Direct in Situ Fabrication of Multicolor Afterglow Carbon Dot Patterns with Transparent and Traceless Features via Laser Direct Writing.

Multicolor afterglow patterns with transparent and traceless features are important for the exploration of new functionalities and applications. Herein, we report a direct in situ patterning technique for fabricating afterglow carbon dots (CDs) based on laser direct writing (LDW) for the first time. We explore a facile step-scanning method that reduces the heat-affected zone and avoids uneven heating, thus producing a fine-resolution afterglow CD pattern with a minimum line width of 80 µm. Unlike previous LDW-induced luminescence patterns, the patterned CD films are traceless and transparent, which is mainly attributed to a uniform heat distribution and gentle temperature rise process. Interestingly, by regulating the laser parameters and CD precursors, an increased carbonization and oxidation degree of CDs could be obtained, thus enabling time-dependent, tunable afterglow colors from blue to red. In addition, we demonstrate their potential applications in the in situ fabrication of flexible and stretchable optoelectronics.

Synergistic Effect of Oxygen Vacancy and High Porosity of Nano MIL-125(Ti) for Enhanced Photocatalytic Nitrogen Fixation.

This work reports that a low-temperature thermal calcination strategy was adopted to modulate the electronic structure and attain an abundance of surface-active sites while maintaining the crystal morphology. All the experiments demonstrate that the new photocatalyst nano MIL-125(Ti)-250 obtained by thermal calcination strategy has abundant Ti3+ induced by oxygen vacancies and high specific surface area. This facilitates the adsorption and activation of N2 molecules on the active sites in the photocatalytic nitrogen fixation. The photocatalytic NH3 yield over MIL-125(Ti)-250 is enhanced to 156.9 µmol g-1 h-1 , over twice higher than that of the parent MIL-125(Ti) (76.2 µmol g-1 h-1 ). Combined with density function theory (DFT), it shows that the N2 adsorption pattern on the active sites tends to be from "end-on" to "side-on" mode, which is thermodynamically favourable. Moreover, the electrochemical tests demonstrate that the high atomic ratio of Ti3+ /Ti4+ can enhance carrier separation, which also promotes the efficiency of photocatalytic N2 fixation. This work may offer new insights into the design of innovative photocatalysts for various chemical reduction reactions.

Neighboring Platinum Atomic Sites Activate Platinum-Cobalt Nanoclusters as High-Performance ORR/OER/HER Electrocatalysts.

The rational design of efficient and multifunctional electrocatalysts for energy conversion devices is one of the major challenges for clean and renewable energy transition. Herein, the local electronic structure of cobalt-platinum nanoclusters is regulated by adjacent platinum atomic site encapsulated in N-doped hollow carbon nanotubes (PtSA -PtCo NCs/N-CNTs) by pyrolysis of melamine-orientation-induced zeolite imidazole metal-organic frameworks (ZIF-67) with thimbleful platinum doping. The introduction of melamine can reactivate adjacent carbon atoms and initiate the oriented growth of nitrogen-doped carbon nanotubes. The systematic analysis suggests the significant role of thimbleful neighboring low-coordinated Pt─N2 in altering the localized electronic structure of PtCo nanoclusters. The optimized PtSA -PtCo NCs/N-CNTs-900 exhibit excellent hydrogen evolution reaction (HER)/oxygen evolution reaction (OER)/oxygen reduction reaction (ORR)/ catalytic performance reaching the current density of 10 mA cm-2 in 1 m KOH under the low 47 (HER) and 252 mV (OER) overpotentials, and a high half-wave potential of 0.86 and 0.89 V (ORR) in 0.1 m KOH and 0.1 m HClO4 , respectively. Remarkably, the PtSA -PtCo NC/N-CNT-900 also presents outstanding catalytic performances toward water splitting and rechargeable Zn-air batteries. The theoretical calculations reveal that optimal regulation of the electronic structure of PtCo nanoclusters by thimbleful neighboring Pt atomic reduces the reaction energy barrier in electrochemical process, facilitating the ORR/OER/HER performance.

ß-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality, affecting preterm infants especially those with very low and extremely low birth weight. ß-glucan has manifested multiple biological effects including anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. This study aimed to investigate the effects of ß-glucan on NEC. METHODS: Neonatal C57BL/6 mice were randomly divided into three groups: Control group, NEC group and ß-glucan group. Newborn 3-day-old mice were gavaged with either 1 mg/ml ß-glucan or phosphate buffer saline at 0.03 ml/g for 7 consecutive days before NEC induction and a NEC model was established with hypoxia combined with cold exposure and formula feeding. All the pups were killed after 72-h modeling. Hematoxylin-eosin staining was performed to assess the pathological injury to the intestines. The mRNA expression levels of inflammatory factors in intestinal tissues were determined using quantitative real-time PCR. The protein levels of TLR4, NF-κB and tight junction proteins in intestinal tissues were evaluated using western blotting and immunohistochemistry. 16S rRNA sequencing was performed to determine the structure of the gut microbiota. RESULTS: ß-glucan administration ameliorated intestinal injury of NEC mice; reduced the intestinal expression of TLR4, NF-κB, IL-1ß, IL-6, and TNF-α; increased the intestinal expression of IL-10; and improved the expression of ZO-1, Occludin and Claudin-1 within the intestinal barrier. Pre-treatment with ß-glucan also increased the proportion of Actinobacteria, Clostridium butyricum, Lactobacillus johnsonii, Lactobacillus murinus, and Lachnospiraceae bacterium mt14 and reduced the proportion of Klebsiella oxytoca g Klebsiella in the NEC model. CONCLUSION: ß-glucan intervention prevents against NEC in neonatal mice, possibly by suppressing the TLR4-NF-κB signaling pathway, improving intestinal barrier function, and partially regulating intestinal microbiota.

Edge-Site-Rich Ordered Macroporous BiOCl Triggers CO Activation for Efficient CO2 Photoreduction.

Endowing a semiconductor with tunable edge active sites will effectively enhance catalytic performance. Herein, an edge-site-rich ordered macroporous BiOCl (BiOCl-P) with abundant dangling bonds is constructed via the colloidal crystal template method. The edge-site-rich ordered macroporous structure provides abundant adsorption sites for CO2 molecules, as well as forms numerous localized electron enrichment areas, accelerating charge transfer. DFT calculations reveal that the dangling bonds-rich configuration can effectively reduce the CO2 activation energy barrier, boost the CO double bond dissociation, and facilitate the proton electron coupling reaction. As a result, the BiOCl-P achieves a higher CO and CH4 generation rate of 78.07 and 3.03 µmol g-1 under 4 h Xe lamp irradiation in a solid-gas system. Finally, the CO2 molecules' conversion process is further investigated by in situ Fourier-transform infrared spectroscopy. This work realizes a new avenue toward the design of vibrant semiconductors on the nanoscale to boost inert CO2 photoreduction.

Pregnancy outcomes after fresh versus vitrified-warmed embryo transfer in women with adenomyosis: a retrospective cohort study.

RESEARCH QUESTION: Is the singleton live birth rate superior for vitrified-warmed versus fresh embryo transfer in women with adenomyosis? DESIGN: This cohort study retrospectively analysed data from the Reproductive Hospital Affiliated to Shandong University between January 2013 and December 2018. A total of 612 women diagnosed with adenomyosis, with 322 fresh embryo transfer cycles and 290 vitrified-warmed embryo transfer cycles, were included in this study. The primary outcome was singleton live birth. Outcomes were adjusted using multivariable logistic regression analysis. RESULTS: Vitrified-warmed embryo transfer was associated with a higher rate of singleton live birth than fresh embryo transfer (25.9% versus 17.4%; P = 0.011). Although there was a trend towards a lower miscarriage rate after vitrified-warmed embryo transfer, the difference did not reach statistical significance (31.3% versus 40.6%; P = 0.111). The clinical pregnancy rate was comparable in the two groups (44.1% versus 44.4%; P = 0.946). Vitrified-warmed embryo transfer also resulted in a lower risk of preterm birth than fresh embryo transfer (7.0% versus 17.5%; P = 0.010). CONCLUSIONS: Vitrified-warmed embryo transfer may be associated with better pregnancy outcomes than fresh embryo transfer among women with adenomyosis. It seems that vitrified-warmed embryo transfer is more appropriate for specific populations.

Discovery of novel sulphonamide hybrids that inhibit LSD1 against bladder cancer cells.

Aim:A series of sulphonamide hybrids were designed, synthesised, and identified as potential lysine-specific demethylase 1 (LSD1) inhibitors.Materials and methods: Bladder cancer cell lines were cultured to evaluate the antiproliferative activity. Inhibitory evaluation of sulphonamide hybrids against LSD1 were performed.Conclusion: sulphonamide derivative L8 exhibited the antiproliferative activity against HTB5, HTB3, HT1376, and HTB1 cells with IC50 values of 1.87, 0.18, 0.09, and 0.93 µM, respectively. Compound L8 as a selective and reversible LSD1 inhibitor could inhibit LSD1 with the IC50 value of 60 nM. It effectively inhibited LSD1 by increasing the expression levels of H3K4me1, H3K4me2, and H3K9me2 in HT1376 cells. To the best of our knowledge, this was the first report which showed that sulphonamide-quinoline-dithiocarbamate hybrids potently inhibited LSD1 in bladder cancer cells. Our studies give the potential application of the sulphonamide-based scaffold for developing LSD1 inhibitors to treat bladder cancer.

Unique Dual-Sites Boosting Overall CO2 Photoconversion by Hierarchical Electron Harvesters.

Low selectivity and poor activity of photocatalytic CO2 reduction process are usually limiting factors for its applicability. Herein, a hierarchical electron harvesting system is designed on CoNiP hollow nano-millefeuille (CoNiP NH), which enables the charge enrichment on CoNi dual active sites and selective conversion of CO2 to CH4 . The CoNiP serves as an electron harvester and photonic "black hole" accelerating the kinetics for CO2 -catalyzed reactions. Moreover, the dual sites form from highly stable CoONiC intermediates, which thermodynamically not only lower the reaction energy barrier but also transform the reaction pathways, thus enabling the highly selective generation of CH4 from CO2 . As an outcome, the CoNiP NH/black phosphorus with dual sites leads to a tremendously improved photocatalytic CH4 generation with a selectivity of 86.6% and an impressive activity of 38.7 µmol g-1  h-1 .

Ultrathin structure of oxygen doped carbon nitride for efficient CO2photocatalytic reduction.

Photocatalytic conversion of carbon dioxide into fuels and valuable chemicals is a promising method for carbon neutralization and solving environmental problems. Through a simple thermal-oxidative exfoliation method, the O element was doped while exfoliated bulk g-C3N4into ultrathin structure g-C3N4. Benefitting from the ultrathin structure of g-C3N4, the larger surface area and shorter electrons migration distance effectively improve the CO2reduction efficiency. In addition, density functional thory computation proves that O element doping introduces new impurity energy levels, which making electrons easier to be excited. The prepared photocatalyst reduction of CO2to CO (116µmol g-1h-1) and CH4(47µmol g-1h-1).

An All-Organic D-A System for Visible-Light-Driven Overall Water Splitting.

Direct water splitting over photocatalysts is a prospective strategy to convert solar energy into hydrogen energy. Nevertheless, because of the undesirable electron accumulation at the surface, the overall water-splitting efficiency is seriously restricted by the poor charge separation/transfer ability. Here, an all-organic donor-acceptor (D-A) system through crafting carbon rings units-conjugated tubular graphitic carbon nitride (C-TCN) is proposed. Through a range of characterizations and theoretical calculations, the incorporation of carbon rings units via continuous π-conjugated bond builds a D-A system, which can drive intramolecular charge transfer to realize highly efficient charge separation. More importantly, the tubular structure and the incorporated carbon rings units cause a significant downshift of the valence band, of which the potential is beneficial to the activation for O2 evolution. When serving as photocatalyst for overall water splitting, C-TCN displays considerable performance with H2 and O2 production rates of 204.6 and 100.8 µmol g-1 h-1 , respectively. The corresponding external quantum efficiency reaches 2.6% at 405 nm, and still remains 1.7% at 420 nm. This work demonstrates that the all-organic D-A system conceptualized from organic solar cell can offer promotional effect for overall water splitting by addressing the charge accumulation problem rooted in the hydrogen evolution reaction.

Anticancer evaluation of a novel dithiocarbamate hybrid as the tubulin polymerization inhibitor.

Novel quinoline-dithiocarbamate hybrids were synthesized and designed by the molecular hybridization strategy. All these derivatives were evaluated for their antiproliferative activity against three selected cancer cell lines (MGC-803, HepG-2 and PC-3). Among them, compound 10c displayed the best antiproliferative activity against PC-3 cells with an IC50 value of 0.43 µM. Celluar mechanisms investigated that compound 10c could inhibit the migration against PC-3 cells by regulation the expression levels of E-cadherin and N-cadherin. Compound 10c induced morphological changes of PC-3 cells and regulated apoptosis-related proteins (Bcl-2, Bax and Cleaved-Parp). In addition, compound 10c inhibited tubulin polymerization in vitro with an IC50 value of 4.02 µM. Importantly, compound 10c inhibited the growth of PC-3 cells in vivo with the low toxicity toward mice. These results suggested that compound 10c might be an antitumor agent with potential for treating prostate cancer.

Accelerating Photogenerated Charge Kinetics via the Synergetic Utilization of 2D Semiconducting Structural Advantages and Noble-Metal-Free Schottky Junction Effect.

Although photocatalysis is one of the most promising technologies for environmental and energy issues, the irreconcilable contradiction between the absorption of the visible light and the strong redox capability of the photocatalyst and the low photocatalytic reaction kinetics result in the poor efficiency. Here, a composite photocatalyst is reported with high redox capability and accelerated reaction kinetics synergistically utilizing 2D semiconducting structural advantages and the noble-metal-free Schottky junction effect. The 2D structure can not only increase the bandgap of the photocatalyst but also improve the transfer and separation of the photogenerated charge carriers. Furthermore, the introduction of the noble-metal-free Schottky junction effect accelerates the photocatalytic reaction kinetics. The Schottky barrier can also prevent the photogenerated charges trapped by the electron acceptor from flowing back to the semiconductor, which can further boost the photocatalytic performance. The transfer process of the photogenerated charge carriers is also researched in detail by the comprehensive characterization methods, which enable the photocatalytic mechanism to be revealed.

Mixed-ownership reform and factor misallocation: Evidence from China.

An enterprise's ownership structure is crucial for factor allocation efficiency. We used Chinese firm-level data to investigate whether changes in state-owned enterprise ownership structure contribute to resource misallocation, leading to high-quality economic development. We found a U-shaped relationship between non-state shareholding and state-owned enterprises' resource allocation efficiency. An optimal range exists for non-state shareholding. When the shareholding of non-state shareholders reaches 10%-20%, the efficiency of resource allocation is at its highest. Additional research has revealed that mixed shareholding has varying impacts on resource allocation, displaying substantial heterogeneity. These insights offer valuable guidance for future mixed-ownership reforms and serve as a practical reference for economic reforms in other nations, particularly developing countries.

Self-Powered Immunoassay of Norovirus in Human Stools by π-Electron-Rich Homojunction for Enhanced Charge Transfer.

Norovirus (NoV) stands as a significant causative agent of nonbacterial acute gastroenteritis on a global scale, presenting a substantial threat to public health. Hence, the development of simple and rapid analytical techniques for NoV detection holds great importance in preventing and controlling the outbreak of the epidemic. In this work, a self-powered photoelectrochemical (PEC) immunosensor of NoV capsid protein (VP1) was proposed by the π-electron-rich carbon nitride homojunction (ER-CNH) as the photoanode. C4N2 ring derived from π-rich locust bean gum was introduced into the tri-s-triazine structure, creating a large π-delocalized conjugated carbon nitride homojunction. This strategy enhances the C/N atomic ratio, which widens light utilization, narrows the bandgap, and optimizes the electronic band structure of carbon nitride. By introduction of a π-rich conjugated structure, p-type domains were induced within n-type domains to build the internal electric field at the interface, thus forming a p-n homojunction to boost carrier separation and transfer. The ER-CNH photoanode exhibited excellent photoelectric performance and water oxidation capacity. Since VP1 inhibits the water oxidation of the ER-CNH photoanode, the open-circuit potential of the as-prepared PEC immunosensor system was reduced for detecting NoV VP1. The self-powered PEC immunosensor achieved a remarkably low detection limit (∼5 fg mL-1) and displayed high stability and applicability for actual stool samples. This research serves as a foundation concept for constructing immunosensors to detect other viruses and promotes the application of self-powered systems for life safety.

Identifying the predictive role and the related drugs of oxidative stress genes in the hepatocellular carcinoma.

BACKGROUND AND AIMS: Oncogenesis and tumor development have been related to oxidative stress (OS). The potential diagnostic utility of OS genes in hepatocellular carcinoma (HCC), however, remains uncertain. As a result, this work aimed to create a novel OS related-genes signature that could be used to predict the survival of HCC patients and to screen OS related-genes drugs that might be used for HCC treatment. METHODS: We used The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database to acquire mRNA expression profiles and clinical data for this research and the GeneCards database to obtain OS related-genes. Following that, biological functions from Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on differentially expressed OS-related genes (DEOSGs). Subsequently, the prognostic risk signature was constructed based on DEOSGs from the TCGA data that were screened by using univariate cox analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox analysis. At the same time, we developed a prognostic nomogram of HCC patients based on risk signature and clinical-pathological characteristics. The GEO data was used for validation. We used the receiver operating characteristic (ROC) curve, calibration curves, and Kaplan-Meier (KM) survival curves to examine the prediction value of the risk signature and nomogram. Finally, we screened the differentially expressed OS genes related drugs. RESULTS: We were able to recognize 9 OS genes linked to HCC prognosis. In addition, the KM curve revealed a statistically significant difference in overall survival (OS) between the high-risk and low-risk groups. The area under the curve (AUC) shows the independent prognostic value of the risk signature model. Meanwhile, the ROC curves and calibration curves show the strong prognostic power of the nomogram. The top three drugs with negative ratings were ZM-336372, lestaurtinib, and flunisolide, all of which inversely regulate different OS gene expressions. CONCLUSION: Our findings indicate that OS related-genes have a favorable prognostic value for HCC, which sheds new light on the relationship between oxidative stress and HCC, and suggests potential therapeutic strategies for HCC patients.

Selenium restored mitophagic flux to alleviate cadmium-induced hepatotoxicity by inhibiting excessive GPER1-mediated mitophagy activation.

Cadmium (Cd) is a common environmental pollutant, while selenium (Se) can ameliorate heavy metal toxicity. Consequently, this study aimed to investigate the protective effects of Se against Cd-induced hepatocyte injury and its underlying mechanisms. To achieve this, we utilized the Dongdagou-Xinglong cohort, BRL3A cell models, and a rat model exposed to Cd and/or Se. The results showed that Se counteracted liver function injury and the decrease in GPER1 levels caused by environmental Cd exposure, and various methods confirmed that Se could protect against Cd-induced hepatotoxicity both in vivo and in vitro. Mechanistically, Cd caused excessive mitophagy activation, evidenced by the colocalization of LC3B, PINK1, Parkin, P62, and TOMM20. Transfection of BRL3A cells with mt-keima adenovirus indicated that Cd inhibited autophagosome-lysosome fusion, thereby impeding mitophagic flux. Importantly, G1, a specific agonist of GPER1, mitigated Cd-induced mitophagy overactivation and hepatocyte toxicity, whereas G15 exacerbates these effects. Notably, Se supplementation attenuated Cd-induced GPER1 protein reduction and excessive mitophagy activation while facilitating autophagosome-lysosome fusion, thereby restoring mitophagic flux. In conclusion, this study proposed a novel mechanism whereby Se alleviated GPER1-mediated mitophagy and promoted autophagosome-lysosome fusion, thus restoring Cd-induced mitophagic flux damage, and preventing hepatocyte injury.

Enhancement of endothelial function and attenuation of portal vein injury using mesenchymal stem cells carrying miRNA-25-3p.

The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases.

Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China.

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

Cadmium exacerbates liver injury by remodeling ceramide metabolism: Multiomics and laboratory evidence.

Cadmium (Cd) is a toxic heavy metal that primarily targets the liver. Cd exposure disrupts specific lipid metabolic pathways; however, the underlying mechanisms remain unclear. This study aimed to investigate the lipidomic characteristics of rat livers after Cd exposure as well as the potential mechanisms of Cd-induced liver injury. Our analysis of established Cd-exposed rat and cell models showed that Cd exposure resulted in liver lipid deposition and hepatocyte damage. Lipidomic detection, transcriptome sequencing, and experimental analyses revealed that Cd mainly affects the sphingolipid metabolic pathway and that the changes in ceramide metabolism are the most significant. In vitro experiments revealed that the inhibition of ceramide synthetase activity or activation of ceramide decomposing enzymes ameliorated the proapoptotic and pro-oxidative stress effects of Cd, thereby alleviating liver injury. In contrast, the exogenous addition of ceramide aggravated liver injury. In summary, Cd increased ceramide levels by remodeling ceramide synthesis and catabolism, thereby promoting hepatocyte apoptosis and oxidative stress and ultimately aggravating liver injury. Reducing ceramide levels can serve as a potential protective strategy to mitigate the liver toxicity of Cd. This study provides new evidence for understanding Cd-induced liver injury at the lipidomic level and insights into the health risks and toxicological mechanisms associated with Cd.

The association between trace metals in both cancerous and non-cancerous tissues with the risk of liver and gastric cancer progression in northwest China.

Liver cancer and gastric cancer have extremely high morbidity and mortality rates worldwide. It is well known that an increase or decrease in trace metals may be associated with the formation and development of a variety of diseases, including cancer. Therefore, this study aimed to evaluate the contents of aluminium (Al), arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in cancerous liver and gastric tissues, compared to adjacent healthy tissues, and to investigate the relationship between trace metals and cancer progression. During surgery, multiple samples were taken from the cancerous and adjacent healthy tissues of patients with liver and gastric cancer, and trace metal levels within these samples were analysed using inductively coupled plasma mass spectrometry (ICP-MS). We found that concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, and Zn in tissues from patients with liver cancer were significantly lower than those in healthy controls (P < 0.05). Similarly, patients with gastric cancer also showed lower levels of Cd, Co, Cr, Mn, Ni, and Zn-but higher levels of Cu and Se-compared to the controls (P < 0.05). In addition, patients with liver and gastric cancers who had poorly differentiated tumours and positive lymph node metastases showed lower levels of trace metals (P < 0.05), although no significant changes in their concentrations were observed to correlate with sex, age, or body mass index (BMI). Logistic regression, principal component analysis (PCA), Bayesian kernel regression (BKMR), weighted quantile sum (WQS) regression, and quantile-based g computing (qgcomp) models were used to analyse the relationships between trace metal concentrations in liver and gastric cancer tissues and the progression of these cancers. We found that single or mixed trace metal levels were negatively associated with poor differentiation and lymph node metastasis in both liver and gastric cancer, and the posterior inclusion probability (PIP) of each metal showed that Cd contributed the most to poor differentiation and lymph node metastasis in both liver and gastric cancer (all PIP = 1.000). These data help to clarify the relationship between changes in trace metal levels in cancerous liver and gastric tissues and the progression of these cancers. Further research is warranted, however, to fully elucidate the mechanisms and causations underlying these findings.