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Abstract Purpose Analyzing the correlation between patients’ basic information, three-dimensional parameters after calcaneal fractures, and the prognosis of calcaneal fractures. Methods A retrospective analysis was conducted on 43 patients with calcaneal fractures who underwent surgical treatment in the Foot and Ankle Surgery, Xi’an Honghui Hospital, from September 2019 to August 2022. Patient demographics including gender and age were collected, as well as the preoperative posterior articular surface collapse area, number of fracture fragments, length, width, height, and volume of the calcaneus obtained from preoperative three-dimensional imaging. Patients were followed up for VAS, AOFAS, and SF-36 scores. Correlation analysis was performed on the obtained data. Results All 43 included patients received complete follow-up, including 40 males and 3 females, with an average follow-up time of 35.37 ± 10.73 months, and an average age of 43.98 ± 12.08 years. All patients’ VAS, AOFAS, and SF-36 scores at the last follow-up showed no correlation with patient age, gender, or the area of posterior articular collapse, number of fracture fragments, length, width, height, or volume of the calcaneus. Conclusions The prognosis of calcaneal fractures is unrelated to three-dimensional factors such as patient age, gender, length, width, height, volume of the calcaneus, area of the posterior joint, and number of fracture fragments.

Abstract Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.

Abstract Body weight is related to both diabetes and cognitive impairment; however, the associations between body mass index (BMI) and cognitive impairment have been reported less frequently among diabetes patients. A total of 1355 patients with type 2 diabetes aged ≥ 60 years were included in this study. The Montreal Cognitive Assessment (MoCA) was administered to assess participants’ cognitive status. We collected self-reported body weight, weight loss and appetite loss data using questionnaires. Associations between body weight status (in childhood, midlife age, and late life), weight loss, appetite changes and cognitive impairment were explored using logistic regression. Among the participants, 41.7% exhibited cognitive impairment. Overweight in childhood and late life was associated with cognitive impairment among diabetes patients (OR 2.63, 95% CI 1.52–4.55; OR 1.32, 95% CI 1.03–1.69). Diabetes patients with cognitive impairment were more likely to report a body weight decline and appetite reduction in the past three months (OR 4.18, 95% CI 2.61–6.71; OR 4.41, 95% CI 2.67–7.29). Higher BMI, weight loss, and appetite reduction were positively correlated with cognitive impairment. Given the risk of cognitive impairment, we suggest that body weight and BMI decline should be monitored in patients with diabetes.

Abstract It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

Abstract Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs‐mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal‐regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin‐11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin‐11 pathways, which are associated with NCK1. The anti‐platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases.

We present a genome assembly from an individual Geum urbanum the (wood avens; Streptophyta; Magnoliopsida; Rosales; Rosaceae). The genome sequence is 1,304.9 megabases in span. Most of the assembly is scaffolded into 21 chromosomal pseudomolecules. The mitochondrial and plastid genomes have also been assembled and are 335.5 and 156.1 kilobases in length respectively. Gene annotation of this assembly on Ensembl identified 50,336 protein-coding genes.

Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14–1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49–1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9–3.8) for the entire cohort and 9.7 (7.5–12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of proinflammatory factors in macrophages stimulated by lipopolysaccharide (LPS). Multiplex proteomic profiling identified the immunoproteasome, which is a specific isoform of the 20s constitutive proteasome, as a substrate that is degraded by selective autophagy. SQSTM1/p62 was found to be a selective autophagy-related receptor that mediated this degradation. Autophagy deficiency or p62 knockdown blocked the effects of LY2874455, leading to the accumulation of immunoproteasomes and increases in inflammatory reactions. Expression of proinflammatory factors in autophagy-deficient macrophages could be reversed by immunoproteasome inhibitors, confirming the pivotal role of immunoproteasome turnover in the autophagy-mediated suppression on the expression of proinflammatory factors. In mice, LY2874455 protected against LPS-induced acute lung injury and dextran sulfate sodium (DSS)-induced colitis and caused low levels of proinflammatory cytokines and immunoproteasomes. These findings suggested that selective autophagy of the immunoproteasome was a key regulator of signaling via the innate immune system.

Interest in searches for Charged Lepton Flavor Violation (CLFV) has continued in the past few decades since the observation of CLFV would indicate a new physics Beyond the Standard Model (BSM). As several future lepton colliders with high luminosity have been proposed, the search for CLFV will reach an unprecedented level of precision. Many BSM models allow CLFV processes at the tree level, such as the R-parity-violating (RPV) Minimal Supersymmetric Standard Model (MSSM), which is a good choice for benchmarking. In this paper, we perform a detailed fast Monte Carlo simulation study on RPV-induced CLFV processes at future lepton colliders, including a 240 GeV circular electron positron collider (CEPC) and a 6 or 14 TeV Muon Collider. As a result, we found that the upper limits on the τ-related RPV couplings will be significantly improved, while several new limits on RPV couplings can be set, which are inaccessible by low-energy experiments.

The massive stockpiling of electrolytic manganese residue (EMR) has caused serious environmental pollution. In this study, EMR, coal gangue (CG), and fly ash (FA) were used as raw materials to obtain the optimal mix ratio based on Design-Expert mixture design. The effects of activator modulus, liquid–solid (L/S) ratio, and curing temperature on the mechanical properties of geopolymers were investigated. The results showed that the compressive strength of the prepared geopolymer was 12.0 MPa, and the 28d leaching of Mn was 0.123 mg/L under the conditions of EMR:CG:FA = 0.43:0.34:0.23, L/S = 0.9, a curing temperature of 60 °C, and a curing time of 24 h. This indicates that the geopolymer is an environmentally friendly material with high compressive strength. The mineral composition of the geopolymer is mainly hydrated calcium silicate and geopolymer gel. In addition, a more stable new mineral phase, MnSiO3, was generated. The Fourier transform infrared (FTIR) spectrogram showed that the peak at 1100 m−1 was shifted to 1112 cm−1, which indicated that a geopolymerization reaction had occurred. Through scanning electron microscopy (SEM) and energy dispersive spectrum (EDS) analysis, it was identified that the geopolymerization produced a large amount of amorphous gelatinous substances with a relatively dense structure, the major elements being oxygen, silicon, aluminum, calcium, and sodium.