enhancer promoter

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. Here, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of antigens and CpG to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant...

Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein we report how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination. We precisely manipulate the immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod-like bacteria)...

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts...

Cucumber (Cucumis sativus, Cs) tendrils are slender vegetative organs that typically require manual removal to ensure orderly growth during greenhouse cultivation. Here, we identified cucumber tendril-less (tl), a Tnt1 retrotransposon-induced insertion mutant lacking tendrils. Map-based cloning identified the mutated gene, CsaV3_3G003590, which we designated as CsTL, which is homologous to Arabidopsis thaliana LATERAL SUPPRESSOR (AtLAS). Knocking out CsTL repressed tendril formation but did not affect branch initiation, whereas overexpression of CsTL resulted in the formation of two or more tendrils in one leaf axil...

CuInS2 (CIS) quantum dots (QDs) represent an important class of colloidal materials with broad application potential, owing to their low toxicity and unique optical properties. Although coating with a ZnS shell has been identified as a crucial method to enhance optical performance, the occurrence of cation exchange has historically resulted in the unintended formation of Cu-In-Zn-S alloyed QDs, causing detrimental blueshifts in both absorption and photoluminescence (PL) spectral profiles. In this study, we present a facile one-pot synthetic strategy aimed at impeding the cation exchange process and promoting ZnS shell growth on CIS core QDs...

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the β2 -adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine. In a murine model of femoral osteotomy combined with cortical impact brain injury, TBI was associated with ADRB2-dependent enhanced fracture healing compared with osteotomy alone...

Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be prominently altered in human SCLC, including, among others, T cell exclusion, downregulation of components of the MHC-class I antigen processing and presentation machinery, or upregulation of macrophage inhibitory checkpoints...

In light of the long-term constraints posed by the "dual carbon" objective, can digital technology emerge as a transformative solution for enterprises to embark on a sustainable development trajectory? The existing body of research has yet to reach a consensus. In order to shed further light on the intricate relationship between digital transformation and ESG performance of enterprises, this study empirically examines the mechanisms and boundaries through which digital transformation influences ESG performance, based on observational data from A-share manufacturing listed companies in Shanghai Stock Exchange and Shenzhen Stock Exchange spanning from 2011 to 2021...

Hydrogen is considered clean energy with broad application prospects for the 21st century, and water electrolysis plays a crucial role in hydrogen production. However, economic limitations and large overpotential values hinder its development. In this study, we deposited nickel (Ni), iron (Fe), and sulfur (S) onto nickel foam (NF) using the constant potential method to form the Ni-S-Fe/NF catalyst, which exhibited an exceptionally low overpotential (31 mV) at a current density of -10 mA cm-2 , and a Tafel slope of 75...

This study explored the acceptability of Children and Teens in Charge of their Health (CATCH), a program for children with spina bifida or cerebral palsy to enhance their physical activity and diet. Qualitative interviews were conducted with children ( n  = 6) and their parents ( n  = 6) who participated in CATCH. Analysis used an environmental systems framework. Microsystem factors impacting acceptability of the program were: Children's motivations for change, their age, and their physical health...

Phosphatidylinositol 3-kinase α (PI3Kα) is a heterodimer of p110α catalytic and p85 adaptor subunits that is activated by agonist-stimulated receptor tyrosine kinases. Although p85α recruits p110α to activated receptors on membranes, p85α loss, which occurs commonly in cancer, paradoxically promotes agonist-stimulated PI3K/Akt signaling. p110α localizes to microtubules via microtubule-associated protein 4 (MAP4), facilitating its interaction with activated receptor kinases on endosomes to initiate PI3K/Akt signaling...

BACKGROUND: Smoking ban policies (SBPs) are potent health interventions and offer the potential to influence antismoking behavior. The Korean government completely prohibited smoking in indoor sports facilities, including billiard halls, since the government revised the National Health Promotion Act in December 2017. OBJECTIVE: This study aimed to examine the impact of the SBP on the economic outcomes of indoor sports facilities, particularly billiard halls. METHODS: This study used credit card sales data from the largest card company in South Korea...

Developing synthetic supramolecular receptors to solubilize, scavenge, recognize, encapsulate, and sense steroids is challenging. Despite a limited number of receptors having affinity with steroids, none exists to bind steroidal bile acids selectively. Herein, we report a C 2 -symmetric metal-organic cage [Pd6 L2 4 ]12+ and an expanded version of the Fujita cage [Pd6 L1 4 ]12+ , built with a conformationally flexible ligand L2 , accessed through coordination-driven self-assembly. We examined both cages for steroid recognition in water: both have certain shared characteristics and distinctive features...

The influence of tourism development and economic policy uncertainties on environmental sustainability is substantial. Promoting responsible tourism and using sustainable tourism practises, like offering eco-friendly lodging, is a key part of protecting natural habitats and lowering carbon footprints. Hence, this study tries to examine the relationship between tourism development, economic policy uncertainty, renewable energy, and natural resources on the ecological footprint of India during 1990-2022. This study applies a novel dynamic ARDL simulation approach for long-run and short-run analyses...

Inflammation plays a crucial role in the pathophysiology of various kidney diseases. Kidney perivascular cells (pericytes/fibroblasts) are responsible for producing proinflammatory molecules, promoting immune cell infiltration, and enhancing inflammation. Vascular adhesion protein-1, expressed in kidney perivascular cells, is an ectoenzyme that catalyzes the oxidative deamination of primary amines with the production of hydrogen peroxide in the extracellular space. Our study demonstrated that blocking this enzyme suppressed hydrogen peroxide production and neutrophil infiltration, thereby reducing renal ischemia-reperfusion injury...

Cytosolic thiouridylase 2 (CTU2) is an enzyme modifying transfer RNAs post-transcriptionally, which has been implicated in breast cancer and melanoma development. And we found CTU2 participated in hepatocellular carcinoma (HCC) progression here. HepG2 cells as well as xenograft nude mice model were employed to investigate the role of CTU2 in HCC development in vitro and in vivo respectively. Further, we defined CTU2 as a Liver X receptor (LXR) targeted gene, with a typical LXR element in the CTU2 promoter. CTU2 expression was activated by LXR agonist and depressed by LXR knockout...

The Electronic Personal Health Record (EPHR) provides an innovative service for citizens and professionals to manage health data, promoting patient-centred care. It enhances communication between patients and physicians and improves accessibility to documents for remote medical information management. The study aims to assess the prevalence of awareness and acceptance of the EPHR in northern Italy and define determinants and barriers to its implementation. In 2022, a region-wide cross-sectional study was carried out through a paper-based and online survey shared among adult citizens...

A molecularly-imprinted electrochemiluminescence sensor was constructed for the determination of fenpropathrin (FPT) by molecular imprinting technology. In this sensing platform, the introduction of CdS@MWCNTs significantly enhanced the initial ECL signal of the luminol-O2 system. Specifically, MWCNTs was used as a carrier to adsorb more CdS, in which CdS acted as a co-reaction promoter for luminescence. Molecularly imprinted polymer (MIP) containing specific recognition sites of FPT was used as the material for selective recognition...

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist...

Heart failure (HF) is a prevalent global disease, particularly impacting developed countries. With the world's aging population, HF's impact on the quantity and quality of life is expected to grow. This review aims to ascertain the frequency, characteristics, and properties of all patient-reported outcomes measures (PROMs) studied in HF patients. We searched Ovid/Medline and Web of Science for original articles about PROMs performed in adults with HF. Using pre-established quality criteria for measurement properties, an overall rating was assigned to evaluate and compare different instruments...