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Direct imaging of single molecules at nanostructured interfaces is a grand challenge with potential to enable new, precise material architectures and technologies. Of particular interest are the structural morphology and spectroscopic signatures of the adsorbed molecule, where modern probes are only now being developed with the necessary spatial and energetic resolution to provide detailed information at the molecule-surface interface. Here, we directly characterize the adsorption of individual m-terphenyl isocyanide ligands on a reconstructed Au(111) surface through scanning tunneling microscopy and inelastic electron tunneling spectroscopy. The site-dependent steric pressure of the various surface features alters the vibrational fingerprints of the m-terphenyl isocyanides, which are characterized with single-molecule precision through joint experimental and theoretical approaches. This study provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual surface-binding ligands.

Colorimetric biosensors based on gold nanoparticle (AuNP) aggregation are often challenged by matrix interference in biofluids, poor specificity, and limited utility with clinical samples. Here, we propose a peptide-driven nanoscale disassembly approach, where AuNP aggregates induced by electrostatic attractions are dissociated in response to proteolytic cleavage. Initially, citrate-coated AuNPs were assembled via a short cationic peptide (RRK) and characterized by experiments and simulations. The dissociation peptides were then used to reversibly dissociate the AuNP aggregates as a function of target protease detection, i.e., main protease (Mpro), a biomarker for severe acute respiratory syndrome coronavirus 2. The dissociation propensity depends on peptide length, hydrophilicity, charge, and ligand architecture. Finally, our dissociation strategy provides a rapid and distinct optical signal through Mpro cleavage with a detection limit of 12.3 nM in saliva. Our dissociation peptide effectively dissociates plasmonic assemblies in diverse matrices including 100% human saliva, urine, plasma, and seawater, as well as other types of plasmonic nanoparticles such as silver. Our peptide-enabled dissociation platform provides a simple, matrix-insensitive, and versatile method for protease sensing.

Our study was to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition to investigate the underlying molecular mechanisms. Aged male (23-32 months old) and female (27-28 months old) C57BL/6J mice were classified as non-, probable-, or sarcopenic based on assessments of grip strength, muscle mass, and treadmill running time, using 2 SDs below the mean of their young counterparts as cutoff points. A 9%-22% prevalence of sarcopenia was identified in 23-26 month-old male mice, with more severe age-related declines in muscle function than mass. Females aged 27-28 months showed fewer sarcopenic but more probable cases compared with the males. As sarcopenia progressed, a decrease in muscle contractility and a trend toward lower type IIB fiber size were observed in males. Mitochondrial biogenesis, oxidative capacity, and AMPK-autophagy signaling decreased as sarcopenia progressed in males, with pathways linked to mitochondrial metabolism positively correlated with muscle mass. No age- or sarcopenia-related changes were observed in mitochondrial biogenesis, OXPHOS complexes, AMPK signaling, mitophagy, or atrogenes in females. Our results highlight the different trajectories of age-related declines in muscle mass and function, providing insights into sex-dependent molecular changes associated with sarcopenia progression, which may inform the future development of novel therapeutic interventions., Introduction Sarcopenia, the loss of muscle mass and function due to aging, affects 25%-45% of older adults in the United States (1) and is associated with increased incidence of falls [...]

Evidence suggests that resources to address campus sexual violence (CSV) are inconsistently offered across institutions of higher education (IHE), and thus there is a need for campuses to continually assess their provision of resources and services to improve the climate and well-being of students. Conducting a periodical scan of resources provided is one way for IHE to assess their adherence to best practices. The current study describes the development of the Services, Policies and Programs Audit (SPPA) tool, created to help IHE evaluate their adherence with best practices related to the provision of services, policies, and programs on campus. The tool was piloted with 18 individuals from 12 different IHE across the country. Exploratory evaluation of the SPPA indicates that it may be a useful tool for self-examination of campus policies, services, and prevention and education efforts. Participants from the 12 IHE who participated in the pilot generally reported that the SPPA was helpful to their efforts. Interrater reliability results indicated that the position of the person who completes the tool impacts the scoring, with those who are more familiar with CSV services scoring higher. This aligns with other research indicating that it is important not only to have resources on campus to address CSV but also to ensure that the campus community is aware of them. The SPPA can potentially serve as one part of a larger toolkit used by IHE to assess their efforts to address CSV.

Confining molecules in the nanoscale environment can lead to dramatic changes of their physical and chemical properties, which opens possibilities for new applications. There is a growing interest in liquefied gas electrolytes for electrochemical devices operating at low temperatures due to their low melting point. However, their high vapor pressure still poses potential safety concerns for practical usages. Herein, we report facile capillary condensation of gas electrolyte by strong confinement in sub-nanometer pores of metal-organic framework (MOF). By designing MOF-polymer membranes (MPMs) that present dense and continuous micropore (~0.8 nm) networks, we show significant uptake of hydrofluorocarbon molecules in MOF pores at pressure lower than the bulk counterpart. This unique property enables lithium/fluorinated graphite batteries with MPM-based electrolytes to deliver a significantly higher capacity than those with commercial separator membranes (~500 mAh g-1 vs.

BackgroundThe Ras signaling pathway is commonly dysregulated in human malignant peripheral nerve sheath tumors (MPNSTs). It is well known that galectin-1 (Gal-1) is essential to stabilize membrane Ras and thereby induce the activation of Ras. However, the role of Gal-1 in MPNST progression remains unknown. The aim of this study was to examine whether Gal-1 knockdown could have an effect on the Ras signaling pathway.MethodsCell viability, apoptosis assay, and colony formation were performed to examine the effects of inhibition of Gal-1 in MPNST cells. We used a human MPNST xenograft model to assess growth and metastasis inhibitory effects of Gal-1 inhibitor LLS2.ResultsGal-1 was upregulated in MPNST patients and was highly expressed in MPNST cells. Knockdown of Gal-1 by small interfering (si)RNA in Gal-1 expressing MPNST cells significantly reduces cell proliferation through the suppression of C-X-C chemokine receptor type 4 (CXCR4) and the rat sarcoma viral oncogene homolog (RAS)/extracellular signal-regulated kinase (ERK) pathway, which are important oncogenic signaling in MPNST development. Moreover, Gal-1 knockdown induces apoptosis and inhibits colony formation. LLS2, a novel Gal-1 allosteric small molecule inhibitor, is cytotoxic against MPNST cells and was able to induce apoptosis and suppress colony formation in MPNST cells. LLS2 treatment and Gal-1 knockdown exhibited similar effects on the suppression of CXCR4 and RAS/ERK pathways. More importantly, inhibition of Gal-1 expression or function by treatment with either siRNA or LLS2 resulted in significant tumor responses in an MPNST xenograft model.ConclusionOur results identified an oncogenic role of Gal-1 in MPNST and that its inhibitor, LLS2, is a potential therapeutic agent, applied topically or systemically, against MPNST.

Objective Study Setting and Design Data Sources and Analytic Sample Principal Findings Conclusions To estimate differences in facility‐level outcomes between nursing homes which reached Institutional Special Needs Plan (I‐SNP) maturity and those which never cared for I‐SNP enrollees.We used a difference‐in‐differences design to estimate the effect of I‐SNP maturity, defined as having at least 33.75% of Medicare long‐stayers in the nursing home enrolled in any I‐SNP. Our main outcome was the hospitalization rate in each nursing home‐year. Secondary outcomes included the share of residents with medication use, fall, urinary tract infection, catheter insertion, pressure ulcer, physical restraint use, increased need for help with activities of daily living (ADLs), and mortality.This repeated cross‐sectional study used 100% Medicare claims, Minimum Data Set assessments, and publicly available Medicare Advantage (MA) plan characteristics data (2004–2021). We included all MA beneficiaries who resided in US nursing homes which reached I‐SNP maturity and those without I‐SNP enrollees.We identified 2530 nursing homes which reached I‐SNP maturity (treated) and 9830 nursing homes without I‐SNP enrollees (untreated). There were some differences observed between these nursing homes, including shares of residents who were White (76.42% vs. 84.84%) and on Medicaid (66.94% vs. 55.45%). These nursing homes were also larger on average (141.76 beds vs. 87.56 beds). From the difference‐in‐differences model, nursing homes which reached I‐SNP maturity experienced declines of 4.1 percentage points (pp) for hospitalizations, 1.0 pp for pressure ulcers, 1.3 pp for urinary tract infections (p < 0.001) alongside increases in the need for help with ADLs, use of antipsychotics, falls, and physical restraints.Nursing homes which reached I‐SNP maturity experienced fewer hospitalizations and pressure ulcers but a decline in function and increase in other negative outcomes. I‐SNPs may be a promising model to improve care for long‐stay residents, but more research is needed to understand potential adverse consequences. [ABSTRACT FROM AUTHOR]

Rising temperatures due to the current climate crisis will soon have devastating impacts on crop performance and resilience. In particular, CO2 assimilation is dramatically limited at high temperatures. CO2 assimilation is accomplished by rubisco, which is inhibited by the binding of inhibitory sugar phosphates to its active site. Plants therefore utilize the essential chaperone rubisco activase (RCA) to remove these inhibitors and enable continued CO2 fixation. However, RCA does not function at moderately high temperatures (42°C), resulting in impaired rubisco activity and reduced CO2 assimilation. We set out to understand temperature-dependent RCA regulation in four different C4 plants, with a focus on the crop plants maize (two cultivars) and sorghum, as well as the model grass Setaria viridis (setaria) using gas exchange measurements, which confirm that CO2 assimilation is limited by carboxylation in these organisms at high temperatures (42°C). All three species express distinct complements of RCA isoforms and each species alters the isoform and proteoform abundances in response to heat; however, the changes are species-specific. We also examine whether the heat-mediated inactivation of RCA is due to biochemical regulation rather than simple thermal denaturation. We reveal that biochemical regulation affects RCA function differently in different C4 species, and differences are apparent even between different cultivars of the same species. Our results suggest that each grass evolved different strategies to maintain RCA function during stress and we conclude that a successful engineering approach aimed at improving carbon capture in C4 grasses will need to accommodate these individual regulatory mechanisms. [ABSTRACT FROM AUTHOR]

The article discusses the potential benefits of Institutional Special-Needs Plans (I-SNPs) for nursing homes, focusing on how these plans could improve care quality and reduce costs. Topics discussed include the financial and clinical implications of I-SNPs, the role of on-site clinicians in enhancing care, and the challenges faced in integrating these plans within the broader Medicare and Medicaid systems.

A large gap in provision of services for children with developmental disabilities (DD) has been identified in Ethiopia, especially in the education system. Including children with disabilities in mainstream schools is encouraged by policies, but progress in this direction has been limited. This study aimed to explore stakeholders' perspectives on contextual factors relevant for inclusive education for children with DD in mainstream schools in Ethiopia, with a focus on Adis Ababa. Data were collected through semi-structured interviews with 39 local stakeholders, comprising caregivers of children with DD, school teachers and principals/managers, non-governmental organisation representatives, government officials, clinicians and academics/consultants. We used template analysis to code the data and map them onto domains of the Context and Setting dimensions of the Context and Implementation of Complex Interventions framework. Stakeholders discussed frameworks in the Legal and Ethical context endorsing the right of all children to education. However, they reported multiple reasons why children with DD in Ethiopia have limited access to education, either in special or mainstream schools. First, individual features, such as gender and support needs, discussed in the Epidemiological context, may affect the likelihood of a child with DD to be accepted in school. Transportation challenges are a key barrier in the Geographical context. Socio-economic and Socio-cultural contexts present barriers at the levels of the nation, school and family, mostly related to limited services and material and financial resources and limited awareness of DD. Stakeholders believe the currently limited but growing commitment in the Political context can support progress towards the removal of these barriers. Our findings can form the basis for development of an implementation plan that addresses such barriers and capitalises on existing facilitators. [ABSTRACT FROM AUTHOR]

Background: Maize stalk rot (MSR) caused by Fusarium graminearum is the primary factor contributing to the reduction in maize yield and quality. However, this soil‐borne disease presents a significant challenge for sustainable control through field management and chemical agents. The screening of novel biocontrol agents can aid in developing innovative and successful strategies for MSR control. Results: A total of 407 strains of bacteria were isolated from the rhizosphere soil of a resistant maize inbred line. One strain exhibited significant antagonistic activity in plate and pot experiments, and was identified as Burkholderia ambifaria H8. The strain could significantly inhibit the mycelial growth and spore germination of F. graminearum, induce resistance to stalk rot, and promote plant growth. The volatile compounds produced by strain H8 and its secondary metabolites in the sterile fermentation broth exhibited antagonistic activity. The primary volatile compound produced by strain H8 was identified as dimethyl disulfide (DMDS) using gas chromatography tandem mass spectrometry. Through in vitro antagonistic activity assays and microscopic observation, it was confirmed that DMDS was capable of inhibiting mycelial growth and disrupting the mycelial structure of F. graminearum, suggesting it may be the major active compound for strain H8. The transcriptome data of F. graminearum further indicated that strain H8 and its volatile compounds could alter pathogenic fungi metabolism, influence the related metabolic pathways, and potentially induce cell apoptosis within F. graminearum. Conclusion: Our results showed that B. ambifaria H8 was capable of producing the volatile substance dimethyl disulfide, which influenced the synthesis and permeability of cell membranes in pathogens. Thus, B. ambifaria H8 was found to be a promising biological control agent against MSR. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Most online media consumption is not driven by a desire to seek out news and politics. However, the public may still encounter politics because it arises organically in communities devoted to non-political subjects. This study examines the potential of popular reality television online discussion forums to serve as online third spaces and stimulate political discussion due to the natural connections that audiences make between the cast members and "real life" in reality-based programming. Based on a quantitative analysis of political comments made to reality television subreddits and a survey of visitors to a popular subreddit focused on The Bachelor television show, the findings not only demonstrate the ability of entertainment-focused online communities to expose a broad segment of the public to political talk, but also point to the obstacles in promoting political discussion that is simultaneously enjoyable, informative, and tolerant of diverse viewpoints. [ABSTRACT FROM AUTHOR]

Background: Improving quality of care provided to short‐stay patients with dementia in nursing homes is a policy priority. However, it is unknown whether dementia‐focused care strategies are associated with improved clinical outcomes or lower utilization and costs for short‐stay dementia patients. Methods: We performed a national survey of nursing home administrators in 2020–2021, asking about the presence of three dementia‐focused care services used for their short‐stay patients: (1) a dementia care unit, (2) cognitive deficiency training for staff, and (3) dementia‐specific occupational therapy. Using Medicare claims, we identified short‐stay episodes for beneficiaries residing in surveyed skilled nursing facilities (SNFs) with and without dementia. We compared clinical, cost, and utilization outcomes for dementia patients in SNFs, which did and did not offer dementia‐focused care services. As a counterfactual control, we compared these differences to those for non‐dementia patients in the same facilities. Our primary quantity of interest was an interaction term between a patients' dementia status and the presence of a dementia‐focused care tool. Results: The study population included 102,860 Medicare episodes of care from 377 SNF survey respondents in 2018–2019. In adjusted comparisons of the interaction between dementia status and the presence of each dementia‐focused care tool, dementia care units were associated with a 1.5‐day increase in healthy days at home in the 90 days following discharge (p = 0.01) and a 3.1% decrease in the likelihood of a subsequent SNF admission (p = 0.001). Cognitive deficiency training was also associated with a 2.0% increase in antipsychotics (p = 0.03), whereas dementia‐specific occupational therapy was associated with a 1.2% increase in falls (p = 0.01) per patient episode. Conclusions: Self‐reported use of dementia care units for short‐stay patients was associated with modestly better performance in some, but not all, outcome measures. This provides hypothesis‐generating evidence that dementia care units could be a promising mechanism to improve care delivery in nursing homes. [ABSTRACT FROM AUTHOR]

Encapsulated cell therapy (ECT) shows significant potential for treating neurodegenerative disorders including Alzheimer's and Parkinson's, which currently lack curative medicines and must be managed symptomatically. This novel technique encapsulates functional cells with a semi‐permeable membrane, providing protection while enabling critical nutrients and therapeutic substances to pass through. Traditional ECT procedures, on the other hand, pose difficulties in terms of cell survival and retrieval. We introduce the Microtube Array Membrane (MTAM), a revolutionary technology that solves these constraints, in this comprehensive overview. Microtube Array Membrane has distinct microstructures that improve encapsulated cells' long‐term viability by combining the advantages of macro and micron scales. Importantly, the MTAM platform improves biosafety by allowing the entire encapsulated unit to be retrieved in the event of an adverse reaction. Our findings show that MTAM‐based ECT has a great potential in a variety of illness situations. For cancer treatment, hybridoma cells secreting anti‐CEACAM 6 antibodies inhibit triple‐negative breast cancer cell lines for an extended period of time. In animal brain models of Alzheimer's disease, hybridoma cells secreting anti‐pTau antibodies successfully reduce pTau buildup, accompanied by improvements in memory performance. In mouse models, MTAM‐encapsulated primary cardiac mesenchymal stem cells dramatically improve overall survival and heart function. These findings illustrate the efficacy and adaptability of MTAM‐based ECT in addressing major issues such as immunological isolation, cell viability, and patient safety. We provide new possibilities for the treatment of neurodegenerative illnesses and other conditions by combining the potential of ECT with MTAM. Continued research and development in this subject has a lot of promise for developing cell therapy and giving hope to people suffering from chronic diseases. [ABSTRACT FROM AUTHOR]