Exosomes From Muscle-Derived Stem Cells Repair Peripheral Nerve Injury by Inhibiting Ferroptosis via the Keap1-Nrf2-Ho-1 Axis.

Currently, the clinical outcomes of peripheral nerve injuries are suboptimal, highlighting the urgent need to understand the mechanisms of nerve injury to enhance treatment strategies. Muscle-derived stem cells (MDSCs) are a diverse group of multipotent cells that hold promise for peripheral nerve regeneration due to their strong antioxidant and regenerative properties. Our research has revealed that severe ferroptosis occurs in the sciatic nerve and ipsilateral dorsal root ganglion following sciatic nerve injury. Interestingly, we have observed that MDSC-derived exosomes effectively suppress cell ferroptosis and enhance cell viability in Schwann cells and dorsal root ganglion cells. Treatment with exosomes led to increased expression of BDNF and P62 in Schwann cells, decreased expression of Keap1, Nrf2, and HO-1 in Schwann cells, and upregulated dorsal root ganglion cells. Rats treated with exosomes exhibited improvements in sciatic nerve function, sensitivity to stimuli, and reduced muscle atrophy, indicating a positive impact on post-injury recovery. In conclusion, our findings demonstrate the occurrence of ferroptosis in the sciatic nerve and dorsal root ganglion post-injury, with MDSC exosomes offering a potential therapeutic strategy by inhibiting ferroptosis, activating the Keap1-Nrf2-HO-1 pathway, and optimizing the post-injury repair environment.

Injectable Self-Healing Antibacterial Hydrogels with Tailored Functions by Loading Peptide Nanofiber-Biomimetic Silver Nanoparticles.

Polymer hydrogels find extensive application in biomedicine, serving specific purposes such as drug delivery, biosensing, bioimaging, cancer therapy, tissue engineering, and others. In response to the growing threat of bacterial infections and the escalating resistance to conventional antibiotics, this research introduces a novel injectable, self-healing antimicrobial hydrogel comprising bioactive aldolized hyaluronic acid (AHA) and quaternized chitosan (QCS). This designed QCS/AHA hydrogel incorporates self-assembling peptide nanofibers (PNFs) and small-sized silver nanoparticles (AgNPs) for tailored functionality. The resulting hybrid QCS/AHA/PNF/AgNPs hydrogel demonstrates impressive rheological characteristics, broad-spectrum antimicrobial efficacy, and high biocompatibility. Notably, its antimicrobial effectiveness against Escherichia coli and S. aureus surpasses 99.9%, underscoring its potential for treating infectious wounds. Moreover, the rheological analysis confirms its excellent shear-thinning and self-healing properties, enabling it to conform closely to irregular wound surfaces. Furthermore, the cytotoxicity assessment reveals its compatibility with human umbilical vein endothelial cells, exhibiting no significant adverse effects. The combined attributes of this bioactive QCS/AHA/PNF/AgNPs hydrogel position it as a promising candidate for antimicrobial applications and wound healing.

Cerebral circulation time on DSA after thrombectomy associated with hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: To investigate the association between cerebral circulation time (CCT) on digital subtraction angiography immediately after thrombectomy and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). METHODS: Retrospectively enrolled consecutive AIS patients presented with large vessel occlusion who received thrombectomy and achieved successful recanalization between January 2019 and June 2021. The time interval from the beginning of the siphon segment of internal carotid artery visualization until the end of the arterial phase during cerebral angiography was calculated as CCT. The independent association of CCT with HT was evaluated using logistic regression analyses. The receiver operating characteristic curve was analyzed to evaluate the association between CCT and HT. RESULTS: Two hundred and twenty-four patients were included, of whom 86 (38.4%) suffered HT. Compared with patients without HT, patients with HT were of advanced age, less commonly male, had more diabetes mellitus, had higher baseline National Institutes of Health Stroke Scale score, lower Alberta Stroke Program Early Computed Tomographic Score, and shorter CCT (P < 0.05). Multivariable logistic regression suggested that CCT was independently associated with HT (adjusted odds ratio, 0.170; 95% confidence interval, 0.004-0.450; P < 0.001). According to the receiver operating characteristic curve, the optimal cut-off value for the strong correlation between CCT and HT was 1.72 s, which had 76.6% sensitivity, 81.6% specificity, and the area under the curve was 0.846. CONCLUSION: Shorter post-thrombectomy CCT was independently associated with HT.

STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.

Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

Two New Alkaloids from Roots of Zea mays and Their Cytotoxic Activity against Hep3B and SW480 Cells.

Two undescribed alkaloids, along with seven known compounds, were isolated from the roots of Zea mays (RM). Their chemical structures were elucidated based on extensive analyses of HR-ESI-MS, 1D and 2D NMR, and CD spectra. Two new alkaloids exhibited moderate inhibition of Hep3B (IC50 values of 11.7±2.4 and 14.2±3.6 µM) and SW480 cells (IC50 values of 33.4±8.2 and 47.3±5.8 µM) compared to that of the positive control compound, Oxaliplatin, IC50 value of 8.4±1.7 and 45.8±5.6 µM, respectively.

By-Products of Zea mays L.: A Promising Source of Medicinal Properties with Phytochemistry and Pharmacological Activities: A Comprehensive Review.

Zea mays (Z. mays) is one of the main cereal crops in the world, and it's by-products have exhibited medicinal properties to explore. This article intends to review the chemical compositions and pharmacological activities of by-products of Z. mays (corn silks, roots, bract, stems, bran, and leaves) which support the therapeutic potential in the treatment of different diseases, with emphasis on the natural occurring compounds and detailed pharmacological developments. Based on this review, 231 natural compounds are presented. Among them, flavonoids, terpenes, phenylpropanoids, and alkaloids are the most frequently reported. The by-products of Z. mays possess diuretic effects, hepatoprotective, anti-diabetic, antioxidant, neuroprotective, anti-inflammatory, anti-cancer, plant protection activity, and other activities. This article reviewed the phytochemistry and pharmacological activities of Z. mays for comprehensive quality control and the safety and effectiveness to enhance future application.

Identification of Genes Associated with Prognosis and Immunotherapy Prediction in Triple-Negative Breast Cancer via M1/M2 Macrophage Ratio.

Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10-15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients.

Analyses on Clinical Efficacy of TIPS in the Treatment of Cirrhotic Portal Hypertension and Relevant Influencing Factors.

The study aimed to explore the clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in treating cirrhotic portal hypertension and relevant influencing factors. 100 patients with cirrhotic portal hypertension receiving TIPS in the 980 hospitals of PLA logistic force from January 2015 to January 2018 were enrolled. Blood was collected from patients to detect liver function indicators [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], renal function indicators [blood urea nitrogen (BUN) and creatinine (Cr)], glucose metabolism indicators [insulin and glucose (GLU)] and inflammatory factors [interleukin-6 (IL-6), IL-8 and CXCL9] before surgery and at1 and 6 month(s) after surgery. Surgical efficacy was evaluated. The physique of patients was examined. The portal venous pressure, diameter and hemorheological indicators of patients were measured. Additionally, postoperative complications and nursing satisfaction were observed. At 1 and 6 month(s) after an operation, the levels of AST, ALT, BUN, Cr, insulin, GLU and inflammatory factors IL-6, IL-8 and CXCL9 and the portal venous pressure were overtly reduced (p<0.05), the postoperative dry weight was increased (p<0.05), the postoperative nursing satisfaction was 97%, the patients with higher satisfaction had fewer complications (p<0.05), the diameter of the portal vein was notably lowered (p<0.05), while the blood flow rate was remarkably raised (p<0.05). After the application of TIPS in the treatment of cirrhotic portal hypertension, the liver function, renal function, glucose metabolism and portal venous pressure and flow rate of patients return to normal, and postoperative complications are clearly reduced after postoperative nursing, proving the overall efficacy. Hence, TIPS is worthy of popularization and application.

Molecular Characterization of an Isoflavone 2'-Hydroxylase Gene Revealed Positive Insights into Flavonoid Accumulation and Abiotic Stress Tolerance in Safflower.

Flavonoids with significant therapeutic properties play an essential role in plant growth, development, and adaptation to various environments. The biosynthetic pathway of flavonoids has long been studied in plants; however, its regulatory mechanism in safflower largely remains unclear. Here, we carried out comprehensive genome-wide identification and functional characterization of a putative cytochrome P45081E8 gene encoding an isoflavone 2'-hydroxylase from safflower. A total of 15 CtCYP81E genes were identified from the safflower genome. Phylogenetic classification and conserved topology of CtCYP81E gene structures, protein motifs, and cis-elements elucidated crucial insights into plant growth, development, and stress responses. The diverse expression pattern of CtCYP81E genes in four different flowering stages suggested important clues into the regulation of secondary metabolites. Similarly, the variable expression of CtCYP81E8 during multiple flowering stages further highlighted a strong relationship with metabolite accumulation. Furthermore, the orchestrated link between transcriptional regulation of CtCYP81E8 and flavonoid accumulation was further validated in the yellow- and red-type safflower. The spatiotemporal expression of CtCYP81E8 under methyl jasmonate, polyethylene glycol, light, and dark conditions further highlighted its likely significance in abiotic stress adaption. Moreover, the over-expressed transgenic Arabidopsis lines showed enhanced transcript abundance in OE-13 line with approximately eight-fold increased expression. The upregulation of AtCHS, AtF3'H, and AtDFR genes and the detection of several types of flavonoids in the OE-13 transgenic line also provides crucial insights into the potential role of CtCYP81E8 during flavonoid accumulation. Together, our findings shed light on the fundamental role of CtCYP81E8 encoding a putative isoflavone 2'-hydroxylase via constitutive expression during flavonoid biosynthesis.

CoS2 /N-Doped Hollow Spheres as an Anode Material for High-Performance Sodium-Ion Batteries.

In this work, we first synthesized polyacrylic acid (PAA) spheres and then used PAA as a template to load Co(OH)2 particles onto its surface. The product of CoS2 nanoparticles dispersed in N-doped hollow spheres (N-HCS) was prepared through sulfurization treatment (CoS2 /S@N-HCS). During the sulfuration process, sulfur penetrates into the PAA, embedding into the graphite layer along with the carbonization process. It was found that during the charging and discharging process, the sulfur in the carbon layer will gradually dissolve out, thereby forming new ion diffusion channels in the carbon spheres and exposing more CoS2 active sites. The CoS2 /S@N-HCS composite exhibits a specific capacity of 729.6 mAh g-1 after 500 cycles at a current density of 1 A g-1 . The sodium-storage mechanism and reaction kinetics of the materials were further measured by in-situ electrochemical impedance spectroscopy, ex-situ X-ray diffraction, capacitance performance evaluation, and galvanostatic intermittent titration technique. The excellent cycling performance and rate capability demonstrated that the CoS2 /S@N-HCS is a potential and prospective anode material for sodium-ion batteries.

Association of the IL-6 Rs1800796 SNP with Concentration/dose Ratios of Tacrolimus and Donor Liver Function after Transplantation.

Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a range of important roles such as in inflammation, immune response, and cell growth regulation. Here, we aimed to assess the potential influence of the IL-6 single nucleotide polymorphism (SNP) rs1800796 on the concentration/dose (C/D) ratios of tacrolimus and donor liver function in Chinese liver transplant patients. A total of 331 liver transplant patients were included in this study. The C/D ratios and the ALT, AST, T-BIL, ALP, and GGT levels were analyzed at different time points in patients with and without the IL-6 rs1800796 SNP. The IL-6 rs1800796 polymorphism in recipients was found to be correlated with the C/D ratios of tacrolimus at months 2 to month 6 after transplantation. Also, the rs1800796 SNP in donors was found to influence liver function (shown in the data of ALT, AST, T-BIL, ALP and GGT) in recipients at the early post-transplant stage after transplantation. In conclusion, the IL-6 rs1800796 polymorphism was associated with the C/D ratios of tacrolimus and post-transplant donor liver function.

Evaluation of ibuprofen contamination in local urban rivers and its effects on immune parameters of juvenile grass carp.

Ibuprofen as a non-steroidal anti-inflammatory drug can be detected in the aquatic environments all over the world. This study evaluated the effects of ibuprofen on the immune parameters of juvenile grass carp at the concentration in real environments which were determined by detecting its concentrations in the surface water of local rivers. The concentration of ibuprofen ranged from 13.2 to 95.5 ng/L with a mean value of 47.9 ng/L in the surface water of local rivers detected by solid-phase extraction followed by LC-MS/MS analysis. Accordingly, juvenile grass carp were exposed to 4.8, 48.0 and 480.0 ng/L of ibuprofen for 14 days. The serum lysozyme activity of these fish decreased, while the serum creatinine levels were not affected after the exposure. Moreover, the mRNA expression of interleukin 6 in the skin and interleukin 1 beta and tumor necrosis factor alpha in the gills was enhanced by this exposure. These results collectively suggest that ibuprofen at environmentally relevant concentration can affect the immune parameters of juvenile grass carp, providing an insight into the possibility of this contaminant to modify the immunostatus of fish.

The PI3Kα inhibitor DFX24 suppresses tumor growth and metastasis in non-small cell lung cancer via ERK inhibition and EPHB6 reactivation.

EPHB6 is a metastasis inhibitory gene that is frequently decreased or deficiency in non-small cell lung cancer (NSCLC), which contributed to the subsequent development of distant metastasis. These suggested the possibility that reactivation of EPHB6 might prevent the metastasis of NSCLC. Nevertheless, EPHB6 expression might also promote cancer cell growth and inhibit cell apoptosis by activating Akt and ERK pathway, apart from inhibition of migration and invasion. In the present study, we developed a novel quinazolin-4(3H)-one analog (DFX24) as a potential PI3Kα inhibitor, which inhibited both cell proliferation and metastasis of NSCLC cell lines. Investigation to the molecular mechanisms revealed DFX24 inhibited the cell growth and metastasis via inhibition of PI3Kα and ERK activity, as well as the increase in EPHB6 expression. In addition, DFX24 also induced cell cycle arrest and tumor cell apoptosis by inhibiting PI3K/Akt pathway and activating mitochondria-dependent pathway, respectively. These findings suggested that DFX24 might be considered as a novel drug candidate and may provide a potential therapy for NSCLC.

Investigating the mechanism of ShuFeng JieDu capsule for the treatment of novel Coronavirus pneumonia (COVID-19) based on network pharmacology.

ShuFeng JieDu capsule (SFJDC), a traditional Chinese medicine, has been recommended for the treatment of COVID-19 infections. However, the pharmacological mechanism of SFJDC still remains vague to date. The active ingredients and their target genes of SFJDC were collected from TCMSP. COVID-19 is a type of Novel Coronavirus Pneumonia (NCP). NCP-related target genes were collected from GeneCards database. The ingredients-targets network of SFJDC and PPI networks were constructed. The candidate genes were screened by Venn diagram package for enrichment analysis. The gene-pathway network was structured to obtain key target genes. In total, 124 active ingredients, 120 target genes of SFJDC and 251 NCP-related target genes were collected. The functional annotations cluster 1 of 23 candidate genes (CGs) were related to lung and Virus infection. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the key target genes. The results suggested that SFJDC cloud be treated COVID-19 by multi-compounds and multi-pathways, and this study showed that the mechanism of traditional Chinese medicine (TCM) in the treatment of disease from the overall perspective.

Analysis of inflammatory parameters and disease severity for 88 hospitalized COVID-19 patients in Wuhan, China.

Background and aim: The outbreak of coronavirus disease 2019 (COVID-19) is quickly turning into a pandemic. We aimed to further clarify the clinical characteristics and the relationship between these features and disease severity. Methods: In this retrospective single-center study, demographic, clinical and laboratory data were collected and analyzed among moderate, severe and critically ill group patients. Results: 88 hospitalization patients confirmed COVID-19 were enrolled in this study. The average age of the patients was 57.11 years (SD, ±15.39). Of these 88 patients, the median body mass index (BMI) was 24.03 (IQR, 21.64-26.61; range 15.05-32.39), the median duration from disease onset to hospital admission were 11 days (IQR, 6.50-14.50). 46.59% patients had one or more comorbidities, with hypertension being the most common (26.14%), followed by diabetes mellitus (12.50%) and coronary atherosclerotic heart disease (CAD) (7.95%). Common symptoms at onset of disease were fever (71.59%), cough (59.09%), dyspnea (38.64%) and fatigue (29.55%). 88 patients were divided into moderate (47 [53.41%]), severe (32 [36.36%]) and critically ill (9 [10.23%]) groups. Compared with severe and moderate patients, lymphocytopenia occurred in 85.71% critically ill patients, and serum IL-2R, IL-6, IL-8, TNF-α, LDH, and cTnI were also increased in 71.42%, 83.33%, 57.14%, 71.43%, 100% and 42.86% in critically ill patients. Through our analysis, the age, comorbidities, lymphocyte count, eosinophil count, ferritin, CRP, LDH, PT and inflammatory cytokines were statistically significant along with the disease severity. Conclusion: We found some clinical characteristic and inflammatory cytokines could reveal the severity of COVID-19 during the outbreak phage. Our research could assist the clinicians recognize severe and critically ill patients timely and focus on the expectant treatment for each patient.

Morphological variation in Cynodon dactylon (L.) Pers., and its relationship with the environment along a longitudinal gradient.

BACKGROUND: Geographical variation in morphological traits may reflect evolutionary patterns of morphological adaptability along environmental gradients. Comprehensive information on longitudinal patterns of morphological trait variation is very meaningful to explore morphological diversity and evolutionary trends in widespread bermudagrass. METHODS: To explore the spatial patterns of morphological traits, we investigated 10 morphological traits of bermudagrass and 10 soil nutrient indexes and collected local climate data for 13 different regions from 119°E to 105°E along the latitude 34°N. RESULTS: Considerable variations in morphological traits were observed at different longitudes, and the variations in most of the evaluated traits within populations were lower than those among populations. All of the 13 different longitudinal sites were divided into three groups based on morphological traits by cluster analysis. The major sources of diversity at the different longitudes were leaf length of the erect shoot, leaf width of the erect shoot, and the internode lengths of the erect shoot and stolon as determined by principal component analysis. Pearson correlation analysis also indicated that longitude was significantly and negatively correlated with these traits as well. Mean average rainfall was significantly correlated with leaf length of the erect shoot and the internode lengths of the erect shoot and stolon, while mean average temperature was only significantly correlated with internode length of the erect shoots. Available sulfur was significantly correlated with internode length of the erect shoot, plant height, and reproductive branch height, while the exchangeable Ca was significantly correlated with internode lengths of the erect shoot and stolon. Soil pH was significantly correlated with the internode length of the stolon. Longitude is an important factor that affects morphological trait variation in wild bermudagrass, and the leaves of the erect shoot and the internode length enlarged significantly with the collection sites moving from east to west. CONCLUSION: Different combinations and interactions of environmental factors (soil and climate) along a longitudinal gradient may have strong effects on one or more morphological traits of bermudagrass.

Determination of Eight Coccidiostats in Eggs by Liquid-Liquid Extraction-Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry.

A method for the simultaneous determination of robenidine, halofuginone, lasalocid, monensin, nigericin, salinomycin, narasin, and maduramicin residues in eggs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The sample preparation method used a combination of liquid-liquid extraction (LLE) and solid-phase extraction (SPE) technology to extract and purify these target compounds from eggs. The target compounds were separated by gradient elution using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC). Tandem mass spectrometry was used to quantitatively and qualitatively analyze the target compounds via electrospray ionization (ESI+) and multiple reaction monitoring mode. The HPLC-MS/MS and UPLC-MS/MS methods were validated according to the requirements defined by the European Union and the Food and Drug Administration. The limits of detection and limits of quantification of the eight coccidiostats in eggs were 0.23-0.52 µg/kg and 0.82-1.73 µg/kg for HPLC-MS/MS, and 0.16-0.42 µg/kg and 0.81-1.25 µg/kg for UPLC-MS/MS, respectively. The eggs were spiked with four concentrations of the eight coccidiostats, and the HPLC-MS/MS and UPLC-MS/MS average recoveries were all higher than 71.69% and 72.26%, respectively. Compared with the HPLC-MS/MS method, utilizing UPLC-MS/MS had the advantages of low reagent consumption, a short detection time, and high recovery and precision. Finally, the HPLC-MS/MS and UPLC-MS/MS methods were successfully applied to detect eight coccidiostats in 40 eggs.

Interactions between PHD3-Bromo of MLL1 and H3K4me3 Revealed by Single-Molecule Magnetic Tweezers in a Parallel DNA Circuit.

Single-molecule force spectroscopy is a powerful tool to directly measure protein-protein interactions (PPI). The high specificity and precision of PPI measurements made it possible to reveal detailed mechanisms of intermolecular interactions. However, protein aggregation due to specific or nonspecific interactions is among the most challenging problems in PPI examination. Here, we propose a strategy of a parallel DNA circuit to probe PPI using single-molecule magnetic tweezers. In contrast to PPI examination using atomic force microscopy, microspheres as probes used in magnetic tweezers avoided the single-probe issue of a cantilever. Negatively charged DNA as a linker circumvented the severe aggregation in the PPI construct with a protein linker. The unnatural amino acid encoded in proteins of interest expanded the choices of biorthogonal conjugation. We demonstrated how to apply our strategy to probe the PPI between the PHD3-Bromo and the histone H3 methylated at K4, a critical epigenetic event in leukemia development. We found a rupture force of 12 pN for breaking the PPI, which is much higher than that required to peel DNA off from a nucleosome, 3 pN. We expect that our methods will make PPI measurements of mechanics and kinetics with great precision, facilitating PPI-related research, e.g., PPI-targeted drug discovery.

Joint skeleton estimation of multiple directed acyclic graphs for heterogeneous population.

The directed acyclic graph (DAG) is a powerful tool to model the interactions of high-dimensional variables. While estimating edge directions in a DAG often requires interventional data, one can estimate the skeleton of a DAG (i.e., an undirected graph formed by removing the direction of each edge in a DAG) using observational data. In real data analyses, the samples of the high-dimensional variables may be collected from a mixture of multiple populations. Each population has its own DAG while the DAGs across populations may have significant overlap. In this article, we propose a two-step approach to jointly estimate the DAG skeletons of multiple populations while the population origin of each sample may or may not be labeled. In particular, our method allows a probabilistic soft label for each sample, which can be easily computed and often leads to more accurate skeleton estimation than hard labels. Compared with separate estimation of skeletons for each population, our method is more accurate and robust to labeling errors. We study the estimation consistency for our method, and demonstrate its performance using simulation studies in different settings. Finally, we apply our method to analyze gene expression data from breast cancer patients of multiple cancer subtypes.

α-Tetralonyl Glucosides from the Green Walnut Husks of Juglans mandshurica and Their Antiproliferative Effects.

Two new α-tetralonyl glucosides, (4S)-4,5,8-trihydroxy-α-tetralone-5-O-ß-D-glucopyranosyl(1 → 6)-ß-D-glucopyranoside (1: ) and (4S)-4,8-dihydroxy-α-tetralone-4-O-ß-D-glucopyranosyl(1 → 6)-ß-D-glucopyranoside (2: ), together with eight known compounds (3:  - 10: ) were isolated from the green walnut husks of Juglans mandshurica. The structural characterization of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HR-ESI-MS experiments. The isolated compounds were assayed for their cytotoxicity against two human cancer cell lines, A549 and HeLa. Four compounds (7:  - 10: ) exhibited inhibitory effects against two human cancer cell lines with GI50 values between 1.3 and 5.8 µM.