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In this study, on the basis of a previous report, a pyrene-anchored nickel complex was designed and synthesized via five steps. The NMR spectra of the synthesized complex were found to exhibit significant proton and carbon chemical shift anisotropy. Cyclic voltammetry spectra showed that the introduction of pyrene slightly influenced the onset potential of CO2 reduction. Lastly, controlled-potential electrolysis experiments disclosed that a pyrene-anchored nickel carbene–isoquinoline (Ni−2) complex selectively converted CO2 into CH4 with a TON value of 2.3 h−1.

Background Loss of ovarian function, as in menopause or after ovariectomy (OVX), is closely associated with obesity and white adipose tissue (WAT) inflammation. Estrogen replacement protects against postmenopausal obesity but increases the risks of carcinogenesis. In the present study, we investigated the effects of long-term treatment of raloxifene (RAL), a selective estrogen receptor modulator, on the features of estrogen deficiency-induced obesity and explored the involvement of canonical and non-canonical Wnt regulation in vivo and in vitro. Methods Adult female rats received bilateral OVX and divided into 5 groups: (1) Sham, (2) OVX, (3) OVX + E 2 : OVX rats were administered with E 2 (50 μg/kg, s.c., 3 times/week), (4) OVX + RAL: OVX rats were treated with RAL (gavage, 1 mg/kg/day) suspended in 0.8% carboxymethylcellulose (CMC), (5) OVX + CMC: 0.8% CMC as vehicle control. All treatments were given for 8 weeks beginning at 1 week after OVX. In 3 T3-L1 cells, the effects of RAL on adipogenesis and lipopolysaccharide (LPS)-induced inflammation were evaluated. Results Treatment with RAL significantly decreased body weight, visceral fat pad mass, adipocyte size and plasma levels of glucose but increased plasma adiponectin. RAL reduced the elevation of HIF-1α, VEGF-A and proinflammatory cytokines (MCP-1 and TNF-α) expression by inhibition of NF-κB p65 and JNK cascades in retroperitoneal WAT. This anti-inflammatory capacity of RAL may result from upregulation of secreted frizzle-related protein 5 (SFRP5), an adipokine that repressed Wnt5a signaling. Furthermore, RAL inhibited adipogenic factors such as PPAR-γ, C/EBP-α, and FABP4, and preserved canonical Wnt10b/β-catenin protein expression. In 3 T3-L1 adipocytes, RAL (20 μM) diminished lipid accumulation and inhibited adipogenic factors accompanied with the induction of β-catenin, which were effectively reversed by the β-catenin inhibitor IWR-1-endo. In addition, RAL reduced LPS-induced NF-κB p65 and p-IκB expression as well as TNF-α secretion. Suppression of SFRP5 by small interfering RNA significantly abrogated the anti-inflammatory effects of RAL. Conclusions Distinct activation of canonical β-catenin on inhibition of adipogenesis and non-canonical SFRP5 on suppression of WAT inflammation may contribute to the beneficial effects of RAL. Therefore, this study provides a rationale for the therapeutic potential of RAL for postmenopausal obesity.

Sepsis is defined as a life-threatening organ dysfunction syndrome with high morbidity and mortality caused by bacterial infection. The major characteristics of sepsis are systemic inflammatory responses accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation (DIC). As a molecular chaperon to repair unfolded proteins, heat shock protein 70 (HSP70) maintains cellular homeostasis and shows protective effects on inflammatory damage. HSP 90 inhibitors were reported to exert anti-inflammatory effects via activation of the heat shock factor-1 (HSF-1), leading to induction of HSP70. We evaluated the beneficial effect of HSP 90 inhibitor NVP-AUY 922 (NVP) on multiple organ dysfunction syndrome induced by lipopolysaccharide (LPS) and further explored the underlying mechanism. NVP (5 mg/kg, i.p.) was administered 20 h prior to LPS initiation (LPS 30 mg/kg, i.v. infusion for 4 h) in male Wistar rats. Results demonstrated that pretreatment with NVP significantly increased survival rate and prevented hypotension at 6 h after LPS injection. Plasma levels of ALT, CRE and LDH as well as IL-1β and TNF-α were significantly reduced by NVP at 6 h after LPS challenge. The induction of inducible NO synthase in the liver, lung and heart and NF-κB p-p65 and caspase 3 protein expression in the heart were also attenuated by NVP. In addition, NVP markedly induced HSP70 and HO-1 proteins in the liver, lung and heart after LPS injection. These results indicated that NVP possessed the anti-inflammatory and antioxidant effects on LPS-induced acute inflammation, which might be associated with HSP70 and HO-1, leading to prevent MODS in sepsis. NVP might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively ( P  < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0 / β0 and HBS1L - MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Myocardial infarction (MI) remains one of the most common cardiovascular diseases and a leading cause of morbidity and mortality worldwide. In recent years, natural polymeric patches have attracted increasing attention as a promising therapeutic platform for myocardial tissue repair. This study explored the fabrication and evaluation of screen-printed electrodes (SPEs) on chitosan film as a novel platform for cardiac patch applications. Chitosan is a biodegradable and biocompatible natural polymer that provides an ideal substrate for SPEs, providing mechanical stability and promoting cell adhesion. Silver ink was employed to enhance electrochemical performance, and the electrodes exhibited strong adhesion and structural integrity under wet conditions. Mechanical testing and swelling ratio analysis were conducted to assess the patch’s physical robustness and aqueous stability. Silver ink was employed to enhance electrochemical performance, which was evaluated using cyclic voltammetry. In vitro, electrical stimulation through the chitosan–SPE patch significantly increased the expression of cardiac-specific genes (GATA-4, β-MHC, troponin I) in bone marrow mesenchymal stem cells (BMSCs), indicating early cardiogenic differentiation potential. In vivo, the implantation of the chitosan–SPE patch in a rat MI model demonstrated good tissue integration, preserved myocardial structure, and enhanced ventricular wall thickness, indicating that the patch has the potential to serve as a functional cardiac scaffold. These findings support the feasibility of screen-printed electrodes fabricated on chitosan film substrates as a cost-effective and scalable platform for cardiac repair, offering a foundation for future applications in cardiac tissue engineering.

PurposeTo study the association of myopia progression with the morphological changes of optic disc and β-peripapillary atrophy (β-PPA) in 8–11 years old primary school students.MethodsThis study was a prospective, school-based investigation. This study included 610 children (1008 eyes) who were continuously observed and had data available from 2016 to 2017 in the Sanhe Cohort Study of the Risk Factors for Myopia (SCSRFM). The children underwent a comprehensive eye examination including measurement of visual acuity, autorefractometry, and posterior segment of the eye. β-PPA regions and optic disc ovality index were identified and measured on the fundus photographs.ResultsThe prevalence of myopia was 72.62% (732/1008) in 2016. In myopic children, the prevalence of the vertical β-PPA, the horizontal β-PPA, and the oval optic disc were 75.68% (554/732), 75.96% (556/732) and, 11.61% (85/732) respectively. From 2016 to 2017, with the progression of vertical β-PPA, horizontal β-PPA, area of β-PPA, and optic disc ovality index, the myopic diopter and the axial length (AL) were increased. The progression of horizontal β-PPA was significantly correlated with the progression of myopic diopter and AL (all p < 0.05). The analysis on the distribution of progression rate of parameters in different groups found that the progression rate of horizontal β-PPA, area of β-PPA, and optic disc ovality index increased with the increase of the progression of diopter and AL. The progression of horizontal β-PPA, area of β-PPA, optic disc ovality index, and diopter in girls were greater than that in boys, and the progression of optic disc ovality index and diopter had a statistical significance (all p < 0.05).ConclusionsThe 1-year follow-up study of the third-grade primary school students showed that with the progression of myopia and the growth of AL, β-PPA and optic disc ovality index also changed. There was a positive correlation between the change of β-PPA and optic disc ovality index and the progression of myopia diopter and AL.

Background and IntroductionInfluenza and pneumococcal infections are major causes of morbidity and mortality among older adults. Under Singapore’s National Adult Immunisation Schedule (NAIS), Singapore citizens aged 65 years and above are eligible for fully subsidised influenza and pneumococcal vaccinations. This project was conducted in a local private primary care group practice (Healthway Medical Group), serving an urban population in Singapore. All participating clinics are part of the national HealthierSG (HSG) initiative, which focuses on preventive care, chronic disease management, vaccination uptake, and personalised health planning.Despite this, vaccination uptake within Healthway Medical Group clinics remained suboptimal in 2024, with a baseline average of 45.7% for influenza and 35% for pneumococcal vaccination. Contributing factors include missed opportunities during registration and consultations, limited patient awareness, and the absence of a systematic recall process. This project aims to improve influenza and pneumococcal vaccination uptake among elderly patients enrolled under HSG through team-based workflow redesign and coordination.MethodsA multidisciplinary team comprising of doctors, nurses, clinic assistants, Delivering On Target (DOT) Primary Care Network (PCN) staff and Quality Improvement (QI) coaches applied Clinical Practice Improvement (CPI) methodology. Workflow analysis, staff surveys, patient feedback, and process mapping were conducted to identify root causes. Interventions were implemented sequentially with the initial clinic and subsequently scaled and expanded to three additional clinics:January 2025: New registration workflow for clinic assistants to identify eligible patients and insert vaccination eligibility clinic alerts.February 2025: New workflow for doctor and reinforcement of vaccination recommendations during consults.End February 2025: Doctor refers resistant patients for nurse counselling on vaccination advocacy.Mid-March 2025: Introduction of pre-clerking clinic alerts to tag eligible patients in advance.April 2025: Generated vaccination patient list for active recall via calls or SMS.Results and ConclusionsBaseline median vaccination uptake in the initial pilot clinic was 41% for influenza and 38% for pneumococcal vaccines (figure 1 and figure 2). Following the implementation of interventions, both influenza and pneumococcal vaccination rates improved significantly, achieving post-intervention medians of 100% and a sustained weekly vaccination rate of 100% (figure 1 and figure 2). When interventions were subsequently scaled to three additional clinics, median influenza vaccination uptake increased from 17.6% to 33.3% (figure 3). However, median pneumococcal vaccination rates remained static at approximately 20% (figure 4), suggesting persistent challenges despite similar workflow enhancements.During the scale and spread, the 3 other clinics faced several challenges, such as system-related delays, manpower constraints due to staff turnover or leave, and patient-related barriers such as preference to wait for the new PCV20 vaccine, and no-shows for scheduled appointments. Despite these challenges, the interventions led to a steady overall increase in vaccination uptake, improved workflow efficiency, better patient understanding of vaccine benefits, and extended outreach to individuals who had not been vaccinated previously.Overall, the project demonstrated that structured, team-based interventions can meaningfully improve vaccination uptake within HSG clinics. The approach strengthened alignment with national preventive care goals by reducing missed vaccination opportunities and fostering consistent delivery of influenza and pneumococcal vaccinations. The key factors supporting this success included effective interprofessional collaboration, and the use of stepwise and scalable PDSA cycles.Abstract 224 Figure 1Weekly influenza vaccination rate (%), healthway medical clinic (cck)Abstract 224 Figure 2Weekly pneumococcal vaccination rate (%), healthway medical clinic (cck)Abstract 224 Figure 3Weekly influenza vaccination rate (%), 3 other healthway medical clinicAbstract 224 Figure 4Weekly pneumococcal vaccination rate (%), 3 other healthway medical clinic

We propose a protein secondary structure prediction method based on position-specific scoring matrix (PSSM) profiles and four physicochemical features including conformation parameters, net charges, hydrophobic, and side chain mass. First, the SVM with the optimal window size and the optimal parameters of the kernel function is found. Then, we train the SVM using the PSSM profiles generated from PSI-BLAST and the physicochemical features extracted from the CB513 data set. Finally, we use the filter to refine the predicted results from the trained SVM. For all the performance measures of our method, Q3 reaches 79.52, SOV94 reaches 86.10, and SOV99 reaches 74.60; all the measures are higher than those of the SVMpsi method and the SVMfreq method. This validates that considering these physicochemical features in predicting protein secondary structure would exhibit better performances.

A series of high entropy alloys (HEAs), AlxNbTiMoV, was produced by a vacuum arc-melting method. Their microstructures and compressive mechanical behavior at room temperature were investigated. It has been found that a single solid-solution phase with a body-centered cubic (BCC) crystal structure forms in these alloys. Among these alloys, Al0.5NbTiMoV reaches the highest yield strength (1,625 MPa), which should be attributed to the considerable solid-solution strengthening behavior. Furthermore, serration and crackling noises near the yielding point was observed in the NbTiMoV alloy, which represents the first such reported phenomenon at room temperature in HEAs.

In this paper, the ferrite grain size was controlled by two annealing methods, which can affect the low-temperature toughness of ferrite nodular cast iron. The annealing temperature ranged from 720 to 750 °C, and one annealing method consisted of constant temperature heating with temperature controlled to ± 1 °C. The other method employed cyclic heating, with a temperature change of 19 ( + 14, − 5) °C and a period of 450 s. The change law of ferrite grain size under low temperature annealing and the effect of ferrite grain size on low-temperature impact toughness were studied. The conditions under which the superheated ferrite does not transform into austenite were determined. The mechanism by which coarse ferrite favors high toughness in nodular cast iron at low temperatures was discussed. Nodular cast iron with tensile strength of 392 MPa, yield strength of 206 MPa, elongation of 26% and impact energy of 13.5 J at − 70 °C was obtained.