Hyperpigmentation is a common skin disorder that affects millions of people worldwide. The growing demand for ameliorating undesirable hyperpigmentary disorders has driven the development of novel intervention strategies. Herein, we identified uralsaponin X, a licorice-derived high-mobility group box 1 (HMGB1) inhibitor, which exerts potent anti-melanogenic effects in zebrafish larval models. Cell culture experiments demonstrated that uralsaponin X did not alter melanin biosynthesis in melanocytes but specifically inhibited HMGB1-mediated melanocyte dendrite extension and melanosome transport to the plasma membrane, thereby reducing the transfer of melanosomes to keratinocytes. Furthermore, we developed a nanoscale co-delivery system to co-encapsulate uralsaponin X and glabridin, a well-known tyrosinase inhibitor, into lipid nanoparticles to enhance skin penetration and achieve a synergistic depigmenting effect. The uralsaponin X- and glabridin-loaded lipid nanoparticle (UG-LNP) effectively improved cellular internalization and skin permeability. In a UVB-triggered hyperpigmentation guinea pig model, UG-LNP demonstrated remarkable depigmenting capacity by suppressing melanin synthesis, melanosome transfer, and inflammatory cell infiltration. Compared with glabridin monotherapy, UG-LNP achieved better in vivo therapeutic outcomes, as demonstrated by the alleviation of UVB-induced epidermal thickening and melanin granule accumulation in the epidermis. Collectively, this study identified uralsaponin X as a novel HMGB1 inhibitor possessing potent anti-hyperpigmentation properties. Furthermore, lipid nanoparticle-based co-delivery of glabridin and uralsaponin X represents a promising therapeutic strategy for the management of hyperpigmentation disorders.

UDP-glucuronosyltransferase 1A8 (UGT1A8), a key human phase II metabolic enzyme, is related to the pathogenesis of endometrial and breast cancers. Nevertheless, its roles in drug-drug interactions and disease mechanisms remain unclear due to the lack of selective real-time monitoring tools. In this work, we developed UPro1A8, the first "off-on" fluorescent probe specifically targeting UGT1A8, designed via a "single-end modification strategy". UPro1A8 demonstrates excellent selectivity and sensitivity for UGT1A8 over other UGT isoforms. It enables real-time visualization of endogenous UGT1A8 activity in living cells, tissue slices, and zebrafish, providing a flexible platform for precise inhibitor evaluation. Screening of a compound library using this probe identified four natural products, namely Ginkgetin, Silibinin, Ledebouriellol, and Antcin C (R), as potent UGT1A8 inhibitors. Collectively, these findings position UPro1A8 as a robust molecular tool for advancing UGT1A8 functional studies.

Background Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are two nociceptive TRP channel subtypes that play central roles in cough hypersensitivity. Purpose This study evaluated the antitussive efficacy of liquiritin apioside (LIQA) and liquiritin (LIQ), two major flavonoid glycosides from licorice, in acute chemically induced cough models, and investigated their modulations of TRPA1 and TRPV1. Methods In guinea pig models, cough was induced by capsaicin (a TRPV1 agonist) and cinnamaldehyde (a TRPA1 agonist), respectively. The inhibitory effects of LIQA and LIQ against TRPA1 and TRPV1 were assessed using electrophysiological profiling and fluorescence-based calcium assays. To elucidate the underlying mechanisms, high-resolution cryo-electron microscopy (cryo-EM) structural analysis, and molecular simulations were conducted. Results LIQA and LIQ significantly reduced cough frequency in the guinea pig models. Electrophysiological profiling revealed that LIQA suppressed human TRPA1 (hTRPA1) channel activity, while LIQ blocked human TRPV1 (hTRPV1) activation. High-resolution cryo-EM structures of hTRPA1/LIQA (2.59 Å) and hTRPV1/LIQ (3.05 Å) complexes were obtained. Structural analysis indicates that LIQA stabilizes hTRPA1 in a closed conformation with T624 at the coupling region site, whereas LIQ interacts with S512 through hydrogen bonding in the deep S4-S5 site of hTRPV1, thereby inhibiting pore opening. Conclusion This study establishes LIQA and LIQ as lead compounds with acute antitussive activities mediated by TRPA1/TRPV1 modulation.

Phosphoric acid-doped polybenzimidazole (PA/PBI) membranes are promising for high-temperature proton exchange membrane fuel cells (HT-PEMFCs), yet their operational flexibility is severely constrained by PA leaching under humid conditions and volatilization at elevated temperatures. To overcome this, we engineer an alkaline micropore-confined gel-state composite membrane by in situ integrating amino-functionalized UiO-66 (UiO-66-NH2) into a three-dimensional porous PBI network via PPA sol–gel process. Unlike conventional systems, this architecture establishes a dual-mode acid retention mechanism: acid–base interactions with –NH2/imidazole sites, and micropore confinement within the interconnected gel-state pores, synergistically suppressing acid loss. Crucially, we reveal that the alkaline, confined micropores facilitate a fundamental proton transport transition from a sluggish vehicle-dominated mechanism to an efficient Grotthuss (hopping) mechanism at sub-zero temperatures. Consequently, the optimized 15 wt% UiO-66-NH2/p-PBI membrane exhibits improved PA retention (58.2% at 80 °C/40% RH for 50 h; 73.1% at 160 °C/0% RH for 60 h), outstanding proton conductivity (peak: 0.261 S cm−1) across a broad temperature range from −20 to 220 °C, superior fuel cell performance (1.46 W cm−2 at 200 °C), and robust long-term durability. By synergistically integrating gel-state structural design with alkaline micropore confinement, this work provides a practical materials strategy to simultaneously resolve the long-standing acid retention–conductivity trade-off, offering a viable pathway with enhanced operational flexibility and reliable performance across a broad temperature range.

Herpes zoster (HZ), caused by reactivation of varicella-zoster virus (VZV), imposes a substantial health burden, particularly in immunocompromised individuals. Although current HZ vaccines provide effective protection, the live-attenuated vaccine shows age-dependent and waning efficacy, whereas the recombinant zoster vaccine relies on a complex adjuvant system that may present manufacturing and supply challenges. mRNA vaccines offer a promising alternative for HZ prevention, but their efficacy depends on optimized lipid nanoparticle (LNPs) that protect mRNA and support efficient intracellular delivery. Here, we formulated LNPs for an mRNA encoding VZV glycoprotein E by partially or completely replacing cholesterol with two cholesterol-related sterols, the plant-derived sterol β-sitosterol and the immunomodulatory metabolite dendrogenin A (DDA). We found that high-level DDA substitution (≥50%) impaired both antigen-specific antibody responses and T-cell immunity. By contrast, complete β-sitosterol replacement (100% SS-LNPs) enhanced EGFP reporter signals in vitro and in vivo and produced numerically higher antigen-specific T-cell responses than cholesterol-based LNPs (Chol-LNPs), with significantly increased CD4+ T-cell polyfunctionality. Transcriptomic analysis further showed that the immune signatures induced by 100% SS-LNPs largely overlapped with those induced by Chol-LNPs, without evidence of a distinct inflammatory transcriptional program. Together, these findings identify β-sitosterol substitution as a promising formulation strategy for VZV mRNA-LNP development.

Ambainis and de Wolf proposed the concept of average-case query complexity of boolean functions and showed that average-case deterministic, average-case bounded-error randomized, and average-case quantum query complexities are not polynomially related. While tools such as the OSSS/OS inequalities provide lower bounds on the average-case deterministic query complexity under a uniform distribution, denoted Dave(f), the understanding of upper bounds is much more limited. To address this gap, we prove two upper bounds on Dave(f) and demonstrate their tightness.First, we establish an upper bound on Dave(f) in terms of the weight wt(f), i.e., the number of inputs on which the output is 1. Specifically, for every f: {0, 1}n → {0, 1} with wt(f)≥4logn, Dave(f)≤logwt(f)logn+O(loglogwt(f)logn), and Dave(f)=O(1) when wt(f)<4logn. Moreover, we show that the upper bound is tight up to an additive logarithmic term for almost all boolean functions.Second, we prove that Dave(F)≤n(1−lognO(k)) for any k-CNF F and log n ≤ k ≤ n0.99, by adapting techniques from Håstad’s switching lemma proof and extending the worst-case analysis to the average-case setting. Moreover, we show that the above bound is tight by exhibiting a k-CNF F with Dave(F)=n(1−lognΘ(k)) for any k ≥ 2log n.

Manganese oxides are among the most promising low-temperature NH3-selective catalytic reduction (NH3-SCR) catalysts. MnO2 with different crystal phases (alpha-, (3-, gamma-, and S-MnO2) exhibits significantly different NH3-SCR performance. The fundamental factors influencing the activity of MnO2 with different crystal phases remain a subject of considerable debate. This study finds that (3- and S-MnO2 show poor activity due to low reactivity and poor NH3 adsorption. In contrast, alpha- and gamma-MnO2 show high activity but differ in optimal reaction temperature windows. The smaller Mn-O coordination number and longer Mn-O bond distance in alpha-MnO2 result in an upward shift of its d-band center. Therefore, alpha-MnO2 exhibits stronger coupling between the Mn-d and N-p orbitals during NH3 adsorption, promoting *NH3 activation. As a result, alpha-MnO2 outperforms gamma-MnO2 in low-temperature catalytic activity. This study reveals the impact of microscopic electronic orbital coupling on macroscopic catalytic performance, providing new insights for developing advanced low-temperature NH3-SCR catalysts.

UDP-glucuronosyltransferase 2B7 (UGT2B7), a pivotal drug-metabolizing enzyme, plays a critical role in conjugating and detoxifying diverse nonpolar xenobiotics. However, few methods exist for conveniently monitoring UGT2B7 function in biological systems. Herein, we developed an integrated strategy, combining structure-based virtual screening with biochemical validation, to create the first UGT2B7-activatable fluorogenic probe that enables in situ detection of UGT2B7 activity. A series of 1,8-naphthalimide derivatives were designed and synthesized based on the PET mechanism. Following the preliminary screening, UPro2B7 demonstrates outstanding isoform specificity and sensitivity. It enables highly effective functional imaging of endogenous UGT2B7, demonstrating specific endoplasmic reticulum (ER) colocalization and high spatial resolution. Critically, UPro2B7 serves as a superior alternative to conventional drug substrates for screening of UGT2B7 inhibitors. Utilizing this probe, we identify Licoagrochalcone A (Lic A) and Glycycoumarin (Gly) as potent UGT2B7 inhibitors, validated in live cells, rat tissues, and zebrafish. Collectively, this work demonstrates an integrated strategy for rationally engineering isoform-specific, UGT2B7-activatable fluorogenic substrate. UPro2B7 serves as a practical and reliable tool for in situ imaging and inhibitor assessment of UGT2B7 activity.

This review summarizes the characteristics, deactivation pathways, and design strategies of Mn-based catalysts for the catalytic oxidation of CVOCs. The objective is to provide insights for the development of highly efficient Mn-based catalysts.

The efficient conversion of waste to renewable energy via photocatalysis is critically limited by sluggish carrier dynamics (separation and transfer), leading to severe charge recombination and diminished performance. Herein, we demonstrate a Co-N bond engineered photocatalyst that enables fast carrier extraction and transfer by anchoring Co3O4 nanoparticles onto g-C3N4, addressing the intrinsic kinetic bottleneck in photocatalytic waste-to-energy systems. The experimental results demonstrated that the introduction of Co3O4 nanoparticles enhanced the number of active sites and the solar light response range of g-C3N4. Moreover, the directional charge transfer driven by the Schottky barrier significantly increased the number of effective charges. As a result, the hybrid catalyst exhibits excellent bifunctional catalytic performance in synchronous hydrogen production (3863.2 mu mol/h/g) and tetracycline (TC) degradation, which is 10 times higher than pure g-C3N4. This study provides theoretical and experimental references for designing multifunctional photocatalytic systems based on interface regulation and has reference significance for the development of environmental remediation and energy conversion synergistic technologies.

Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by a profoundly immunosuppressive tumor microenvironment, which features a dense desmoplastic stroma enriched with cancer-associated fibroblasts (CAFs) that collectively impede the efficacy of immunotherapies. Although oncolytic viruses (OVs) have demonstrated promising potential in eliciting antitumor immunity, the mechanisms by which stromal components modulate OV efficacy remain poorly understood.Methods To investigate the interplay between immune and stromal components in PDAC following OV treatment, we employed murine and patient-derived tumor models. We characterized immune cell populations using single-cell RNA sequencing and flow cytometry. Functional studies included the engineering of a next-generation oncolytic herpes simplex virus expressing FLT3 ligand, OX40 ligand, and interleukin-12 (IL-12), combined with CD40 agonist antibodies to restore dendritic cell (DC) function and enhance T-cell responses.Results We identified a novel immunosuppressive circuit wherein monocytes, sensing damage-associated molecular patterns and pathogen-associated molecular patterns from OV-infected tumor cells, secrete interleukin-1β. This, in turn, triggers IL-6 production by CAFs, creating an IL-6-rich milieu that impairs DC maturation and co-stimulatory signaling, thereby attenuating T cell-mediated antitumor immunity and restricting OV therapeutic efficacy. Importantly, combination therapy with the engineered OV and CD40 agonist antibodies restored DC functionality and elicited robust tumor-specific T-cell responses in both murine and patient-derived models.Conclusion Our findings reveal a previously unrecognized monocyte-CAF-DC axis that mediates resistance to OV therapy through IL-1β and IL-6-driven suppression of DC function in PDAC. This study provides a mechanistically informed and translationally promising approach to overcome stromal immune suppression, restore effective antitumor immunity, and improve therapeutic outcomes for patients with PDAC.

Hybrid heterojunction solar cells based on poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT: PSS) and silicon (Si) have attracted considerable interest due to their potential for high efficiency, low-cost materials, and facile fabrication. However, their performance is often limited by suboptimal spectral management and interfacial recombination. In this study, we present an optimized dual-layer PEDOT: PSS (PH1000) architecture, incorporating ethylene glycol (EG) and dimethyl sulfoxide (DMSO) dopants in films with thicknesses of ≥ 110 nm and ≥ 60 nm, respectively. This bilayer configuration enhances light absorption, reduces Fresnel reflection, and improves charge extraction through tailored interfacial engineering. The resulting device demonstrates reduced Fresnel reflection, significant increase in Voc and Jsc due to the customized PEDOT: PSS architecture owing to improved charge extraction and reduced recombination losses. The device with dual-layer PEDOT: PSS film exhibits a significantly higher Voc of 604.8 mV and Jsc of 16.57 mA/cm2 without any additional adaptations. Additionally, it has a fill factor of 61.03

Imparting vivid colors to photovoltaic devices has traditionally required sacrificing power conversion efficiency, a trade-off that limits their adoption in building-integrated photovoltaics (BIPV) and other aesthetics-driven applications. Here, we overcome this constraint by integrating short-range correlated disordered dielectric nanostructures onto high-efficiency organic-silicon heterojunction solar cells. These wavelength-scale nanospheres act dually to suppress broadband specular reflection, thereby enhancing light harvesting, and to generate coherent off-specular scattering that yields iridescent structural colors. To explore this mechanism, we developed a large-scale theoretical framework that decouples collective disorder from single-particle scattering responses, enabling quantitative prediction of the color-efficiency interplay in assemblies of more than 2000 nanoparticles. Experimentally, the iridescent device achieves a power conversion efficiency of 8.17%, compared with 7.3% for the reference device without PS nanospheres, while exhibiting high-saturation CIE 1931 color coordinates. This work demonstrates that vivid coloration does not require strong reflection, overturning the long-standing efficiency-aesthetics trade-off and opening pathways to next-generation BIPV that combine performance with visual appeal.

We study the average-case deterministic query complexity of boolean functions under a uniform input distribution, denoted by D_ave(f) , the minimum average depth of zero-error decision trees that compute a boolean function f. This measure has found several applications across diverse fields, yet its understanding is limited. We study boolean functions with fixed weight, where weight is defined as the number of inputs on which the output is 1. We prove D_ave(f) ≤max{log wt (f)/log n + O(loglog wt (f)/log n), O(1) } for every n-variable boolean function f, where wt (f) denotes the weight. For any 4log n ≤ m(n) ≤ 2^n-1 , we prove the upper bound is tight up to an additive logarithmic term for almost all n-variable boolean functions with fixed weight wt (f) = m(n) . Håstad’s switching lemma or Rossman’s switching lemma [Comput. Complexity Conf. 137, 2019] implies D_ave(f) ≤ n(1 - 1/O(w)) or D_ave(f) ≤ n(1 - 1/O(log s)) for CNF/DNF formulas of width w or size s, respectively. We show there exists a DNF formula of width w and size ⌈ 2^w / w ⌉ such that D_ave(f) = n (1 - log n/ (w)) for any w ≥ 2log n .

Disorder is often considered the opposite of order, lacking quantitative methods and being difficult to control. Disordered nanostructures can be conveniently prepared by bottom-up approaches, such as self-assembly, but their intrinsic randomness is often considered to lead to unpredictable results, impeding reproducibility and application. Here, we demonstrate that deterministic, angle-dependent visual appearances induced by specific correlated disorder can be achieved through bottom-up approaches, and reveal plenty of room for tailoring color appearance between order and random disorder. Two unprecedented iridescent visual appearances, backscattering iridescence (rainbow-like color transition covering more than five distinct colors at backscattering angles), and specular iridescent halo (gradual color changes in the visible light range around specular reflection direction), are proposed and demonstrated to be induced by correlated disorder at different degrees, which is regulated by interparticle distance. Besides elucidating the mechanism of iridescence generation, a comprehensive protocol for predicting the color appearance is established, and agrees well with experimental results. Combining bottom-up process, materials with low absorption, and tailored spatial disorder, we have endowed solar cells with colorful appearances, while maintaining the performance, which can serve as a solution for photovoltaic-integrated architectures and vehicles. This study advances the understanding of how disorder shapes color and angular appearance, and will find applications in energy photonics, dazzling arts, and anticounterfeiting.

Surface treatment is a pivotal technique for enhancing the properties of industrial-grade bulk c-silicon wafers, revolutionizing their applicability in both PV and MEMS applications. In this paper we presents a brief overview of recent advancements in anisotropic etching methodologies, elucidating their role in tailoring surface morphology, roughness, and texturing of silicon wafers with precision and control. Fundamental insights into the chemical reactions governing the anisotropic etching process are explored, highlighting its capacity to produce intricate surface structures beneficial for light management in PV cells and optimized mechanical characteristics for MEMS devices. Encompassing diverse anisotropic etching solutions and their effects on surface morphology, addressing the intricate interplay between etchant composition, temperature, and process duration. Strategies for achieving superior selectivity, reproducibility, and uniformity across large-scale silicon wafers are discussed, elucidating the nuanced control required for industrial implementation.

A Sc(OTf)3-catalyzed diastereoselective [4 + 2] cycloaddition reaction of 3-benzylideneindoline-2-thiones with 2-alkylidene malonates has been realized, leading to biologically important indole-annulated thiopyran derivatives in moderate to good yields. Moreover, a gram-scale reaction and chemical transformation of the cycloadduct into a sulfone were carried out to further extend the synthetic utility.