Recent Experience Affects Delay Discounting: Evidence across Temporal Framing, Signs, and Magnitudes.

Delay discounting, the decrease in outcome value as a function of delay to receipt, is an extensive area of research. How delays are framed (i.e., temporal framing), as well as the sign and magnitude of an outcome, produce important effects on the degree to which outcomes are discounted. Here, we examined how recent experience (i.e., order of presentation) modifies these well-known findings. Experiment 1 examined the effects of temporal framing across gains and losses. Regardless of outcome sign, the order of task presentation affected the effect of temporal framing. In particular, when typical delay frames (e.g., 1 week) preceded delays framed as actual dates (e.g., February 15), discounting was less in the date-framed task. However, when dates were followed by the delay frame, there was no difference in the degree of discounting. The experience of date-framed delays persisted or carried over to the delay-framed task. Experiment 2 examined recent experience and the magnitude effect. In particular, $10 and $100 were discounted similarly between-subjects when it was the first task completed. However, once participants completed the second magnitude task, the magnitude effect was present both within-subjects and across subjects. Furthermore, $10 was discounted more steeply when it followed $100, and $100 was discounted less steeply when it followed $10. The impact of recent experience on delay discounting has important implications for understanding mechanisms that may contribute to delay discounting. Recent experience should be considered when designing delay discounting experiments as well as when implementing interventions to reduce steep delay discounting.

COVID-19 Federal Funding To Health Centers: Tracking Distribution, Locations, And Patient Characteristics.

In 2020 and 2021, health centers received federal funding to support their COVID-19 pandemic response, yet little is known about how the funds were distributed. This study identified ten sources of funding distributed to 1,352 centers, ranging from $19 to $1.22 billion per center. When we examined patient and organizational characteristics by quartiles of funding per patient, health centers in the highest-funded quartile (quartile 4) were more likely rural and in the South; employed lower percentages of physicians; and had the highest percentages of sicker, uninsured, and unhoused patients. Centers in the lowest-funded quartile (quartile 1) were more likely urban, employed lower percentages of nurse practitioners, and had the highest percentages of Medicaid enrollees. With the end of pandemic-related funding in 2023, combined with Medicaid unwinding concerns, targeted investment is needed to mitigate a financial cliff and help maintain health centers' capacity to provide high-quality services to those most in need.

Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons.

Delivering macromolecules across biological barriers such as the blood-brain barrier limits their application in vivo. Previous work has demonstrated that Toxoplasma gondii, a parasite that naturally travels from the human gut to the central nervous system (CNS), can deliver proteins to host cells. Here we engineered T. gondii's endogenous secretion systems, the rhoptries and dense granules, to deliver multiple large (>100 kDa) therapeutic proteins into neurons via translational fusions to toxofilin and GRA16. We demonstrate delivery in cultured cells, brain organoids and in vivo, and probe protein activity using imaging, pull-down assays, scRNA-seq and fluorescent reporters. We demonstrate robust delivery after intraperitoneal administration in mice and characterize 3D distribution throughout the brain. As proof of concept, we demonstrate GRA16-mediated brain delivery of the MeCP2 protein, a putative therapeutic target for Rett syndrome. By characterizing the potential and current limitations of the system, we aim to guide future improvements that will be required for broader application.

Exploring the Complex Chemistry and Degradation of Ascorbic Acid in Aqueous Nanoparticle Synthesis.

Ascorbic acid (AA) is the most widely used reductant for noble metal nanoparticle (NP) synthesis. Despite the synthetic relevance, its aqueous chemistry remains misunderstood, due in part to various assumptions about its reduction pathway which are insufficiently supported by experimental evidence. This study aims to provide an understanding of the complex chemistry associated with AA under aqueous conditions. We demonstrate that (i) AA undergoes appreciable degradation in alkaline solution on a timescale relevant to NP synthesis, (ii) contrary to popular belief, AA does not degrade into dehydroascorbic acid (DHA), nor is DHA the oxidized product of AA under noble metal NP synthetic conditions, (iii) DHA, which readily degrades under alkaline conditions, can also effectively reduce metal salt precursors to metal NPs, (iv) neither ascorbate nor dehydroascorbate act as surface capping agents post-synthetically on the NPs (v) AA degradation time greatly affects the morphology and polydispersity of the resultant NP. Results from our mechanistic investigation enabled us to utilize purposefully-aged reductants to achieve control over shape yield and monodispersity in the seed-mediated synthesis of Au nanorods. Our findings have important implications for achieving monodispersed products in the many metal NP synthesis reactions that make use of AA as a reducing agent.

Identification of a Novel Protein Phosphatase 2A Activator, PPA24, as a Potential Therapeutic for FOLFOX-Resistant Colorectal Cancer.

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC50 values in the range of 2.36-6.75 µM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

Probabilistic Techno-Economic Assessment of Medium-Scale Photoelectrochemical Fuel Generation Plants.

Photoelectrochemical (PEC) systems are promising approaches for sustainable fuel processing. PEC devices, like conventional photovoltaic-electrolyzer (PV-EC) systems, utilize solar energy for splitting water into hydrogen and oxygen. Contrary to PV-EC systems, PEC devices integrate the photoabsorber, the ionic membrane, and the catalysts into a single reactor. This integration of elements potentially makes PEC systems simpler in design, increases efficiency, offers a cost advantage, and allows for implementation with higher flexibility in use. We present a detailed techno-economic evaluation of PEC systems with three different device designs. We combine a system-level techno-economic analysis based on physical performance models (including degradation) with stochastic methods for uncertainty assessments, also considering the use of PV and EC learning curves for future cost scenarios. For hydrogen, we assess different PEC device design options (utilizing liquid or water vapor as reactant) and compare them to conventional PV-EC systems (anion or cation exchange). We show that in the current scenario, PEC systems (with a levelized cost of hydrogen of 6.32 $/kgH2 ) located in southern Spain are not yet competitive, operating at 64% higher costs than the PV-driven anion exchange EC systems. Our analysis indicates that PEC plants' material and size are the most significant factors affecting hydrogen costs. PEC designs operating with water vapor are the most economical designs, with the potential to cost about 10% less than PV-EC systems and to reach a 2 $/kgH2 target by 2040. If a sunlight concentrator is incorporated, the PEC-produced hydrogen cost is significantly lower (3.59 $/kgH2 in the current scenario). Versions of the concentrated PEC system that incorporate reversible operation and CO2 reduction indicate a levelized cost of storage of 0.2803 $/kWh for the former and a levelized cost of CO of 0.546 $/kgCO for the latter. These findings demonstrate the competitiveness and viability of (concentrated) PEC systems and their versatile use cases. Our study shows the potential of PEC devices and systems for hydrogen production (current and future potential), storage applications, and CO production, thereby highlighting the importance of sustainable and cost-effective design considerations for future advancements in technology development in this field.

A multispectral 3D live organoid imaging platform to screen probes for fluorescence guided surgery.

Achieving complete tumor resection is challenging and can be improved by real-time fluorescence-guided surgery with molecular-targeted probes. However, pre-clinical identification and validation of probes presents a lengthy process that is traditionally performed in animal models and further hampered by inter- and intra-tumoral heterogeneity in target expression. To screen multiple probes at patient scale, we developed a multispectral real-time 3D imaging platform that implements organoid technology to effectively model patient tumor heterogeneity and, importantly, healthy human tissue binding.

H2Se-evolving bio-heterojunctions promote cutaneous regeneration in infected wounds by inhibiting excessive cellular senescence.

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.

Sociodemographic representation in randomized controlled trials for anxiety-related disorders in the U.S.: A systematic review (1993-2023).

Cognitive behavioral therapies have been identified as evidence-based treatments for anxiety-related disorders. However, data supporting the effectiveness of these treatments have been largely collected from participants with majoritized identities, potentially limiting the extent to which they can be considered "evidence-based" for clients from minoritized groups. The current review examined sociodemographic representation and quality of sociodemographic reporting in randomized controlled trials for anxiety-related disorders in the U.S. between 1993 and 2023. We conducted a systematic literature review of U.S.-based randomized controlled trials of cognitive behavioral therapies for anxiety-related disorders, extracted data on sociodemographic variables, and rated quality of reporting. Data from 55 eligible studies (N = 4492) indicated that white and female identities were overrepresented relative to the U.S. population, with variables like disability status, sexual orientation, and religious identification consistently ignored. In addition, quality of reporting was generally poor (mean = 3.6 out of 10), with many studies failing to account for demographic variables in their analyses or description of study limitations. Publication year, sample size, and NIH funding status did not significantly predict gender representation (% women), ethnoracial representation (% white), or quality of reporting. These findings underscore the importance of critically evaluating to whom "evidence-based" treatments apply and increasing diversity of clinical samples, to ensure that evidence-based treatments are inclusive. Recommendations for future research, clinical implications, and limitations are discussed.

Probing ligand conformation and net dimensionality in a series of tetraphenylethene-based metal-organic frameworks.

Tetraphenylethene-based ligands with lowered symmetry are promising building blocks for the construction of novel luminescent metal-organic frameworks (MOFs). However, few examples have been reported, and predicting the ligand conformation and the dimensionality of the resulting MOF remains challenging. In order to uncover how synthetic conditions and accessible ligand conformations may affect the resulting MOF structure, four new MOF structures were synthesized under solvothermal conditions using the meta-coordinated tetraphenylethene-based ligand m-ETTC and paddlewheel SBUs composed of Co(II), Cu(II), and Zn(II). WSU-10 (WSU = Washington State University) is formed with either Zn or Cu comprising stacked psuedo-2D layers. The dimensionality of WSU-10 can be intentionally increased through the addition of pyrazine as a pillar ligand into the synthesis, forming the 3D structure WSU-11. The third structure, WSU-20, is formed by the combination of Zn or Co with m-ETTC and is intrinsically 3D without the use of a pillar ligand; interestingly, this is the result of a distortion in the paddlewheel SBU. Finally, Cu was also found to form a new structure (WSU-12), which displays an m-ETTC conformation unique from that found in the other isolated MOFs. Structural features are compared across the series and a mechanistic relationship between WSU-10 and -20 is proposed, providing insight into the factors that can encourage the generation of frameworks with increased dimensionality.

The effect of color on license plate recall.

Previous research has shown there are particular patterns of license plate designs that are easier to recall. Missouri license plate patterns (AB1-C2D) somewhat diverge from what research suggests works best for recall. The current study examined whether incorporating color into license plates would improve recall, and also whether awareness or explanation of license plate formats would affect recall accuracy. Across two experiments, participants viewed license plate stimuli with and without color and attempted to recall them. The hypothesis was that incorporating color would improve recall, but the hypothesis was not supported. Results also did not show that prior exposure or explanation of formats affected accuracy. Future research should explore additional ways to improve license plate designs that would be easy to implement. Such improvements to license plate design would be useful because efforts to improve the public's awareness of formats would be expensive and likely ineffective.

Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V2C MXene bio-heterojunctions (2D2-bioHJs) is devised. Under ultrasonication, 2D2-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D2-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.

Recent progress in electrode materials for micro-supercapacitors.

Micro-supercapacitors (MSCs) stand out in the field of micro energy storage devices due to their high power density, long cycle life, and environmental friendliness. The key to improving the electrochemical performance of MSCs is the selection of appropriate electrode materials. To date, both the composition and structure of electrode materials in MSCs have become a hot research topic, and it is urgent to compose a review to highlight the most important research achievements, major challenges, opportunities, and encouraging perspectives in this field. In this review, research background of MSCs is first reviewed followed by their working principles, structural classifications, and physiochemical and electrochemical characterization techniques. Next, various materials and preparation methods are summarized, and the relationship between the MSC performance and structure and composition of materials are discussed in depth. Finally, this review provides a comprehensive suggestion on accelerating the development of electrode materials to facilitate the commercialization of MSCs.

Pediatric human nose organoids demonstrate greater susceptibility, epithelial responses, and cytotoxicity than adults during RSV infection.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections, causing significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe as compared to healthy adults is not fully understood. In the present study, we infect both pediatric and adult human nose organoid-air liquid interface (HNO-ALIs) cell lines with two contemporary RSV isolates and demonstrate how they differ in virus replication, induction of the epithelial cytokine response, cell injury, and remodeling. Pediatric HNO-ALIs were more susceptible to early RSV replication, elicited a greater overall cytokine response, demonstrated enhanced mucous production, and manifested greater cellular damage compared to their adult counterparts. Adult HNO-ALIs displayed enhanced mucus production and robust cytokine response that was well controlled by superior regulatory cytokine response and possibly resulted in lower cellular damage than in pediatric lines. Taken together, our data suggest substantial differences in how pediatric and adult upper respiratory tract epithelium responds to RSV infection. These differences in epithelial cellular response can lead to poor mucociliary clearance and predispose infants to a worse respiratory outcome of RSV infection.

Uranyl uptake into metal-organic frameworks: a detailed X-ray structural analysis.

Metal-organic frameworks (MOF) are a subclass of porous framework materials that have been used for a wide variety of applications in sensing, catalysis, and remediation. Among these myriad applications is their remarkable ability to capture substances in a variety of environments ranging from benign to extreme. Among the most common and problematic substances found throughout the world's oceans and water supplies is [UO2]2+, a common mobile ion of uranium, which is found both naturally and as a result of anthropogenic activities, leading to problematic environmental contamination. While some MOFs possess high capability for the uptake of [UO2]2+, many more of the thousands of MOFs and their modifications that have been produced over the years have yet to be studied for their ability to uptake [UO2]2+. However, studying the thousands of MOFs and their modifications presents an incredibly difficult task. As such, a way to narrow down the numbers seems imperative. Herein, we evaluate the binding behaviors as well as identify the specific binding sites of [UO2]2+ incorporated into six different Zr MOFs to elucidate specific features that improve [UO2]2+ uptake. In doing so, we also present a method for the determination and verification of these binding sites by Anomalous wide-angle X-ray scattering, X-ray fluorescence, and X-ray absorption spectroscopy. This research not only presents a way for future research into the uptake of [UO2]2+ into MOFs to be conducted but also a means to evaluate MOFs more generally for the uptake of other compounds to be applied for environmental remediation and improvement of ecosystems globally.

Composition-tunable transition metal dichalcogenide nanosheets via a scalable, solution-processable method.

The alloying of two-dimensional (2D) transition metal dichalcogenides (TMDs) is an established route to produce robust semiconductors with continuously tunable optoelectronic properties. However, typically reported methods for fabricating alloyed 2D TMD nanosheets are not suitable for the inexpensive, scalable production of large-area (m2) devices. Herein we describe a general method to afford large quantities of compositionally-tunable 2D TMD nanosheets using commercially available powders and liquid-phase exfoliation. Beginning with Mo(1-x)WxS2 nanosheets, we demonstrate tunable optoelectronic properties as a function of composition. We extend this method to produce Mo0.5W0.5Se2 MoSSe, WSSe, and quaternary Mo0.5W0.5SSe nanosheets. High-resolution scanning transmission electron microscopy (STEM) imaging confirms the atomic arrangement of the nanosheets, while an array of spectroscopic techniques is used to characterize the chemical and optoelectronic properties. This transversal method represents an important step towards upscaling tailored TMD nanosheets with a broad range of tunable optoelectronic properties for large-area devices.

Altering phosphorylation in cancer through PP2A modifiers.

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase integral to the regulation of many cellular processes. Due to the deregulation of PP2A in cancer, many of these processes are turned toward promoting tumor progression. Considerable research has been undertaken to discover molecules capable of modulating PP2A activity in cancer. Because PP2A is capable of immense substrate specificity across many cellular processes, the therapeutic targeting of PP2A in cancer can be completed through either enzyme inhibitors or activators. PP2A modulators likewise tend to be effective in drug-resistant cancers and work synergistically with other known cancer therapeutics. In this review, we will discuss the patterns of PP2A deregulation in cancer, and its known downstream signaling pathways important for cancer regulation, along with many activators and inhibitors of PP2A known to inhibit cancer progression.

Climbing the Hydrogen Evolution Volcano with a NiTi Shape Memory Alloy.

Alkaline water electrolysis is a sustainable way to produce green hydrogen using renewable electricity. Even though the rates of the cathodic hydrogen evolution reaction (HER) are 2-3 orders of magnitude less under alkaline conditions than under acidic conditions, the possibility of using non-precious metal catalysts makes alkaline HER appealing. We identify a novel and facile route for substantially improving HER performance via the use of commercially available NiTi shape memory alloys, which upon heating undergo a phase transformation from the monoclinic martensite to the cubic austenite structure. While the room-temperature performance is modest, austenitic NiTi outperforms Pt (which is the state-of-the-art HER electrocatalyst) in terms of current density by ≤50% at 80 °C. Surface ensembles presented by the austenite phase are computed with density functional theory to bind hydrogen more weakly than either metallic Ni or Ti and to have binding energies ideally suited for HER.

Predictors of non-offending caregiver support in cases of child sexual abuse.

BACKGROUND: In cases of child sexual abuse (CSA), a supportive non-offending caregiver (NOC) is important for the child's overall well-being and adjustment. NOC support is also predictive of CSA cases moving forward to prosecution. Limited research has studied CSA case factors in relation to NOC supportive behaviors across numerous support dimensions. OBJECTIVE: We investigated what case details predicted four different dimensions of caregiver support. PARTICIPANTS AND SETTINGS: In this secondary analysis, a sample of 500 CSA cases from four prosecutors' offices in one New England state from 2009 to 2013 were randomly selected and reviewed. METHOD: This study used regression analysis to test 13 case characteristics (e.g., disclosure of abuse, NOC's relationship to perpetrator) as predictors of NOC support dimensions: belief of victim, support of prosecution, protection of victim, and whether a child protective services neglect report was filed against the caregiver. RESULTS: When the perpetrator was their romantic partner, the NOC was less likely to protect and believe the child victim, yet more likely to support prosecution. NOCs were more likely to demonstrate belief when the child disclosed to them first. CONCLUSION: Our findings reveal the importance of the key case factors that are predictive of NOC support. This is the first study to examine these many case factors in relation to these four dimensions of support. Knowledge of these predictors can play an important role in better understanding the complexity of NOC support predictors and facilitating interventions designed to enhance such support.

MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.