Nitrate input inhibited the biodegradation of erythromycin through affecting bacterial network modules and keystone species in lake sediments.

Antibiotic contamination and excessive nitrate loads are generally concurrent in aquatic ecosystems. However, little is known about the effects of nitrate input on the biodegradation of antibiotics. In this study, the effects of nitrate input on microbial degradation of erythromycin, a typical macrolide antibiotic widely detected in lake sediments, were investigated. The results showed that the nitrate input significantly inhibited the erythromycin removal and such an inhibitory effect was strengthened with the increased input dosages. Nitrate input significantly increased sediment nitrite concentration, indicating enhanced denitrification under high nitrate pressure. Bacterial network module and keystone species analysis showed that nitrate input enriched the keystone species involved in denitrification (e.g., Simplicispira and Denitratisoma). In contrast, some potential erythromycin-degrading bacteria (e.g., Desulfatiglandales, Pseudomonadales, Nitrospira) were inhibited by nitrate input. The variations in dominant bacterial groups implied competition between denitrification and erythromycin degradation in response to nitrate input. Based on the partial least squares path modeling analysis, keystone species (total effect: 0.419) and bacterial module (total effect: 0.403) showed strong association with erythromycin removal percentage. This indicated that the inhibitory effect of nitrate input on erythromycin degradation was mainly explained by bacterial network modules and keystone species. These findings will help us to assess the bioremediation potential of antibiotic-contaminated sediments suffering from excessive nitrogen discharge concurrently.

Ofloxacin weakened treatment performance of rural domestic sewage in an aerobic biofilm system by affecting biofilm resistance, bacterial community, and functional genes.

Ofloxacin (OFL) is a typical fluoroquinolone antibiotic widely detected in rural domestic sewage, however, its effects on the performance of aerobic biofilm systems during sewage treatment process remain poorly understood. We carried out an aerobic biofilm experiment to explore how the OFL with different concentrations affects the pollutant removal efficiency of rural domestic sewage. Results demonstrated that the OFL negatively affected pollutant removal in aerobic biofilm systems. High OFL levels resulted in a decrease in removal efficiency: 9.33% for chemical oxygen demand (COD), 18.57% for ammonium (NH4+-N), and 8.49% for total phosphorus (TP) after 35 days. The findings related to the chemical and biological properties of the biofilm revealed that the OFL exposure triggered oxidative stress and SOS responses, decreased the live cell number and extracellular polymeric substance content of biofilm, and altered bacterial community composition. More specifically, the relative abundance of key genera linked to COD (e.g., Rhodobacter), NH4+-N (e.g., Nitrosomonas), and TP (e.g., Dechlorimonas) removal was decreased. Such the OFL-induced decrease of these genera might result in the down-regulation of carbon degradation (amyA), ammonia oxidation (hao), and phosphorus adsorption (ppx) functional genes. The conventional pollutants (COD, NH4+-N, and TP) removal was directly affected by biofilm resistance, functional genes, and bacterial community under OFL exposure, and the bacterial community played a more dominant role based on partial least-squares path model analysis. These findings will provide valuable insights into understanding how antibiotics impact the performance of aerobic biofilm systems during rural domestic sewage treatment.

High-temperature stress response: Insights into the molecular regulation of American shad (Alosa sapidissima) using a multi-omics approach.

High temperature is an important abiotic stressor that limits the survival and growth of aquatic organisms. American shad (Alosa sapidissima), a migratory fish suitable for culturing at low temperatures, is known for its delicious taste and thus has high economic value. Studies concerning changes in A. sapidissima under high temperature are limited, especially at the gene expression and protein levels. High-temperature stress significantly reduced the survival rates and increased vacuolar degeneration and inflammatory infiltration in the gills and liver. High temperature increased the activities of SOD, CAT, and cortisol, with a trend of initial increase followed by decreases in MDA, ALP, and LDH, and irregular changes in T-AOC and Na-K-ATPase. Comprehensive analysis of the transcriptome, proteome, and metabolome of gills from fish treated with different culture temperatures (24, 27, and 30 °C) revealed that differentially expressed genes, proteins, and metabolites were highly enriched in pathways involved in protein digestion and absorption, protein processing in endoplasmic reticulum, metabolic pathways, and purine metabolism. Gene expression and protein profiles indicated that genes coding for antioxidants (i.e., cat and alpl) and members of the heat shock protein (i.e., HSP70, HSP90AA1, and HSP5) were significantly upregulated. Additionally, a conjoint analysis revealed that several key enzymes, including nucleoside diphosphate kinase 2, adenosine deaminase, and ectonucleoside triphosphate diphosphohydrolase 5/6 were altered, thereby affecting the metabolism of guanosine, guanine, and inosine. An interaction network further confirmed that levels of the essential amino acids DL-arginine and L-histidine were significantly reduced, and corticosterone levels were significantly increased, suggesting that A. sapidissima may be more dependent on amino acids for energy in vivo. Overall, this work suggests that living in a high-temperature environment leads to differential defense responses in fishes. The results provide novel perspectives for studying the molecular basis of adaptation to climate change in A. sapidissima and for genetic selection.

Regulatory mechanisms of submerged macrophyte on bacterial community recovery in decabromodiphenyl ether contaminated sediment: Microbiological and metabolomic perspectives.

Polybrominated diphenyl ether contamination in sediments poses serious threats to human health and ecological safety. Despite the broad application of submerged macrophytes for remediating pollutants, their regulatory influence on bacterial communities in contaminated sediments remains unclear. Herein, we analyzed the effects of decabromodiphenyl ether (BDE-209) and Hydrilla verticillata on sediment bacterial community and function using 16S rRNA gene sequencing and sediment metabolomics. Results showed that BDE-209 significantly inhibited sediment bacterial diversity and metabolic functions. It also enhanced bacterial interactions and altered both the bacterial community and metabolite composition. Uridine and inosine were critical metabolites that positively co-occurred with bacterial taxa inhibited by BDE-209. Notably, planting H. verticillata effectively alleviated the adverse impacts of BDE-209 by reducing its residuals, increasing the total organic carbon, and modifying metabolic profiles. Such mitigation was evidenced by enhancing bacterial diversity, restoring metabolic functions, and attenuating bacterial interactions. However, mitigation effectiveness depended on treatment time. Additionally, propionic acid, palmitic acid, and palmitoleic acid may facilitate the restoration of phylum Proteobacteria and class Planctomycetacia in H. verticillata planted sediment. Together, these findings improve understanding of BDE-209's impacts on aquatic ecosystems and provide valuable insights for ecological restoration using submerged macrophytes.

Blocking Dectin-1 prevents colorectal tumorigenesis by suppressing prostaglandin E2 production in myeloid-derived suppressor cells and enhancing IL-22 binding protein expression.

Dectin-1 (gene Clec7a), a receptor for ß-glucans, plays important roles in the host defense against fungi and immune homeostasis of the intestine. Although this molecule is also suggested to be involved in the regulation of tumorigenesis, the role in intestinal tumor development remains to be elucidated. In this study, we find that azoxymethane-dextran-sodium-sulfate-induced and ApcMin-induced intestinal tumorigenesis are suppressed in Clec7a-/- mice independently from commensal microbiota. Dectin-1 is preferentially expressed on myeloid-derived suppressor cells (MDSCs). In the Clec7a-/- mouse colon, the proportion of MDSCs and MDSC-derived prostaglandin E2 (PGE2) levels are reduced, while the expression of IL-22 binding protein (IL-22BP; gene Il22ra2) is upregulated. Dectin-1 signaling induces PGE2-synthesizing enzymes and PGE2 suppresses Il22ra2 expression in vitro and in vivo. Administration of short chain ß-glucan laminarin, an antagonist of Dectin-1, suppresses the development of mouse colorectal tumors. Furthermore, in patients with colorectal cancer (CRC), the expression of CLEC7A is also observed in MDSCs and correlated with the death rate and tumor severity. Dectin-1 signaling upregulates PGE2-synthesizing enzyme expression and PGE2 suppresses IL22RA2 expression in human CRC-infiltrating cells. These observations indicate a role of the Dectin-1-PGE2-IL-22BP axis in regulating intestinal tumorigenesis, suggesting Dectin-1 as a potential target for CRC therapy.

Continuously Flow Photothermal Catalysis Efficiently CO2 Reduction Over S-Scheme 2D/0D Bi5 O7 I-OVs/Cd0.5 Zn0.5 S Heterojunction with Strong Interfacial Electric Field.

Using CO2 , water, and sunlight to produce solar fuel is a very attractive process, which can synchronously reduce carbon and convert solar energy into hydrocarbons. However, photocatalytic CO2 reduction is often limited by the low selectivity of reduction products and poor photocatalytic activity. In this study, S-scheme Bi5 O7 I-OVs/Cd0.5 Zn0.5 S (Bi5 O7 I-OVs/CZS-0.5) heterojunction with strong interfacial electric field (IEF) is prepared by in situ growth method. The performance of reduction CO2 to CO is studied by continuous flow photothermal catalytic (PTC) CO2 reduction platform. 12.5% Bi5 O7 I-OVs/CZS-0.5 shows excellent CO yield of 58.6 µmol g-1  h-1 and selectivity of 98.4%, which are 35.1 times than that of CZS-0.5 under visible light. The charge transfer path of the S-scheme through theoretical calculation (DFT), in situ irradiation Kelvin probe force microscope (ISI-KPFM) and in situ irradiation X-ray photoelectron spectroscopy (ISI-XPS) analysis, is verified. The study can provide useful guidance and reference for improving activity by oxygen vacancy induced strong IEF and the development of a continuous flow PTC CO2 reduction system.

MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing.

The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC.

Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA-Dependent Suppression of Oxidative Phosphorylation.

The tumor suppressor p53 is somatically mutated in half of all human cancers. Paradoxically, the wild-type p53 (WTp53) is often retained in certain human cancers, such as hepatocarcinoma (HCC). We discovered a physiological and oncogenic role of WTp53 in suppressing pyruvate-driven oxidative phosphorylation by inducing PUMA. PUMA inhibits mitochondrial pyruvate uptake by disrupting the oligomerization and function of mitochondrial pyruvate carrier (MPC) through PUMA-MPC interaction, which depends on IκB kinase-mediated phosphorylation of PUMA at Ser96/106. High expression levels of PUMA are correlated with decreased mitochondrial pyruvate uptake and increased glycolysis in HCCs and poor prognosis of HCC patients. These findings are instrumental for cancer drug discovery aiming at activating WTp53 or restoring WTp53 activity to p53 mutants.

Fluorescence red-shift of gold-silver nanoclusters upon interaction with cysteine and its application.

In this work, gold-silver alloy nanoclusters (AuAg NCs) were demonstrated as a novel probe for fluorescent detection of cysteine (Cys). The alloy nanoclusters were fabricated by bovine serum albumin as a template and NaBH4 as a reducer. They showed a red emission at 650 nm. The interaction between AuAg NCs and Cys was investigated. The thiol group in Cys molecules has strong affinity on the surface of metals, which results in variation of fluorescence peak wavelength. It was further demonstrated that this red-shift of fluorescence had a good linear relationship with the concentration of Cys in the range of 2-100 µM. The method was successfully applied for human plasma analysis with satisfactory results. This novel strategy was expected to provide a potential opportunity for extending the application of novel metal nanoclusters in fluorescence.

Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling.

Long non-coding RNAs (lncRNAs) have emerged as a new class of gene expression regulators playing key roles in many biological and pathophysiological processes. Here, we identify cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic lncRNA. CCRR is downregulated in a mouse model of heart failure (HF) and in patients with HF, and this downregulation slows cardiac conduction and enhances arrhythmogenicity. Moreover, CCRR silencing induces arrhythmias in healthy mice. CCRR overexpression eliminates these detrimental alterations. HF or CCRR knockdown causes destruction of intercalated discs and gap junctions to slow longitudinal cardiac conduction. CCRR overexpression improves cardiac conduction by blocking endocytic trafficking of connexin43 (Cx43) to prevent its degradation via binding to Cx43-interacting protein CIP85, whereas CCRR silence does the opposite. We identified the functional domain of CCRR, which can reproduce the functional roles and pertinent molecular events of full-length CCRR. Our study suggests CCRR replacement a potential therapeutic approach for pathological arrhythmias.

BiOCl Decorated NaNbO3 Nanocubes: A Novel p-n Heterojunction Photocatalyst With Improved Activity for Ofloxacin Degradation.

BiOCl/NaNbO3 p-n heterojunction photocatalysts with significantly improved photocatalytic performance were fabricated by a facile in-situ growth method. The obtained BiOCl/NaNbO3 samples were characterized by UV-vis absorption spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), photocurrent (PC) and photoluminescence spectroscopy (PL). The photocatalytic activity of the BiOCl/NaNbO3 samples was investigated by the degradation of a typical antibiotic Ofloxacin (OFX). The experimental results showed that BiOCl/NaNbO3 composites exhibited much higher photocatalytic activity for OFX degradation compared to pure NaNbO3 and BiOCl. The degradation percent of OFX reached 90% within 60 min, and the apparent rate constant was about 8 times as that of pure NaNbO3 and BiOCl. The improved activity can be attributed to the formation of p-n junction between NaNbO3 and BiOCl. The formed p-n junction facilitated the separation of photogenerated holes and electrons, thereby enhancing photocatalytic activity. In addition, the composite photocatalyst showed satisfactory stability for the degradation of OFX. Due to the simple synthesis process, high photocatalytic activity, and the good recyclability of these composite photocatalysts, the results of this study would provide a good example for the rational design of other highly efficient heterojunction photocatalytic materials.

Carnitine-acylcarnitine translocase deficiency with c.199-10 T>G and novel c.1A>G mutation: Two case reports and brief literature review.

RATIONALE: Carnitine-acylcarnitine translocate deficiency (CACTD) is a rare and life-threatening, autosomal recessive disorder of fatty acid ß-oxidation characterized by hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy, liver dysfunction, and muscle weakness; culminating in early death. To date, CACTD cases screened from the Chinese mainland population, especially patient with compound heterozygote with c.199-10T>G and a novel c.1A>G mutation in the SLC25A20 gene has never been described. PATIENT CONCERNS: Herein, we report 2 neonatal cases of CACTD identified from the mainland China. These 2 patients were presented with severe metabolic crisis and their clinical conditions deteriorate rapidly and both died of cardiorespiratory collapse in the first week of life. We present the clinical and biochemical features of 2 probands and a brief literature review of previously reported CACTD cases with the c.199-10T>G mutation. DIAGNOSES: The acylcarnitine profiles by tandem-mass-spectrometry and the mutation analysis of SLC25A20 gene confirmed the diagnosis of CACTD in both patients. Mutation analysis demonstrated that patient No. 1 was homozygous for c.199-10T>G mutation, while patient No. 2 was a compound heterozygote for 2 mutations, a maternally-inherited c.199-10T>G and a paternally-inherited, novel c.1A>G mutation. INTERVENTIONS: Both patients were treated with an aggressive treatment regimen include high glucose and arginine infusion, respiratory, and circulatory support. OUTCOMES: The first proband died 3 days after delivery due to sudden cardiac arrest. The second patient's clinical condition, at one time, was improved by high glucose infusion, intravenous arginine, and circulatory support. However, the patient failed to wean from mechanical ventilation. Unfortunately, her parents refused further treatment due to fear of financial burdens. The patient died of congestive heart failure in the 6th day of life. LESSONS: We report the first 2 cases of CACTD identified from the mainland China. Apart from a founder mutation c.199-10T>G, we identified a novel c.1A>G mutation. Patients with CACTD with a genotype of c.199-10T>G mutation usually presents with a severe clinical phenotype. Early recognition and appropriate treatment is crucial in this highly lethal disorder. This case series highlights the importance of screening for metabolic diseases including CACTD in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period.

Circulating long non-coding RNAs NRON and MHRT as novel predictive biomarkers of heart failure.

This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for heart failure (HF). We measured the circulating levels of 13 individual lncRNAs which are known to be relevant to cardiovascular disease in the plasma samples from 72 HF patients and 60 non-HF control participants using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) methods. We found that out of the 13 lncRNAs tested, non-coding repressor of NFAT (NRON) and myosin heavy-chain-associated RNA transcripts (MHRT) had significantly higher plasma levels in HF than in non-HF subjects: 3.17 ± 0.30 versus 1.0 ± 0.07 for NRON (P < 0.0001) and 1.66 ± 0.14 versus 1.0 ± 0.12 for MHRT (P < 0.0001). The area under the ROC curve was 0.865 for NRON and 0.702 for MHRT. Univariate and multivariate analyses identified NRON and MHRT as independent predictors for HF. Spearman's rank correlation analysis showed that NRON was negatively correlated with HDL and positively correlated with LDH, whereas MHRT was positively correlated with AST and LDH. Hence, elevation of circulating NRON and MHRT predicts HF and may be considered as novel biomarkers of HF.

Molecular characterization and expression analysis of four cathepsin L genes in the razor clam, Sinonovacula constricta.

Cathepsin L (CTSL) is a lysosomal cysteine protease involved in immune responses in vertebrates. However, few studies exist regarding the role of cathepsin L in bivalves. In this study, we isolated and characterized four cathepsin L genes from the razor clam Sinonovacula constricta, referred to as CTSL1, CTSL2, CTSL3 and CTSL4. These four genes contained typical papain-like cysteine protease structure and enzyme activity sites with ERWNIN-like and GNFD-like motifs in the proregion domain and an oxyanion hole (Gln) and a catalytic triad (Cys, His and Asn) in the mature domain. Expression analysis of the four transcripts revealed a tissue-specific pattern with high expression of CTSL1 and CTSL3 in liver and gonad tissues and high expression of CTSL2 and CTSL4 in liver and gill tissues. During the developmental stages, the four transcripts showed the highest expression in the juvenile stage; however, CTSL3 had a much higher expression level than the other three transcripts during embryogenesis. The four transcripts showed significant changes in expression as early as 4 h or 8 h after infection with Vibrio anguillarum. The fact that bacterial infection can induce expression of the four CTSL transcripts suggests that these transcripts are important components of the innate immunity system of the clam.

Identification of immune genes of the Agamaki clam (Sinonovacula constricta) by sequencing and bioinformatic analysis of ESTs.

The Agamaki clam (Sinonovacula constricta) is an economically important shellfish in Asia. However, genomic research on this species is still in its infancy, and genomic resources are largely unavailable. The objective of this study was to generate expressed sequence tags (ESTs) from a normalized liver complementary DNA library and to identify genes that function in immune defense. A total of 5,296 ESTs were sequenced, from which 540 contigs and 3,473 singletons were identified. BLAST homology analysis indicated that only 20.7% of these ESTs were homologues of known genes while the remaining 79.3% appeared to be novel sequences. Based on sequence similarities, 43 putative immune genes were identified that encode proteases and protease inhibitors, adhesive proteins, stress proteins, lysosomal enzymes, and signal transduction regulators. Our study thus provides both a large collection of novel transcripts and a detailed annotation of immune genes for an important bivalve species.

A liquid chromatography/mass spectrometry-based method for the selection of ATP competitive kinase inhibitors.

The currently approved kinase inhibitors for therapeutic uses and a number of kinase inhibitors that are undergoing clinical trials are directed toward the adenosine triphosphate (ATP) binding site of protein kinases. The 5'-fluorosulfonylbenzoyl 5'-adenosine (FSBA) is an ATP-affinity reagent that covalently modifies a conserved lysine present in the nucleotide-binding site of most kinases. The authors have developed a liquid chromatography/mass spectrometry-based method to monitor binding of ATP competitive protein kinase inhibitors using FSBA as a nonselective activity-based probe for protein kinases. Their method provides a general, rapid, and reproducible means to screen and validate selective ATP competitive inhibitors of protein kinases.