Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A.

Albeit N1-Methyladenosine (m1A) RNA modification represents an important regulator of RNA metabolism, the role of m1A modification in carcinogenesis remains enigmatic. Herein, we found that histone lactylation enhances ALKBH3 expression and simultaneously attenuates the formation of tumor-suppressive promyelocytic leukemia protein (PML) condensates by removing the m1A methylation of SP100A, promoting the malignant transformation of cancers. First, ALKBH3 is specifically upregulated in high-risk ocular melanoma due to excessive histone lactylation levels, referring to m1A hypomethylation status. Moreover, the multiomics analysis subsequently identified that SP100A, a core component for PML bodies, serves as a downstream candidate target for ALKBH3. Therapeutically, the silencing of ALKBH3 exhibits efficient therapeutic efficacy in melanoma both in vitro and in vivo, which could be reversed by the depletion of SP100A. Mechanistically, we found that YTHDF1 is responsible for recognition of the m1A methylated SP100A transcript, which increases its RNA stability and translational efficacy. Conclusively, we initially demonstrated that m1A modification is necessary for tumor suppressor gene expression, expanding the current understandings of dynamic m1A function during tumor progression. In addition, our results indicate that lactylation-driven ALKBH3 is essential for the formation of PML nuclear condensates, which bridges our knowledge of m1A modification, metabolic reprogramming, and phase-separation events.

Engineered bone marrow mesenchymal stem cell-derived exosomes loaded with miR302 through the cardiomyocyte specific peptide can reduce myocardial ischemia and reperfusion (I/R) injury.

BACKGROUND: MicroRNA (miRNA)-based therapies have shown great potential in myocardial repair following myocardial infarction (MI). MicroRNA-302 (miR302) has been reported to exert a protective effect on MI. However, miRNAs are easily degraded and ineffective in penetrating cells, which limit their clinical applications. Exosomes, which are small bioactive molecules, have been considered as an ideal vehicle for miRNAs delivery due to their cell penetration, low immunogenicity and excellent stability potential. Herein, we explored cardiomyocyte-targeting exosomes as vehicles for delivery of miR302 into cardiomyocyte to potentially treat MI. METHODS: To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered exosomes with cardiomyocyte specific peptide (CMP, WLSEAGPVVTVRALRGTGSW). Afterwards, the engineered exosomes were characterized and identified using transmission electron microscope (TEM) and Nanoparticle Tracking Analysis (NTA). Later on, the miR302 mimics were loaded into the engineered exosomes via electroporation technique. Subsequently, the effect of the engineered exosomes on myocardial ischemia and reperfusion (I/R) injury was evaluated in vitro and in vivo, including MTT, ELISA, real-time quantitative polymerase chain reaction (PCR), western blot, TUNNEL staining, echocardiogram and hematoxylin and eosin (HE) staining. RESULTS: Results of in vitro experimentation showed that DSPE-PEG-CMP-EXO could be more efficiently internalized by H9C2 cells than unmodified exosomes (blank-exosomes). Importantly, compared with the DSPE-PEG-CMP-EXO group, DSPE-PEG-CMP-miR302-EXO significantly upregulated the expression of miR302, while exosomes loaded with miR302 could enhance proliferation of H9C2 cells. Western blot results showed that the DSPE-PEG-CMP-miR302-EXO significantly increased the protein level of Ki67 and Yap, which suggests that DSPE-PEG-CMP-miR302-EXO enhanced the activity of Yap, the principal downstream effector of Hippo pathway. In vivo, DSPE-PEG-CMP-miR302-EXO improved cardiac function, attenuated myocardial apoptosis and inflammatory response, as well as reduced infarct size significantly. CONCLUSION: In conclusion, our findings suggest that CMP-engineered exosomes loaded with miR302 was internalized by H9C2 cells, an in vitro model for cardiomyocytes coupled with potential enhancement of the therapeutic effects on myocardial I/R injury.

Dimethyl Carbonate Synthesis from CO2 over CeO2 with Electron-Enriched Lattice Oxygen Species.

Direct synthesis of dimethyl carbonate (DMC) from CO2 plays an important role in carbon neutrality, but its efficiency is still far from the practical application, due to the limited understanding of the reaction mechanism and rational design of efficient catalyst. Herein, abundant electron-enriched lattice oxygen species were introduced into CeO2 catalyst by constructing the point defects and crystal-terminated phases in the crystal reconstruction process. Benefitting from the acid-base properties modulated by the electron-enriched lattice oxygen, the optimized CeO2 catalyst exhibited a much higher DMC yield of 22.2 mmol g-1 than the reported metal-oxide-based catalysts at the similar conditions. Mechanistic investigations illustrated that the electron-enriched lattice oxygen can provide abundant sites for CO2 adsorption and activation, and was advantageous of the formation of the weakly adsorbed active methoxy species. These were facilitating to the coupling of methoxy and CO2 for the key *CH3OCOO intermediate formation. More importantly, the weakened adsorption of *CH3OCOO on the electron-enriched lattice oxygen can switch the rate-determining-step (RDS) of DMC synthesis from *CH3OCOO formation to *CH3OCOO dissociation, and lower the corresponding activation barriers, thus giving rise to a high performance. This work provides insights into the underlying reaction mechanism for DMC synthesis from CO2 and methanol and the design of highly efficient catalysts.

Disrupting methyl-CpG-binding protein 2 expression induces the transformation of induced pluripotent stem cell cardiomyocytes into pacemaker-like cells by insulin gene enhancer binding protein 1.

BACKGROUND: The experiment will explore whether interfering with the expression of methyl-CpG-binding protein 2 (MecP2) can enhance the ability of insulin gene enhancer binding protein 1 (ISL1) to induce iPSC-CMs to differentiate into pacemaker-like cells. METHODS: Differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes (CMs) can be induced via the regulation of the Wnt signaling pathway. Real-time quantitative PCR (qPCR), western blotting, immunofluorescence staining, and patch-clamp technique were used to analyze the ability of ISL1 to induce the transformation of iPSC-CMs into pacemaker-like cells. Calcium spark, patch-clamp technique, and real-time qPCR were used to verify whether disrupting the expression of MeCP2 enhanced this ability of ISL1 to induce the differentiation of iPSC-CMs into pacemaker cells. Transplant pacemaker-like cardiomyocytes into the myocardium of mice to observe whether the pacemaker cells can survive in the tissue for a long time. RESULTS: RT-qPCR and patch-clamp analyses showed that overexpression of ISL1 induced the successful differentiation of iPSC-CMs into pacemaker cells. ISL1-overexpressing pacemaker-like cells possessed typical characteristics of pacemaker morphology, including action potential and If inward current. Chromatin immunoprecipitation results showed that MeCP2 bound to the promoter region of HCN4. Following disruption of MeCP2 expression, the gene expression of sinoatrial node-specific transcription factors, If inward current, and cardiac rhythm changes in iPSC-CMs resembled those of sinoatrial node pacemaker cells. Therefore, ISL1 induced the differentiation of iPSC-CMs into pacemaker-like cells, and knockdown of MeCP2 increased this effect. Frozen section results showed that surviving pacemaker-like cells could still be observed in myocardial tissue after 45 days. CONCLUSIONS: Experiments have found that interfering with the expression of MeCP2 can increase the ability of ISL1 to induce iPSC-CM cells to differentiate into pacemaker-like cells. And the pacemaker-like cells obtained in this experiment can survive in myocardial tissue for a long time.

Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation.

BACKGROUND: The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking. AIM: We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients. METHOD: Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events. RESULTS: Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke. CONCLUSION: Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

Orthogonal polarization multi-wavelength Brillouin random fiber laser with triple Brillouin frequency shift space.

A novel multi-wavelength Brillouin random fiber laser with the channel space of triple Brillouin frequency shift and high polarization orthogonality between adjacent wavelengths (TOP-MWBRFL), to the best of our knowledge, is experimentally demonstrated. The TOP-MWBRFL is structured in a ring form by cascading two Brillouin random cavities of single-mode fiber (SMF) and one Brillouin random cavity of polarization-maintaining fiber (PMF). Based on polarization pulling properties of stimulated Brillouin scattering in long-distance SMFs and PMFs, the states of polarization (SOPs) of lasing light from SMF random cavities are linearly bounded to the SOPs of local pump light, whereas the SOP of lasing light from the PMF random cavity is strictly clamped on one of the principal axes of the PMF. Thus, the TOP-MWBRFL can stably emit multi-wavelength light with high polarization extinction ratio (>35d B) between adjacent wavelengths without precise polarization feedback. In addition, the TOP-MWBRFL can also work in one polarization mode to stably lase multi-wavelength light with SOP uniformity as high as 37 dB.

Publication Trends of Research on Head and Neck Squamous Cell Carcinoma During 2002 to 2022: A 20-Year Bibliometric Study.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Our study attempted to analyze the research trends in HNSCC and compare contributions from different countries, institutions, journals, and authors. MATERIALS AND METHODS: The authors extracted publications in this field from 2002 to 2022 from the Web of Science database. Microsoft Excel and VOSviewer were performed to collect data on publication numbers, analyze publication trends, and visualize relevant results. RESULTS: A total of 1903 publications were screened. In the past 20 years, the United States contributed the most publications and citations in the HNSCC research. China ranked second in the number of publications. The Ophthalmic Plastic and Reconstructive Surgery was the most productive journal concerning HNSCC. ESMAELIB of the University of Texas System and ROSENTHAL EL of Stanford University had published the most publications in this field. Keywords were categorized into 3 clusters: basic study, clinical feature study, and treatment-related study. The keywords "reflectance confocal microscopy", "raman-spectroscopy", and "confocal laser endomicroscopy" were most frequently emerged in the recent years. Management-related research has been recognized as a potential focus in the HNSCC.

[Advances in pharmacological effects of jujuboside B].

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.

Insights into the Diffusion Behaviors of Water over Hydrophilic/Hydrophobic Catalysts During the Conversion of Syngas to High-Quality Gasoline.

Although considerable efforts towards directly converting syngas to liquid fuels through Fischer-Tropsch synthesis have been made, developing catalysts with low CO2 selectivity for the synthesis of high-quality gasoline remains a big challenge. Herein, we designed a bifunctional catalyst composed of hydrophobic FeNa@Si-c and HZSM-5 zeolite, which exhibited a low CO2 selectivity of 14.3 % at 49.8 % CO conversion, with a high selectivity of 62.5 % for gasoline in total products. Molecular dynamic simulations and model experiments revealed that the diffusion of water molecules through hydrophilic catalyst was bidirectional, while the diffusion through hydrophobic catalyst was unidirectional, which were crucial to tune the water-gas shift reaction and control CO2 formation. This work provides a new fundamental understanding about the function of hydrophobic modification of catalysts in syngas conversion.

The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Exosome-derived miR-127-5p promotes embryonic-like stem cells differentiation into pacemaker cell through NKx2.5 down-regulation.

Available evidence suggests the involvement of microRNAs (miRNAs) in the pathological process of several diseases. Nonetheless, molecular mechanism underlying biological effects of miRNAs such as pacemaker exosome-derived miR-127-5p in embryonic-like stem cells (ESCs) differentiation into pacemaker cell is yet to be clarified. Through real time quantitative polymerase chain reaction (qPCR) or western blotting (WB) techniques, levels of miRNAs, miR-127-5p, and NKx2.5 expressions were quantitatively measured. Cellular differentiation (CD) was probed with flow cytometric (FC) and WB techniques. Prediction of miR-127-5p association with NKx2.5 was studied through bioinformatics tools before verification with luciferase assays. Promotion of ESCs differentiation to pacemaker through miR-127-5p was measured with qPCR and WB techniques. Through the same assaying methods, up-regulation of pace-making genes (Shox2, HCN4, Cx45, Tbx3 and Tbx18) expression was observed in Nkx2.5 knockdown group. However, Nkx2.5 expression was down-regulated during differentiation of pacemaker-like cells into ESCs. Furthermore, techniques (such as qPCR, WB, immunofluorescent staining and FC) were employed to demonstrate that overexpressed miR-127-5p could suppress NKx2.5 expression. Through NKx2.5 targeting, ESCs could be differentiated into pacemaker-like cells with miR-127-5p possibly serving as a crucial positive regulator. On the account of our findings, further researches are needed to unearth the possible underlying mechanism and role of exosome-derived miRNAs in cell signaling.

m6A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common and deadly eye cancer in adults. Both UM and CM originate from melanocytes and exhibit an aggressive growth pattern with high rates of metastasis and mortality. The integral membrane glycoprotein beta-secretase 2 (BACE2), an enzyme that cleaves amyloid precursor protein into amyloid beta peptide, has been reported to play a vital role in vertebrate pigmentation and metastatic melanoma. However, the role of BACE2 in ocular melanoma remains unclear. In this study, we showed that BACE2 was significantly upregulated in ocular melanoma, and inhibition of BACE2 significantly impaired tumor progression both in vitro and in vivo. Notably, we identified that transmembrane protein 38B (TMEM38B), whose expression was highly dependent on BACE2, modulated calcium release from endoplasmic reticulum (ER). Inhibition of the BACE2/TMEM38B axis could trigger exhaustion of intracellular calcium release and inhibit tumor progression. We further demonstrated that BACE2 presented an increased level of N6-methyladenosine (m6A) RNA methylation, which led to the upregulation of BACE2 mRNA. To our knowledge, this study provides a novel pattern of BACE2-mediated intracellular calcium release in ocular melanoma progression, and our findings suggest that m6A/BACE2/TMEM38b could be a potential therapeutic axis for ocular melanoma.

Combined homocysteine and apoE rs429358 and rs7412 polymorphism in association with serum lipid levels and cognition in Chinese community-dwelling older adults.

BACKGROUND: ApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults. METHODS: A cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements. RESULTS: Participants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p <  0.05). Cognition of the subjects was found to be significantly associated with high serum tHcy level and ApoE genetic polymorphism (p <  0.05). Independent of age, BMI, education levels, smoking and alcohol drinking, the worst cognitive ability were detected in the high serum tHcy level subjects with ApoE rs429358C/T and rs7412 C/T as compare with other groups, especially orientation function, memory and delayed recall ability and attention ability. CONCLUSION: High serum tHcy level in combination with ApoE rs429358 and rs7412 variants might be linked with serum lipid levels and cognition, particularly for orientation function and memory and delayed recall ability in old Chinese adults.

A frailty index based on routine laboratory data predicts increased risk of mortality in Chinese community-dwelling adults aged over 55 years: a five-year prospective study.

BACKGROUND: Frailty can be operationalized based on the accumulation of deficits using a frailty index (FI) and is associated with an increased risk of adverse health outcomes. Here, we aim to compare validity of a FI from laboratory data with that of the common clinical FI for prediction of mortality in adults aged 55 + years, also examine whether combined FI could improve identification of adults aged 55 + years at increased risk of death. METHODS: Data for this analysis were obtained from the Beijing Longitudinal Study of Aging that involved 1,257 community-dwelling Chinese people, aged 55 + years at baseline. The main outcome measure was 5-year mortality. An FI-self-report based on 30 self-reported health-related data was constructed. An FI-lab was developed using laboratory data, in addition to pulse, systolic and diastolic blood pressure, pulse pressure, body mass index (BMI) and waist. A combined FI comprised all items from each FI. Kaplan-Meier survival curve and Cox proportional hazards models were performed to evaluate the risk of each FI on death. The area under receiver operating characteristic(ROC) curves were used to compare the discriminative performance of each FI. RESULTS: Of 1257 participants, 155 died and 156 lost at the end of the 5-year follow-up. The mean FI-self-report score was 0.11 ± 0.10, the FI-lab score was 0.33 ± 0.14 and FI-combined score was 0.19 ± 0.09. Higher frailty level defined by each FI was associated with higher risk of death. After adjustment for age and sex, Cox proportional hazards models showed that the higher scores of frailty were associated with a higher risk of mortality for each FI, the hazard ratios for the FI-self-report and FI-lab and FI-combined were 1.04 (1.03 to 1.05) and 1.02 (1.01 to 1.03) and 1.05 (1.04 to 1.07), respectively. The areas under the ROC curve were 0.79 (0.77-0.82) for the FI-self-report, 0.77(0.75-0.80) for the FI-lab and 0.81(0.78-0.82) for FI-combined. CONCLUSIONS: A FI from laboratory data can stratify older adults at increased risk of death alone and in combination with FI based on self-report data. Assessment in clinical settings of creating an FI using routine collected laboratory data needs to be further developed.

Presence, sources, and risk assessment of heavy metals in the upland soils of northern China using Monte Carlo simulation.

The spatial dynamics of heavy metal contamination in the upland soils of northern China are relatively unknown, despite the region's high contribution to the national grain output. In this study, the concentrations of As, Cd, Co, Cr, Cu, Mn, Pb, Sb, Sc, Ti, and Zn and subsequent ecological and human health risks were investigated in three major grain producing areas (Hexi Corridor, L1; Hetao irrigation area, L2; and eastern Inner Mongolia, L3) of northern China. Among the heavy metals, Ti had the highest average concentration of 3.02 g/kg, followed by Mn (470 mg/kg), Cr (56.6 mg/kg), Zn (34.3 mg/kg), Pb (19.4 mg/kg), Cu (17.8 mg/kg), Co (9.66 mg/kg), Sc (7.26 mg/kg), As (5.35 mg/kg), Sb (0.73 mg/kg), and Cd (0.17 mg/kg). Generally, the heavy metal concentrations decreased from west to east (L1 > L2 > L3) across northern China. Moreover, three potential sources of the heavy metal were distinguished, including natural process, anthropogenic activities (industrial development and agricultural cultivation), and atmospheric deposition. Although the contamination of the single metal (including Cd, Cr, Cu, and Pb) was moderate in L1 and L2, the combined contamination was low in the upland soils. It was noted that Cd posed a moderate to considerable ecological risk on the upland soils in northern China. This metal was the most sensitive factor in assessing the combined ecological risk, with a contribution rate of 91.56-94.84%. Considering the ingestion exposure, the current concentrations of the metals posed minimal risks to human health. Furthermore, children experienced higher health risks than adults. Present study analyzed the probabilistic distribution of contamination, ecological, and health risk of heavy metals in upland soils of northern China, providing fundamental information for better agricultural heavy metal pollution assessment in China.

The extraction of polycyclic aromatic hydrocarbons from water samples with aromatic-dithiocarbamate modified magnetic nanoparticles.

Considering the urgent need for the analysis of trace-level pollutants in water samples, the pre-concentration of micropollutants in water samples has been the focus of extensive research. Among current pretreatment methods, the solid phase extraction (SPE) technique has received enormous attention because of its low cost, ease of operation and high efficiency. In this work, a new adsorbent (Fe3O4@Au@DTC NPs) was acquired through modification of Fe3O4 nanoparticles (NPs) with gold (Au) and dithiocarbamate (DTC). To investigate their application ability, the adsorbent were utilized as an SPE adsorbent to enrich polycyclic aromatic hydrocarbons in water (PAHs, fluoranthene, pyrene, benzo anthracene, benzo fluoranthene, benzo pyrene). The obtained Fe3O4@Au@DTC NPs were confirmed by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), and UV-Vis spectrum. Under optimal conditions, the calibration curves were obtained in the range of 10-500 ng L-1, while the limit of detection (LOD) ranged in 1.17-2.31 ng L-1. Furthermore, 50 mg of Fe3O4@Au@DTC NPs could extract trace PAHs from 500 mL real water samples into 1 mL eluent, and the spiked recoveries of five PAHs in river water and tap water reached 72-106% with relative standard deviations varying between 3.3-5.18%. Through the conversion of amines into DTC, we acquire desiring group modified Fe3O4 NPs, which showed great prospects in magnetic solid-phase extraction sphere and environmental field.

Complete genome sequencing of Peyer's patches-derived Lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity.

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.

Multiple microRNAs regulate tacrolimus metabolism through CYP3A5.

The CYP3A5 gene polymorphism accounts for the majority of inter-individual variability in tacrolimus pharmacokinetics. We found that the basal expression of CYP3A5 in donor grafts also played a significant role in tacrolimus metabolism under the same genetic conditions after pediatric liver transplantation. Thus, we hypothesized that some potential epigenetic factors could affect CYP3A5 expression and contributed to the variability. We used a high-throughput functional screening for miRNAs to identify miRNAs that had the most abundant expression in normal human liver and could regulate tacrolimus metabolism in HepaRG cells and HepLPCs. Four of these miRNAs (miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26-5p) were selected for testing. We found that these miRNAs inhibited tacrolimus metabolism that was dependent on CYP3A5. Putative miRNAs targeting key drug-metabolizing enzymes and transporters (DMETs) were selected using an in silico prediction algorithm. Luciferase reporter assays and functional studies showed that miR-26b-5p inhibited tacrolimus metabolism by directly regulating CYP3A5, while miR-29a-5p, miR-99a-5p, and miR-532-5p targeted HNF4α, NR1I3, and NR1I2, respectively, in turn regulating the downstream expression of CYP3A5; the corresponding target gene siRNAs markedly abolished the effects caused by miRNA inhibitors. Also, the expression of miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26b-5p in donor grafts were negatively correlated with tacrolimus C/D following pediatric liver transplantation. Taken together, our findings identify these miRNAs as novel regulators of tacrolimus metabolism.

Impact of chemotherapy on prognosis of resectable pathological T3N0M0 esophageal cancer patients: a population-based study.

Aims: This study aimed to retrospectively determine the influence factors and survival effects of chemotherapy in pathological T3N0M0 esophageal cancer (EC) patients based on histological type. Methods: A total of 1136 pathological T3N0M0 EC patients who had surgery were chosen from the Surveillance, Epidemiology and End Results database. The patients were divided into subgroups based on histological type and chemotherapy status. Multivariate logistic regression, log-rank test and Cox regression were used to identify prognostic risk factors and survival differences. A propensity score matching analysis was applied to adjust the covariates. The impact of additional chemotherapy was also assessed in patients who had postoperative radiotherapy. Results: The 5-year overall survival was 36.4% for all patients. Chemotherapy was an independent protective factor of survival in both adenocarcinoma and squamous cell carcinoma patients. In the survival analysis, chemotherapy significantly improved the prognosis of EC patients, both for adenocarcinoma and squamous cell carcinoma. Propensity score matching analysis validated these results. Conclusion: Chemotherapy is recommended for pathological T3N0M0 EC patients regardless of histological type.

Lay abstract The prognosis of patients with different histological types of esophageal cancer varies. Chemotherapy is important treatment for these patients. However, the survival benefits of chemotherapy with regard to histological type and clinical stage are unclear. Here the authors used a public database to explore the prognostic value of chemotherapy and survival influence factors in these patients.

The link of depression, untreated hypertension, and diabetes with mortality in postmenopausal women: A cohort study.

OBJECTIVE: To explore the association of depression, as well as untreated hypertension or diabetes with all-cause death in community-based postmenopausal women in Beijing. METHODS: A cohort of 863 community-based postmenopausal women with no history of cardiovascular heart disease (CHD), stroke, cancer, or dementia was investigated on 20 July-28 September 2009 at baseline. Depression was diagnosed using the 30-item Center for Epidemiologic Studies Depression (CES-D) scale with CES-D ≥ 11. Meanwhile, data on health behavior, physical comorbidity, and social support at baseline were collected. These individuals were followed up from 20 July to 30 August 2014. All-cause mortality and cause of death were surveyed. RESULTS: After a median follow-up of 4.97 years, 120 subjects died of all-cause. Twenty-four died of stroke, 19 died of myocardial infarction, 21 died of cancer. The others died of aging, infection, and accident. Depression and untreated HP were significantly associated with all-cause mortality in Cox models after full adjustment for all of the potential confounders (Depression HR: 2.16, 95%CI: 1.35-3.46; Untreated hypertension HR: 1.84, 95%CI: 1.12-3.02). However, negative correlation of untreated diabetes on all-cause mortality was observed in this population (HR: 1.36, 95%CI: 0.75-2.49). When depression was co-existing with hypertension/diabetes, the HR for mortality elevated significantly (Depression co-existing with hypertension HR = 3.87, 95% CI: 2.07-7.23; Depression co-existing with diabetes HR = 5.02, 95% CI: 1.5-16.79). CONCLUSIONS: It is suggested we should take sufficient care of postmenopausal females with depression and control blood pressure and glucose more effectively. Abbreviations: HP: Hypertension; DM: Diabetes; TC: Cholesterol; TG: Triglyceride; BMI: Body-Mass Index; CES-D: Center for Epidemiologic Studies Depression; CDC: Centers for Disease Control and Prevention; HR: Hazard Ratio; CI: Confidence Interval; ADL: Activities of daily living scale.