Panic buying, the sudden, affectively driven surge in purchasing essential goods in excess of rational need, has been widely documented during health crises but remains underexplored as a response to economic policies such as tariffs. Critically, panic buying must be distinguished from rational stockpiling: while anticipatory purchasing in response to tariff-induced price increases may reflect sound intertemporal decision-making, panic buying is characterized by purchases exceeding individually optimal levels and driven by negative affect, perceived scarcity, and social contagion rather than objective risk assessment alone. This article extends the integrated psychodynamic model of panic buying developed by Cooper and Gordon (1) to address tariff-induced consumer behavior, clarifying its psychological underpinnings and broader significance. The article examines how well-established frameworks from behavioral economics, including Prospect Theory, scarcity heuristics, and affect-based models, account for much of the surface phenomenology of tariff-induced panic buying, while arguing that psychodynamic mechanisms explain a clinically significant residual: namely, why a subset of individuals exhibits panic buying that is disproportionate to objective threat, resistant to rational persuasion, and recurrent across successive economic crises. The article introduces three core psychodynamic mechanisms operating across a five-phase model: (1) developmental vulnerability rooted in economic trauma; (2) threat activation involving projection and splitting; and (3) behavioral enactment via displacement and transitional object dynamics. Each mechanism is distinguished conceptually, linked to specific phases of the model, and operationalized with proposed measurement strategies. By providing a clinically actionable framework that complements existing behavioral and economic accounts, the analysis contributes to both therapeutic practice and public policy during periods of economic uncertainty.

Wetland plants must supply oxygen to their rhizomes and roots to maintain aerobic respiration despite soil anoxia. Excess oxygen can diffuse into the environment, strongly affecting rhizosphere biogeochemistry. This radial oxygen loss (ROL) has often been observed to increase in the daytime, perhaps supported by photosynthetic oxygen production and stomatal opening. However, dynamics in rhizosphere oxygen pools do not derive exclusively from diel cycles. Using oxygen-sensitive planar optodes (and simultaneous leaf gas exchange measurements), we compared the timing and magnitude of variation in rhizosphere oxygen pools due to diel cycles vs root and rhizome development in the widespread aquatic macrophyte Typha angustifolia. Diel cycles drove only slight variation in oxygen pool sizes (c. 5% oxygen saturation). Strongly oxygenated regions - regularly 25-30% oxygen saturation - appeared as roots and rhizomes grew, and then disappeared after several days of maturation. Expansive plumes of oxygen also developed upon the emergence of lateral roots and persisted for several weeks. These results indicate that root and rhizome development are dominant determinants of ROL in T. angustifolia. Seasonal and environmental controls over timing of belowground development likely have strong implications for rhizosphere biogeochemistry ranging from microbe-controlled decomposition to redox-sensitive transformation of metals in natural and managed systems.

Pulmonary fibrosis is a progressive and life-threatening lung disorder characterized by excessive fibrogenesis and impaired respiratory function. Nerandomilast, a preferential phosphodiesterase 4B inhibitor, is currently approved for the treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis in several countries following its demonstrated clinical efficacy in Phase III trials. However, its cellular mechanisms of action remain incompletely understood. In this study, we investigated the effects of nerandomilast on a bleomycin-induced mouse model of lung fibrosis. Nerandomilast treatment attenuates fibrotic remodeling and preserves alveolar epithelial architecture. Single-cell transcriptomic analyses revealed altered alveolar epithelial cell state dynamics accompanied by increased cell cycle-associated pathways in alveolar type 2 cells and an increased relative abundance of alveolar type 2 cells. Consistent with the single-cell findings, nerandomilast was associated with an increased SFTPC-positive area and the preservation of alveolar epithelial architecture in vivo. Collectively, our findings suggest that nerandomilast attenuates fibrotic remodeling while modulating alveolar epithelial cell state dynamics, which may provide a possible cellular explanation for its clinical efficacy in patients with pulmonary fibrosis.

Toll-like receptor 7 (TLR7) and TLR8 respond to pathogen-derived single-stranded RNA (ssRNA), orchestrating innate immune defense responses upon infections. However, aberrant recognition of endogenous ssRNAs by these sensors can cause various pathologies, including systemic lupus erythematosus (SLE), familial histiocytosis, immunodeficiency, and bone marrow failure. Recent insights into genetic variations in TLR7/8 and functionally associated genes have elucidated the mechanisms that prevent excessive TLR7/8 activation. Specifically, TLR7/8 responses are negatively regulated by several mechanisms, including the TLR-specific chaperone UNC93B1, lysosomal NADPH oxidase NOX2, the lysosomal nuclease PLD4, and the lysosomal nucleoside transporter SLC29A3. Given the link between dysregulated TLR7/8 activation and diseases development, therapeutic agents targeting these receptors are currently under clinical trials to evaluate their efficacy in treating SLE.

In healthy kidneys without injury or compensatory hypertrophy, glomerular volume generally correlates with the podocyte number. In this study, we investigated whether experimentally increasing podocyte numbers can expand glomerular volume. We generated transgenic mice in which the SV40 large T antigen (SV40T) was selectively expressed in podocytes in a doxycycline-inducible manner. In adult mice, doxycycline treatment successfully induced cell cycle re-entry in podocytes, albeit with low efficiency. However, prolonged treatment caused proteinuria and podocyte injury. When doxycycline was administered during embryogenesis, newborn mice clearly exhibited an increase in podocyte proliferation, leading to an average of 54% increase in podocyte number. These additional podocytes frequently formed multiple layers and detached into Bowman's space or tubular lumen; consequently, the glomerular tuft area did not increase. By postnatal Day 7, excess podocytes disappeared, and podocyte counts returned to levels comparable to those in control mice. These findings indicate that glomerular volume is determined at or before the S-shaped body stage, and that forced increases in podocyte number induced by SV40T at later developmental stages are insufficient to expand glomerular volume.

Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity, yet it remains profoundly underutilized. Patients seeking MBS face pretreatment requirements, including mandatory psychological evaluation, documented failed diet attempts, and months of lifestyle interventions that are substantially more extensive than those required for most common gastrointestinal procedures. These requirements were initially developed with patient safety in mind, but evidence has accumulated that many lack outcome-specific support and have become barriers to care, particularly as third-party payers have increasingly used them to restrict access. Meanwhile, potent obesity management medications (OMMs) are prescribed with relatively limited oversight, often to individuals with preclinical disease, at costs that raise questions about economic sustainability. The Lancet Diabetes & Endocrinology Commission's distinction between preclinical obesity (excess adiposity with preserved organ function) and clinical obesity (a systemic illness characterized by objective organ dysfunction or substantial limitations of daily activities) provides a framework for evaluating current treatment access patterns. A critical implication of this framework, which warrants further exploration, is that it may narrow the population for whom medical treatment is considered necessary: for individuals with preclinical obesity, excess adiposity represents a risk state requiring monitoring and evidence-based counseling, not generally an ongoing illness requiring pharmacotherapy or surgery. This paper examines whether the current pattern, relatively low barriers to expensive, chronic pharmacotherapy for preclinical or early-stage disease; relatively high barriers to durable, cost-effective surgery for established clinical obesity, represents a departure from severity-matched care that warrants systematic reconsideration.

The actin-rich cell cortex is a viscoelastic structure essential for processes such as cell migration and division, yet the full spectrum of actin assembly factors that build and regulate the cortex in mammalian cells remains incompletely defined. While the Arp2/3 complex generates actin networks mostly comprising short, branched filaments, formins like mDia1 and mDia3 assemble long, linear filaments capable of withstanding the high mechanical load produced by myosin-driven contraction at the cell rear. To obtain a complete inventory of formins that regulate mechanics of the contractile cortex in B16-F1 melanoma cells, we systematically screened Diaphanous-related formins (DRFs) for interactions with Rho-family GTPases regulating contractility. This screen led to the identification of Daam1/2 and FMNL2/3 as cortical formins, since active variants of these formins as well as the endogenous proteins prominently localized to the rear cortex of polarized B16-F1 cells. Yeast two-hybrid (Y2H) and GST pull-down assays revealed prominent interactions of Daam1/2 with active RhoA, RhoB, RhoC, RhoD, and Cdc42, and weaker binding to Rac1 and Rif. Pyrene-actin polymerization and single-filament TIRF assays further demonstrated that these GTPases effectively relieve autoinhibition of Daam-family formins, with Daam1 and 2 emerging as a potent elongators. In line with this, CRISPR/Cas9-generated Daam1/2 double-knockout cells exhibited multiple defects, including formation of multiple leading edges, impaired random 2D migration, reduced focal adhesion (FA) turnover and inefficient rear retraction. However, contrary to earlier work, we found no evidence that Daam1/2 regulate the formation of finger-like protrusions. By comparison, FMNL2 appears to act as a dual-role formin at both the cell front and rear, interacting with and being activated by several GTPases linked to contractility and protrusion. Analytical ultracentrifugation further clarified previous inconsistencies by showing that the affinity of FMNL2 for GTPases, particularly for Rac1, depends on the length of its N-terminal fragment and the presence of the full FH3 domain. Finally, we show that cells lacking Daam1/2 and mDia1/3 display pronounced cortical defects, including reduced rigidity, excessive blebbing, and delayed cytokinesis, demonstrating that these formins cooperate to preserve cortical architecture and function.

Non-contact inline Raman spectroscopy is used as a fast, flexible, and safe method for monitoring and optimizing continuous-flow processes involving highly hazardous and corrosive materials. The synthesis of nitroguanidine (NQ), an energetic material, was characterized and optimized as a model for hazardous reactions. The contactless, flexible, and real-time analysis in this environment was implemented using a clip-on adapter for a Raman probe downstream of the microflow reactor. Initial experiments focus on characterizing the in situ formation of the nitration agent, the nitronium ion (NO2[+]), and identifying an optimal nitric acid volume fraction between 10 and 20% v/v for maximum NO2[+] yield. The PAT setup was then used to rapidly optimize reaction parameters (residence time, reactor temperature, and stoichiometry) to enhance reactor output while maintaining high yield. Increasing the reaction temperature to 70 °C effectively reduces system pressure due to the lower viscosity of the reaction stream, while simultaneously increasing yield. Reduced residence times enable higher output with only minimal yield loss (6.3 min, 97%). The analysis of the molar ratio of the reagents further revealed that using a slight excess of nitric acid maintains the yield while avoiding product losses due to back reaction during subsequent processing. To verify the long-term repeatability of the reactor for synthesis, the reaction was performed several times under optimized conditions.

With the increasing rates of cesarean section (CS), cesarean section scar defect (CSD) has become an escalating clinical concern due to uterine dysfunction and reduced fertility. However, the biological basis of CSD remains poorly understood, particularly the mechanisms of impaired uterine repair after CS and the causes of failure in conventional repair surgeries. This study integrates metabolomics, transcriptomics, a newly developed mouse model, and functional assays to elucidate the complex interplay between senescence and fibrosis in CSD. Our findings identify upregulation of the PGES/prostaglandin E2 (PGE2) axis as a key upstream event that disrupts uterine healing. Elevated PGE2 preferentially induces early senescence of macrophages, which transmit pro-senescent signals to uterine fibroblasts through IL-1β/IL-1R signaling. This sequential senescence cascade drives excessive fibroblast activation and progressive fibrosis, ultimately impairing uterine structure and function. In mouse CS models, inhibition of the PGES/PGE2 pathway and anti-aging strategies significantly attenuate fibrosis and restore coordinated myometrial and endometrial repair. Our findings uncover a macrophage-fibroblast senescence relay to fibrotic scar formation in CSD and provide a translational rationale for targeting PGE2 signaling and senescence to improve uterine repair after CS.

Although excessive dietary sodium intake is a well-recognized risk factor for hypertension, accumulating evidence indicates that it leads to broader metabolic consequences. Here, we investigated the renal and skeletal consequences of high salt loading and the protective effects of esaxerenone, a selective nonsteroidal mineralocorticoid receptor (MR) antagonist. Male Sprague-Dawley rats were infused with aldosterone and fed an 8% sodium chloride diet for 4 weeks (Aldo-HS), with or without esaxerenone. Trabecular bone architecture was assessed by micro-computed tomography, three-dimensional morphometry, and histomorphometry. Kidney and bone transcriptomes were analyzed using RNA sequencing and weighted gene co-expression network analysis. Aldo-HS rats developed marked renal calcium wasting without changes in serum calcium, phosphate, parathyroid hormone, or fibroblast growth factor 23 levels. Fractional calcium excretion was strongly inversely correlated with trabecular bone volume (r = -0.74, p < 0.001). Aldosterone-salt loading induced substantial trabecular bone loss, which was prevented by esaxerenone. Bone transcriptomic analysis demonstrated suppression of extracellular matrix gene programs; a collagen-enriched gene module (including Col1a1, Col1a2, Col11a1) was tightly linked to calcium wasting (r = -0.97, p < 0.001), partially restored by MR blockade, and overlapped with loci associated with bone mineral density in human genome-wide association studies. Aldosterone-salt loading induces trabecular bone loss accompanied by imbalance in bone remodeling and renal calcium wasting. MR blockade preserves skeletal integrity, supporting a modifiable bone-kidney axis and providing translational insight into skeletal complications of mineralocorticoid excess.

Obesity arises when a chronic energy surplus overwhelms the storage capacity of adipocytes and subsequently causes systemic metabolic dysfunction. Adaptive thermogenesis, primarily mediated by uncoupling protein 1 (Ucp1) in adipocytes, serves to counteract obesity by dissipating excess energy as heat. Despite extensive studies on thermogenic regulation, the phosphatases that regulate this protective metabolic pathway remain poorly understood. Here we identify dual-specificity phosphatase 4 (Dusp4) as a critical modulator of adipocyte thermogenesis via direct modulation of CREB-regulated transcription coactivator 3 (Crtc3). Dusp4-knockout mice exhibit impaired thermogenic capacity, diminished Ucp1 expression, and increased susceptibility to diet-induced obesity coupled with severe insulin resistance. Mechanistically, Dusp4 directly dephosphorylates serine residues on Crtc3, facilitating its nuclear translocation and subsequent transcriptional activation of Ucp1. Depot-targeted restoration of catalytically active Dusp4 in inguinal adipose tissue rescues local thermogenic gene expression and reinstates Crtc3 dephosphorylation-dependent Ucp1 induction in Dusp4-knockout mice. Collectively, these findings identify Dusp4 as a key upstream phosphatase orchestrating the Crtc3-Ucp1 thermogenic axis, and highlight its potential as a therapeutic target for obesity-associated metabolic disorders.

Accumulating evidence demonstrates that antibody-dependent cellular phagocytosis (ADCP), mediated by tumor-associated macrophages via Fcγ receptors (FcγR), represents a key Fc-dependent effector mechanism for selected antitumor monoclonal antibodies, including rituximab in B-cell malignancies, trastuzumab in HER2-positive cancers, cetuximab in EGFR-expressing tumors, and daratumumab in multiple myeloma. Beyond direct tumor cell clearance, macrophage-driven ADCP acts as a critical innate-adaptive immune bridge by facilitating antigen processing, intercellular immune crosstalk and downstream adaptive immune activation. However, ADCP is not uniformly beneficial. Depending on target antigen properties, macrophage functional state, and tumor microenvironmental cues, excessive or dysregulated ADCP may instead drive macrophage dysfunction, immunosuppressive remodeling, adaptive resistance, and dose-limiting toxicities. These observations highlight the need for a more selective and mechanistically informed framework for understanding and therapeutically harnessing ADCP in cancer immunotherapy.

The capacity for excess manganese to alter dopaminergic systems resulting in neurobehavioral deficits is clear, yet far less is known the impact of chronic, lower, sub-toxic manganese exposures. Manganese exposure may affect dopamine synthesis and metabolism, and as such impact drug efficacy. These may also occur to a greater extent in populations with genetic variants that render them more vulnerable to intellectual developmental disabilities. DAT[T356M/+] mice were used as a model of altered dopamine transport via an autism-linked single nuclear polymorphism in the dopamine transporter. Following 12 weeks feeding of manganese (2400 ppm) mild changes in spontaneous and repetitive behaviors such as climbing and rearing were induced by both genotype and manganese although the patterns differed according to age and sex. Female mice also exhibited a decrease in activity in response to amphetamine compared to control-fed mice (70 ppm) littermates independent of the decreased response observed in DAT[T356M/+] mice. Males showed a more robust effect of genotype suppression of the amphetamine response but no further effect of manganese. Behavioral changes occurred in the absence of significant impact of dietary manganese on body weight. Manganese exposure was associated with altered gene expression in nucleus accumbens relating to metal transport (Slc11a2, Slc39a8, Slc39a14, Slc30a10) and dopamine regulation (TH, Slc6a3) that did not show clear differences according to sex. Changes at the RNA level were not replicated in protein expression changes measured in the striatum. There were no changes in levels of dopamine or metabolites in the cortex according to genotype or manganese, although manganese exposure was associated with decreased norepinephrine and increased serotonin. SNCA has a regulatory role in dopamine neurotransmission and snca gene expression was significantly down regulated by both DAT[T356M/+] genotype and manganese diets. The altered dopamine changes and response to amphetamine between sexes in presence of Mn highlights the potential role of sub-toxic exposures to heavy metals in moderating behavioral profiles and drug responses. The lack of consistent differences according to sex, genotype and exposure across all outcomes also suggests the complexity of the specific pathways and mechanisms driving the behavioral differences.

Acute kidney injury (AKI) is a severe complication in hospitalized patients, with ferroptosis playing a critical role in its pathogenesis, characterized by excessive oxidative stress and exaggerated inflammation. Despite its high mortality, no specific pharmacotherapy is currently available. To address this challenge, we engineered a macrophage membrane‑based biomimetic nanovesicle system (Emo/VE‑mcNVs) for targeted co‑delivery of emodin and vitamin E. By exploiting the injury‑guided homing capability of macrophages, the nanovesicles were fabricated through camouflaging emodin/vitamin E‑coloaded liposomes (Emo/VE‑LPs) with macrophage membranes. This design conferred enhanced biocompatibility, reduced macrophage uptake, immune evasion, and inflammatory tropism, enabling targeted drug delivery to injured kidneys. Cellular studies demonstrated that Emo/VE‑mcNVs were efficiently internalized by renal tubular epithelial cells (HK‑2) and markedly relieved cisplatin‑induced oxidative stress, ferroptosis, and inflammatory responses. In a murine AKI model, intravenous administration of Emo/VE‑mcNVs resulted in pronounced renal accumulation, significantly reduced serum creatinine and blood urea nitrogen levels, ameliorated renal histopathological damage, restored ferroptosis‑related markers, and suppressed local oxidative stress and inflammatory cytokine expression. Collectively, treatment with Emo/VE‑mcNVs improves AKI therapeutic outcomes through a synergistic antioxidant, anti‑inflammatory, and anti‑ferroptosis mechanism, offering a promising nanotherapeutic strategy for clinical management of acute kidney injury.