Biology and Life Sciences

Abstract: Background: Type 2 inflammation is a hallmark of allergic asthma, and the central role of CD4 Th2 cells in this process is well established. Nevertheless, how CD4 Th2 cells spatially organize and interact with structural cells within tissues to promote airway microenvironment remodeling remains unclear. Methods: In this research, we employed 10x Genomics Visium spatial transcriptomics technology to examine spatial gene expression patterns in lung tissues from a mouse model of asthma induced by house dust mite (HDM). By integrating the SPOTlight algorithm with single-cell transcriptomic reference data, we conducted cell type deconvolution of spatial spots, developed spatial feature scores for CD4 Th2 cells and fibroblasts, and utilized spatially constrained CellChat analysis to deduce ligand-receptor communication between these two cell types in the bronchial microenvironment. Results: Our findings revealed that in asthmatic conditions, CD4 Th2 cells transitioned from a scattered distribution to notable clustering around the bronchi, exhibiting specific spatial co-localization with fibroblasts in the bronchial area (correlation coefficient R=0.19, P=0.0023). In contrast, no positive correlation was found between these cells in non-bronchial regions (R=-0.1, P=0.0001). Further cell communication analysis showed that under normal conditions, interactions between CD4 Th2 cells and fibroblasts were mainly driven by extracellular matrix (ECM)-related signals, particularly the Collagen-Integrin pathway. However, in asthma, this interaction pattern shifted to a pathological form characterized by Cdh1-Cdh1 mediated cell adhesion signaling. Conclusion: This study illustrates that CD4 Th2 cells and fibroblasts establish region-specific spatial cooperative relationships within the asthmatic bronchial microenvironment, with their communication patterns evolving from maintaining tissue structure to facilitating immune cell anchoring and adhesion. These insights offer a novel perspective on the spatial coupling mechanisms underlying type 2 inflammation and airway remodeling.

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques, neurofibrillary tau tangles, neuroinflammation, and progressive cognitive decline. Beyond these classical pathological features, emerging evidence implicates microbial dysbiosis as a contributing factor, with the gut and oral microbiomes currently providing the strongest evidence for microbiome AD associations. In contrast, the ocular microbiome represents a biologically plausible but largely unexplored candidate whose potential contribution to AD pathogenesis remains hypothetical and requires rigorous investigation. The ocular surface shares embryological, anatomical, and functional connections with the central nervous system, and the retina has emerged as a non-invasive window into neurodegenerative brain changes. Bacterial taxa detected in ocular specimens, including Cutibacterium acnes and Acinetobacter johnsonii, overlap with those reported in some studies of AD brain tissue, prompting speculation about an ocular–brain microbial interface. However, this overlap does not establish microbial trafficking, and no direct evidence currently supports the proposition that ocular microorganisms translocate to, colonize, or contribute causally to AD brain pathology. This review critically appraises the existing evidence, graded by methodological rigor and evidence strength, across gut, oral, nasal, ear, and ocular microbiome compartments. We address the substantial methodological challenges inherent in low-biomass microbiome research, emphasize the importance of distinguishing contamination artifacts from biological signals, and delineate the evidence gaps that separate association from causation. We conclude by proposing a research framework that places the ocular microbiome as an emerging hypothesis warranting experimental validation, rather than an established contributor to AD.

Abstract: Respiratory viral infections are a major cause of global morbidity and mortality, partly because they increase susceptibility to secondary bacterial pneumonia and sepsis. Coronaviruses, influenza viruses, parainfluenza viruses, rhinoviruses, and respiratory syncytial virus have each been associated with impaired macrophage antibacterial function, although the underlying evidence differs among virus families. Direct lysosomal-pH measurements and mechanistically resolved links between infection and lysosomal de-acidification are strongest for coronaviruses. Using β-coronaviruses as the primary model for the effect of direct lysosomal disruption on macrophage antimicrobial capacity, this review examines lysosomal exploitation during viral egress, impaired phagosome-lysosome fusion, E-protein-mediated proton conductance, and ORF3a-associated lysosomal injury. It further proposes that the magnitude of these effects is shaped by host-dependent immunometabolic processes. Mitochondrial dysfunction, NAD⁺ depletion, and disrupted mitochondria-lysosome coupling may reduce the ability of macrophages to preserve lysosomal acidity, autophagic competence, and bacterial killing during viral challenge. Together, these mechanisms describe how coronavirus infection compromises macrophage antibacterial defense, and how the resulting susceptibility to secondary bacterial infection is further modulated by the metabolic and inflammatory state of the host cell.

Abstract: Protein conformational inheritance is documented across bacteria, fungi, and neurons, and while several authors have argued for its conceptual inclusion in molecular inheritance frameworks, a concise, widely adopted formal vocabulary that unifies these literatures remains lacking. Naming by pathological outcome rather than mechanism has partitioned prion disease research, adaptive conformational biology, and protein engineering into separate silos despite a shared mechanistic basis. This review formalises the shared mechanism with three terms. Alt-F protein (alternatively folded protein) names the mechanistic class irrespective of outcome. Conformoreplication names the protein-to-protein templated propagation of fold geometry — a third conceptual extension of the Central Dogma. The conformotype is the third molecular inheritance tier, transmitted through cell division independently of DNA sequence or epigenetic marks, initiated by post-translational modifications acting as environmental transducers, and regulated by the chaperone network. The framework identifies blind spots in three research fields that the current sequence-centric paradigm structurally excludes: AMR surveillance that cannot detect conformationally-encoded resistance in genotypically susceptible isolates; industrial biotechnology that screens enzyme variants by sequence but not conformational state; and neurodegeneration therapeutics that targets downstream aggregates rather than the upstream chaperone regulatory failure. To move beyond conceptual identification of these blind spots, the review operationalises each through a concrete analytical pipeline — integrating conformational proteomics, MSA-subsampled AlphaFold screening, and chaperone modulation assays — demonstrating that the conformotype framework is not merely taxonomic but immediately actionable across all three fields.

Abstract: Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains an important constraint to water buffalo (Bubalus bubalis) productivity and a zoonotic risk within Pakistan's dairy sector. In this study, we performed a genome-wide association scan for single intradermal comparative cervical tuberculin (SICCT) reactor status in Nili-Ravi buffalo using the Axiom Buffalo array (90K), followed by a focused evaluation of the SLC11A1 (NRAMP1) candidate region. After quality control, 45,183 SNPs were retained for analysis, and a confirmed subset of 85 animals was used for the targeted study (50 SICCT-negative and 35 SICCT-positive). No marker achieved genome-wide significance in the full scan. However, within the SLC11A1 interval, the strongest nominal association was observed for AX-85139659 (odds ratio = 13.2, Fisher's P = 0.0039), followed by AX-85109412 (odds ratio = 0.09, P = 0.0092) and AX-85128873 (odds ratio = 0.14, P = 0.0457). The first two SNPs were located within a shared 27 kb haplotype block, with complete linkage disequilibrium (D′ = 1.00, r² = 0.76), suggesting that they are likely inherited together rather than representing independent signals. The identified SNPs in the SLC11A1 region provide preliminary evidence for genetic variation associated with bTB resistance in Nili-Ravi buffalo and warrant validation in larger populations.

Abstract: Induced pluripotent stem cells (iPSCs) are prone to genomic instability during prolonged culture, with recurrent chromosomal aberrations conferring selective advantages. Replication stress is a major driver of this instability, yet the repertoire of replication stress‑sensitive loci in iPSCs remains largely unexplored. Here, we mapped aphidico-lin‑sensitive fragile sites (asFS) in three independent iPSC lines using classical cytogenetic break analysis combined with Monte Carlo simulation and MiDAS mapping directly on banded metaphase chromosomes. We identified 28 asFS, which segregated into a highly active Major cluster (8 sites, accounting for 59% of breaks among asFS) and a less active Minor cluster (20 sites). Five universal asFS (9p21, 6q25-26, 20p11-12, 10q22, Xq25) were present in all three lines, representing a tissue‑specific fragility signature of pluripotent stem cells, with Xq25 shifting into the Major cluster after correction for X chromosome dosage. Minor asFS showed preferential co‑localization with physical breakpoints or minimal overlapping regions of recurrent culture‑acquired aberrations, including 20q11.21 (BCL2L1), 1q32 (MDM4), 8q24 (MYC), 17q21 (WNT3‐WNT9B), and 18q21 (DCC/FRA18B). MiDAS mapping validated most asFS and revealed additional replication stress‑sensitive loci in pericentromeric and subtelomeric regions that are difficult to score by conventional G‑banding. Comparison with fragile site maps from other cell types con-firmed tissue specificity, showing that the iPSC asFS repertoire is distinct in rank order and relative activity. Collectively, our findings indicate that the asFS repertoire in iPSCs is hierarchically organized into a stable universal core and a variable peripheral component, and suggest that Minor asFS may serve as initial substrates for adaptive culture‑acquired rearrangements. This work provides a framework for understanding how replication stress and clonal selection shape the mutational landscape of pluripotent stem cells

Abstract: Mammalian cells contain numerous membrane-bound organelles, of which endosomes serve as the initial destination for endocytosed molecules. Therapeutic agents are also internalized by cells and transported to endosomes or phagosomes, and subsequently delivered to lysosomes for degradation. Therefore, these agents require drug delivery systems (DDSs) that enable their escape from endosomes into the cytosol before lysosomal degradation; however, endosomal escape is a major limitation of current DDSs. Studies of bacterial phagosomal escape have revealed mechanisms by which host cells detect damage to organelle membranes. These membrane damage-sensing molecules also recognize membrane damage caused by artificial DDSs or physical energy-based insults. In this review, we summarize molecular mechanisms underlying the early stages of membrane damage in the plasma membrane, lysosomes and bacteria-containing vacuoles (BCVs) to better understand the early stages of endosomal membrane damage in the absence of pathogens. We summarize recent advances in galectins, endosomal sorting complexes required for transport (ESCRT) complexes, sphingomyelin, stress granules, phosphatidylinositol 4-phosphate (PI4P) at membrane contact sites, as well as annexins. We also discuss the recruitment kinetics of these molecules to damaged membranes. Although the recruitment kinetics vary depending on cell type and experimental conditions, this information provides a timeframe for the events following membrane damage, including damage sensing, membrane repair, and degradation of damaged organelles. We also discuss a potential fourth event, fusion between the plasma membrane and endosomes or lysosomes for membrane repair in annexin section. Finally, we summarize approaches for inducing “sterile” endosomal membrane damage. Future development of these approaches may facilitate the design of novel DDSs and physical energy-based strategies for manipulating specific organelles.

Abstract: Background/Objectives: This 12-week randomized controlled trial investigated whether progressive resistance training combined with vitamin D supplementation produces synergistic improvements in cardiometabolic profiles and functional capacities compared with monotherapies in elderly Korean women with type 2 diabetes mellitus (T2DM) and vitamin D deficiency. Methods: In a 2×2 factorial design, 52 women (aged 65–80 years) with T2DM and serum 25(OH)D <20 ng/mL were assigned to four groups: Exercise + Vitamin D (Ex+VitD, n=15), Exercise + Placebo (Ex+Placebo, n=13), Vitamin D only (VitD, n=11), or Control (n=13). Exercise groups completed supervised progressive resistance training three times weekly, and vitamin D groups received 2,000 IU/day cholecalciferol. Results: The Ex+VitD group achieved significant improvements in HbA1c (−0.13%, p=0.019), fasting glucose (−0.79 mmol/L, p<0.001), insulin (−1.96 μU/mL, p=0.050), and HOMA-IR (−0.77, p=0.020). Serum 25(OH)D increased substantially (+15.57 ng/mL, p<0.001). Calcitonin rose exclusively in the Ex+VitD group (+2.57 pg/mL, p<0.001, d=3.34), while monotherapies showed no change. Total cholesterol (−23.93 mg/dL), triglycerides (−25.07 mg/dL), and LDL-cholesterol (−10.20 mg/dL) decreased significantly. Both exercise groups showed marked strength gains (chair stand +8.33 to +10.00 repetitions, p<0.001) and balance improvements (functional reach +2.47 to +4.46 cm, p≤0.033). Conclusions: Twelve weeks of progressive resistance training combined with vitamin D supplementation produced synergistic improvements in glycemic control, insulin sensitivity, calcitonin secretion, muscular strength, and lipid metabolism in elderly women with T2DM and vitamin D deficiency, targeting complementary pathways that neither intervention engaged alone.

Abstract: Microbiological bioproducts constitute a rapidly growing group of preparations used in modern agriculture and play a significant role in achieving the goals of sustainable crop production. Because they contain live microorganisms or their metabolites, they promote plant growth and development, increase nutrient availability, improve soil properties, and suppress pathogen development, thereby representing a promising alternative to conventional fertilizers and chemical plant protection products. The aim of this study was to analyze the current state of knowledge on the application of microorganisms in agriculture, with a particular focus on their mechanisms of action, bioproduct formulation principles, and the legal requirements for their registration and marketing in Poland and the European Union. The paper presents a classification of microbiological bioproducts and compares their properties with those of chemical products. The stages of product formulation, including strain selection and identification, mass production, the choice of appropriate carriers, and stabilization methods, are discussed. Furthermore, the primary mechanisms of microbial action on plants are characterized, including biological nitrogen fixation, phosphate solubilization, the production of phytohormones and siderophores, and pathogen biocontrol mechanisms. In addition, the current legal regulations governing the classification, registration, and quality and safety requirements of agricultural microbiological products are outlined. The analysis indicates that microbiological bioproducts have significant potential to support sustainable crop production and mitigate the negative environmental impacts of agriculture. However, their widespread adoption requires further advancements in formulation technologies, quality standardization, and the improvement and harmonization of existing legal framework.

Abstract: Huge strides have been made in our ability to assign protein location or molecules that modify proteins (function). These improvements have been borne out of novel methodologies that are each compatible with proteomics analytical methods. Unfortunately, our ability to assign function and location simultaneously has not progressed. This is mainly traceable to significant, and apparently irreconcilable differences in the way spatial and functional omics methods are performed. Filling these gaps is a significant problem, but could open ways to novel small molecule interventions. We discuss why uniting spatial and functional paradigms has proven difficult in terms of the chemistry behind the processes used. Based on these discussions, we introduce a new concept “spatiofunctional omics”. This approach is designed to deliver both spatial and functional intelligence in a single experiment. Several recent publications from our laboratory testify to the utility of spatiofunctional omics as a paradigm. We further discuss methods to inherently correct for potential low spatial resolution by combining spatiofunctional approaches with traditional proximity profiling data. We proceed to discuss how developing new techniques that can be blended with existing, complementary strategies, offers improved reliability. We finally extend this logic to the notion that no technique will cover all the multidimensional space required to assay the downstream effects of protein-specific “functionalization”. It is thus inherently important that spatiofunctional profiling methods be compatible with a wide range of protocols. REX technologies offer such possibilities.

Abstract: The origin of creation and the emergence of subjective experience remain among the deepest unsolved questions in science. We propose a unified hypothesis in which 'creation' is any entity or process with a beginning and an end in space and time. This premise implies the existence of a universal ground state as the source which is all-pervading, eternal, uniform and memoryless. All observable phenomena arise as cyclical fluctuations within this ground state, which simultaneously serves as a stable universal reference (ground zero) enabling the detection of change. We redefine consciousness as a measurement problem enabled by this universal ground zero reference, with subjective experience originating from the resonance and energy redistribution between perceived signals and stored memory cycles. This re-frames the hard problem of consciousness by grounding perception in a universal substrate present at every point in the universe. The apparent differences in awareness between different points in space is arising from their state of evolution with variation in memory capacity and responsiveness.

Abstract: Background/Objectives: Albania occupies a key geographic position in the Balkan Pen-insula, yet its fine scale population structure and genetic relationship with neighboring European populations, remain incompletely characterized. This study investigated the regional genetic structure of the Albanian population and its affinities within the broader European context using autosomal short tandem repeats (STR) markers. Methods: A total of 2000 unrelated individuals representing all 12 administrative regions of Albania were genotyped for 16 autosomal STR loci (D3S1358, VWA, D16S539, D2S1338, D8S1179, D21S11, D18S51, D19S433, THO1, FGA, D10S1248, D22S1045, D2S441, D1S1656, D12S391 and SE33) together with the Amelogenin sex marker. Individuals were grouped into Northern, Central and Southern Albania. Population structure was evaluated using Principal Component Analysis (PCA), pairwise Weir-Cockerham F_ST estimates, Nei’s standard genetic distance, and phylogenetic reconstruction. Comparative analysis in-cluded reference populations from Greece, Italy, Montenegro, Bosnia and Herzegovina, Slovenia, Slovakia, Hungary, Germany and France, using published allele frequency data. Results: PCA demonstrated extensive overlap among individuals from all three Albanian regions, with no distinct regional clustering. The principal components explained only a small proportion of the total genetic variation (PC1 = 0.80%; PC2 = 0.77%), indicating minimal population substructure. F_ST estimates between Northern, Central and South Albania were consistently close to zero, with bootstrap – derived 95% confidence inter-vals overlapping zero for all comparisons, confirming the absence of statistically signif-icance regional differentiation. Nei’s genetic distances among the analyzed European populations varies from approximately 0.004 to 0.014, consistent with the low levels of differentiation typically observed among European STR datasets. Phylogenetic analysis identified three major clusters: Albania and Greece formed the closest genetic pair, with Montenegro and subsequently Italy joinig this southeastern cluster: France and Germany clustered together; whereas Bosnia nd Herzegovina, Slovenia, Slovakia and Hungary formed a distinct Central Balkan/Central European cluster. Conclusions: The Albanian population exhibits a high degree of genetic homogeneity across its geographic regions, reflecting extensive historical gene flow and limited inter-nal population stratification. Comparative analyses place Albanians in close genetic proximity to neighboring southeastern European populations, particularly Greece, while preserving the broader genetic structure expected across Europe.

Abstract: Spring low temperature stress (SLTS) frequently occurs during with the critical stage from stamen and pistil differentiation to anther connective formation in wheat, severely disrupting young spike development and reducing grain yield (GY). Although postponed phosphorus (P) and potassium (K) fertilization can alleviate SLTS-induced damage, but the optimal basal–topdressing ratio of P and K fertilizers remains unclear. In this study, wheat cultivar Yannong 19 was subjected to three temperature regimes (11℃, 4℃, and −4℃) at the anther connective stage in climate chambers, and four P-K fertilization modes with basal: topdressing ratios of 10:0 (R1, control), 7:3 (R2), 5:5 (R3), and 3:7 (R4) were evaluated. The effects of these treatments on soil nutrient availability, plant N/P/K uptake and utilization, and GY were investigated. Results showed that SLTS inhibited soil organic carbon decomposition, reduced soil nutrient availability, suppressed photosynthesis and soluble sugar accumulation, decreased fertilizer use efficiency, and significantly reduced grain number per spike, 1000-grain weight, and GY. Postponed P-K fertilization (R2-R4) promoted organic carbon mineralization, increased soil total N, available P and available K contents, reduced soil C/N and N/P stoichiometric ratios, enhanced plant nutrient uptake and translocation, improved photosynthetic capacity and cold resistance, and promoted dry matter accumulation. Consequently, grains number per spike, 1000-grain weight and GY increased by up to 11.2%, 6.3% and 38.5%, respectively, under postponed fertilization regimes. Among all modes, R3 (5:5) exhibited the best overall performance. These findings demonstrate that postponed P-K fertilization, particularly with a balanced basal−topdressing ratio, is an effective strategy to mitigate SLTS-induced yield losses in wheat by improving soil nutrient supply, plant physiological status, and fertilizer efficiency.

Abstract: Chinese hamster ovary (CHO) cells are the principal platform for manufacturing recombinant biopharmaceuticals, but sustained production can exceed the protein-folding capacity of the endoplasmic reticulum (ER). Binding immunoglobulin protein (BiP/GRP78), encoded by Hspa5, is a major ER chaperone that supports folding and modulates unfolded protein response (UPR) signaling, yet its overexpression has been reported as beneficial or inhibitory depending on the product. Here, we stably overexpressed the Chinese hamster Hspa5 coding sequence in a CHO line producing a dulaglutide analogue comprising a modified GLP-1 peptide fused to human IgG4 Fc and compared BiP-overexpressing (DUL-BiP) cells with empty-vector (DUL-Neo) controls in fed-batch culture. At constant temperature, BiP overexpression did not alter viable cell density or viability, but DUL-BiP cells maintained higher late-stage cell-specific productivity, prolonged productive secretion by approximately two days, and reached a 40% higher final titer; under a temperature shift, maximal cell density decreased. Control cells induced endogenous BiP only at late culture stages, whereas DUL-BiP cells maintained an elevated BiP level from the start. Intracellular GLP-1–Fc did not accumulate progressively, and culture-associated changes in cleaved ATF6, eIF2α phosphorylation, and CHOP persisted in both lines. Constitutive host-derived BiP expression therefore enlarges the secretory reserve, sustaining late-stage secretion rather than increasing growth; the benefit depends on product-specific folding requirements.

Abstract: Bioactive peptides are an important source of therapeutic molecules and molecular scaffolds involved in defense, signaling, and immune regulation. Despite the extraordinary diversity of Coleoptera, the structural landscape of beetle-derived bioactive peptides remains largely unexplored, limiting our understanding of their evolutionary diversity and biotechnological potential. Here, we performed a large-scale structural survey of predicted toxin-like peptide scaffolds across publicly available Coleoptera transcriptomes by integrating transcriptome mining, peptide maturation prediction, physicochemical characterization, AlphaFold 3 structural modeling, structural similarity analyses, and interpretable machine learning. We identified 291 candidate peptides, of which 155 contained canonical signal peptides and 273 produced mature peptides within the expected size range of known bioactive peptides. Structural analyses revealed that, despite extensive sequence diversity, many candidates converged toward a comparatively restricted repertoire of compact cysteine-rich architectures, suggesting that structural conservation exceeds primary sequence conservation during peptide diversification. Comparative structural analyses further identified recurrent protein architectures shared across multiple beetle lineages, while machine learning prioritization integrated structural and biochemical descriptors to identify high-confidence candidates for future functional characterization. These analyses establish the first structural atlas of predicted toxin-like peptides across Coleoptera and demonstrate that structure-guided transcriptome mining provides a powerful framework for uncovering evolutionarily conserved bioactive peptide scaffolds that would remain largely undetected using sequence-based approaches alone. Beyond expanding our understanding of peptide evolution in beetles, this resource is a foundation for future structural, functional, and biotechnological exploration of bioactive peptides in underexplored animal groups.

Abstract: The loss of a companion animal can provoke grief whose intensity rivals human bereavement, yet its biological basis remains largely uncharted. This structured narrative review synthesizes neurobiological, endocrinological, immunological, and psychosocial evidence into a mechanistic framework offered not as established fact but as a source of testable hypotheses. We trace the substrates of the human-animal bond across six interacting systems and propose how disruption of each upon an animal's death may drive grief. Three carry comparatively robust analogical support (oxytocinergic signaling, hypothalamic-pituitary-adrenal [HPA] axis regulation, and neuroinflammatory activation) and three are more exploratory (dopaminergic, serotonergic, and endocannabinoid pathways). Integrating extracted study-level data into transparent prioritization heuristics, we identify the HPA axis, assessed with its coupled oxytocinergic partner, as the most defensible first target for a direct biomarker study, a conclusion robust across three methodologically independent analyses. No direct pet-loss evidence yet supports any proposal, and this gap is the review's central motivation. As applied context, we address euthanasia-related guilt, disenfranchised grief under East Asian norms (a tentative "double disenfranchisement" hypothesis we want tested), assessment instruments, evidence-graded therapies, a Korean tool-development roadmap, and One Health research priorities.

Abstract: Background: Glucagon-like peptide-1 (GLP-1) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists reduce cardiovascular events, but the underlying cardiac structural remodeling remains unclear. Objectives: This study evaluated longitudinal cardiac remodeling associated with semaglutide and tirzepatide in a real-world cohort and determined its weight-loss dependency. Methods: Using electronic health records from a federated network, we analyzed longitudinal echocardiograms of patients prescribed semaglutide or tirzepatide, stratified by 12-month weight loss into super-responders (>15%), moderate-responders (5%-15%), and minimal-responders (<5%). Additionally, GLP-1/GIP patients with >5% weight loss were propensity-matched with non-GLP-1/GIP weight-loss medication control patients on demographics and baseline body mass index. Results: Among 3,500 GLP-1/GIP patients (422 weight-loss super-responders, 1,426 moderate-responder, 1,652 minimal-responders), left ventricular (LV) mass decreased across all groups proportional to weight loss (super-responders: 198.4 ± 69.6 to 176.6 ± 66.0 g; moderate-responders: 210.7 ± 74.0 to 195.8 ± 68.1 g; minimal-responders: 216.1 ± 68.4 to 204.8 ± 67.4 g; p < 0.001). Left atrial volume and LV systolic and diastolic function did not change. Among weight-loss super-responders, semaglutide (n = 159) showed greater LV mass reduction than tirzepatide (n = 89) (Cohen’s d = -0.389 vs. -0.263), while tirzepatide showed small improvements in right ventricular function. Compared to matched non-GLP-1/GIP controls (n = 118/group), GLP-1/GIP patients exhibited significant LV mass reduction not observed in controls despite similar weight loss. Conclusions: Real-world findings demonstrate that incretin-based therapies are associated with reverse cardiac remodeling characterized by weight-loss-dependent and incretin-specific mechanisms, with potentially distinct structural targets among agents.

Abstract: Background: Pilonidal sinus disease (PSD) is a chronic inflammatory condition predominantly affecting young adults. Minimally invasive techniques such as pit-picking have gained increasing popularity; however, recurrence rates remain a significant concern. Microwave ablation (MWA) has recently emerged as a novel adjunctive modality that may improve treatment durability through enhanced destruction of residual sinus epithelium. Materials and Methods: This retrospective multicenter comparative cohort study included 403 consecutive patients treated for PSD between January 2022 and January 2024. Among these, 200 patients underwent pit-picking combined with MWA (MWA group) and 203 underwent pit-picking alone (PP group). Recurrence was defined as any clinical reappearance of pit, abscess, or discharging sinus confirmed at follow-up. Primary outcome was disease recurrence; secondary outcomes included operative time, postoperative pain (VAS), complications, SSI, wound healing time, pain-free sitting, and return to work. Multivariable logistic regression and Kaplan–Meier analysis were performed. Results: MWA group demonstrated superior postoperative outcomes: shorter pain-free sitting (2 vs 4 days), healing time (11 vs 16 days), and return to work (3 vs 5 days). Overall complication rates were lower (4.5% vs 11.3%; OR 0.37, 95% CI 0.16–0.84; p=0.018). Recurrence rates were significantly reduced (5.5% vs 13.8%; OR 0.36, 95% CI 0.17–0.75; p=0.006). MWA treatment remained an independent predictor of reduced recurrence on multivariable analysis (adjusted OR 0.35, 95% CI 0.16–0.76; p=0.007). Conclusion: Pit-picking combined with microwave ablation is a safe and effective minimally invasive treatment strategy for PSD, significantly improving postoperative recovery, reducing morbidity, and lowering recurrence rates. Further prospective randomized studies with longer follow-up are warranted.

Abstract: Taste supports survival by helping animals identify useful nutrients and avoid harmful excess. Sodium is essential for extracellular fluid balance, osmotic regulation, nerve transmission, muscle contraction, and nutrient transport, but it is continually lost and must be replaced through diet. This review proposes the Sodium Priority Hypothesis: sodium is a primary nutritional target whose consumption is enabled by converging sensory mechanisms. Sodium chloride provides the dominant route to pure saltiness, while sodium-linked umami, bitterness suppression, and taste-mixture modulation may further support sodium acquisition and food acceptance. Potassium provides an important contrast because it is essential but has weaker salty quality, bitter or metallic side notes, and does not reproduce sodium’s bitterness-suppressing effect in model savory systems. By linking sodium detection, sodium-linked umami, bitterness suppression, and food-mixture modulation with appetite and potential pre-ingestive or post-ingestive regulation, the hypothesis extends the taste-nutrition interface to sodium acquisition. The hypothesis does not reject umami as a protein-related signal, but proposes that sodium-linked umami may have dual relevance for protein food recognition and sodium acquisition. This framework generates testable predictions and may inform sodium reduction, food reformulation, and dietary guidance.

Abstract: Background. The dominant clinical manifestation of aging is not mortality but the progressive depletion of functional reserve—the surplus physiological capacity separating independent function from disability. Existing geroscience frameworks describe the molecular processes of aging in extraordinary detail yet offer the point-of-care clinician little basis for prioritizing targets. Objective. To reframe functional aging as a control-systems problem and to define the minimum set of physiological capacities whose preservation maintains functional reserve. Framework. Aging is modeled as progressive instability within a coupled, bidirectional mitochondrial–epigenetic regulatory axis. Candidate capacities were evaluated against three operational criteria—independence, necessity, and modifiability. Results. Five capacities satisfy these criteria: bioenergetic capacity, endocrine signaling integrity, molecular quality control, adaptive (hormetic) stress response, and neuro-autonomic regulation. Each protects the central axis; together they govern the trajectory of functional reserve. Modifiable interventions are mapped onto these capacities in a separate operational layer. Conclusions. The framework yields a causally ordered, clinically actionable, and falsifiable architecture in which functional reserve is the primary therapeutic target and lifespan a downstream consequence. It is testable against existing longitudinal cohorts without new data collection.