Structure evolution at the gate-tunable suspended graphene-water interface.

Graphitic electrode is commonly used in electrochemical reactions owing to its excellent in-plane conductivity, structural robustness and cost efficiency1,2. It serves as prime electrocatalyst support as well as a layered intercalation matrix2,3, with wide applications in energy conversion and storage1,4. Being the two-dimensional building block of graphite, graphene shares similar chemical properties with graphite1,2, and its unique physical and chemical properties offer more varieties and tunability for developing state-of-the-art graphitic devices5-7. Hence it serves as an ideal platform to investigate the microscopic structure and reaction kinetics at the graphitic-electrode interfaces. Unfortunately, graphene is susceptible to various extrinsic factors, such as substrate effect8-10, causing much confusion and controversy7,8,10,11. Hereby we have obtained centimetre-sized substrate-free monolayer graphene suspended on aqueous electrolyte surface with gate tunability. Using sum-frequency spectroscopy, here we show the structural evolution versus the gate voltage at the graphene-water interface. The hydrogen-bond network of water in the Stern layer is barely changed within the water-electrolysis window but undergoes notable change when switching on the electrochemical reactions. The dangling O-H bond protruding at the graphene-water interface disappears at the onset of the hydrogen evolution reaction, signifying a marked structural change on the topmost layer owing to excess intermediate species next to the electrode. The large-size suspended pristine graphene offers a new platform to unravel the microscopic processes at the graphitic-electrode interfaces.

Genetic factors of grain cadmium concentration in Polish wheat (Triticum polonicum L.).

Wheat (Triticum aestivum L.) is one of the most important crops worldwide and a major source of human cadmium (Cd) intake. Limiting grain Cd concentration (Gr_Cd_Conc) in wheat is necessary to ensure food safety. However, the genetic factors associated with Cd uptake, translocation and distribution and Gr_Cd_Conc in wheat are poorly understood. Here, we mapped quantitative trait loci (QTLs) for Gr_Cd_Conc and its related transport pathway using a recombinant inbred line (RIL) population derived from 2 Polish wheat varieties (RIL_DT; dwarf Polish wheat [DPW] and tall Polish wheat [TPW]). We identified 29 novel major QTLs for grain and tissue Cd concentration; 14 novel major QTLs for Cd uptake, translocation, and distribution; and 27 major QTLs for agronomic traits. We also analyzed the pleiotropy of these QTLs. Six novel QTLs (QGr_Cd_Conc-1A, QGr_Cd_Conc-3A, QGr_Cd_Conc-4B, QGr_Cd_Conc-5B, QGr_Cd_Conc-6A, and QGr_Cd_Conc-7A) for Gr_Cd_Conc explained 8.16% to 17.02% of the phenotypic variation. QGr_Cd_Conc-3A, QGr_Cd_Conc-6A, and QGr_Cd_Conc-7A pleiotropically regulated Cd transport; 3 other QTLs were organ-specific for Gr_Cd_Conc. We fine-mapped the locus of QGr_Cd_Conc-4B and identified the candidate gene as Cation/Ca exchanger 2 (TpCCX2-4B), which was differentially expressed in DPW and TPW. It encodes an endoplasmic reticulum membrane/plasma membrane-localized Cd efflux transporter in yeast. Overexpression of TpCCX2-4B reduced Gr_Cd_Conc in rice. The average Gr_Cd_Conc was significantly lower in TpCCX2-4BDPW genotypes than in TpCCX2-4BTPW genotypes of the RIL_DT population and 2 other natural populations, based on a Kompetitive allele-specific PCR marker derived from the different promoter sequences between TpCCX2-4BDPW and TpCCX2-4BTPW. Our study reveals the genetic mechanism of Cd accumulation in wheat and provides valuable resources for genetic improvement of low-Cd-accumulating wheat cultivars.

Shifting landscapes of human MTHFR missense-variant effects.

Most rare clinical missense variants cannot currently be classified as pathogenic or benign. Deficiency in human 5,10-methylenetetrahydrofolate reductase (MTHFR), the most common inherited disorder of folate metabolism, is caused primarily by rare missense variants. Further complicating variant interpretation, variant impacts often depend on environment. An important example of this phenomenon is the MTHFR variant p.Ala222Val (c.665C>T), which is carried by half of all humans and has a phenotypic impact that depends on dietary folate. Here we describe the results of 98,336 variant functional-impact assays, covering nearly all possible MTHFR amino acid substitutions in four folinate environments, each in the presence and absence of p.Ala222Val. The resulting atlas of MTHFR variant effects reveals many complex dependencies on both folinate and p.Ala222Val. MTHFR atlas scores can distinguish pathogenic from benign variants and, among individuals with severe MTHFR deficiency, correlate with age of disease onset. Providing a powerful tool for understanding structure-function relationships, the atlas suggests a role for a disordered loop in retaining cofactor at the active site and identifies variants that enable escape of inhibition by S-adenosylmethionine. Thus, a model based on eight MTHFR variant effect maps illustrates how shifting landscapes of environment- and genetic-background-dependent missense variation can inform our clinical, structural, and functional understanding of MTHFR deficiency.

Hydrogen Sulfide Attenuates Mesenchymal Stem Cell Aging Progress via the Calcineurin-NFAT Signaling Pathway.

Aging is a gradual process that is coupled with a decline in the regenerative capacity of stem cells and a subsequent reduction in tissue function and repair. Hydrogen sulfide (H2S) plays an important role in maintaining the function of stem cells. The present study aimed to investigate the role of H2S in mesenchymal stem cell aging and the underlying mechanism and to provide novel insights into stem cell therapies in elderly people. Bone marrow mesenchymal stem cells (BMMSCs) were isolated from young mice (2 months) and from old mice (12 months). Senescence-associated ß-galactosidase (SA-ß-Gal) activity, reactive oxygen species (ROS) production, ROS scavenging enzymes, and the expression of cell-cycle-related genes were compared between those young and old BMMSCs. The expression of H2S-producing enzymes and the production of H2S in BMMSCs were examined. In vitro osteogenic differentiation and cell senescence were analyzed in young and old BMMSCs before and after H2S treatment. The underlying mechanism was investigated using calcineurin and NFAT1 inhibitors or a Foxp3 siRNA. Bone volume/tissue volume (BV/TV) of femurs in mice was examined using micro-CT with or without systemic injection of an H2S donor. Here, we found that H2S levels in BMMSCs declined with age. When the generation of H2S was blocked with the CBS inhibitor hydroxylamine and the CSE inhibitor dl-propargylglycine, BMMSCs underwent senescence. The elevation of H2S levels rescued BMMSC function in vitro and prevented bone loss in vivo. Mechanistically, H2S represses cell aging via the calcineurin-NFAT1 signaling pathway.

Comparison of machine learning-based CT fractional flow reserve with cardiac MR perfusion mapping for ischemia diagnosis in stable coronary artery disease.

OBJECTIVES: To compare the diagnostic performance of machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and cardiac magnetic resonance (MR) perfusion mapping for functional assessment of coronary stenosis. METHODS: Between October 2020 and March 2022, consecutive participants with stable coronary artery disease (CAD) were prospectively enrolled and underwent coronary CTA, cardiac MR, and invasive fractional flow reserve (FFR) within 2 weeks. Cardiac MR perfusion analysis was quantified by stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Hemodynamically significant stenosis was defined as FFR ≤ 0.8 or > 90% stenosis on invasive coronary angiography (ICA). The diagnostic performance of CT-FFR, MBF, and MPR was compared, using invasive FFR as a reference. RESULTS: The study protocol was completed in 110 participants (mean age, 62 years ± 8; 73 men), and hemodynamically significant stenosis was detected in 36 (33%). Among the quantitative perfusion indices, MPR had the largest area under receiver operating characteristic curve (AUC) (0.90) for identifying hemodynamically significant stenosis, which is in comparison with ML-based CT-FFR on the vessel level (AUC 0.89, p = 0.71), with comparable sensitivity (89% vs 79%, p = 0.20), specificity (87% vs 84%, p = 0.48), and accuracy (88% vs 83%, p = 0.24). However, MPR outperformed ML-based CT-FFR on the patient level (AUC 0.96 vs 0.86, p = 0.03), with improved specificity (95% vs 82%, p = 0.01) and accuracy (95% vs 81%, p < 0.01). CONCLUSION: ML-based CT-FFR and quantitative cardiac MR showed comparable diagnostic performance in detecting vessel-specific hemodynamically significant stenosis, whereas quantitative perfusion mapping had a favorable performance in per-patient analysis. CLINICAL RELEVANCE STATEMENT: ML-based CT-FFR and MPR derived from cardiac MR performed well in diagnosing vessel-specific hemodynamically significant stenosis, both of which showed no statistical discrepancy with each other. KEY POINTS: • Both machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and quantitative perfusion cardiac MR performed well in the detection of hemodynamically significant stenosis. • Compared with stress myocardial blood flow (MBF) from quantitative perfusion cardiac MR, myocardial perfusion reserve (MPR) provided higher diagnostic performance for detecting hemodynamically significant coronary artery stenosis. • ML-based CT-FFR and MPR from quantitative cardiac MR perfusion yielded similar diagnostic performance in assessing vessel-specific hemodynamically significant stenosis, whereas MPR had a favorable performance in per-patient analysis.

Metabolic dysfunction, rather than obesity, is a risk factor for chronic kidney disease in Chinese population.

BACKGROUND: Metabolic dysfunction and obesity are closely related to chronic kidney disease (CKD). However, studies on the relationship between various metabolic syndrome-body mass index (MetS-BMI) phenotypes and the risk of CKD in the Chinese population have not yet been explored. MATERIALS AND METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) 2015 were analyzed in this study. This study enrolled 12,054 participants. Participants were divided into six distinct groups according to their MetS-BMI status. Across the different MetS-BMI groups, the odd ratios (ORs) for CKD were determined using multivariable logistic regression models. RESULTS: The prevalence of CKD was higher in metabolically unhealthy groups than in the corresponding healthy groups. Moreover, the fully adjusted model showed that all metabolically unhealthy individuals had an increased risk of developing CKD compared to the metabolically healthy normal weight group (OR = 1.62, p = 0.002 for the metabolically unhealthy normal weight group; OR = 1.55, p < 0.001 for the metabolically unhealthy overweight group; and OR = 1.77, p < 0.001 for the metabolically unhealthy obesity group. CONCLUSIONS: This study is the first to evaluate the relationship between the MetS-BMI phenotype and renal prognosis in the Chinese population. Individuals with normal weights are at different risk of developing CKD depending on their different metabolic phenotypes.

4d-2p-4f Gradient Orbital Coupling Enables Tandem Catalysis for Simultaneous Abatement of N2O and CO on Atomically Dispersed Rh/CeO2 Catalyst.

N2O and CO coexist in various industrial and mobile sources. The synergistic reaction of N2O and CO to generate N2 and CO2 has garnered significant research interest, but it remains extremely challenging. Herein, we constructed an atomically dispersed Rh-supported CeO2 catalyst with asymmetric Rh-O-Ce sites through gradient Rh 4d-O 2p-Ce 4f orbital coupling. This design effectively regulates the 4f electron states of Ce and promotes the electron filling of the O 3π* antibonding orbital to facilitate N-O bond cleavage. Near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) reveals that CO reacts with the surface-adsorbed O* generated by N2O decomposition through self-tandem catalysis, accelerating the rate-limiting step in N2O decomposition and activating the synergistic reaction of N2O and CO at temperatures as low as 115 °C. This work can guide the development of high-performance catalysts using the strategy of high-order orbital hybridization combined with the tandem concept to achieve versatile catalytic applications.

Water-Driven Surface Lattice Oxygen Activation in MnO2 for Promoted Low-Temperature NH3-SCR.

Water is ubiquitous in various heterogeneous catalytic reactions, where it can be easily adsorbed, chemically dissociated, and diffused on catalyst surfaces, inevitably influencing the catalytic process. However, the specific role of water in these reactions remains unclear. In this study, we innovatively propose that H2O-driven surface lattice oxygen activation in γ-MnO2 significantly enhances low-temperature NH3-SCR. The proton from water dissociation activates the surface lattice oxygen in γ-MnO2, giving rise to a doubling of catalytic activity (achieving 90% NO conversion at 100 °C) and remarkable stability. Comprehensive in situ characterizations and calculations reveal that spontaneous proton diffusion to the surface lattice oxygen reduces the orbital overlap between the protonated oxygen atom and its neighboring Mn atom. Consequently, the Mn-O bond is weakened and the surface lattice oxygen is effectively activated to provide excess oxygen vacancies available for converting O2 into O2-. Therefore, the redox property of Mn-H is improved, leading to enhanced NH3 oxidation-dehydrogenation and NO oxidation processes, which are crucial for low-temperature NH3-SCR. This work provides a deeper understanding and fresh perspectives on the water promotion mechanism in low-temperature NOx elimination.

Modulating the Activity and SO2 Resistance of α-Fe2O3 Catalysts for NH3-SCR of NOx via Crystal Facet Engineering.

The development of Fe-based catalysts for the selective catalytic reduction of NOx by NH3 (NH3-SCR of NOx) has garnered significant attention due to their exceptional SO2 resistance. However, the influence of different sulfur-containing species (e.g., ferric sulfates and ammonium sulfates) on the NH3-SCR activity of Fe-based catalysts as well as its dependence on exposed crystal facets of Fe2O3 has not been revealed. This work disclosed that nanorod-like α-Fe2O3 (Fe2O3-NR) predominantly exposing (110) facet performed better than nanosheet-like α-Fe2O3 (Fe2O3-NS) predominantly exposing (001) facet in NH3-SCR reaction, due to the advantages of Fe2O3-NR in redox properties and surface acidity. Furthermore, the results of the SO2/H2O resistance test at a critical temperature of 250 °C, catalytic performance evaluations on Fe2O3-NR and Fe2O3-NS sulfated by SO2 + O2 or deposited with NH4HSO4 (ABS), and systematic characterization revealed that the reactivity of ammonium sulfates on Fe2O3 catalysts to NO(+O2) contributed to their improved catalytic performance, while ferric sulfates showed enhancing and inhibiting effects on NH3-SCR activity on Fe2O3-NR and Fe2O3-NS, respectively; despite this, Fe2O3-NR showed higher affinity for SO2 + O2. This work set a milestone in understanding the NH3-SCR reaction on Fe2O3 catalysts in the presence of SO2 from the aspect of crystal facet engineering.

Understanding the Ecological Robustness and Adaptability of the Gut Microbiome in Plastic-Degrading Superworms (Zophobas atratus) in Response to Microplastics and Antibiotics.

Recent discoveries indicate that several insect larvae are capable of ingesting and biodegrading plastics rapidly and symbiotically, but the ecological adaptability of the larval gut microbiome to microplastics (MPs) remains unclear. Here, we described the gut microbiome assemblage and MP biodegradation of superworms (Zophobas atratus larvae) fed MPs of five major petroleum-based polymers (polyethylene, polypropylene, polystyrene, polyvinyl chloride, and polyethylene terephthalate) and antibiotics. The shift of molecular weight distribution, characteristic peaks of C═O, and metabolic intermediates of residual polymers in egested frass proved depolymerization and biodegradation of all MPs tested in the larval intestines, even under antibiotic suppression. Superworms showed a wide adaptation to the digestion of the five polymer MPs. Antibiotic suppression negatively influenced the survival rate and plastic depolymerization patterns. The larval gut microbiomes differed from those fed MPs and antibiotics, indicating that antibiotic supplementation substantially shaped the gut microbiome composition. The larval gut microbiomes fed MPs had higher network complexity and stability than those fed MPs and antibiotics, suggesting that the ecological robustness of the gut microbiomes ensured the functional adaptability of larvae to different MPs. In addition, Mantel's test indicated that the gut microbiome assemblage was obviously related to the polymer type, the plastic degradability, antibiotic stress, and larval survival rate. This finding provided novel insights into the self-adaptation of the gut microbiome of superworms in response to different MPs.

Strikingly Facile Cleavage of N-H/N-O Bonds Induced by Surface Frustrated Lewis Pair on CeO2(110) to Boost NO Reduction by NH3.

Ceria with surface solid frustrated Lewis pairs (FLPs), formed by regulating oxygen vacancies, demonstrate remarkable ability in activating small molecules. In this work, we extended the application of FLPs on CeO2(110) to the selective catalytic reduction of NO by NH3 (NH3-SCR), finding a notable enhancement in performance compared to ordinary CeO2(110). Additionally, an innovative approach involving H2 treatment was discovered to increase the number of FLPs, thereby further boosting the NH3-SCR efficiency. Typically, NH3-SCR on regular CeO2 follows the Eley-Rideal (E-R) mechanism. However, density functional theory (DFT) calculations revealed a significant reduction in the energy barriers for the activation of N-O and N-H bonds under the Langmuir-Hinshelwood (L-H) mechanism with FLPs present. This transition shifted the reaction mechanism from the E-R pathway on regular R-CeO2 to the L-H pathway on FLP-rich FR-CeO2, as corroborated by the experimental findings. The practical application of FLPs was realized by loading MoO3 onto FLP-rich FR-CeO2, leveraging the synergistic effects of acidic sites and FLPs. This study provides profound insights into how FLPs facilitate N-H/N-O bond activation in small molecules, such as NH3 and NO, offering a new paradigm for catalyst design based on catalytic mechanism research.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

Measurements of the gravitational constant using two independent methods.

The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10-11 and 6.674484 × 10-11 cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.

Intestinal microbial community well explain larval growth than feed types.

Black soldier fly larvae (BSFL) are considered a sustainable ingredient in livestock feed. However, addressing issues related to feed substrate and intestinal microbiota is essential to ensure optimal larval development. The aim of this study was to assess and elucidate the contribution of substrate nutrients and intestinal microbes to protein and fat synthesis in BSFL. The results showed that larvae that were fed high-quality feed (chicken feed) had high fat biomass, while larvae that were fed medium-quality feed (wheat bran) had high protein biomass. These results indicate that the original nutritional content of the feed cannot fully explain larval growth and nutrient utilization. However, the phenomenon could be explained by the functional metabolism of intestinal microbes. Chicken feed enhanced the fatty acid metabolism of middle intestine microorganisms in larvae within 0-7 days. This process facilitated larval fat synthesis. In contrast, wheat bran stimulated the amino acid metabolism in posterior intestine microorganisms in larvae within 4-7 days, leading to better protein synthesis. The findings of this study highlight the importance of the microbial functional potential in the intestine in regulating protein and lipid synthesis in BSFL, which is also influenced by the type of feed. In conclusion, our study suggests that both feed type and intestinal microbes play a crucial role in efficiently converting organic waste into high-quality insect protein and fat. Additionally, a mixed culture of chicken feed and wheat bran was found to be effective in promoting larval biomass while reducing feed costs. KEY POINTS: • Intestinal microbes explain BSFL growth better than feed substrates. • Chicken feed promotes fatty acid synthesis in the middle intestine • Wheat bran promotes amino acid synthesis in the posterior intestine.

Association of myopia and astigmatism with postoperative ocular high order aberration after small incision lenticule extraction.

OBJECTIVE: To investigate the correlation between higher-order aberrations (HOA) after small incision lenticule extraction (SMILE) and the severity of myopia and astigmatism, along with the relevant factors. These findings will provide valuable insights for decreasing the occurrence of HOA after SMILE and enhancing visual quality. METHODS: A total of 75 patients (150 eyes) with myopia and astigmatism who underwent SMILE were categorized into four groups based on the severity of myopia and astigmatism: Myopia Group 1 (Group M1, spherical diopter ranged from -1.00 D to -4.00 D), Myopia Group 2 (Group M2, spherical diopter ranged from -4.10 D to -10.00 D), Astigmatism Group 1 (Group A1, cylindrical diopter ranged from 0 D to -1.00 D), and Astigmatism Group 2 (Group A2, cylindrical diopter ranged from -1.10 D to -3.00 D). A comprehensive assessment was performed to examine the association between HOA and various relevant factors, including a detailed analysis of the subgroups. RESULTS: Group M1 had significantly lower levels of total eye coma aberration (CA), corneal total HOA (tHOA), internal tHOA, and vertical CA ( Z 3 - 1 ) after SMILE than Group M2 (P < 0.05). Similarly, Group A1 had significantly lower levels of total eye tHOA, CA, trefoil aberration (TA), corneal tHOA, TA, and vertical TA ( Z 3 - 3 ) after SMILE than Group A2 (P < 0.05). Pearson correlation analysis indicated a statistically significant positive relationship between the severity of myopia/astigmatism and most HOA (P < 0.05). Subgroup evaluations demonstrated a notable increase in postoperative HOA associated with myopia and astigmatism in Groups M2 and A2 compared with the control group. Lenticule thickness, postoperative central corneal thickness (CCT), postoperative uncorrected distance visual acuity (UDVA), and postoperative corneal Km and Cyl were strongly correlated with most HOA. Age, eyes, and postoperative intraocular pressure (IOP) were only associated with specific HOA. CONCLUSION: HOA positively correlated with the severity of myopia and astigmatism after SMILE. However, this relationship was not linear. HOA after SMILE was influenced by various factors, and additional specialized investigations are required to establish its clinical importance.

Associations between sensory impairment and functional limitations among older Chinese adults: mediating roles of social isolation and cognition.

BACKGROUND: The high prevalence of sensory impairment and functional limitations in older adults is a significant concern, yet there is limited understanding of the relationship between these two conditions. Therefore, the objective of this study was to investigate the pathways connecting sensory impairment and functional limitations by examining serial multiple mediating effects of social isolation and cognition in older adults. METHODS: Using the China Health and Retirement Longitudinal Study dataset, a sample of 4871 older adults was selected. The study variables included sensory impairment, functional limitations, social isolation and cognition, and other covariates. A hierarchical multiple linear regression model was used to assess the association between sensory impairment and functional limitations. Mediation analysis was conducted to explore the sequential multiple mediating effects of social isolation and cognitive function in the relationship between sensory impairment and functional limitations. RESULTS: Our findings revealed a significant and positive association between sensory impairment and functional limitations (B = 0.615, 95% CI: 0.397, 0.834). After adjusting for social isolation and cognitive function, the impact of sensory impairment on functional limitations accounted for 87.19% of the total effect. Additionally, approximately 12.81% of the significant relationship between dual sensory impairment and functional limitations was mediated by social isolation and cognitive function. A serial multiple mediating pathway (sensory impairment → social isolation → cognition → functional limitations) was identified, with a coefficient of 0.013 (95% CI: 0.006, 0.020). CONCLUSIONS: Our study provides evidence for the mediating effects of social isolation and cognition in the relationship between sensory impairment and functional limitations. Given the prevalence of functional limitations among older adults with sensory impairment, it is crucial to consider social isolation and cognitive function in efforts to reduce the burden of disability care. Future validation of these findings through longitudinal studies is necessary.

Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

A DTI-based radiomics model for predicting epidermal growth factor receptor (EGFR) amplification in adult IDH1-wild glioblastomas.

BACKGROUND: Molecular alteration events are common in glioblastomas, the isocitrate dehydrogenase (IDH)-wild of which have had poor survival results so far. The progress of radiomics-based model provides novel sights for its preoperatively noninvasive prediction. PURPOSE: To develop a radiomics-based model for predicting epidermal growth factor receptor (EGFR) amplification status in IDH1-wild glioblastomas of adults by pretreatment diffusion tensor imaging (DTI). MATERIAL AND METHODS: A total of 124 patients with diagnosed glioblastomas were retrospectively collected. Six conventional magnetic resonance imaging (MRI) features of all the tumors were evaluated visually. Patients were divided into the training (n = 87) and the test set (n = 37) with a ratio of 7:3. Radiomics features were extracted from two regions of the glioblastomas, which were the total tumor (ROI_1) and the solid portion of tumor (ROI_2). The radiomics features extracted from the DTI and T1-contrast-enhanced (T1C) images were selected using the least absolute shrinkage and selection operator (LASSO) regression algorithm. Logistic regression analysis was conducted to develop models for EGFR amplification prediction in the training set. RESULTS: The radiomics model based on ROI_1 demonstrated favorable discrimination in both the training (area under the curve [AUC] = 0.86) and the test set (AUC = 0.82) (P < 0.05). Combining the radiomics features and the conventional feature tumor location, no significant improvement of AUCs was achieved (AUC = 0.86 and 0.81). CONCLUSION: The radiomics model derived from pretreatment DTI may have potential in differentiating the EGFR mutation status in glioblastomas.

C-176 reduces inflammation-induced pain by blocking the cGAS-STING pathway in microglia.

OBJECTIVE: Inflammatory pain, is caused by lesions or diseases of the somatosensory tissue, is a prevalent chronic condition that profoundly impacts the quality of life. However, clinical treatment for this type of pain remains limited. Traditionally, the stimulation of microglia and subsequent inflammatory reactions are considered crucial elements to promote the worsening of inflammatory pain. Recent research has shown the crucial importance of the cGAS-STING pathway in promoting inflammation. It is still uncertain if the cGAS-STING pathway plays the role in the fundamental cause of inflammatory pain. We aim to explore the treatment of inflammatory pain by interfering with cGAS-STING signaling pathway. METHODS: In this study, we established an inflammatory pain model by CFA into the plantar of mice. Activation of microglia, various inflammatory factors and cGAS-STING protein in the spinal dorsal horn were evaluated. Immunofluorescence staining was used to observe the cellular localization of cGAS and STING. The cGAS-STING pathway proteins expression and mRNA expression of indicated microglial M1/M2 phenotypic markers in the BV2 microglia were detected. STING inhibitor C-176 was intrathecal injected into mice with inflammatory pain, and the pain behavior and microglia were observed. RESULTS: This research showed that injecting CFA into the left hind paw of mice caused mechanical allodynia and increased inflammation in the spine. Our research results suggested that the cGAS-STING pathway had a function in the inflammation mediated by microglia in the spinal cord dorsal horn. Blocking the cGAS-STING pathway using STING antagonists (C-176) led to reduced release of inflammatory factors and prevented M1 polarization of BV2 microglia in a laboratory setting. Additionally, intrathecal administration of C-176 reduced the allodynia in CFA treated mice. CONCLUSION: Our results suggest that inhibiting microglial polarization through the cGAS-STING pathway represents a potential novel therapeutic strategy for inflammatory pain.

Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.