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In this case series, the authors aim to illustrate a technique for reinforcing tissue above deep-brain stimulator (DBS) surgical sites to prevent wound breakdown and decrease postoperative infectious risks. Twelve patients were implanted with DBS electrodes and an implantable pulse generator. Fish acellular dermal matrix was utilized following successful placement and tunneling of DBS leads to reinforce the surgical wound closure above the DBS cranial burr hole cover. This matrix was placed under the galea and above the pericranium in each patient before standard galea and skin closure techniques after the implants were placed. Eleven of 12 patients had the implant placed during surgery. One patient was excluded due to an allergy to the graft material. No patients at any point during the follow-up period showed any clinically significant signs of wound breakdown or infection at the surgical site. There was one report of suture extrusion without any associated infection or wound breakdown. In this case series, the authors demonstrate that the use of fish skin acellular dermal matrix is a safe and effective strategy that can be utilized during DBS placement to further bolster the skin above DBS burr hole covers to aid in wound healing and decrease postoperative surgical site infections.

A silicon single-photon avalanche diode (SPAD) fabricated in a 40 nm CMOS image sensor (CIS) technology is reported. An N-well/deep P-well (DPW) structure on a CIS epitaxial wafer is employed, where the N-well and lightly doped epitaxial layer form a virtual guard ring that suppresses edge breakdown. The device exhibits a breakdown voltage of 22.7 V, a peak photon detection probability (PDP) of 89.4% at 660 nm and 3 V excess bias voltage, and a median dark count rate (DCR) of 0.6 cps/µm². A timing jitter of 144 ps full width at half maximum and an afterpulsing probability below 0.3% are achieved. Temperature-dependent measurements show a pronounced PDP redshift at 60 °C, accompanied by enhanced peak and long-wavelength PDP. The SPAD is suitable for high-performance low-light visible imaging applications.

Two-dimensional (2D) semiconductors enable atomically thin channels and attractive electrostatics, but practical scaling increasingly hinges on gate-dielectric integration rather than channel performance. A key challenge is forming high-quality dielectrics on chemically inert, dangling-bond-free 2D surfaces while pushing equivalent oxide thickness to the sub-nanometer regime without excessive leakage, traps, or electrical breakdown. This review addresses the materials and process physics that govern dielectric formation in 2D devices, with an emphasis on atomic layer deposition nucleation, surface pretreatment and functionalization, and the use of seed and buffer layers for conformal high-κ oxides. The roles of layered insulators, such as hexagonal boron nitride, are discussed in terms of interface quality, electrostatic scaling limits, and transport limitations. The impact of dielectrics and processing on leakage mechanisms, defect generation, device-to-device variability, and reliability metrics, including time-dependent dielectric breakdown, bias-temperature instability, hysteresis, and threshold-voltage drift, is examined. Finally, we highlight van der Waals dry integration and dielectric transfer approaches that reduce process-induced damage and support wafer-scale uniformity, as well as opportunities for mixed-dimensional and 3D stacked architectures across logic, memory, and emerging functional systems. [Image: see text]

Reducing saturated fat while preserving the sensory quality of full-fat foods remains a major formulation challenge because fat contributes simultaneously to body, lubrication, flavor delivery, and thermal transitions. Carbohydrate-protein (CP) hydrogels are increasingly explored as oil-free fat replacers, but many systems are developed and evaluated in isolation, with limited benchmarking against the full-fat references they are intended to replace. This review considers the literature from two benchmarking prospectives: (i) bulk-fat analog benchmarking, in which self-standing gels are compared with bulk fats; and, (ii) product-level benchmarking, in which CP hydrogels are assessed within specific food matrices against full-fat controls. Across both paradigms, the evidence indicates that successful fat replacement cannot be predicted by a single instrumental match. Instead, performance depends on convergence across rheology, tribology, microstructure, water distribution, breakdown behavior, and thermal response. In practical terms, the most transferable design criteria are rheological compatibility within the relevant processing and consumption ranges, lubrication behavior that supports creaminess and mouthcoating, microstructural length scales that avoid graininess or chalkiness, and category-specific thermal and breakdown behavior that reproduces full-fat transitions such as meltability, softening, or juiciness. Viewing the literature through these two benchmarking logics helps distinguish when bulk similarity is informative, when in-product benchmarking is essential, and why apparently promising CP hydrogels often fail in real food application.

High-electron-mobility transistors (HEMTs) based on wide bandgap (WBG) materials like gallium nitride (GaN) are vital for next-generation power electronics and high-frequency applications, offering high breakdown voltage, electron mobility, and power density. The global shift toward electrification and sustainability is driving demand for GaN and silicon carbide (SiC) power devices. However, challenges such as current collapse and increased channel resistance under high-power conditions hinder performance. To address these limitations, numerous solutions have been explored, with simulation emerging as an indispensable starting point. Technology Computer-Aided Design (TCAD) simulations play a critical role by enabling accurate modeling, performance optimization, and reduced experimental effort. This paper reviews key and advanced physical models in TCAD simulations of GaN HEMTs, covering mechanisms such as carrier transport, thermal effects, and impact ionization. Mobility models-FLDMOB, Albrecht, Gansat, Yamaguchi, Brooks-Herring, and Conwell-Weisskopf-are analyzed for capturing velocity saturation and nonlocal transport. Recombination models like Shockley-Read-Hall and Auger are discussed in relation to carrier lifetime, while impact ionization models, including van-Overstraeten-de-Man, Selberherr, and Okuto-Crowell, are evaluated for breakdown prediction. Emphasis is placed on choosing models suited to specific structures and conditions to ensure simulation accuracy. Advanced modeling enhances TCAD's predictive power, supporting innovation in GaN-based power electronics.

This paper applies principles and perspectives emerging from free energy neuroscience to the psychoanalytic concept of the death drive. The aim is to offer a contemporary reappraisal of this controversial aspect of psychoanalytic theory and its link to psychosis. The paper begins with a review of the death drive as proposed by Sigmund Freud, before proceeding to briefly outline Karl Friston's free energy principle. Building on proposals from Gustaw Sikora and Bernard Penot, it then explores how the combined and coordinating processes of minimising [binding] free energy and dismantling [unbinding] inexpedient generative models of reality may be understood as essential to life, growth, and adaptation. The question is thus raised: if a periodic unbinding-even destruction and demise-of generative models is vital to adaptive living, how might the death drive be conceptualised? The paper then proceeds to develop the notion that what Freud identified as the (defused) death drive may reflect a critical breakdown in the reciprocal ebb and flow of binding free energy/unbinding generative models of reality. Two illustrations-both of which concern psychotic phenomena-are given in an attempt to depict how the death drive in defused form may be recognised as manifesting both as arrested unbinding and/or interminable binding. The discussion explores how such a breakdown in the vital rhythms of life and self-organisation can sabotage the ability to think, compromise the mind's capacity to function as a container, and produce a boundless infinitisation of experience therein.

The blood - brain barrier (BBB) plays a central role in maintaining central nervous system (CNS) homeostasis, and its disruption is a defining feature of malignant brain tumors such as glioblastoma. Emerging evidence indicates that BBB dysfunction not only alters the tumor microenvironment but also shapes the mutational processes that drive genomic instability in CNS malignancies. This review synthesizes current understanding of the biological mechanisms linking BBB breakdown with distinct mutational signatures, including those arising from oxidative stress, hypoxia-induced replication stress, lipid peroxidation, inflammation, and metabolic reprogramming. Advances in next-generation sequencing, coupled with computational tools such as non-negative matrix factorization, Bayesian modeling, and deep learning, have enabled precise extraction of these signatures and their integration with multi-omics data. Clinically, BBB-associated mutational signatures offer significant promise for therapeutic stratification, prediction of treatment response, and noninvasive monitoring through cerebrospinal fluid - derived circulating tumor DNA. Despite these advances, challenges persist due to limited tissue accessibility, low-yield CSF samples, incomplete mechanistic models, and the lack of CNS-specific analytical frameworks. A deeper understanding of BBB-driven mutational processes, supported by improved computational approaches and integrative datasets, holds potential to advance precision oncology in neuro-oncology.

Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis and Graves' disease, arise from thyroid-specific autoimmunity driven by a breakdown of immune tolerance and dysregulated T-cell responses. Within this immune network, imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells has emerged as a major determinant of persistent inflammation and defective immune restraint. These two subsets are supported by distinct but interconnected metabolic programs. Th17 cells preferentially engage glycolytic and anabolic pathways to sustain inflammatory activity, whereas Treg cells rely more strongly on oxidative metabolism and mitochondrial fitness to preserve lineage stability and suppressive function. In AITDs, these intracellular programs are further reshaped by disease-associated microenvironmental cues, including excess iodine, oxidative stress, lactate accumulation, inflammatory cytokines, and tissue-derived stromal signals. This review summarizes how glucose, lipid, mitochondrial, and amino acid metabolism collectively regulate Th17 and Treg differentiation and function. We further examine how these pathways are altered in AITDs and distorted in thyroid and orbital tissues to amplify immune disequilibrium. Finally, we discuss emerging therapeutic strategies aimed at targeting immune metabolic circuits to restore immune homeostasis.

Flavonoids bridge plant defence and acclimation, helping land plants translate UV-B/high light, drought, heat, salinity, and cold into metabolic and physiological change. Recent studies map lineage biases in flavonoid scaffolds and show that core enzymes assemble into endoplasmic reticulum (ER)-associated metabolons, with auxiliary reactions detected at the tonoplast and in the nucleus. After synthesis, cellular pools are set by ABC and MATE transporters, GST ligandins, and vesicle-mediated trafficking. Regulatory layers include MBW-centred transcription-factor networks wired into Ca2+, ROS, and JA/SA/ABA signalling, while late tailoring (hydroxylation, glycosylation, O-methylation, and acylation) modulates solubility, stability, localisation, and bioactivity. Under UV, drought, high temperature, salt stress, freezing, nutrient imbalance, and metal toxicity, distinct chemotypes contribute to photoprotection and to biotic defence as phytoalexins and anti-herbivore deterrents. We propose that flavonoids act not only as redox-active, membrane-protective metabolites but also as signals that reset transcriptional and hormonal programmes; pathogens and insects can blunt this interface via detoxification, efflux, and enzymatic breakdown. Key quantitative gaps include in vivo antioxidant weight relative to enzyme cycles, branch-specific flux partitioning, and links between tissue patterning and protection. Priorities are outlined for deploying stress-responsive flavonoid repertoires to boost crop resilience under combined stresses without yield penalties.

Ischemic stroke (IS) disrupts the blood-brain barrier (BBB), thereby aggravating neurological deterioration. Loss of tight junction (TJ) and adherens junction (AJ) proteins is a key event in BBB breakdown, but the upstream mechanisms remain incompletely understood. Here, we investigated whether LS21013A-06 (A06), a phosphodiesterase-4 inhibitor, protects brain microvascular endothelial cells and preserves BBB integrity after ischemia/reperfusion, with particular focus on whether its protective effects are PKA-dependent and accompanied by changes in leukocyte cell-derived chemotaxin-2 (LECT2). In human brain microvascular endothelial cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R), LECT2 knockdown preserved TJ and AJ proteins, reduced Bax upregulation, restored Bcl-2 expression, and diminished reactive oxygen species accumulation. A06 pretreatment (3 μM) recapitulated these effects and markedly reduced OGD/R-induced LECT2 expression. The PKA inhibitor H89 (5 μM) abolished A06-mediated LECT2 suppression, junctional preservation, and reductions in apoptosis and reactive oxygen species, whereas LECT2 overexpression similarly abrogated the protective effects of A06. In a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model, post-ischemic A06 administration (1 or 3 mg/kg, intraperitoneally) improved neurological scores and motor performance, reduced infarct volume and Evans blue extravasation, and increased ZO-1, VE-cadherin, and Occludin levels in peri-infarct cortex, together with reduced LECT2 expression and attenuated apoptosis-related changes in Bcl-2 and Bax. These findings indicate that A06 preserves BBB integrity after experimental ischemia. Mechanistically, its protective effects were PKA-dependent and accompanied by reduced LECT2 levels, preserved junctional proteins, and attenuated apoptosis-related changes. A06 enhanced PKA signaling, whereas PKA silencing blunted both its protective effects and the associated reduction in LECT2 expression.

The core pathological mechanism of osteoporosis (OP) resides in the imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Furthermore, the accumulation of reactive oxygen species (ROS) and pro-inflammatory factors in bone tissue induces disorders in the immune microenvironment, which substantially elevates the risk of fracture. Inspired by the biological behaviors of sea cucumbers, we designed and constructed a bone-targeting platform (BA@PDA-PA) based on black phosphorus (BP) and amorphous calcium carbonate (ACC). This platform enables precise targeted therapy for diseased bone tissue while improving drug bioavailability. Upon reaching the target site, BA@PDA-PA can respond to the acidic microenvironment of OP lesions, and then release BP and calcium ions (Ca2+) on demand. Specifically, BP efficiently scavenges local excessive ROS and improves the immune microenvironment. Meanwhile, the Ca2+ released from ACC degradation, along with the low phosphorus oxides derived from BP breakdown, work together to promote osteoblast proliferation and differentiation while inhibiting osteoclast activity. This establishes a synergistic therapeutic mechanism involving "targeted delivery, microenvironment regulation, and bone metabolism remodeling." In vivo experimental results demonstrate that this platform significantly improves the pathological bone microstructure of OP mice, thereby providing a promising therapeutic strategy for OP treatment.

For the past half-century, psychiatric drug development has largely focused on tweaking neurotransmitter receptors and chemical pathways. Yet despite billions of dollars invested and major advances in neuroscience, truly innovative treatments for mental illness remain scarce. Disorders like depression, schizophrenia, and post-traumatic stress disorder (PTSD) continue to be managed with drugs discovered decades ago that often provide only partial relief, with remission rates of approximately 30-40% for treatment-resistant depression and 60-70% of schizophrenia patients experiencing persistent symptoms despite medication. This stagnation has prompted a paradigm shift - what if the key to treating mental illness is not just which receptor a drug targets, but how it changes the brain's processing of sensory information? In this treatise, I propose that many psychiatric conditions stem from breakdowns in the brain's sensory filtering mechanisms, the neural circuits that gate irrelevant stimuli before they consume valuable processing resources, and that effective therapies must restore these filtering functions. While computational psychiatry has long recognized that mental illness may reflect failures in predictive filtering, the specific neural substrate implementing this gating remains underspecified. Here the cerebellum emerges as a critical hub: neuroanatomically positioned to perform bottom-up sensory gating before cortical processing, housing more than half the brain's neurons in an architecture ideally suited for distilling signal from noise and showing state-dependent disruption of cerebellar-cortical connectivity during symptom provocation in PTSD. Intriguingly, psychedelic drugs may act as recalibration triggers for these neural filters, acutely disrupting entrenched filtering architectures and reopening windows of plasticity through which maladaptive sensory weightings can be reset. This cerebellar filtering framework offers a neuroanatomically specified extension of predictive processing theory, generates falsifiable predictions, and suggests novel therapeutic targets for conditions that have resisted a half-century of receptor-focused drug development.

Adaptive walking relies on proactive gaze behaviour to plan foot placement and maintain stability. This study examined how mental workload and task complexity affect gaze behaviour and gait biomechanics during a precision target-stepping task in healthy young adults. We also quantified the frequency of cross-stepping during the experimental task. Twenty-three participants (18-23 years) walked along an L-shaped pathway containing raised stepping targets under single-task (ST) and dual-task (DT) conditions. Targets had four different layouts to create high and low difficulty conditions. Eye movements were recorded using mobile eye-tracking, and gait kinematics were recorded via motion capture. Compared with ST, DT walking produced slower walking speeds, longer stance times, and reduced velocity between stepping targets, indicating a more inefficient gait strategy. In addition, eye-tracking analyses revealed fewer and shorter fixations on task-relevant targets and a greater number of fixations directed toward task-irrelevant areas and, saccadic amplitudes were reduced despite increased outside fixations, suggesting a breakdown in visual exploration between proximal and distal regions of the walkway. In ST conditions, cross-stepping was more frequent than in DT. These findings indicate that increased mental workload compromises proactive gaze behaviour, likely through working-memory and attentional limitations that disrupt feedforward gait planning. Contrary to expectation, cross-stepping occurred more often during ST than DT walking, suggesting that in this population cross-stepping may not be a maladaptive strategy. Overall, these results highlight the cognitive demands of adaptive walking even in young, low-risk individuals and underscore the importance of preserving visual-motor coordination under cognitive stress.