Soil-borne vascular pathogens pose serious threats to agriculture with complex invasion strategies that remain poorly characterized compared to foliar pathogens. While foliar pathogens like Magnaporthe oryzae employ specialized appressoria to penetrate plant surfaces through a combination of mechanical force and enzymatic degradation, the invasion mechanisms of vascular pathogens that lack classical appressoria have remained largely theoretical. The nanoscale processes governing root penetration and colonization by these pathogens are particularly challenging to visualize due to technical limitations of conventional microscopy. Here we show, using phase-contrast X-ray computed microtomography and advanced microscopy, that Fusarium oxysporum (Fo) employs distinct mitogen-activated protein kinase (MAPK) cascades to orchestrate root invasion through unprecedented morphological plasticity. We identify previously undocumented appressoria-like structures that facilitate physical penetration, while demonstrating that Fo exhibits remarkable cellular adaptability, reducing hyphal diameter by more than 20-fold (from 5 μm to 220 nm) to navigate confined plant spaces, a dramatic morphological transition previously thought impossible. By using cellulase-deficient mutants, we demonstrate that cellulolytic activity is dispensable for surface breach and submicrometric hyphal colonization, establishing that mechanical force generation rather than enzymatic degradation is the primary determinant of successful host penetration. Three-dimensional reconstruction reveals a quantitative correlation between fungal proliferation and progressive embolism formation, with distinct MAPK pathways differentially regulating penetration force generation (Fmk1), osmotic adaptation during apoplastic colonization (Hog1), and directional growth toward vascular tissues (Mpk1). These findings provide a mechanistic framework for vascular wilt pathogenesis and reveal potential targets for controlling these economically devastating plant diseases.
While systemic immune dysregulation is well-documented in HIV infection, its impact on blood and respiratory tract viromes remains poorly understood. This study characterizes HIV-associated alterations in viral communities and examines their clinical relevance. Using viral metagenomics, we compare 203 ART-treated HIV-positive individuals and 120 healthy controls. HIV infection significantly restructures the blood virome, shifting from bacteriophage dominance (96.2% in controls) to eukaryotic virus predominance (69.1%). Increased alpha diversity, significant β-diversity divergence, and heightened dispersion heterogeneity are observed in HIV cases. Consistent enrichment of Flaviviridae, Parvoviridae, and Anelloviridae is detected. Throat viromes maintain phage dominance (>90%) but exhibit strain-level diversification, including Microviridae proliferation. Network analysis reveals Retroviridae-Anelloviridae co-dynamics (r = +0.562) and identifies Picobirnaviridae as a key interactor. Functional analysis shows enriched viral replication and host modulation genes. Compartment-specific disruption patterns nominate Pegivirus C, parvovirus B19, and Anelloviruses as potential biomarkers. Cross-kingdom viral interactions suggest novel mechanisms influencing disease progression and support future virome-targeting adjunct therapies.
Despite advancements in biomimetic and regenerative dentistry, contemporary prosthetic restorations, though clinically successful, remain fundamentally imperfect replications of the natural tooth's inherent biological perfection. Crucially, while these advancements remain vital, the dental discipline has increasingly shifted from preventive focus to a reparative focus. Given that dental decay-the primary concern in a dental practice-is a highly predictable and preventable condition and that tooth loss is a largely avoidable outcome, we propose that the future of the discipline lies in transitioning focus from substitution of lost or damaged tooth parts to the preservation of what is hitherto biologically irreplaceable. Reviewing current dental practice and research, this perspective article challenges the dental community to maximize tooth longevity by acknowledging that in dentistry-more than any other medical discipline-prevention remains the cure. Our challenge invokes the 'paradox of knowledge'-where expanded understanding unveils deeper unknown-to bring to the fore that the more we uncover the intricacies of the dental bioarchitecture, the clearer it becomes that preservation of the invaluable and irreproducible natural tooth structure, rather than its repair, is the achievable path forward. This realization warrants a paradigm "U-turn" towards the light at the starting end of the reparative tunnel. We contend that a successful shift from tooth replacement or regeneration to tooth preservation is twofold: it requires a mindful appraisal of contemporary scientific knowledge concerning the tooth mechano-biology as an unparalleled organ in the body, as well as a fundamental reexamination of the values of a profession existing to alleviate people's suffering.
The tumor microenvironment undergoes dynamic biomechanical alterations during hepatocellular carcinoma (HCC) progression. However, the identification and characterization of biomechanically specialized macrophage subsets remains unexplored. In this study, single-cell RNA sequencing and spatial transcriptomics were used to characterized the spatial distribution patterns, phenotypic plasticity, and mechanoresponsive behaviors of IL4I1+ macrophages. Atomic force microscopy revealed substantial biomechanical heterogeneity within HCC tissues. Complementary in vitro and in vivo mechanobiology models demonstrated that macrophages dynamically respond to biomechanical cues and actively promote HCC progression. Furthermore, using a multimodal drug discovery platform combined with experimental validation, we elucidated IL4I1+ macrophages as a critical therapeutic target for HCC. Our findings demonstrate that IL4I1+ macrophages exhibit a distinct mechanosensitive phenotype capable of dynamically responding to biomechanical cues. Biomechanical-driven-IL4I1+ macrophages promote HCC progression by orchestrating multifaceted oncogenic programs, including enhanced tumor cell proliferation (n = 3, p <0.05), migratory capacity (n = 3, p <0.01), stem-like properties (n = 6, p <0.001), and immune evasion potential. SB505124 treatment significantly attenuated HCC progression in preclinical models, concomitant with a reduction in IL4I1+ macrophages (n = 5, p <0.001). Our study established that IL4I1+ macrophages respond to biomechanical cues within the tumor microenvironment and functionally convert them into immunosuppressive and pro-tumorigenic signals. These findings offer new insights into HCC mechanobiology and highlight IL4I1+ macrophage as a promising target for combination therapy. The tumor microenvironment undergoes dynamic biomechanical changes in HCC progression. However, biomechanically responsive macrophage subsets remain poorly characterized. Here, we identify IL4I1+ macrophages as a biomechanics-sensing subpopulation that promotes HCC progression by fostering an immunosuppressive microenvironment and enhancing tumor proliferation, migration, and stemness. Our study unveils a novel mechanism by which macrophages regulate tumor progression from a biomechanical perspective and proposes a potential therapeutic strategy via targeted inhibition of IL4I1+ macrophages.
With the accelerating pace of population aging in China, depression among older adults has emerged as a significant public health challenge. Existing research has yet to fully elucidate the underlying processes linking community environment to depression among older adults, particularly from an age-differentiated perspective. To address this gap, this study constructed an integrated model positing aging anxiety and social adaptation stress as mediators and age as a moderator, aiming to systematically examine the pathways associated with the relationship between community environment and depression among older adults and their heterogeneity across age groups. Using valid data from 10,562 respondents in the 2023 China Longitudinal Aging Social Survey (CLASS 2023), the analysis was conducted via structural equation modeling. The findings indicate: first, a significant negative correlation exists between community environment and depression; second, both aging anxiety and social adaptation stress exhibit significant indirect associations in this relationship, with the indirect effect of social adaptation stress being stronger. More importantly, the association between community environment and depression is stronger for older-old adults and is primarily linked to the pathway involving aging anxiety. In contrast, its association with depression in younger-old adults is channeled to a larger extent through social adaptation stress. This study unveils the pattern of dual pathways and differential patterns related to age that characterize the relationship between community environment and depression among older adults. The findings provide empirical evidence and theoretical support for future efforts to build age friendly communities and implement stratified healthy aging policies.
Insecticides and herbicides are utilized worldwide in agricultural practices, and these hazardous materials retained in the environment impose potential threats to pollinators, including bumblebees. However, whether and how short-term exposure to sublethal concentrations of insecticide/herbicide induces lasting toxicity effects in newly emerged gynes remain uncharacterized. In this study, we comprehensively investigated the long-term consequences of short-term exposure to sublethal imidacloprid (IMI) and glyphosate (GLY) (singly or combined) on bumblebee (Bombus terrestris) gynes under different exposure regimens through integrated physiological and transcriptomic analyses. Short-term exposure of gynes to IMI alone and IMI + GLY mixtures not only impacted survival, tissue development, nutrient reserves, mating, diapause energy metabolism, and reproduction of queens but also caused transgenerational toxicity affecting offspring development and performance. In contrast, GLY exposure alone adversely affected tissue development, nutrient reserves, diapause energy metabolism, and offspring development of queens. Notably, compared to direct exposure, starvation exacerbated the adverse effects of IMI exposure on queens' diapause survival and energy metabolism and aggravated the impacts of GLY exposure on gynes' ovarian development and lipid reserves. For combined IMI + GLY exposure, starvation mainly amplified physiological disturbances related to queens' diapause survival, energy metabolism, and offspring development and performance. The observed defects in short-term IMI- and IMI + GLY-exposed gynes may result from altered nutrient metabolic pathways. Collectively, our research unveils the lasting toxicity of short-term mixed insecticide/herbicide exposure on gynes/queens and their offspring from physiological and molecular perspectives, underscoring the urgent need for regulatory consideration of combined pesticide risks in bumblebee conservation.
In materials with broken inversion symmetry, nonreciprocal magneto-transport manifests as a bilinear dependence of charge conductivity on electric and magnetic fields. This phenomenon is rooted in symmetry and electronic quantum geometry and is relevant for rectification and detection technologies. Experimental studies generally attribute nonreciprocal magneto-transport to Zeeman-driven mechanisms and exhibit quadratic scaling with conductivity. Here, we report a microscopic mechanism based on Lorentz skew scattering in BiTeBr, arising from the cooperation of classical Lorentz force and quantum skew scattering, exhibiting a quartic scaling of the nonreciprocal response. Systematic measurements on samples with different mobilities reveal a crossover between Zeeman-related and Lorentz-skew scattering-dominated regimes, uncovering the mobility plays a central role in determining the dominant mechanism. Our finding unveils the leading mechanism in high-mobility systems and suggests a universal principle towards strong nonreciprocal response by enhancing electronic relaxation time in topological materials, rendering guidance for low-dissipation rectifiers and high-performance quantum electronics.
Previous studies have demonstrated that porcine blood polypeptide (PBP) could mitigate plant damage under adverse conditions. This study was conducted to systematically investigate the possible role of PBP in enhancing drought resistance in wheat through comprehensive physiological and biochemical analyses, as well as transcriptomic analysis. Morphological observations revealed that PBP-primed seedlings exhibited improved growth, biomass accumulation and root system under drought stress. Physiological and biochemical analyses demonstrated that primed seedlings existed significantly higher values in Pn, Gs, Tr, Fv/Fm, Fv'/Fm', ΦPSII and NPQ. Additionally, increased contents of total chlorophyll, Pro, TSS, and RWC were observed, along with enhanced activities of antioxidant enzymes, such as SOD, CAT, APX, and POD. In contrast, concentrations of H2O2, O2-, MDA, and REC were significantly reduced. Principal component analysis (PCA) indicated that PBP alleviated drought-induced damage primarily through enhancing antioxidant capacity and osmotic adjustment. Transcriptome analysis showed that PBP triggered an active adaptation mechanism against drought, as evidenced by the significant enrichment of DEGs involved in "ion transport", "glyoxysome", and "MAPK signaling pathway". Correlation analysis revealed that expression levels of genes enriched in aforementioned terms were, on the whole, significantly positively correlated with both enzyme activities and levels of osmotic regulatory substances. Overall, this study unveils a novel application for PBP, establishes a theoretical basis for its use in improving drought resistance in wheat, and provides an innovative strategy for boosting wheat production in arid and semi-arid regions.
The severe acute respiratory syndrome coronavirus 2 spike glycoprotein enables infection through a key conformational transition that exposes its receptor binding domain (RBD). Experimental evidence indicates that spike mutations, particularly the early D614G variant, alter the rate of this conformational shift, potentially increasing viral infectivity. We conducted extensive weighted ensemble simulations of the Ancestral, Delta, and Omicron BA.1 spike strains to investigate relationships between sequence mutations and RBD opening dynamics. We observe that Ancestral, Delta, and Omicron BA.1 spike RBDs open differently. Via dynamical network analysis, we identified two allosteric communication networks connecting all S1 domains: the established N2R linker and a newly investigated antiparallel R2N linker. In Delta and Omicron BA.1 variant spikes, RBD opening is facilitated by both linkers, while the Ancestral strain relies predominantly on the N2R linker. In the Ancestral spike, the D614-K854 salt bridge impedes allosteric communication through the R2N linker, whereas the loss of this salt bridge in all subsequent variants of concerns allows for increased local flexibility, thereby accelerating RBD opening. Hydrogen-deuterium mass spectrometry experiments validate these altered dynamics in the D614 region. This study unveils a "hidden" network, connecting the N-terminal domain to the RBD via the 614-proximal region, and the D614G mutation reshapes the fitness landscape of these critical viral glycoproteins.
Radiotherapy is a mainstay of cancer treatment, yet its efficacy is still substantially restricted due to radioresistance. The mechanisms underlying radioresistance remain elusive, impeding drug development and therapeutics. Here, using a high-throughput random gene perturbation method based on piggyBac transposon, we screened and identified CABLES1, an adaptor protein, as a key regulator of tumor radioresistance. The function of CABLES1 in radioresistance was further validated in multiple human cell lines in vitro and a mouse xenograft model in vivo. High expression of CABLES1 is significantly correlated with radioresistance in cancer patients. Mechanistically, CABLES1 interacts with XRCC6/XRCC5 heterodimer and activates DNA-PKcs by promoting DNA-PK holoenzyme formation, thus facilitating the efficiency of nonhomologous end-joining (NHEJ) repair and radioresistance. Notably, YTHDF1 recognizes METTL14-deposited m6A modification on CABLES1 mRNA to enhance its translation in response to ionizing radiation (IR), thereby sustaining the elevation of NHEJ repair capacity and radioresistance. Through high-throughput screening of a small molecule library, we showed that theaflavin 3,3'-digallate (TF-3) specifically disrupts the CABLES1-XRCC6 interaction, thereby sensitizing cancer cells to radiotherapy. Together, our study unveils the molecular mechanism by which CABLES1 potentiates tumor radioresistance, providing a novel synthetic lethal strategy for targeting cancer.
Swine wastewater represents a complex pollution matrix laden with antibiotics, heavy metals, and ammonia, demanding integrated remediation strategies. While microalgae offer a sustainable solution, their efficacy is often limited by low stress tolerance and degradation capacity. Here, we applied adaptive evolution to Chlorella sorokiniana, yielding an evolved strain with significantly enhanced simultaneous removal of ammonia, Cu2+, Zn2+, and antibiotics from real swine wastewater. The evolved strain maintained stable performance across multiple treatment cycles under both microbe-rich and sterile conditions, accompanied by reproducible enrichment of specific bacterial taxa. Transcriptomic analysis identified a novel and highly upregulated metallohydrolase (MHO), which was functionally validated as a key mediator of coremediation through overexpression and mutagenesis. Structural modeling and docking revealed that Cu2+/Zn2+ jointly stabilize the active conformation of MHO, enabling metal-dependent degradation of enrofloxacin and sulfadiazine into less toxic derivatives. The enzyme and the evolved strain exhibited broad pH and temperature tolerance, along with broad-spectrum degradation ability toward multiple fluoroquinolones and sulfonamides. This study unveils a previously unrecognized microalgal detoxification mechanism and demonstrates adaptive evolution as a powerful tool for engineering robust strains for complex wastewater bioremediation.
Catalytic ozonation stands as a pivotal solution for water purification by targeting recalcitrant pollutants. Yet, breaking the intrinsic "adsorption-activation" trade-off is critical for advancing catalytic ozonation and remains a formidable challenge due to the rigid electronic structure of conventional catalysts. Herein, a curvature strain engineering strategy is proposed to modulate the intrinsic activity of single-atom Co sites on hollow carbon spheres. By regulating the support curvature, we introduce precise tensile strain onto the Co-N4 moieties. Theoretical and experimental investigations reveal that although this geometric distortion elongates Co-N bonds, the downshift of the d-band center not only stabilizes the structure by minimizing antibonding orbital filling but also optimizes Co-N/O orbital overlap, establishing a low-resistance hybridization channel. This enables a synergistic "Push-Pull" mechanism: the electron-deficient Co center firmly anchors O3 and stabilizes surface-adsorbed oxygen species (AOS, *O and *OO) ("Pull"); simultaneously, the curvature-induced charge accumulation drives electrons through the optimized orbital channel to trigger O3 activation ("Push"). Quantitative analysis unveils that the curvature-dependent enhancement of single-atom Co as strong Lewis acid sites directly boosts O3 utilization efficiency. Consequently, the high-curvature catalyst exhibits exceptional intrinsic activity for ·OH and AOS generation, significantly outperforming its low-curvature counterparts. Furthermore, this robust atomic structure translates to impressive long-term stability, while the strong anchoring of AOS confers exceptional resistance to environmental interferences. Practical application in real biological effluent demonstrated efficient mineralization and detoxification. This work advances the atomic-level design of robust ozonation catalysts by shifting the paradigm from chemical doping to geometric topological modulation.
Hypoxic pulmonary hypertension (HPH) is a representative vascular remodeling disease with a poor prognosis. Previous findings from our study have implicated the NICD4 (NOTCH4 intracellular domain) in pulmonary artery smooth muscle cells (PASMCs) in the pathogenesis of HPH. However, the underlying regulatory mechanisms remain unclear. In this study, we aimed to elucidate the potential regulatory mechanism of NICD4 in HPH. Using coimmunoprecipitation combined with mass spectrometry, we identified USP8 (ubiquitin-specific peptidase 8) as a novel binding protein of NICD4 in PASMCs. The functional role of USP8 was investigated in vivo using smooth muscle cell-specific Usp8 knockout (Usp8Acta2-/-) mice and in vitro using primarily cultured PASMCs, alongside pharmacological inhibition with DUB-IN-2. USP8 was significantly upregulated in lung tissues from patients with HPH due to interstitial lung disease or chronic obstructive pulmonary disease, HPH rodent models, as well as in hypoxic PASMCs. Usp8 deficiency in Acta2-positive mice (Usp8Acta2-/-) or pharmacological inhibition of USP8 by DUB-IN-2 markedly attenuated HPH development. In vitro, USP8 knockdown suppressed hypoxia-induced PASMC proliferation, migration, and apoptosis resistance by modulating the NICD4-MAPK pathway. Mechanistically, USP8 was bound directly to NICD4 to maintain its stability by removing the K48-linked ubiquitin chain on NICD4 at lysine 1760, thus preventing proteasomal degradation. Furthermore, USP8 can be transcriptionally upregulated by CSL/NICD4 under hypoxia, forming a NICD4/USP8-positive feedback loop. Our study unveils a critical NICD4/USP8-positive feedback loop that drives HPH pathogenesis, highlighting the importance of ubiquitination in pulmonary vascular remodeling. Targeted disruption of this loop represents a promising therapeutic strategy for HPH.
Repeated (parallel or convergent) evolution is often taken as evidence of adaptation and is relevant to the predictability of evolution. However, much remains unknown about the genetic basis of repeated evolution. Here, we use genome editing to progressively knock out all the complete transposable elements (TEs), a rich source of mutations, in the fission yeast Schizosaccharomyces pombe. While progressive knockout has no apparent effect on the biology or fitness of S. pombe under normal conditions, certain TE knockout strains exhibit growth arrest under acid challenge. We next perform parallel replay experiments by evolving S. pombe strains with a single TE and without TE under acid stress. Adaptation occurs rapidly and repeatedly. We do not detect any new TE insertions at appreciable frequencies, indicating that the observed repeated adaptation is not driven by TE insertions. Instead, revival mutations in SPBC409.08, a pseudogene that encodes a putative transporter of the major facilitator superfamily, repeatedly undergo hard or soft selective sweeps and drive adaptation in all the replicates. Although the revival mutations exhibit a trend of diminishing returns, they also repeatedly become fixed in all evolved wild type populations. This work unveils the significance of pseudogene revival on repeated evolution and thus evolutionary predictability.
A cross-sectional design was employed to elucidate the interplay of dietary pattern index scores and seminal and serum biochemical parameters in men presenting to our infertility clinics. Ninety men with idiopathic infertility were enrolled. Semen was collected and evaluated following the World Health Organization (WHO) 2010 guideline for semen analysis (SA). Participants' dietary habits were evaluated using a 168-item semi-quantitative food frequency questionnaire (FFQ). Independent samples t-tests were performed to compare groups with normal and abnormal semen quality parameters in terms of demographic characteristics, energy intake, and initial semen analysis results. The association between dietary scores-the Alternative Healthy Eating Index (AHEI), the dietary total antioxidant capacity (dTAC), and the dietary inflammatory index (DII)-and semen parameters, specifically total antioxidant capacity (TAC) and tumor necrosis factor-alpha (TNF-α) levels, was investigated using one-way analysis of variance (ANOVA) followed by Tukey's post hoc tests for multiple comparisons. Higher intake of advanced glycation end products (AGE) was associated with abnormal semen parameters (p = 0.04). No other significant differences in serum/semen biochemistry were detected (all p-values > 0.05). There were no associations between dTAC, AHEI, and DII scores, and TAC or TNF-α (all p-values > 0.05). However, AHEI quartiles showed significant differences in seminal AGE levels (p = 0.002). Semen malondialdehyde (MDA) levels were higher in the abnormal semen group (1.03 ± 0.28 vs. 0.95 ± 0.22; p = 0.09). No associations were observed between dTAC or DII scores and oxidative stress markers (all p-values > 0.05). AHEI quartiles showed a similar pattern in serum MDA and AGE levels. This study adds to the evidence regarding the dietary impact on male fertility.
Rauvolfia serpentina roots are a therapeutic mainstay in traditional medicines and across time have been seamlessly integrated into the modern medical framework. Its seeds, however, are largely untapped. This study uniquely promotes bioresource valorization and sustainability by unveiling the therapeutic potential of R. serpentina seeds. With quorum sensing-driven remarkable survival strategies, drug-resistant Pseudomonas aeruginosa is a WHO-listed critical priority pathogen. Quorum sensing inhibitors have emerged as promising alternatives to conventional bactericidal antibiotics. Fatty acids (FAs) are also known to interfere with quorum sensing-mediated bacterial pathogenicity rather than exerting selective pressure. In the similar context, here we show the anti-pseudomonal and anti-quorum sensing potential of supercritical-fluid-(CO2)-extract/oleoresins of R. serpentina seeds (RsSO). GC-MS/MS analysis identified long-chain FAs in RsSO. In Caenorhabditis elegans-P. aeruginosa infection model, RsSO demonstrated notable anti-infective property by rescuing host's survival, life span, progeny, behavior patterns and decreasing infection load. RsSO reduced growth and viability of P. aeruginosa and significantly attenuated key virulence factors, including alginate, pyocyanin, siderophores, rhamnolipids and proteases. RsSO interfered in quorum sensing and biofilm formation by downregulating the expression of lasA, rhlR, pelA and algD genes. Quorum sensing inhibition was further validated using the bioindicator microbial strain, Chromobacterium violaceum. Overall, the study highlights the therapeutic potentials of R. serpentina seeds, that are traditionally reserved for germplasm maintenance, for targeting pseudomonal virulence and pathogenesis.
Rechargeable magnesium batteries (RMBs) promise high safety and volumetric energy density, yet their development is limited by the lack of electrolytes enabling reversible Mg anodes. Functional additives provide an effective route to regulate electrolyte structures and interfacial chemistry. Among them, amine and phosphate ester additives, as representative N and O-donor species, exhibit distinct but not yet fully understood roles. This review establishes a unified framework bridging solvation regulation and interfacial reconstruction. The competitive Mg2+ solvation governs the ion pairing configurations, thereby dictating the desolvation and interfacial reactivity. Additive promoted interphase formation is further elucidated through suppressed electrolyte decomposition, construction of conductive SEI components, and solvation-mediated interfacial evolution. Collectively, this review establishes a unified framework in which electrolyte additives act as active molecular regulators that simultaneously tune coordination chemistry, ion association, and interfacial reaction pathways. The insights derived herein highlight key design principles, including modulation of Mg2+ solvation, control of ion-pairing configurations, and programming of interphase chemistry via selective additive participation. These understandings are expected to guide the rational development of next-generation Mg electrolytes toward highly reversible and practically viable RMB systems.
Hypertriglyceridemia is a less frequent yet clinically significant cause of acute pancreatitis, accounting for approximately 4-10% of cases, and is often overlooked when routine laboratory analysis is hindered by lipemia-related analytical interference. We describe two cases of severe hypertriglyceridemia-induced pancreatitis presenting with acute abdominal pain and markedly elevated triglyceride levels. The first case involved polygenic hypertriglyceridemia triggered by undiagnosed diabetes. The second case represented secondary, alcohol-related hypertriglyceridemia. In both cases, lipemia-related laboratory interference complicated the initial evaluation, but prompt recognition and treatment with intravenous insulin led to rapid clinical and biochemical improvement. These cases highlight the need for early consideration of hypertriglyceridemia in pancreatitis of unclear etiology, awareness of laboratory artifacts, and prompt triglyceride-lowering therapy to prevent complications.
Metapopulation models, which consider epidemic spread across interconnected regions, can provide more accurate epidemic predictions compared to isolated models for the corresponding regions. Still, their added complexity and data requirements raise questions about their tangible benefits over simpler, localized models. We develop and validate two networked compartmental metapopulation models for predicting influenza-like illness across Europe: a detailed network-based model, including international travel dynamics, and a simpler mean-field model, aggregating average regional data. The network is constructed using public mobility data and complemented with population densities at border regions. Incidence data of influenza-like illnesses from 28 countries are integrated using an Extended Kalman filter. We show that networked epidemic models effectively capture epidemic dynamics across regions and epidemic phases. The models enable accurate forecasts, missing data imputation, and actionable insights: network models outperform isolated models in forecasting epidemic progression, particularly during critical periods such as wave onsets and peaks, and maintain reliability in scenarios with missing data. The findings unveil and quantify the advantages of metapopulation models for epidemic forecasting in interconnected regions, and pave the way to the integration of mobility and epidemic surveillance to improve the monitoring and prediction of spreading diseases. Flu and other respiratory illnesses spread quickly across countries, especially in regions like Europe where people travel frequently. To better understand and predict these patterns, we built two mathematical models that predict how flu-like illnesses move between countries using information about travel dynamics and national illness reports. These models were tested using data from 28 European countries and found that they can track and forecast outbreaks more accurately than models that look at each country on its own. The models were especially good at predicting when new waves of illness would start and peak, and they could also fill in gaps when some countries had missing or delayed data. These results show that combining mobility and health data can improve how we monitor and anticipate disease spread, helping public health agencies respond faster and more effectively.
Licking as a form of tactile input is widely employed to assess pain levels, suggesting that it may be a restorative behavior in response to injury. However, the exact brain neural mechanisms underlying licking-induced analgesia remain to be elucidated. In this study, we establish a mouse research paradigm to investigate licking-induced analgesia and report that licking behavior significantly reduces pain sensation and pain-related aversion in male mice by triggering the activation of glutamatergic neurons within the gracile nucleus (Gr). Furthermore, we describe the efferent projections from the Gr to the zona incerta (ZI). Importantly, glutamatergic and GABAergic ZI neurons with Gr input (GrZI) neuronal ensembles are efferent to the hindlimb region of the primary somatosensory cortex (S1HL) and the ventral tegmental area (VTA), which regulate the sensory and affective components of licking-induced analgesia, respectively. These findings unveil critical cross-modal supraspinal pathways that enable tactile input to differentially regulate the sensory and affective components of nociception.