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A new speciesLeioproctus zephyr(Hymenoptera: Colletidae) is described from both sexes.Leioproctus zephyrsp. nov.is remarkable in featuring a large longitudinal ridge on the clypeus. This diagnostic morphological feature present in both sexes, along with various other distinctive characters including the male genitalia, female hind-tibial spur, and glossa morphology, clearly distinguish this species from all otherLeioproctus. Along with these unique traits,L. zephyrcannot be classified into any of the existing subgenera ofLeioproctus, sharing some, but not all, of the characters of the subgeneraCeratocolletes,Charicolletes,ProtomorphaandOdontocolletes. DNA barcoding with the CO1 gene confirmed the sexes belonged to the same species and it did not match any previously barcoded species. This species is restricted to native vegetation remnants in the southwest Western Australian biodiversity hotspot, and is highly specialised, foraging only on a few species in the genusJacksonia(Fabaceae). The unusual clypeus may be an adaptation for foraging on the keeled papilionaceous flowers. The limited number of sites this species has been collected from and its oligolectic diet suggestL. zephyrshould be considered to be a species of conservation concern. Further taxonomic research is required to determine the phylogenetic position of this unusualLeioproctus.

Nanomaterials (NMs) inevitably adsorb proteins in blood and form "protein corona" upon intravenous administration as drug carriers, potentially changing the biological properties and intended functions. Inspired by anti-adhesion properties of natural proteins, herein, we employed the one-bead one-compound (OBOC) combinatorial peptide library method to screen anti-adhesion peptides (AAPs) against proteins. The library beads displaying random peptides were screened with three fluorescent-labeled plasma proteins. The nonfluorescence beads, presumed to have anti-adhesion property against the proteins, were isolated for sequence determination. These identified AAPs were coated on gold nanorods (GNRs), enabling significant extension of the blood circulating half-life of these GNRs in mice to 37.8 h, much longer than that (26.6 h) of PEG-coated GNRs. In addition, such AAP coating was found to alter the biodistribution profile of GNRs in mice. The bioinspired screening strategy and resulting peptides show great potential for enhancing the delivery efficiency and targeting ability of NMs.

Bipartite networks of flowering plants and their visitors (potential pollinators) are increasingly being used in studies of the structure and function of these ecological interactions. Whilst they hold much promise in understanding the ecology of plant–pollinator networks and how this may be altered by environmental perturbations, like land-use change and invasive species, there is no consensus about the scale at which such networks should be constructed and analysed. Ecologists, however, have emphasised that many processes are scale dependent. Here, we compare network- and species-level properties of ecological networks analysed at the level of a site, pooling across sites within a given habitat for each month of surveys, and pooling across all sites and months to create a single network per habitat type. We additionally considered how these three scales of resolution influenced conclusions regarding differences between networks according to two contrasting habitat types (urban bushland remnants and residential gardens) and the influence of honey bee abundance on network properties. We found that most network properties varied markedly depending on the scale of analysis, as did the significance, or lack thereof, of habitat type and honey bee abundance on network properties. We caution against pooling across sites and months as this can create unrealistic links, invalidating conclusions on network structure. In conclusion, consideration of scale of analysis is also important when conducting and interpreting plant–pollinator networks.

In addition to efficacious vaccines and antiviral therapeutics, reliable and flexible in-home personal use diagnostics for the detection of viral antigens are needed for effective control of the COVID-19 pandemic. Despite the approval of several PCR-based and affinity-based in-home COVID-19 testing kits, many of them suffer from problems such as a high false-negative rate, long waiting time, and short storage period. Using the enabling one-bead-one-compound (OBOC) combinatorial technology, several peptidic ligands with a nanomolar binding affinity toward the SARS-CoV-2 spike protein (S-protein) were successfully discovered. Taking advantage of the high surface area of porous nanofibers, immobilization of these ligands on nanofibrous membranes allows the development of personal use sensors that can achieve low nanomolar sensitivity in the detection of the S-protein in saliva. This simple biosensor employing naked-eye reading exhibits detection sensitivity comparable to some of the current FDA-approved home detection kits. Furthermore, the ligand used in the biosensor was found to detect the S-protein derived from both the original strain and the Delta variant. The workflow reported here may enable us to rapidly respond to the development of home-based biosensors against future viral outbreaks.

Amiloride and its derivatives have long attracted attention as potential anticancer therapeutic agents. Several original studies characterized amilorides as inhibitors of sodium-proton antiporter tumor growth and urokinase plasminogen activator-mediated metastasis. However, more recent observations indicate that amiloride derivatives are specifically cytotoxic toward tumor cells relative to normal cells and have the capacity to target tumor cell populations resistant to currently-employed therapies. A major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with EC50 values in the high micromolar to low millimolar range. Here we report structure-activity relationship observations that underscore the importance of the guanidinium group and the presence of lipophilic substituents at the C(5) position of the amiloride pharmacophore in promoting cytotoxicity. Moreover, we demonstrate that our most potent derivative called LLC1 is cytotoxic toward mouse mammary tumor organoids and drug-resistant populations of various breast cancer cell lines, and induces lysosomal membrane permeabilization as a prelude to lysosome-dependent cell death. Our observations offer a roadmap for the future development of amiloride-based cationic amphiphilic drugs that engage the lysosome to specifically kill breast tumor cells.

The methods of OB2C library and LLS compounds synthesis

General methods for library synthesis Table S1. MS and purity for cyclic peptide 1 derivatives Synthesis of focused libraries Table S2. Amino acids used in the synthesis of focused Library 1 and 2 Table S3. Amino acids used in the synthesis of focused Library 1. Table S4. Amino acids used in the synthesis of focused Library 2 NMR study of peptide 1 and 4 Experimental Constraints and Structure Calculation Table S5. Chemical shifts of peptide 1 at 295K, DMSO-d6. Table S6. Chemical shifts of peptide 4 at 295K, DMSO-d6. Table S7. Structure statistics for the ensembles of 15 calculated structures of peptide 1 and peptide 4 Figure S1. Representative regions of the 2D NOESY spectrum of 1 and 4. Figure S2. Superimposed solution structures are the ensembles of 15 structures for peptide 1 and 4. In vivo and ex vivo optical imaging Abbreviations Reference

Supplementary Figure from Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer

Purpose:Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer–specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI.Experimental Design:SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies.Results:PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P < 0.0001), and 93.03% (P < 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P < 0.0001), and 75.96% (P < 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial.Conclusions:In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.

This work describes the discovery of a bead-bound membrane-active peptide (MAP), LBF127, that selectively binds fungal giant unilamellar vesicles (GUVs) over mammalian GUVs. LBF127 was re-synthesized in solution form and demonstrated to have antifungal activity with limited hemolytic activity and cytotoxicity against mammalian cells. Through systematic structure-activity relationship studies, including N- and C-terminal truncation, alanine-walk, and d-amino acid substitution, an optimized peptide, K-oLBF127, with higher potency, less hemolytic activity, and cytotoxicity emerged. Compared to the parent peptide, K-oLBF127 is shorter by three amino acids and has a lysine at the N-terminus to confer an additional positive charge. K-oLBF127 was found to have improved selectivity toward the fungal membrane over mammalian membranes by 2-fold compared to LBF127. Further characterizations revealed that, while K-oLBF127 exhibits a spectrum of antifungal activity similar to that of the original peptide, it has lower hemolytic activity and cytotoxicity against mammalian cells. Mice infected with

Diabetic ischemic wound treatment remains a critical clinical challenge. Neovascularization plays a significant role in wound healing during all stages of the tissue repair process. Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds, particularly diabetic wounds in highly ischemic conditions. We previously identified a cyclic peptide LXW7 that specifically binds to integrin αvβ3 on endothelial progenitor cells (EPCs) and endothelial cells (ECs), activates vascular endothelial growth factor (VEGF) receptors, and promotes EC growth and maturation. In this study, we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY, and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix (ECM) scaffolds. We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment. When applied in an established Zucker Diabetic Fatty (ZDF) rat ischemic skin flap model, LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing, enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment. Altogether, this study provides a promising novel treatment to accelerate diabetic ischemic wound healing, thereby reducing limb amputation and mortality of diabetic patients., Graphical abstract Schematics for the fabrication of ligand modified scaffolds.Image 1, Highlights • Diabetic foot ulcers represent a significant healthcare burden. • Neovascularization plays a significant role in all stages of the wound healing process. • Endothelial progenitor cells (EPCs) have the potential to facilitate neovascularization. • LXW7-DS-SILY promoted EPC attachment and growth on ECM scaffolds in vitro. • LXW7-DS-SILY improved neovascularization and wound healing in ZDF rat ischemic model.

In Australia, the European honeybee (Apis mellifera) is an exotic, abundant, super-generalist species. Introduced two centuries ago, it thrives in the absence of many diseases adversely impacting honeybees elsewhere. Australia’s native bees may be vulnerable to competition with honeybees, leading to reduced abundances, reproductive output or even loss of bee species. We review the literature concerning competition between honeybees and Australian native bees in order to: (1) identify the valuence and strength of honeybee associations with native bees, and how this varies according to the response variable measured; (2) assess potential research biases; (3) use ecological theory to explain variation in results; and (4) identify key knowledge gaps. We found honeybees typically comprised the majority of individuals in surveys of Australian bee communities. Data on whether honeybees outcompete native bees is equivocal: there were no associations with native bee abundance, species richness, or reproductive output in most cases. However, there were more negative than positive associations. Data indicate effects of honeybees are species-specific, and more detailed investigations regarding how different species and life-history traits affect interactions with honeybees is needed. We propose the following investigations to address deficiencies in the current literature: greater geographic and landscape representation; trait-based investigations; quantifying resource availability and overlap; disease and predator interactions; experimental feral colony removals; and studies spanning multiple seasons and years. Identifying conditions under which honeybees have negative, neutral or positive effects on native bees, and how the ecological traits of native bees are affected by honeybee competition can guide conservation and management.

Although stem cell-derived extracellular vesicles (EVs) have remarkable therapeutic potential for various diseases, the therapeutic efficacy of EVs is limited due to their degradation and rapid diffusion after administration, hindering their translational applications. Here, we developed a new generation of collagen-binding EVs, by chemically conjugating a collagen-binding peptide SILY to EVs (SILY-EVs), which were designed to bind to collagen in the extracellular matrix (ECM) and form an EV-ECM complex to improve EVs' in situ retention and therapeutic efficacy after transplantation. Methods: SILY was conjugated to the surface of mesenchymal stem/stromal cell (MSC)-derived EVs by using click chemistry to construct SILY-EVs. Nanoparticle tracking analysis (NTA), ExoView analysis, cryogenic electron microscopy (cryo-EM) and western-blot analysis were used to characterize the SILY-EVs. Fluorescence imaging (FLI), MTS assay, ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the collagen binding and biological functions of SILY-EVs in vitro. In a mouse hind limb ischemia model, the in vivo imaging system (IVIS), laser doppler perfusion imaging (LDPI), micro-CT, FLI and RT-qPCR were used to determine the SILY-EV retention, inflammatory response, blood perfusion, gene expression, and tissue regeneration. Results:In vitro, the SILY conjugation significantly enhanced EV adhesion to the collagen surface and did not alter the EVs' biological functions. In the mouse hind limb ischemia model, SILY-EVs presented longer in situ retention, suppressed inflammatory responses, and significantly augmented muscle regeneration and vascularization, compared to the unmodified EVs. Conclusion: With the broad distribution of collagen in various tissues and organs, SILY-EVs hold promise to improve the therapeutic efficacy of EV-mediated treatment in a wide range of diseases and disorders. Moreover, SILY-EVs possess the potential to functionalize collagen-based biomaterials and deliver therapeutic agents for regenerative medicine applications.

In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells

PDF file - 36K, Mitochondrial membrane potential in HER2 siRNA treated cells

Purpose: The majority of patients with prostate cancer who are treated with androgen-deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of galectin-1 (Gal-1) is associated with prostate cancer progression and poor clinical outcome. The role of Gal-1 in tumor progression is largely unknown. Here, we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1 inhibitor, LLS30, in mCRPC.Experimental Design: Cell viability, colony formation, migration, and invasion assays were performed to examine the effects of inhibition of Gal-1 in CRPC cells. We used two human CRPC xenograft models to assess growth-inhibitory effects of LLS30. Genome-wide gene expression analysis was conducted to elucidate the effects of LLS30 on metastatic PC3 cells.Results: Gal-1 was highly expressed in CRPC cells, but not in androgen-sensitive cells. Gal-1 knockdown significantly inhibited CRPC cells' growth, anchorage-independent growth, migration, and invasion through the suppression of androgen receptor (AR) and Akt signaling. LLS30 targets Gal-1 as an allosteric inhibitor and decreases Gal-1–binding affinity to its binding partners. LLS30 showed in vivo efficacy in both AR-positive and AR-negative xenograft models. LLS30 not only can potentiate the antitumor effect of docetaxel to cause complete regression of tumors, but can also effectively inhibit the invasion and metastasis of prostate cancer cells in vivo.Conclusions: Our study provides evidence that Gal-1 is an important target for mCRPC therapy, and LLS30 is a promising small-molecule compound that can potentially overcome mCRPC. Clin Cancer Res; 24(17); 4319–31. ©2018 AACR.

PDF file - 89K, Enhanced gap filling rates in HER2+ versus HER2- BCSCs

PDF file - 540K, Protein profiling analysis of HER2+ versus HER2- BCSCs

Increasing literature suggests that cell adhesion molecule α4β1 integrin plays a pivotal role in autoimmune diseases and cancer development. Noninvasive visualization of α4β1 integrin in vivo will facilitate the understanding of its involvement in disease progression and development of targeted therapies. Due to the lack of high-affinity targeting ligands, molecular imaging of α4β1 integrin is much less explored than that of αvβ3 and αvβ5 integrins. We have recently reported using the one bead–one compound combinatorial library method to identify a peptidomimetic, LLP2A, that preferentially binds to activated α4β1 integrin. Here, we described the use of LLP2A-Cy5.5 conjugate as an in vivo optical imaging probe in a human lymphoma xenograft model. This univalent LLP2A-Cy5.5 conjugate retained the binding activity and specificity to α4β1 integrin as shown by cell binding assays using α4β1-positive Molt-4 T-leukemia cells. The subcutaneous Molt-4 tumor was clearly visualized from 1 to 24 h after tail vein injection of the conjugate. Direct imaging and confocal microscopic examination of excised tumors and organs confirmed the accumulation of LLP2A in tumors and revealed very little or no uptake in normal organs except for lymph nodes. Kidney uptake was high when the whole organ was scanned but it was negative when examined microscopically, suggesting that LLP2A bound to the renal tubules loosely. Tumor uptake of LLP2A-Cy5.5 conjugate was blocked by excess unlabeled LLP2A. This study showed that the combinatorial chemical library-derived peptidomimetic LLP2A can be easily developed into an optical imaging probe for noninvasively monitoring of activated α4β1 integrin in vivo. [Mol Cancer Ther 2008;7(2):432–7]

Supplementary tables

Supplementary Methods from In vivo optical imaging of human lymphoma xenograft using a library-derived peptidomimetic against α4β1 integrin

PDF file - 513K, IHS of co-activation of HER2/CD44 cells in tumor tissues

Purpose: To understand the role of HER2-associated signaling network in breast cancer stem cells (BCSC) using radioresistant breast cancer cells and clinical recurrent breast cancers to evaluate HER2-targeted therapy as a tumor eliminating strategy for recurrent HER2−/low breast cancers.Experimental Design: HER2-expressing BCSCs (HER2+/CD44+/CD24−/low) were isolated from radiation-treated breast cancer MCF7 cells and in vivo irradiated MCF7 xenograft tumors. Tumor aggressiveness and radioresistance were analyzed by gap filling, Matrigel invasion, tumor-sphere formation, and clonogenic survival assays. The HER2/CD44 feature was analyzed in 40 primary and recurrent breast cancer specimens. Protein expression profiling in HER2+/CD44+/CD24−/low versus HER2−/CD44+/CD24−/low BCSCs was conducted with two-dimensional difference gel electrophoresis (2-D DIGE) and high-performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) analysis and HER2-mediated signaling network was generated by MetaCore program.Results: Compared with HER2-negative BCSCs, HER2+/CD44+/CD24−/low cells showed elevated aldehyde dehydrogenase (ALDH) activity and aggressiveness tested by Matrigel invasion, tumor sphere formation, and in vivo tumorigenesis. The enhanced aggressive phenotype and radioresistance of the HER2+/CD44+/CD24−/low cells were markedly reduced by inhibition of HER2 via siRNA or Herceptin treatments. Clinical breast cancer specimens revealed that cells coexpressing HER2 and CD44 were more frequently detected in recurrent (84.6%) than primary tumors (57.1%). In addition, 2-D DIGE and HPLC/MS-MS of HER2+/CD44+/CD24−/low versus HER2−/CD44+/CD24−/low BCSCs reported a unique HER2-associated protein profile including effectors involved in tumor metastasis, apoptosis, mitochondrial function, and DNA repair. A specific feature of HER2–STAT3 network was identified.Conclusion: This study provides the evidence that HER2-mediated prosurvival signaling network is responsible for the aggressive phenotype of BCSCs that could be targeted to control the therapy-resistant HER2−/low breast cancer. Clin Cancer Res; 18(24); 6634–47. ©2012 AACR.

PDF file - 187K, Enhanced aggressiveness of C6 and HER2 cells

PDF file - 112K

PDF file - 79K, Peptide and protein HPLC-MS/MS identification data for all proteins included in Table S1

PDF file - 80K, Proteins identified by HPLC-MS/MS analysis are categorized into functional groups

The αvβ3 integrin, expressed on the surface of various normal and cancer cells, is involved in numerous physiologic processes such as angiogenesis, apoptosis, and bone resorption. Because this integrin plays a key role in angiogenesis and metastasis of human tumors, αvβ3 integrin ligands are of great interest to advances in targeted therapy and cancer imaging. In this report, one-bead one-compound (OBOC) combinatorial libraries containing the arginine-glycine-aspartic acid (RGD) motif were designed and screened against K562 myeloid leukemia cells that had been transfected with the human αvβ3 integrin gene. Cyclic peptide LXW7 was identified as a leading ligand with a built-in handle that binds specifically to αvβ3 and showed comparable binding affinity (IC50 = 0.68 ± 0.08 μmol/L) to some of the well-known RGD “head-to-tail” cyclic pentapeptide ligands reported in the literature. The biotinylated form of LXW7 ligand showed similar binding strength as LXW7 against αvβ3 integrin, whereas biotinylated RGD cyclopentapeptide ligands revealed a 2- to 8-fold weaker binding affinity than their free forms. LXW7 was able to bind to both U-87MG glioblastoma and A375M melanoma cell lines, both of which express high levels of αvβ3 integrin. In vivo and ex vivo optical imaging studies with the biotinylated ligand/streptavidin-Cy5.5 complex in nude mice bearing U-87MG or A375M xenografts revealed preferential uptake of biotinylated LXW7 in tumor. When compared with biotinylated RGD cyclopentapeptide ligands, biotinylated LXW7 showed higher tumor uptake but lower liver uptake. Mol Cancer Ther; 9(10); 2714–23. ©2010 AACR.

Supplementary materials and methods

Supplementary Data from The Use of One-Bead One-Compound Combinatorial Library Technology to Discover High-Affinity αvβ3 Integrin and Cancer Targeting Arginine-Glycine-Aspartic Acid Ligands with a Built-in Handle

Supplementary Figures

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Supplementary Figures 1-4, Methods from Halogenated Benzimidazole Carboxamides Target Integrin α4β1 on T-Cell and B-Cell Lymphomas

Integrin α4β1 is an attractive but poorly understood target for selective diagnosis and treatment of T-cell and B-cell lymphomas. This report focuses on the rapid microwave preparation, structure-activity relationships, and biological evaluation of medicinally pertinent benzimidazole heterocycles as integrin α4β1 antagonists. We documented tumor uptake of derivatives labeled with 125I in xenograft murine models of B-cell lymphoma. Molecular homology models of integrin α4β1 predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. The high-affinity halogenated ligands identified offer attractive tools for medicinal and biological use, including fluoro and iodo derivatives with potential radiodiagnostic (18F) or radiotherapeutic (131I) applications, or chloro and bromo analogues that could provide structural insights into integrin-ligand interactions through photoaffinity, cross-linking/mass spectroscopy, and X-ray crystallographic studies. Cancer Res; 70(13); 5448–56. ©2010 AACR.

Romantic partners routinely regulate each other’s emotions; this phenomenon is known as extrinsic emotion regulation. Previous research investigating emotion regulation in couples has typically examined self-report of emotion regulation from only one member of the couple. It is therefore unclear how much romantic partners agree on which emotion regulation strategies their partner uses and whether this agreement or the unique perspective of each person is the stronger predictor of relationship quality. In the current study (N=395 romantic couples), we applied a bifactor model to assess the extent to which extrinsic emotion regulation processes (expressive suppression, downward social comparison, humor, distraction, direct action, reappraisal, receptive listening, and valuing) related to relationship quality, comparing: a) the unique perspective of the regulator, b) the unique perspective of the target, and c) the shared perspective (consensus) between the target and regulator. The results indicated that it is the target’s, rather than the regulator’s perspective of emotion regulation that predicts the relationship quality of both members of the romantic couple. Overall, these findings suggest that it is not what the regulator thinks they do to regulate their romantic partner’s emotions that relates to relationship quality, but rather the target’s perceptions of the regulation attempt.

Emotionally intelligent people tend to have higher wellbeing. It is possible that their high emotional intelligence (EI) also affects the wellbeing of the people they interact with. This is particularly true in romantic relationships, where a person’s EI may play an important role in their partner’s emotional experiences. The current study (N = 407 romantic dyads) uses actor-partner interdependence models to examine the associations between EI (ability and self-rated) and wellbeing (psychological wellbeing, life satisfaction, affect). Self-rated EI showed consistent actor effects on all wellbeing variables with relatively large effects. Actor effects for ability EI were much smaller and inconsistent for males versus females. Partner effects were largely significant for self-rated, but not ability EI. The results suggest that romantic partners’ EI impacts some aspects of wellbeing and provides further empirical support for researching the dyadic effects of EI.

Previous research has shown that eliciting retrospective confidence ratings during problem-solving enhances performance in high self-efficacy individuals but impairs performance in low self-efficacy individuals. In the current study, we examined whether judgments of solvability, a metacognitive rating made prior to participants’ first-order responses are similarly reactive and whether, like retrospective confidence ratings, this effect is moderated by pre-existing self-efficacy. In two experiments, we showed that judgments of solvability are reactive, but this effect is not moderated by pre-existing self-efficacy. We argue that eliciting metacognitive ratings prior to a participant’s response changes metacognitive control, without necessarily activating self-evaluative thoughts. These results are encouraging for the use of judgments of solvability as an education intervention.

Cognitive flexibility is the ability to adapt to changing contingencies and demands over time. It is often assessed by complex problem solving tasks (e.g., microworld simulations), which require individuals to maintain a goal state over trials. Yet typically analyses summarises performance by mean accuracy per person, which assumes performance is a constant and ignores the trial-by-trial trajectory of individuals that reveal strategy . We tested n = 83 psychology students aged 16 to 45 in a microworld task under different conditions of stochasticity and delay. We modelled trial-by-trial performance according to a prospective model of the true task contingencies versus a reactive strategy adapting to feedback from the last trial,. Most individuals (~66%) appeared to adopt a reactive strategy, however when the task contingencies were immediate, people were more likely to act prospectively. Performance in the microworld task depends on the strategy which varies by person and with the task contingencies.

The lack of vascularization associated with deep burns delays the construction of wound beds, increases the risks of infection, and leads to the formation of hypertrophic scars or disfigurement. To address this challenge, we have fabricated a multi-functional pro-angiogenic molecule by grafting integrin αvβ3 ligand LXW7 and collagen-binding peptide (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY (LDS), and further employed this to functionalize collagen-based Integra scaffolds. Using a large deep burn wound model in C57/BLK6 mice (8–10 weeks old, 26–32g, n = 39), we demonstrated that LDS-modified collagen-based Integra scaffolds loaded with endothelial cells (ECs) accelerate wound healing rate, re-epithelialization, vascularization, and collagen deposition. Specifically, a 2 cm × 3 cm full-thickness skin burn wound was created 48 h after the burn, and then wounds were treated with four groups of different dressing scaffolds, including Integra + ECs, Integra + LDS, and Integra + LDS + ECs with Integra-only as the control. Digital photos were taken for wound healing measurement on post-treatment days 1, 7, 14, 21, 28, and 35. Post-treatment photos revealed that treatment with the Intgera + LDS + ECs scaffold exhibited a higher wound healing rate in the proliferation phase. Histology results showed significantly increased re-epithelialization, increased collagen deposition, increased thin and mixed collagen fiber content, increased angiogenesis, and shorter wound length within the Integra + LDS + ECs group at Day 35. On Day 14, the Integra + LDS + ECs group showed the same trend. The relative proportions of collagen changed from Day 14 to Day 35 in the Integra + LDS + ECs and Integra + ECs groups demonstrated decreased thick collagen fiber deposition and greater thin and mixed collagen fiber deposition. LDS-modified Integra scaffolds represent a promising novel treatment to accelerate deep burn wound healing, thereby potentially reducing the morbidity associated with open burn wounds. These scaffolds can also potentially reduce the need for autografting and morbidity in patients with already limited areas of harvestable skin.

The field of bioaesthetics seeks to understand how modern humans may have first developed art appreciation and is informed by considering a broad range of fields including painting, sculpture, music and the built environment. In recent times there has been a diverse range of art and communication media representing bees, and such work is often linked to growing concerns about potential bee declines due to a variety of factors including natural habitat fragmentation, climate change, and pesticide use in agriculture. We take a broad view of human art representations of bees to ask if the current interest in artistic representations of bees is evidenced throughout history, and in different regions of the world prior to globalisation. We observe from the earliest records of human representations in cave art over 8,000 years old through to ancient Egyptian carvings of bees and hieroglyphics, that humans have had a long-term relationship with bees especially due to the benefits of honey, wax, and crop pollination. The relationship between humans and bees frequently links to religious and spiritual representations in different parts of the world from Australia to Europe, South America and Asia. Art mediums have frequently included the visual and musical, thus showing evidence of being deeply rooted in how different people around the world perceive and relate to bees in nature through creative practice. In modern times, artistic representations extend to installation arts, mixed-media, and the moving image. Through the examination of the diverse inclusion of bees in human culture and art, we show that there are links between the functional benefits of associating with bees, including sourcing sweet-tasting nutritious food that could have acted, we suggest, to condition positive responses in the brain, leading to the development of an aesthetic appreciation of work representing bees.

Human serum albumin (HSA) is the most abundant protein in human blood plasma. It plays a critical role in the native transportation of numerous drugs, metabolites, nutrients, and small molecules. HSA has been successfully used clinically as a noncovalent carrier for insulin (e.g., Levemir), GLP-1 (e.g., Liraglutide), and paclitaxel (e.g., Abraxane). Site-specific bioconjugation strategies for HSA only would greatly expand its role as the biocompatible, non-toxic platform for theranostics purposes. Using the enabling one-bead one-compound (OBOC) technology, we generated combinatorial peptide libraries containing myristic acid, a well-known binder to HSA at Sudlow I and II binding pockets, and an acrylamide. We then used HSA as a probe to screen the OBOC myristylated peptide libraries for reactive affinity elements (RAEs) that can specifically and covalently ligate to the lysine residue at the proximity of these pockets. Several RAEs have been identified and confirmed to be able to conjugate to HSA covalently. The conjugation can occur at physiological pH and proceed with a high yield within 1 h at room temperature. Tryptic peptide profiling of derivatized HSA has revealed two lysine residues (K225 and K414) as the conjugation sites, which is much more specific than the conventional lysine labeling strategy with N-hydroxysuccinimide ester. The RAE-driven site-specific ligation to HSA was found to occur even in the presence of other prevalent blood proteins such as immunoglobulin or whole serum. Furthermore, these RAEs are orthogonal to the maleimide-based conjugation strategy for Cys34 of HSA. Together, these attributes make the RAEs the promising leads to further develop in vitro and in vivo HSA bioconjugation strategies for numerous biomedical applications.

Purpose: Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer–specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI. Experimental Design: SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies. Results: PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P < 0.0001), and 93.03% (P < 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P < 0.0001), and 75.96% (P < 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial. Conclusions: In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.

Gamete fusion is a critical event of mammalian fertilization. A random one-bead one-compound combinatorial peptide library represented synthetic human egg mimics and identified a previously unidentified ligand as Fc receptor–like 3, named MAIA after the mythological goddess intertwined with JUNO. This immunoglobulin super family receptor was expressed on humanoolemmaand played a major role during sperm-egg adhesion and fusion. MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. The complexity of the MAIA isotype may offer a cryptic sexual selection mechanism to avoid genetic incompatibility and achieve favorable fitness outcomes.

Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3β1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4β1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.

As a measure of cytotoxic potency, half-maximal inhibitory concentration (IC50) is the concentration at which a drug exerts half of its maximal inhibitory effect against target cells. It can be determined by various methods that require applying additional reagents or lysing the cells. Here, we describe a label-free Sobel-edge-based method, which we name SIC50, for the evaluation of IC50. SIC50 classifies pre-processed phase-contrast images with a state-of-art vision transformer and allows for the continuous assessment of IC50 in a faster and more cost-efficient manner. We have validated this method using four drugs and 1536-well plates, as well as built a first-of-its-kind web application. We anticipate this method will assist in the high-throughput screening of chemical libraries (e.g., small molecule drugs, siRNA, and microRNA and drug discovery.