Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway.

BACKGROUND: Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. PURPOSE: This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. METHODS: C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. RESULTS: The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. CONCLUSIONS: Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin.

Spontaneous neural activity underlying neutral and happy speech recognition in noise and its association with psychiatric symptoms in patients with schizophrenia.

BACKGROUND: Deficits in speech and emotion perception are intertwined with psychiatric symptoms. How the happy prosody embedded in speech affects target speech-in-noise recognition (TSR) and relates to psychiatric symptoms in patients with schizophrenia (SCHs) remains unclear. This study examined spontaneous brain activity underlying happy TSR and its association with psychiatric symptom dimensions in SCHs. METHODS: Fifty-four SCHs and 59 healthy control participants (HCs) underwent the TSR task, Positive and Negative Syndrome Scale (PANSS) assessment, and magnetic resonance imaging scanning. Multivariate analyses of partial least squares (PLS) regression were used to explore the associations between whole-brain fractional amplitude of low-frequency fluctuations (fALFF), happy-neutral TSR (target pseudo-sentences were uttered in happy and neutral prosodies), and five PANSS factor scores (excitement/hostility, depression/anxiety, cognition, positive, and negative). RESULTS: The happy prosody did not alter TSR or TSR changing rates in either SCHs or HCs. SCHs exhibited lower happy and neutral TSR than HCs. A fALFF PLS component (including precentral/postcentral gyrus, Subcallosal Cortex, several temporal regions, and cerebellum) was associated with happy and neutral TSR. SCHs demonstrated higher PLS fALFF scores and PLS TSR scores than HCs. In SCHs, PLS fALFF scores were correlated with the PANSS positive factor score, and PLS TSR scores were correlated with the PANSS cognition factor score. CONCLUSIONS: The positive-psychiatric-symptoms-related spontaneous activity profile was associated with happy and neutral TSR, contributing to the cognition psychiatric symptoms dimension. The findings suggest the potential to improve positive and cognitive symptoms by enhancing happy and neutral TSR in schizophrenia based on neuroplasticity.

Transcriptomics Reveals the Pathway for Increasing Brassica chinensis L. Yield under Foliar Application of Titanium Oxide Nanoparticles.

In this study, Brassica chinensis L seedlings after 6 weeks of soil cultivation were treated with foliar application of TiO2 NPs (20 mg/L) for different times. Transcriptomics analysis was employed to investigate the impact of TiO2 NPs on the physiology, growth, and yield of B. chinensis L. Results showed that TiO2 NPs' exposure significantly increased the biomass, total phosphorus, and catalase enzyme activity by 23.60, 23.72, and 44.01%, respectively, compared to the untreated ones (not bulk or ion).TiO2 NPs increased the leaf chlorophyll content by 4.9% and photosynthetic rate by 16.62%, which was attributed to the upregulated expression of seven genes (PetH, PetF, PsaF, PsbA, PsbB, PsbD, and Lhcb) associated with electron transport in photosystem I and light-harvesting in leaves. The water balance of B. chinensis was improved correlating with the altered expressions of 19 aquaporin genes (e.g., PIP2;1 and NIP6;1). The expressions of 58 genes related to plant hormone signaling and growth were dysregulated, with notable downregulations in GA20, SnRK2, and PP2C and upregulations of DELLAs, SAM, and ETR. Moreover, the 11 tricarboxylic acid cycle genes and 13 glycolysis genes appear to stimulate pathways involved in promoting the growth and physiology of B. chinensis. This research contributes valuable insights into new strategies for increasing the yield of B. chinensis.

Determination of standard molar volume of 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide on titanium dioxide surface.

The fluids near the solid substrate display different properties compared to the bulk fluids owing to the asymmetric interaction between the fluid and substrate; however, to the best of our knowledge, no work has been conducted to determine the interfacial properties of fluids experimentally. In this work, we combined a pycnometer with experimental measurements and data processing to determine the standard thermodynamic properties of interfacial fluids for the first time. In the study, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Hmim][NTf2]) and titanium dioxide (P25) were chosen as the probes to prove the concept. It was found that, with the combination of the Gay-Lussac pycnometer and the colligative law, together with selecting a suitable solvent, it is possible and reliable to determine the standard molar volume of the immobilized [Hmim][NTf2]. Compared to the bulk phase, the molar volumes of [Hmim][NTf2] on the P25 surface reduce by 20.8%-23.7% at temperatures from 293.15 to 323.15 K, and the reduction degrees decrease with increasing temperatures. The newly determined standard thermodynamic data was used to obtain the model parameters of hybrid electrolyte perturbed-chain statistical associating fluid theory density functional theory (ePC-SAFT-DFT), and further predictions of the density of interfacial ionic liquids with different film thicknesses were proved to be reliable in comparison with the experiment results.

Connectivity Reveals the Relationships between Human Brain Areas Associated with High-Level Linguistic Processing and Macaque Brain Areas.

Cross-species research has advanced human understanding of brain regions, with cross-species comparisons using magnetic resonance imaging technology becoming increasingly common. Currently, cross-species research on human language regions has primarily focused on traditional brain areas such as the Broca region. While some studies have indicated that human language function also involves other language regions, the corresponding relationships between these brain regions in humans and macaques remain unclear. This study calculated the strength of the connections between the high-level language processing regions in human and macaque brains, identified homologous target areas based on the structural connections of white-matter fiber bundles, and compared the connectivity profiles of both species. The results of the experiment demonstrated that macaques possess brain regions which exhibit connectivity patterns resembling those found in human high-level language processing regions. This discovery suggests that while the function of a human brain region is specialized, it still maintains a structural connectivity similar to that seen in macaques.

Empagliflozin's role in early tubular protection for type 2 diabetes patients.

BACKGROUND: Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. METHODS: A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. RESULTS: Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. CONCLUSION: Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.

Facing the solid waste of cotton straw and plastic mulch film mixture in China: Centralized or decentralized pyrolysis facility?

The widespread use of plastic mulch film (PMF) has led to significant environmental pollution, with PMF residues dispersed and mixed with straw and soil, posing challenges for recycling. Here, we proposed the mobile pyrolysis facility for the cotton straw and mulch film mixture (CMM) to mitigate the collection, storage, and transportation costs, while the application of co-pyrolysis technology for CMM conversion could improve the added value of products. Additionally, centralized combustion power generation and centralized pyrolysis systems were also established to evaluate and compare their sustainability from economic and environmental perspectives. Results showed that mobile pyrolysis has better economic performance than the centralized scenarios, due to its high internal rate of return (31 %) and significant net present value (29.21 M USD). Meanwhile, the mobile pyrolysis facility achieved a GWP of -1.298 kgCO2-eq/kg, reducing emissions by 70.79 % and 38.82 % compared to the two centralized scenarios. In conclusion, mobile pyrolysis technology provides a promising solution for PMF residue recycling because of its economically competitive approach with a lower carbon footprint.

Nomogram for Predicting Hypoglycemia in Type 2 Diabetes Mellitus Patients Treated with Insulin Pump During Enteral Nutrition.

Purpose: To develop a prediction model for hypoglycemia in type 2 diabetes mellitus (T2DM) patients treated with an insulin pump during enteral nutrition. Methods: This retrospective study included T2DM patients treated with an insulin pump during enteral nutrition at the First Affiliated Hospital of Jinan University, Guangzhou Red Cross Hospital, Foshan First People's Hospital, and Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2016 and December 2023. The patients were randomized 3:1 to the training and validation sets. The risk factors for hypoglycemia were analyzed. A prediction model was developed. Results: This study included 122 patients, and 57 patients had at least one hypoglycemic event during their hospitalization (46.72%). The multivariable logistic regression analysis showed that the time to reach the glycemic targets (odds ratio (OR)=1.408, 95% confidence interval (CI)=1.084-1.825, P=0.006), average glycemia (OR=0.387, 95% CI=0.233-0.643, P=0.010), coronary heart disease (OR=0.089, 95% CI=0.016-0.497, P<0.001), and the administration of hormone therapy (OR=6.807, 95% CI=1.128-41.081, P=0.037) were independently associated with hypoglycemia. A nomogram was built. The receiver operating characteristics analysis showed that the area under the curve of the model was 0.872 (95% CI=0.0.803-0.940) for the training set and 0.839 (95% CI=0.688-0.991) in the validation set. Conclusion: A nomogram was successfully built to predict hypoglycemia in T2DM patients treated with an insulin pump during enteral nutrition, based on the time to reach the glycemic targets, average glycemia, coronary heart disease, and the administration of hormone therapy.

Functional Characterization of the MeSSIII-1 Gene and Its Promoter from Cassava.

Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the MeSSIII-1 gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the MeSSIII-1 gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots. MeSSIII-1 expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava. MeSSIII-1 expression patterns were further confirmed in proMeSSIII-1 transgenic cassava. The promoter deletion analysis showed that the -264 bp to -1 bp MeSSIII-1 promoter has basal activity. The range from -1228 bp to -987 bp and -488 bp to -264 bp significantly enhance promoter activity. The regions from -987 bp to -747 bp and -747 bp to -488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the MeSSIII-1 gene and for further in-depth exploration of the regulatory network of its internal functional elements.

Multimodal fused deep learning for drug property prediction: Integrating chemical language and molecular graph.

Accurately predicting molecular properties is a challenging but essential task in drug discovery. Recently, many mono-modal deep learning methods have been successfully applied to molecular property prediction. However, mono-modal learning is inherently limited as it relies solely on a single modality of molecular representation, which restricts a comprehensive understanding of drug molecules. To overcome the limitations, we propose a multimodal fused deep learning (MMFDL) model to leverage information from different molecular representations. Specifically, we construct a triple-modal learning model by employing Transformer-Encoder, Bidirectional Gated Recurrent Unit (BiGRU), and graph convolutional network (GCN) to process three modalities of information from chemical language and molecular graph: SMILES-encoded vectors, ECFP fingerprints, and molecular graphs, respectively. We evaluate the proposed triple-modal model using five fusion approaches on six molecule datasets, including Delaney, Llinas2020, Lipophilicity, SAMPL, BACE, and pKa from DataWarrior. The results show that the MMFDL model achieves the highest Pearson coefficients, and stable distribution of Pearson coefficients in the random splitting test, outperforming mono-modal models in accuracy and reliability. Furthermore, we validate the generalization ability of our model in the prediction of binding constants for protein-ligand complex molecules, and assess the resilience capability against noise. Through analysis of feature distributions in chemical space and the assigned contribution of each modal model, we demonstrate that the MMFDL model shows the ability to acquire complementary information by using proper models and suitable fusion approaches. By leveraging diverse sources of bioinformatics information, multimodal deep learning models hold the potential for successful drug discovery.

Developing an Improved Cycle Architecture for AI-Based Generation of New Structures Aimed at Drug Discovery.

Drug discovery involves a crucial step of optimizing molecules with the desired structural groups. In the domain of computer-aided drug discovery, deep learning has emerged as a prominent technique in molecular modeling. Deep generative models, based on deep learning, play a crucial role in generating novel molecules when optimizing molecules. However, many existing molecular generative models have limitations as they solely process input information in a forward way. To overcome this limitation, we propose an improved generative model called BD-CycleGAN, which incorporates BiLSTM (bidirectional long short-term memory) and Mol-CycleGAN (molecular cycle generative adversarial network) to preserve the information of molecular input. To evaluate the proposed model, we assess its performance by analyzing the structural distribution and evaluation matrices of generated molecules in the process of structural transformation. The results demonstrate that the BD-CycleGAN model achieves a higher success rate and exhibits increased diversity in molecular generation. Furthermore, we demonstrate its application in molecular docking, where it successfully increases the docking score for the generated molecules. The proposed BD-CycleGAN architecture harnesses the power of deep learning to facilitate the generation of molecules with desired structural features, thus offering promising advancements in the field of drug discovery processes.

Paeonia lactiflora Pall. ameliorates acetaminophen-induced oxidative stress and apoptosis via inhibiting the PKC-ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PLP), a traditional Chinese medicine, is recognized for its antioxidative and anti-apoptotic properties. Despite its potential medicinal value, the mechanisms underlying its efficacy have been less explored, particularly in alleviating acute liver injury (ALI) caused by excessive intake of acetaminophen (APAP). AIM OF THE STUDY: This study aims to elucidate the role and mechanisms of PLP in mitigating oxidative stress and apoptosis induced by APAP. MATERIALS AND METHODS: C57BL/6 male mice were pre-treated with PLP for seven consecutive days, followed by the induction of ALI using APAP. Liver pathology was assessed using HE staining. Serum indicators, immunofluorescence (IF), immunohistochemical (IHC), and transmission electron microscopy were employed to evaluate levels of oxidative stress, ferroptosis and apoptosis. Differential expression proteins (DEPs) in the APAP-treated and PLP pre-treated groups were analyzed using quantitative proteomics. Subsequently, the potential mechanisms of PLP pre-treatment in treating ALI were validated using western blotting, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) analysis. RESULTS: The UHPLC assay confirmed the presence of three compounds, i.e., albiflorin, paeoniflorin, and oxypaeoniflorin. Pre-treatment with PLP was observed to ameliorate liver tissue pathological damage through HE staining. Further confirmation of efficacy of PLP in alleviating APAP-induced liver injury and oxidative stress was established through liver function serum biochemical indicators, IF of reactive oxygen species (ROS) and IHC of glutathione peroxidase 4 (GPX4) detection. However, PLP did not demonstrate a significant effect in alleviating APAP-induced ferroptosis. Additionally, transmission electron microscopy and TUNEL staining indicated that PLP can mitigate hepatocyte apoptosis. PKC-ERK pathway was identified by proteomics, and subsequent molecular docking, molecular dynamics simulations, and SPR verified binding of the major components of PLP to ERK protein. Western blotting demonstrated that PLP suppressed protein kinase C (PKC) phosphorylation, blocking extracellular signal-regulated kinase (ERK) phosphorylation and inhibiting oxidative stress and cell apoptosis. CONCLUSION: This study demonstrates that PLP possesses hepatoprotective abilities against APAP-induced ALI, primarily by inhibiting the PKC-ERK cascade to suppress oxidative stress and cell apoptosis.

Optimized therapeutic potential of Yinchenhao decoction for cholestatic hepatitis by combined network meta-analysis and network pharmacology.

BACKGROUND: Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD. PURPOSE: To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored. METHODS: We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques. RESULTS: Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness. CONCLUSION: Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.

Separation of Mono-/Divalent Ions via Controlled Dynamic Adsorption/Desorption at Polythiophene Coated Carbon Surface with Flow-Electrode Capacitive Deionization.

Capacitive deionization for selective separation of ions is rarely reported since it relies on the electrostatic attraction of oppositely charged ions with no capability to distinguish ions of different valent states. Using molecular dynamic simulation, a screening process identified a hybrid material known as AC/PTh, which consists of activated carbon with a thin layer of polythiophene (PTh) coating. By utilizing AC/PTh as electrode material implementing the short-circuit cycle (SCC) mode in flow-electrode capacitive deionization (FCDI), selective separation of mono-/divalent ions can be realized via precise control of dynamic adsorption and desorption of mono-/divalent ions at a particular surface. Specifically, AC/PTh shows strong interaction with divalent ions but weak interaction with monovalent ions, the distribution of divalent ions can be enriched in the electric double layer after a couple of adsorption-desorption cycles. At Cu2+/Na+ molar ratio of 1:40, selectivity toward divalent ions can reach up to 110.3 in FCDI SCC mode at 1.0 V. This work presents a promising strategy for separating ions of different valence states in a continuously operated FCDI device.

Molecular insights into experimental models and therapeutics for cholestasis.

Cholestatic liver disease (CLD) is a range of conditions caused by the accumulation of bile acids (BAs) or disruptions in bile flow, which can harm the liver and bile ducts. To investigate its pathogenesis and treatment, it is essential to establish and assess experimental models of cholestasis, which have significant clinical value. However, owing to the complex pathogenesis of cholestasis, a single modelling method can merely reflect one or a few pathological mechanisms, and each method has its adaptability and limitations. We summarize the existing experimental models of cholestasis, including animal models, gene-knockout models, cell models, and organoid models. We also describe the main types of cholestatic disease simulated clinically. This review provides an overview of targeted therapy used for treating cholestasis based on the current research status of cholestasis models. In addition, we discuss the respective advantages and disadvantages of different models of cholestasis to help establish experimental models that resemble clinical disease conditions. In sum, this review not only outlines the current research with cholestasis models but also projects prospects for clinical treatment, thereby bridging basic research and practical therapeutic applications.

Accurate prediction of solvent flux in sub-1-nm slit-pore nanosheet membranes.

Nanosheet-based membranes have shown enormous potential for energy-efficient molecular transport and separation applications, but designing these membranes for specific separations remains a great challenge due to the lack of good understanding of fluid transport mechanisms in complex nanochannels. We synthesized reduced MXene/graphene hetero-channel membranes with sub-1-nm pores for experimental measurements and theoretical modeling of their structures and fluid transport rates. Our experiments showed that upon complete rejection of salt and organic dyes, these membranes with subnanometer channels exhibit remarkably high solvent fluxes, and their solvent transport behavior is very different from their homo-structured counterparts. We proposed a subcontinuum flow model that enables accurate prediction of solvent flux in sub-1-nm slit-pore membranes by building a direct relationship between the solvent molecule-channel wall interaction and flux from the confined physical properties of a liquid and the structural parameters of the membranes. This work provides a basis for the rational design of nanosheet-based membranes for advanced separation and emerging nanofluidics.

Enhanced CO2 Capture through SAPO-34 Impregnated with Ionic Liquid.

The concurrent utilization of an adsorbent and absorbent for carbon dioxide (CO2) adsorption with synergistic effects presents a promising technique for CO2 capture. Here, 1-butyl-3-methylimidazole acetate ([Bmim][Ac]), with a high affinity for CO2, and the molecular sieve SAPO-34 were selected. The impregnation method was used to composite the hybrid samples of [Bmim][Ac]/SAPO-34, and the pore structure and surface property of prepared samples were characterized. The quantity and kinetics of the sorbed CO2 for loaded samples were measured using thermogravimetric analysis. The study revealed that SAPO-34 could retain its pristine structure after [Bmim][Ac] loading. The CO2 uptake of the loaded sample was 1.879 mmol g-1 at 303 K and 1 bar, exhibiting a 20.6% rise compared to that of the pristine SAPO-34 recording 1.558 mmol g-1. The CO2 uptake kinetics of the loaded samples were also accelerated, and the apparent mass transfer resistance for CO2 sorption was significantly reduced by 11.2% compared with that of the pure [Bmim][Ac]. The differential scanning calorimetry method revealed that the loaded sample had a lower CO2 desorption heat than that of the pure [Bmim][Ac], and the CO2 desorption heat of the loaded samples was between 30.6 and 40.8 kJ mol-1. The samples exhibited good cyclic stability. This material displays great potential for CO2 capture applications, facilitating the reduction of greenhouse gas emissions.

Rational synthesis of a heparan sulfate saccharide that promotes the activity of BMP2.

Heparan sulfate (HS) is a glycosaminoglycan (GAG) found throughout nature and is involved in a wide range of functions including modulation of cell signalling via sequestration of growth factors. Current consensus is that the specificity of HS motifs for protein binding are individual for each protein. Given the structural complexity of HS the synthesis of libraries of these compounds to probe this is not trivial. Herein we present the synthesis of an HS decamer, the design of which was undertaken rationally from previously published data for HS binding to the growth factor BMP-2. The biological activity of this HS decamer was assessed in vitro, showing that it had the ability to both bind BMP-2 and increase its thermal stability as well as enhancing the bioactivity of BMP-2 in vitro in C2C12 cells. At the same time no undesired anticoagulant effect was observed. This decamer was then analysed in vivo in a rabbit model where higher bone formation, bone mineral density (BMD) and trabecular thickness were observed over an empty defect or collagen implant alone. This indicated that the HS decamer was effective in promoting bone regeneration in vivo.

Pain Sensitivity and Acute Postoperative Pain in Patients Undergoing Abdominal Surgery: The Mediating Roles of Pain Self-Efficacy and Pain Catastrophizing.

BACKGROUND: Inadequately managed postoperative pain remains a common issue. Examining factors like pain sensitivity, pain catastrophizing, and pain self-efficacy can help improve postoperative pain management. While these factors have been identified as potential predictors of acute postoperative pain, their effects have been inconsistent. Few studies have explored the interactions between these factors. AIM: To investigate the influence of preoperative pain sensitivity, pain catastrophizing, and pain self-efficacy on acute postoperative pain in abdominal surgery patients and to determine the mediating roles of pain catastrophizing and pain self-efficacy in the relationship between pain sensitivity and acute postoperative pain, as per the gate control theory. METHODS: A total of 246 patients were enrolled in this study. General information was collected before surgery, and the Pain Sensitivity Questionnaire (PSQ), Pain Catastrophizing Scale (PCS), and Pain Self-Efficacy Questionnaire (PSEQ) were administered. After surgery, patients' average pain scores over the 24 hours were reported using the Numerical Rating Scale (NRS). Correlation analyses and a structural equation model were used to examine the relationships among these variables. RESULTS: NRS scores over 3 during the 24 hours post-surgery were reported by 21.54% of patients. Postoperative acute pain was found to be associated with pain sensitivity (rs = 0.463, p < .001), pain catastrophizing (rs = 0.328, p < .001), and pain self-efficacy (rs = -0.558, p < .001). A direct effect on postoperative acute pain was exerted by pain sensitivity (effect = 0.250, p = .001), along with indirect effects through: (A) pain catastrophizing (effect = 0.028, p = .001); (B) pain self-efficacy (effect = 0.132, p = .001); and (C) the chain mediation of pain self-efficacy and pain catastrophizing (effect = 0.021, p = .008). CONCLUSIONS: The severity of postoperative acute pain can be predicted by pain self-efficacy and pain catastrophizing, and the connection between moderate pain sensitivity and postoperative acute pain severity is mediated by them. Therefore, intervention programs aimed at boosting pain self-efficacy and reducing pain catastrophizing can enhance postoperative pain outcomes for abdominal surgery patients.

Assessing early tubular protective effects of SGLT2 inhibitor empagliflozin against type 2 diabetes mellitus using functional magnetic resonance imaging.

AIMS: To observe the alterations in functional magnetic resonance imaging parameters in normoalbuminuric type 2 diabetic patients undergoing SGLT2 inhibitor empagliflozin treatment and investigate the early tubular protective effects of the inhibitor. METHODS: This study was performed in normoalbuminuric type 2 diabetes mellitus patients (UACR < 30 mg/g, eGFR ≥ 60 ml/min/1.73 m2). The patients were divided into the intervention group (empagliflozin) and the control group (27 cases each). The intervention group was treated with 10 mg/day empagliflozin tablets orally, while the control group had adjustments to their basic treatment stage. The patients were treated for 6 weeks. RESULTS: The baseline clinical data of the two groups were comparable (P˃0.05). The intervention group exhibited better improvements in blood lipid profiles and more significant reductions in blood uric acid levels compared to the control group (P < 0.05). The two groups had No significant difference in blood pressure changes (P˃0.05). Notably, the intervention group demonstrated a greater reduction in UACR and a more substantial decline in eGFR than the control group (P < 0.05). Regarding functional magnetic resonance imaging parameters, the MD value of the renal medulla region in the intervention group increased after treatment, while the MR2* value of the renal medulla region decreased (P < 0.05). CONCLUSIONS: SGLT2 inhibitor empagliflozin can reduce UACR and eGFR levels in early type 2 diabetic patients with normal proteinuria. Moreover, empagliflozin therapy led to an increase in the MD value and a decrease in the MR2* value of the renal medulla, evidencing the early tubular protective effects of this therapy.