Licochalcone A promotes renewal of intestinal mucosa through modulating uc.173.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal. AIM OF THE STUDY: This study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal. MATERIALS AND METHODS: IE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa. RESULTS: The expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration. CONCLUSION: Results in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity.

High-resolution neuraminidase inhibition profiling of Arnebia euchroma (Royle) I.M. Johnst. based on HR-MS and target isolation: An example study of anti-infectious constituents in traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicines (TCMs) are an important source to discover new anti-infectious drugs. Neuraminidases (NAs) not only play a key role on human health, but also are promising targets for anti-infectious drugs. Arnebia euchroma which is a widely used traditional Chinese medicine with the effect of cooling blood and detoxifying showed potential inhibitory activities on both bacterial NA and virus NA, suggesting that the material basis of A. euchroma deserves in-depth study. AIM OF THE STUDY: To investigate the anti-infectious constituents of A. euchroma based on NA inhibition. MATERIAL AND METHODS: A HPLC-DAD system incorporated an auto-sampler was used for micro-fractionation. A nanoliter liquid handler and a high sensitive multimode plate reader system were used for high throughput NA inhibition screening. Thus a high-resolution NA inhibition profiling platform was constructed. The structures of potential active components in A. euchroma obtained by the high-resolution bioassay profiling were identified by DAD and MS in parallel. Then, a target and rapid isolation of NAIs from A. euchroma was achieved under the guidance of the spectrum-effect relationship obtained above. Finally, the isolated compounds were elucidated by extensive spectroscopic methods and their bioactivities were validated by in vitro assay and molecular docking. RESULTS: 16 potential active ingredients in A. euchroma were isolated and identified, including a new mero-monoterpenoid. The in vitro bioassay results revealed that 12 out of the 16 isolated compounds showed potent inhibitory activities on bacterial NA (IC50s = 1-6 µM) and five of them exhibited potent anti-microbial activities on methicillin-resistant Staphylococccus aureus (MRSA) with MICs in the range of 0.5-4 µg/mL. Furthermore, some isolated compounds showed equal or even better inhibitory activities on oseltamivir resistant viral NA than oseltamivir sensitive NA. The mechanism study in silicon revealed that these natural compounds possessed absolutely different binding modes on the bacterial and viral NAs. CONCLUSIONS: Our study gave a clear spectrum-effect relationship of A. euchroma, providing a scientific evidence for future study of the multi-components synergistic effect of TCMs.

DNA hypomethylation-associated transcriptional rewiring enables resistance to heavy metal mercury (Hg) stress in rice.

Mercury (Hg) is an important hazardous pollutant that can cause phytotoxicity and harm human health through the food chain. Recently, rice (Oryza sativa L.) has been confirmed as a potential Hg bioaccumulator. Although the genetic and molecular mechanisms involved in heavy metal absorption and translocation in rice have been investigated for several heavy metals, Hg is largely neglected. Here, we analyzed one Hg-resistant line in rice (RHg) derived from a DNA methyltransferase-coding gene, OsMET1-2 heterozygous mutant. Compared with its isogenic wild-type (WT), RHg exhibited a significantly higher survival rate after Hg treatment, ameliorated oxidative damage, and lower Hg uptake and translocation. RNAseq-based comparative transcriptomic analysis identified 34 potential Hg resistance-related genes involved in phytohormone signaling, abiotic stress response, and zinc (Zn) transport. Importantly, the elevated expression of Hg resistance-related genes in RHg was highly correlated with DNA hypomethylation in their putative promoter regions. An ionomic analysis unraveled a negative correlation between Zn and Hg in roots. Moreover, Hg concentration was effectively decreased by exogenous application of Zn in Hg-stressed rice plants. Our findings indicate an epigenetic basis of Hg resistance and reveal an antagonistic relationship between Hg and Zn, providing new hints towards Hg detoxification in plants. ENVIRONMENTAL IMPLICATION: Mercury (Hg) as an important hazardous pollutant adversely impacts the environment and jeopardizes human health, due to its chronicity, transferability, persistence, bioaccumulation and toxicity. In this paper, we identified 34 potential genes that may significantly contribute to Hg resistance in rice. We find the expression of Hg resistance-related genes was highly correlated with DNA hypomethylation in their putative promoter regions. Our results also revealed an antagonistic relationship between Hg and Zinc (Zn), providing new hints towards Hg detoxification in plants. Together, findings of this study extend our current understanding of Hg tolerance in rice and are informative to breed seed non-accumulating rice cultivars.

Chinese herb pollen derived micromotors as active oral drug delivery system for gastric ulcer treatment.

Considerable efforts have been devoted to treating gastric ulcers. Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time. Herein, we develop novel Chinese herb pollen-derived micromotors as active oral drug delivery system for treating gastric ulcer. Such Chinese herb pollen-derived micromotors are simply produced by asymmetrically sputtering Mg layer onto one side of pollen grains. When exposed to gastric juice, the Mg layer can react with the hydrogen ions, resulting in intensive generation of hydrogen bubbles to propel the micromotors. Benefiting from the autonomous motion and unique spiny structure, our micromotors can move actively in the stomach and adhere to the surrounding tissues. Besides, their special architecture endows the micromotors with salient capacity of drug loading and releasing. Based on these features, we have demonstrated that our Chinese herb pollen-derived micromotors could effective deliver berberine hydrochloride and show desirable curative effect on the gastric ulcer model of mice. Therefore, these Chinese herb pollen-derived micromotors are anticipated to serve as promising oral drug delivery carriers for clinical applications.

Distribution and major driving elements of antibiotic resistance genes in the soil-vegetable system under microplastic stress.

Microplastics (MPs) and antibiotic resistance genes (ARGs) are both enriched in soil-vegetable systems as a consequence of the prolonged use of agricultural mulches. MPs can form unique bacterial communities and provide potential hosts for ARGs. Therefore, MPs stress may promote the spread of ARGs from soil to crops. Increasing ARGs pollution in soil-vegetable system. In our research, we investigated the distribution and major driving elements of antibiotic resistance genes in the soil-vegetable system under microplastic stress. The results showed that MPs treatment decreased the relative abundance of ARGs in non-rhizosphere soil. High concentrations of MPs promoted the enrichment of tetracycline antibiotic resistance genes in rhizosphere soil. MPs treatment promoted the enrichment of ARGs and mobile genetic elements (MGEs) in lettuce tissues, and the overall abundance of ARGs in root after 0.5 %, 1 %, and 2 % (w/w, dry weight) polyethylene (PE) administration was considerably higher compared to that in the untreated group (p < 0.05). At the same time, high PE concentrations promoted the spread of sulfa ARGs from root to leaf. MPs also impacted the bacterial communities in the soil-plant system, and the changes in ARGs as well as MGEs in each part of the soil-vegetable system were significantly correlated with the bacterial diversity index (p < 0.05). Correlation analysis and network analysis showed that bacterial communities and MGEs were the main drivers of ARGs variation in soil-lettuce systems.

Co-exposure to UV-aged microplastics and cadmium induces intestinal toxicity and metabolic responses in earthworms.

Aged microplastics (MPs) alter the interaction with heavy metals due to changes in surface properties. However, the combined toxicological effects of aged MPs on heavy metals in soil remain poorly understood. In this study, earthworms were employed as model animals to investigate the effects of aged MPs on the biotoxicity of cadmium (Cd) by simulating the exposure patterns of original and UV-aged MPs (polylactic acid (PLA) and polyethylene (PE)) with Cd. The results showed that UV-aging decreased the zeta potential and increased the specific surface area of the MPs, which enhanced the bioaccumulation of Cd and caused more severe oxidative stress to earthworms. Meanwhile, the earthworm intestines exhibited increased tissue damage, including chloragogenous tissue congestion lesions, and typhlosole damage. Furthermore, the combined exposure to UV-aged MPs and Cd enhanced the complexity of the microbial network in the earthworm gut and interfered with endocrine disruption, membrane structure, and energy metabolic pathways in earthworms. The results emphasized the need to consider the degradation of MPs in the environment. Hence, we recommend that future toxicological studies use aged MPs that are more representative of the actual environmental conditions, with the results being important for the risk assessment and management of MPs.

Methylene Blue-Stained Single-Stranded DNA Aptamers as a Highly Efficient Electronic Switch for Quasi-Reagentless Exosomes Detection: An Old Dog with New Tricks.

Improving the convenience, sensitivity, and cost-effectiveness of electrochemical biosensors is crucial for advancing their clinical diagnostic applications. Herein, we presented an elegant approach to construct electrochemical aptasensors for tumor-derived exosome detection by harnessing the alterable interaction between methylene blue (MB) and DNA aptamer. In detail, the anti-EpCAM aptamer, named SYL3C, was found to exhibit a strong affinity toward MB due to the specific interaction between MB and unbound guanine bases. Thereby, SYL3C could be stained with MB to arouse a strong electrochemical signal on a gold electrode (AuE). Upon binding to EpCAM-positive exosomes, SYL3C underwent a conformational transformation. The resulting conformation, or exosomes-SYL3C complex, not only reduced the accumulation of MB on SYL3C by obstructing the accessibility of guanines to MB but also impeded the transfer of electrons from the bound MB to AuE, leading to a notable decrease in the electrochemical signal. Using MB-stained SYL3C as an electronic switch, an electrochemical aptasensor was readily established for the detection of EpCAM-positive exosome detection. Without the need for signal amplification strategies, expensive auxiliary reagents, and complex operation, this unique signal transduction mechanism alone could endow the aptasensor with ultrahigh sensitivity. A limit of detection (LOD) of 234 particles mL-1 was achieved, surpassing the performance of most reported methods. As a proof of concept, the aptasensor was applied to analyze clinical serum samples and effectively distinguish non-small-cell lung cancer (NSCLC) patients from healthy individuals. As EpCAM exhibits broad expression in exosomes derived from different tumor sources, the developed aptasensor holds promise for diagnosing other tumor types.

Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment.

The initiation and progression of cancer are intricately linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorectal cancers (CRCs) and mouse CRC models, ask how these interactions are altered in human tumor organoid (tumoroid) cultures, and functionally recapitulate human myeloid-carcinoma interactions in vitro. Tumoroid cultures suppress gene expression programs involved in inflammation and immune cell migration, providing a reductive platform for re-establishing carcinoma-immune cell interactions in vitro. Introduction of human monocyte-derived macrophages into tumoroid cultures instructs macrophages to acquire immunosuppressive and pro-tumorigenic gene expression programs similar to those observed in vivo. This includes hallmark induction of SPP1, encoding Osteopontin, an extracellular CD44 ligand with established oncogenic effects. Taken together, these findings offer a framework for understanding CRC-TME interactions and provide a reductionist tool for modeling specific aspects of these interactions.

Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS.

Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both in vivo and in vitro. In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin in vitro. When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4.

Self-assembled miR-134-5p inhibitor nanoparticles ameliorate experimental bronchopulmonary dysplasia (BPD) via suppressing ferroptosis.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants with increased levels of reactive oxygen species (ROS) and ferroptosis. Herein, we designed a peptide-based nanoparticle to deliver therapeutic molecules to pulmonary, thereby ameliorating BPD. The BPD-induced damages of lung tissues were detected by H&E and immunohistochemistry staining. Inflammatory cytokines, Fe2+, and ROS levels were quantified by the indicated kits, respectively. The targeting relationship was verified by luciferase reporter assay and pull-down assay. Subsequently, self-assembled miR-134-5p inhibitor nanoparticles with pulmonary epithelial cell-targeting were synthesized. The characteristics were detected by transmission electron microscopy, luminescence imaging, and dynamic light scattering. A significant ferroptosis was observed in the BPD mice. The protein level of GPX4 was decreased significantly compared to the control group. Constantly, miR-134-5p showed positive regulation on ferroptosis by targeting GPX4. The designed nanoparticles were mainly accumulated in the lung region. Besides, it ameliorated experimental bronchopulmonary dysplasia via suppressing ferroptosis, in vivo and in vitro. Our findings provided a miR-134-5p/GPX4 axis in regulating ferroptosis of BPD and prompted the potential of applying the peptide-based nanoparticle to BPD treatment.

Neutralization of extracellular histones by sodium-Β-O-methyl cellobioside sulfate in septic shock.

BACKGROUND: Extracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-ß-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model. METHODS: This randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65-75 mmHg. The experiment was blinded and lasted maximum 24 h. RESULTS: During the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70-90] mmHg for early treatment, 57 [70-90] mmHg for late treatment, and 55 [49-60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived. CONCLUSIONS: Neutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.

Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs.

Lymphatic vessels (LVs) interdigitated with blood vessels, travel and form an extensive transport network in the musculoskeletal system. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, by near infrared indocyanine green lymphatic imaging (NIR-ICG), we examined lymphatic draining function at the tibial fracture sites and found lymphatic drainage insufficiency (LDI) occurred as early as two weeks after fracture. Sufficient lymphatic drainage facilitates fracture healing. In addition, we identified that lymphatic platelet thrombosis (LPT) blocks the draining lymphoid sinus and LVs, caused LDI and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage decreased neutrophils and increased M2-like macrophages of hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). These findings demonstrate that LPT limits bone regeneration by blocking lymphatic drainage from transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone repair.

Re-UNet: a novel multi-scale reverse U-shape network architecture for low-dose CT image reconstruction.

In recent years, the growing awareness of public health has brought attention to low-dose computed tomography (LDCT) scans. However, the CT image generated in this way contains a lot of noise or artifacts, which make increasing researchers to investigate methods to enhance image quality. The advancement of deep learning technology has provided researchers with novel approaches to enhance the quality of LDCT images. In the past, numerous studies based on convolutional neural networks (CNN) have yielded remarkable results in LDCT image reconstruction. Nonetheless, they all tend to continue to design new networks based on the fixed network architecture of UNet shape, which also leads to more and more complex networks. In this paper, we proposed a novel network model with a reverse U-shape architecture for the noise reduction in the LDCT image reconstruction task. In the model, we further designed a novel multi-scale feature extractor and edge enhancement module that yields a positive impact on CT images to exhibit strong structural characteristics. Evaluated on a public dataset, the experimental results demonstrate that the proposed model outperforms the compared algorithms based on traditional U-shaped architecture in terms of preserving texture details and reducing noise, as demonstrated by achieving the highest PSNR, SSIM and RMSE value. This study may shed light on the reverse U-shaped network architecture for CT image reconstruction, and could investigate the potential on other medical image processing.

Formation, structure and functional characteristics of amyloid fibrils formed based on soy protein isolates.

Food protein-derived amyloid fibrils possess great untapped potential applications in food and other biomaterials. The objective of this report was to investigate the formation mechanism, structure and functional characterization of soy protein amyloid fibrils (SPF) through hydrolysis and heating (pH 2.0, 85 °C, 0-24 h) of soy protein isolate (SPI). Fibrillation growth analysis indicated polypeptide hydrolysis upon hydrolytic heating, and the amyloid fibrils were basically formed 8 h later. The microstructure of SPF was monitored by transmission electron microscopy and scanning electron microscopy, exhibiting change from an irregular spherical structure to a coiled, intertwined thread-like polymer. The secondary structures of SPI all changed drastically during the fibrillation process was characterized by Fourier transform infrared spectroscopy, which the α-helical and ß-turned content decreasing by 12.67 % and 5.07 %, respectively, and the content of ordered ß-folded structures increasing with heating time, finally increasing to 53.61 % at 24 h. The fluorescence intensity of the endogenous fluorescence spectra decreased and the maximum emission wavelength was red-shifted, suggesting that the fibrillation unfolded the protein structure, hydrolyzed and self-assembled into amyloid fibrils aggregates obscuring the aromatic amino acid residues. The emulsification activity, emulsion stability and viscosity of SPF improved with the increase in protein fibrillation.

Ethyl caffeate combined with fluconazole exhibits efficacy against azole-resistant oropharyngeal candidiasis via the EFGR/JNK/c-JUN signaling pathway.

Ethyl caffeate (EC) is a phenylpropanoid compound derived from Elephantopus scaber. In our previous work, EC was investigated to have a strong synergistic antifungal effect against azole-resistant strains of Candida albicans when combined with fluconazole (FLU). However, the protective effect and mechanism of EC + FLU on oropharyngeal candidiasis (OPC) caused by drug-resistant strains of C. albicans have not been investigated. This study aimed to investigate the protective effect and mechanism of EC combined with FLU against C. albicans-resistant strains that lead to OPC. An OPC mouse model revealed that EC + FLU treatment reduced fungal load and massive hyphal invasion of tongue tissues, and ameliorated the integrity of the tongue mucosa. Periodic acid-Schiff staining results showed more structural integrity of the tongue tissues and reduced inflammatory cell infiltration after EC + FLU treatment. Phosphorylation of EGFR (epidermal growth factor receptor) and other proteins in the EFGR/JNK (c-Jun N-terminal kinase)/c-JUN (transcription factor Jun) signaling pathway was significantly downregulated by EC + FLU. EGFR and S100A9 mRNA expression were also reduced. The above results were verified in FaDu cells. ELISA results showed that the concentration of inflammatory factors in the cell supernatant was significantly reduced after EC combined with FLU treatment. Molecular docking revealed that EC exhibited high binding energy to EGFR. In conclusion, EC enhances the susceptibility of azole-resistant C. albicans to FLU, and the underlying mechanism is related to the inhibition of the EGFR/JNK/c-JUN signaling pathway. This result suggests that EC has potential to be developed as an antifungal sensitizer to treat OPC caused by azole-resistant C. albicans.

Curcumin promotes renewal of intestinal epithelium by miR-195-3p.

ETHNOPHARMACOLOGICAL RELEVANCE: Turmeric (Curcuma longa) has been used to treat gastrointestinal disorders in the Indian Ayurvedic medical system. According to the theory behind traditional Chinese medicine, turmeric can be distributed in the spleen meridian, for which it has been used as a digestive aid. Curcumin (Cur), a natural polyphenol compound originally derived from turmeric, has anti-inflammatory activity and can assist in treating inflammatory bowel disease. AIMS OF THE STUDY: To investigate curcumin's protective effects on intestinal epithelium and explore the underlying miR-195-3p-related mechanisms. MATERIALS AND METHODS: The miR-195-3p mimics were used to over-express miR-195-3p. The in vitro effects of Cur and miR-195-3p on the intestine were shown utilizing intestinal cryptlike epithelial cell line-6 (IEC-6) cells. By fasting for 48 h, an intestinal mucosal atrophy model of SD rats was created in vivo. Cur (25 or 50 mg/kg) was assessed for its protective effect on intestinal epithelium. Glycyrrhetinic acid (GA) with an intestinal protective effect reported in our previous research was adopted as a positive drug for the in vivo and in vitro bioactivity evaluation since there is no universally positive drug for either intestinal mucosal restitution or miR-195-3p modulation. RESULTS: Cur protects the intestinal epithelium and promotes its repair after injury via down-regulating miR-195-3p. In vitro experiments showed that Cur inhibited the apoptosis of IEC-6 cells, stimulated their growth, and down-regulated the level of miR-195-3p in cells. When miR-195-3p was overexpressed, the viability of IEC-6 cells decreased while the apoptosis rate increased. All the above detrimental effects were alleviated after curcumin intervention. Moreover, Cur reversed the effect of miR-195-3p on its downstream occludin. In vivo, results showed that 48-h fasting impaired the integrity of the small intestinal mucosa (abnormal crypt structure and reduced goblet cell number), which was ameliorated by Cur treatment. In addition, the Cur treatment reversed both the increased expression level of miR-195-3p and decreased levels of ki-67 and occludin caused by fasting. CONCLUSIONS: Cur could promote the proliferation and repair after injury of the intestinal mucosa by down-regulating miR-195-3p.

Negative Life Events on Depression of Vocational Undergraduates in the Partial Least Squares Structural Equation Modeling Approach Perspective: A Mediated Moderation Model.

BACKGROUND: Following China's strategy of developing applied and compound social talents, vocational undergraduates are surging rapidly, and it is essential to understand the causes of their depression to effectively prevent and intervene in schools. OBJECTIVE: We aimed to investigate the relationship between negative life events (NLEs) and depression among vocational undergraduates in China, along with the mediating role of loneliness and the moderating role of socioeconomic status (SES). METHODS: A convenience sample survey was conducted at a vocational education university (N = 1487), and analyzed using partial least squares structural equation modeling. RESULTS: Findings showed that NLEs directly predicted depression (ß = 0.399, 95% CI [0.339, 0.452], p < 0.001) among vocational undergraduates. Furthermore, this relationship was partially mediated by loneliness (ß = 0.182, 95% CI [0.145, 221], p < 0.001); SES moderated the link between NLEs and depression (ß = 0.051, 95% CI [0.004, 092], p < 0.05), but not between NLEs and loneliness (p > 0.05). CONCLUSIONS: The current study highlights the impact of NLEs on depression among vocational undergraduates, indicating the importance of addressing NLEs and consequent feelings of loneliness to promote mental health. In addition, the moderating role of SES underscores the necessity of targeted interventions to mitigate the impact of NLEs on depression. The present study contributes to our understanding of the unique characteristics of depression in vocational undergraduates and has practical implications for psychological support services. Moreover, it probably has broader implications for addressing mental health challenges in global education settings for vocational undergraduates.

Online monitoring of fatigue damage in welded joints using diffuse ultrasound.

Fatigue damage is a common cause of failure in welded structures, and it is often difficult to detect it in the early stage. While ultrasonic-based methods can effectively monitor crack propagation, it remains a significant challenge to indicate the initiation of cracks. In this study, a novel method is proposed to monitor the diffuse ultrasonic field affected by ratcheting strain and microcracks formed in welded joints during fatigue degradation. The energy density in the diffuse ultrasonic signal is computed and correlated with different fatigue cycles, allowing for online monitoring of fatigue damage in welded joints. Six butt and cross-welded joints were studied under different fatigue conditions, and digital image correlation (DIC) technology was used for comparison throughout the fatigue tests. The results indicate that the correlation coefficient of the energy density in diffuse ultrasound exhibits a significant decreasing trend when crack initiation occurs, providing a unique signal to indicate crack initiation in welded joints. This signal may appear earlier than that from ratcheting strain monitored by DIC due to ultrasound's sensitivity to internal damages.