Browse Articles

AMP-36 exhibits potent therapeutic efficacy against MRSA pneumonia through membrane-target mechanism

Abstract The rapid emergence of multidrug-resistant (MDR) bacteria poses a critical challenge in hospital-acquired infections, particularly methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Antimicrobial peptides (AMPs) are promising therapeutic candidates due to their broad-spectrum antibacterial activity. Here, we report AMP-36, a 36-amino acid antimicrobial peptide rationally designed and synthesized from SAAP-148, exhibits potent antibacterial activity. AMP-36 displayed low micromolar minimum inhibitory concentrations and rapid bactericidal activity in vitro, achieving near-complete bacterial killing within 8 h. In the murine pneumonia model, AMP-36 significantly reduced bacterial burden in bronchoalveolar lavage fluid (BALF) and markedly alleviated lung inflammation. Scanning electron microscopy (SEM) revealed pronounced disruption of MRSA cell membranes following AMP-36 treatment, indicating membrane damage as the primary antibacterial mechanism. Transcriptomic analysis further demonstrated its broad transcriptional alterations. Collectively, these findings highlight AMP-36 as a promising therapeutic candidate for MRSA pneumonia and provide mechanistic insights into its antimicrobial action.

Comparable immunogenicity from murine blood collection methods in intranasal gonococcal vaccination with ACP and MtrE supports refinement of preclinical vaccine studies

Environmental transformational leadership and employee green behavior through psychological mechanisms

Metabolomics study of the effects of zinc sulfate in minimal hepatic encephalopathy

Abstract Minimal hepatic encephalopathy (MHE) is a cognitive, motor, and sleep-related disorder resulting from liver impairment, often linked to elevated ammonia levels. Zinc deficiency is common in patients with cirrhosis and has been associated with cognitive dysfunction. Zinc supplementation has shown promise in improving MHE, but the underlying metabolic mechanisms remain unclear. To investigate the therapeutic effects of zinc sulfate on metabolic changes in the striatum of MHE rats using 1 H-NMR-based metabolomics. We established a rat model of MHE using partial portal vein ligation and administered zinc sulfate to a subset of rats. A control group was included for comparison. Behavioral assessments of spatial learning and memory were performed using the Morris water maze (MWM). Striatum metabolites were analyzed through 1 H-NMR spectroscopy, and key metabolic pathways were identified using statistical analyzes. Zinc supplementation improved cognitive performance in the MHE rats, evidenced by reduced escape latency in the MWM. Metabolomics analysis identified 47 metabolites, with 10 key metabolites showing significant differences between MHE and control groups. Zinc supplementation normalized several disrupted pathways, including those related to glycolysis, glutamine metabolism, and BCAA metabolism. Key metabolites affected by zinc included lactate, alanine, glutamate, and branched-chain amino acids. Zinc sulfate supplementation alleviates cognitive impairments in MHE rats by restoring disrupted metabolic pathways, including nitrogen metabolism. The findings suggest that zinc plays a therapeutic role in improving brain function in MHE.

Surface hydrophobicity and rigidity determines protein corona on orally delivered nanoparticles treating colitis

Peripheral blood mononuclear cell gene expression signatures predict long-term survivorship in canine DLBCL

Abstract Pet dogs spontaneously develop a form of diffuse large B cell lymphoma (DLBCL) that recapitulates many of the features of double hit ( MYC/BCL2 ) human DLBCL. We recently completed a clinical trial in dogs with DLBCL using a combination of canine anti-CD20 antibody and low dose doxorubicin followed by one of three small molecule immune-modulating agents (KPT-9274, TAK-981 or RV1001). Clinical outcomes and tumor specific biomarkers of response from these dogs have been previously reported. In this study, we used the NanoString Canine IO panel to assess dynamic changes in gene counts from peripheral blood mononuclear cells (PBMCs) collected longitudinally from these from dogs over the course of their treatment to identify immune correlates associated with early relapse versus long-term survivorship. Increases in interferon-stimulated gene (ISG) signatures and immune skewing genes [ CCR9 , CD209 (DC-SIGN), CMKLR and DDX58 (RIG-I)] were associated with shorter (< 400 day) survival times and early relapse. In contrast, CD1E and CCL14 were elevated post-immunotherapy in long-term (> 400 day) survivors, suggesting that these may be associated with protective immune signatures. Examining genes that were expressed in short- versus long-term survivors early on in the treatment regimen identified TBHD , NPNT and ISG20 as elevated in dogs with shorter survival times at day 7. To facilitate point-of-care PBMC gene expression testing that could be used to distinguish those dogs likely to require more intensive treatment regimens in advance of relapse, we developed qPCR assays for TBHD , NPNT and ISG20 . Together these data provide proof of principle that biomarker interrogation in PBMCs can help predict early relapse and poor responders to inform clinical management of DLBCL.

Sub-5 nm high-entropy nanoalloys beyond the hume-rothery limit

Reducing PTSD symptoms through unconscious intervention

Intrusive traumatic memories are a hallmark symptom of posttraumatic stress disorder (PTSD). Conventional therapies typically require explicit and emotionally distressing reexposure to trauma cues, often leading to high dropout rates among severely affected patients. This study examined whether trauma memory intrusions could be effectively reduced through unconscious intervention, minimizing emotional distress by subliminally presenting trauma-related visual cues during bilateral eye movement intervention, a core component of eye movement desensitization and reprocessing. Four experiments tested this approach: two utilizing an analogue trauma paradigm in healthy participants (N = 164), one clinical study with PTSD patients (N = 60), and one supplementary experiment in a subclinical sample (N = 30). Results demonstrated that this unconscious intervention significantly reduced the frequency of intrusive memories and effectively alleviated PTSD symptoms, with the frequency of intrusion decreasing by 56% and lasting at least 2 mo in PTSD patients. Critically, patients previously unable to tolerate conventional exposure therapy became capable of consciously confronting trauma cues postintervention. This unconscious intervention approach is brief (under 2 h total), minimally distressing, and requires limited patient disclosure, offering a promising alternative or adjunct to traditional trauma-focused treatments. It may substantially enhance treatment accessibility and tolerability for severely traumatized individuals otherwise unable to engage with traditional therapies.

An efficient prediction based data collection method for wireless sensor networks using hybrid fuzzy clustering and optimized deep maxout neural networks

Reversible crosslinking strategy for dynamic strain regulation in inverted perovskite solar cells

SonoPIN enables precise, noninvasive, and efficient intracellular delivery of PROTACs

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising molecular approach for degrading undruggable proteins and for overcoming drug resistance in cancer therapy. However, their clinical translation remains limited by challenges such as poor cell membrane permeability, limited intracellular uptake, and potential off-target toxicity. To overcome these barriers, we developed Sonoporation-assisted Precise Intracellular Nanodelivery (SonoPIN), an ultrasound-driven, aptamer-guided microbubble system that enables rapid delivery of therapeutic molecules with cell selectivity. By leveraging aptamer-conjugated microbubbles and ultrasound-induced sonoporation, SonoPIN transiently permeabilizes the membranes of target cells, while leaving nontarget cells undisturbed. Using BRD4, a well-characterized oncogenic transcriptional coactivator and validated PROTAC target critically involved in cancer cell survival, as a model system, we demonstrate that SonoPIN facilitates highly efficient intracellular delivery of fluorescently labeled PROTACs. SonoPIN achieves a sevenfold increase in intracellular fluorescence after 60 s of ultrasound stimulation, resulting in a 70% reduction in BRD4 protein levels specifically in cancer cells. Importantly, BRD4 degradation is undetectable in noncancerous cells. Consequently, approximately 50% of the targeted cancer cells undergo apoptosis while nontarget cells retain more than 99% viability, underscoring the high selectivity of the SonoPIN system. Our study indicates that SonoPIN represents an innovative, noninvasive delivery platform for PROTAC therapeutics, offering a rapid and precise approach for targeted drug delivery in cancer treatment.

Enhancing safety and early warning capabilities in mining through microseismic monitoring technology

Increased spread of global flash droughts threatens vegetation productivity resilience

Stretch and flow at the gliovascular interface: High-fidelity modeling of astrocyte endfeet

Astrocyte endfeet form a near-continuous sheath around the brain’s vasculature, defining the perivascular spaces (PVS) that are crucial for brain fluid flow and solute transport. Yet, their precise physiological role remains poorly understood. Using 3D electron microscopy data, we created a high-fidelity poroelastic computational model of an arteriole segment with surrounding endfeet and parenchyma to investigate tissue displacement and fluid flow within the PVS, endfeet, and extracellular space in response to blood vessel pulsations. Our model predicts that arteriole dilations compress the PVS while expanding the overall endfoot sheath volume due to tangential stretch. Moreover, fluid exchange primarily occurs through inter-endfoot gaps, driven by pressure differences, rather than across the aquaporin-4 (AQP4) rich endfoot membrane. PVS stiffness critically modulates these dynamics: Increased stiffness of the PVS, for instance, due to vessel pathology or aging, would minimize or even reverse fluid exchange at the gliovascular interface. While AQP4 mediated water movement has a negligible impact on pulsation-driven mechanics, it significantly enhances osmotically driven fluid flow. Overall, our findings elucidate the complex balance of forces governing gliovascular mechanics and suggest that PVS composition strongly influences endfoot-parenchymal fluid exchange.

Temperature control performance change of EPS foam box with ice packing in aircraft cargo hold

Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice

Nonreciprocal buckling makes active filaments polyfunctional

Active filaments are a workhorse for propulsion and actuation across biology, soft robotics, and mechanical metamaterials. However, artificial active rods suffer from limited robustness and adaptivity because they rely on external control, or are tethered to a substrate. Here, we bypass these constraints by demonstrating that nonreciprocal interactions lead to large-scale unidirectional dynamics in free-standing slender structures. By coupling the bending modes of a buckled beam antisymmetrically, we transform the multistable dynamics of elastic snap-through into persistent cycles of shape change. In contrast to the critical point underpinning beam buckling, this transition to self-snapping is mediated by a critical exceptional point, at which bending modes simultaneously become unstable and degenerate. Upon environmental perturbation, our active filaments exploit self-snapping for a range of functionality including crawling, digging, and walking. Our work advances critical exceptional physics as a guiding principle for programming instabilities into functional active materials.

Multi-omics feature engineering driven by biomedical foundation models improves drug response prediction for inflammatory bowel disease patients

Metagenomic profiling of antimicrobial resistance in wastewater from metropolitan cities of India

Narrative “twist” shifts within-individual neural representations of dissociable story features

Given the same input, understanding of that input can differ depending on context. How does the brain represent the latent mental frameworks that support different interpretations of the same sensory information? In this study, participants listened to the same auditory narrative twice; the narrative had a plot twist in the middle that dramatically shifted interpretations of the story. Using a within-subject design that held both the stimulus and the individual constant, we leveraged reinterpretation-driven shifts in neural activity between the two listens to identify where representations of different narrative elements are updated under a new interpretative framework. We separated the narrative into three interrelated levels—the overall narrative model, episodes, and characters—to determine where reinterpretation-driven updates to each element were reflected in brain activity. Neural activity patterns associated with interpretations and reinterpretations of these three elements were observed in overlapping but partially distinct sets of temporal, parietal, and prefrontal regions. Results suggest that heteromodal cortex represents specific narrative elements according not to their surface features, but to latent conceptual frameworks for understanding those elements, which can shift under a new narrative interpretation.