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Optimization based evaluation of biological activities and chemical composition of Russula vinosa
Host-directed treatments for tuberculous meningitis utilizing a multi-platform approach across mouse and human models
Atmospheric Pressure Ammonia Synthesis via CO <sub>2</sub> -Coupled Hydrogenation
Biodegradable PLGA nanoparticles of acyclovir and an acyclovir prodrug for potential enhanced therapy against HSV-1 infection
Abstract Herpes simplex virus-1 (HSV-1) is a widespread, recurrent infection that causes herpes simplex keratitis (HSK), an ocular disease that can lead to vision impairment. Conventional acyclovir (ACY) therapy is limited by poor bioavailability, rapid clearance, and frequent dosing. We developed an esterified acyclovir prodrug (ACPD) formulated as biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to improve stability, enable sustained release, and enhance antiviral activity against HSV-1. ACPD was synthesized, ACY-NPs and ACPD-NPs were prepared by nanoprecipitation and single-emulsion solvent evaporation method respectively. Optimized NPs measured 200–300 nm with polydispersity indices of 0.23–0.47 and zeta potentials of − 27 to − 29 mV. ACPD-NPs provided sustained release for 28 days. Cytotoxicity in Vero cells yielded CC50 values of 960 µM (ACY-NPs) and 1000 µM (ACPD-NPs). In HSV-1-infected Vero cells, ACY-NPs exhibited greater antiviral efficacy than free ACY, whereas ACPD and ACPD-NPs showed limited plaque reduction because the tested in vitro media lacked esterase to convert ACPD to ACY. When tested with esterase, cleavage was confirmed by RP-HPLC. Evaluation of ACPD-NPs therapeutic efficacy should be further validated in ocular tissues and in an in vivo ocular model, where esterase enzymes are present. Since corneal tissues contain esterase, its activation may improve ACPD efficacy in in vivo models, which in turn increases bioavailability and overall therapeutic efficacy of ACPD-NPs.
Catalytic electrophilic arene C–H chlorination by rethinking the century-old willgerodt reagent
Prospective comparison of PFBN and PFNA in treating elderly unstable intertrochanteric fractures
High-throughput antigen discovery using Functional Genomic Vaccinology (FGV) identifies protective Streptococcus pneumoniae vaccine candidates
Abstract The discovery of protective antigens remains a major bottleneck in bacterial vaccine development. To overcome this limitation, we present Functional Genomic Vaccinology (FGV), a high-throughput antigen discovery platform integrating genome-wide antigen prediction, proteome-scale screening, and experimental immunogenicity validation to identify protective bacterial antigens. Using FGV, 222 conserved S. pneumoniae proteins are expressed in vitro, incorporated into a protein microarray, and coupled to magnetic beads for mouse vaccination. Protein array analysis shows significant IgG responses in 40% of the screened proteins. Antigen-specific responses measured in human sera guide the prioritisation of 22 candidates, which undergo further studied for their serological and Th17 responses. Four antigens combined in a multicomponent vaccine induces protection from pneumonia and sepsis in mice, with epitope mapping revealing potential protective sites for each protein. These results establish FGV as a scalable, experimentally driven approach for bacterial vaccine discovery and demonstrate its applicability in developing protective pneumococcal vaccines.
Variable NAA concentrations regulate efficient somatic embryogenesis and plant regeneration mediated by FELBs and RTBs in Allium fistulosum
Abstract Somatic embryogenesis (SE) underpins plant regeneration, genetic transformation and virus-free seedling propagation, yet efficient SE systems using root explants remain lacking in Allium fistulosum . Here, we establish and characterize two novel high-efficiency SE pathways mediated by frog egg-like bodies (FELBs) and rhizoid tubers (RTBs) in A. fistulosum , and clarify the regulatory effects of NAA, 2,4-D and TDZ on morphogenesis and plant regeneration. Screening of multiple explants demonstrated that only root segments and stem tips could form translucent mucilaginous callus, while single 2,4-D treatment failed to induce callus at all tested concentrations. Under dark conditions, 10 mg/L NAA maximized callus induction (94.233%) and FELB formation (87.833%) in root explants with significant dose-dependent effects. Phytocytohistological analysis confirmed that FELBs/RTBs develop via three unique stages (pro-embryo, globular embryo, heart/torpedo transitional embryo), distinct from the five canonical stages of typical somatic embryos. For RTB pathway, 5.0 mg/L NAA induced the maximum rhizoid number (54.867 per explant), and subsequent treatment with 20.0 mg/L TDZ under high light achieved optimal RTB production (51.333 per explant). Stage-specific BAP application yielded 100% FELB germination and over 90% RTB plantlet regeneration, with both regenerated seedlings exhibiting > 90% acclimatization survival rates. This study first elucidates the ontogeny of FELB and RTB in monocot A. fistulosum . This is the first study characterizing FELB/RTB developmental stages and ontogeny in a monocot, showing striking homology to eudicotyledons, confirming that FELB- and RTB-mediated somatic embryogenesis can also be achieved in monocots. These optimized systems provide robust technical support for high-frequency regeneration, genetic modification and virus-free seedling production of Allium crops.
An annulus fibrosus anchored nanovector reprograms osteopontin driven macrophages in preclinical disc degeneration models
Abstract Intervertebral disc degeneration is a major cause of low back pain and is associated with inflammatory macrophages that promote annulus fibrosus degeneration via osteopontin signaling. Here we report an annulus fibrosus anchored nanovector carrying small interfering RNA targeting osteopontin. The nanovector first binds annulus fibrosus cells via a targeting peptide and is subsequently activated by reactive oxygen species in inflammatory microenvironments to release macrophage targeted hybrid nanovesicles. This sequential design enables local retention in disc tissue and subsequent delivery to osteopontin expressing macrophages. Using human single cell transcriptomic analysis, in vitro macrophage and annulus fibrosus cell coculture assays, mouse macrophage depletion and infiltration models, and rat disc injury models, we show that this strategy reduces pro inflammatory macrophage polarization, preserves extracellular matrix integrity, and improves disc structure. These findings support an inflammation responsive immunomodulatory approach for disc repair in preclinical models.
Global macroecological patterns of larval size in decapods are governed by temperature and dissolved oxygen
Abstract Macroecological patterns of life history traits, such as larval size, are fundamental to understanding the biogeography and diversity of marine invertebrates. The long-established Thorson’s Rule hypothesizes an increase in maternal energy allocation per offspring with increasing latitude, primarily as an adaptation to offset slower development in cold, food-limited waters. Here, we conduct the largest analysis to date on decapod crustaceans using the size of the first larval instar as a proxy for per offspring investment, to test whether reproductive and developmental patterns are governed by environmental factors on an evolutionary timescale. Our results confirm a strong phylogenetic signal in larval size and reveal that it systematically increases with latitude and greater water depth. This pattern aligns with ambient habitat conditions of lower temperature and higher dissolved oxygen. As expected, we found a strong inverse relationship between larval size and the number of larval stages, confirming that larger, provisioned offspring undergo abbreviated development. In addition, our findings support the hypothesis that increased per offspring investment and larval abbreviation represent a conservative, bet-hedging evolutionary strategy to minimize the vulnerable planktonic duration in cold, high-latitude and deep-sea environments. The deep-sea trend is, therefore, a conceptual extension of the latitudinal gradient into the vertical dimension. This study consolidates the notion that temperature, oxygen and developmental constraint, are the overriding global drivers of offspring investment strategies in decapod crustaceans, shaping their evolutionary pathways and global macroecological patterns.
Root-inspired hierarchical hydrogel-electrode interface enables ultrasensitive sensing
Interactions between automated cooling irrigation and basal leaf removal in cv. Barbera grapevines
Abstract Over a span of two years, a study on Barbera explored the interactive effects of localized cluster nebulization compared to uncooled vines, alongside the presence or absence of late basal leaf removal, using a full factorial design. In this design, basal leaf removal was implemented in both cooled and uncooled vines. The cooling system employed foggers that delivered a water flow of 11.2 L/h, automatically activating when air temperature exceeded 33 °C and relative humidity dropped below 55%. Throughout both seasons, assessments were made on leaf gas exchange, water status, yield components, and grape composition at harvest. In 2025, additional measurements included cluster temperature, soil water potential, and the evaluation of nebulized water dripping onto the soil. While the presence or absence of basal leaf removal had a minor effect on the gas exchange of the immediately upper leaves, leaf function was positively influenced by cooling in both seasons. In 2025, a direct correlation between cooling and non-limiting pre-dawn water potential was established. On average, the presence of basal leaves around the cluster reduced their temperature by 3–4 °C, while nebulization achieved up to 12 °C of cluster cooling. Late basal defoliation had minimal impact on must composition. Conversely, cooling did not affect yield per vine but resulted in higher malic acid at harvest and significantly reduced the concentration and content of total anthocyanins and phenolics compared to uncooled vines. In the absence of cooling, maintaining leaves around the cluster is crucial for controlling sunburn. This study highlights two main and novel findings: (i) the impact on final grape composition can vary depending on how cluster cooling is achieved (e.g., through simple shading or berry wetting), particularly concerning berry pigmentation; (ii) under the chosen activation conditions, under the row soil management and weather and soil characteristics, the irrigation system effectively serves a dual function: providing the expected cooling and enhancing soil moisture with consequent benefits for leaf physiology.
Solar and thermal dual-band electrochromic windows for energy-efficient buildings
The impact of ESG peer pressure on corporate green transformation under dual horizontal and vertical networks
Vactosertib plus pembrolizumab in patients with non-microsatellite instability-high metastatic colorectal or gastric cancer: a multicenter, phase Ib/IIa study
Addressing current ecological impediments in Pakistan through lab-grown meat
Abstract The environment and food security are seriously threatened by the growing demand for food brought on by Pakistan’s expanding population. Lab-grown meat has been proposed globally as a sustainable alternative because it offers reductions of up to 96% in water use, 99% in land use, 45% in energy use, and 96% in greenhouse gas emissions compared to conventional meat production. It also has the potential to address ethical and health issues. Although research on lab-grown meat has advanced globally, this is the first empirical study to look at consumer acceptance and awareness in Pakistan. The purpose of this study is to evaluate how consumer acceptance and rejection are influenced by awareness, perceived benefits and concerns, and socio-demographic characteristics. A cross-sectional online survey was used to collect data from 102 university personnel and students, and the data were analyzed in R. The results showed that acceptability levels are strongly influenced by eco-activism, food preferences, and gender. These findings provide the first empirical evidence on Pakistani consumer perceptions of lab-grown meat and offer insights for researchers, policymakers, climate activists, and meat-industry stakeholders to understand the knowledge gap and the factors driving adoption of lab-grown meat for a sustainable food system.