Network pharmacology and experimental verification of the mechanism of licochalcone A against Staphylococcus aureus pneumonia.

Staphylococcus aureus strains cause the majority of pneumonia cases and are resistant to various antibiotics. Given this background, it is very important to discover novel host-targeted therapies. Licochalcone A (LAA), a natural plant product, has various biological activities, but its primary targets in S. aureus pneumonia remain unclear. Therefore, the purpose of this study was to identify its molecular target against S. aureus pneumonia. Network pharmacology analysis, histological assessment, enzyme-linked immunosorbent assays, and Western blotting were used to confirm the pharmacological effects. Network pharmacology revealed 33 potential targets of LAA and S. aureus pneumonia. Enrichment analysis revealed that these potential genes were enriched in the Toll-like receptor and NOD-like receptor signaling pathways. The results were further verified by experiments in which LAA alleviated histopathological changes, inflammatory infiltrating cells and inflammatory cytokines (TNF, IL-6, and IL-1ß) in the serum and bronchoalveolar lavage fluid in vivo. Moreover, LAA treatment effectively reduced the expression levels of NF-κB, p-JNK, p-p38, NLRP3, ASC, caspase 1, IL-1ß, and IL-18 in lung tissue. The in vitro experimental results were consistent with the in vivo results. Thus, our findings demonstrated that LAA exerts anti-infective effects on S. aureus-induced lung injury via suppression of the Toll-like receptor and NOD-like receptor signaling pathways, which provides a theoretical basis for understanding the function of LAA against S. aureus pneumonia and implies its potential clinical application.

Mechanisms of surface groups regulating developmental toxicity of graphene-based nanomaterials via glycerophospholipid metabolic pathway.

Surface modification of graphene-based nanomaterials (GBNs) may occur in aquatic environment and during intentional preparation. However, the influence of the surface groups on the developmental toxicity of GBNs has not been determined. In this study, we evaluated the developmental toxicity of three GBNs including GO (graphene oxide), RGO (reduced GO) and RGO-N (aminated RGO) by employing zebrafish embryos at environmentally relevant concentrations (1-100 µg/L), and the underlying metabolic mechanisms were explored. The results showed that both GO and RGO-N disturbed the development of zebrafish embryos, and the adverse effect of GO was greater than that of RGO-N. Furthermore, the oxygen-containing groups of GBNs play a more important role in inducing developmental toxicity compared to size, defects and nitrogen-containing groups. Specifically, the epoxide and hydroxyl groups of GBNs increased their intrinsic oxidative potential, promoted the generation of ROS, and caused lipid peroxidation. Moreover, a significant decrease in guanosine and abnormal metabolism of multiple glycerophospholipids were observed in all three GBN-treated groups. Nevertheless, GO exposure triggered more metabolic activities related to lipid peroxidation than RGO or RGO-N exposure, and the disturbance intensity of the same metabolite was greater than that of the other two agents. These findings reveal underlying metabolic mechanisms of GBN-induced developmental toxicity.

Cystic Plate Approach Combined with Indocyanine Green（ICG） Fluorescence in Laparoscopic Anatomical Hepatectomy.

BACKGROUND: The in-depth understanding of the fine anatomy of the liver has promoted the development of modern liver surgery. With the rapid popularity of laparoscopic hepatectomy, the membrane structure of the liver and its ability to dissect the intra- and extra-hepatic vascular system more conveniently and accurately has been gradually emphasized. OBJECTIVE: Exploring the value of extrahepatic sheath dissection of the hepatic pedicle in minimally invasive anatomical hepatectomy with cystic plate approach. This study aims to assess the benefits of integrating the cystic plate approach with real-time guided laparoscopic anatomical hepatectomy, in comparison with conventional laparoscopic anatomical hepatectomy. MATERIALS AND METHODS: Based on the theory of cystic plate and hepatic portal plate, we have pioneered the fluorescence real-time guided cystic plate approach in hepatectomy. The article focuses on the anatomical knowledge and technical difficulties of anatomical hepatectomy with fluoroscopic laparoscopic cystic plate approach and explores the safety and practicality of the cystic plate approach in laparoscopic anatomical hepatectomy. Additionally, a retrospective cohort study was also conducted to compare the operation time, intraoperative blood loss, and postoperative complications between the cystic plate approach and the conventional approach during fluoroscopic laparoscopic hepatectomy. RESULTS: A total of 38 patients who met the inclusion criteria underwent laparoscopic hepatectomy between January 2019 and November 2022. No significant disadvantages were found in terms of operation time and intraoperative blood loss during the surgeries. Furthermore, the postoperative indications, including liver function indexes on the first postoperative day, WBC, and the postoperative hospital stay, were also not affected, thus proving the safety of the cystic approach. Importantly, through the cystic plate approach, the target liver pedicle was fully freed, and then the segments to be resected were precisely marked by positive or negative staining, followed by hepatectomy under real-time fluoroscopic guidance. This approach is extremely advantageous in anatomical liver segment resections, especially in right posterior lobe or hemi-hepatectomy, without increasing intraoperative bleeding or postoperative complication rates. CONCLUSION: This technique allows for easy and safe freeing of the target liver pedicle using membrane structures, and also allows for precise anatomical hepatectomy in combination with real-time fluoroscopic laparoscopic navigation.

Mitigated N2O emissions from submerged-plant-covered aquatic ecosystems on the Changjiang River Delta.

Submerged plants affect nitrogen cycling in aquatic ecosystems. However, whether and how submerged plants change nitrous oxide (N2O) production mechanism and emissions flux remains controversial. Current research primarily focuses on the feedback from N2O release to variation of substrate level and microbial communities. It is deficient in connecting the relative contribution of individual N2O production processes (i.e., the N2O partition). Here, we attempted to offer a comprehensive understanding of the N2O mitigation mechanism in aquatic ecosystems on the Changjiang River Delta according to stable isotopic techniques, metagenome-assembly genome analysis, and statistical analysis. We found that the submerged plant reduced 45 % of N2O emissions by slowing down the dissolved inorganic nitrogen conversion velocity to N2O in sediment (Vf-[DIN]sed). It was attributed to changing the N2O partition and suppressing the potential capacity of net N2O production (i.e., nor/nosZ). The dominated production processes showed a shift with increasing excess N2O. Meanwhile, distinct shift thresholds of planted and unplanted habitats reflected different mechanisms of stimulated N2O production. The hotspot zone of N2O production corresponded to high nor/nosZ and unsaturated oxygen (O2) in unplanted habitat. In contrast, planted habitat hotspot has lower nor/nosZ and supersaturated O2. O2 from photosynthesis critically impacted the activities of N2O producers and consumers. In summary, the presence of submerged plants is beneficial to mitigate N2O emissions from aquatic ecosystems.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Organic-Inorganic Hybrid Glasses of Atomically Precise Nanoclusters.

Organic-inorganic atomically precise nanoclusters provide indispensable building blocks for establishing structure-property links in hybrid condensed matter. However, robust glasses of ligand-protected nanocluster solids have yet to be demonstrated. Herein, we show [Cu4I4(PR3)4] cubane nanoclusters coordinated by phosphine ligands (PR3) form robust melt-quenched glasses in air with reversible crystal-liquid-glass transitions. Protective phosphine ligands critically influence the glass formation mechanism, modulating the glasses' physical properties. A hybrid glass utilizing ethyldiphenylphosphine-based nanoclusters, [Cu4I4(PPh2Et)4], exhibits superb optical properties, including >90% transmission in both visible and near-infrared wavelengths, negligible self-absorption, near-unity quantum yield, and high light yield. Experimental and theoretical analyses demonstrate the structural integrity of the [Cu4I4(PPh2Et)4] nanocluster, i.e., iodine-bridged tetranuclear cubane, has been fully preserved in the glass state. The strong internanocluster CH-π interactions found in the [Cu4I4(PPh2Et)4] glass and subsequently reduced structural vibration account for its enhanced luminescence properties. Moreover, this highly transparent glass enables performant X-ray imaging and low-loss waveguiding in fibers drawn above the glass transition. The discovery of "nanocluster glass" opens avenues for unraveling glass formation mechanisms and designing novel luminescent glasses of well-defined building blocks for advanced photonics.

Neuroligin1 in excitatory synapses contributes to long-term cognitive impairments after repeated neonatal sevoflurane exposures.

BACKGROUND: Repeated sevoflurane exposures in neonatal rats may lead to neuronal apoptosis affecting long-term cognitive function, the mechanism is unknown. Neuroligin1 (NL1) is essential for normal excitatory transmission and long-term synaptic plasticity in the hippocampus of intact animals. Herein, we explore the role of NL1 in hippocampal excitatory synapses on long-term cognitive impairments induced by repeated sevoflurane exposures in neonatal rats. METHODS: From postnatal day six (P6) to P8, neonatal rats were exposed to 30% oxygen or 3% sevoflurane +30% oxygen for 2 h daily. Rats from each litter were randomly assigned to five groups: control group (Con), native control adeno-associated virus (NC-AAV) group (Con + NC-AAV), sevoflurane group (Sev), sevoflurane + recombinant RNAi adeno-associated virus targeting NL1 downregulation (NL1--AAV) group (Sev + NL1--AAV) and control + recombinant RNAi adeno-associated virus targeting NL1 upregulation (NL1+-AAV) group (Con + NL1+-AAV). Animals were injected with NC-AAV or NL1-AAV into the bilateral hippocampal CA1 area and caged on P21. From P35 to P40, behavioral tests including open field (OF), novel object recognition (NOR), and fear conditioning (FC) tests were performed to assess cognitive function in adolescent rats. In another experiment, rat brains were harvested for immunofluorescence staining, western blotting, co-immunoprecipitation, and real-time polymerase chain reaction (PCR). RESULTS: We found that the mRNA and protein levels of NL1 were substantially higher in the Sev group than in the Con group. Immunofluorescence showed that NL1 and PSD95 were highly colocalized in hippocampal CA1 area and vesicular GABA transporter (vGAT) around neurons decreased after repeated sevoflurane exposures. Co-immunoprecipitation showed that the amount of PSD95 with NL1 antibody was significantly increased in the Sev group compared to the Con group. These rats had a poorer performance in the NOR and FC tests than control rats when they were adolescents. These results were reversed by NL1--AAV injection into the CA1 area. NL1+-AAV group was similar to the Sev group. CONCLUSION: We have demonstrated that repeated neonatal sevoflurane exposures decreased inhibitory synaptic inputs (labelled by vGAT) around neurons, which may influence the upregulation of NL1 in hippocampal excitatory synapses and enhanced NL1/PSD95 interaction, ultimately leading to long-term cognitive impairments in adolescent rats. Injecting NL1--AAV reversed this damage. These results suggested that NL1 in excitatory synapses contributes to long-term cognitive impairments after repeated neonatal sevoflurane exposures.

Iron-containing nanominerals for sustainable phosphate management: A comprehensive review and future perspectives.

Adsorption, which is a quick and effective method for phosphate management, can effectively address the crisis of phosphorus mineral resources and control eutrophication. Phosphate management systems typically use iron-containing nanominerals (ICNs) with large surface areas and high activity, as well as modified ICNs (mICNs). This paper comprehensively reviews phosphate management by ICNs and mICNs in different water environments. mICNs have a higher affinity for phosphates than ICNs. Phosphate adsorption on ICNs and mICNs occurs through mechanisms such as surface complexation, surface precipitation, electrostatic ligand exchange, and electrostatic attraction. Ionic strength influences phosphate adsorption by changing the surface potential and isoelectric point of ICNs and mICNs. Anions exhibit inhibitory effects on ICNs and mICNs in phosphate adsorption, while cations display a promoting effect. More importantly, high concentrations and molecular weights of natural organic matter can inhibit phosphate adsorption by ICNs and mICNs. Sodium hydroxide has high regeneration capability for ICNs and mICNs. Compared to ICNs with high crystallinity, those with low crystallinity are less likely to desorb. ICNs and mICNs can effectively manage municipal wastewater, eutrophic seawater, and eutrophic lakes. Adsorption of ICNs and mICNs saturated with phosphate can be used as fertilizers in agricultural production. Notably, mICNs and ICNs have positive and negative effects on microorganisms and aquatic organisms in soil. Finally, this study introduces the following: trends and prospects of machine learning-guided mICN design, novel methods for modified ICNs, mICN regeneration, development of mICNs with high adsorption capacity and selectivity for phosphate, investigation of competing ions in different water environments by mICNs, and trends and prospects of in-depth research on the adsorption mechanism of phosphate by weakly crystalline ferrihydrite. This comprehensive review can provide novel insights into the research on high-performance mICNs for phosphate management in the future.

Ultrabroad bandwidth of quasi-parametric amplification beyond the phase-matching limit.

Quasi-parametric amplification (QPA), a variant of optical parametric amplification, can release the phase-matching requirement owing to the introduction of idler dissipation, and thus may support ultrabroad bandwidth. Here we establish the gain-dispersion equation for QPA, which reveals the interplay of signal gain, idler dissipation and phase mismatch. The idler dissipation dramatically enhances the gain bandwidth, which breaks the limit set by phase matching. We theoretically demonstrate that QPA with strong dissipation allows high-efficiency few-cycle pulse amplification in those nonlinear crystals without a magic phase-matching solution.

Effect of Weight Loss on the Apnea Hypopnea Index is Related to Waist Circumference in Chinese Adults with Overweight and Obesity.

Purpose: The present study aimed to evaluate the efficiency of traditional anthropometric and body composition parameters in predicting apnea hypopnea index (AHI) change after weight loss. Patients and Methods: Chinese adults with overweight and obesity were included into this study containing two parts. A cross-sectional study was conducted in 137 individuals using the baseline data from two weight loss intervention trials. The second part was the weight-loss intervention study conducted in 60 overweight and obese patients with obstructive sleep apnea (OSA). All participants underwent physical examination, bioelectrical impedance analysis and overnight polysomnography. Multivariate linear regression models were used to identify the most accurate parameters to predict AHI and the mediation analysis to evaluate the mediators between weight loss and AHI reduction. Results: Waist circumference (WC), body mass index and fat mass were positively associated with AHI after adjusting multiple collinearities in the cross-sectional study. After weight-loss intervention, body weight decreased from 94.6 ± 15.3 to 88.0 ± 13.9 kg, and AHI decreased from 41.9 (13.0,66.9) to 20.7 (8.7,51.2) events/h. Among these parameters, only percentage changes in WC and AHI across the intervention were positively intercorrelated after controlling for covariates (adjusted r = 0.271, P = 0.041). The mediation analysis supported WC as a mediator between weight loss and AHI reduction (standardized indirect effect [95% CI] = 4.272[0.936,7.999]). Conclusion: Both general and abdominal obesity are of high prognostic value for OSA. WC as an easily accessible parameter mediates the effects of weight loss in decreasing OSA severity.

Developing a novel lithium-ion battery anode material via thiol functionalization of diatom frustules plus Ag modification.

The biosilicification of diatoms allows for the customization of the synthesis of functionalized diatom frustules. The S active sites (-SH) on diatom frustules were created by adding the organic silicon sources tetramethoxysilane (TMOS) and (3-mercaptopropyl)trimethoxysilane (MPTMS). The mechanisms of adsorption-reduction and the indirect effects of S active sites on electrochemical performance were declared. The DBS@C-Ag-3 anode material sourced from the cultivation condition with a silicon source of TMOS:MPTMS = 3:1 shows the best comprehensive performance and delivers a discharge capacity of ∼660 mAh·g-1 after 1000 cycles at 1 A·g-1. The electrochemical performance of DBS@C-Ag anode materials is also found to be dominated by structure at high temperatures and conductivity at low temperatures. Such a diatom frustule structure with sulfhydryl functionalization is promising for anode materials, and it suggests a biological strategy for creating other electrode materials by modifying them with metals to improve electrochemical performances.

A densely connected causal convolutional network separating past and future data for filling missing PM2.5 time series data.

Air pollution poses a significant threat to human health and the environment globally. Precise analysis and prediction of pollutant concentrations are essential for monitoring and managing air quality. However, reliable analysis and prediction require comprehensive and high-quality data, which is often compromised due to missing data during collection. Unfortunately, conventional methods for addressing missing data fall short of providing adequate solutions. The missing data for air quality indicators are commonly systematic, with all data points missing for extended periods. This makes it difficult to establish correlations and populate the missing data accurately. To address this problem, we propose a Densely Connected Causal Convolutional Network Separating Past and Future Data (DCCN-SPF), a deep learning-based model that fills in continuous missing PM2.5 concentration data in the original dataset. It extracts features from past and future data separately using densely connected causal convolutional networks and incorporates linear interpolation and deep learning structures to improve prediction accuracy. Using air quality monitoring data from the China Environmental Monitoring Station between 2017 and 2021 in Beijing, we compare our proposed model with baseline models and find that our model outperforms others in predicting PM2.5 concentrations. The evaluation metrics MAE and RMSE are used, revealing significant reductions of 8.7-21.6 % for MAE and 7.1-23.5 % for RMSE in favor of our proposed DCCN-SPF model.

High-Efficiency Circularly Polarized Light-Emitting Diodes Based on Chiral Metal Nanoclusters.

Circularly polarized light-emitting diodes (CP-LEDs) are critical for next-generation optical technologies, ranging from holography to quantum information processing. Currently deployed chiral luminescent materials, with their intricate synthesis and processing and limited efficiency, are the main bottleneck for CP-LEDs. Chiral metal nanoclusters (MNCs) are potential CP-LED materials, given their ease of synthesis and processability as well as diverse structures and excited states. However, their films are usually plagued by inferior electronic quality and aggregation-caused photoluminescence quenching, necessitating their incorporation into host materials; without such a scheme, MNC-based LEDs exhibit external quantum efficiencies (EQEs) < 10%. Herein, we achieve an efficiency leap for both CP-LEDs and cluster-based LEDs by using novel chiral MNCs with aggregation-induced emission enhancement. CP-LEDs using enantiopure MNC films attain EQEs of up to 23.5%. Furthermore, by incorporating host materials, the devices yield record EQEs of up to 36.5% for both CP-LEDs and cluster-based LEDs, along with electroluminescence dissymmetry factors (|gEL|) of around 1.0 × 10-3. These findings open a new avenue for advancing chiral light sources for next-generation optoelectronics.

The effects of increasing emission Fee rates on Chinese firms' emissions: Evidence from a quasi-experiment.

Over the last four decades, the Chinese government has predominantly employed emission fees as a regulatory strategy to mitigate pollution from firms. However, the effectiveness of escalating emission fee rates on the emission levels of Chinese firms has not been examined. This study utilizes data from more than 80,000 Chinese firms spanning 2004-2013, employing difference-in-differences models to assess the effects of rising emission fee rates on firm emissions. The findings indicate the following: (1) Increased emission fee rates substantially reduce sulfur dioxide and chemical oxygen demand emissions among Chinese firms; (2) These heightened fees encourage firms to implement both end-of-pipe treatment and source control for sulfur dioxide and end-of-pipe treatment for chemical oxygen demand; (3) The emission reduction effects vary according to firm ownership and size. This research offers empirical evidence on the efficacy of emission fee systems and provides valuable insights for developing market incentive-based environmental regulations in the future.

The ecological role of microbiome at community-, taxonomic - and genome-levels in black-odorous waters.

Black-odorous waters (BOWs) are heavily polluted waters where microbial information remains elusive mechanistically. Based on gene amplicon and metagenomics sequencing, a comprehensive study was conducted to investigate the microbial communities in urban and rural BOWs. The results revealed that microbial communities' assembly in urban and rural BOWs was predominantly governed by stochastic factors at the community level. At the taxonomic level, there were 62 core species (58.48%) in water and 207 core species (44.56%) in sediment across urban and rural areas. Notably, significant differences were observed in the functional genetic composition of BOWs between urban and rural areas. Specifically, rural areas exhibited an enhanced abundance of genes involved in nitrogen fixation, Fe2+ transport, and sulfate reduction. Conversely, urban areas showed higher abundances of some genes associated with carbon fixation, nitrification and denitrification. A sulfur-centered ecological model of microbial communities was constructed by integrating data from the three levels of analysis, and 14 near-complete draft genomes were generated, representing a substantial portion of the microbial community (35.04% in rural BOWs and 29.97% in urban BOWs). This research provides significant insights into the sustainable management and preservation of aquatic ecosystems affected by BOWs.

Synthesis, structure, theoretical calculation and antibacterial property of two novel Zn(II)/Ni(II) compounds based on 3, 5-dichlorosalicylaldehyde thiocarbamide ligand.

Two new compounds namely [Zn(L1)phen]31 and Ni(L1)phen(MeOH) 2 (L1 = 3, 5-dichlorosalicylaldehyde thiosemicarbazone) were synthesized by the slow evaporation method at room temperature. The structure of ligand L1 was determined using 1H NMR and 13C NMR spectra. X-ray single crystal diffraction analysis revealed that compounds 1-2 can form 3D supramolecular network structures through π···π stacking and hydrogen bonding interactions. The DFT calculation shows that the coordination of ligand and metal is in good agreement with the experimental results. Hirshfeld surface analysis revealed that H…H and Cl…H interactions were the predominant interactions in compounds 1-2. Energy framework analysis indicated that dispersion energy played a dominant role in the energy composition of compounds 1-2. The inhibitory effects of compounds 1-2 against Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA) were tested using the paper disk diffusion method (1: E. coli: 18 mm, MRSA: 17 mm, 2: E. coli: 15 mm, MRSA: 16 mm). Ion releasing experiments were conducted to assess the ion release capacity of compounds 1-2 (Zn2+, 4 days, 38.33 µg/mL; Ni2+, 4 days, 29.12 µg/mL). Molecular docking demonstrated the interaction modes of compounds 1-2 with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and dihydrofolate reductase (DHFR) in bacteria, involving hydrophobic, stacking, hydrogen bonding and halogen bonding interactions. The generation of reactive oxygen species (ROS) in bacteria under the presence of compounds 1-2 were evaluated using a fluorescent dye known as dichlorodihydrofluorescein diacetate (DCFH-DA). Potential antibacterial mechanisms of compounds 1-2 were proposed.

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism.

Fatty acid ß-oxidation (FAO) is a central catabolic pathway with broad implications for organismal health. However, various fatty acids are largely incompatible with standard FAO machinery until they are modified by other enzymes. Included among these are the 4-hydroxy acids (4-HAs)-fatty acids hydroxylated at the 4 (γ) position-which can be provided from dietary intake, lipid peroxidation, and certain drugs of abuse. Here, we reveal that two atypical and poorly characterized acyl-CoA dehydrogenases (ACADs), ACAD10 and ACAD11, drive 4-HA catabolism in mice. Unlike other ACADs, ACAD10 and ACAD11 feature kinase domains N-terminal to their ACAD domains that phosphorylate the 4-OH position as a requisite step in the conversion of 4-hydroxyacyl-CoAs into 2-enoyl-CoAs-conventional FAO intermediates. Our ACAD11 cryo-EM structure and molecular modeling reveal a unique binding pocket capable of accommodating this phosphorylated intermediate. We further show that ACAD10 is mitochondrial and necessary for catabolizing shorter-chain 4-HAs, whereas ACAD11 is peroxisomal and enables longer-chain 4-HA catabolism. Mice lacking ACAD11 accumulate 4-HAs in their plasma while comparable 3- and 5-hydroxy acids remain unchanged. Collectively, this work defines ACAD10 and ACAD11 as the primary gatekeepers of mammalian 4-HA catabolism and sets the stage for broader investigations into the ramifications of aberrant 4-HA metabolism in human health and disease.

Clay-supported bio-based Lewis acid ionic liquid as a potent catalyst for the dehydration of fructose to 5-hydroxymthylfurfural.

Caffeine and halloysite nanoclay mineral that are bio-based compounds were utilized to synthesize a novel Lewis acid heterogeneous catalyst. To this aim, halloysite was functionalized with 2,4,6-trichloro-1,3,5-triazine and reacted with caffeine, which was then converted to ionic liquid via a reaction with ZnCl2. The catalyst was applied for promoting the dehydration of fructose to 5-hydroxymethylfurfural. To investigate the effects of the reaction variables, response surface methodology was used. The product was achieved in 98.5% in 100 min using a catalyst loading of 30 wt% at 100 °C. Moreover, the catalyst was recyclable up to six runs with slight zinc leaching. Comparison of the catalytic activity of the catalyst with that of halloysite and a control catalyst with one caffeine-based Lewis acid ionic liquid confirmed the superior activity of the former and the important role of 2,4,6-trichloro-1,3,5-triazine for increasing the number of the grafted caffeine and thus the acidic sites of the catalyst. A plausible reaction mechanism was proposed, and the activity of the catalyst for other carbohydrates was also studied. According to the results, this catalyst catalyzed the reaction of other substrates to furnish 5-hydroxymethylfurfural in low to moderate yields. According to the kinetic studies, the activation energy was estimated to be 22.85 kJ/mol.

Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain. METHODS: This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events. RESULTS: In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method. CONCLUSIONS: Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS. TRIAL REGISTRATION: The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).