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In a solid, the electronic subsystem can exhibit incipient order with lower point group symmetry than the crystal lattice. Ultrafast external fields that couple exclusively to electronic order parameters have rarely been investigated, however, despite their potential importance in inducing exotic effects. Here we show that when inversion symmetry is broken by the antiferromagnetic order in Cr2O3, transmitting a linearly polarized light pulse through the crystal gives rise to an in-plane rotational symmetry-breaking (from C3to C1) via optical rectification. Using interferometric time-resolved second harmonic generation, we show that the ultrafast timescale of the symmetry reduction is indicative of a purely electronic response; the underlying spin and crystal structures remain unaffected. The symmetry-broken state exhibits a dipole moment, and its polar axis can be controlled with the incident light. Our results establish a coherent nonlinear optical protocol by which to break electronic symmetries and produce unconventional electronic effects in solids.

Previous studies showed that cal-miR2911, featuring an atypical biogenesis, could target genes of virus and in turn inhibit virus replication. Given its especial sequence motif and cross-kingdom potential, the stability of miR2911 under digestive environment and its impact on intestinal microbes in mice were examined. The results showed that miR2911 was of considerable stability during oral, gastric, and intestinal digestion. The coingested food matrix enhanced its stability in the gastric phase, contributing to the existence of miR2911 in mouse intestines. The survival miR2911 promoted the growth of Bifidobacteriumin mice and maintained the overall composition and diversity of the gut microbiota. miR2911 specifically entered the cells of Bifidobacterium adolescentisand potentially modulated the gene expression as evidenced by the dual-luciferase assay. The current study provided evidence on the cross-kingdom communication between dietary miRNAs and gut microbes, suggesting that modulating target bacteria using miRNAs for nutritional and therapeutic ends is promising.

NADPH oxidase 4 (NOX4) plays an important role in the regulation of oxidative stress, which is associated with endometriosis. This study aims to investigate the effects of NOX4 in endometriosis and its molecular mechanisms. Clinical specimens were collected, and human endometrial stromal cells (HESCs) were isolated. The knockdown of NOX4 cell lines was established on the HESCs and induced by peritoneal fluid. The levels of NOX4 were determined by using immunohistochemistry (IHC) staining, western blotting, and qPCR, respectively. The levels of oxidative stress markers were determined by using western blotting and ELISAs, respectively. The correlation of NOX4 and oxidative stress markers was analyzed by the Pearson correlation coefficient. The levels of NOX4 were dramatically elevated in the ectopic endometrium. Besides, oxidative stress biomarkers were also dysregulated in the ectopic endometrium as compared to the normal endometrium. Pearson’s correlation coefficient analysis revealed a relationship between NOX4 and oxidative stress biomarkers in the ectopic endometrium. NOX4 modulated the expressions of oxidative stress markers in endometrial stromal cells stimulated by the peritoneal fluid from endometriosis. The effects of NOX4 on endometriosis are in part by its regulatory effects against oxidative stress.

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red “O” staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

RNA modifications, also termed epitranscriptomic marks, encompass chemical alterations to individual nucleotides, including processes such as methylation and editing. These marks contribute to a wide range of biological processes, many of which are related to host immune system defense. The functions of immune-related RNA modifications can be categorized into three main groups: regulation of immunogenic RNAs, control of genes involved in innate immune response, and facilitation of adaptive immunity. Here, we provide an overview of recent research findings that elucidate the contributions of RNA modifications to each of these processes. We also discuss relevant methods for genome-wide identification of RNA modifications and their immunogenic substrates. Finally, we highlight recent advances in cancer immunotherapies that aim to reduce cancer cell viability by targeting the enzymes responsible for RNA modifications. Our presentation of these dynamic research avenues sets the stage for future investigations in this field.

To test the feasibility and effectiveness of a mindfulness-based intervention in rural-to-urban migrant Chinese children using trained community volunteers.

Emerging contaminants(ECs) have aroused great concerns due to their widespread presence as well as their potential health and ecological risks. Currently monitoring data about ECs in Chinese rural areas are still limited. In this study, Taige Canal basin was selected as a typical rural area for a pilot study. The occurrence of ECs, including pharmaceutical and personal care products(PPCPs), pesticides, plasticizers and flame retardants, in surface water and aquaculture ponds, as well as in wastewater treatment facilities, was comprehensively investigated. The effectiveness of rural decentralized wastewater treatment facilities and centralized wastewater treatment plant(WWTP) in removing ECs was also analyzed. Among 126 commonly used pesticides for target analysis, 25 compounds were detected in surface water with high frequency of >80%. Besides, 55 PPCPs, 21 pesticides and 18 other industrial products were identified by non-target analysis using high resolution mass spectrometry(HRMS). Totally 18 compounds were detected in surface water with a frequency of >60% and 6 of them were found in all samples, including irbesartan, valsartan, propazine, buprofezin, bis(2-ethylhexyl) phthalate(DEHP) and tri-(2-chloroisopropyl) phosphate(TCPP), with mean concentrations of 3022, 195, 125, 218, 3738 and 545 ng/L, respectively. There are 29 compounds(11 PPCPs, 8 pesticides and 10 other industrial products) detected in water samples from the aquaculture ponds, of which 13 compounds were found in all three ponds. The removal efficiencies of ECs in wastewater treatment facilities are generally limited, except valsartan(82%–86%), nobiletin(100%) and diisodecylphthalate(100%) were found to be significantly removed.

Lignin molecules contain alcohol hydroxyl and phenolic hydroxyl, so lignin can be used instead of toxic bisphenol A (BPA) to synthesize epoxy resin, which can not only reduce the amount of formaldehyde emission but also achieve the purpose of waste utilization and environmental protection. In this study, the lignin of Eucalyptus urophyllawas extracted with ionic liquid as the extraction agent, and subsequently phenolated by methylphenol as phenolic agent with concentrated sulfuric acid as catalyst to prepare phenolated lignin (PLG). Then, using NaOH as catalyst, the PLG was epoxidized with epoxy chloropropane (ECH) to synthesize the lignin-based epoxy resin (LGEP). The extraction of lignin and the synthesis of LGEP were investigated by the single-factor and orthogonal test, and the Eucalyptus urophyllaraw materials, lignin, PLG, and LGEP were characterized by UV, FTIR, XRD, SEM, and TGA. The results demonstrated that when the ionic liquid was [ChCl][Gly], the temperature was 90 °C, the time was 4 h, and the liquid-solid ratio was 20:1; the extraction rate of lignin reached 93.73%, and the purity of the regenerated lignin was 96.3%. The mass ratio of PLG to ECH was 1:2.5, the mass fraction of NaOH was 20% of the mass of PLG, the reaction time was 3 h, and the reaction temperature was 95 °C. Under this condition, the epoxy value of LGEP was 0.364.

Prolonged high temperature is a critical environmental factor contributing to the mass mortality of clams in summer. We investigated the growth and development of Cyclina sinensiscultured at different temperatures (25, 28, 31, and 34 °C) and their physiological and biochemical responses following a long period of exposure. The mortality rates at 31 °C and 34 °C were significantly higher than at 25 °C and 28 °C after 48 d (P < 0.05). The overall survival rates at 25 °C and 28 °C did not differ significantly from the control group (at natural seawater temperature), but were significantly lower at 31 °C and 34 °C (P< 0.05). The growth parameters of C. sinensisin all of the experimental groups were significantly higher than in the control group (P< 0.05), with the highest specific growth rate at 28 °C. The shell to soft tissue ratio was greatly increased in the 31 °C and 34 °C groups and was significantly higher than in the other groups after 32 d (P < 0.05). The condition factor at 28 °C was significantly higher than in the other groups (P < 0.05), and started to decline after 32 days at 31 °C and 34 °C. The hepatopancreatic and gonadotropic indexes were significantly lower at 31 °C and 34 °C than in the control group (P< 0.05). Appropriate temperature rises increased the filtration rate and ingestion rate but these were clearly inhibited at 31 °C and 34 °C. The activities of superoxide dismutase, catalase, acid phosphatase (ACP), and lysozyme (LZM) were significantly reduced at 31 °C and 34 °C (P< 0.05). The activities of ACP, LZM, amylase, and the proteases were significantly increased at 28 °C (P< 0.05). Our study showed that high temperatures accelerate the growth of shells but inhibit the growth of soft tissues, negatively affecting the development, physiology, and biochemistry of C. sinensis. Cyclina sinensisdemonstrates better overall performance at 28 °C, but aquaculture production would be severely affected if the temperature reaches, or exceeds 31 °C.

This paper reports findings from a recent survey of 1115 respondents from 34 rural counties/villages in 11 Chinese provinces. It investigates consumers' reaction towards the advertising market by incorporating the use of information sources and perceived source credibility into the advertising effectiveness literature. This is the first time that information about long-overlooked Chinese rural consumers based on probability sampling has become available to western readers. The results show that rural Chinese consumers utilise a variety of information sources when making their purchase decision, and for different product categories different information sources are preferred. Although perceived source credibility is a reliable predictor for information sources use, the most trusted information source might not always be the most used source. While television is by far the most frequent source of information for any type of product, Chinese rural consumers may trust different sources differently, depending on the type of product.

Previous experimental research found that the pre-exposure of publicity about advertisements has two distinct but related effects in advertised brand recall: (a) a facilitative effect on publicized brands and (b) [...]

This paper presents research gathered from consumer responses to advertisements that appeared during the Super Bowl television transmissions between 1992 and 1997. Results show that positive significant relationships were found between humorous advertisements upon memory and that such advertisements are more effective in low-involvement products.

Quantum spin liquids (QSLs) are topologically ordered states of matter that host fractionalized excitations. A particular route towards a QSL is via strongly bond-dependent interactions on the hexagonal lattice. A number of Ru- and Ir-based candidate Kitaev QSL materials have been pursued, but all have appreciable non-Kitaev interactions. Using time-domain terahertz spectroscopy, we observed a broad magnetic continuum over a wide range of temperatures and fields in the honeycomb cobalt-based magnet BaCo2(AsO4)2, which has been proposed to be a more ideal version of a Kitaev QSL. Applying an in-plane magnetic field of ~0.5 T suppresses the magnetic order, and at higher fields, applying the field gives rise to a spin-polarized state. Under a 4 T magnetic field that was oriented principally out of plane, a broad magnetic continuum was observed that may be consistent with a field-induced QSL. Our results indicate BaCo2(AsO4)2is a promising QSL candidate.

Resilience can play an important role in enabling disadvantaged students to succeed academically. However, few studies in low-resource contexts have evaluated resilience as a process (including a child’s internal capabilities and external resources, like the internal capabilities of a child’s caregiver) and as an outcome (e.g., academic achievement). In the current study, we examined the associations among students’ self-reported internal capabilities, their external resources (e.g., caregivers’ internal capabilities), and their academic resilience (operationalized as performance on a math test). The study was conducted among 1609 primary and secondary school students in rural China using the Connor–Davidson Resilience Scale (CD-RISC) to measure internal capabilities. Student CD-RISC scores were positively associated with external resources including caregiver CD-RISC scores, maternal education level, high levels of perceived social support, recreational reading, and involvement in group-based activities at school. A one-point increase in students’ CD-RISC scores was associated with a 0.01 SD increase in math score (p< 0.001), and the math scores of students whose CD-RISC scores were in the bottom quartile were 0.18 SD lower than those of their peers (p< 0.01). High levels of perceived social support and recreational reading were also associated with academic resilience in the adjusted equation. Directions for future research and policy implications are discussed.

In order to solve the problems of poor fault tolerance and low fault identification rate, a fault location method based on the correlation of main frequency components is proposed. Based on the distribution network of main frequency components extracted by Prony algorithm, this paper introduces the fault location model of low-voltage active distribution network built by hierarchical algorithm, and realises the correlation of main frequency components based on the research of fault location method of low-voltage active distribution network based on intelligent algorithm. The experimental results show that the fault tolerance rate of the proposed method based on the correlation of main frequency components is over 76% and the fault recognition rate is over 60%, which appears to be higher than several other methods. It is consequently believed that the proposed method may stand a good chance to offer better fault location performance.

ABSTRACTmicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene regulation. The presence of miRNAs in extracellular biofluids is increasingly recognized. However, most previous characterization of extracellular miRNAs focused on their overall expression levels. Alternative sequence isoforms and modifications of miRNAs were rarely considered in the extracellular space. Here, we developed a highly accurate bioinformatic method, called miNTA, to identify 3’ non-templated additions (NTAs) of miRNAs using small RNA-sequencing data. Using miNTA, we conducted an in-depth analysis of miRNA 3’ NTA profiles in 1047 extracellular RNA-sequencing data sets of 4 types of biofluids. This analysis identified hundreds of miRNAs with 3’ uridylation or adenylation, with the former being more prevalent. Among these miRNAs, up to 53% (22%) had an average 3’ uridylation (adenylation) level of at least 10% in a specific biofluid. Strikingly, we found that 3’ uridylation levels enabled segregation of different types of biofluids, more effectively than overall miRNA expression levels. This observation suggests that 3’ NTA levels possess fluid-specific information relatively robust to batch effects. In addition, we observed that extracellular miRNAs with 3’ uridylations are enriched in processes related to angiogenesis, apoptosis, and inflammatory response, and this type of modification may stabilize base-pairing between miRNAs and their target genes. Together, our study provides a comprehensive landscape of miRNA NTAs in human biofluids, which paves way for further biomarker discoveries. The insights generated in our work built a foundation for future functional, mechanistic, and translational discoveries.

For an advertiser, is it better to place a television advertisement in a pod of fewer ads? Within a same pod, are some positions better than others? Some advertisers suspect [...]

Two surveys conducted in 1987 shows that Chinese viewers welcomed the comeback of advertising although enthusiasm was less than was thought in the past. Public attitudes toward commercial advertising were very much reserved and slightly calculated. Results also find that mass advertising was effective as a marketing tool.

As two kinds of sulfonamide antibiotics (SAs), sulfadiazine (SD), and sulfamethoxazole (SMX) have been found in wastewater. In this study, the removal of SD and SMX through O3, UV, and UV/O3processes were investigated, and the effects of Cl–, Ca2+, and HCO3–/CO32–on SAs removal were explored. SAs could be decomposed through hydroxylation and hydrolysis. Appropriate 80% and 55% of SD and SMX could be quickly decomposed in 12 mg/L O3solutions. SD is easier to be ozonized than SMX because the unsaturated degree of pyrimidine ring is higher than that of isoxazole ring. The SD removal rate by UV/O3process was lower than that by ozonation because SD was mainly decomposed by direct ozonation, and the O3molecules were decomposed under UV light. Nevertheless, the SMX removal was promoted since SMX was mainly degraded by •OH. The ions in water may affect the decomposition of SAs. As the •OH capturer in water, Cl–or HCO3–/CO32–reacts with •OH to produce radicals with weaker oxidizing ability, resulting in the reduction in the SAs removal rates. Meanwhile, they can accelerate the decomposition of O3to O2, which limits the direct oxidation by O3molecules. The removal of SAs was promoted in the presence of Ca2+because the complexation of Ca2+with the pollutants can promote the indirect oxidation process. Furthermore, Ca2+can reduce the activation energies of the degradation reaction because of its role as an electron transporter, thus facilitating the degradation of SD and SMX.

Human stem-cell-derived models provide the promise of accelerating our understanding of brain disorders, but not knowing whether they possess the ability to mature beyond mid- to late-fetal stages potentially limits their utility. We leveraged a directed differentiation protocol to comprehensively assess maturation in vitro. Based on genome-wide analysis of the epigenetic clock and transcriptomics, as well as RNA editing, we observe that three-dimensional human cortical organoids reach postnatal stages between 250 and 300 days, a timeline paralleling in vivo development. We demonstrate the presence of several known developmental milestones, including switches in the histone deacetylase complex and NMDA receptor subunits, which we confirm at the protein and physiological levels. These results suggest that important components of an intrinsic in vivo developmental program persist in vitro. We further map neurodevelopmental and neurodegenerative disease risk genes onto in vitro gene expression trajectories to provide a resource and webtool (Gene Expression in Cortical Organoids, GECO) to guide disease modeling.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr-NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr-led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivostudy was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

MoS2as atomically thin semiconductor is highly sensitive to ambient atmosphere (e.g., oxygen, moisture, etc.) in optical and electrical properties. Here we report a controlled gas molecules doping of monolayer MoS2via atomic-layer-deposited Al2O3films. The deposited Al2O3films, in the shape of nanospheres, can effectively control the contact areas between ambient atmosphere and MoS2that allows precise modulation of gas molecules doping. By analyzing photoluminescence (PL) emission spectra of MoS2with different thickness of Al2O3, the doped carrier concentration is estimated at ∼2.7 × 1013cm–2based on the mass action model. Moreover, time-dependent PL measurements indicate an incremental stability of single layer MoS2as the thicknesses of Al2O3capping layer increase. Effective control of gas molecules doping in monolayer MoS2provides us a valuable insight into the applications of MoS2based optical and electrical devices.

Hexafluoropropylene oxide dimer acid (HFPO–DA, ammonium salt with trade name: GenX) has been recently detected in river water worldwide. There are significant concerns about its persistence, and potential adverse effects to the biota. In this study, the degradability of GenX by typical advanced redox technologies (UV/persulfate and UV/sulfate) is investigated. Results demonstrate that <5% GenX is oxidized after 3 h in UV/persulfate system, which is much lower than ∼27% for PFOA. In comparison, GenX can be readily degraded and defluorinated by hydrated electron (eaq–) generated by UV/sulfite system. Specifically, GenX is not detectable after 2 h, and >90% of fluoride ion is recovered 6 h later. This is attributed to the accumulation and subsequent degradation of CF3CF2COOH and CF3COOH, which are stable intermediates of GenX degradation. Mechanistic investigations suggest that the etheric bond in the molecule is a favorable attack point for the eaq–. Such finding is corroborated by quantum chemical calculations. The side CF3- at the α-carbon probably acts as an effective barrier that prevents GenX from being cleaved by SO4–• or OH• at its most sensible point (i.e. the carboxyl group). This study illustrates that reduction by UV/sulfite might be a promising technology to remove GenX from contaminated water.

Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which is significantly under-explored. Here, we present an in-depth study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and read biases. Applied to PacBio RNA-seq data, L-GIREMI affords a high accuracy in RNA editing identification. Additionally, our analysis uncovered novel insights about RNA editing occurrences in single molecules and double-stranded RNA structures. L-GIREMI provides a valuable means to study nucleotide variants in long-read RNA-seq.

Supplemental Digital Content is available in the text.Evidences for the personalized use of nonsteroidal anti-inflammatory drugs (NSAIDs) in colorectal cancer (CRC) prevention and treatment that include consideration of prostaglandin E2levels are necessary. This study was designed as a case-control study including 60 CRC patients and 120 cancer-free controls. A sensitive empirical method, precolumn derivatization HPLC, was used to determine plasma PGE2levels. The TaqMan SNP Genotyping Assay was used for the genotyping of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms. Multivariate logistic regression analysis suggested that 1 log10(PGE2) increase would result in a 3.64-fold increase in the risk of CRC. Moreover, subjects with log10(PGE2) level in the 75th percentile had a significantly higher risk of CRC than those with log10(PGE2) levels in the 25th percentile [odds ratio (OR), 3.50; 95% confidence interval (CI), 1.35−9.05]. This association was more evident after adjustment for history of NSAIDs use (OR, 3.85; 95% CI, 1.46−10.16). Preliminarily, 260.02 and 414.95 pg/ml might be proposed as the preventive and warning cutoff values of plasma PGE2for CRC. The preferred NSAIDs dose for patients with the AG+GG (rs689466) and CC+CT (rs5275) genotypes should be higher than that of patients carrying AA or TT genotypes, despite the presence of equal plasma PGE2levels. We show for the first time that the plasma PGE2level is associated with the risk of CRC. We provide a preliminary suggestion for NSAIDs doses adjustment according to PTGS2 genotypes after consideration of plasma PGE2levels.

Alternative splicing is an RNA processing mechanism that affects most genes in human, contributing to disease mechanisms and phenotypic diversity. The regulation of splicing involves an intricate network of cis-regulatory elements and trans-acting factors. Due to their high sequence specificity, cis-regulation of splicing can be altered by genetic variants, significantly affecting splicing outcomes. Recently, multiple methods have been applied to understanding the regulatory effects of genetic variants on splicing. However, it is still challenging to go beyond apparent association to pinpoint functional variants. To fill in this gap, we utilized large-scale data sets of the Genotype-Tissue Expression (GTEx) project to study genetically modulated alternative splicing (GMAS) via identification of allele-specific splicing events. We demonstrate that GMAS events are shared across tissues and individuals more often than expected by chance, consistent with their genetically driven nature. Moreover, although the allelic bias of GMAS exons varies across samples, the degree of variation is similar across tissues versus individuals. Thus, genetic background drives the GMAS pattern to a similar degree as tissue-specific splicing mechanisms. Leveraging the genetically driven nature of GMAS, we developed a new method to predict functional splicing-altering variants, built upon a genotype-phenotype concordance model across samples. Complemented by experimental validations, this method predicted >1000 functional variants, many of which may alter RNA-protein interactions. Lastly, 72% of GMAS-associated SNPs were in linkage disequilibrium with GWAS-reported SNPs, and such association was enriched in tissues of relevance for specific traits/diseases. Our study enables a comprehensive view of genetically driven splicing variations in human tissues.

Abstract

The remarkable success of iodine deficiency disorders (IDD) elimination in China has been achieved through a mandatory universal salt iodization (USI) program. The study aims to estimate the relationship between urinary iodine concentration (UIC) and iodine content in edible salt to assess the current iodine nutritional status of school aged children.A total of 5565 students from 26 of 39 districts/counties in Chongqing participated in the study, UIC and iodine content in table salt were measured. Thyroid volumes of 3311 students were examined by ultrasound and goiter prevalence was calculated.The overall median UIC of students was 222 μg/L (IQR: 150-313 μg/L). Median UIC was significantly different among groups with non-iodized salt (iodine content <5 mg/kg), inadequately iodized salt (between 5 and 21 mg/kg), adequately iodized (between 21 and 39 mg/kg) and excessively iodized (>39 mg/kg) salt (P< 0.01). The total goiter rate was 1.9% (60/3111) and 6.0% (186/3111) according to Chinese national and WHO reference values, respectively. Thyroid volume and goiter prevalence were not different within the three iodine nutritional status groups (insufficient, adequate and excessive, P> 0.05).The efficient implementation of current USI program is able to reduce the goiter prevalence in Chongqing as a low incidence of goiter in school aged children is observed in this study. The widened UIC range of 100–299 μg/L indicating sufficient iodine intake is considered safe with a slim chance of causing goiter or thyroid dysfunction. Further researches were needed to evaluate the applicability of WHO reference in goiter diagnose in Chongqing or identifying more accurate criteria of normal thyroid volume of local students in the future.

•This study is the first bioinformatics analysis to use ESTIMATE and programming visualization software to explore the role of P2Y family genes (P2Ys) in 33 cancer types.•We identified new information on the differential expression of P2Ys and disease survival based on the analysis of big data on pan-cancer.•The expression of P2Ys was associated with the level of immune cell infiltration and tumor microenvironment.•This study provided insight into the significance of P2Y family genes in pan-cancer.

Recently, luminescent metal–organic framework (MOF) materials have attracted considerable attention in fluorescence sensing. In this essay, we prepared a new cluster-based CaII-MOFs {[Ca1.5(μ8-HL1)(DMF)2]·DMF}n(1) with good water dispersibility, excellent photoluminescence properties (FL quantum yield of 20.37%) and great fluorescence stability. Further, it was employed to design as an “off–on” fluorescence sensor for sensitive detection of l-cysteine. This proposed strategy was that fluorescence of CaII-MOFs 1was quenched for providing a low fluorescence background by the introduction of Pb2+forming the CaII-MOFs 1/Pb2+hybrid system. The quenching effect could be ascribed to the static quenching mechanism because of the formation of ground-state complexes and coordination interactions between the free carboxyl of H4L1ligands of CaII-MOFs 1and Pb2+. Then, with the addition of l-cysteine into the CaII-MOFs 1/Pb2+hybrid system, the fluorescence signal was immediately restored. This result was because the Pb2+was gradually released from the hybrid system by chelation interactions between the −SH groups of l-cysteine and Pb2+. This method received a relative wide linear range varying from 0.05 to 40 μM and a low detection limit of 15 nM for detection of l-cysteine. This proposed strategy was also successfully applied to detect l-cysteine in human serum samples with satisfactory recoveries from 95.9 to 101.5%.

Three super city clusters in eastern China, that is, Beijing‐Tianjin‐Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD), have been developed in recent decades. The spatial and diurnal variations of summer hourly rainfall over these city clusters and their possible link to the urbanization are investigated in this study, with the Climate Prediction Center Morphing technique (CMORPH) satellite precipitation estimates at high spatial‐temporal resolutions for 2004‐2009. Although the summer rainfall in eastern China is mainly characterized by large‐scale pattern, significant regional rainfall features over the three city clusters can be clearly observed, which are related to the clustered urbanization. Large hourly rainfall intensity is found over the city clusters or downwind from them. Those regions with large hourly rainfall intensity are named as the city cluster impacted regions (CCIRs), contrast to the surrounding mountainous regions where high frequency and large amount but low hourly intensity of rainfall occur. Location and geometry of each CCIR are unique because of the distinctive geography and structures among city clusters. The CCIR situates right over YRD, but it is shifted to the downwind region with an elongated shape for BTH and a circular shape for PRD. More heavy rain but less light rain occurs over the CCIRs than the surrounding regions. Diurnal variations of light rain amount and frequency can be influenced by both mountain and urbanization, and a diurnal cycle amplitude increase related to the urbanization is detected only over the CCIR of YRD where the terrains are mostly low and flat. Large hourly rainfall intensity is found over the city clusters of eastern China or downwind from themThose regions with large hourly rainfall intensity are named as the city cluster impacted regions (CCIRs)More heavy rain but less light rain occurs over the CCIRs than the surrounding regions

The occurrence and removal of 39 targeted pharmaceuticals and personal care products (PPCPs) from source water, through a drinking water treatment plant (DWTP) to the water supply station, were investigated around the central part of Yangtze River Delta in China using both grab sampling and continuous sampling. Totally 24 of the 39 targeted PPCPs were detected in raw water, and 12 PPCPs were detected in the finished water. The highest observed concentration was enrofloxacin (85.623 ng/L) in raw water. Removal efficiencies were remarkably negative correlated with log Kow(r= - 0.777, p<0.01) after calibration control of concentration, indicating that more soluble PPCPs are easier to remove by the combined process (prechlorination and flocculation/precipitation), the concentration level also had a great impact on the removal efficiency. The normal process in the pilot DWTP seems to be ineffective for PPCPs control, with the limited removal efficiency of less than 30% for each step: pre-chlorination, flocculation and precipitation, post-chlorination and filter. There were notable differences between the data from continuous sampling and grab sampling, which should be considered for different monitoring purposes. The chlorination and the hydrolytic decomposition of PPCPs in the water supply pipe may attenuate PPCPs concentration in the pipeline network. The PPCPs examined in the effluent of DWTP do not impose a potential health risk to the local consumers due to their RQ value lower than 0.00067.

Objective: Few studies have reported blood lead levels (BLLs) in Haitian children, despite the known presence of lead from environmental factors such as soil, water, leaded paint and gasoline, improperly discarded batteries, and earthquakes. We sought to determine the prevalence of elevated blood lead levels (EBLLs) among healthy Haitian children.Methods: We enrolled children aged 9 months to 6 years from 3 geographic areas in Haiti (coastal, urban, and mountain) from March 1 through June 30, 2015. We obtained anthropometric measurements, household income, potential sources of lead exposure, and fingerstick BLLs from 273 children at 6 churches in Haiti. We considered a BLL ≥5 μg/dL to be elevated.Results: Of 273 children enrolled in the study, 95 were from the coastal area, 78 from the urban area, and 100 from the mountain area. The median BLL was 5.8 μg/dL, with higher levels in the mountain area than in the other areas (P< .001). BLLs were elevated in 180 (65.9%) children. The prevalence of EBLL was significantly higher in the mountain area (82 of 100, 82.0%; P< .001) than in the urban area (42 of 78, 53.8%) and the coastal area (56 of 95, 58.9%; P< .001). Twenty-eight (10.3%) children had EBLLs ≥10 μg/dL and 3 (1.1%) children had EBLLs ≥20 μg/dL. Exposure to improperly discarded batteries (P= .006) and living in the mountain area (P< .001) were significant risk factors for EBLLs.Conclusions: More than half of Haitian children in our study had EBLLs. Public health interventions are warranted to protect children in Haiti against lead poisoning.

Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of postmortem brains of people with ASD. We observed a global bias for hypoediting in ASD brains, which was shared across brain regions and involved many synaptic genes. We show that the Fragile X proteins FMRP and FXR1P interact with RNA-editing enzymes (ADAR proteins) and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA-editing alterations in ASD and Fragile X syndrome, establishing this as a molecular link between these related diseases. Our findings, which are corroborated across multiple data sets, including dup15q (genomic duplication of 15q11.2-13.1) cases associated with intellectual disability, highlight RNA-editing dysregulation in ASD and reveal new mechanisms underlying this disorder.

This study evaluated the stiffness of tissue surrounding thyroid nodules using shear wave elastography (SWE). A total of 128 thyroid nodules in 108 patients were examined with conventional ultrasound imaging and SWE. The maximum Young modulus value was measured to evaluate the stiffness of the thyroid nodules (E) and the 2‐mm perinodular region (Eshell). The number of thyroid fibrocytes was evaluated by Masson trichrome staining and image‐processing software. The arrangement of the fibrous structure was also classified. The mean age ± SD of the 108 patients was 33.12 ± 13.34 years (range, 18–80 years). Thirty‐nine thyroid nodules were classified as benign and 89 as malignant. Eshellwas significantly higher for malignant nodules (95.0 ± 21.9 kPa) compared with benign nodules (48.1 ± 17.0 kPa; P< .001). Eshellyielded an area under the receiver operator characteristic curve value of 0.951, which was used for the diagnosis of nodules. There was a high positive correlation between E and Eshellin the malignant group (R= 0.722; P< .001) and a moderate positive correlation in the benign group (R= 0.601; P< .001). Percentages of fibrocytes correlated highly with Eshellin all samples as well as in malignant samples (R= 0.867 and R= 0.729, respectively; P< .001). The degree of disorder of the tissue surrounding thyroid nodules was positively correlated with Eshell(R= 0.833). Perinodular stiffness has potential to improve diagnosis of thyroid nodules.

This paper shows that product category is an important moderator of the relationship between commercial liking and memory. In this multi-year survey of responses to commercials shown on the Super [...]

To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study. A transcriptome-wide association study highlights the Trpv2ion channel as a key locus for cocaine self-administration as well as identifying 17 additional genes, including Arhgef26, Slc18b1, and Slco5a1. We find numerous instances where alternate splice site selection or RNA editing altered transcript abundance. Our work emphasizes the importance of Trpv2, an ionotropic cannabinoid receptor, for the response to cocaine.

The anti-adhesion effect of polylactic acid (PLA) membrane with diamond-like carbon (DLC) depositing is 44.72%, enhanced by 23.11% compared to PLA.DLC deposited on PLA membranes has been shown to effectively reduce the levels of reactive oxygen species, leading to a decrease in the expression of pro-inflammatory cytokines within peritendinous adhesion tissue.DLC decelerates PLA biodegradation and lactic production, which reduces the number of CD68+CD206+macrophages within peritendinous adhesion tissue.

The mechanism of nonionic surfactants improving the cellulose conversion is still controversial. To protect enzyme stability and prevent unproductive adsorption of cellulase to lignin, which have been thought of as the chief factors for the improvement of nonionic surfactants on cellulolytic hydrolysis, were evaluated in this work. SDS-PAGE detection showed that the enzyme could not aggregate in the enzymatic hydrolysis process whether the polysorbates (Tweens) were present or not. Tweens had different capabilities to retain and even improve enzymes’ activities, but these capabilities had little relation to enhancing the enzymatic hydrolysis of treated sugar cane bagasse (SCB). Tweens could increase the adsorption of cellulase to lignins and SCB samples, which was different from the current viewpoint that nonionic surfactants could impede the adsorption of cellulase to lignin. After discussion, it was proposed that the nonionic surfactants initially lubricated the access of cellulase to cellulose and subsequently combined with the free chemical groups released from lignin to impede the adsorption of cellulase to lignin with the enzymatic hydrolysis proceeding.

Shape-tunable hollow silica nanomaterials, including hollow silica nano-spheres and nano-tadpoles, were synthesized with a one-step soft-templating method. A possible particle growth mechanism was proposed. Films were built from these shape-tunable hollow silica nanomaterials with refractive indices as low as 1.045, which is, to the best of our knowledge, the third-lowest value ever reported so far. For the first time, the refractive indices of films were tuned by changing the morphology of building blocks. These films are intrinsically hydrophobic. Moreover, the process used to prepare these nanomaterials without the need for expensive equipment or any post-treatment is well suited for industrial production on large surfaces.

In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene products. By tackling these processes in isolation, recent studies have enabled substantial progress in understanding their global RNA targets and regulatory pathways. However, the interplay between individual steps of RNA processing, an essential aspect of gene regulation, remains poorly understood. By sequencing the RNA of different subcellular fractions, we examined the timing of adenosine-to-inosine (A-to-I) RNA editing and its impact on alternative splicing. We observed that >95% A-to-I RNA editing events occurred in the chromatin-associated RNA prior to polyadenylation. We report about 500 editing sites in the 3′ acceptor sequences that can alter splicing of the associated exons. These exons are highly conserved during evolution and reside in genes with important cellular function. Furthermore, we identified a second class of exons whose splicing is likely modulated by RNA secondary structures that are recognized by the RNA editing machinery. The genome-wide analyses, supported by experimental validations, revealed remarkable interplay between RNA editing and splicing and expanded the repertoire of functional RNA editing sites.

The epithelial–mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they coregulate a set of cassette exon events, with the majority showing discordant splicing regulation. Discordant splicing events regulated by hnRNPM show a positive correlation with splicing during EMT; however, concordant events do not, indicating the role of hnRNPM in regulating alternative splicing during EMT is more complex than previously understood. Motif enrichment analysis near hnRNPM–ESRP1 coregulated exons identifies guanine–uridine rich motifs downstream from hnRNPM-repressed and ESRP1-enhanced exons, supporting a general model of competitive binding to these cis-elements to antagonize alternative splicing. The set of coregulated exons are enriched in genes associated with cell migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of coregulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtyping. This study identifies complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts.

Extensive pre-mRNA back-splicing generates numerous circular RNAs (circRNAs) in human transcriptome. However, the biological functions of these circRNAs remain largely unclear. Here we report that N6-methyladenosine (m6A), the most abundant base modification of RNA, promotes efficient initiation of protein translation from circRNAs in human cells. We discover that consensus m6A motifs are enriched in circRNAs and a single m6A site is sufficient to drive translation initiation. This m6A-driven translation requires initiation factor eIF4G2 and m6A reader YTHDF3, and is enhanced by methyltransferase METTL3/14, inhibited by demethylase FTO, and upregulated upon heat shock. Further analyses through polysome profiling, computational prediction and mass spectrometry reveal that m6A-driven translation of circRNAs is widespread, with hundreds of endogenous circRNAs having translation potential. Our study expands the coding landscape of human transcriptome, and suggests a role of circRNA-derived proteins in cellular responses to environmental stress.

Cellulose degradation is inevitable during the production of furfural from biomass under the acidic systems; meanwhile, the simultaneous high yields of furfural and cellulose degradation product (5-HMF or levulinic acid) are hard to be achieved. To solve the problem and avoid the waste of cellulose, a method of producing furfural and preserving cellulosic residue was explored. Sugarcane bagasse was firstly pre-treated by phosphoric acid to obtain soluble xylo-oligosaccharides. And compared to the low furfural yields in phosphoric acid-water system based on response surface analysis, high furfural yields were obtained in the phosphoric acid-tetrahydrofuran (THF) system, meanwhile only trace cellulose was degraded. Furthermore, by a two-step rising temperature method, furfural yield reached to 66.59 mol%, and cellulose was depolymerised into glucooligosaccharides. After recovery of furfural, this research also investigated the conversion of glucooligosaccharides catalysed by the residual phosphoric acid, and it was found levulinic acid and extremely high yields of formic acid generated at 200°C. [Received: January 12, 2016; Accepted: July 27, 2016]

This study aimed to investigate the amendatory effects of Fu brick tea aqueous extract (FTE) on constipation and its underlying molecular mechanism. The administration of FTE by oral gavage (100 and 400 mg/kg·bw) for 5 weeks significantly increased fecal water content, improved difficult defecation, and enhanced intestinal propulsion in loperamide (LOP)-induced constipated mice. FTE also reduced colonic inflammatory factors, maintained the intestinal tight junction structure, and inhibited colonic Aquaporins (AQPs) expression, thus normalizing the intestinal barrier and colonic water transport system of constipated mice. 16S rRNA gene sequence analysis results indicated that two doses of FTE increased the Firmicutes/Bacteroidota(F/B) ratio at the phylum level and increased the relative abundance of Lactobacillusfrom 5.6 ± 1.3 to 21.5 ± 3.4% and 28.5 ± 4.3% at the genus level, subsequently resulting in a significant elevation of colonic contents short-chain fatty acids levels. The metabolomic analysis demonstrated that FTE improved levels of 25 metabolites associated with constipation. These findings suggest that Fu brick tea has the potential to alleviate constipation by regulating gut microbiota and its metabolites, thereby improving the intestinal barrier and AQPs-mediated water transport system in mice.

New evidence reveals that bol-miR159, an miRNA rich in fruits and vegetables, cross-kingdomly functions in mammalian bodies. However, whether the miRNA could regulate gut microbiota remains unclear. Here, the effect of miR159 on mouse intestinal microbes was comprehensively examined. The results showed that supplementation of miR159 to the chow diet significantly enhanced the diversity of mouse gut microbiota without causing pathological lesions or inflammatory responses on the intestines. At the phylum level, miR159 increased the abundance of Proteobacteria and decreased the Firmicute-to-Bacteroidetes (F/B) ratio. miR159 had prebiotic-like effects on mouse gut microbiota, as it promoted the growth of the bacteria that is beneficial for maintaining gut health. The miRNA can target bacteria genes and get into the bacteria cells. The data provide direct in vivoevidence on the crosstalk between plant miRNAs and intestinal microbes, highlighting the potential for miRNA-based strategies that modulate gut microbes to improve host health.