Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.

Unassembled and partially assembled subunits of multi-protein complexes have emerged as major quality control clients, particularly under conditions of imbalanced gene expression such as stress, aging, and aneuploidy. The factors and mechanisms that eliminate such orphan subunits to maintain protein homeostasis are incompletely defined. Here, we show that the UBR4-KCMF1 ubiquitin ligase complex is required for the efficient degradation of multiple unrelated orphan subunits from the chaperonin, proteasome cap, proteasome core, and a protein targeting complex.

Extracellular volume expansion drives vertebrate axis elongation.

The vertebrate bauplan is primarily established via the formation of embryonic tissues in a head-to-tail progression. The mechanics of this elongation, which requires the presomitic mesoderm (PSM), remain poorly understood. Here, we find that avian PSM explants can elongate autonomously when physically confined in vitro, producing a pushing force promoting posterior elongation of the embryo.

[Nosocomial gastrointestinal infections and Clostridioides difficile].

German surveillance data from 2022 reported a prevalence of nosocomial infections among hospitalized patients of 5,2%. Clostridioides-difficile-infections (CDI) are the most frequent cause of nosocomial diarrhea. They are usually caused by antibiotic exposure and the subsequent changes in the gut microbiota.

Distribution of strontium isotopes (Sr/Sr) in surface waters of the Amazon basin: A basis for studies on provenance.

The Sr/Sr isotope ratio has been widely used as an indicator of provenance and migration of aquatic animals, and has applications in other areas such as in environmental and forensic studies. However, the modeling of the spatial distribution in the Amazon basin is still incipient, preventing large-scale applications. In this study, we present a baseline of the Sr/Sr isotope ratio in surface waters of the Amazon basin to infer the provenance and migration patterns of fish.

SMARCA2 protein: Structure, function and perspectives of drug design.

SMARCA2 is an ATPase that regulates chromatin structure via ATP pathways, controlling cell division and differentiation. SMARCA2's bromodomain and ATPase domain, crucial for chromatin remodeling and cell regulation, are therapeutic targets in cancer treatment. This review explores the role of SMARCA2 in cancer development by studying its protein structure and physiological functions.

Design, synthesis and evaluation of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives as next generation selective RET inhibitors overcoming RET solvent front mutations (G810C/R).

RET is a well-recognized drug target for cancer treatment. Despite the promising efficacy of selective second-generation RET inhibitors Selpercatinib and Pralsetinib, the clinical benefits have been compromised due to the quickly developed resistance to these drugs. RET G810 mutations at the solvent front site have been identified as the major on-target mutations contributing to resistance against Selpercatinib and Pralsetinib.

Influences of rainfall characteristics on water saving and stormwater control performances of rainwater harvesting systems.

Rainwater harvesting systems (RHS) are extensively executed to manage stormwater control and water shortage issues in cities. However, the influences of rainfall characteristics on the performances of RHS are still not deeply explored. In this research, a methodology framework is developed to explore the influences of rainfall characteristics on stormwater control and water saving performances of RHS, by using daily precipitation data during 1968-2017 at 30 stations across the Beijing region as a testbed.

Comparative analysis of global urban land surface phenology between the MODIS and VIIRS products and extraction methods.

The reliability of land surface phenology (LSP) derived from satellite remote sensing is crucial for obtaining accurate estimates of the phenological response of vegetation to future climate change in urban ecosystems. Differences in phenological definition and extraction methodology using remote sensing can generate systemic errors in estimating the phenological temperature sensitivity to predict the biological response of vegetation. Here, we evaluated the start of the season (SOS), the end of the season (EOS), and the growing season length (GSL) between the Terra and Aqua combined Moderate Resolution Imaging Spectroradiometer (MODIS) Land Cover Dynamics (MCD12Q2) and the Suomi National Polar-Orbiting Partnership NASA Visible Infrared Imaging Radiometer Suite (VIIRS) Land Cover Dynamics (VNP22Q2) over 1470 urban clusters worldwide.

Development of a predictive model for pediatric intranasal drug delivery with nasal sprays: Leveraging intersubject variability in anatomical dimensions, administration-related parameters, and airway patency.

In this study, we examined the correlation between anatomical dimensions, spray administration parameters, pressure drop across 40 pediatric nasal cavities, and in vitro posterior drug delivery (PDD) using Nasacort ALLERGY 24HR and FLONASE SENSIMIST nasal suspensions sprays, with different nozzle and actuation designs. The importance of each parameter and their interaction in the outcome (PDD) was evaluated. To do so, initially we measured anatomical and administration-related parameters, and the pressure drop of each cavity.

Intensive care clinician attitudes and perceptions towards whānau participation in adult intensive care bedside ward rounds in Aotearoa New Zealand: An online survey.

Background: Clinical practice guidelines endorse family involvement in ward rounds to improve communication and engagement between patients, whānau (family), and healthcare teams, yet the practice has not been universally implemented. Whānau inclusion in adult bedside rounds is often met with hesitation by intensive care unit (ICU) healthcare clinicians, and reasons for this have not been explored in Aotearoa, New Zealand.

Objectives: The aim of this study was to assess attitudes and perceptions of ICU clinicians towards whānau-family inclusion in adult ICU ward rounds in Aotearoa New Zealand.

Modeling of hydrogeochemical processes influencing uranium migration in anthropized arid environments with application to the Teloua aquifer.

Sandstone-hosted uranium is mined in the Sahel regions of Niger. The Teloua aquifer is located beneath the ore-processing facilities of one such former mine, COMINAK. The pores of the sandstone bedrock are partially filled by tosudite, a clay with sorption capacities.

Coloured overlays improve reading speed and reading experience in patients with post-COVID-19 syndrome.

High prevalences of visual dysfunction and reading-related symptoms have been found in patients with rehabilitation needs after COVID-19 infection. The purpose of this study was to study the effects of coloured overlays on reading speed and reading experience. Twenty-nine patients (45.

Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.

An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.

Street-scale black carbon modelling over the West Midlands, United Kingdom: Sensitivity test of traffic emission factor adjustments.

Black carbon is harmful for climate, environment, and human health. Road traffic is one of the major sources for black carbon in urban areas. This study develops a street scale air quality model configuration for the dispersion of black carbon concentrations across the West Midlands, UK, incorporating updated road traffic emission factors.

An integrated and multifunctional homemade cell sensor platform based on Si-d-CQDs and CRISPR-Cas12a for CD31 detection during endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EndMT) plays a crucial role in the initiation and progression of atherosclerosis and various disease processes. Cluster of differentiation 31 (CD31) is a significant marker in EndMT. Detecting CD31 is essential for early-stage monitoring of EndMT and diagnosing atherosclerosis.

A stretchable, adhesive, and wearable hydrogel-based patches based on a bilayer PVA composite for online monitoring of sweat by artificial intelligence-assisted smartphones.

Real-time monitoring of sweat using wearable devices faces challenges such as limited adhesion, mechanical flexibility, and accurate detection. In this work, we present a stretchable, adhesive, bilayer hydrogel-based patch designed for continuous monitoring of sweat pH and glucose levels using AI-assisted smartphones. The patch is composed of a bottom PVA hydrogel layer functionalized with colorimetric reagents and glucose oxidase enzyme, while the top PVA-sucrose layer enhances skin adhesion and protects against air moisture.

Prolgolimab with chemotherapy as first-line treatment for advanced non-squamous non-small-cell lung cancer.

Background: Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing 'LALA' mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC).

Methods: 292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (≤36 months).

Unveiling heterointerface activation effects with different titanium dioxide crystal phases for electrocatalytic nitrate-to-ammonia reduction.

Nitrate pollution poses severe risks to aquatic ecosystems and human health. The electrocatalytic nitrate reduction reaction (NITRR) offers a promising environmental and economic solution for nitrate pollution treatment and nitrogen source recovery; however, it continues to experience limited efficiency in neutral electrolytes. This study explores the heterointerface activation effects of TiO/CuO heterogeneous catalysts with rutile (R-TiO) and anatase (A-TiO) phases and reveals that R-TiO is an active crystal phase with high nitrate reduction performance.

Long-term response mechanism of bacterial communities to chemical oxidation remediation in petroleum hydrocarbon contaminated groundwater.

The limited understanding of microbial response mechanism remains as a bottleneck to evaluate the long-term remediation effectiveness of in situ chemical oxidation in contaminated groundwater. In this study, we investigated long-term response of bacterial communities throughout five remediation stages of pre-oxidation, early-oxidation, late-oxidation, early-recovery and late-recovery. By analyzing bacterial biomass, taxa, diversity and metabolic functions, this work identified the consistently suppressed glyceraldehyde-3-phosphate dehydrogenase pathway and the enrichment of naphthalene degradation pathways for secondary products, suggesting persistent oxidation stress and enhanced microbial utilization of lower-molecular weight carbon sources at the oxidation and early-recovery stages.

Enantioselection behaviors and risk assessments of chiral pesticide ethiprole and its chiral metabolite ethiprole amide in five kinds of vegetables.

Ethiprole is a second-generation phenylpyrazole insecticide used in agricultural production as an alternative to fipronil due to its lower toxicity to bees. Ethiprole amide is chiral metabolite of ethiprole, but information regarding its formation and degradation in vegetables is limited. Here, the absolute configuration of ethiprole amide enantiomer was determined through circular dichroism, and the behaviors of chiral ethiprole and its metabolites in five kinds of vegetables were studied through field experiments.

Experimental and computational analysis of lipophilicity and plasma protein binding properties of potent tacrine based cholinesterase inhibitors.

The lipophilicity of thirteen tacrine/piperidine-4-carboxamide derivatives was assessed using reversed-phase thin-layer chromatography (RP-TLC) with MeOH and acetonitrile (ACN) as organic modifiers. Among the parameters evaluated, the R and C values obtained using MeOH were identified as the most reliable for characterizing the lipophilicity of the investigated compounds. The observed differences in lipophilicity among the derivatives resulted from a delicate interplay of substituent effects (hydrophobicity, polarity, steric hindrance, and electronic effects), positional influence, and characteristics of the organic modifier.

Unveiling the interplay between knowledge, self-efficacy, and pro-environmental behavior about climate change in a sample of rural community-dwelling older adults: A national correlational study.

Background: Climate change is a global health concern that affects all of humanity, but it disproportionately impacts older adults, particularly those living in rural communities. Older adults lack the ability to actively engage in pro-environmental actions aimed at adapting to and mitigating the harmful effects of climate change.

Aim: To investigate the relationship between knowledge, self-efficacy, and pro-environmental behavior regarding climate change, as well as to identify the factors that predict pro-environmental behavior in a sample of rural community-dwelling older adults.

Factors associated with ICU stays after endovascular treatments for unruptured intracranial aneurysms: A review study.

Background: For unruptured intracranial aneurysms (UIAs), conservative management is often possible. However, when direct treatment is warranted, endovascular treatments (EVTs) provide an effective minimally invasive approach. These procedures still necessitate careful patient monitoring, frequently in the Intensive Care Unit (ICU).

Multi-group structure analysis and molecular docking of aptamers and small molecules: A case study of chloramphenicol.

Aptamers, a kind of short nucleotide sequences with high specificity and affinity with targets, have attracted extensive attention in recent years. Molecular docking method (MDM) is the most common method to explore the binding mode and recognition mechanism of aptamers and small molecules, which generally use the target to dock with the highest scoring tertiary structural model of the aptamer, and the highest scoring result is used as the predicted model. However, this prediction results may miss out the true interaction pattern due to the fact that aptamers are not completely rigid and the natural aptamers conformations are not in a single state.

Confirming the validity and reliability of the Placement Evaluation Tool to evaluate midwifery practice placements (PET-Midwifery).

Problem: In Australia, program accreditation requirements include that education providers monitor and evaluate teaching and learning environments and provide evidence of outcomes being used to inform program quality improvement. Yet, closing this loop has proven challenging.

Background: The Australian National Placement Evaluation Centre (NPEC) functions to measure the quality of placements through student evaluations.