The Graduate Center, CUNY

Understanding how peptide sequence relates to supramolecular dynamics and consequent solid-state material properties remains a central challenge for rational peptide materials design. Here, we use N-terminal proline as a strategic conformational constraint in minimalist tripeptides (PXX; P = proline, X = phenylalanine (F) or tryptophan (W)) to isolate side-chain contributions from backbone and show that simple aromatic exchange dictates crystallization pathways and solid-state dynamics. In this design, proline rigidifies the backbone, the central residue supports assembly, and the C-terminal aromatic residue dictates conformational adaptability. Combining molecular dynamics simulations with NMR and fluorescence spectroscopy, we show that peptides with W at the C-terminus, with a diverse interaction space, display shallow energy landscapes with multiple accessible states, whereas a C-terminal F, with a stringent hydrophobic nature and limited interaction space, restricts the peptide into fewer conformations. As a result, PXF peptides form soluble supramolecular aggregates, while PXW peptides access more adaptable conformations that promote crystallization. Solid-state characterization reveals that these sequence-encoded supramolecular dynamics directly influence bulk properties: W-containing peptides form stiff crystals with dynamic, wettable surfaces, whereas F analogues yield static, hydrophobic materials. Together, these results establish how aromatic-residues dictate supramolecular assembly and crystallization, offering a straightforward approach to engineering dynamic properties in solid-state peptide materials.

TP53mutations occur in 80-90% of triple-negative breast cancers (TNBCs) and drive genomic instability and metastatic progression. Poly (ADP-ribose) polymerase (PARP) is critical for DNA repair and replication fork stability. How oncogenic signaling influences PARP function to sustain proliferation during replication stress remains unclear. Mutant p53 (mtp53) R273H associates tightly with chromatin, forms complexes with PARP, and enhances PARP recruitment to replication forks [1–3]. The C-terminal region of mtp53 mediates mtp53-PARP and mtp53-Poly (ADP-ribose) (PAR) interactions that facilitate S phase progression [4, 5]. The PARP inhibitor talazoparib (TAL) combined with the alkylating agent temozolomide (TMZ) produces synergistic cytotoxicity selectively in mtp53, but not wild-type p53 (wtp53), breast cancer cells and organoids. Herein we evaluated the mechanism of mtp53-associated cell death and tested if this could translate to a preclinical xenograft model. We found that TMZ+TAL treatment induced elevated cleaved PARP and γH2AX and reduced the metastasis-promoting oncoprotein MDMX. In orthotopic xenografts expressing mtp53 R273H, but not wtp53, combination therapy significantly decreased circulating tumor cells (CTCs) and lung metastases. Transcriptomic profiling of tumors from combination treated animals demonstrated downregulation ofMDMX,VEGF,andNF-κB, consistent with the observed suppression of CTCs and lung metastasis, and increased γH2AX, indicative of replication stress in mtp53 xenografts. Inhibition of metastasis was also observed in mtp53 R273H WHIM25 and p53-undetectable WHIM6 TNBC patient-derived xenografts (PDX). The mtp53 C-terminal domain (347-393) demonstrated a critical tumor promoting function, as CRISPR-mediated deletion impaired replication fork progression, tumor growth, and metastatic dissemination. DNA fiber combing showed that expression of full-length mtp53 R273H, but not C-terminal deleted Δ347-393, supported sustained single-stranded DNA gaps (ssGAPs) following Poly (ADP-ribose) glycohydrolase (PARG) inhibition. These findings support that mtp53 uses C-terminal amino acids to exploit PARP to enable replication stress adaptation and that mtp53 is a predictive biomarker for combined PARP inhibitor and DNA damaging therapies targeting TNBC.Significance statementTP53mutations are the most common genetic alterations in TNBC and a major driver of replication stress and metastasis. This study shows that missense mutant p53 uses C-terminal amino acids to reprogram PARP activity to maintain tumor cell survival under replication stress. We demonstrate that p53 status governs the response to combined PARP inhibitor (PARPi) and DNA-damaging chemotherapy, establishing an additional molecular basis beyond BRCA1 mutations for treating TNBC with PARPi therapy. These findings reveal a previously unrecognized mechanism by which the mutant p53-PARP axis enables replication stress tolerance and drives cancer metastasis. We show mutation of p53 in TNBC provides an additional biomarker-guided framework to improve PARPi therapeutic outcomes.

Vaccination is an important strategy to protect pregnant people, fetuses, and infants from severe influenza and COVID-19. However, as of April 2025 in the United States, only 14% of pregnant women had received the 2024-2025 COVID-19 vaccine, while influenza vaccine uptake among pregnant women was 38% compared to 57% in 2020. Our study assessed the perceived safety of receiving these vaccines during pregnancy within a community-based national cohort. Participants reported safety perceptions of vaccination during pregnancy and were categorized as (1) endorsing the safety of both COVID-19 and influenza vaccines, (2) endorsing the safety of only the influenza vaccine, (3) endorsing the safety of only the COVID-19 vaccine and (4) endorsing the safety of neither vaccine during pregnancy. We examined sociodemographics, behaviors, and beliefs correlated with these four categories. Log-binomial models were used to estimate the prevalence ratios of (a) endorsing the safety of only influenza vaccine versus endorsing the safety of both COVID-19 and influenza vaccines during pregnancy, and (b) endorsing safety of neither versus both vaccines during pregnancy. In total, 40% of adults (N = 1725) endorsed the safety of both vaccines during pregnancy, 18% (N = 751) endorsed the safety of only the influenza vaccine, 4% (N = 183) endorsed the safety of only the COVID-19 vaccine, and 38% (N = 1621) did not endorse the safety of either vaccine during pregnancy. Participants who were non-Hispanic Black, reported inconsistent vaccination habits, and expressed low trust in government and healthcare providers were more likely to endorse the safety of only the influenza vaccine or neither vaccine compared with endorsing both vaccines. These findings highlight the need to build trust in the medical system, reduce access barriers, and use equitable, community-driven messaging to strengthen confidence in the safety of receiving the COVID-19 and influenza vaccines during pregnancy.

Passivation of surface defects of cesium lead halide (CsPbX3, X = Cl, Br, I) nanocrystals is crucial to improving the stability and photoluminescence of these materials for further optoelectronic applications. Many ligands have been examined for surface passivation; however, a ligand design principle for improved photoluminescence quantum yield (PLQY) is still not available. Here, we report a combined computational and experimental study to systematically investigate 27 commercially available ligands and develop foundational guidelines. Using first-principles density functional theory, we calculated the binding energy of the ligands on the CsPbBr3 nanocrystal. We find a volcano relationship between ligand binding energy and the experimental PLQY, which reveals the negative impact of overly strong binding energy. We further perform electronic structure analysis and time-resolved optical spectroscopy to reveal that these strong-binding ligands can withdraw more electrons from the surface and induce trap states within the bandgap. With this, we develop a design principle for the PLQY of CsPbBr3 nanocrystals, highlighting the importance of the ligand binding energy comparable to that of the native halide species. We further applied this design principle to quantum-confined CsPbCl3 and CsPbI3 nanocrystals, and our computational predictions have been successfully validated by experiments.

Nonlocal metasurfaces offer a platform to reduce footprint, power consumption and processing time in image processing and computing. Most implementations, however, are limited to single operations and confined to spatially symmetric functions that comply with reciprocity. Here, we introduce a nonreciprocal metasurface that leverages magneto-optical phenomena combined with nonlocality to execute edge detection or noise mitigation on images as a function of the observer position. Our work opens the door to ultra-compact, multifunctional devices that combine nonlocality and nonreciprocity for all-optical image processing, with potential applications in augmented reality, remote sensing, and biomedical imaging.

At present, the traditional anthraquinone method is the main method for producing high-quality and high-concentration H2O2, but it involves the use of H2, resulting in high carbon emissions and certain risks. The double-electron oxygen reduction reaction has become a more environmentally friendly alternative method for producing H2O2. However, at high overpotentials, the production and conversion rates of H2O2 are still limited. Here, we report an electrochemical method that can convert H2O and formaldehyde into high-concentration H2O2 and high-value formate salts with high product purity under environmental conditions. At a current density of 30 milliamperes per square centimeter, continuous operation for 5 hours can produce 6.522% (m/v) H2O2, and the product does not contain acid, alkali, or excessive impurities. Faraday efficiency reaches 83%. The chronopotentiometry method shows stable current performance of the electrode after 360 hours of operation. This low-carbon, safe, and sustainable approach provides a promising alternative to traditional H2O2 production.

Mitochondria maintain a distinct biochemical environment that cooperates with pro-apoptotic BAX and BH3‑only proteins (e.g., BIM) to promote mitochondrial outer membrane permeabilization (MOMP), the key event to initiate physiological and pharmacological forms of apoptosis. The sphingosine-1-phosphate metabolite 2-trans-hexadecenal (2t‑hexadecenal) is a bioactive lipid that supports BAX-dependent MOMP. Using integrated structural and computational approaches, we determine that 2t‑hexadecenal binds within a distinct, dynamic region-a hydrophobic cavity formed by core-facing residues of α5, α6, and gated by α8-we now term the "BAX actuating funnel" (BAF). Complementary biochemical and biophysical techniques reveal that 2t-hexadecenal non-covalently interacts with the BAF and cooperates with BIM to stimulate intramolecular activation of monomeric BAX prior to membrane association. BAX α8 mobility and proline 168-mediated allostery are critical determinants for 2t-hexadecenal synergy with BAX and BIM, as is alkenal length to stimulate BAF function. Collectively, this work imparts detailed molecular insights into how pro-apoptotic BCL-2 proteins and bioactive lipids non-covalently cooperate to initiate the mitochondrial pathway of apoptosis with implications for biological and therapeutic regulation.

<h2>Abstract</h2> Steatotic liver disease (SLD) is a spectrum of highly prevalent liver disease that is encountered at many different healthcare levels. Awareness about metabolic dysfunction-associated SLD (MASLD), MetALD (MASLD and increased alcohol intake) and ALD (alcohol-related liver disease) is increasing beyond hepatology, as highlighted by the various SLD guidelines that have been issued by scientific societies from different disciplines, such as endocrinology. The guidance presented here aims to improve cross-disciplinary knowledge and know-how by providing guidance to healthcare professionals from a global, holistic, multi-society and -stakeholder perspective. The patient trajectory was used as an overarching anchor point to ensure uniform guidance at all points along the SLD spectrum, with the ultimate goal of improving patient identification and optimising their care. This consensus guidance covers patient identification and risk stratification, relevant cross-disciplinary primary and secondary care approaches, referral to and from tertiary care and strategies for disease management and monitoring. Strategies at each point of the patient trajectory are recommended and stratified as optimal (i.e., "nice-to-have") or minimal (i.e., "must-have"), per expert-opinion, making them adaptable to differences in healthcare settings, levels of resource availability and policies.