Forecasting vaping health risks through neural network model prediction of flavour pyrolysis reactions.

Vaping involves the heating of chemical solutions (e-liquids) to high temperatures prior to lung inhalation. A risk exists that these chemicals undergo thermal decomposition to new chemical entities, the composition and health implications of which are largely unknown. To address this concern, a graph-convolutional neural network (NN) model was used to predict pyrolysis reactivity of 180 e-liquid chemical flavours. The output of this supervised machine learning approach was a dataset of probability ranked pyrolysis transformations and their associated 7307 products. To refine this dataset, the molecular weight of each NN predicted product was automatically correlated with experimental mass spectrometry (MS) fragmentation data for each flavour chemical. This blending of deep learning methods with experimental MS data identified 1169 molecular weight matches that prioritized these compounds for further analysis. The average number of discrete matches per flavour between NN predictions and MS fragmentation was 6.4 with 92.8% of flavours having at least one match. Globally harmonized system classifications for NN/MS matches were extracted from PubChem, revealing that 127 acute toxic, 153 health hazard and 225 irritant classifications were predicted. This approach may reveal the longer-term health risks of vaping in advance of clinical diseases emerging in the general population.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

How incubation temperature affects hatchling performance in reptiles: an integrative insight based on plasticity in metabolic enzyme.

Evaluating the effects of temperature variations on animals plays an important role in understanding the threat of climate warming. The effects of developmental temperature on offspring performance are critical in evaluating the effects of warming temperatures on the fitness of oviparous species, but the physiological and biochemical basis of this developmental plasticity is largely unknown. In this study, we incubated eggs of the turtle Pelodiscus sinensis at low (24 °C), medium (28 °C), and high (32 °C) temperatures, and evaluated the effects of developmental temperature on offspring fitness, and metabolic enzymes in the neck and limb muscles of hatchlings. The hatchlings from eggs incubated at the medium temperature showed better fitness-related performance (righting response and swimming capacity) and higher activities of metabolic enzymes (hexokinase, HK; lactate dehydrogenase, LDH) than hatchlings from the eggs incubated at high or low temperatures. In addition, the swimming speed and righting response were significantly correlated with the HK activities in limb (swimming speed) and neck (righting response) muscles, suggesting that the developmental plasticity of energy metabolic pathway might play a role in determining the way incubation temperature affects offspring phenotypes. Integrating the fitness-related performance and the activities of metabolic enzymes, we predict that the P. sinensis from high latitude would not face the detrimental effects of climate warming until the average nest temperatures reach 32 °C.

Cucurbit[8]uril-based supramolecular theranostics.

Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host-guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed.

Exploration on pharmacological mechanisms of YZP against neuropathic pain via inhibiting spinal inflammation and the rationality of its compatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuanhu Zhitong Prescription (YZP) is a well-known traditional Chinese medicine (TCM) formula for neuropathic pain (NP) therapy with a satisfying clinical efficacy. However, the underlying pharmacological mechanism and its compatibility principle remain unclear. AIM OF THE STUDY: This study aims to investigate the analgesic and compatibility mechanisms of YZP on neuropathic pain (NP) at the gene and biological process levels. MATERIALS AND METHODS: The chronic constriction injury (CCI) rats were intragastrically administrated with extracts of YZP, YH and BZ separately, and then mechanical hypersensitivity were measured to evaluate the analgesic effects between YH and BZ before and after compatibility. Then, RNA-seq and bioinformatics analyses were performed to elucidate the potential mechanisms underlying YZP's analgesia and compatibility. Finally, the expression levels and significant differences of key genes were analyzed. RESULTS: Behaviorally, both YZP and YH effectively alleviated mechanical allodynia in CCI rats, with YZP being superior to YH. In contrast, we did not observe an analgesic effect of BZ. Genetically, YZP, YH, and BZ reversed the expression levels of 52, 34, and 42 aberrant genes in the spinal cord of CCI rats, respectively. Mechanically, YZP was revealed to alleviate NP mainly by modulating the inflammatory response and neuropeptide signaling pathway, which are the dominant effective processes of YH. Interestingly, the effective targets of YZP were especially enriched in leukocyte activation and cytokine-mediated signaling pathways. Moreover, BZ was found to exert an adjunctive effect in enhancing the analgesic effect of YH by promoting skeletal muscle tissue regeneration and modulating calcium ion transport. CONCLUSIONS: YH, as the monarch drug, plays a dominant role in the analgesic effect of YZP that effectively relieves NP by inhibiting the spinal inflammation and neuropeptide signaling pathway. BZ, as the minister drug, not only synergistically enhances analgesic processes of YH but also helps to alleviate the accompanying symptoms of NP. Consequently, YZP exerted a more potent analgesic effect than YH and BZ alone. In conclusion, our findings offer new insights into understanding the pharmacological mechanism and compatibility principle of YZP, which may support its clinical application in NP therapy.

Jiegeng decoction ameliorated acute pharyngitis through suppressing NF-κB and MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly recorded in "Treatise on Febrile Diseases". JGD has been extensively utilized to treat sore throat and lung diseases for thousands of years in China. However, the pharmacological effect and mechanism of JGD on acute pharyngitis (AP) remain unclear. AIM OF THE STUDY: Our research aimed to reveal the pharmacological effect of JGD on AP and its potential mechanisms. MATERIALS AND METHODS: The chemical components of JGD were analyzed based on the UPLC-MS analysis. The anti-inflammatory effect of JGD was evaluated by NO production using the Griess assay in RAW.246.7 cells. The mRNA expression of iNOS, IL-1ß, IL-10, TNF-α, IL-6 and MCP-1 was determined by qRT-PCR in vitro. A 15% ammonia-induced AP model was established. The histopathology, the inflammatory cytokines IL-6 and MCP-1 in serum and the apoptosis-related genes caspease-8 and caspease-3 were determined by H&E staining, ELISA and qRT-PCR, respectively. The expression levels of p-p65, p65, p-JNK, JNK, p-p38, p38, p-ERK1/2, ERK1/2, and COX2 were measured through western blotting. RESULTS: Nine compounds, including liquiritin, liquiritin apiosde, liquiritigenin, platycodin D, platycoside A, licorice saponin J2, licorice saponin G2, glycyrrhizic acid, and licochalcone A, were identified. JGD significantly inhibited NO production and regulated the mRNA expression levels of cytokines in LPS-stimulated RAW264.7 cells. The results of in vivo experiments confirmed that JGD ameliorated AP through improving the pathological state of pharyngeal tissue, decreasing the serum levels of IL-6 and MCP-1 and preventing the tissue mRNA expression of caspease-8 and caspease-3. Furthermore, JGD also inhibited the NF-κB and MAPK pathways in the AP model. CONCLUSIONS: This study suggested that JGD could alleviate AP through its anti-inflammation via NF-κB and MAPK pathways, which supported the traditional application of JGD for the treatment of throat diseases.

SLMFNet: Enhancing land cover classification of remote sensing images through selective attentions and multi-level feature fusion.

Land cover classification (LCC) is of paramount importance for assessing environmental changes in remote sensing images (RSIs) as it involves assigning categorical labels to ground objects. The growing availability of multi-source RSIs presents an opportunity for intelligent LCC through semantic segmentation, offering a comprehensive understanding of ground objects. Nonetheless, the heterogeneous appearances of terrains and objects contribute to significant intra-class variance and inter-class similarity at various scales, adding complexity to this task. In response, we introduce SLMFNet, an innovative encoder-decoder segmentation network that adeptly addresses this challenge. To mitigate the sparse and imbalanced distribution of RSIs, we incorporate selective attention modules (SAMs) aimed at enhancing the distinguishability of learned representations by integrating contextual affinities within spatial and channel domains through a compact number of matrix operations. Precisely, the selective position attention module (SPAM) employs spatial pyramid pooling (SPP) to resample feature anchors and compute contextual affinities. In tandem, the selective channel attention module (SCAM) concentrates on capturing channel-wise affinity. Initially, feature maps are aggregated into fewer channels, followed by the generation of pairwise channel attention maps between the aggregated channels and all channels. To harness fine-grained details across multiple scales, we introduce a multi-level feature fusion decoder with data-dependent upsampling (MLFD) to meticulously recover and merge feature maps at diverse scales using a trainable projection matrix. Empirical results on the ISPRS Potsdam and DeepGlobe datasets underscore the superior performance of SLMFNet compared to various state-of-the-art methods. Ablation studies affirm the efficacy and precision of SAMs in the proposed model.

Microfluidic Immunosensor Platform for Sensitive Detection of Human Epidermal Growth Factor Receptor-2 Based on Enhanced Cathode Electrochemiluminescence of Bimetallic Nanoclusters.

In this work, a microfluidic immunosensor chip was developed by incorporating microfluidic technology with electrochemiluminescence (ECL) for sensitive detection of human epidermal growth factor receptor-2 (HER2). The immunosensor chip can achieve robust reproducibility in mass production by integrating multiple detection units in a series. Notably, nanoscale materials can be better adapted to microfluidic systems, greatly enhancing the accuracy of the immunosensor chip. Ag@Au NCs closed by glutathione (GSH) were introduced in the ECL microfluidic immunosensor system with excellent and stable ECL performance. The synthesized CeO2-Au was applied as a coreaction promoter in the ECL signal amplification system, which made the result of HER2 detection more reliable. In addition, the designed microfluidic immunosensor chip integrated the biosensing system into a microchip, realizing rapid and accurate detection of HER2 by its high throughput and low usage. The developed short peptide ligand NARKFKG (NRK) achieved an effective connection between the antibody and nanocarrier for improving the detection efficiency of the sensor. The immunosensor chip had better storage stability and sensitivity than traditional detection methods, with a wide detection range from 10 fg·mL-1 to 100 ng·mL-1 and a low detection limit (LOD) of 3.29 fg·mL-1. In general, a microfluidic immunosensor platform was successfully constructed, providing a new idea for breast cancer (BC) clinical detection.

Research advances in the molecular classification of gastric cancer.

Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis.

Preparation and characterization on the eco-friendly corn starch based adhesive of with salient water resistance, mildew resistance.

Starch adhesive is a commonly used bonding glue that is sustainable, formaldehyde-free and biodegradable. However, there are obviously some problems related to its high viscosity, poor water and mildew resistance. Hence, exploring a starch-based adhesive with good properties that satisfies the requirements of wood processing presents the context of the current research. Thus, corn starch was used as raw material to form oxidized starch (OCS) via oxidation using sodium periodate, it was reacted with a synthesis polyurea compound that prepared from hexanediamine-urea (HU) obtained by deamination to yield a oxidized starch-hexanediamine-urea adhesive (denoted hereafter as OCSHU). The oxidation process was optimized in terms of oxidant concentration, reaction time and temperature. Furthermore, the impact of HU addition on the mechanical properties of the adhesive was explored. Results indicate adhesive exhibited outstanding shear strength, when 13 % of NaIO4 was used as an oxidant to treat starch at 55 °C for 24 h, and involved in a subsequent reaction with 40 % of HU. The dry shear strength, 24 h cold water strength, 3 h hot water strength and 3 h boiling water strength are 1.84, 1.50, 1.32, and 1.31 MPa. Meantime, OCSHU adhesive solution revealed good storage stability whereas cured resin exhibited mildew resistance. The developed adhesive is a simple and green biomass wood adhesive.

Spatially confined CuFe2O4 nanosphere in N/O-codoped porous carbon mimetics for triple-mode sensing of antibiotics and visual detection of neurotransmitters in biofluids.

BACKGROUND: Carbon-based nanozymes have recently received enormous concern, however, there is still a huge challenge for inexpensive and large-scale synthesis of magnetic carbon-based "Two-in-One" mimics with both peroxidase (POD)-like and laccase-like activities, especially their potential applications in multi-mode sensing of antibiotics and neurotransmitters in biofluids. Although some progresses have been made in this field, the feasibility of biomass-derived carbon materials with both POD-like and laccase-like activities by polyatomic doping strategy is still unclear. In addition, multi-mode sensing platform can provide a more reliable result because of the self-validation, self-correction and mutual agreement. Nevertheless, the use of magnetic carbon-based nanozyme sensors for the multi-mode detection of antibiotics and neurotransmitters have not been investigated. RESULTS: We herein report a shrimp shell-derived N, O-codoped porous carbon confined magnetic CuFe2O4 nanosphere with outstanding laccase-like and POD-like activities for triple-mode sensing of antibiotic d-penicillamine (D-PA) and chloramphenicol (CPL), as well as colorimetric detection of neurotransmitters in biofluids. The magnetic CuFe2O4/N, O-codoped porous carbon (MCNPC) armored mimetics was successfully fabricated using a combined in-situ coordination and high-temperature crystallization method. The synthesized MCNPC composite with superior POD-like activity can be used for colorimetric/temperature/smartphone-based triple-mode detection of D-PA and CPL in goat serum. Importantly, the MCNPC nanozyme can also be used for colorimetric analysis of dopamine and epinephrine in human urine. SIGNIFICANCE: This work not only offered a novel strategy to large-scale, cheap synthesize magnetic carbon-based "Two-in-One" armored mimetics, but also established the highly sensitive and selective platforms for triple-mode monitoring D-PA and CPL, as well as colorimetric analysis of neurotransmitters in biofluids without any tanglesome sample pretreatment.

Genomic and Transcriptomic Significance of Multiple Primary Lung Cancers Detected by Next-Generation Sequencing in Clinical Settings.

Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management. However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient. Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. 214 non-small cell lung cancer patients with multiple tumors were enrolled, and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared. 4 patients were regrouped with NGS 10 results. Master panel resolved the classifications of 6 undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells etc., P < 0.05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells etc., P < 0.001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0.0001). Additionally, NECTIN4 (P < 0.05) and LILRB4 were linked to improved disease-free survival in the MPLC. In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.

Enhanced carboxylation of furoic salt with CO2 by ZnCl2 coordination for efficient production of 2,5-furandicarboxylic acid.

C-H carboxylation of furoic acid (FA) with CO2 is an atom-efficient strategy to produce 2,5-furandicarboxylic acid (2,5-FDCA) from lignocellulose. The existing carbonate-promoted CO2 carboxylation processes rely on the use of large amounts of expensive Cs2CO3 as a deprotonating reagent and molten salt. Substitution of Cs with other cheap and abundant alkali ions (such as K and Na) can reduce the use of Cs, but it faces the problem of a low yield of 2,5-FDCA. This study found that the addition of catalytic amounts of ZnCl2 as a Lewis acid can increase the yield of 2,5-FDCA in the CO2 carboxylation reaction of Na/K-FA in a molten salt reaction system. 1H NMR analysis and DFT calculations confirmed that ZnCl2 coordinates with the furan ring through electron transfer from the conjugated furan ring to Zn2+, thereby activating the H at the C5 position of Na/K-FA. This coordination lengthened the C5-H bond and lowered its heterolytic dissociation energy, making it more susceptible to being deprotonated by CO32- and subsequently carboxylated by CO2. The developed Lewis acid coordination strategy provides a new idea for the efficient construction of C-C bonds between CO2 and aromatics through carbonate-promoted C-H carboxylation.

Diagnostic Value of Single LH and LH/FSH Ratio at 60-minute after GnRHa Stimulation Test for Central Precocious Puberty.

OBJECTIVES: To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. METHODS: Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors' hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann-Whitney U test, spearman's correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. RESULTS: LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman's correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. CONCLUSIONS: The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment.

SCOPE: This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. METHODS AND RESULTS: Mature milk is collected from the mothers of term and preterm infants. Using high-throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let-7 and miR-148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR-3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR-3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). CONCLUSION: This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.

F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

Phenylbutyric acid inhibits hypoxia-induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF-4/CHOP pathway.

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia. To verify the underlying mechanisms of 4-PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4-PBA restored hypoxia-induced trophoblast viability, inhibited HIF-1α protein expression, inflammation, and PERK/ATF-4/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4-PBA decreased hypoxia-induced apoptosis in trophoblasts. The results of the JC-1 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4-PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin-1, LC3II, and decreased p62 were seen in hypoxia-stimulated cells. These changes were reversed by 4-PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4-PBA on the viability, apoptosis, and autophagosome number of hypoxia-induced trophoblasts. In summary, 4-PBA reduces autophagy and apoptosis via the PERK/ATF-4/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4-PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.

Correction: Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice.

Correction for 'Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice' by Yanru Li et al., Food Funct., 2024, 15, 2295-2313, https://doi.org/10.1039/D3FO05076A.

Self-Assembly-Induced Enhancement of Cathodic Electrochemiluminescence of Copper Nanoclusters for a Split-Type Matrix Metalloproteinase 14 Sensing Platform.

The unique optoelectronic and tunable luminescent characteristics of copper nanoclusters (Cu NCs) make them extremely promising as luminophores. However, the limited luminescence intensity and stability of Cu NCs have restricted their application in the field of electrochemiluminescence (ECL). Herein, a self-assembly-induced enhancement strategy was successfully employed to enhance the cathodic ECL performance of flexible ligand-stabilized Cu NCs. Specifically, Cu NCs form ordered sheetlike structures through intermolecular force. The restriction of ligand torsion in this self-assembled structure leads to a significant improvement in the ECL properties of the Cu NCs. Experimental results demonstrate that the assembled nanoscale Cu NC sheets exhibit an approximately three-fold increase in cathodic ECL emission compared to the dispersed state of Cu NCs. Furthermore, assembled nanoscale Cu NCs sheets were utilized as signal probes in conjunction with a specific short peptide derived from the catalytic structural domain of matrix metalloproteinase 14 (MMP 14) as the identification probe, thereby establishing a split-type ECL sensing platform for the quantification of NMP 14. The investigation has revealed the exceptional performance of assembled nanoscale Cu NCs sheets in ECL analysis, thus positioning them as novel and promising signal probes with significant potential in the field of sensing.

Screening for potential warning biomarkers in cows with ketosis based on host-microbiota co-metabolism analysis.

Introduction: The risk of ketosis is assessed by monitoring changes in plasma metabolites and cow behavior during the peripartum period. However, little is known about changes in the fecal bile acid and microbiota of cows before parturition. Therefore, this study clarified the bile acid profile and screened potential warning biomarkers in heifers 7 days before calving. Methods: Ninety healthy cows were tracked in the transition period, and plasma and feces were collected 7 days before calving, on calving day, and 7 days after calving. The cows were divided into ketosis and healthy groups based on the blood ß-hydroxybutyric acid levels from day 7 after calving. The levels of serum biochemical indices were measured at three time points using commercial kits. Ten cows in the ketosis group (KET-7) and 10 healthy cows (HEA-7) were randomly selected 7 days before calving for metabolome and 16S rRNA amplicon sequencing. Results: No significant differences in serum energy-related indices were observed 7 days before calving. The major bile acids in the feces of the KET-7 group were non-conjugated secondary bile acids (UnconSBA). Differential bile acids were primarily derived from UnconSBA. The potential ketosis warning metabolite in feces for 7 days before delivery was isodeoxycholic acid. The abundance of Rikenellaaceae-RC9-gut-group in the KET-7 group increased, whereas the abundance of Oscillospiraceae UCG-010 bacteria significantly decreased. Lactobacillus and Prevotella-9 in feces were potential warning biomarkers for ketosis in dairy cows 7 days before calving. The variation in differential bile acids in the plasma, consistent with the feces, was mainly derived from UnconSBA. Lithocholic acid in the plasma was a potential ketosis warning metabolite 7 days before delivery. Conclusion: Ketotic cows experienced bile acid metabolism disorders 7 days before calving, and the gut microbiota was closely related to bile acid metabolism disorders. Future studies should investigate the relationship between secondary bile acids and the development of ketosis.