Integrated proteomic, phosphoproteomic, and N-glycoproteomic analyses of small extracellular vesicles from C2C12 myoblasts identify specific PTM patterns in ligand-receptor interactions.

Small extracellular vesicles (sEVs) are important mediators of intercellular communication by transferring of functional components (proteins, RNAs, and lipids) to recipient cells. Some PTMs, including phosphorylation and N-glycosylation, have been reported to play important role in EV biology, such as biogenesis, protein sorting and uptake of sEVs. MS-based proteomic technology has been applied to identify proteins and PTM modifications in sEVs. Previous proteomic studies of sEVs from C2C12 myoblasts, an important skeletal muscle cell line, focused on identification of proteins, but no PTM information on sEVs proteins is available.In this study, we systematically analyzed the proteome, phosphoproteome, and N-glycoproteome of sEVs from C2C12 myoblasts with LC-MS/MS. In-depth analyses of the three proteomic datasets revealed that the three proteomes identified different catalogues of proteins, and PTMomic analysis could expand the identification of cargos in sEVs. At the proteomic level, a high percentage of membrane proteins, especially tetraspanins, was identified. The sEVs-derived phosphoproteome had a remarkably high level of tyrosine-phosphorylated sites. The tyrosine-phosphorylated proteins might be involved with EPH-Ephrin signaling pathway. At the level of N-glycoproteomics, several glycoforms, such as complex N-linked glycans and sialic acids on glycans, were enriched in sEVs. Retrieving of the ligand-receptor interaction in sEVs revealed that extracellular matrix (ECM) and cell adhesion molecule (CAM) represented the most abundant ligand-receptor pairs in sEVs. Mapping the PTM information on the ligands and receptors revealed that N-glycosylation mainly occurred on ECM and CAM proteins, while phosphorylation occurred on different categories of receptors and ligands. A comprehensive PTM map of ECM-receptor interaction and their components is also provided.In summary, we conducted a comprehensive proteomic and PTMomic analysis of sEVs of C2C12 myoblasts. Integrated proteomic, phosphoproteomic, and N-glycoproteomic analysis of sEVs might provide some insights about their specific uptake mechanism.

Effect of Alloying Elements in Steels on the Interfacial Structure and Mechanical Properties of Mg to Steel by Laser-GTAW Hybrid Direct Lap Welding.

Mg alloy AZ31B was directly bonded to SK7 with a low alloy content, DP980 with a high Mn content, 316L with a high Cr and high Ni content by laser-gas tungsten arc welding (GTAW) and hybrid direct lap welding. The results showed that the tensile loads of AZ31B/SK7 and AZ31B/DP980 joints were 283 N/mm and 285 N/mm respectively, while the tensile load of AZ31B/316L joint was only 115 N/mm. The fracture and interface microstructures were observed using scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and identified through X-ray diffractometry (XRD). For AZ31B/SK7 and AZ31B/DP980, the interface of the front reaction area and the keyhole reaction area was mainly composed of an Fe-Al phase and an Al-Mn phase. However, for AZ31B/316L, the interface of the keyhole reaction area was mainly composed of an Fe-Al phase and an Al-Mn phase, but a multi-layer composite structure consisting of the Mg17Al12 compound layer and eutectic layer was formed in the front reaction area, which led to a deterioration in the joint property. The influencing mechanism of Mn, Cr and Ni elements in steel on the properties and interface structure of the laser-GTAW lap joint between the Mg alloy and the steel was systematically analyzed.

M1 Macrophage-Derived Exosome LncRNA PVT1 Promotes Inflammation and Pyroptosis of Vascular Smooth Muscle Cells in Abdominal Aortic Aneurysm by Inhibiting miR-186-5p and Regulating HMGB1.

Abdominal aortic aneurysm (AAA) is a chronic vascular degenerative disease. Vascular smooth muscle cells (VSMCs) are essential for maintaining the integrity of healthy blood vessels. Macrophages play an important role in the inflammatory process of AAA. However, the effect of macrophage-derived exosome LncRNA PVT1 on VSMCs is unclear. Exosomes from M1 macrophages (M1φ-exos) were isolated and identified. The expression of LncRNA PVT1 in M1φ-exos was determined. AAA cell model was constructed by treating VSMCs with Ang-II. AAA cell model was treated with M1φ exosomes transfected with si-LncRNA PVT1 (M1φsi-LncRNA PVT1-exo). VSMCs were transfected with miR-186-5p mimic and oe-HMGB1. Cell viability was detected by CCK-8. The accumulation of LDH was detected by ELISA. Western blot was used to detect the expression of HMGB1, inflammatory factors (IL-6, TNF-α and IL-1ß) and pyroptosis-related proteins (GSDMD, N-GSDMD, ASC, NLRP3, Caspase-1 and Cleaved-Capase-1). Cell pyroptosis rate was detected by flow cytometry. At the same time, the targeting relationship between miR-186-5p and LncRNA PVT1 and HMGB1 was verified by double fluorescein experiment. Exosomes from M1φ were successfully extracted. The expression of LncRNA PVT1 in M1φ-exos was significantly increased. M1φ-exo promotes inflammation and pyroptosis of VSMCs. M1φsi-LncRNA PVT1-exos inhibited the inflammation and pyroptosis of VSMCs. LncRNA PVT1 can sponge miR-186-5p mimic to regulate HMGB1 expression. MiR-186-5p mimic further inhibited inflammation and pyroptosis induced by M1φsi-LncRNA PVT1-exos. However, oe-HMGB1 could inhibit the reversal effect of miR-186-5p mimic. LncRNA PVT1 in exosomes secreted by M1φ can regulate HMGB1 by acting as ceRNA on sponge miR-186-5p, thereby promoting cell inflammatory and pyroptosis and accelerating AAA progression.

Evaluation of the Existence of Post-COVID-19 Tachycardia in a Community Healthcare System.

Background: Post-coronavirus disease 2019 (COVID-19) syndrome derives from lingering symptoms after an acute COVID-19 infection. Palpitation was one of the most common symptoms of post-COVID-19 syndrome that correlated with objective data such as persisting sinus tachycardia; but to our best knowledge, there is a scarcity of research regarding the association of COVID-19 and sinus tachycardia in the post-acute setting. Therefore, the purpose was to identify if there is an association between COVID-19 infection and sinus tachycardia in the post-acute phase, namely post-COVID-19 tachycardia (PCT) other than inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS). Methods: This retrospective observational study entails 1,425 patients admitted for COVID-19 infection with the interest in finding an association with PCT. The prevalence of PCT was evaluated using descriptive statistics, predictions of patient characteristics and comorbidities were identified using multinomial logistic regression, and associations between patient comorbidities and characteristics were evaluated with corresponding Pearson Chi-square test and post hoc tests Phi and Cramer's V. Results: The percentage of patients with PCT in our sample of interest was an average of 28.18%. There was a strong association of PCT with patients of age group less than 65 years. Other clinical characteristics, such as shorter length of stay, unknown smoking status, and patients with commercial type insurance, had significant association with PCT. COVID-19 severity categorized as "less severe", readmission rates within 30 days, and patients with less comorbidities were more likely to be associated with PCT. Conclusions: PCT is likely a separate entity from IST and POTS, and an important entity under the umbrella of post-COVID-19 syndrome. It warrants further studies to elucidate the underlying pathophysiology and to confirm its presence as a distinct entity.

Strategies to Improve the Quantum Computation Accuracy for Electrochemical Windows of Ionic Liquids.

Rational design of ionic liquids (ILs) with wide electrochemical windows (ECWs) for high-voltage cathodes is essential to elevating the energy density of current rechargeable batteries. It is significant to determine appropriate strategies for accurately predicting the ECWs of ILs. In this study, we compare the calculated ECWs based on three quantum methods, including the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) method, the ionization potential-electron affinity (IP-EA) method, and the thermodynamic method, under four unique combinations of simulation environments, and assess the discrepancies between the calculated and the experimental results of ECWs. For the three quantum methods, although HOMO-LUMO and IP-EA methods show limited prediction accuracy compared to the experimental values, they can qualitatively rank the anodic limits of anions and the cathodic limits of cations. For the thermodynamic method, we demonstrate that the highest accuracy can be achieved by considering the most rational redox reaction process. By varying the calculation environments, the calculated ECWs tend to be underestimated by considering separate cations and anions of ILs under gas phase, whereas they always exhibit overestimated results when calculating based on the cation-anion pairs. When the computation considers isolated ions with the solvent model plus proper thermodynamic corrections, we observe improved consistency with the experimental results. Though all methods have limitations to achieving perfect predictions of ECWs, we believe rational selection of calculation methods based on application-oriented scenarios can balance the efficiency and accuracy of the results for the development of a high-throughput and accurate database of ECWs for ILs.

Predicting drug-induced liver injury using graph attention mechanism and molecular fingerprints.

Drug-induced liver injury (DILI) is a significant issue in drug development and clinical treatment due to its potential to cause liver dysfunction or damage, which, in severe cases, can lead to liver failure or even fatality. DILI has numerous pathogenic factors, many of which remain incompletely understood. Consequently, it is imperative to devise methodologies and tools for anticipatory assessment of DILI risk in the initial phases of drug development. In this study, we present DMFPGA, a novel deep learning predictive model designed to predict DILI. To provide a comprehensive description of molecular properties, we employ a multi-head graph attention mechanism to extract features from the molecular graphs, representing characteristics at the level of compound nodes. Additionally, we combine multiple fingerprints of molecules to capture features at the molecular level of compounds. The fusion of molecular fingerprints and graph features can more fully express the properties of compounds. Subsequently, we employ a fully connected neural network to classify compounds as either DILI-positive or DILI-negative. To rigorously evaluate DMFPGA's performance, we conduct a 5-fold cross-validation experiment. The obtained results demonstrate the superiority of our method over four existing state-of-the-art computational approaches, exhibiting an average AUC of 0.935 and an average ACC of 0.934. We believe that DMFPGA is helpful for early-stage DILI prediction and assessment in drug development.

Targeting integrin α5 in fibroblasts potentiates colorectal cancer response to PD-L1 blockade by affecting extracellular-matrix deposition.

BACKGROUND: One reason patients with cancer cannot benefit from immunotherapy is the lack of immune cell infiltration in tumor tissues. Cancer-associated fibroblasts (CAFs) are emerging as central players in immune regulation that shapes tumor microenvironment (TME). Earlier we reported that integrin α5 was enriched in CAFs in colorectal cancer (CRC), however, its role in TME and cancer immunotherapy remains unclear. Here, we aimed to investigate the role for integrin α5 in fibroblasts in modulating antitumor immunity and therapeutic efficacy combined with checkpoint blockade in CRC. METHODS: We analyzed the CRC single-cell RNA sequencing (scRNA-seq) database to define the expression of ITGA5 in CRC tumor stroma. Experimentally, we carried out in vivo mouse tumor xenograft models to confirm the targeting efficacy of combined α5ß1 inhibition and anti-Programmed death ligand 1 (PD-L1) blockade and in vitro cell-co-culture assay to investigate the role of α5 in fibroblasts in affecting T-cell activity. Clinically, we analyzed the association between α5 expression and infiltrating T cells and evaluated their correlation with patient survival and immunotherapy prognosis in CRC. RESULTS: We revealed that ITGA5 was enriched in FAP-CAFs. Both ITGA5 knockout fibroblasts and therapeutic targeting of α5 improved response to anti-PD-L1 treatment in mouse subcutaneous tumor models. Mechanistically, these treatments led to increased tumor-infiltrating CD8+ T cells. Furthermore, we found that α5 in fibroblasts correlated with extracellular matrix (ECM)-related genes and affected ECM deposition in CRC tumor stroma. Both in vivo analysis and in vitro culture and cell killing experiment showed that ECM proteins and α5 expression in fibroblasts influence T-cell infiltration and activity. Clinically, we confirmed that high α5 expression was associated with fewer CD3+ T and CD8+ T cells, and tissues with low α5 and high CD3+ T levels correlated with better patient survival and immunotherapy response in a CRC cohort with 29 patients. CONCLUSIONS: Our study identified a role for integrin α5 in fibroblasts in modulating antitumor immunity by affecting ECM deposition and showed therapeutic efficacy for combined α5ß1 inhibition and PD-L1 blockade in CRC.

Dietary Supplement with Tribulus terrestris L. Extract Exhibits Protective Effects on Ischemic Stroke Rats.

SCOPE: Among herbal dietary supplements, the extract of Tribulus terrestris L. (TT) has been used as a commercially registered product in multiple studies. The previous studies demonstrate the protective effect of gross saponins of TT (GSTTF) on ischemic stroke. However, the mechanism by which GSTTF protects against ischemic stroke is still unclear. METHODS AND RESULTS: The study applies molecular biology and unbiased transcriptomics to explore the pathways and targets underlying the therapeutic impact of GSTTF in treating ischemic stroke. The mRNA of brain tissues from different groups is analyzed using a transcriptomics method. The data reveal that treatment with GSTTF significantly reduces elevated CRP, IL-6, and Ca2+ levels induced by middle cerebral artery occlusion (MCAO). A total of 61 differentially expressed genes (DEGs) are identified, GSTTF is found to effectively reverse the abnormal mRNA expression levels in rat brain tissues affected by ischemic stroke models. These positive effects of GSTTF are likely achieved through the suppression of calcium ion and the MyD88/IKK/NF-κB signaling pathway. CONCLUSIONS: This study uncovers the mechanisms behind the efficacy of GSTTF in treating ischemic stroke, which not only expands its potential medicinal applications but also confirmed its potential as a dietary supplement.

Colorectal cancer-associated T cell receptor repertoire abnormalities are linked to gut microbiome shifts and somatic cell mutations.

As with many diseases, tumor formation in colorectal cancer (CRC) is multifactorial and involves immune, environmental factors and various genetics that contribute to disease development. Accumulating evidence suggests that the gut microbiome is linked to the occurrence and development of CRC, and these microorganisms are important for immune maturation. However, a systematic perspective integrating microbial profiling, T cell receptor (TCR) and somatic mutations in humans with CRC is lacking. Here, we report distinct features of the expressed TCRß repertoires in the peripheral blood of and CRC patients (n = 107) and healthy donors (n = 30). CRC patients have elevated numbers of large TCRß clones and they have very low TCR diversity. The metagenomic sequencing data showed that the relative abundance of Fusobacterium nucleatum (F. nucleatum), Escherichia coli and Dasheen mosaic virus were elevated consistently in CRC patients (n = 97) compared to HC individuals (n = 30). The abundance of Faecalibacterium prausnitzii and Roseburia intestinalis was reduced in CRC (n = 97) compared to HC (n = 30). The correlation between somatic mutations of target genes (16 genes, n = 79) and TCR clonality and microbial biomarkers in CRC had been investigated. Importantly, we constructed a random forest classifier (contains 15 features) based on microbiome and TCR repertoires, which can be used as a clinical detection method to screen patients for CRC. We also analysis of F. nucleatum-specific TCR repertoire characteristics. Collectively, our large-cohort multi-omics data aimed to identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC, which is of possible etiological and diagnostic significance.

Integrated prediction of water pollution and risk assessment of water system connectivity based on dynamic model average and model selection criteria.

In recent years, with the rapid development of economy and society, river water environmental pollution incidents occur frequently, which seriously threaten the ecological health of the river and the safety of water supply. Water pollution prediction is an important basis for understanding development trends of the aquatic environment, preventing water pollution incidents and improving river water quality. However, due to the large uncertainty of hydrological, meteorological and water environment systems, it is challenging to accurately predict water environment quality using single model. In order to improve the accuracy and stability of water pollution prediction, this study proposed an integrated learning criterion that integrated dynamic model average and model selection (DMA-MS) and used this criterion to construct the integrated learning model for water pollution prediction. Finally, based on the prediction results of the integrated learning model, the connectivity risk of the connectivity project was evaluated. The results demonstrate that the integrated model based on the DMA-MS criterion effectively integrated the characteristics of a single model and could provide more accurate and stable predictions. The mean absolute percentage error (MAPE) of the integrated model was only 11.1%, which was 24.5%-45% lower than that of the single model. In addition, this study indicates that the nearest station was the most important factor affecting the performance of the prediction station, and managers should pay increased attention to the water environment of the control section that is close to their area. The results of the connectivity risk assessment indicate that although the water environment risks were not obvious, the connectivity project may still bring some risks to the crossed water system, especially in the non-flood season.

[Efficacy and safety of multiple-dose intravenous tranexamic acid for reducing blood loss in complex tibial plateau fractures: A prospective randomized controlled trial].

Objective: To investigate the efficacy and safety of multiple-dose intravenous tranexamic acid (TXA) for reducing blood loss in complex tibial plateau fractures with open reduction internal fixation by a prospective randomized controlled trial. Methods: A study was conducted on patients with Schatzker type Ⅳ-Ⅵ tibial plateau fractures admitted between August 2020 and December 2022. Among them, 88 patients met the selection criteria and were included in the study. They were randomly allocated into 3 groups, the control group (28 cases), single-dose TXA group (31 cases), and multiple-dose TXA group (29 cases), using a random number table method. There was no significant difference ( P>0.05) in terms of age, gender, body mass index, the Schatzker type and side of fracture, laboratory examinations [hemoglobin (Hb), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), international normalized ratio (INR), D-dimer, and interleukin 6 (IL-6)], and preoperative blood volume. The control group received intravenous infusion of 100 mL saline at 15 minutes before operation and 3, 6, and 24 hours after the first administration. The single-dose TXA group received intravenous infusion of 1 g TXA (dissolved in 100 mL saline) at 15 minutes before operation, followed by an equal amount of saline at each time point after the first administration. The multiple-dose TXA group received intravenous infusion of 1 g TXA (dissolved in 100 mL saline) at each time point. The relevant indicators were recorded and compared between groups to evaluate the effectiveness and safety of TXA, including hospital stays, operation time, occurrence of infection; the occurrence of lower extremity deep vein thrombosis, intermuscular vein thrombosis, and pulmonary embolism at 1 week after operation; the lowest postoperative Hb value and Hb reduction rate, the difference (change value) between pre- and post-operative APTT, PT, Fib, and INR; D-dimer and IL-6 at 24 and 72 hours after operation; total blood loss, intraoperative blood loss, hidden blood loss, drainage flow during 48 hours after operation, and postoperative blood transfusion. Results: ① TXA efficacy evaluation: the lowest Hb value in the control group was significantly lower than that in the other two groups ( P<0.05), and there was no significant difference between the single- and multiple-dose TXA groups ( P>0.05). The Hb reduction rate, total blood loss, intraoperative blood loss, drainage flow during 48 hours after operation, and hidden blood loss showed a gradual decrease trend in the control group, single-dose TXA group, and multiple-dose TXA group. And differences were significant ( P<0.05) in the Hb reduction rate and drainage flow during 48 hours after operation between groups, and the total blood loss and hidden blood loss between control group and other two groups. ② TXA safety evaluation: no lower extremity deep vein thrombosis or pulmonary embolism occurred in the three groups after operation, but 3, 4, and 2 cases of intermuscular vein thrombosis occurred in the control group, single-dose TXA group, and multiple-dose TXA group, respectively, and the differences in the incidences between groups were not significant ( P>0.05). There was no significant difference in the operation time between groups ( P>0.05). But the length of hospital stay was significantly longer in the control group than in the other groups ( P<0.05); there was no significant difference between the single- and multiple-dose TXA groups ( P>0.05). ③ Effect of TXA on blood coagulation and inflammatory response: the incisions of the 3 groups healed by first intention, and no infections occurred. The differences in the changes of APTT, PT, Fib, and INR between groups were not significant ( P>0.05). The D-dimer and IL-6 in the three groups showed a trend of first increasing and then decreasing over time, and there was a significant difference between different time points in the three groups ( P<0.05). At 24 and 72 hours after operation, there was no significant difference in D-dimer between groups ( P>0.05), while there was a significant difference in IL-6 between groups ( P<0.05). Conclusion: Multiple intravenous applications of TXA can reduce perioperative blood loss and shorten hospital stays in patients undergoing open reduction and internal fixation of complex tibial plateau fractures, provide additional fibrinolysis control and ameliorate postoperative inflammatory response.

Identification of a Non-Invasive Urinary Exosomal Biomarker for Diabetic Nephropathy Using Data-Independent Acquisition Proteomics.

Diabetic nephropathy (DN), as the one of most common complications of diabetes, is generally diagnosed based on a longstanding duration, albuminuria, and decreased kidney function. Some patients with the comorbidities of diabetes and other primary renal diseases have similar clinical features to DN, which is defined as non-diabetic renal disease (NDRD). It is necessary to distinguish between DN and NDRD, considering they differ in their pathological characteristics, treatment regimes, and prognosis. Renal biopsy provides a gold standard; however, it is difficult for this to be conducted in all patients. Therefore, it is necessary to discover non-invasive biomarkers that can distinguish between DN and NDRD. In this research, the urinary exosomes were isolated from the midstream morning urine based on ultracentrifugation combined with 0.22 µm membrane filtration. Data-independent acquisition-based quantitative proteomics were used to define the proteome profile of urinary exosomes from DN (n = 12) and NDRD (n = 15) patients diagnosed with renal biopsy and Type 2 diabetes mellitus (T2DM) patients without renal damage (n = 9), as well as healthy people (n = 12). In each sample, 3372 ± 722.1 proteins were identified on average. We isolated 371 urinary exosome proteins that were significantly and differentially expressed between DN and NDRD patients, and bioinformatic analysis revealed them to be mainly enriched in the immune and metabolic pathways. The use of least absolute shrinkage and selection operator (LASSO) logistic regression further identified phytanoyl-CoA dioxygenase domain containing 1 (PHYHD1) as the differential diagnostic biomarker, the efficacy of which was verified with another cohort including eight DN patients, five NDRD patients, seven T2DM patients, and nine healthy people. Additionally, a concentration above 1.203 µg/L was established for DN based on the ELISA method. Furthermore, of the 19 significantly different expressed urinary exosome proteins selected by using the protein-protein interaction network and LASSO logistic regression, 13 of them were significantly related to clinical indicators that could reflect the level of renal function and hyperglycemic management.

Proteomics protocol for obtaining extracellular vesicle from human plasma using asymmetrical flow field-flow fractionation technology.

Plasma extracellular vesicles (EVs) represent a potential resource for biomarkers of multiple diseases. Here, we present a protocol for obtaining EVs from human plasma using asymmetrical flow field-flow fractionation technology. We describe steps for using tandem mass tags to perform comparative proteomic studies of a large clinical cohort. We then detail targeted quantitative analysis of differential proteins based on a parallel reaction monitoring technique. For complete details on the use and execution of this protocol, please refer to Wu et al. (2020)1 and Li et al. (2023).2.

Effects of bacteria on early-stage litter decomposition in Wudalianchi volcanic forest.

To understand the role of microorganisms in litter decomposition and nutrient cycling in volcanic forest ecosystem, we conducted in-situ litterbag decomposition experiment and used Illumina MiSeq high-throughput sequencing to analyze the response of bacterial community structure and diversity during the decomposition of litters from Larix gmelinii, Betula platyphylla and Populus davidiana, the dominant tree species in volcanic lava plateau of Wudalianchi. The results showed that mass remaining percentage of litters of three species after 18-month decomposition was 63.9%-68.1%. Litter of B. platyphylla decomposed the fastest, with significant difference in N, C:N, and N:P before and after decomposition. The richness of bacterial species and diversity index differed significantly among the three litters. Proteobacteria, Actinomycetes, and Bacteroidetes were the dominant bacterial groups at the phylum level, while Rhizobium, Sphingomonas, and Pseudomonas were the dominant groups at the genus level, with significant difference among the three litters. After 18 months, the dominant bacterial groups in litter tended to be consistent with those in volcanic lava platform soil. In the volcanic forest ecosystem, bacterial diversity and community structure were mainly affected by P, C:N, and N:P in the litter.

Carbon nanodots constructed by ginsenosides and their high inhibitory effect on neuroblastoma.

BACKGROUND: Neuroblastoma is one of the common extracranial tumors in children (infants to 2 years), accounting for 8 ~ 10% of all malignant tumors. Few special drugs have been used for clinical treatment currently. RESULTS: In this work, herbal extract ginsenosides were used to synthesize fluorescent ginsenosides carbon nanodots via a one-step hydrothermal method. At a low cocultured concentration (50 µg·mL- 1) of ginsenosides carbon nanodots, the inhibition rate and apoptosis rate of SH-SY5Y cells reached ~ 45.00% and ~ 59.66%. The in vivo experiments showed tumor volume and weight of mice in ginsenosides carbon nanodots group were ~ 49.81% and ~ 34.14% to mice in model group. Since ginsenosides were used as sole reactant, ginsenosides carbon nanodots showed low toxicity and good animal response. CONCLUSION: Low-cost ginsenosides carbon nanodots as a new type of nanomedicine with good curative effect and little toxicity show application prospects for clinical treatment of neuroblastoma. It is proposed a new design for nanomedicine based on bioactive carbon nanodots, which used natural bioactive molecules as sole source.

Machine learning-guided discovery of ionic polymer electrolytes for lithium metal batteries.

As essential components of ionic polymer electrolytes (IPEs), ionic liquids (ILs) with high ionic conductivity and wide electrochemical window are promising candidates to enable safe and high-energy-density lithium metal batteries (LMBs). Here, we describe a machine learning workflow embedded with quantum calculation and graph convolutional neural network to discover potential ILs for IPEs. By selecting subsets of the recommended ILs, combining with a rigid-rod polyelectrolyte and a lithium salt, we develop a series of thin (~50 µm) and robust (>200 MPa) IPE membranes. The Li|IPEs|Li cells exhibit ultrahigh critical-current-density (6 mA cm-2) at 80 °C. The Li|IPEs|LiFePO4 (10.3 mg cm-2) cells deliver outstanding capacity retention in 350 cycles (>96% at 0.5C; >80% at 2C), fast charge/discharge capability (146 mAh g-1 at 3C) and excellent efficiency (>99.92%). This performance is rarely reported by other single-layer polymer electrolytes without any flammable organics for LMBs.

Synthesis, isolation, characterization of C3-C11 bridge-bond isomer of paclitaxel and its antitumor effect via inducing A549 cells pyroptosis.

During the chemical manufacturing control processing of new paclitaxel formulations, a photodegradation impurity called C3-C11 bridge-bond isomer appeared. Our work describes the synthesis, isolation, purification, and structural characterization methods using four spectroscopies: FT-IR, UV, NMR (1H and 13 C), and LC-MS. In addition, we discovered that the C3-C11 bridge-bond isomer can promote A549 cells pyroptosis, and increase pyroptosis-related proteins, including cleaved-caspase 3, cleaved-PARP, GSDME-N, and lactate dehydrogenase, thus making it anti-tumor effects. The study offered data suggesting that the C3-C11 bridge bond isomer may be used as an anti-tumour drug in the future.

Differential proteomic patterns of plasma extracellular vesicles show potential to discriminate ß-thalassemia subtypes.

The observed specificity of ß-thalassemia-subtype phenotypes makes new diagnostic strategies that complement current screening methods necessary to determine each subtype and facilitate therapeutic regimens for different patients. Here, we performed quantitative proteomics of plasma-derived extracellular vesicles (EVs) of ß-thalassemia major (TM) patients, ß-thalassemia intermedia (TI) patients, and healthy controls to explore subgroup characteristics and potential biomarkers. Plasma quantitative proteomics among the same cohorts were analyzed in parallel to compare the biomarker potential of both specimens. EV proteomics showed significantly more abnormalities in immunity and lipid metabolism in TI and TM, respectively. The differential proteomic patterns of EVs were consistent with but more striking than those of plasma. Notably, we also found EV proteins to have a superior performance for discriminating ß-thalassemia subtypes. These findings allowed us to propose a diagnostic model consisting of five proteins in EVs with subtyping potential, demonstrating the ability of plasma-derived EVs for the diagnosis of ß-thalassemia patients.

Comprehensive Proteomics Analysis Identifies CD38-Mediated NAD+ Decline Orchestrating Renal Fibrosis in Pediatric Patients With Obstructive Nephropathy.

Obstructive nephropathy is one of the leading causes of kidney injury and renal fibrosis in pediatric patients. Although considerable advances have been made in understanding the pathophysiology of obstructive nephropathy, most of them were based on animal experiments and a comprehensive understanding of obstructive nephropathy in pediatric patients at the molecular level remains limited. Here, we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction and healthy kidney tissues. Intriguingly, the proteomics revealed extensive metabolic reprogramming in kidneys from individuals with ureteropelvic junction obstruction. Moreover, we uncovered the dysregulation of NAD+ metabolism and NAD+-related metabolic pathways, including mitochondrial dysfunction, the Krebs cycle, and tryptophan metabolism, which led to decreased NAD+ levels in obstructed kidneys. Importantly, the major NADase CD38 was strongly induced in human and experimental obstructive nephropathy. Genetic deletion or pharmacological inhibition of CD38 as well as NAD+ supplementation significantly recovered NAD+ levels in obstructed kidneys and reduced obstruction-induced renal fibrosis, partially through the mechanisms of blunting the recruitment of immune cells and NF-κB signaling. Thus, our work not only provides an enriched resource for future investigations of obstructive nephropathy but also establishes CD38-mediated NAD+ decline as a potential therapeutic target for obstruction-induced renal fibrosis.