumors. Currently, the primary treatment method for BC involves surgery, with the subsequent utilization of radiotherapy and chemotherapy. However, these subsequent treatments often fall short of effectively treating BC due to their side effects and harm to healthy tissues. Today, a range of nanoparticles are being developed to target BC cells without affecting the surrounding healthy tissues. This in-depth review, based on studies, seeks to shed light on these specially designed nanoparticles and their potential in BC treatment. Typically, therapeutic drugs or naturally occurring bioactive compounds are incorporated into precisely crafted nanoparticles. This enhances their solubility, longevity in the bloodstream, and distribution in the body while also minimizing side effects and immune reactions. Nanoparticles have been designed to address the shortcomings of standalone therapeutics and traverse various biological obstacles spanning the systemic, microenvironmental, and cellular that differ among patients and diseases. We prioritize breakthroughs in nanoparticle design to surpass diverse delivery obstacles and believe that smart nanoparticle engineering not only enhances effectiveness for general delivery but also allows customized solutions for specific needs, ultimately leading to better outcomes for patients. [ABSTRACT FROM AUTHOR]

Dual-frequency ultrasounds have demonstrated significant potential in augmenting thermal ablation efficiency for tumor treatment. Ensuring proper impedance matching between the dual-frequency transducer and the power amplifier system is imperative for equipment safety. This paper introduces a novel dual-frequency impedance matching network utilizing L-shaped topology and employing a genetic algorithm to compute component values. Implementation involved an adjustable capacitor and inductor network to achieve dual-frequency matching. Subsequently, the acoustic parameters of the dual-frequency HIFU transducer were evaluated before and after matching, and the effects of ultrasound thermal ablation with and without matching were compared. The proposed dual-frequency impedance matching system effectively reduced the standing wave ratio at the two resonance points while enhancing transmission efficiency. Thermal ablation experiments with matching circuits showed improved temperature rise efficiencies at both frequencies, resulting in an expanded ablation zone. The dual-frequency impedance matching method significantly enhances the transmission efficiency of the dual-frequency ultrasound system at two operational frequencies, thereby ensuring equipment safety. It holds promising prospects for application in dual-frequency ultrasound treatment. [ABSTRACT FROM AUTHOR]

Hectorite is trioctahedral clay mineral that possess unique characteristics of surface reactivity and adsorption, cation exchange capacity and easy delamination in water into individual nano layers. Thus, hectorite can be a promising nanocarrier with biocompatibility, high payload and controlled release of drug. Therefore, in the present study, hectorite has been used for the delivery of two hydrophobic molecules; chemotherapeutic drug DDP [Cis-diamminedichloroplatinum (II)] and natural photosensitizer hypocrellin A (HA) for combinatorial therapy. The experimental results has been fitted to l-type (Langmuir) adsorption isotherm. The adsorption isotherm showed higher affinity of DDP toward the hectorite with almost comparable CEC value of initial silicate layer of hectorite. The loading of drug into nanoclay was further characterize by using SEM, FTIR, XRD, DLS and TGA, which suggest the presence of DDP molecules in between the interparticle and photosensitizer on the surface of nanoclay. After, adsorption the characteristic properties such as photostability and photobleaching of HA has been significantly improved. The photobleaching efficiencies of free HA and Ht-DDP-HA was 72.8 and 55.2%, respectively, and the 1O2 generation quantum yield was 0.86. The in vitro release rate is twofold higher in the presence of laser light and ultrasonic waves. The drug release profile was found to be best fitted by Higuchi square root model, which implicate that release of drug from matrix as square root of time-dependent process and diffusion controlled. The in vitro efficacy of Ht-DDP-HA showed the potent anti-cancerous ability due to combinatorial effect by 2.01 and 1.69 fold times higher efficacy than free DDP and HA, respectively. Flow cytometry data shows the synergistic effect of combined therapy by showing maximum apoptotic and necrotic percentage. [ABSTRACT FROM AUTHOR]

Background: The development of new perioperative treatment modalities to activate the immune system in colorectal cancer might have a beneficial effect on reducing the risk of recurrence after surgery. Calcium electroporation is a promising treatment modality that potentially modulates the tumor microenvironment. The aim of this study was to evaluate the safety of the procedure in the neoadjuvant setting in localized left-sided colorectal cancer (CRC). Methods: The study included patients with potentially curable sigmoid or rectal cancer with no indication for other neoadjuvant treatment. Patients were offered calcium electroporation as a neoadjuvant treatment before elective surgery. Follow-up visits were conducted on the preoperative day before elective surgery, POD2, POD14, and POD30, with an evaluation of adverse events, impact on elective surgery, clinical examination, and quality of recovery. Results: Endoscopic calcium electroporation was performed as an outpatient procedure in all 21 cases, with no procedure-related complications reported. At follow-up, five adverse events were registered, two of which were classified as serious adverse events. Surgery was performed as planned in 19 patients (median time to surgery, 8 days), and the final two patients underwent surgery with a delay due to adverse events (14 and 33 days). No significant impact on the quality of recovery scores nor inflammatory markers were seen before and after calcium electroporation, nor baseline and POD30. Conclusions: Endoscopic calcium electroporation is a safe and feasible procedure in patients with potentially curable CRC. The study showed limited side effects and limited impact on the following elective surgical resection. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9- CAMK2A -EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9- CAMK2A -EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9- CAMK2A -EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability. [ABSTRACT FROM AUTHOR]

X‐rays are rays that penetrate the human tissue and are capable of penetrating water, air, and oxygen in various biological tissues or tumors. In recent years, significant progress has been made in the research of X‐ray‐excited luminescent materials for cancer diagnosis and treatment. In this study, the application of X‐ray‐excited luminescent materials is reviewed for tumor imaging and therapy. First, two classes of luminescent materials are briefly introduced for a form of enhanced X‐ray computed tomography, X‐ray‐excited optical luminescence imaging. Subsequently, the design of multifunctional hybrid materials is evaluated for radiotherapy and other treatments and their synergistic effects under X‐ray excitation are studied. Finally, current key issues and solutions in the field are discussed in detail. [ABSTRACT FROM AUTHOR]

The intratumoral injection of therapeutic agents responsive to external stimuli has gained considerable interest in treating accessible tumors due to its biocompatibility and capacity to reduce side effects. For the first time, a novel approach is explored to investigate the feasibility of utilizing low-intensity ultrasound in combination with intratumoral injection of drug-loaded magnetic nanoparticles (MNPs) to thermal necrosis and chemotherapy with the objective of maximizing tumor damage while avoiding harm to surrounding healthy tissue. In this study, a mathematical framework is proposed based on a multi-compartment model to evaluate the effects of ultrasound transducer's specifications, MNPs size and distribution, and drug release in response to the tumor microenvironment characteristics. The results indicate that while a higher injection rate may increase interstitial fluid pressure, it also simultaneously enhances the concentration of the therapeutic agent. Moreover, by increasing the power and frequency of the transducer, the acoustic pressure and intensity can be enhanced. This, in turn, increases the impact on accumulated MNPs, resulting in a rise in temperature and localized heat generation. Results have demonstrated that smaller MNPs have a lower capacity to generate heat compared to larger MNPs, primarily due to the impact of sound waves on them. It is worth noting that smaller MNPs have been observed to have enhanced diffusion, allowing them to effectively spread within the tumor. However, their smaller size also leads to rapid elimination from the extracellular space into the bloodstream. To summarize, this study demonstrated that the local injection of MNPs carrying drugs not only enables localized chemotherapy but also enhances the effectiveness of low-intensity ultrasound in inducing tissue thermal necrosis. The findings of this study can serve as a valuable and reliable resource for future research in this field and contribute to the development of personalized medicine. [ABSTRACT FROM AUTHOR]

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell proliferation and reduction of transsulfuration pathway metabolites. Combination of HSF1 and CBS knockout decreases tumor size for a small cell PCa xenograft mouse model. Our study thus provides new insights into the molecular mechanism of HSF1 function and an effective therapeutic strategy against advanced PCa. HSF1 regulates the conversion of homocysteine to cystathionine in the trans-sulfuration pathway by altering levels of cystathionine-β-synthase (CBS), and targeting CBS decreases pancreatic cancer growth while leaving benign prostate cells largely unaffected. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli‐responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli‐responsive mechanisms and strategies used for tumor radio‐sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli‐responsive nanomaterials for radio‐sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli‐response, and multi stimuli‐response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X‐ray, light, and ultrasound. Dual stimuli‐response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli‐response involves the combination of pH/ROS/GSH and X‐ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli‐responsive nanomaterials for tumor radio‐sensitization. [ABSTRACT FROM AUTHOR]

Nowadays, smart hydrogels are being widely studied by researchers because of their advantages such as simple preparation, stable performance, response to external stimuli, and easy control of response behavior. Photo‐controllable smart hydrogels (PCHs) are a class of responsive hydrogels whose physical and chemical properties can be changed when stimulated by light at specific wavelengths. Since the light source is safe, clean, simple to operate, and easy to control, PCHs have broad application prospects in the biomedical field. Therefore, this review timely summarizes the latest progress in the PCHs field, with an emphasis on the design principles of typical PCHs and their multiple biomedical applications in tissue regeneration, tumor therapy, antibacterial therapy, diseases diagnosis and monitoring, etc. Meanwhile, the challenges and perspectives of widespread practical implementation of PCHs are presented in biomedical applications. This study hopes that PCHs will flourish in the biomedical field and this review will provide useful information for interested researchers. [ABSTRACT FROM AUTHOR]

Cancer directly affects one in every three people, and mortality rates strongly correlate with the stage at which diagnosis occurs. Each of the multitude of methods used in cancer diagnostics has its own set of advantages and disadvantages. Two common drawbacks are a limited information value of image based diagnostic methods and high invasiveness when opting for methods that provide greater insight. Microfluidics offers a promising avenue for isolating circulating tumor cells from blood samples, offering high informational value at predetermined time intervals while being minimally invasive. Microscale AcoustoFluidics, an active method capable of manipulating objects within a fluid, has shown its potential use for the isolation and measurement of circulating tumor cells, but its full potential has yet to be harnessed. Extensive research has focused on isolating single cells, although the significance of clusters should not be overlooked and requires attention within the field. Moreover, there is room for improvement by designing smaller and automated devices to enhance user-friendliness and efficiency as illustrated by the use of bulk acoustic wave devices in cancer diagnostics. This next generation of setups and devices could minimize streaming forces and thereby enable the manipulation of smaller objects, thus aiding in the implementation of personalized oncology for the next generation of cancer treatments. [ABSTRACT FROM AUTHOR]

Background: The accuracy and precision of patient position in radiotherapy process have dramatic impacts on the tumor local control and therapy‐related side effects, and there exist demands to explore effective positioning solutions, particularly in the era with great progress in imaging recognition and matching. Purpose: Superficial vessel‐based near infrared‐assisted patient position recognition and real‐time monitoring system (VIPS) was proposed to develop an automated, operator‐independent and skin marker‐free imaging system to improve patient setup and intrafractional motion monitoring. Methods: VIPS includes two components, the imaging module and the image alignment software. Using a simulated blood vessel model, multiple NIR sources with various wavelength and bolus (pseudo‐skin) were evaluated in terms of imaging quality to determine the optimal light source and the upper limit of superficial fatty tissue thickness. Then the performance of VIPS with reference to either CBCT or laser setup system was conducted using 3D phantom and clinical cases enrolled into the registered clinical trial. The position displacement from VIPS and laser system was compared, as well as the systematic and random errors of VIPS setup procedure. Results: The NIR light source with the combined wavelengths of 760 nm + 940 nm (S760+940 nm) provided the best performance among multiple tested light sources. The bolus (superficial fatty layer) thickness over 5 mm could dramatically compromise the NIR detection of vessels beneath. In the phantom study, the translational positional displacements according to VIPS guidance were within the submillimeter level with reference to CBCT, indicative of high setup accuracy. The clinical trial showed the prototype VIPS could effectively detect and control position displacement of patients in translational and rotational directions within an acceptable range, which was non‐inferior to conventional laser/skin marker system. Conclusion: This proof‐of‐concept study validated the feasibility and reliability of VIPS in guiding radiotherapy setup. However, limitations and technical challenges should be resolved prior to further clinical evaluation, including isocenter alignment, potential NIR image distortion and the impact of the superficial tissues on the recognition of vessels. [ABSTRACT FROM AUTHOR]

Radical treatments and active surveillance are valid therapeutic approaches for low-risk prostate cancer. The oncologic effectiveness and morbidity of Radical Prostatectomy (RP) and radiotherapy have been broadly validated. Focal therapies pursue to reduce the morbidity observed after radical treatments, while preserving the oncologic effectiveness. This study aims to review the state-of-the-art about principles, oncologic effectiveness, morbidity, and side-effects associated with leading focal therapies. We review and summarize articles related with Cryotherapy, High-Intensity Focal Ultrasound (HIFU), Photodynamic Therapy (PDT), and Irreversible Electroporating (IRE) published in MEDLINE from 2000 to 2022. There is a wide heterogeneity in terms of the measurement of effectiveness and morbidity. Hence, comparing different energies, strategies and protocols seem to be unprecise and controversial. Cryosurgery and HIFU have reported more clinical experience than PDT and IRE. Biochemical recurrence rate after the first session varied from 4.5% to 23%, and up to 20% of patients underwent a salvage radical treatment. The reported incidence of erectile disfunction and urinary incontinence ranges from 3% to 50% and 0% to 34%, respectively. None randomized clinical trial comparing any focal therapy to any radical treatment has been published. We conclude that the expansion of focal therapies requires the consolidation of MRI-guided fusion biopsies in everyday clinical practice. Short-term oncologic effectiveness has been proved and supports their usefulness in low-risk patients unfit for surgical treatment. However, long-term effects and the clinical experience in intermediate and high-risk patients remains limited. Currently none of the focal therapies can be considered the Gold Standard for low-risk patients. [ABSTRACT FROM AUTHOR]

Focused Ultrasound (FUS)-triggered nano-sized drug delivery, as a smart stimuli-responsive system for treating solid tumors, is computationally investigated to enhance localized delivery of drug and treatment efficacy. Integration of thermosensitive liposome (TSL), as a doxorubicin (DOX)-loaded nanocarrier, and FUS, provides a promising drug delivery system. A fully coupled partial differential system of equations, including the Helmholtz equation for FUS propagation, bio-heat transfer, interstitial fluid flow, drug transport in tissue and cellular spaces, and a pharmacodynamic model is first presented for this treatment approach. Equations are then solved by finite element methods to calculate intracellular drug concentration and treatment efficacy. The main objective of this study is to present a multi-physics and multi-scale model to simulate drug release, transport, and delivery to solid tumors, followed by an analysis of how FUS exposure time and drug release rate affect these processes. Our findings not only show the capability of model to replicate this therapeutic approach, but also confirm the benefits of this treatment with an improvement of drug aggregation in tumor and reduction of drug delivery in healthy tissue. For instance, the survival fraction of tumor cells after this treatment dropped to 62.4%, because of a large amount of delivered drugs to cancer cells. Next, a combination of three release rates (ultrafast, fast, and slow) and FUS exposure times (10, 30, and 60 min) was examined. Area under curve (AUC) results show that the combination of 30 min FUS exposure and rapid drug release leads to a practical and effective therapeutic response. [ABSTRACT FROM AUTHOR]

With the advancement of micro/nanotechnologies, multielectrodes arrays (MEAs) with different three‐dimensional (3D) micro/nanostructures have been developed to achieve intracellular action potential recording of cardiomyocytes. However, the effect of the 3D micro/nanostructures density on the intracellular recording has not been fully investigated. In this work, 3D tunable nanodensity electrode arrays (TNDEA) are fabricated by hydrothermal synthesis and standard microfabrication to explore the effect of nanodensity regulation on intracellular biosensing. By low‐voltage electroporation, the signal quality of intracellular potentials recorded by the low‐nanodensity TNDEA showed was significantly improved compared to those recorded by the high‐nanodensity TNDEA. The low‐nanodensity TNDEA improved the amplitude (up to 7.7 mV), signal‐to‐noise ratio (SNR) (up to 69.46 dB), recording duration (up to 83 min), and recording yield (∼100%). The 3D nanodensity regulating strategy has achieved sensitive and prolonged intracellular biosensing of action potentials and is expected to be a powerful electrophysiological research tool in the biomedical field. [ABSTRACT FROM AUTHOR]

This paper creates an approximate three-dimensional model for normal and cancerous cervical cells using image processing and computer-aided design (CAD) tools. The model is then exposed to low-frequency electric pulses to verify the work with experimental data. The transmembrane potential, pore density, and pore radius evolution are analyzed. This work adds a study of the electrodeformation of cells under an electric field to investigate cytoskeleton integrity. The Maxwell stress tensor is calculated for the dispersive bi-lipid layer plasma membrane. The solid displacement is calculated under electric stress to observe cytoskeleton integrity. After verifying the results with previous experiments, the cells are exposed to a nanosecond pulsed electric field. The nanosecond pulse is applied using a drift-step rectifier diode (DSRD)-based generator circuit. The cells' transmembrane voltage (TMV), pore density, pore radius evolution, displacement of the membrane under electric stress, and strain energy are calculated. A thermal analysis of the cells under a nanosecond pulse is also carried out to prove that it constitutes a non-thermal process. The results showed differences in normal and cancerous cell responses to electric pulses due to changes in morphology and differences in the cells' electrical and mechanical properties. This work is a model-driven microdosimetry method that could be used for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Currently, spatiotemporal theranostic nanoprobes are in great demand, owing to their enhanced target therapy and precise dynamic tracing of in vivo drug fate. Herein, this study highlights the successful development of dynamic theranostic nanoprobes, which are facilely established via self‐assembly between glutathione (GSH)‐responsive dasatinib (DAS) dimers and indocyanine green (ICG). The DAS dimers endow the nanoprobes with aggregation‐induced emission (AIE) characteristic, whose emission wavelength successfully redshifts from 420 to 810 nm compared to DAS‐based nanoprobes, the same as that of ICG, thus improving the total fluorescence intensity. Moreover, the nanoprobes exhibit a dynamic fluorescence intensity conversion that first decreases and then increases at the tumor site via intracellular GSH‐triggered AIE quenching and fluorescence re‐enhancement of ICG, therefore achieving precise tumor diagnosis, prognosis evaluation, and spatiotemporal tracing of drug fate compared to other imaging strategies. Furthermore, the nanoprobes show long‐term circulation stability via suitable particle sizes and zeta potentials, improved tumor accumulation via extracellular protonation and active cellular uptake, efficient drug release via response to the intracellular milieu, and enhanced apoptosis via targeting to intracellular kinase, therefore achieving the significant tumor inhibition. Thus, the spatiotemporal theranostic nanoprobes can dynamically monitor the targeted tumor therapy, greatly advancing their application in clinics. [ABSTRACT FROM AUTHOR]

Ferroptosis therapy induced by iron‐catalyzed Fenton reaction has offered enormous opportunities for tumor therapy. Unfortunately, high catalytic activity ferrous (Fe2+)‐based therapeutic agent has remained challenging due to the instability of Fe2+. Herein, an X‐ray‐activated Fe2+ supply platform, termed "PFCN", containing the core of CaWO4 nanoscintillator to emit ultraviolet (UV) light and Fe3O4 decorated on the surface to deliver excessive Fe2+ is proposed. Under X‐ray excitation, the UV light emitted by CaWO4 can catalyze ferric (Fe3+) to generate Fe2+, which further cascades the Fenton reaction to induce highly toxic hydroxyl radicals generation. More importantly, immunogenic cell death‐associated immunotherapy is simultaneously triggered during this process. Experiments conducted in vitro and in vivo revealed that X‐ray‐triggered PFCN shows superior tumor therapeutic efficacy, contributing i) enhanced radiotherapy; ii) X‐ray‐activated ferroptosis therapy; and iii) ferroptosis/radiotherapy‐induced immunotherapy. Besides, PFCN can be utilized as an MR/CT dual‐mode imaging contrast agent for tumor diagnosis and treatment monitoring. The study provides a novel example of an X‐ray‐activated ferrous‐regeneration platform for imaging‐guided augmenting tumor ferroptosis/immunotherapy [ABSTRACT FROM AUTHOR]

The intensity of the interaction between a helium cold atmospheric plasma jet (CAPJ) and a dielectric surface or animal skin is compared in experiment and numerical simulation. A cold plasma jet at atmospheric pressure is generated by a sinusoidal or positive pulsed voltage with different pulse durations in optimal modes. The impact effect is estimated on the basis of measured and calculated currents, line intensities in the CAPJ spectrum and temperature fields. The measured CAPJ characteristics show that the pulsed voltage for the CAPJ excitation is preferable compared to the sinusoidal mode. Varying the pulse duration of the periodic pulsed voltage makes it possible to obtain the maximum current and electric field strength at the surface within the permissible temperature in the contact area of the CAPJ with the skin of mice (<42°C). It is shown that the results of the CAPJ study obtained in physical experiments using a dielectric plate are applicable for tumor-bearing mice treatment. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal laxity is a widespread and undertreated medical condition associated especially with vaginal parity. Aim: To evaluate the efficacy and safety of electroporation therapy treatment of vulvovaginal laxity by the Jett Plasma for Her II device. Methods: The Jett Plasma for Her II Study is a multicentric, prospective, randomized, single-blinded, and controlled study. Women presenting with vaginal laxity were randomized to receive electroporation therapy delivered to the vaginal tissue (active—82 patients) vs. therapy with zero intensity (placebo—9 patients). Results: A total of 91 subjects whose average age was 48.69 ± 10.89 were included. Due to the results of a one-way analysis of variance, it may be concluded that in the case of the vaginal laxity questionnaire (VLQ), there is a statistically significant difference between actively treated patients and the placebo group (F1,574 = 46.91; p < 0.001). In the case of the female sexual function index (FSFI), a one-way ANOVA test also showed a statistically significant difference between the actively treated patients and the placebo group (F1,278 = 7.97; p = 0.005). In the case of the incontinence impact questionnaire-7 (IIQ-7), a one-way ANOVA test showed a statistically significant difference between the actively treated patients and the placebo group (F1,384 = 15.51; p < 0.001). It confirms that improvement of vaginal laxity is conjoined with benefits in symptoms of urinary incontinence. Biopsy performed after the end of the treatment shows an increase in the vaginal mucosa thickness by an average of 100.04% in the active group. The treatment was well tolerated with no adverse events. No topical anesthetics were required. Conclusions: Treatments of vulvovaginal laxity by electroporation therapy achieved significant and sustainable 12-month effectiveness. Responses to the questionnaires also suggest subjective improvement in self-reported sexual function, incontinence, sexual satisfaction, and urogenital distress. [ABSTRACT FROM AUTHOR]

Micro/nanorobots are promising for a wide range of biomedical applications (such as targeted tumor, thrombus, and infection therapies in hard‐to‐reach body sites) because of their tiny size and high maneuverability through the actuation of external fields (e.g., magnetic field, light, ultrasound, electric field, and/or heat). However, fully synthetic micro/nanorobots as foreign objects are susceptible to phagocytosis and clearance by diverse phagocytes. To address this issue, researchers have attempted to develop various cytomembrane‐camouflaged micro/nanorobots by two means: (1) direct coating of micro/nanorobots with cytomembranes derived from living cells and (2) the swallowing of micro/nanorobots by living immunocytes via phagocytosis. The camouflaging with cytomembranes or living immunocytes not only protects micro/nanorobots from phagocytosis, but also endows them with new characteristics or functionalities, such as prolonging propulsion in biofluids, targeting diseased areas, or neutralizing bacterial toxins. In this review, we comprehensively summarize the recent advances and developments of cytomembrane‐camouflaged medical micro/nanorobots. We first discuss how cytomembrane coating nanotechnology has been employed to engineer synthetic nanomaterials, and then we review in detail how cytomembrane camouflage tactic can be exploited to functionalize micro/nanorobots. We aim to bridge the gap between cytomembrane‐cloaked micro/nanorobots and nanomaterials and to provide design guidance for developing cytomembrane‐camouflaged micro/nanorobots. [ABSTRACT FROM AUTHOR]

Thermal effects during bone surgery pose a common challenge, whether using mechanical tools or lasers. An irrigation system is a standard solution to cool the tissue and reduce collateral thermal damage. In bone surgery using Er:YAG laser, insufficient irrigation raises the risk of thermal damage, while excessive water lowers ablation efficiency. This study investigated the potential of optical coherence tomography to provide feedback by relating the temperature rise with the photo-thermal expansion of the tissue. A phase-sensitive optical coherence tomography system (central wavelength of λ=1.288 μm, a bandwidth of 60.9 nm and a sweep rate of 104.17 kHz) was integrated with an Er:YAG laser using a custom-made dichromatic mirror. Phase calibration was performed by monitoring the temperature changes (thermal camera) and corresponding cumulative phase changes using the phase-sensitive optical coherence tomography system during laser ablation. In this experiment, we used an Er:YAG laser with 230 mJ per pulse at 10 Hz for ablation. Calibration coefficients were determined by fitting the temperature values to phase later and used to predict the temperature rise for subsequent laser ablations. Following the phase calibration step, we used the acquired values to predict the temperature rise of three different laser-induced cuts with the same parameters of the ablative laser. The average root-mean-square error for the three experiments was measured to be around 4 °C. In addition to single-point prediction, we evaluated this method's performance to predict the tissue's two-dimensional temperature rise during laser osteotomy. The findings suggest that the proposed principle could be used in the future to provide temperature feedback for minimally invasive laser osteotomy. [ABSTRACT FROM AUTHOR]

With the rapid development of sonodynamic therapy (SDT), sonosensitizers have evolved from traditional treatments to comprehensive diagnostics and therapies. Sonosensitizers play a crucial role in the integration of ultrasound imaging (USI), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) diagnostics while also playing a therapeutic role. This review was based on recent articles on multifunctional sonosensitizers that were used in SDT for the treatment of cancer and have the potential for clinical USI, CT, and MRI applications. Next, some of the shortcomings of the clinical examination and the results of sonosensitizers in animal imaging were described. Finally, this paper attempted to inform the future development of sonosensitizers in the field of integrative diagnostics and therapeutics and to point out current problems and prospects for their application. [ABSTRACT FROM AUTHOR]

In recent years, an increasing number of scientists have focused on conducting experiments on laser ablation of bone tissue. The purpose of this study was to summarize the prognosis of tissue and the extent of thermal damage in past hard tissue ablation experiments, and review the evidence for the feasibility of laser osteotomy in surgery. An electronic search of PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science (WOS) for relevant English-language articles published through June 2023 was conducted. This review includes 48 literature reports on laser ablation of hard tissues from medical and biological perspectives. It summarizes previous studies in which the ideal ablation rate, depth of ablation, and minimal damage to bone tissue and surrounding soft tissues were achieved by changing the laser type, optimizing the laser parameter settings, or adding adjuvant devices. By observing their post-operative healing and inflammatory response, this review aims to provide a better understanding of pulsed laser ablation of hard tissues. Previous studies suggest that laser osteotomy has yielded encouraging results in bone resection procedures. We believe that low or even no thermal damage can be achieved by experimentally selecting a suitable laser type, optimizing laser parameters such as pulse duration and frequency, or adding additional auxiliary cooling devices. However, the lack of clinical studies makes it difficult to conclusively determine whether laser osteotomy is superior in clinical applications. [ABSTRACT FROM AUTHOR]

Finite element analysis is used in this study to investigate the effect of media inhomogeneity on the electric field distribution in a sample composed of cells and their extracellular matrix. The sample is supposed to be subjected to very high pulsed electric field. Numerically computed electric field distribution and transmembrane potential at the cell membrane in electroporation conditions are considered in order to study cell behavior at different degrees of inhomogeneity. The different inhomogeneity grade is locally obtained using a representative model of fixed volume with cell–cell distance varying in the range of 1–283 um. The conductivity of the extracellular medium was varied between plain collagen and a gel-like myxoid matrix through combinations of the two, i.e., collagen and myxoid. An increase in the transmembrane potential was shown in the case of higher aggregate. The results obtained in this study show the effect of the presence of the cell aggregates and collagen on the transmembrane potential. In particular, by increasing the cell aggregation in the two cases, the transmembrane potential increased. Finally, the simulation results were compared to experimental data obtained by culturing HCC1954 cells in a hyaluronic acid-based scaffold. The experimental validation confirmed the behavior of the transmembrane potential in presence of the collagen: an increase in electroporation at a lower electric field intensity was found for the cells cultured in the scaffolds where there is the formation of collagen areas. [ABSTRACT FROM AUTHOR]

Metal chelator‐based contrast agents are used as tumor navigators for cancer diagnosis. Although approved metal chelators show excellent contrast performance in magnetic resonance imaging (MRI), large doses are required for cancer diagnoses due to rapid clearance and nonspecific accumulation throughout the body, which can compromise safety. The present study describes an enzyme‐responsive metal delivery system, in which enzyme overexpressed in the tumor microenvironment selectively activates the tumor uptake of gadolinium (Gd). Gd was loaded into enzyme‐responsive macrocyclam (ErMC) modified with a PEGylated enzyme‐cleavable peptide resulting in Gd@ErMC. The PEGylated shell layer protected Gd@ErMC from nonspecific binding in the blood, increasing the half‐life of the contrast agent. Specific cleavage of the PEGylated shell layer by the enzyme selectively liberated Gd from Gd@ErMC at the tumor site. Evaluation of the in vivo distribution of Gd@ErMC in tumor‐bearing mice by MRI and positron emission tomography (PET) showed that Gd@ErMC had an extended half‐life and was highly specific. Histological and serological analysis of Gd@ErMC‐treated mice showed that this agent was safe. This novel enzyme‐responsive contrast agent delivery system shows promise as specific theranostic agent for MR‐guided radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc (IVD) degeneration is a major contributor to low back pain (LBP), yet there are no clinical therapies targeting the underlying pathology. The annulus fibrosus (AF) plays a critical role in maintaining IVD structure/function and undergoes degenerative changes such as matrix catabolism and inflammation. Thus, therapies targeting the AF are crucial to fully restore IVD function. Previously, we have shown nonviral delivery of transcription factors to push diseased nucleus pulposus cells to a healthy phenotype. As a next step in a proof‐of‐concept study, we report the use of Scleraxis (SCX) and Mohawk (MKX), which are critical for the development, maintenance, and regeneration of the AF and may have therapeutic potential to induce a healthy, pro‐anabolic phenotype in diseased AF cells. Methods: MKX and SCX plasmids were delivered via electroporation into diseased human AF cells from autopsy specimens and patients undergoing surgery for LBP. Transfected cells were cultured over 14 days and assessed for cell morphology, viability, density, gene expression of key phenotypic, inflammatory, matrix, pain markers, and collagen accumulation. Results: AF cells demonstrated a fibroblastic phenotype posttreatment. Moreover, transfection of SCX and MKX resulted in significant upregulation of the respective genes, as well as SOX9. Transfected autopsy cells demonstrated upregulation of core extracellular matrix markers; however, this was observed to a lesser effect in surgical cells. Matrix‐degrading enzymes and inflammatory cytokines were downregulated, suggesting a push toward a pro‐anabolic, anti‐inflammatory phenotype. Similarly, pain markers were downregulated over time in autopsy cells. At the protein level, collagen content was increased in both MKX and SCX transfected cells compared to controls. Conclusions: This exploratory study demonstrates the potential of MKX or SCX to drive reprogramming in mild to moderately degenerate AF cells from autopsy and severely degenerate AF cells from surgical patients toward a healthy phenotype and may be a potential nonviral gene therapy for LBP. [ABSTRACT FROM AUTHOR]