Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation.

N6-methyladenosine (m6A), installed by the Mettl3/Mettl14 methyltransferase complex, is the most prevalent internal mRNA modification. Whether m6A regulates mammalian brain development is unknown. Here, we show that m6A depletion by Mettl14 knockout in embryonic mouse brains prolongs the cell cycle of radial glia cells and extends cortical neurogenesis into postnatal stages. m6A depletion by Mettl3 knockdown also leads to a prolonged cell cycle and maintenance of radial glia cells. m6A sequencing of embryonic mouse cortex reveals enrichment of mRNAs related to transcription factors, neurogenesis, the cell cycle, and neuronal differentiation, and m6A tagging promotes their decay. Further analysis uncovers previously unappreciated transcriptional prepatterning in cortical neural stem cells. m6A signaling also regulates human cortical neurogenesis in forebrain organoids. Comparison of m6A-mRNA landscapes between mouse and human cortical neurogenesis reveals enrichment of human-specific m6A tagging of transcripts related to brain-disorder risk genes. Our study identifies an epitranscriptomic mechanism in heightened transcriptional coordination during mammalian cortical neurogenesis.

Integrated Bioinformatics Analysis to Identify a Novel Four-Gene Prognostic Model of Breast Cancer and Reveal Its Association with Immune Infiltration.

Liquid-liquid phase separation (LLPS) impact immune signaling in cancer and related genes have shown prognostic value in breast cancer (BRCA). However, the crosstalk between LLPS and immune infiltration in BRCA remain unclear. Therefore, we aimed to develop a novel prognostic model of BRCA related to LLPS and immune infiltration. BRCA-related, liquid-liquid phase separation (LLPS)-related genes, and differentially expressed genes (DEGs) were identified using public databases. Mutation and drug sensitivity analyses were performed using Gene Set Cancer Analysis database. Univariate cox regression and LASSO Cox regression were used for the construction and verification of prognostic model. Kaplan-Meier analysis was performed to evaluate overall survival (OS). Gene set variation analysis was conducted to analyze key pathways. CIBERSORT was used to assess immune infiltration and its correlation with prognostic genes was determined through Pearson analysis. A total of 6056 BRCA-associated genes, 3775 LLPS-associated genes, and 4049 DEGs, resulting in 314 overlapping genes. Twenty-eight prognostic genes were screened, and some of them were mutational and related to drug sensitivity Subsequently, a prognostic model comprising L1CAM, EVL, FABP7, and CST1 was built. Patients in high-risk group had shorter OS than those in low-risk group. The infiltrating levels of CD8+ T cells, macrophages M0, macrophages M2, dendritic cells activated, and mast cells resting was altered in high-risk group of breast cancer patients compared to low-risk group. L1CAM, EVL, FABP7, and CST1 were related to these infiltrating immune cells. L1CAM, EVL, FABP7, and CST1 were potential diagnostic biomarkers and therapeutic targets for BRCA.

miR-520e and its promoter region DNA methylation as potential biomarkers in atherosclerosis.

In atherosclerosis, DNA methylation plays a key regulatory role in the expression of related genes. However, the molecular mechaism of these processes in HUVECs are unclear. Here, using high-throughput sequencing from the Infinium HumanMethylation450 assay, we manifested that the cg19564375 methylation of miR-520e promoter region in the peripheral blood of acute coronary syndrome (ACS) patients was higher than that of healthy controls. As shown by RQ-MSP, the upstream DNA methylation level of the miR-520e promoter region was considerably increased in ACS patients. miR-520e was markedly down-regulated in ACS patients compared with healthy controls. In the ox-LDL-induced HUVECs injury model, DNA methylation of the upstream region of miR-520e was significantly increased. With increasing concentrations of the methylase inhibitor 5-Aza, miR-520e expression was upregulated. The silence of methyltransferase DNMT1, rather than DNMT3a or DNMT3b, abolished the influence of miR-520e expression by ox-LDL treatment in HUVECs. A dual luciferase reporter assay revealed that miR-520e regulated the TGFBR2 3'-UTR region. After silencing TGFBR2, the promoting effect of miR-520e inhibitor on cell proliferation and migration may be attenuated. In conclusion, the expression of miR-520e is modified by its promoter region DNA methylation, and miR520e and its promoter region DNA methylation may be potential biomarkers in atherosclerosis.

MS-CASPT2 studies on the mechanistic photophysics of tellurium-substituted guanine and cytosine.

Sulfur-substituted nucleobases are highly promising photosensitizers that are widely used in photodynamic therapy, and there are numerous studies exploring their unique photophysical behaviors. However, relevant photophysical investigations on selenium and tellurium substitutions are still rare. Herein, the high-level multistate complete-active-space second-order perturbation (MS-CASPT2) method was performed for the first time to explore the excited-state relaxation processes of tellurium-substituted guanine (TeG) and cytosine (TeC). Based on the electronic state properties in the Franck-Condon (FC) region, we found that the lowest five (S0, S1, S2, T1, and T2) and six (S0, S1, S2, T1, T2 and T3) states will participate in the nonadiabatic transition processes of TeG and TeC systems, respectively. In these electronic states, two kinds of minimum and intersection structures (i.e., planar and twisted structures) were obtained for both TeG and TeC systems. The linearly interpolated internal coordinate (LIIC) paths and spin-orbit coupling (SOC) constants revealed several possible planar and twisted excited-state decay channels, which could lead the systems to the lowest reactive triplet state of T1. Small energy barriers in the T1 state will trap the TeG and TeC systems for a while before they finally populate to the ground state. Although tellurium substitution would further redshift the absorption wavelength and enhance the intersystem crossing (ISC) rate to the T1 state compared with sulfur and selenium substitutions, the rapid ISC process of T1 → S0 may make it a less effective photosensitizer to sensitize the molecular oxygen. We believe our present work will provide important mechanistic insights into the photophysics of tellurium-substituted nucleobases.

Mechanistic Photophysics of Tellurium-Substituted Uracils: Insights from Multistate Complete-Active-Space Second-Order Perturbation Calculations.

The photophysical mechanisms of tellurium-substituted uracils were studied at the multistate complete-active-space second-order perturbation level with a particular focus on how the position and number of tellurium substitutions affect their nonadiabatic relaxation processes. Electronic structure analysis reveals that the lowest several excited states are closely concerned with the n and π orbitals at the Te7-C2 [Te8-C4] moiety of 2-tellurouracil (2TeU) [4TeU and 24TeU]. Both planar and twisted minima were optimized for 2TeU, whereas only planar ones were obtained for 4TeU and 24TeU, except for a twisted T1 minimum of 4TeU. Based on intersection structures and linearly interpolated internal coordinate paths, we proposed several feasible excited-state deactivation paths. It is found that the relaxation channels for 2TeU are more complicated than those of 4TeU and 24TeU. The electronic population transfer to the T1 state for 2TeU is easier than that for 4TeU and 24TeU in consideration of the barrier heights from the S2 Franck-Condon point to the S2/S1 or S2/T2 intersections. In addition, the recovery of the ground state from the T1 state for 2TeU will be more efficient than that for the other two systems as well.

Reproducibility and relative validity of a semi-quantitative food frequency questionnaire for the Chinese lactating mothers.

BACKGROUND: The dietary nutritional status of the lactating mothers is related to maternal health and has a significant impact on the growth and development of infants through the secretion of breast milk. The food frequency questionnaire (FFQ) is the most cost-effective dietary assessment method that can help obtain information on the usual dietary pattern of participants. Until now, the FFQs have been used for different populations in China, but there are few FFQs available for the lactating mothers. We aimed to develop a semi-quantitative, 156-item FFQ for the Chinese lactating mothers, and evaluate its reproducibility and relative validity. METHODS: A total of 112 lactating mothers completed two FFQs and one 3-d dietary record (3DR). The first FFQ (FFQ1) was conducted during postpartum at 60-65 days and the second FFQ (FFQ2) during subsequent follow-up at 5 weeks. The 3DR was completed with portion sizes assessed using photographs taken by the respondent before and after eating (instant photography) 1 week after FFQ1. RESULTS: For reproducibility, the Spearman's correlation coefficients for food ranged from 0.34 to 0.68, and for nutrients from 0.25 to 0.61. Meanwhile, the intra-class correlation coefficients for food ranged from 0.48 to 0.87, and for nutrients from 0.27 to 0.70. For relative validity, the Spearman's correlation coefficients for food ranged from 0.32 to 0.56, and for nutrients from 0.23 to 0.72. The energy-adjusted coefficients for food ranged from 0.26 to 0.55, and for nutrients from 0.22 to 0.47. Moreover, the de-attenuation coefficients for food ranged from 0.34 to 0.67, and for nutrients from 0.28 to 0.77. The Bland-Altman plots also showed reasonably acceptable agreement between the two methods. CONCLUSIONS: This FFQ is a reasonably reproducible and a relative valid tool for assessing dietary intake of the Chinese lactating mothers.

Favorable function of Ectonucleoside triphosphate diphosphohydrolase 1 high expression in thyroid carcinoma.

BACKGROUND: Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) has been proved to play a vital role in human cancers. Nevertheless, the exact role of ENTPD1 in thyroid carcinoma (THCA) remained unclear. This study aimed to evaluate its prognostic value and reveal the potential regulatory mechanism in THCA. RESULTS: (1) Higher expression of ENTPD1 was found in THCA tissue compared with normal tissue (all P < 0.05). ENTPD1 expression was associated with age, sub-type and clinical stage of THCA patients (all P < 0.05). Immunohistochemistry showed its higher expression in patients with early stage. (2) ENTPD1 high expression was associated with favorable overall survival of THCA patients (all P < 0.05), especially for male patients and those with advanced stage, B-cells and Natural killer T-cells decreased (all P < 0.05). (3) Pathway analysis indicated that ENTPD1 mainly participated in metabolic process and negatively regulated metabolism-related pathway such as butanoate metabolism, pyruvate metabolism and fatty acid metabolism ((all P < 0.05). (4) ENTPD1 appeared genetic alteration in THCA, and the main mutation type of ENTPD1 was missense substitution (15.89%). (5) A weak correlation between ENTPD1 expression and methylation was found (P < 0.001). Methylation of ENTPD1 in THCA was lower than in normal group (P < 0.001), but it did not correlate with any clinical phenotypes of THCA patients. CONCLUSIONS: ENTPD1 was highly expressed in THCA, and ENTPD1 high expression contributed to the prognosis of THCA patients. The present study inferred that ENTPD1 might serve as a metabolism-related gene and play a critical role in THCA through regulating metabolic pathways.

Identification of potential biomarkers and metabolic pathways based on integration of metabolomic and transcriptomic data in the development of breast cancer.

OBJECTIVE: Breast cancer (BC) is the most common type of malignant tumor and the most common cause of cancer-related mortality among women. Metabolic reprogramming is considered a hallmark of cancer, and the study of BC metabolism may be the key to the development of new strategies for diagnosis and treatment. In this study, we aimed to explore the potential metabolites and gene biomarkers for BC through the integration of metabolomics and transcriptomic data, which could further understand BC tumor biology. METHODS: Transcriptome dataset GSE139038 was downloaded to explore the differentially expressed genes (DEGs) between BC and normal control (NC) samples. Metabolomics dataset MTBLS326 was downloaded and preprocessed to obtain altered metabolites. Then, the principal component analysis (PCA) and linear models were used to reveal DEGs-metabolites relations. Finally, the pathway enrichment analysis of altered metabolites was performed. RESULTS: A total of 280 DEGs and eight metabolites were explored between BC and NC samples. The liner module analysis investigated 28 DEGs-metabolites interactions including WASP family member 3 (WASF3)-lactate, ras-related protein Rab-7B (RAB7B)-lactate, and methyltransferase-like 7A (METTL7A)-pyruvate. Finally, pathways analysis showed that these metabolites (such as lactate and pyruvate) were mainly enriched in pathways like disorders of the Krebs cycle. CONCLUSIONS: Combining with the transcriptomic and metabolomics data, we found that lactate, pyruvate, WASF3, RAB7B, and METTL7A might be used as novel biomarkers and potential therapeutic targets for BC. In addition, the disorders of the Krebs cycle pathway might affect the progression of BC.

Selenium substitution effects on excited-state properties and photophysics of uracil: a MS-CASPT2 study.

The photophysics of selenium-substituted nucleobases has attracted recent experimental attention because they could serve as potential photosensitizers in photodynamic therapy. Herein, we present a comprehensive MS-CASPT2 study on the spectroscopic and excited-state properties, and photophysics of 2-selenouracil (2SeU), 4-selenouracil (4SeU), and 2,4-selenouracil (24SeU). Relevant minima, conical intersections, crossing points, and excited-state relaxation paths in the lowest five electronic states (i.e., S0, S1, S2, T2, and T1) are explored. On the basis of these results, their photophysical mechanisms are proposed. Upon photoirradiation to the bright S2 state, 2SeU quickly relaxes to its S2 minimum and then moves in an essentially barrierless way to a nearby S2/S1 conical intersection near which the S1 state is populated. Next, the S1 system arrives at an S1/T2/T1 intersection where a large S1/T1 spin-orbit coupling of 430.8 cm-1 makes the T1 state populated. In this state, a barrier of 6.8 kcal mol-1 will trap 2SeU for a while. In parallel, for 4SeU or 24SeU, the system first relaxes to the S2 minimum and then overcomes a small barrier to approach an S2/S1 conical intersection. Once hopping to the S1 state, there exists an extended region with very close S1, T2, and T1 energies. Similarly, a large S1/T1 spin-orbit coupling of 426.8 cm-1 drives the S1→ T1 intersystem crossing process thereby making the T1 state populated. Similarly, an energy barrier heavily suppresses electronic transition to the S0 state. The present work manifests that different selenium substitutions on uracil can lead to a certain extent of different vertical and adiabatic excitation energies, excited-state properties, and relaxation pathways. These insights could help understand the photophysics of selenium-substituted nucleobases.

Adsorptive removal of gallic acid from aqueous solution onto magnetic ion exchange resin.

Finding an appropriate adsorbent with high adsorption capacity, quick adsorption kinetics and easy regeneration was crucial to the removal of gallic acid (GA) from water and wastewater. Our aims were to investigate whether a magnetic ion exchange (MIEX) resin had the three merits mentioned above, and investigate the feasibility of GA adsorption on MIEX resin, and the adsorption kinetics, equilibrium, thermodynamics, regeneration and mechanism using batch tests. The uptake of GA increased with increasing GA concentration. The GA concentration influenced the time needed to reach equilibrium, but the adsorption could be completed within 120 min. Elevating temperature facilitated the GA removal. The removal percent remained above 95.0% at pH 5.0-11.0. Carbonate and bicarbonate promoted the GA removal; conversely chloride, sulfate and nitrate restrained the GA removal significantly. The adsorption kinetics could be fitted well with the pseudo second-order model, and the film diffusion governed the whole adsorption rate. The equilibrium data followed the Redlich-Peterson isotherm model. The adsorption was a spontaneous, endothermic and entropy driven process. The ion exchange dominated the removal mechanism. The spent MIEX resin was well regenerated by sodium chloride. Therefore, MIEX resin is a potential adsorbent for removing GA quickly and efficiently from water and wastewater.

Manipulating osa-MIR156f Expression by D18 Promoter to Regulate Plant Architecture and Yield Traits both in Seasonal and Ratooning Rice.

BACKGROUND: Rice (Oryza sativa L.) feeds more than half of the world's population. Ratooning rice is an economical alternative to the second seasonal rice, thus increasing the yield of ratooning rice is highly important. RESULTS: Here we report an applicable transgenic line constructed through the manipulation of osa-MIR156f expression in rice shoot using the OsGA3ox2 (D18) promoter. In seasonal rice, the D18-11 transgenic line showed moderate height and more effective tillers with normal panicle. In ratooning rice, axillary buds outgrew from the basal node of the D18-11 transgenic line before the harvest of seasonal rice. More effective tillers produced by the outgrowth of axillary buds contributed to the plant architecture improvement and yield increase. Additionally, it was found that osa-miR156f down-regulated the expression of tillering regulators, such as TEOSINTE BRANCHED1 (TB1) and LAX PANICLE 1 (LAX1). The expression of DWARF10, DWARF27 and DWARF53, three genes being involved in the biosynthesis and signaling of strigolactone (SL), decreased in the stem of the D18-11 transgenic line. CONCLUSION: Our results indicated that the manipulation of osa-MIR156f expression may have application significance in rice genetic breeding. This study developed a novel strategy to regulate plant architecture and grain yield potential both in the seasonal and ratooning rice.

Generation of Active Mn(III)aq by a Novel Heterogeneous Electro-permanganate Process with Manganese(II) as Promoter and Stabilizer.

Our study on the synergetic effect of electrolysis and permanganate (E-PM) revealed a novel alternative method for generating active Mn(III)aq heterogeneously by electrochemically activating PM with Mn2+ as promoter and stabilizer. We systematically explored the generation mechanism of Mn(III)aq. It indicated that all three components (electrolysis + PM + Mn2+) were necessary to facilitate the generation of active Mn(III) in the E-PM-Mn2+ process. It was worth noting that Mn2+, as essential promoter and Mn(III)aq stabilizer, could considerably enhance the concentration of Mn(III) in the E-PM-Mn2+ process. Further study revealed that the active Mn(III) was mainly produced on cathode rather than in aqueous solution or on anode. In addition, the soluble Mn(III)aq generated in the E-PM-Mn2+ process was demonstrated to be very efficient for the degradation and mineralization of diclofenac (DCF) as well as methyl blue, carbamazepine, phenol, sulfamethoxazole, and nitrobenzene. Moreover, the effects of the main operating parameters (Mn2+ dosage, PM dosage, applied current density, pH of solution, and contaminant concentration) and different water matrices on the E-PM-Mn2+ process were investigated systematically. Possible degradation pathways of DCF in the E-PM-Mn2+ process were also proposed. The results demonstrated that the E-PM-Mn2+ system based on active Mn(III)aq could create a more efficient, sustainable, and less energy costing technology for water treatment.

Idiopathic recurrent facial palsy: Facial nerve decompression via middle cranial fossa approach.

OBJECTIVE: To introduce our experience of preventing further episodes of idiopathic recurrent facial palsy by facial nerve decompression via middle cranial fossa approach. METHODS: Twelve cases (surgery group) who had idiopathic recurrent facial palsy underwent facial nerve decompression via middle cranial fossa approach, and 6 cases (control group) who declined surgery accepted conservative treatment. Further episodes of facial palsy and final outcomes of facial nerve were recorded. Facial nerve function was assessed by House-Brackmann facial nerve grade system. RESULTS: Only 8.3% of the patients (one case) in the surgery group had further episodes of facial palsy on the surgical side, but up to 64.7% of the patients (4 cases) in the control group suffered further episodes (p<0.05). 11 patients (91.7%) in the surgery group recovered to Grade I or Grade II in contrast to 3 cases (50%) in the control group. CONCLUSIONS: Facial nerve decompression via middle cranial fossa approach was able to prevent further episodes of idiopathic recurrent facial palsy, and surgical decompression seemed to achieve better outcomes of facial nerve than conservative treatment.

Polystyrene microplastics enhanced the toxicity of cadmium to rice seedlings: Evidence from rice growth, physiology, and element metabolism.

Microplastics (MPs) and cadmium (Cd) are toxic to rice; however, the effects and mechanisms of their combined exposure are unclear. The combined exposure effects of polystyrene microplastics (PS-MPs) with different particle sizes (1-10 µm, 50-150 µm) and concentrations (50, 500 mg·L-1) and Cd on rice were explored. PS-MPs combined with Cd amplifies the inhibition of each individual exposure on the height and biomass of rice seedlings, and they showed antagonistic effects. PS-MPs reduced the content of chlorophyll and increased the content of carotenoid rice seedlings significantly. High concentrations of PS-MPs enhanced the inhibition of Cd on chlorophyll content. Cd, PS-MPs single and combined exposures significantly altered the antioxidant enzyme (POD, CAT, SOD) activities in rice seedlings. Under PS-MPs exposure, overall, the MDA content in shoots and roots exhibited opposite trends, with a decrease in the former and an increase in the latter. In comparison with Cd treatment, the combined exposures' shoot and root MDA content was reduced. Cd and PS-MPs showed "low concentration antagonism, high concentration synergism" on the composite physiological indexes of rice seedlings. PS-MPs significantly increased the Cd accumulation in shoots. PS-MPs promoted the root absorption of Cd at 50 mg·L-1 while inhibited at 500 mg·L-1. Cd and PS-MPs treatments interfered with the balance of microelements (Mn, Zn, Fe, Cu, B, Mo) and macroelements (S, P, K, Mg, Ca) in rice seedlings; Mn was significantly inhibited. PS-MPs can enhance of Cd's toxicity to rice seedlings. The combined toxic effects of the two contaminants appear to be antagonistic or synergistic, relying on the particle size and concentration of the PS-MPs. Our findings offer information to help people understanding the combined toxicity of Cd and MPs on crops.

Multiple Photoisomerization Pathways of the Green Fluorescent Protein Chromophore in a Reversibly Photoswitchable Fluorescent Protein: Insights from Quantum Mechanics/Molecular Mechanics Simulations.

Herein, we have employed a combined CASPT2//CASSCF approach within the quantum mechanics/molecular mechanics (QM/MM) framework to explore the early time photoisomerization of rsEGFP2 starting from its two OFF trans states, i.e., Trans1 and Trans2. The results show similar vertical excitation energies to the S1 state in their Franck-Condon regions. Considering the clockwise and counterclockwise rotations of the C11-C9 bond, four pairs of the S1 excited-state minima and low-lying S1/S0 conical intersections were optimized, based on which we determined four S1 photoisomerization paths that are essentially barrierless to the relevant S1/S0 conical intersections leading to efficient excited-state deactivation to the S0 state. Most importantly, our work first identified multiple photoisomerization and excited-state decay paths, which must be seriously considered in the future. This work not only sheds significant light on the primary trans-cis photoisomerization of rsEGFP2 but also aids in the understanding of the microscopic mechanism of GFP-like RSFPs and the design of novel GFP-like fluorescent proteins.

Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature.

BACKGROUND: The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors are missing, information needed for improved prognosis and treatment. METHODS: To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and 3 microbe targets (bacteria, fungi, and cytomegalovirus). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in surgically resected tumor samples from 12 patients with early-stage lung cancer. RESULTS: Bacterial burden was significantly higher in tumor cells compared with T cells, macrophages, other immune cells, and stroma. This burden increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that lung intratumor bacteria derive from the latter route of entry. Expression of oncogenic ß-catenin was strongly correlated with bacterial burden, as were tumor histological subtypes and environmental factors. CONCLUSIONS: Intratumor bacteria were enriched with tumor cells and associated with multiple oncogenic pathways, supporting a rationale for reducing the local intratumor microbiome in lung cancer for patient benefit. TRIAL REGISTRATION NUMBER: NCT00242723, NCT02146170.

Altered serum human cytomegalovirus microRNA levels are common and closely associated with the inflammatory status in patients with fever.

Background: Fever has a complicated etiology, and diagnosing its causative factor is clinically challenging. Human cytomegalovirus (HCMV) infection causes various diseases. However, the clinical relevance, prevalence, and significance of HCMV microRNAs (miRNA) in association with fever remain unclear. In the present study, we analyzed the HCMV miRNA expression pattern in the serum of patients with fever and evaluate its clinical associations with occult HCMV infection status in immune disorders. Methods: We included serum samples from 138 patients with fever and 151 age-gender-matched controls in this study. First, the serum levels of 24 HCMV miRNAs were determined using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in the training set. The markedly altered miRNAs were verified in the validation and testing sets. The serum HCMV IgG/IgM and DNA titers in the testing cohort were also assessed using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively. Results: The majority of HCMV miRNAs were markedly upregulated in the serum of fever patients. We selected the five most significantly altered HCMV miRNAs: hcmv-miR-US4-3p, hcmv-miR-US29-3p, hcmv-miR-US5-2-3p, hcmv-miR-UL112-3p, and hcmv-miR-US33-3p for validation. These miRNAs were also significantly elevated in the serum of fever patients in the validation and testing sets compared with the controls. Logistic regression analysis revealed that the five miRNAs were novel potential risk factors for fever. Notably, the serum levels of four of the five confirmed HCMV miRNAs were significantly associated with blood C-reaction protein concentrations. Moreover, the five HCMV miRNA levels were closely correlated with the HCMV DNA titers in the testing cohort. Conclusion: HCMV infection and activation are common in fever patients and could be novel risk factors for fever. These differentially expressed HCMV miRNAs could enable HCMV activation status monitoring in immune disorders.

Identification of TNIK as a novel potential drug target in thyroid cancer based on protein druggability prediction.

ABSTRACT: Thyroid cancer is a common endocrine malignancy; however, surgery remains its primary treatment option. A novel targeted drug for the development and application of targeted therapy in thyroid cancer treatment remain underexplored.We obtained RNA sequence data of thyroid cancer from The Cancer Genome Atlas database and identified differentially expressed genes (DEGs). Then, we constructed co-expression network with DEGs and combined it with differentially methylation analysis to screen the key genes in thyroid cancer. PockDrug-Server, an online tool, was applied to predict the druggability of the key genes. Finally, we constructed protein-protein interaction (PPI) network to observe potential targeted drugs for thyroid cancer.We identified 3 genes correlated with altered DNA methylation level and oncogenesis of thyroid cancer. According to the druggable analysis and PPI network, we predicted TRAF2 and NCK-interacting protein kinase (TNIK) sever as the drug targeted for thyroid cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that genes in protein-protein interaction network of TNIK enriched in mitogen-activated protein kinase signaling pathway. For drug repositioning, we identified a targeted drug of genes in PPI network.Our study provides a bioinformatics method for screening drug targets and provides a theoretical basis for thyroid cancer targeted therapy.

Ciprofloxacin removal by ultrasound-enhanced carbon nanotubes/permanganate process: In situ generation of free reactive manganese species via electron transfer.

Recently, free reactive manganese species (RMnS) generated via permanganate catalytic oxidation technology has been applied to contaminants abatement and sludge dewatering. This study proposed a novel free RMnS generation method in ultrasound enhanced carbon nanotube (CNTs)/permanganate process (UCP) for organics removal. Taking ciprofloxacin as a target contaminant, the removal efficiency in the UCP process (9.78 s-1) was remarkably higher than that of the permanganate (0.71 s-1) and CNTs/permanganate (2.57 s-1) processes. CNTs could enrich manganese compounds and ciprofloxacin, and act as an electronic platform for the electronic transfer from ciprofloxacin to manganese compounds for free RMnS generation, which was revealed by DFT calculation and spectrum analysis. Meanwhile, ultrasound further regulated the generation of RMnS as it could transform the inactive solid Mn(IV) into free RMnS. In the UCP process, non-free radical modes including RMnS oxidation (49.8%) and electron transfer (23.5%) were the dominant processes for ciprofloxacin removal in the UCP process, and hydroxyl radical oxidation (13.2%), CNTs adsorption (5.5%), and PM oxidation (8.0%) also contributed to ciprofloxacin removal. Interestingly, CNTs could be well reused in the UCP process as more than 88.75% of ciprofloxacin was removed after five times reuse of CNTs. The UCP process provides a novel strategy for rapid contaminants removal in water treatment via continuous generation of free RMnS.

Association between dietary fatty acid patterns based on principal component analysis and fatty acid compositions of serum and breast milk in lactating mothers in Nanjing, China.

This study aimed to comprehensively analyze dietary fatty acids (FAs) to evaluate their association with FA compositions of maternal serum and breast milk and assess their effects on mothers and infants. Overall, 121 healthy lactating Chinese mothers at 30-50 days of postpartum were enrolled and instructed to complete a Food Frequency Questionnaire, together with venous blood and breast milk sample collections. Dietary FA patterns were derived by principal component analysis with varimax rotation. Serum and breast milk FA compositions were detected using capillary gas chromatography and presented as relative concentrations (weight percentage of total FAs, %). Daily energy intake, absolute intake of most nutrients, and percentage of energy intake provided by these nutrients significantly varied among the different dietary FA patterns. There were significant differences in serum polyunsaturated fatty acid (PUFA) levels (P = 0.011); in monounsaturated fatty acid and PUFA proportions in breast milk with respect to four patterns (P = 0.002 and P = 0.026, respectively); and in n-6 PUFA, n-3 PUFA, linoleic acid, γ-linolenic acid, α-linolenic acid, and docosahexaenoic acid levels in breast milk (P = 0.027, P = 0.007, P = 0.048, P = 0.034, P = 0.020, and P = 0.002, respectively). Furthermore, maternal weight retention and length-for-age z scores, weight-for-age z scores and head circumference-for-age z scores of infants with respect to the four patterns exhibited significant differences (P = 0.038, P = 0.030, P = 0.034, and P<0.001, respectively). The results demonstrated the effect of dietary FA patterns on FA compositions of serum and breast milk, and patterns mainly characterized by LC-PUFA may have potentially beneficial effects on maternal postpartum recovery and infant growth.