Silver-quercetin-loaded honeycomb-like Ti-based interface combats infection-triggered excessive inflammation via specific bactericidal and macrophage reprogramming.

Excessive inflammation caused by bacterial infection is the primary cause of implant failure. Antibiotic treatment often fails to prevent peri-implant infection and may induce unexpected drug resistance. Herein, a non-antibiotic strategy based on the synergy of silver ion release and macrophage reprogramming is proposed for preventing infection and bacteria-induced inflammation suppression by the organic-inorganic hybridization of silver nanoparticle (AgNP) and quercetin (Que) into a polydopamine (PDA)-based coating on the 3D framework of porous titanium (SQPdFT). Once the planktonic bacteria (e.g., Escherichia coli, Staphylococcus aureus) reach the surface of SQPdFT, released Que disrupts the bacterial membrane. Then, AgNP can penetrate the invading bacterium and kill them, which further inhibits the biofilm formation. Simultaneously, released Que can regulate macrophage polarization homeostasis via the peroxisome proliferators-activated receptors gamma (PPARγ)-mediated nuclear factor kappa-B (NF-κB) pathway, thereby terminating excessive inflammatory responses. These advantages facilitate the adhesion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), concomitantly suppressing osteoclast maturation, and eventually conferring superior mechanical stability to SQPdFT within the medullary cavity. In summary, owing to its excellent antibacterial effect, immune remodeling function, and pro-osteointegration ability, SQPdFT is a promising protective coating for titanium-based implants used in orthopedic replacement surgery.

Enhancing 5-Hydroxymethylfurfural Production from Fructose Using Triethylbenzylammonium Chloride-Based Acidic Deep Eutectic Solvents: Optimization and Acidity Impact.

5-Hydroxymethylfurfural (5-HMF) is an important biomass-based platform compound that links biomass feedstocks with petrochemical refinery products. In this work, we developed a novel approach using TEBAC-based acidic deep eutectic solvents (ADESs) to synthesize 5-HMF through the dehydration of fructose. Our approach demonstrates significant improvements in both 5-HMF yield and process efficiency compared to conventional solvent systems. Under optimal experimental conditions (90°C, 4.5 h), a maximum 5-HMF yield of 97.77±3.20% was achieved at a TEBAC:acetic acid ratio of 2:3 with 1 wt% fructose loading.  Notably, our system inhibits the formation of by-products such as levulinic acid (LA) and formic acid (FA), which are commonly detected in other dehydration processes. Additionally, higher 5-HMF yields of 76.67±0.33% and 73.51±1.14% were achieved with 10 wt% and 20 wt% fructose loadings, respectively, further highlighting the scalability of the process. The  acidity of ADESs was found to significantly affect the dehydration rate and yield, as demonstrated through Hammett's acidity function analysis. The key innovation of our study lies in the strategic selection of hydrogen bond donors and acceptors in the DES, enabling both high efficiency and selectivity in 5-HMF production. These findings provide a promising pathway for large-scale biomass conversion with reduced by-product formation.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation.

BACKGROUND: An association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with acute respiratory distress syndrome (ARDS), including patients with COVID-19 (COVID-19-related acute respiratory distress syndrome (C-ARDS)) undergoing IMV, has not been rigorously evaluated. The use of emulations of a target trial in intensive care unit research remains in its infancy. To inform future, large ARDS target trials, we explored using a target trial emulation approach to analyse data from a cohort of IMV adults with C-ARDS to determine whether maintaining daily ∆p<15 cm H2O (in addition to traditional low tidal volume ventilation (LTVV) (tidal volume 5-7 cc/PBW+plateau pressure (Pplat) ≤30 cm H2O), compared with LTVV alone, affects the 28-day mortality. METHODS: To emulate a target trial, adults with C-ARDS requiring >24 hours of IMV were considered to be assigned to limited ∆P or LTVV. Lung mechanics were measured twice daily after ventilator setting adjustments were made. To evaluate the effect of each lung-protective ventilation (LPV) strategy on the 28-day mortality, we fit a stabilised inverse probability weighted marginal structural model that adjusted for baseline and time-varying confounders known to affect protection strategy use/adherence or survival. RESULTS: Among the 92 patients included, 27 (29.3%) followed limited ∆P ventilation, 23 (25.0%) the LTVV strategy and 42 (45.7%) received no LPV strategy. The adjusted estimated 28-day survival was 47.0% (95% CI 23%, 76%) in the limited ∆P group, 70.3% in the LTVV group (95% CI 37.6%, 100%) and 37.6% (95% CI 20.8%, 58.0%) in the no LPV strategy group. INTERPRETATION: Limiting ∆P may not provide additional survival benefits for patients with C-ARDS over LTVV. Our results help inform the development of future target trial emulations focused on evaluating LPV strategies, including reduced ∆P, in adults with ARDS.

SlFSR positively regulates ethylene biosynthesis and lycopene accumulation during fruit ripening in tomato.

Transcription factors (TFs) are crucial for regulating fruit ripening in tomato (Solanum lycopersicum). The GRAS (GAI, RGA, and SCR) TFs are involved in various physiological processes, but their role in fruit ripening has seldom been reported. We have previously identified a gene encoding GRAS protein named SlFSR (Fruit Shelf-life Regulator), which is implicated in fruit ripening by regulating cell wall metabolism; however, the underlying mechanism remains unclear. Here, we demonstrate that SlFSR proteins are localized to the nucleus, where they could bind to specific DNA sequences. SlFSR acts downstream of the master ripening regulator RIN and could collaborate with RIN to control the ripening process by regulating expression of ethylene biosynthesis genes. In SlFSR-CR (CRISPR/Cas9) mutants, the initiation of fruit ripening was not affected but the reduced ethylene production and a delayed coloring process occurred. RNA-sequencing (RNA-seq) and promoter analysis reveal that SlFSR directly binds to the promoters of two key ethylene biosynthesis genes (SlACO1 and SlACO3) and activates their expression. However, SlFSR-CR fruits displayed a significant down-regulation of key rate-limiting genes (SlDXS1 and SlGGPPS2) in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, which may account for the impaired lycopene synthesis. Altogether, we propose that SlFSR positively regulates ethylene biosynthesis and lycopene accumulation, providing valuable insights into the molecular mechanisms underlying fruit ripening.

Network Pharmacology and in vitro Experimental Verification on Intervention of Oridonin on Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer (NSCLC). METHODS: The target molecules of oridonin were retrieved from SEA, STITCH, SuperPred and TargetPred databases; target genes associated with the treatment of NSCLC were retrieved from GeneCards, DisGeNET and TTD databases. Then, the overlapping target molecules between the drug and the disease were identified. The protein-protein interaction (PPI) was constructed using the STRING database according to overlapping targets, and Cytoscape was used to screen for key targets. Molecular docking verification were performed using AutoDockTools and PyMOL software. Using the DAVID database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8, cell proliferation EdU image kit, and Annexin V-FITC/PI apoptosis kit respectively. Moreover, real-time quantitative PCR and Western blot were used to verify the potential mechanisms. RESULTS: Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified, including tumor protein 53 (TP53), Caspase-3, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase kinase 8 (MAPK8), and mammalian target of rapamycin (mTOR). Molecular docking showed that oridonin and its key target molecules bind spontaneously. GO and KEGG enrichment analyses revealed cancer, apoptosis, phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and other signaling pathways. In vitro experiments showed that oridonin inhibited the proliferation, induced apoptosis, downregulated the expression of Bcl-2 and Akt, and upregulated the expression of Caspase-3. CONCLUSION: Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC, and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.

Sn-Doping-Induced Biphasic Structure Advances Ductile Ag2S-Based Thermoelectrics.

Due to its inherent ductility, Ag2S shows promise as a flexible thermoelectric material for harnessing waste heat from diverse sources. However, its thermoelectric performance remains subpar, and existing enhancement strategies often compromise its ductility. In this study, a novel Sn-doping-induced biphasic structuring approach is introduced to synergistically control electron and phonon transport. Specifically, Sn-doping is incorporated into Ag2S0.7Se0.3 to form a biphasic composition comprising (Ag, Sn)2S0.7Se0.3 as the primary phase and Ag2S0.7Se0.3 as the secondary phase. This biphasic configuration achieves a competitive figure-of-merit ZT of 0.42 at 343 K while retaining exceptional ductility, exceeding 90%. The dominant (Ag, Sn)2S0.7Se0.3 phase bolsters the initially low carrier concentration, with interfacial boundaries between the phases effectively mitigating carrier scattering and promoting carrier mobility. Consequently, the optimized power factor reaches 5 µW cm-1 K-2 at 343 K. Additionally, the formation of the biphasic structure induces diverse micro/nano defects, suppressing lattice thermal conductivity to a commendable 0.18 W m-1 K-1, thereby achieving optimized thermoelectric performance. As a result, a four-leg in-plane flexible thermoelectric device is fabricated, exhibiting a maximum power density of ≈49 µW cm-2 under the temperature difference of 30 K, much higher than that of organic-based flexible thermoelectric devices.

CRISPR-CLEAR: Nucleotide-Resolution Mapping of Regulatory Elements via Allelic Readout of Tiled Base Editing.

CRISPR tiling screens have advanced the identification and characterization of regulatory sequences but are limited by low resolution arising from the indirect readout of editing via guide RNA sequencing. This study introduces CRISPR-CLEAR, an end-to-end experimental assay and computational pipeline, which leverages targeted sequencing of CRISPR-introduced alleles at the endogenous target locus following dense base-editing mutagenesis. This approach enables the dissection of regulatory elements at nucleotide resolution, facilitating a direct assessment of genotype-phenotype effects.

Effects of Rotary and Deep Tillage on Soil Environment and Melon Root Development.

Tillage practices significantly influence crop yield and soil quality. This study investigated the impact of rotary tillage (RT) and deep tillage (DT) on soil properties, microbial diversity, and melon (Cucumis melo L.) root growth and yield. RT involved breaking up the topsoil to a depth of 15 cm using a rotary tiller, while DT employed a rotary tiller followed by a moldboard plow to turn the soil layer over to a depth of 35 cm. The melon variety "Nasimi" was used as the material. Our findings revealed a remarkable response of soil phosphorus to tillage practices. High-throughput sequencing results revealed a significant impact of tillage practices on the soil fungal composition, richness, and diversity but little impact on the bacterial communities. Compared to RT, DT markedly enhanced melon root length, root surface area, root volume, and mean root diameter by 47.42%, 56.70%, 58.83%, and 27.28%, respectively. Additionally, DT treatments significantly increased melon yield (53.46%) compared to RT. The results indicate that DT improves soil nutrient availability, affects soil fungal community characteristics, and optimizes root distribution in soil, thereby improving melon yield. The findings offer valuable theoretical insights for the implementation of effective tillage practices in open-field melon cultivation.

Enhancing daily living and cognitive functions in traumatic brain injury patients through Orem's self-care theory.

Introduction: This research seeks to investigate how early rehabilitation nursing, guided by Orem's self-care theory, affects cognitive function, neurological function, and daily living skills in individuals who have suffered a traumatic brain injury (TBI). Methods: A study was conducted with 108 patients with traumatic brain injury who were hospitalized at our facility from January 2021 to March 2023. Based on their admission dates, the participants were separated into a control group (n = 56) and an observation group (n = 52). The control group received standard nursing care, while the observation group received a combination of conventional treatment and nursing interventions based on Orem's self-care model. The research assessed alterations in the ability to perform daily tasks (Activities of Daily Living, ADL), neurological health (National Institutes of Health Stroke Scale, NIHSS; Glasgow Coma Scale, GCS), and cognitive abilities (Montreal Cognitive Assessment Scale, MoCA; Mini-Mental State Examination, MMSE) in both sets of participants prior to and following 4 and 8 weeks of nursing assistance. Results: Following the intervention, the group being observed showed notably increased ADL scores at 4 weeks (p < 0.001) and 8 weeks (p < 0.001) in comparison to the control group. At 4 weeks and 8 weeks after nursing, the observation group had significantly lower NIHSS scores compared to the control group (4 weeks after nursing, p = 0.03; 4 weeks after nursing, p < 0.001). GCS score comparison showed the similar results (4 weeks after nursing, p = 0.013; 4 weeks after nursing, p = 0.003). Moreover, the participants in the observation group had notably higher MoCA and MMSE scores in comparison with the control group 4 and 8 weeks after nursing (all p < 0.001). Conclusion: Orem's self-care theory improves patients' cognitive, neurological, and daily living functions of TBI patients during early rehabilitation nursing. This method helps enhance the level of care given by healthcare professionals, leading to more thorough and compassionate nursing care for patients.

Identification of AS1842856 as a novel small-molecule GSK3α/ß inhibitor against Tauopathy by accelerating GSK3α/ß exocytosis.

Glycogen synthase kinase-3α/ß (GSK3α/ß) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/ß inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/ß. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/ß content in a FOXO1-independent manner. Specifically, AS directly bound to GSK3α/ß, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/ß content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood-brain barrier (BBB) using an imaging mass microscope. Long-term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/ß expression in the brain. Altogether, AS represents a novel small-molecule GSK3α/ß inhibitor that facilitates GSK3α/ß exocytosis, holding promise as a therapeutic agent for GSK3α/ß hyperactivation-associated disorders.