Functional Differentiation Research Articles

Effect of immersion time on bacterial community structure and sulfur metabolism in biofilm on concrete surface in sewer environment

This study focuses on an overlooked but critical issue: the composition and functional expression of microbial communities on the concrete surface in different areas of sewer pipes. Three immersion conditions were applied to simulate the duration of concrete in different areas ofsewers exposed to sewage, including short-term (L1), long-term (L2) and permanent immersion (L3). The properties of concrete under different immersion conditions and the bacterial diversity and functional capabilities in biofilms on the concrete surface were analyzed. Results showed that the L1 group was dominated by Halothiobacillus, whereas Desulfomicrobium was prominent in the L3 group. Significant differences in the predominant functional microbial communities and metabolic functional genes further confirmed the strong impact of immersion time on the pathways of microbial sulfur metabolism and concrete performance in sewer environment. Compared with the L2 and L3 groups, the decreased sewage immersion time resulted in an increase in the abundance and metabolic activity of sulfur-oxidizing bacteria in the L1 group. Hence, greater mass loss and gypsum production of concrete was found in the L1 group. The structural and functional differentiation of bacterial communities on the concrete surface observed in this study contributes to a better understanding of the uneven corrosion in real sewer pipes.

Stomatal evolution and plant adaptation to future climate.

Global climate change is affecting plant photosynthesis and transpiration processes, as well as increasing weather extremes impacting socio-political and environmental events and decisions for decades to come. One major research challenge in plant biology and ecology is the interaction of photosynthesis with the environment. Stomata control plant gas exchange and their evolution was a crucial innovation that facilitated the earliest land plants to colonize terrestrial environments. Stomata couple homoiohydry, together with cuticles, intercellular gas space, with the endohydric water-conducting system, enabling plants to adapt and diversify across the planet. Plants control stomatal movement in response to environmental change through regulating guard cell turgor mediated by membrane transporters and signaling transduction. However, the origin, evolution, and active control of stomata remain controversial topics. We first review stomatal evolution and diversity, providing fossil and phylogenetic evidence of their origins. We summarize functional evolution of guard cell membrane transporters in the context of climate changes and environmental stresses. Our analyses show that the core signaling elements of stomatal movement are more ancient than stomata, while genes involved in stomatal development co-evolved de novo with the earliest stomata. These results suggest that novel stomatal development-specific genes were acquired during plant evolution, whereas genes regulating stomatal movement, especially cell signaling pathways, were inherited ancestrally and co-opted by dynamic functional differentiation. These two processes reflect the different adaptation strategies during land plant evolution.

Epigenetic impact of hypothyroidism on the functional differentiation of the mammary gland in rats

Mammary gland (MG) lactogenic differentiation involves epigenetic mechanisms. We have previously shown that hypothyroidism (HypoT) alters the MG transcriptome in lactation. However, the role of thyroid hormones (T3 and T4 a. k.a. THs) in epigenetic differentiation of MG is still unknown. We used a model of post-lactating HypoT rats to study in MG: a) Methylation and expression level of Gata3, Elf5, Stat6, Stat5a, Stat5b; b) Expression of Lalba, IL-4Rα and Ncoa1 mRNA; c) Histone H3 acetylation and d) Estrogen and progesterone concentration in serum. HypoT increases the estrogen serum level, decreases the progesterone level, promotes methylation of Stat5a, Stat5b and Stat6, decreasing their mRNA level and of its target genes (Lalba and IL-4Rα) and increases the Ncoa1 mRNA expression and histone H3 acetylation level. Our results proved that HypoT alters the post-lactation MG epigenome and could compromise mammary functional differentiation.

Advancing robust regression: Addressing asymmetric noise with the BLINEX loss function

In real-world applications, regression performance is significantly impeded by complex noise. The choice of loss function is pivotal in building robust regression models, which broadly fall into two categories: bounded symmetric loss functions and asymmetric loss functions. The former struggle with asymmetric noise, while the latter are formulated as segmented functions involving complicates optimization. To handle various noise within a concise framework, we propose a robust regression model based on the asymmetric bounded linear-exponential (BLINEX) loss function, called BXSVR. Firstly, the asymmetry of the BLINEX loss function enables BXSVR to apply different penalties to positively and negatively skewed noise with equal regression error magnitudes to balance the effect of asymmetric noise. Secondly, the boundedness of the BLINEX loss function allows BXSVR to mitigate the detrimental effects of large noise. Thirdly, the smoothness and differentiability of the BLINEX loss function contributes to the optimization of BXSVR. Due to the above properties, BSXVR can adaptively and effectively manage diverse noise scenarios. We use the Nesterov accelerated gradient (NAG) algorithm to optimize BSXVR and analyze the complexity of our algorithm. Extensive experiments on synthetic datasets, real-world datasets, and an application dataset confirm that BXSVR is more competitive than other benchmark methods in terms of various measures.

High-efficiency scattering field modeling in metallic components: a machine-learning-inspired approach

We present a highly efficient method for characterizing the scattering field distribution of surface plasmon polaritons in metallic components by combining the eXtended Pseudospectral Frequency-Domain (X-PSFD) method with an iterative, machine-learning-inspired procedure. Shifting away from traditional matrix operations, we utilize the “Adam” optimizer—an effective and swift machine learning algorithm—to solve the scattering field distribution. Our method encompasses the derivation of the associated cost function and gradient differentiation of the field, leveraging spectral accuracy at Legendre collocation points in the Helmholtz equation. We refine the total-field/scattered-field (TF/SF) formulation within the X-PSFD framework for optimized incident field management and employ Chebyshev–Lagrange interpolation polynomials for rapid, accurate computation of broad-band results. To ensure global accuracy, we introduce unique physical boundary conditions at subdomain interfaces. Demonstrating our method’s robustness and computational efficiency, we model perfect electric conductors (PECs) and silver nanocylinders, and we apply our approach to analyze the excited electric field on subtly distorted metallic surfaces, particularly plasmonic structures, thereby validating its wide-ranging effectiveness.

Naturally occurring polymorphisms reveal the cis-regulatory sites and transcription factors controlling follicular and marginal zone B cells

Abstract The splenic B cell compartment consists of follicular (FoB) and marginal zone (MZB) B cells. In contrast to FoB, MZB exist in a poised state and rapidly respond to blood-borne pathogens in the absence of T cell help, predominately generating a rapid wave of short-lived plasma cells. These differences in responses are driven by differential genetic and epigenetic priming of each subset. MZB epigenetic programming are enriched for bHLH, POU, Rel and RUNT motifs, whereas FoB are enriched for IRF and KLF motifs. MZB also exhibit increased expression of genes associated with Notch signaling, Myc, and mTORC1 pathways. However, it is unclear how sequence specific transcription factors directly and indirectly regulate distinct states in MZB and FoB that underpin B cell activation, differentiation, and acquisition of effector functions. To address this, we generated an F1 hybrid model which utilizes naturally occurring polymorphism present in the wild-derived mouse line Spret/EiJ compared to the reference strain C57BL/6. The monoallelic polymorphisms present in this F1 generation allows us to use the allelic imbalance to dissect how alterations in genetic features impact TF binding, epigenetic architecture, and ultimately resulting gene expression programs. MZB and FoB were sorted from naive (Spret x B6) F1’s and subject to RNA and ATAC-seq. This study aims to define the cis-regulatory mechanisms responsible for the epigenetic and transcriptional differences of FoB and MZB cells.

Enhanced Human Skeletal Muscle Cell Differentiation via the Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

Musculoskeletal diseases, including sarcopenia, are increasingly affecting billions globally. Individuals afflicted with such diseases experience impaired ability to regenerate muscle following injury or volumetric loss. Regeneration is vital for maintaining healthy muscle function and muscle cell differentiation plays a significant role. Our previous studies show that Prostaglandin E2 (PGE2) increases mouse muscle cell differentiation and improves muscle function. Adequate levels of PGE2 in muscle are therefore required for proper regeneration. 15-Hydroxyprostaglandin dehydrogenase (15-PDGH) is an enzyme which degrades PGE2. Previously, studies in rat muscle cells that were treated with SW0033291 (referred hereafter as SW), an inhibitor of 15-PDGH, showed that muscle cell differentiation was enhanced. There is no published study of SW effects on human skeletal muscle myogenesis. Our hypothesis is that when human skeletal muscle cells are treated with SW, the differentiation will be enhanced. To study the effects of SW on human muscle cell differentiation, first the cytotoxicity of SW on human primary skeletal muscle cells (HPSMC) from a young healthy woman were treated with 25, 50, 100, 500 and 1000nM SW for 24h and 48h. No cytotoxicity of SW was detected in all SW-treated groups compared to control group (p>0.05). The effects of SW on myogenic differentiation were measured on day 4 using the methodology of Fusion Index (FI). To study the molecular mechanisms of SW on myogenesis, the expression of myogenic regulator genes (MyoD, MyoG and Mhc) were analyzed by RT-qPCR after the treatment of SW. At day 4 of differentiation, compared to control, no obvious difference of FI was found in 25, 50, 100, and 500nM SW-treated groups (p > 0.05), while a significant increase in FI was found in the 1000nM (p < 0.05) SW0033291-treated group (p<0.05). These results suggest that SW enhances HPMC differentiation. Compared to control, in 25, 50, 100, and 500nM SW-treated groups, the expression of all three genes was not significantly changed (p > 0.05). In the 1000nM SW-treated group, the expression of the myogenic markers MyoD, MyoG and Mhc increased significantly (p < 0.05) by 1.83±0.21-fold, 1.47±0.18-fold, and 2.09±0.37-fold, respectively. These findings confirm our original hypothesis that SW enhances HPSMC differentiation. In conclusion, these results show initial promising application for maintaining proper PGE2 levels and thus allowing for proper human muscle cell differentiation and potential clinical applications in a wide range of musculoskeletal disorders. This work was directly supported by NIH-National Institutes of Aging P01AG039355 (MB) and the George W. and Hazel M. Jay and Evanston Research Endowments (MB). Authors were supported by NIH Grants: National Institutes of Aging (NINDS) 2-R01NS105621; NIA-R01AG056504, NIA-2R01AG060341, National Institutes of Diabetes, Digestive, and Kidney Diseases Kidney (NIDDK)-1R01DK119066 to MB, and National Institutes of Neurological Disorders and Stroke (NINDS) 2-R01NS105621 to MB. Also, NIH/NIDC 1R01DE031872-01 (VV). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Intraspecific variation in fine root morphology of European beech: a root order-based analysis of phenotypic root morphospace

Fine roots are multifunctional organs that may change function with ageing or root branching events from primarily absorptive to resource transport and storage functions. It is not well understood, how fine root branching patterns and related root functional differentiation along the longitudinal root axis change with soil chemical and physical conditions. We examined the variation in fine root branching patterns (the relative frequency of 1st to 4th root orders) and root morphological and chemical traits of European beech trees with soil depth (topsoil vs. subsoil) and soil chemistry (five sites with acid to neutral/alkaline bedrock). Bedrock type and related soil chemistry had an only minor influence on branching patterns: base-poor, infertile sites showed no higher fine root branching than base-rich sites. The contribution of 1st-order root segments to total fine root length decreased at all sites from about 60% in the topsoil (including organic layer) to 45% in the lower subsoil. This change was associated with a decrease in specific root area and root N content and an increase in mean root diameter with soil depth, while root tissue density did not change consistently. We conclude that soil depth (which acts through soil physical and chemical drivers) influences the fine root branching patterns of beech much more than soil chemical variation across soil types. To examine whether changes in root function are indeed triggered by branching events or result from root ageing and diameter growth, spatially explicit root physiological and anatomical studies across root orders are needed.

Differentiation of self, relationship quality, and family functioning among middle adulthood married couples

The purpose of this research was to examine the relationship between differentiation of self, relationship quality, and family functioning among middle-aged married couples in India. The study utilized a purposive sampling method, evaluating 200 participants (100 males and 100 females) aged 40 to 60 years through self-report questionnaires, including the Relationship Assessment Scale, the Differentiation of Self Inventory-Short Form, and the FACES IV Questionnaire. The analyses using regression and correlation techniques revealed significant relationships among differentiation of self, relationship quality, and family functioning. Additionally, no differences were found between nuclear and joint family types, potentially reflecting evolving societal norms and diminishing distinctions between these family structures. This data will further explore the complex interplay between differentiation of self and relationship quality of married couples and how these factors influence family functioning in middle adulthood.

Rungkad Hakekat Penuntutan dalam penjelasan Pasal 132 Undang-Undang nomor 1 tahun 2023 tentang Kitab Undang-Undang Hukum Pidana (KUHP BARU) dan Kegalauan Penyidik/ Penyidik Pembantu Polri

This is different from the term Wetboek van Strafprocesrecht, which in Indonesian means "Criminal Procedure Code". According to legal expert from Hasanuddin University Makassar; Hamzah (1985:13) the Dutch Minister of Justice emphasized that the term "Strafvordering" covers all criminal prosecution procedures. Therefore, it can be concluded that the Criminal Procedure Code in Indonesia is not a descendant of Dutch blue blood/a colonial product, while also confirming that the current Criminal Procedure Code does not merely discuss prosecution procedures. The explanation of Article 132 of the Law of the Republic of Indonesia Number 1 of 2023 concerning the Criminal Code reads "in this provision what is meant by "prosecution" is the judicial process which begins with an investigation". The explanation of Article 132 of the new Criminal Code is a butterfly effect phenomenon if not receiving special attention will certainly damage the essence of prosecutorial authority which is neatly structured in the Indonesian criminal procedural justice system. The explanation of Article 132 of the new Criminal Code does not at all understand Stufenbau's legal theory where the expanded role of prosecutors is in direct contrast to Article 30 paragraph (4) of the Law. -The 1945 Constitution which is the ground norm or basic norm. Apart from that, the Explanation of Article 132 of the New Criminal Code is too vulgar to rebel against the principle of Functional Differentiation which is already compatible with the Indonesian criminal procedural justice system. It requires awareness of all Polri personnel through education about the latent dangers of the explanation of Article 132 of the New Criminal Code. This is in order to explain that this article slightly confuses the existence of investigators/assistant investigators of the National Police so that investigative authority should not be compromised.

Comparative Anatomy of the Dentate Mossy Cells in Nonhuman Primates: Their Spatial Distributions and Axonal Projections Compared With Mouse Mossy Cells.

Glutamatergic mossy cells (MCs) mediate associational and commissural connectivity, exhibiting significant heterogeneity along the septotemporal axis of the mouse dentate gyrus (DG). However, it remains unclear whether the neuronal features of MCs are conserved across mammals. This study compares the neuroanatomy of MCs in the DG of mice and monkeys. The MC marker, calretinin, distinguishes two subpopulations: septal and temporal. Dual-colored fluorescence labeling is utilized to compare the axonal projection patterns of these subpopulations. In both mice and monkeys, septal and temporal MCs project axons across the longitudinal axis of the ipsilateral DG, indicating conserved associational projections. However, unlike in mice, no MC subpopulations in monkeys make commissural projections to the contralateral DG. In monkeys, temporal MCs send associational fibers exclusively to the inner molecular layer, while septal MCs give rise to wide axonal projections spanning multiple molecular layers, akin to equivalent MC subpopulations in mice. Despite conserved septotemporal heterogeneity, interspecies differences are observed in the topological organization of septal MCs, particularly in the relative axonal density in each molecular layer along the septotemporal axis of the DG. In summary, this comparative analysis sheds light on both conserved and divergent features of MCs in the DG of mice and monkeys. These findings have implications for understanding functional differentiation along the septotemporal axis of the DG and contribute to our knowledge of the anatomical evolution of the DG circuit in mammals.

Four phospholipase A2 genes encoded in the western flower thrips genome and their functional differentiation in mediating development and immunity

Eicosanoids are synthesized from phospholipids by the catalytic activity of phospholipase A2 (PLA2). Even though several PLA2s are encoded in the genome of different insect species, their physiological functions are not clearly discriminated. This study identified four PLA2 genes encoded in the western flower thrips, Frankliniella occidentalis. Two PLA2s (Fo-PLA2C and Fo-PLA2D) are predicted to be secretory while the other two PLA2s (Fo-PLA2A and Fo-PLA2B) are intracellular. All four PLA2 genes were expressed in all developmental stages, of which Fo-PLA2B and Fo-PLA2C were highly expressed in larvae while Fo-PLA2A and Fo-PLA2D were highly expressed in adults. Their expressions in different tissues were also detected by fluorescence in situ hybridization. All four PLA2s were detected in the larval and adult intestines and the ovary. Feeding double-stranded RNAs specific to the PLA2 genes specifically suppressed the target transcript levels. Individual RNA interference (RNAi) treatments led to significant developmental retardation, especially in the treatments specific to Fo-PLA2B and Fo-PLA2D. The RNAi treatments also showed that Fo-PLA2B and Fo-PLA2C expressions were required for the induction of immune-associated genes, while Fo-PLA2A and Fo-PLA2D expressions were required for ovary development. These results suggest that four PLA2s are associated with different physiological processes by their unique catalytic activities and expression patterns.

Biological function of bladder smooth muscle cells regulated by multi-modal biomimetic stress

Previous studies have shown that growth arrest, dedifferentiation, and loss of original function occur in cells after multiple generations of culture, which are attributed to the lack of stress stimulation. To investigate the effects of multi-modal biomimetic stress (MMBS) on the biological function of human bladder smooth muscle cells (HBSMCs), a MMBS culture system was established to simulate the stress environment suffered by the bladder, and HBSMCs were loaded with different biomimetic stress for 24 h. Then, cell growth, proliferation and functional differentiation were detected. The results showed that MMBS promoted the growth and proliferation of HBSMCs, and 80 cm H 2O pressure with 4% stretch stress were the most effective in promoting the growth and proliferation of HBSMCs and the expression level of α-smooth muscle actin and smooth muscle protein 22-α. These results suggest that the MMBS culture system will be beneficial in regulating the growth and functional differentiation of HBSMCs in the construction of tissue engineered bladder.

Characteristics of urban network and city functions in the Yangtze River Delta Region: A multi-scale perspective

The development of cities and regions emerges from the complex associations at various spatial levels, highlighting the importance of a multi-scale approach to analyzing regional urban networks. This study attempts to establish a new analysis framework encompassing national, regional, and local dimensions by employing a population flow network in the Yangtze River Delta in China. It explores the inter-city connections and spatial structures of regional urban networks as well as the correlations and differentiations of urban functions under multi-scale interaction. The results indicate that: (1) Regional network demonstrates notable multi-scale interactions with an explicit hierarchical structure; (2) The roles and positions of different cities vary significantly across scales due to economic, administrative, locational, and transportation differences; (3) Different city types can drive their evolution by navigating through rescaling in a diverse multi-scale environment; (4) A positive correlation is observed when comparing the functional behaviors of cities across various scales. This study provides insights for cities to identify their strategic roles and adapt development strategies within the wider network framework, offering theoretical and practical contributions to multi-scale urban networks analysis.

Functional Differentiation of the Succinate Dehydrogenase Subunit SdhC Governs the Sensitivity to SDHI Fungicides, ROS Homeostasis, and Pathogenicity in Fusarium asiaticum.

Succinate dehydrogenase (SDH) is an integral component of the tricarboxylic acid cycle (TCA) and respiratory electron transport chain (ETC), targeted by succinate dehydrogenase inhibitors (SDHIs). Fusarium asiaticum is a prominent phytopathogen causing Fusarium head blight (FHB) on wheat. Here, we characterized the functions of the FaSdhA, FaSdhB, FaSdhC1, FaSdhC2, and FaSdhD subunits. Deletion of FaSdhA, FaSdhB, or FaSdhD resulted in significant growth defects in F. asiaticum. The FaSdhC1 or FaSdhC2 deletion mutants exhibited substantial reductions in fungal growth, conidiation, virulence, and reactive oxygen species (ROS). The FaSdhC1 expression was significantly induced by pydiflumetofen (PYD). The ΔFaSdhC1 mutant displayed hypersensitivity to SDHIs, whereas the ΔFaSdhC2 mutant exhibited resistance against most SDHIs. The transmembrane domains of FaSdhC1 are essential for regulating mycelial growth, virulence, and sensitivity to SDHIs. These findings provided valuable insights into how the two SdhC paralogues regulated the functional integrity of SDH, ROS homeostasis, and the sensitivity to SDHIs in phytopathogenic fungi.

Functional differentiation of olive PLP_deC genes: insights into metabolite biosynthesis and genetic improvement at the whole-genome level.

This study identified 16 pyridoxal phosphate-dependent decarboxylases in olive at the whole-genome level, conducted analyses on their physicochemical properties, evolutionary relationships and characterized their activity. Group II pyridoxal phosphate-dependent decarboxylases (PLP_deC II) mediate the biosynthesis of characteristic olive metabolites, such as oleuropein and hydroxytyrosol. However, there have been no report on the functional differentiation of this gene family at the whole-genome level. This study conducted an exploration of the family members of PLP_deC II at the whole-genome level, identified 16 PLP_deC II genes, and analyzed their gene structure, physicochemical properties, cis-acting elements, phylogenetic evolution, and gene expression patterns. Prokaryotic expression and enzyme activity assays revealed that OeAAD2 and OeAAD4 could catalyze the decarboxylation reaction of tyrosine and dopa, resulting in the formation of their respective amine compounds, but it did not catalyze phenylalanine and tryptophan. Which is an important step in the synthetic pathway of hydroxytyrosol and oleuropein. This finding established the foundational data at the molecular level for studying the functional aspects of the olive PLP_deC II gene family and provided essential gene information for genetic improvement of olive.

Cytochemical localization and synthesis mechanism of the glucomannan in pseudobulbs of Bletilla striata Reichb. f.

The dried pseudobulbs of Bletilla striata, an important traditional Chinese medicine named BaiJi, have an extraordinary polysaccharide content and excellent prospects for medicinal effects. However, the distribution and molecular mechanism underlying biosynthesis are poorly understood. In this study, chemical and immunologic analyses were performed in representative tissues of B. striata, and the results showed that what are conventionally termed Bletilla striata polysaccharides (BSPs) are water-soluble polysaccharides deposited only in pseudobulbs. The structural component of BSPs is glucomannan, with a mannose:glucose mass ratio of ~3:2. BSPs are present in the parenchyma of the pseudobulbs in cells known as glucomannan idioblasts and distributed in the cytoplasm within cellular membranes, but are not contained in the vacuole. Comparative transcriptomics and bioinformatics analyses mapped the pathway from sucrose to BSP and identified BsGPI, BsmanA, and BsCSLAs as the key genes of BSP biosynthesis, suggesting that the functional differentiation of the cellulose synthase-like family A (CSLA) may be critical for the flow of glucomannan to the BSP or cell wall. Subsequently, virus-mediated gene silencing showed that silencing of two CSLAs (Bs03G11846 and Bs03G11849) led to a decrease in BSP content, and yeast two-hybrid and luciferase complementation experiments confirmed that four CSLAs (Bs03G11846, Bs03G11847, Bs03G11848, and Bs03G11849) can form homo- or heterodimers, suggesting that multiple CSLAs may form a large complex that functions in BSP synthesis. Our results provide cytological evidence of BSP and describe the isolation and characterization of candidate genes involved in BSP synthesis, laying a solid foundation for further research on its regulation mechanisms and the genetic engineering breeding of B. striata.

Theranostic Risk Stratification for Thyroid Cancer in the Genomic Paradigm.

Theranostics define diagnostic evaluations directing patient-specific therapeutic decisions. Molecular theranostics involves genomic, transcriptomic, proteomic, metabolomic and finally phenonic definitions thyroid cancer differentiation. It is the functional differentiation that determines the sensitivity and accuracy of RAI imaging as well as the effectiveness of RAI treatment. Total thyroidectomy is performed to empower an anticipated RAI treatment. A preoperative determination of the genomic and transcriptomic profile of the tumor is a strong predictor of response to therapeutic interventions. This article discusses the oncopathophysiologic basis of the theranostic risk stratification approach.

Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis.

γδ T cells play a crucial role in immune surveillance and serve as a bridge between innate and adaptive immunity. However, the metabolic requirements and regulation of γδ T-cell development and function remain poorly understood. In this study, we investigated the role of liver kinase B1 (Lkb1), a serine/threonine kinase that links cellular metabolism with cell growth and proliferation, in γδ T-cell biology. Our findings demonstrate that Lkb1 is not only involved in regulating γδ T lineage commitment but also plays a critical role in γδ T-cell effector function. Specifically, T-cell-specific deletion of Lkb1 resulted in impaired thymocyte development and distinct alterations in γδ T-cell subsets in both the thymus and peripheral lymphoid tissues. Notably, loss of Lkb1 inhibited the commitment of Vγ1 and Vγ4 γδ T cells, promoted the maturation of IL-17-producing Vγ6 γδ T cells, and led to the occurrence of fatal autoimmune hepatitis (AIH). Notably, clearance of γδ T cells or blockade of IL-17 significantly attenuated AIH. Mechanistically, Lkb1 deficiency disrupted metabolic homeostasis and AMPK activity, accompanied by increased mTORC1 activation, thereby causing overactivation of γδ T cells and enhanced apoptosis. Interestingly, activation of AMPK or suppression of mTORC1 signaling effectively inhibited IL-17 levels and attenuated AIH in Lkb1-deficient mice. Our findings highlight the pivotal role of Lkb1 in maintaining the homeostasis of γδ T cells and preventing IL-17-mediated autoimmune diseases, providing new insights into the metabolic programs governing the subset determination and functional differentiation of thymic γδ T cells.

The uncertain Malthusian model on time scales

This work offers a real-world application for the study of fuzzy dynamic equations. First, we propose the novel concept of granular delta differentiability for fuzzy-valued functions defined on time scales with the help of the relative distance measure fuzzy arithmetic and horizontal membership functions. Then, fundamental foundations of fuzzy calculus on time scales are provided. Discussion on the Malthusian model defined on particular time scales to illustrate the proposed approach is presented.