Biology and Life Sciences

Abstract: Background: dengue fever is a viral infection caused by the Dengue Virus (DENV), a positive-sense RNA virus belonging to Flaviviridae family. The virus is transmitted to humans through the bite of the Aedes aegypti mosquito. Worldwide, between 100 and 400 million cases are reported annually. The infection in humans can cause three clinical forms which are related to severity: dengue without warnings signs, dengue with warnings signs, and severe dengue. Mutations in some genes that code for immune system proteins have been linked to the appearance of severe clinical forms of the disease, including TNF-α. The TNF-α plays a key role in the immunopathogenesis of the disease: mutations in this gene can increase the production of TNF-α, favoring cytokine storms and vascular damage, which is associated with severe clinical forms of the disease. Therefore, it is important to study the immunopathogenesis of the disease in the human to try to predict and control the onset of severe clinical forms and fatal cases. Methods: This study explores the link between TNF-α promoter gene polymorphism and dengue severity. We re-cruited 92 laboratory-confirmed dengue cases, including 30 dengue without warnings signs, 43 dengue with warnings signs, and 19 severe dengue. Genotyping was done using amplification by PCR (polymerase chain reaction), Sanger sequencing, and bio-informatics analysis of the TNF-α gene promoter mutations. A logistic regression assessed the association between -308 G/A TNF-α mutation and dengue severity. Results: the mutated genotype -308 G/A TNF-α was detected in 10.5% of severe cases. Interestingly, Severe cases showed higher odds of carrying the mutation than those without warnings signs. Severe cases were twice as likely to possess this mutation compared to those with warnings signs, however, no statistically significant differences were found. Genotype frequencies were consistent with Hardy-Weinberg equilibrium (p = 0.112). The estimated post hoc statistical power was 11.3%. Conclusions: Although no statistically significant association was detected, the TNF-α -308G/A polymorphism showed a trend toward increased susceptibility to severe dengue, with a higher frequency among severe cases than among patients with or without warnings signs.

Abstract: Background/Objective Krüppel-like factor 5 (KLF5) as a member of the zinc finger protein family has been reported in hepatocellular carcinoma (HCC). However, the KLF5 as a novel biomarker for patients with chronic liver diseases (CLD) remains to be identified. This study investigated the clinical values of KLF5 in CLD malignant transformation. Methods KLF5 transcripts from the TCGA database were analyzed with functions and related signaling pathways. Under the ethics committee consent, microarrays were constructed from HCC and noncancerous tissues. KLF5 distribution and expression were analyzed by multiplex immunofluorescence or Western blotting. Bloods were collected from a cohort of cases with CLD. Serum KLF5 levels were quantitatively detected by an enzyme-linked immune-sorbent assay. Results KLF5 at mRNA levels were signifi-cantly upregulating expressed (P<0.001) in HCC tissues more than these in normal livers from the TCGA database. Strong KLF5 expressions were verified in human HCC cell lines or tissues. Clini-copathological features of high KLF5 levels were remarked related (P<0.001) to tumor size, AFP level, HBV infection, tumor/node/metastasis stage and overall survival rate. Furthermore, the in-cidence of KLF5 in the HCC group were significantly higher (P<0.001) more than those in cases with liver cirrhosis or chronic hepatitis. Also, KLF5 was an independent prognostic factor for HCC. Interestingly, the co-expressions of KLF5 with Wnt3a promoted CLD malignant transfor-mation. Conclusion Upregulated KLF5 was associated with CLD malignancy and could be as a promising diagnostic or prognostic biomarker for HCC.

Abstract: Traditional training models in asymmetric sports are based on strong lateralization and side-dominance, a legacy of 19th-century medical dogma. This Scoping Review examines the modern concept of bilateral kinesiophysics, challenging historical assumptions about the superiority of unilateral dominance. A systematic literature review was conducted based on the PRISMA guidelines for scoping reviews. Databases (PubMed, Web of Science, EBSCO, Scopus) were searched for studies on neuroplasticity, interhemispheric transfer (IHTT), cross-education, and sports biomechanics. Evidence suggests that early bimanual and bilateral training optimizes interhemispheric communication, inducing hypertrophy of the corpus callosum and shortening the interhemispheric transfer time (IHTT). The Bilateral Access Model demonstrates that the brain creates abstract, limb-independent motor engrams that are shared by both hemispheres. Moving away from unilateral motor training will lead to an evolution of sports such as tennis and volleyball from a qualitative and spectator perspective. Furthermore, structured bilateral stimulation potentially enhances cognitive adaptability and motor-memory consolidation by optimizing transcallosal pathway efficiency and increasing commissural integrity.

Abstract: Human orphan genes lack identifiable orthologs and remain poorly characterized. We investigated patient-level disease-associated expression changes of human orphan gene transcripts using paired RNA-sequencing data from 220 patients across four cohorts: psoriasis, laryngeal squamous cell carcinoma (LSCC), hepatocellular carcinoma (HCC), and lung adenocarcinoma (LAC). RNA-seq reads were quantified against a combined GRCh37-based reference containing 2,190 human orphan transcripts and 196,317 other transcripts. Significant upregulation versus downregulation of orphan transcripts was observed in 21 versus 3 patients with psoriasis, 26 versus 27 with LSCC, 19 versus 51 with HCC, and 69 versus 0 with LAC (Benjamini-Hochberg-adjusted P < 0.01). These patterns were largely preserved after excluding zero-abundance transcripts and aggregating transcripts into 1,226 orphan gene loci. Rank-based analysis changed the predominant direction in some cohorts, most notably LAC, but retained marked between-cohort differences and bidirectionality within several cohorts. Expression-matched non-orphan controls showed substantially fewer significant directional changes in three cohorts and failed to reproduce the orphan-gene pattern in LAC, indicating that low abundance alone cannot explain the observations. Clinical variables did not readily account for this heterogeneity. Patient-level directional heterogeneity is an underappreciated feature of human orphan gene expression that can be obscured by conventional group-level differential-expression analysis in studies of human disease.

Abstract: Astragalus L. species are recognized for their prominent biological activities, making them useful in the treatment of several diseases. Astragalus spruneri (AS), a perennial prostrate herbaceous wild plant endemic to Southeast Europe and Turkey, remains insufficiently explored to date. The present study investigated total phenolic content, DPPH radical-scavenging activity, and in vitro cytotoxic activity of extracts from aerial parts of A. spruneri. We analyzed the potential of methanolic (ASM) and ethanolic (ASE) extracts to induce cell death in MCF-7 cells using the Incucyte® Cytotox NIR dye and bright-field microscopy. ASE of the leaf was richer in flavonoids, whereas ASM of the leaf displayed higher antioxidant activity than the stem. Live-cell analysis showed that ASE of the leaf exhibited the highest cytotoxic potency (EC50 = 125 μg/mL after 48 hours) and induced a time- and concentration-dependent increase in Cytotox NIR signal. Compared with the vehicle control, ASE of the leaf produced an earlier onset and more significant sustained cytotoxic activity in MCF-7 cells. Western blot analysis further demonstrated that AS extract modulated PUMA protein expression. The Cytotox NIR assay provided new insights into distinct extract- and tissue-dependent cytotoxic responses against MCF-7 cancer cells, with ethanolic leaf extracts exhibiting the most prominent effect. Thus, it can be concluded that A. spruneri serves as a valuable source of natural bioactive compounds with promising cytotoxic activity. Hence, further research is needed to confirm its anticancer potential and assess its safety profile.

Abstract: KRAB-zinc finger proteins (KZFPs) constitute one of the largest and most rapidly evolving families of transcription factors in vertebrates, with particularly extensive expansion and diversification in mammals. While several KZFPs are conserved across species, numerous lineage- and species-specific genes have emerged during mammalian evolution, with a large fraction recognizing and repressing transposable elements (TEs), and particularly endogenous retroviruses (ERVs). The evolutionary relationship between KZFPs and ERVs has traditionally been interpreted through an “arms-race” model, in which recurrent retroviral invasions drive the emergence of new KZFP specificities, while retroelements evolve to escape host repression. This review examines the evidence linking the evolutionary dynamics of KZFPs and ERVs and discuss how their relationship may extend beyond reciprocal adaptation at the level of sequence recognition. In particular, recent comparative genomic analyses reveal that young KZFP genes are frequently organized in highly repetitive genomic clusters that are themselves enriched in young ERVs. Structural variation and segmental duplication within these regions can simultaneously expand KZFP and ERV copy numbers, providing a potential genomic mechanism for their concerted diversification. These observations motivate an “arm-in-arm” model, in which KZFPs and ERVs are not only antagonistic evolutionary partners but can also become physically and evolutionarily intertwined within the same genomic environments. The possibility that KZFP clusters may have a dual role in the evolutionary fate of retroviral sequences is also considered: while KZFP-mediated repression can limit the deleterious effects of newly integrated retroelements and facilitate their persistence, the repetitive and structurally dynamic nature of these loci may create opportunities for subsequent duplication and diversification. Together, these observations broaden the classical arms-race framework and highlight how the interplay between retroviral invasion, host defense, genomic architecture, and sequence cooption can contribute to the generation of genomic and regulatory diversity.

Abstract: Background: Hepatitis B (HBV) infection remains a major public health challenge in Latin America and the Caribbean (LAC), a region characterized by disparities in re-search capacity and limited molecular surveillance. A comprehensive assessment of research output and viral genetic diversity is crucial for informing region-specific control strategies. Methods: An integrated analysis combining bibliometrics, text-mining, and genomics was performed on HBV-related publications indexed in PubMed, Scopus, and Web of Science (1970–2024), along with 9,528 HBV nucleotide sequences from GenBank. Results: The study identified 4,083 publications, of which 72.1% (2,942) originated from Brazil, Mexico, and Argentina. Most were original articles (75.8%; 2,749/3,628) and involved human subjects (95.8%; 2,471/2,580), with a primary focus on serological markers, co-infections, vaccination, genotype characterization, liver pathology, and transfusion safety. Conversely, hepatocellular carcinoma, antiviral therapy, and met-abolic comorbidities were notably underrepresented. In vitro studies were limited, primarily examining viral replication, disease mechanisms, and gene expression, whereas animal studies focused on vaccine development, infection dynamics, and immune responses. Phylogenetic analysis identified eight circulating HBV genotypes (A–H), with genotypes A (43.4%; 4,138/9,528), F (29.3%; 2,787/9,528), and D (19.8%; 1,885/9,528) predominating. Genotype H was found mainly in Mexico (3.2%; 306/9,528). Notably, non-A genotypes accounted for most infections and showed dis-tinct geographic clustering (p < 0.001). Conclusion: HBV research in LAC is marked by pronounced regional disparities in scientific output, critical gaps in experimental and clinical research, and high viral di-versity. These findings underscore the need to strengthen regional research capacity and develop targeted strategies for HBV prevention, treatment, and vaccination to achieve hepatitis B elimination in the region.

Abstract: The new yearly 1.1 million cancer surges and considerably increasing mortality, post-decades of decline, require urgent and effective therapy. Targeted anticancer therapy is an attractive strategy for treating cancer by targeting critical receptors. Homologous Mouse Double-Minute RINGs (MDM2-MDMX RING) negatively regulate the p53 tumour-suppressing role by promoting proteasomal degradation. Interventively, Hinok., MMRi62, MMRi64, and MMRi71 exert a therapeutic downregulation against MDM2-MDMX RING heterodimer by activating p53’s apoptotic arm, but their binding mechanisms remain poorly understood due to the RING domain’s high structural flexibility and lack of co-crystal structures. This study reveals the underlying dynamic conformational stability and flexibility of the MDM_2G443T-MDMX interface, and the potential mechanistic inhibitor binding using the all-atom MD simulations. The MMRi64-bound and Hinok-bound systems exhibited the lowest RMSD values (2.28 Å and 2.34 Å, respectively), indicating significant protein stabilization. MMRi71-bound (1.03 Å) and MMRi64-bound (1.30 Å) complexes displayed the lowest mean RMSF values, demonstrating that these ligands lock the protein into a rigid conformation. Conversely, the MMRi62-bound system showed the highest average RMSD and the highest RMSF (1.74 Å), identifying it as the most flexible complex. The ligand-bound MDM2G443T-MDMX complex underwent notable secondary structure transitions. MMGB/PBSA calculations revealed favorable binding free energies (-22.69, -26.42, and -20.30 kcal/mol) for the key interactions. Arg444, Pro445, Lys473, and Pro476 provided the highest binding free energy contributions to the RING domains. Over the 200 ns simulation, Hinok demonstrated dual interactions with both MDM2G443T-MDMX RING domains, highlighting a potential dual-inhibition mechanism, whereas MMRis interacted selectively with MDM2.

Abstract: Computational biomarkers derived directly from high-dimensional omics data often show limited reproducibility, interpretability, and generalizability. This study evaluates a mechanism-based strategy that integrates curated signaling models with gene-expression data through extreme currents (ECs), minimal steady-state subpathways derived from stoichiometric network models. BioModels models were converted to ECs using PoCaB, ECs were mapped to ENTREZ gene identifiers, and expression of genes within each EC was summarized by the first principal component to generate pathway-informed quantitative features. Features across models were combined and evaluated using Elastic Net, Sparse Group Lasso, gradient boosting, pathway-model boosting, and stacking. Predictive performance and feature-selection stability were assessed using repeated 10 × 10 cross-validation in a breast cancer survival dataset and a prostate cancer case-control dataset. In breast cancer, EC-based methods achieved predictive performance similar to conventional gene- and pathway-based representations. The key advantage was therefore not higher accuracy but greater mechanistic interpretability: each EC feature remains linked to a defined steady-state subpathway in a curated signaling model. Gradient boosting and pathway-model boosting selected features more consistently but produced less sparse models, whereas Sparse Group Lasso and stacking yielded smaller signatures with lower selection stability. In prostate cancer, classification was near-perfect across methods, again making interpretability, stability, and sparsity more informative than marginal differences in accuracy. These results support EC features as a biologically structured and more mechanistically interpretable representation that can preserve predictive performance comparable to conventional alternatives while exposing a practical trade-off between sparse signatures and stable feature selection.

Abstract: The airway epithelial barrier (AEB) is a critical transducer that maintains respiratory homeostasis. This review proposes a novel dual-domain respiratory exposome framework that conceptualizes how the external exposome (cumulative inhaled exposures) and the internal exposome (endogenous immune, metabolic, and endocrine networks) converge to modulate epithelial resilience dynamically. Excessive cumulative pressure disrupts this homeostatic balance, compromising junctional integrity, triggering oxidative stress, and provoking inflammation. These perturbations contribute to maladaptive airway remodeling in chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD). Furthermore, emerging biologics that target epithelial alarmins and barrier-disruptive mediators are summarized. Finally, a next-generation precision medicine paradigm that leverages computational modeling to integrate individual expotypes (external exposure profiles) with endotypes (internal molecular signatures) is outlined. This framework offers a unified strategy for restoring AEB function and optimizing CRD management.

Abstract: Shift work among nurses is a known contributor to circadian rhythm disruptions and related health risks. However, empirical evidence on the circadian phase in this population remains limited. In Japan, the adoption of two-shift systems with 16 h night shifts has reduced the frequency of night work compared to that with traditional rotating schedules. The aim of this study was to quantitatively assess the circadian phases in nurses working on such schedules using the dim light melatonin onset (DLMO). Questionnaires were administered to 31 day-shift nurses and 27 two-shift nurses, of whom 24 and 19, respectively, underwent DLMO assessments. Saliva samples were collected hourly between 20:00 and 24:00 after a day shift in the non-shift work group and before and after a night shift in the shift work group. The baseline DLMO did not differ significantly between groups (21:26 vs. 21:34). Although it was significantly delayed by approximately 30 min following a single night shift (p < 0.01), the magnitude of the phase delay was relatively small. Among shift workers, a later DLMO was associated with greater social jet lag and a shorter phase angle, indicating greater circadian misalignment. These findings suggest that the Japanese two-shift schedule induces only mild and transient circadian disruptions at the group level. However, nurses with a delayed circadian phase may be more vulnerable to circadian misalignment, highlighting the importance of considering individual circadian phases when evaluating adaptations to shift work.

Abstract: Selective fetal growth restriction (sFGR) remains a leading cause of perinatal morbidity in multiple pregnancies; however, its pathogenesis is not yet fully elucidated. Investigating amino acid metabolism in weight-discordant twins may uncover critical metabolic pathways involved in this condition, given the essential roles of amino acids in fetal growth and energy supply. The use of dried blood spots (DBS) enables the non-invasive, retrospective evaluation of neonatal metabolic profiles, providing a unique opportunity to identify sFGR biomarkers and clarify differences between monochorionic (MC) and dichorionic (DC) placentation. In the present study, we profiled 23 amino acids in DBS from 23 twin pairs (11 discordant and 12 concordant), stratified by chorionicity, to identify specific metabolic signatures associated with sFGR and to evaluate their temporal dynamics and clinical significance. Our findings demonstrate that chorionicity determines the amino acid signature of discordance. In MC twins, the larger co-twin displayed significantly elevated glycine, α- and γ-aminobutyric acids, serine, asparagine, and citrulline, alongside reduced proline and tryptophan. In DC twins, the larger co-twin exhibited higher α-aminobutyric acid, valine, leucine, arginine, and citrulline, whereas glycine was elevated in the smaller co-twin. Pathway enrichment analysis further revealed the enrichment of amino acid transport and protein synthesis pathways in MC discordance, and nitric oxide (NO)-dependent signaling in DC discordance. Longitudinal follow-up demonstrated a statistically significant attenuation of intrapair differences for several amino acids by the second time point.

Abstract: Predicting how missense variants alter protein function is central to resolving the genotype-to-phenotype equation, a task now addressed by numerous computational predictors. The most accurate are increasingly opaque, however, limiting both their mechanistic value and their adoption in the clinic. Here we present QAFIsplit, a redesign of the Quantitative Assessment of Functional Impact framework that models variant effect in two interpretable stages: the mutation tolerance of a position, and the deviation introduced by a specific substitution. Framed as the prediction of a molecular endophenotype, QAFIsplit reaches state-of-the-art quantitative accuracy on independent deep mutational scanning benchmarks, surpassing black-box predictors such as AlphaMissense in most protein domains. Carried into clinical variant classification, it performs on par with established clinical tools without ever being trained on clinical labels, and complements meta-predictors without penalty. In the CAGI 7 community experiment, QAFI-based strategies were submitted blindly to four independent disease-gene challenges, backed by strong pre-submission clinical validation (AUC up to 0.99).

Abstract: Nematode growth medium (NGM) has been the standard culture medium for Caenorhabditis elegans for over five decades and contains peptone to support proliferation of the bacterial food source, Escherichia coli OP50. However, the increasing use of paraformaldehyde (PFA)-killed OP50 in studies of metabolism, aging, and host-microbe interactions raise the question of whether peptone remains necessary once bacterial proliferation has been eliminated. Here, we systematically compared conventional and peptone-free NGM using PFA-killed OP50 as the bacterial food source. Peptone removal completely prevented residual bacterial proliferation and markedly reduced fungal contamination, thereby improving culture stability. Although worms cultured on peptone-free NGM exhibited reduced food preference and pharyngeal pumping, they maintained normal growth, reproduction, embryonic viability, lifespan, and chemotactic behavior. Peptone-free NGM also reduced basal intracellular reactive oxygen species (ROS) and lipid accumulation, accompanied by downregulation of genes involved in oxidative stress responses and lipogenesis. In addition, worms displayed enhanced locomotor activity and significantly greater resistance to oxidative, ultraviolet, and thermal stress. Collectively, these findings demonstrate that peptone is dispensable when PFA-killed OP50 is used as the bacterial food source. Peptone-free NGM therefore represents a simple, inexpensive, and practical refinement of the conventional culture system for C. elegans studies employing PFA-killed bacterial diets.

Abstract: The fundamental laws of physics are generally time-reversible. In contrast, the second law of thermodynamics is time-irreversible with respect to macroscopic variables, establishing a link between the arrow of time, entropy growth, coarse-graining, and causality. These are all indispensable prerequisites for life, which is a macroscopic physical process that is necessarily time-irreversible, scale-irreducible, entropy-sensitive, and causally driven. We consider these questions within the axiomatic framework of causal set theory and formulate the law of conservation of causality in terms of fluid dynamics. Its corollary is the principle of causal equivalence, which states that there is no causally preferred scale of observation with respect to conservation laws. Nevertheless, scale still matters. A perfect observer like Laplace’s demon capable of tracking the behavior of matter with unlimited precision at the atomic scale might not detect any signs of life in the universe. Instead, we can agree that life, causality, and the second law of thermodynamics, with their time-irreversible processes, are manifested at macroscopic scales, but nothing of this sort, nor even the arrow of time, exists at the microscopic scales.

Abstract: Anticancer peptides (ACPs) are frequently discussed as a single therapeutic class, yet the term encompasses molecules that perform markedly different jobs: direct tumor-cell killing, intracellular target inhibition, tumor homing and penetration, immune modu-lation, or selective delivery of a separate payload. This functional diversity creates op-portunity, but it also obscures why many potent peptides fail during translation. In this review, we organize ACPs according to their intended pharmacologic role and examine the molecular and product-development principles that determine whether an active sequence can become a useful medicine. Charge, amphipathicity, conformation, target affinity, cellular entry, protease resistance, tissue exposure, and manufacturability must be optimized as an integrated profile rather than as independent attributes. Repre-sentative clinical programs—including the oncolytic peptide LTX-315, the cell-penetrating peptide p28, the stapled peptide ALRN-6924, the tumor-penetrating peptide CEND-1, and the cyclic integrin inhibitor cilengitide—illustrate both the reach of peptide pharmacology and recurrent causes of attrition. We propose a developabil-ity-centered workflow that links mechanism, route of administration, pharmacokinetics, pharmacodynamics, biomarker strategy, formulation, and chemistry, manufacturing, and controls from the beginning of discovery. For the next generation ACP development, the most credible opportunities lie in route-matched local or regional therapy, mecha-nism-based combinations, experimentally constrained artificial intelligence, and pep-tide-enabled delivery systems supported by fit-for-purpose translational models.

Abstract: The following review is an integration and synthesis of a subset of the central auditory nervous system (CANS) and auditory processing (AP) literature of the last 25 years. It encompasses many different aspects of AP, and aims to contribute to an auditory neuroscience knowledgebase suitable for audiologists. ‘Nature’ enables the neonate to be born with an innate and immature auditory nervous system. It is then the turn of ‘nurture’ to play its part, with activity and experiences driving the development. An early ‘nurturing’ experience is when caregivers sing lullabies to infants, with this serving to enhance the fundamental amplitude modulation components that contribute to the formation of a linguistic brain. With the auditory cortical circuits, maturation is a prolonged process, and it is at least adolescence before they approach the precision of the adult brain. Throughout the course of maturation the CANS is constantly and continuously being remodelled, reflecting the dynamic, protracted and activity-dependent nature of most brain development. One consequence of the combination of a prolonged CANS maturation and the unique listening experiences of a childhood is that it is the norm for there to be individual differences in the AP capabilities of similar aged schoolchildren. Negative listening experiences during childhood may sometimes sufficiently hinder an individual's auditory system development to be the cause of listening difficulties. Such listening difficulties can be experienced by children even though the outcome of their standard hearing test is a ‘normal’ pure tone audiogram. Auditory training (AT) offers treatment for some, and equates to additional and intensive ‘nurturing’ of the CANS.

Abstract: Background: Probiotics have been found to be beneficial for human beings through the modulation of intestinal bacteria and inhibition of pathogens. In light of the increased prevalence of multidrug resistant uropathogens, there is a need for alternative therapies than antibiotics. Objectives: This study assessed the capacity of three probiotics (Lactobacillus acidophilus, Lactic Acid Bacillus and Probiotic Consortium) to inhibit three important uropathogens; Escherichia coli, Klebsiella and Staphylococcus aureus with a view of understanding their antibacterial mechanism of action. Methods: In vitro co-cultures were set up to monitor the growth of the pathogens, the development of biofilms and acidification of the culture media for 24 hours. Biofilm biomass inhibition was assessed using crystal violet microtiter plate assays. The molecular responses to probiotics of Escherichia coli was also assessed by analysis of transcriptomics of cell envelope stress genes (omp) and molecular chaperones (dnaK, chap). Results: The efficacy of biofilm inhibition was highly strain-dependent, such that Lactobacillus acidophilus always showed significantly greater broad spectrum biofilm inhibition than both the probiotic consortium and Lactic Acid Bacillus. Escherichia coli Biofilm Inhibition: L. acidophilus gave the highest inhibition of 66.67%, whereas the probiotic consortium inhibited 59.05% of the biofilms and Lactic Acid Bacillus 3.81%. Klebsiella Biofilm Inhibition: The best biofilm inhibition was observed with L. acidophilus with 78.00% compared to the probiotic consortium (61.11%) and Lactic Acid Bacillus (42.50%). Staphylococcus aureus Biofilm Inhibition: L. acidophilus showed maximal biofilm inhibition of 69.09% compared to 54.55% inhibition from the probiotic consortium. Inhibition showed high correlation with medium acidification and antimicrobial metabolite production. Transcriptome analysis: treatment with L. acidophilus caused severe cell envelope stress in E. coli (5.4-fold increase in expression of omp) and impaired intracellular stress response in E. coli with the inhibition of molecular chaperone (dnaK -4.0-fold and chap -2.6-fold. Conclusion: Lactobacillus acidophilus is a strong broad spectrum antibiofilm agent that targets Gram-negative and Gram-positive uropathogens. Antimicrobial activity of this bacterium is exerted through acidification, metabolite production, cell envelope stress induction, and regulation of stress response mechanisms.

Abstract: From the non-equilibrium thermodynamic perspective of the origin of life as a photochemical dissipative structuring (entropy driven) process, we assess the probability of carbon-based life arising on Earth-like analogues orbiting different main-sequence stellar types (O7 V to M2 V). Using black-body spectra normalized to Earth’s solar constant, we calculate surface photon fluxes for an atmosphere like early Archean Earth's in the productive dissipative structuring (P, soft UV-C + UV-B, 205–320 nm) and destructive ionization (D, hard UV-C + EUV, < 205 nm) regions. Stationary concentrations of fundamental molecules and times to reach 99% of these are computed for different chemical degradation (e.g., deamination, hydrolysis, oxidation, etc.) rate constants of, k = 10^-7, 10^-6, and 10^-5 s^-1. For a nominal chemical degradation rate constant of k = 10^-6 s^-1 (t_1/2= 8 days), results show F-, G-, and K-type stars provide the highest stationary concentrations of fundamental molecules and short rise times (weeks to months), while quiescent M-type stars yield extremely low concentrations (∼ 10^-7 relative to G stars) and require years to reach even these values. Flaring M stars improve stationary concentrations by about an order of magnitude (∼ 10^-6 relative to G stars) but produce adverse planet surface environments for complex evolution through dissipative structuring. From this non-equilibrium thermodynamic perspective, carbon-based life like Earth's is to be found most probably on F-, G-, and high-mass K-type stars, with intelligent life arising only on G-type stars. Low mass K- and M-dwarfs are highly unlikely to harbor life unless seeded via panspermia. Biosignatures related to the thermodynamic imperative of photon dissipation are proposed.

Abstract: Marine invertebrates, particularly the sea cucumber (Isostichopus badionotus), represent a rich reservoir of bioactive collagen peptides with high biomedical potential. This study employed a combined proteomic and computational polypharmacology approach to identify and optimize low-molecular-weight (LMW) collagen peptides for regenerative and metabolic applications. LC-MS/MS analysis of a 1–3 kDa enzymatic hydrolysate derived exclusively from purified I. badionotus body wall collagen successfully identified Alpha-2 collagen as the primary constituent. Crucially, the analysis revealed the natural presence of both the angiogenic RGD (Arg-Gly-Asp) and osteogenic GPR (Gly-Pro-Arg) motifs. In silico blind molecular docking demonstrated that the native sequences possessed moderate polypharmacological affinities for Integrin α_V β_3, Dipeptidyl peptidase-4 (DPP4), and Cyclooxygenase-2 (COX-2). Rational structural modification yielded optimized variants (Loc1d and Loc2g) with vastly superior thermodynamic binding scores. Ultimately, a dual-motif chimeric peptide, Loc3a (YGPRGDPRG), was designed, achieving unparalleled binding against ACE (−225.12), DPP4 (−217.25), and Integrin α_V β₃ (−183.93). Physicochemical and ADMET profiling confirmed these peptides are exceptionally stable (Loc3a Instability Index = −36.17), non-allergenic, and possess a pharmacokinetic profile uniquely suited for safe, localized topical application. Supported by systems biology protein-protein interaction (PPI) networks, these findings position the rationally designed I. badionotus collagen derivatives as highly promising, multi-target therapeutic candidates for the simultaneous management of chronic wounds, oxidative stress, and metabolic dysregulation.