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Abstract Background Patients with knee osteoarthritis (KOA) often experience persistent pain and functional impairment after total knee arthroplasty (TKA), which presents challenges for pain management. Accurate preoperative assessment of pain characteristics is crucial for tailoring individualized treatment plans. The PainDETECT Questionnaire has been widely used to identify neuropathic components in chronic pain and has been validated for its reliability and validity across various cultural contexts. However, a culturally adapted version tailored to Chinese patients is currently lacking. This study aims to translate and culturally adapt PainDETECT for Chinese patients and evaluate its validity in TKA patients in China. Methods This study followed international guidelines to translate and adapt the PainDETECT Questionnaire (PDQ) into Chinese (PDQ-CV). A cohort of 241 knee osteoarthritis (KOA) patients completed the PDQ-CV, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol-5 Dimensions-5 Levels (EQ-5D-5 L), and Central Sensitization Inventory Chinese Version (CSI-CV). We assessed internal consistency using Cronbach’s alpha and test-retest reliability via intraclass correlation coefficient (ICC). Construct and structural validity were evaluated through Pearson correlations and factor analyses. Results The PDQ-CV demonstrated good acceptability among KOA patients, with no floor or ceiling effects observed. Internal consistency was high (Cronbach’s α = 0.896), and test-retest reliability was excellent (ICC = 0.994; 95% CI: 0.943–1.045). The PDQ-CV total score showed significant positive correlations with WOMAC (r = 0.589, P

Abstract Achieving a synergy of biocompatibility and extreme environmental adaptability with excellent mechanical property remains challenging in the development of synthetic materials. Herein, a “bottom-up” solution-interface-induced self-assembly strategy is adopted to develop a compressible, anti-fatigue, extreme environment adaptable, biocompatible, and recyclable organohydrogel composed of chitosan-lignosulfonate-gelatin by constructing noncovalent bonded conjoined network. The ethylene glycol/water solvent induced lignosulfonate nanoparticles function as bridge in chitosan/gelation network, forming multiple interfacial interactions that can effectively dissipate energy. The organohydrogel exhibits high compressive strength (54 MPa) and toughness (3.54 MJ/m3), 100 and 70 times higher than those of pure chitosan/gelatin hydrogel, meanwhile, excellent self-recovery and fatigue resistance properties. Even when subjected to severe compression up to a strain of 0.5 for 500,000 cycles, the organohydrogel still remains intact. This organohydrogel also demonstrates notable biocompatibility both in vivo and vitro, environment adaptability at low temperature, as well as recyclability. Such all natural organohydrogel provides a promising route towards the development of high-performance load-bearing materials.

Abstract Background Hepatocellular carcinoma (HCC) continues to be a major cause of cancer-related death worldwide, primarily due to delays in diagnosis and resistance to existing treatments. Recent research has identified ATP-dependent chromatin remodeling-related genes (ACRRGs) as promising targets for therapeutic intervention across various types of cancer. This development offers potential new avenues for addressing the challenges in HCC management. Methods This study integrated bioinformatics analyses and experimental approaches to explore the role of ACRRGs in HCC. We utilized data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), applying machine learning algorithms to develop a prognostic model based on ACRRGs’ expression. Experimental validation was conducted using quantitative real-time Polymerase Chain Reaction (qRT-PCR), Western blotting, and functional assays in HCC cell lines and xenograft models. Results Our bioinformatics analysis identified four key ACRRGs—MORF4L1, HDAC1, VPS72, and RUVBL2—that serve as prognostic markers for HCC. The developed risk prediction model effectively distinguished between high-risk and low-risk patients, showing significant differences in survival outcomes and predicting responses to immunotherapy in HCC patients. Experimentally, MORF4L1 was demonstrated to enhance cancer stemness by activating the Hedgehog signaling pathway, as supported by both in vitro and in vivo assays. Conclusion ACRRGs, particularly MORF4L1, play crucial roles in modulating HCC progression, offering new insights into the molecular mechanisms driving HCC and potential therapeutic targets. Our findings advocate for the inclusion of chromatin remodeling dynamics in the strategic development of precision therapies for HCC.

Objective: M6A methylation-regulated macrophages play an important role in the occurrence and development of arteriosclerosis. However, their role in lower extremity arteriosclerosis remains unclear. Therefore, this study aims to explore the key factors that regulate arteriosclerosis methylation in the lower extremities and the mechanism by which they affect arteriosclerosis by influencing macrophage polarization. Methods: The m6A methylation levels in peripheral blood mononuclear cells (PBMCs) of patients with lower extremity atherosclerosis was investigated using the Dot blot method. Additionally, the expression levels of RNA methyltransferases and demethylases were examined using ELISA and Western blotting. Inflammatory macrophages were established using RAW264.7 cells stimulated with LPS (100 ng/mL), and the expression of ALKBH5 and ITGB1 was evaluated using Western blotting. Immunofluorescence staining was conducted to assess the expression of M1 macrophage markers (F4/80+CD86) and M2 macrophage markers (F4/80+CD206) in renal tissue. ELISA was employed to measure the levels of cytokines (IL-6, IL-1β, TNF-a, IL-10, and TGF-β) and plasma lipid levels in mice. An atherosclerosis model was established in ApoE−/− mice through balloon pull surgery and high-fat feeding. Oil Red O staining and hematoxylin and eosin (HE) staining were performed to measure the area of atherosclerotic plaques and the size of the necrotic core in mouse femoral artery, respectively. Additionally, Starbase2.0 was used for downstream target gene prediction of ALKBH5. The half-life of ITGB1 was evaluated using RT-qPCR. Results: The m6A methylation levels were significantly increased in PBMCs of patients with lower extremity atherosclerosis. Among them, the expression of the RNA demethylase ALKBH5 was the lowest in PBMCs of patients with lower extremity atherosclerosis. Further analysis revealed that ALKBH5 can alleviate the progression of lower extremity atherosclerosis and promote the polarization of M2 macrophages. ALKBH5 can reduce the stability of ITGB1 through demethylation. Mechanistically, ALKBH5 influences macrophage polarization and mitigates lower extremity atherosclerosis by affecting the demethylation of ITGB1. Conclusion: ALKBH5 promotes M2 macrophage polarization and alleviates lower extremity atherosclerosis by regulating the demethylation of ITGB1. A deeper understanding of this process not only helps elucidate the molecular mechanisms of atherosclerosis but also provides possibilities for the development of new therapeutic strategies.

PurposeThe purpose of this investigation is to assess and contrast the effectiveness of the two EuroQol five dimensions questionnaire (EQ-5D) versions—EQ-5D-3L and EQ-5D-5L—in assessing one-year quality of life outcomes for patients with knee osteoarthritis (KOA) undergoing unicompartmental knee arthroplasty (UKA).Material and methodFrom the medical records at the Honghui Hospital, Xi’an Jiaotong University, 402 individuals aged 50 and above, who were one-year post-operation, were selected to fill out survey questionnaires during their return hospital visits. Of these, 231 respondents (57.5%) completed the questionnaire; 228 completed both versions, and 56 completed the EQ-5D retest questionnaire. The assessment included missing data, ceiling effects, informativity and discriminatory power, as well as response consistency, redistribution properties, and inconsistency. Reliability and validity were also evaluated.ResultsThe results indicate that the EQ-5D-5L surpasses the EQ-5D-3L in construct validity, informativity, detection precision, and discriminatory power. Consistency reliability is also better in the EQ-5D-5L than in the EQ-5D-3L. Both instrument versions maintained reliable levels of test–retest reliability.ConclusionIn patients with KOA undergoing UKA, the EQ-5D-5L has proven superior in measurement capabilities when compared with the EQ-5D-3L one-year post-operation. Thus, it is advised to utilize the EQ-5D-5L for ongoing assessments of quality of life in this specific group of patients.

Background and purpose: The poor prognosis of subarachnoid hemorrhage (SAH) is closely linked to neuroinflammation and neuronal apoptosis. The CCL2/CCR2 signaling axis, a cytoplasmic pathway responsible for recruiting immune cells, plays a significant role in regulating neuroinflammation in neurological diseases. Bindarit, an inhibitor of chemokine CC motif ligand 2(CCL2), has been shown to demonstrate neuroprotective effects in various central nervous system diseases. This study aimed to investigate the anti-inflammatory effects of Bindarit after SAH. Methods: Pre-processed RNA-seq transcriptome datasets GSE79416 from the Gene Expression Omnibus (GEO) database were analyzed to identify genes differentially expressed between mice with SAH and control mice using bioinformatics methods. Bindarit, a CCL2 inhibitor, was administered intraperitoneally one hour after SAH. Recombinant CCL2 protein was administered via the lateral ventricle one hour before SAH induction. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. Results: Analysis of GSE79416 datasets revealed upregulation of CCL2 expression, identifying it as a hub gene in SAH. Following SAH, CCL2 expression increased in rat brain tissue, reaching the highest level 24 h after SAH. Bindarit improved the short-term and long-term neurological deficits after SAH and also exhibited the anti-inflammatory effects following SAH. Conversely, administration of recombinant CCL2 protein attenuated the protective effects of Bindarit. In vitro, Bindarit significantly reduced neuronal inflammation. Conclusion: Endogenous CCL2 expression was upregulated in the rat SAH model. Bindarit improved neurological functions and reduced neuroinflammation by regulating the CCL2/CCR2/NF-κB pathway in early brain injury after SAH.

Climate change and the energy crisis are impeding global economic and sustainable development. As a high-carbon emissions industry, construction can practice green construction to reduce carbon emissions and mitigate global warming. Based on data from China's Beijing-Tianjin-Hebei region during the period 2010 to 2020, the spatiotemporal pattern and its influencing factors on the green development of construction were studied by using spatial econometric methods. The findings indicate that the level of green development of the construction industry in the region followed an alternating pattern of rising and falling but demonstrated a gradual overall upward trend during the period. The spatial distribution pattern shows that Beijing, Tianjin, and Shijiazhuang are the core cities, driving the development of surrounding smaller cities and that the influencing factors of green construction are technological innovation, industrial investment, urban greening level, labor force level, and urbanization level. This study provides scientific support and policy recommendations for narrowing the imbalance in the green development level of construction between regions in China and reducing carbon emissions generated by the construction industry. [ABSTRACT FROM AUTHOR]

BackgroundAcute type A aortic dissection (ATAAD) is a life-threatening condition that often requires total aortic arch replacement (TAR) combined with frozen elephant trunk (FET) implantation. Despite advancements in surgical techniques and preoperative management, postoperative acute kidney injury (AKI) remains a prevalent complication that significantly affects patient prognosis, particularly severe AKI. The aim of this study was to investigate the predictive value of perioperative lactate levels in severe postoperative AKI after TAR.MethodsA cohort analysis of 328 patients who underwent TAR with frozen elephant trunk implantation at Xijing Hospital, Xi’an, China, between September 2019 and September 2023 was conducted. Patients were categorized according to AKI severity into non-AKI, mild-AKI, and severe-AKI cohorts, and lactate levels were measured at nine perioperative time points. The primary endpoint was severe AKI (Kidney Disease: Improving Global Outcomes stage 3). Uni-and multivariate logistic regression analyses were performed to identify risk factors for severe AKI. Subgroup analysis substantiated the robustness of lactate levels in predicting severe AKI.ResultsIn total, 45.4% of patients developed mild AKI postoperatively and 20.7% developed severe AKI. Patients with severe postoperative AKI exhibited higher preoperative lactate levels. Multivariate stepwise backward logistic regression analysis identified lactate levels at 12 h postoperatively ([Lacpo12h], cutoff value: 3.3 mmol/L; sensitivity: 63.2%; specificity: 72.3%) as an independent predictor of severe AKI. The subgroup analysis underscored the consistent predictive capacity of Lacpo12h. The 30-day mortality rate was markedly elevated in the severe-AKI cohort, with deceased patients exhibiting a significantly higher Lacpo12h.ConclusionAmong patients with acute type A aortic dissection undergoing TAR, high perioperative lactate levels were closely associated with postoperative AKI. Lacpo12h is a reliable and effective predictor of severe postoperative AKI, highlighting its clinical utility in risk stratification and management strategies.

Abstract A chemical investigation of Streptomyces sp. GZWMJZ-662, an endophytic actinomycete isolated from Houttuynia cordata Thunb., has yielded eleven bohemamine dimers (1–11). Notably, the newly identified dibohemamines I–O (1–7) have not been previously reported. Their structures were elucidated through detailed spectroscopic analysis, encompassing high-resolution electrospray ionization mass, nuclear magnetic resonance, infrared radiation, ultraviolet–visible, and electronic circular dichroism spectroscopy. Dibohemamine I (1) exhibited selective cytotoxic effects against the cancer cell lines 786-O and GBC-SD among the 18 cell lines evaluated, with the half-inhibitory concentration values of 3.24 ± 0.20 and 7.36 ± 0.41 μM, respectively. Graphical Abstract

Gaussia Luciferase (GLuc) is a renowned reporter protein that can catalyze the oxidation of coelenterazine (CTZ) and emit a bright light signal. GLuc comprises two consecutive repeats that form the enzyme body and a central putative catalytic cavity. However, deleting the C-terminal repeat only limited reduces the activity (over 30% residual luminescence intensity detectable), despite being a key part of the cavity. How does the remaining GLuc (tGLuc) catalyze CTZ? To address this question, we built a structural model of tGLuc by removing the C-terminal repeat from the resolved structure of intact GLuc, and verified that the cavity-forming component in GLuc remains stable and provides an open-mouth cavity in tGLuc during 500 ns MD simulations in water. Docking simulation and a followed umbrella sampling analysis further revealed that the cavity on tGLuc has a high affinity for CTZ, with a binding energy of up to -114 kJ/mol. Moreover, R76, a validated activity-critical amino acid residue, resides in the cavity and forms a stable hydrogen bond with CTZ. Then, we constructed a cluster model to examine the CTZ oxidation pathway in the cavity using Density Functional Theory (DFT) calculations. The result showed that the pathway consists of four elementary reactions, with the highest Gibbs energy barrier being 65.4 kJ/mol. Both intramolecular electron transfer and the convergence of S1/S0 potential energy surfaces occurred in the last elementary reaction, which was regarded as the reported Chemically-Initiated-Electron-Exchange-Luminescence (CIEEL) reaction. Geometry and wavefunction analysis on the pathway indicated that R76 plays a vital role in CTZ oxidation, which first anchors the environmental oxygen molecule and induces it to form a singlet biradical state, facilitating its attack on CTZ. Subsequently, R76 and the adjacent Q88, positioned near R76 through the tGLuc refolding process, stabilize the transition states and facilitate the emergence of radical electrons on CTZ at the onset of the CIEEL reaction, which contributes to the subsequent intramolecular electron transfer and the production of excited amide product. This study provides a comprehensive explanation of tGLuc's catalytic mechanism. However, it is important to note that these findings are specific to tGLuc and may not extend to other CTZ-based luciferases, particularly those lacking arginine in their catalytic cavities, which likely operate via distinct mechanisms.