Machine learning for predicting halogen radical reactivity toward aqueous organic chemicals.

Rapid advances in machine learning (ML) provide fast, accurate, and widely applicable methods for predicting free radical-mediated organic pollutant reactivity. In this study, the rate constants (logk) of four halogen radicals were predicted using Morgan fingerprint (MF) and Mordred descriptor (MD) in combination with a series of ML models. The findings highlighted that making accurate predictions for various datasets depended on an effective combination of descriptors and algorithms. To further alleviate the challenge of limited sample size, we introduced a data combination strategy that improved prediction accuracy and mitigated overfitting by combining different datasets. The Light Gradient Boosting Machine (LightGBM) with MF and Random Forest (RF) with MD models based on the unified dataset were finally selected as the optimal models. The SHapley Additive exPlanations revealed insights: the MF-LightGBM model successfully captured the influence of electron-withdrawing/donating groups, while autocorrelation, walk count and information content descriptors in the MD-RF model were identified as key features. Furthermore, the important contribution of pH was emphasized. The results of the applicability domain analysis further supported that the developed model can make reliable predictions for query compounds across a broader range. Finally, a practical web application for logk calculations was built.

L-AP Alleviates Liver Injury in Septic Mice by Inhibiting Macrophage Activation via Suppressing NF-κB and NLRP3 Inflammasome/Caspase-1 Signal Pathways.

Liver injury and progressive liver failure are severe life-threatening complications in sepsis, further worsening the disease and leading to death. Macrophages and their mediated inflammatory cytokine storm are critical regulators in the occurrence and progression of liver injury in sepsis, for which effective treatments are still lacking. l-Ascorbic acid 6-palmitate (L-AP), a food additive, can inhibit neuroinflammation by modulating the phenotype of the microglia, but its pharmacological action in septic liver damage has not been fully explored. We aimed to investigate L-AP's antisepticemia action and the possible pharmacological mechanisms in attenuating septic liver damage by modulating macrophage function. We observed that L-AP treatment significantly increased survival in cecal ligation and puncture-induced WT mice and attenuated hepatic inflammatory injury, including the histopathology of the liver tissues, hepatocyte apoptosis, and the liver enzyme levels in plasma, which were comparable to NLRP3-deficiency in septic mice. L-AP supplementation significantly attenuated the excessive inflammatory response in hepatic tissues of septic mice in vivo and in cultured macrophages challenged by both LPS and ATP in vitro, by reducing the levels of NLRP3, pro-IL-1ß, and pro-IL-18 mRNA expression, as well as the levels of proteins for p-I-κB-α, p-NF-κB-p65, NLRP3, cleaved-caspase-1, IL-1ß, and IL-18. Additionally, it impaired the inflammasome ASC spot activation and reduced the inflammatory factor contents, including IL-1ß and IL-18 in plasma/cultured superannuants. It also prevented the infiltration/migration of macrophages and their M1-like inflammatory polarization while improving their M2-like polarization. Overall, our findings revealed that L-AP protected against sepsis by reducing macrophage activation and inflammatory cytokine production by suppressing their activation in NF-κB and NLRP3 inflammasome signal pathways in septic liver.

The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma.

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

The application of machine learning methods for prediction of heavy metal by activated carbons, biochars, and carbon nanotubes.

Carbonaceous materials are commonly used as adsorbents for heavy metals. The determination of the adsorption capacity needs time and energy, and the key factors affecting the adsorption capacity have not been determined. Therefore, a new and efficient method is needed to predict the adsorption capacity and explore the decisive factors in the adsorption process. In this study, three tree-based machine learning models (i.e., random forest, gradient boosting decision tree, and extreme gradient boosting) were developed to predict the adsorption capacity of eight heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) on activated carbons, biochars, and carbon nanotubes using 3674 data points extracted from 151 journal articles. After a comprehensive comparison, the gradient boosting decision tree had the best performance for a combined model based on all data (R2 = 0.9707, RMSE = 0.1420). Moreover, independent models were developed for three datasets classified by the adsorbent and eight datasets classified by the heavy metals. In addition, a graphical user interface was built to predict the adsorption capacity of heavy metals. This study provides a novel strategy and convenient tool for the removal of heavy metals and can help to improve the removal efficiency of heavy metals to build a healthier world.

Evaluation of multiplexed sensitivity encoding diffusion-weighted imaging in detecting uterine lesions: Image quality optimization.

PURPOSE: To compare the image quality of multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE-DWI) and single-shot echo-planar imaging (SS-EPI-DWI) techniques in uterine MRI. METHODS: Eighty-eight eligible patients underwent MUSE-DWI and SS-EPI-DWI examinations simultaneously using a 3.0 T MRI system. Two radiologists independently performed quantitative and qualitative analysis of the two groups of images using a double-blind method. The weighted Kappa test was used to evaluate the interobserver agreement. Wilcoxon's rank sum test was used for qualitative parameters, and paired t-test was used for quantitative parameters. Spearman rank correlation analysis was used to obtained correlation between pathological results and mean apparent diffusion coefficient (ADC) value. RESULTS: The qualitative and quantitative analysis of the images by the two radiologists were in good or excellent agreement, with weighted kappa value ranging from 0.636 to 0.981. The scores of total subjective image quality (15.4 ± 0.99) and signal-to-noise ratio (158.99 ± 60.71) of MUSE-DWI were significantly higher than those of SS-EPI-DWI (12.93 ± 1.62 P < 0.001; 130.23 ± 48.29 P < 0.05). It effectively reduced image distortion and artifact, and had better lesion conspicuity. There was no significant difference in contrast-to-noise ratio score and average ADC values between the two DWI sequences. The average ADC values of the two DWI sequences were highest in the normal uterus group and lowest in the endometrial cancer group, with statistically significant differences among groups (P < 0.01). In addition, the average ADC values of the two DWI sequences were negatively correlated with the type of lesions, decreasing with the malignancy of the lesions (r = -0.805 P < 0.01, r = -0.815 P < 0.01). CONCLUSION: Compared to SS-EPI-DWI, MUSE-DWI can significantly reduce distortion, artifacts, and fuzziness in MRI of uterine lesions, which is more conducive to lesion detection.

The Predictive Value of Hemoglobin to Red Cell Blood Distribution Width Ratio Combined with Serum Sodium for MACE of Acute Heart Failure with Preserved Ejection Fraction in Elderly Patients.

Purpose: To investigate the predictive value of hemoglobin (Hb) to red blood cell distribution width (RDW) (Hb/RDW) ratio in combination with serum sodium for major adverse cardiovascular events (MACE) in elderly acute heart failure patients with preserved ejection fraction at 30 days after discharge. Methods: 130 elderly acute heart failure patients with preserved ejection fraction were enrolled and followed up at 30 days after discharge. They were classified into the MACE group (n=11) and none-MACE group (n=119). On the day of admission, clinical baseline characteristics were measured and results from laboratory tests were gathered. The correlation and predictive value of Hb/RDW and serum sodium with the occurrence of MACE at 30 days after discharge in acute heart failure patients with preserved ejection fraction in the elderly were analyzed. Results: Spearman correlation analysis showed that the occurrence of MACE was negatively correlated with Hb/RDW, serum sodium (r=-0.209, r=0.291, p<0.05) and Hb/RDW (OR=0.484, 95% CI:0.254, 0.922), serum sodium (OR=0.779, 95% CI:0.646,0.939) were independent risk factors (p<0.05) analyzed by multifactorial logistic. Receiver operating characteristic curves (ROC) analysis showed that the area under the curve (AUC) for the prediction of MACE by Hb/RDW was 0.73, with an optimal threshold of 9.28, sensitivity 81.80%, specificity 70.60%, positive predictive value (PPV) 20.50%, negative predictive value (NPV) 97.70%; the AUC of serum sodium for predicting the occurrence of MACE was 0.76, with an optimal threshold of 140.35 mmol/L, sensitivity 90.90%, specificity 57.10%, PPV 16.40%, NPV 98.60%; and the AUC of Hb/RDW combined serum sodium to predict the occurrence of MACE was 0.83, with sensitivity 90.90%, specificity 78.20%, PPV 27.80% and NPV 98.90%. Conclusion: Hb/RDW and serum sodium had negative correlation with MACE and were independent risk factors of 30-day MACE; Hb/RDW combined with serum sodium can predict 30-day MACE occurrence in elderly acute heart failure patients with preserved ejection fraction.

Prediction of antibiotic sorption in soil with machine learning and analysis of global antibiotic resistance risk.

Although the sorption of antibiotics in soil has been extensively studied, their spatial distribution patterns and sorption mechanisms still need to be clarified, which hinders the assessment of antibiotic resistance risk. In this study, machine learning was employed to develop the models for predicting the soil sorption behavior of three classes of antibiotics (sulfonamides, tetracyclines, and fluoroquinolones) in 255 soils with 2203 data points. The optimal independent models obtained an accurate predictive performance with R2 of 0.942 to 0.977 and RMSE of 0.051 to 0.210 on test sets compared to combined models. Besides, a global map of the antibiotic sorption capacity of soil predicted with the optimal models revealed that the sorption potential of fluoroquinolones was the highest, followed by tetracyclines and sulfonamides. Additionally, 14.3% of regions had higher antibiotic sorption potential, mainly in East and South Asia, Central Siberia, Western Europe, South America, and Central North America. Moreover, a risk index calculated with the antibiotic sorption capacity of soil and population density indicated that about 3.6% of soils worldwide have a high risk of resistance, especially in South and East Asia with high population densities. This work has significant implications for assessing the antibiotic contamination potential and resistance risk.

Irisin attenuates vascular remodeling in hypertensive mice induced by Ang II by suppressing Ca2+-dependent endoplasmic reticulum stress in VSMCs.

Vascular remodeling plays a vital role in hypertensive diseases and is an important target for hypertension treatment. Irisin, a newly discovered myokine and adipokine, has been found to have beneficial effects on various cardiovascular diseases. However, the pharmacological effect of irisin in antagonizing hypertension-induced vascular remodeling is not well understood. In the present study, we investigated the protection and mechanisms of irisin against hypertension and vascular remodeling induced by angiotensin II (Ang II). Adult male mice of wild-type, FNDC5 (irisin-precursor) knockout, and FNDC5 overexpression were used to develop hypertension by challenging them with Ang II subcutaneously in the back using a microosmotic pump for 4 weeks. Similar to the attenuation of irisin on Ang II-induced VSMCs remodeling, endogenous FNDC5 ablation exacerbated, and exogenous FNDC5 overexpression alleviated Ang II-induced hypertension and vascular remodeling. Aortic RNA sequencing showed that irisin deficiency exacerbated intracellular calcium imbalance and increased vasoconstriction, which was parallel to the deterioration in both ER calcium dysmetabolism and ER stress. FNDC5 overexpression/exogenous irisin supplementation protected VSMCs from Ang II-induced remodeling by improving endoplasmic reticulum (ER) homeostasis. This improvement includes inhibiting Ca2+ release from the ER and promoting the re-absorption of Ca2+ into the ER, thus relieving Ca2+-dependent ER stress. Furthermore, irisin was confirmed to bind to its receptors, αV/ß5 integrins, to further activate the AMPK pathway and inhibit the p38 pathway, leading to vasoprotection in Ang II-insulted VSMCs. These results indicate that irisin protects against hypertension and vascular remodeling in Ang II-challenged mice by restoring calcium homeostasis and attenuating ER stress in VSMCs via activating AMPK and suppressing p38 signaling.

Application of Four-Dimensional Pelvic Floor Ultrasound in the Diagnosis of Postpartum Pelvic Floor Dysfunction and Evaluation of Curative Effect.

Objective: To explore the application of four-dimensional pelvic floor ultrasound in the diagnosis of postpartum pelvic floor dysfunction (PFD) and evaluation of curative effect. Methods: A total of 100 patients with postpartum PFD undergoing vaginal delivery in the hospital were enrolled as the research objects between January 2020 and January 2023. A total of 100 postpartum women with good pelvic floor muscle function during the same period were enrolled as a control group. Both groups underwent four-dimensional pelvic floor ultrasound detection. The bladder neck descent (BND), retrovesical angle (RVA), urethral tilt angle (UTA), urethral rotation angle (ROT), levator ani thickness under rest state (LATr), levator ani thickness under Valsalva state (LATs), levator ani hiatus area under rest state (LHAr) and levator ani hiatus area under Valsalva state (LHAs) in both groups were compared. The patients in the study group were given Kegel training for pelvic floor muscle rehabilitation exercise and bio-feedback electrical stimulation. According to the clinical curative effect, patients in the study group were divided into a recovery group (n=87) and a non-recovery group (n=13). The value of four-dimensional pelvic floor ultrasound in the diagnosis of PFD and evaluation of curative effect was analyzed. Results: In the observation group, BND, RVA, UTA, ROT, LHAr, and LHAs were higher, while LATr and LATs were lower compared to the control group. (P < .05). The results of ROC curves analysis showed that the AUC of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs in the diagnosis of PFD was 0.818, greater than that of the single index (0.728, 0.705, 0.680, 0.715, 0.677, 0.696, 0.719, 0.654; P < .05). BND, RVA, UTA, ROT, LHAr, and LHAs in the non-recovery group were higher than those in the recovery group, while LATr and LATs were lower than those in the recovery group (P < .05). The results of ROC curves analysis showed that the Area Under the Curve (AUC）of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs for predicting the curative effect were 0.804, greater than that of a single index (0.725, 0.653, 0.651, 0.744, 0.733, 0.720, 0.661, 0.718; P < .05). Conclusion: Four-dimensional pelvic floor ultrasound can be applied to intuitively evaluate the structure and function of postpartum pelvic floor tissues, which can provide a reliable basis for the diagnosis of postpartum PFD and evaluation of curative effect.

Reveal the relationship between the quality and the cuticle composition of Satsuma mandarin (Citrus unshiu) by postharvest heat treatment.

To investigate the influence of heat treatment (HT) on Satsuma mandarin fruit's postharvest quality and cuticle composition, we immersed the fruit for 3 min in hot water at 52°C and subsequently stored them at room temperature (25°C) for 28 days, and fruit quality parameters, such as good fruit rate, weight loss rate, firmness, total soluble solids, total titratable acidity, and ascorbic acid content, were monitored. Additionally, changes in the peel's cuticle composition were analyzed, and wax crystal morphologies on the fruit surface were examined using scanning electron microscopy (SEM). The findings revealed that appropriate HT effectively preserved fruit quality. The main compositions of wax and cutin on the fruit's surface remained consistent between the HT and the CK during storage. The total content of wax and cutin initially increased, peaking on the 14th day of storage, and then decreased, falling below the levels observed on day 0. Notably, the total amount of cutin in the HT group exceeded that of the control group. Specifically, ω-hydroxy fatty acids with mid-chain oxo groups and mid-oh-ω-hydroxy fatty acids constituted approximately 90% of the total cutin content. Moreover, the HT group exhibited higher (p < 0.05) total wax content in relation to the control. Fatty acids and alkanes were the predominant components, accounting for approximately 87.5% of the total wax. SEM analysis demonstrated that HT caused wax crystals to melt and redistribute, effectively filling wax gaps. It suggests that HT holds promising potential as a green, safe, and eco-friendly commercial treatment for preserving the postharvest quality of Satsuma mandarin. PRACTICAL APPLICATION: In this study, Satsuma citrus (Citrus unshiu) underwent heat treatment (HT) and was subsequently preserved at room temperature (25°C) for 28 days. The findings revealed that HT significantly improved fruit quality compared to the control group. These findings provide valuable insights into the advancement of eco-friendly and pollution-free citrus preservation methods, offering essential strategies and process parameters for their practical application.

The effectiveness of a workplace violence prevention strategy based on situational prevention theory for nurses in managing violent situations: a quasi-experimental study.

BACKGROUND: Workplace violence (WPV) poses a significant occupational hazard for nurses. The efficacy of current education and training programs in mitigating WPV incidence among nurses remains uncertain, possibly due to insufficient consideration of clinical contexts and nurses' specific needs. Therefore, this study developed a WPV prevention strategy based on the actual requirements of clinical nurses and situational prevention theory and aimed to explore its application effects. METHODS: Under the guidance of situational prevention theory, a WPV prevention strategy for nurses was constructed through literature review, semi-structured interviews and focus group discussion. This study adopted a self-controlled research design, and trained 130 nurses selected from a comprehensive tertiary grade A hospital in Suzhou in this WPV prevention strategy. Data were collected through structured questionnaires, including the revised WPV questionnaire, WPV severity grading scale, and hospital WPV coping resources scale. The WPV incidence, severity, and WPV coping resource scores of nurses were collected before the intervention, as well as at 3 months, 6 months, and 9 months after training. RESULTS: The WPV prevention strategy comprised 11 prevention plans based on 11 high-risk situational elements of WPV. Each prevention plan included the WPV prevention flowchart, treatment principle, and communication strategy. The strategy demonstrated excellent feasibility and practicality. Following the intervention, the overall incidence of WPV among nurses significantly decreased from 63.85% (baseline) to 46.15% (9 months after training) (P < 0.05). After the training, the severity of psychological violence (Wald χ² = 20.066, P < 0.001) and physical violence (Wald χ² = 9.100, P = 0.028) reported by nurses decreased compared to the baseline (P < 0.05). Moreover, the overall WPV coping resource score significantly increased from [66.50 (57.00, 77.25) points] (baseline) to [80.00 (68.00, 97.25) points] (9 months after training) (P < 0.05). CONCLUSIONS: The described WPV prevention strategy, grounded in situational prevention theory and tailored to the needs of clinical nurses, effectively reduced WPV incidence, mitigated its severity, and enhanced nurses' WPV coping resources. This approach offered new avenues for nurses in the prevention of WPV.

The Non-Nutritional Factor Types, Mechanisms of Action and Passivation Methods in Food Processing of Kidney Bean (Phaseolus vulgaris L.): A Systematic Review.

Kidney beans (KBs), as a traditional edible legume, are an important food crop of high nutritional and economic value worldwide. KBs contain a full range of amino acids and a high proportion of essential amino acids, and are rich in carbohydrates as well as vitamins and minerals. However, KBs contain a variety of non-nutritional factors that impede the digestion and absorption of nutrients, disrupt normal metabolism and produce allergic reactions, which severely limit the exploitation of KBs and related products. Suppressing or removing the activity of non-nutritional factors through different processing methods can effectively improve the application value of KBs and expand the market prospect of their products. The aim of this review was to systematically summarize the main types of non-nutritional factors in KBs and their mechanisms of action, and to elucidate the effects of different food processing techniques on non-nutritional factors. The databases utilized for the research included Web of Science, PubMed, ScienceDirect and Scopus. We considered all original indexed studies written in English and published between 2012 and 2023. We also look forward to the future research direction of producing KB products with low non-nutritional factors, which will provide theoretical basis and foundation for the development of safer and healthier KB products.

mRNA-LNP vaccination-based immunotherapy augments CD8+ T cell responses against HPV-positive oropharyngeal cancer.

Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.

Optimal government and manufacturer incentive contracts for green production with asymmetric information.

Governments commonly utilize subsidy policy to incentivize manufacturers to produce green products, promoting sustainable development. However, in the presence of information asymmetry, some manufacturers may dishonestly misrepresent the green degree of their products to secure higher subsidies. This study examines different incentive contracts between the government and a green product manufacturer who keeps private information of a product's green-degree in a principal-agent model. Lump-sum transfer and fixed- and flexible-proportion benefit-sharing contracts are proposed to investigate screening and improving green-degree issues. To further enhance the flexible-proportion benefit-sharing contract, we construct a non-linear coordinated contract based on the Nash bargaining solution. The revelation principle and Nash bargaining are performed for comparison and analysis of the contracts. We find that the lump-sum contract reveals true green-degree information but fails to impel manufacturers to improve product's green-degree in developing countries where green product development is in initial stages. In contrast, both fixed- and flexible- proportion benefit-sharing contracts are effective in reveling and enhancing green-degree. The non-linear coordination contract optimizes resource allocation and achieves Pareto improvement. An applied case study for inkjet printer operations and numerical experiments corroborate our model findings.

Irisin protects against doxorubicin-induced cardiotoxicity by improving AMPK-Nrf2 dependent mitochondrial fusion and strengthening endogenous anti-oxidant defense mechanisms.

Irisin, a new exercise-mediated myokine, plays an important role in cardiovascular diseases by regulating cell energy metabolism. The induction of mitochondrial dysfunction and oxidative stress are the crucial mechanisms involved in doxorubicin-induced cardiomyocyte damage and cardiac dysfunction, but the mitochondria-dependent protective mechanisms of irisin in DOX-impaired cardiomyocytes are poorly understood. In this study, we exposed mouse-FNDC5 (irisin-precursor)-knockout, FNDC5 transgenic mice and their WT littermates, as well as cultured neonatal rat cardiomyocytes to DOX at a dosage of 4 mg/kg (once a week for 4 weeks) in vivo and 2 µM in vitro, respectively, then investigated how irisin alleviated DOX-induced oxidative stress and myocardial injury. Irisin knockout worsened, while irisin overexpression attenuated DOX-induced mortality, body weight loss, myocardial atrophy, damage and oxidative stress, cardiac remodeling and dysfunction in mice. Exogenous irisin supplementation (20 nM) also relieved these DOX-induced damage in cardiomyocytes. Intriguingly, irisin activated AMPK-Nrf2 signaling axis, and then up-regulated the transcription and protein expression of the downstream target genes of Nrf2, including mitochondrial fusion-related genes (mitofusin 1/2 and Optic Atrophy Type 1) and endogenous anti-oxidant genes, to promote mitochondrial fusion, improve mitochondrial dynamics and mitochondrial function, and reduced oxidative stress damage in DOX-induced cardiomyocytes. These results suggest that irisin protects the hearts from DOX-induced cardiotoxicity by improving mitochondrial dynamics and strengthening the endogenous anti-oxidant system through an AMPK-Nrf2 axis dependent manner, thus reducing DOX-induced oxidative stress injury in cardiomyocytes.

Interface engineering of Ni2P/MoOx decorated NiFeP nanosheets for enhanced alkaline hydrogen evolution reaction at high current densities.

The rational design of high-performance non-noble metal electrocatalysts at large current densities is important for the development of sustainable energy conversion devices such as alkaline water electrolyzers. However, improving the intrinsic activity of those non-noble metal electrocatalysts remains a great challenge. Therefore, Ni2P/MoOx decorated three-dimensional (3D) NiFeP nanosheets (NiFeP@Ni2P/MoOx) with abundant interfaces were synthesized using facile hydrothermal and phosphorization methods. NiFeP@Ni2P/MoOx exhibits excellent electrocatalytic activity for hydrogen evolution reaction (HER) at a high current density of -1000 mA cm-2 with a low overpotential of 390 mV. Surprisingly, it can operate steadily at a large current density of -500 mA cm-2 for 300 h, indicating its long-term durability under high current densities. The boosted electrocatalytic activity and stability can be ascribed to the as-fabricated heterostructures via interface engineering, leading to modifying the electronic structure, improving the active area, and enhancing the stability. Besides, the 3D nanostructure is also beneficial for exposing abundant accessible active sites. Therefore, this research proposes a considerable route for fabricating non-noble metal electrocatalysts by interface engineering and 3D nanostructure applied in large-scale hydrogen production facilities.

Effects of Ferroptosis on Cardiovascular Diseases.

Ferroptosis is a novel form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which causes membrane injury. Under the catalysis of iron ions, cells deficient in glutathione peroxidase (GPX4) cannot preserve the balance in lipid oxidative metabolism, and the buildup of reactive oxygen species on the membrane lipids leads to cell death. An increasing body of evidence suggests that ferroptosis plays a significant role in the development and occurrence of cardiovascular diseases. In this paper, we mainly elaborated on the molecular mechanisms regulating ferroptosis and its impact on cardiovascular disease to lay the groundwork for future studies on the prophylaxis and treatment of this patient population.

Programmed cell death 10 increased blood-brain barrier permeability through HMGB1/TLR4 mediated downregulation of endothelial ZO-1 in glioblastoma.

Dysfunction of blood brain barrier (BBB) contributes to the development of peritumoral edema (PTE) and GBM progression. Programmed cell death 10 (PDCD10) exerts various influence on cancers, especially in glioblastoma (GBM). We previously found that PDCD10 expression was positively correlated with PTE extent in GBM. Thus, the present study aims to investigate the emerging role of PDCD10 in regulating BBB permeability in GBM. Here we found that in vitro indirect co-culture of endothelial cells (ECs) with Pdcd10-overexpressed GL261 cells resulted in a significant increase of FITC-Dextran (MW, 4000) leakage by reducing endothelial zonula occluden-1 (ZO-1) and Claudin-5 expression in ECs respectively. Overexpression of Pdcd10 in GBM cells (GL261) triggered an increase of soluble high mobility group box 1 (HMGB1) release, which in turn activated endothelial toll like receptor 4 (TLR4) and downstream NF-κB, Erk1/2 and Akt signaling in ECs through a paracrine manner. Moreover, Pdcd10-overexpressed GL261 cells facilitated a formation of abnormal vasculature and increased the BBB permeability in vivo. Our present study demonstrates that upregulation of PDCD10 in GBM triggered HMGB1/TLR4 signaling in ECs and significantly decreased endothelial ZO-1 expression, which in turn dominantly increased BBB permeability and contributed to tumor progression in GBM.

Low-dose of zeolitic imidazolate framework-8 nanoparticle cause energy metabolism disorder through lysosome-mitochondria dysfunction.

Understanding the underlying interaction between nanoparticle and organelles is conclusive to the nanotoxicology. According to existing literatures, lysosome is a crucial target of the nanoparticle carrier. Meanwhile, mitochondria could provide the essential energy for nanopaticles entering/exiting the cell. Based on the investigation of lysosome-mitochondria connection, we decoded the effects of low-dose ZIF-8 on energy metabolism, which are still largely obscure beforehand. In this research, low-dose ZIF-8 NPs were utilized to explore the effects on vascular endothelial cells, the first cells exposed to NPs during intravenous injection. Consequently, ZIF-8 could damage the energy metabolism, mainly manifested as mitochondrial fission, the decreased ATP production, and lysosomal dysfuction, which would subsequently affect the cell survival, proliferation and protein expression. This study highlights the fundamental understanding for exploring the regulation of nanoscale ZIF-8 in biological processes and its further application in biomedical field.

[Frontiers and development in live-cell super-resolution fluorescence microscopy].

This paper reviews the research progress on live-cell super-resolution fluorescence microscopy, discusses the current research status and hotspots in this field, and summarizes the technological application of super-resolution fluorescence microscopy for live-cell imaging. To date, this field has gained progress in numerous aspects. Specifically, the structured illumination microscopy, stimulated emission depletion microscopy, and the recently introduced minimal photon fluxes microscopy are the current research hotspots. According to the current progress in this field, future development trend is likely to be largely driven by artificial intelligence as well as advances in fluorescent probes and relevant labelling methods.