Serum uric acid levels and health outcomes in CKD: a prospective cohort study.

BACKGROUND: Hyperuricemia is prevalent in individuals with chronic kidney disease (CKD). Elevated serum uric acid (SUA) concentrations have been considered an independent risk factor for the onset of CKD. However, the relationship between SUA concentrations and long-term health outcomes among patients with CKD remains unclear. METHODS: We performed a prospective cohort study with nationally representative sample to investigate the relationship between SUA concentrations and mortality risk including all-cause, cardiovascular disease (CVD) and cancer mortality, among patients with CKD. The weighted restricted cubic spline analyses combined with the multivariate-adjusted Cox proportional hazard models were used to test the nonlinearity of relationship. RESULTS: The 6642 patients participating in National Health and Nutrition Examination Survey 1999-2018 were enrolled. During 656 885 person-months of follow-up time, 2619 all-cause deaths were recorded, including 1030 CVD deaths and 458 cancer deaths. Our study presented J-shaped non-linear relationships between SUA concentrations and all-cause and CVD mortality with inflection points at 311.65 µmol/L and 392.34 µmol/L, respectively. When SUA concentration was higher than those inflection points, every increase of 50 µmol/L SUA was associated with 11.7% and 17.0% greater multivariable-adjusted hazard ratio of all-cause and CVD mortality, respectively. In addition, a negative linear correlation with cancer mortality was detected. CONCLUSION: These findings suggested that maintaining appropriate SUA concentrations may improve long-term health outcomes among CKD patients. The corresponding inflection points of J-shaped non-linear relationships were 311.65 and 392.34 µmol/L for all-cause and CVD mortality. Further clinical trials are required to investigate uric acid-lowering targets.

Re-evaluation and modification of dehydrogenase activity tests in assessing microbial activity for wastewater treatment plant operation.

Reliable and cost-effective methods for monitoring microbial activity are critical for process control in wastewater treatment plants. The dehydrogenase activity (DHA) test has been recognized as an efficient measure of biological activity due to its simplicity and broad applicability. Nevertheless, the existing DHA test methods suffer from imperfections and are difficult to implement as routine monitoring techniques. In this work, an accurate and cost-effective modified DHA approach was developed and the procedure for the DHA test was critically evaluated with respect to the standard construction, sample pretreatment, incubation and extraction conditions. The feasibility of the modified DHA test was demonstrated by comparison with the oxygen uptake rate and adenosine triphosphate in a sequencing batch reactor. The sensitivities of the two typical tetrazolium salts to toxicant inhibition by heavy metals and antibiotics were compared, revealing that 2,3,5-triphenyltetrazolium chloride (TTC) exhibited a higher sensitivity. Furthermore, the sensitivity mechanism of the two DHA tests was elucidated through electrochemical experiments, theoretical analysis and molecular simulations. Both tetrazolium salts were found to be effective artificial electron acceptors due to their low redox potentials. Molecular docking simulations revealed that TTC could outperform other tetrazolium salts in accepting electrons and hydrogens from dehydrogenase. Overall, the modified DHA approach presents an accurate and cost-effective way to measure microbial activity, making it a practical tool for wastewater treatment plants.

Enforcing energy consumption promotes microbial extracellular respiration for xenobiotic bioconversion.

Extracellular electron transfer (EET) empowers electrogens to catalyse the bioconversion of a wide range of xenobiotics in the environment. Synthetic bioengineering has proven effective in promoting EET output. However, conventional strategies mainly focus on modifications of EET-related genes or pathways, which leads to a bottleneck due to the intricate nature of electrogenic metabolic properties and intricate pathway regulation that remain unelucidated. Herein, we propose a novel EET pathway-independent approach, from an energy manipulation perspective, to enhance microbial EET output. The Controlled Hydrolyzation of ATP to Enhance Extracellular Respiration (CHEER) strategy promotes energy utilization and persistently reduces the intracellular ATP level in Shewanella oneidensis, a representative electrogenic microbe. This approach leads to the accelerated consumption of carbon substrate, increased biomass accumulation and an expanded intracellular NADH pool. Both microbial electrolysis cell and microbial fuel cell tests exhibit that the CHEER strain substantially enhances EET capability. Analysis of transcriptome profiles reveals that the CHEER strain considerably bolsters biomass synthesis and metabolic activity. When applied to the bioconversion of model xenobiotics including methyl orange, Cr(VI) and U(VI), the CHEER strain consistently exhibits enhanced removal efficiencies. This work provides a new perspective and a feasible strategy to enhance microbial EET for efficient xenobiotic conversion.

Heterogeneous Fenton water purification catalyzed by iron phosphide (FeP).

Heterogeneous Fenton reaction has a great application potential in water purification, but efficient catalysts are still lacking. Iron phosphide (FeP) has a higher activity than the conventional Fe-based catalysts for Fenton reactions, but its ability as a Fenton catalyst to directly activate H2O2 remains unreported. Herein, we demonstrate that the fabricated FeP has a lower electron transfer resistance than the typical conventional Fe-based catalysts, i.e., Fe2O3, Fe3O4, and FeOOH, and thus could active H2O2 to produce hydroxyl radicals more efficiently. In the heterogeneous Fenton reactions for sodium benzoate degradation, the FeP catalyst presents a superior activity with a reaction rate constant more than 20 times those of the other catalysts (i.e., Fe2O3, Fe3O4, and FeOOH). Moreover, it also exhibits a great catalytic activity in the treatment of real water samples and has a good stability in the cycling tests. Furthermore, the FeP could be loaded onto a centimeter-sized porous carbon support and the prepared macro-sized catalyst exhibits an excellent water treatment performance and can be well recycled. This work reveals a great potential of FeP as a catalyst for heterogeneous Fenton reactions and may inspire further development and practical application of highly efficient catalysts for water purification.

Specific cytokine patterns in Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis compared to Kawasaki disease in children.

The aim of the study was to test whether the cytokine profile could be used as a marker to differentiate between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and Kawasaki disease (KD). A total of 70 hospitalized children with HLH and KD admitted to hospital for the first time from March 2017 to December 2021 were enrolled in this study. Fifty-five healthy children were enrolled as normal controls. All patients and normal controls were tested for the six cytokines including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) by flow cytometry. IL-10 and IFN-γ levels were significantly higher in children with EBV-HLH than in the KD, IL-6 was lower in EBV-HLH patients than in the KD. IL-10/IL-6 ratio, IFN-γ/IL-6 ratio and IL10/IFN-γ ratio in children with EBV-HLH were significantly much higher than children in the KD group. When the diagnostic cutoff values of IL-10, IFN-γ, IL-10/IL-6 ratio and IFN-γ/IL-6 ratio were >13.2 pg/ml, >71.0 pg/ml, >0.37 and >1.34, respectively, the sensitivity and specificity of the diagnosis of EBV-HLH disease were 91.7% and 97.1%, 72.2% and 97.1%, 86.1% and 100.0%, and 75.0% and 97.1%, respectively. Notably high IL-10 and IFN-γ and moderately elevated IL-6 suggest the diagnosis of EBV-HLH, while high IL-6 levels with low IL-10 or IFN-γ concentration would suggest KD. Additionally, IL-10/IL-6 ratio or IFN-γ/IL-6 ratio could be used as an index to differentiate between EBV-HLH and KD.

Joint Application of Multiple Inflammatory Cytokines in Diagnosis of Gout Flare.

Purpose: This study aimed to explore the accuracy for joint application of inflammatory cytokines in diagnosis of gout flare by comparison with peripheral blood cells. Methods: We collected the clinical data of 96 acute gout patients and 144 remission gout patients, and compared the levels of peripheral blood cells, inflammatory cytokines and blood biochemistry indexes between acute and remission gout. We respectively assessed the area under curves (AUCs) for single and multiple inflammatory cytokines including C-reactive protein (CRP), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and single and multiple peripheral blood cells including platelet (PLT), white blood cell (WBC), percentages of neutrophils (N%), lymphocytes (L%), eosinophils (E%), basophils (B%) in diagnosis of acute gout by receiver operating characteristic (ROC) curve analysis. Results: By contrast with remission gout, the levels of PLT, WBC, N%, CRP, IL-1ß, IL-6 and TNF-α increased, and the levels of L%, E% and B% decreased in acute gout. The AUCs of PLT, WBC, N%, L%, E% and B% in diagnosis of acute gout were respectively 0.591, 0.601, 0.581, 0.567, 0.608 and 0.635, while the AUC for joint application of these peripheral blood cells was 0.674. Moreover, the AUCs of CRP, IL-1ß, IL-6 and TNF-α in diagnosis of acute gout were respectively 0.814, 0.683, 0.622 and 0.746, while the AUC for joint application of these inflammatory cytokines was 0.883, reflecting significantly higher levels than peripheral blood cells. Conclusion: The joint application of multiple inflammatory cytokines can better distinguish acute gout from remission gout compared with peripheral blood cells.

Microbial mixotrophic denitrification using iron(II) as an assisted electron donor.

Mixotrophic denitrification processes have a great potential in nitrogen removal in biological wastewater treatment processes. However, so far, few studies have focused on the mixotrophic denitrification system using Fe(II) as an exclusively assisted electron donors and the underlying mechanisms in such a process remain unclear. Furthermore, the mechanisms by which microorganisms cover carbon, nitrogen, phosphorus and iron in an iron-assisted mixotrophic system remain unrevealed. In this work, we explore the feasibility of using Fe(II) as an assisted electron donor for enhancing simultaneous nitrogen and phosphorus removal via long-term reactor operation and batch tests. The results show that Fe(II) could provide electrons for efficient nitrate reduction and that biological reactions played a predominant role in these systems. In these systems Thermomonas, a strain of nitrate-reduction Fe(II)-oxidation bacterium, was enriched and accounted for a maximum abundance of 60.2%. These findings indicate a great potential of the Fe(II)-assisted mixotrophic denitrification system for practical use as an efficient simultaneous nitrogen and phosphorus removal process.

Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma.

Emerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed that NAT10 enhanced the metastasis ability and apoptosis resistance of HCC cells in ERS and ERS state. NAT10 could upregulate the modification level of HSP90AA1 mRNA ac4C, maintain the stability of HSP90AA1, and upregulate the expression of HSP90AA1, which further promotes the metastasis of ERS hepatoma cells and the resistance to apoptosis of Lenvatinib. This study proposes a novel mechanism by which NAT10-mediated mRNA ac4C modification regulates tumor metastasis. In addition, we demonstrated the regulatory effect of NAT10-HSP90AA1 on metastasis and drug resistance of ERS in HCC cells.

Tastin promotes non-small-cell lung cancer progression through the ErbB4, PI3K/AKT, and ERK1/2 pathways.

Tastin might be involved in tumorigenesis, but its role in non-small-cell lung cancer (NSCLC) has not been adequately explored. This work aimed to examine tastin's role in NSCLC and to explore the underlying mechanism. The Gene Expression Omnibus (GEO), Gene Expression Database of Normal and Tumor tissues (GENT), and Cancer Genome Atlas (TCGA) databases were used. Four GEO datasets (GSE81089, GSE40419, GSE74706, and GSE19188) containing gene expression data for NSCLC and normal tissue samples were analyzed for tastin mRNA expression. Tastin expression levels in different tissues were compared using the GENT website. TCGA biolinks were used to download gene expression quantification (n = 594) and overall survival data (n = 535). In total, 30 lung adenocarcinoma and 25 lung squamous cell carcinoma cases were enrolled. In addition, four-week-old male BALB/c nude mice (n = 9/group) were used to establish xenograft mouse models. Furthermore, cultured HEK293T, A549, and NCI-H226 cells assessed. Immunoblot, hematoxylin and eosin (H&E) staining, immunohistochemistry, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), fluorescence microscopy, flow cytometry, lentiviral transduction, and MTT, colony formation, wound healing, and Transwell assays were carried out. Tastin expression levels were markedly increased in NSCLC tumor tissue specimens and correlated with a poorer prognosis. Silencing of tastin inhibited the proliferative and migratory abilities of NSCLC cells. Bioinformatic analysis suggested that tastin interacts with ErbB4. The PI3K/AKT and ERK1/2 downstream pathways were suppressed in tastin-deficient cells. In conclusion, tastin might be involved in NSCLC growth and invasion and is a potential therapeutic target in NSCLC.

Exosomal NAMPT from chronic lymphocytic leukemia cells orchestrate monocyte survival and phenotype under endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress has been reported to be transmitted from tumor cells to immune cells via exosome and implicated in immune escape. However, the influence of ER stress on monocytes in chronic lymphocytic leukemia (CLL) cells is largely unknown. Here, we observed the expression of ER stress markers (GRP78, ATF6, PERK, IRE1a, and XBP1s) in CLL cells. The increasing mRNA expression of these ER stress response components was positively correlated with more aggressive disease. Exosome from ER stress inducer tunicamycin (TM)-primed CLL cells (ERS-exo) up-regulated the expression of ER stress marker on monocytes, indicating ER stress is transmissible in vitro via exosome. Treatment with ERS-exo promoted the survival of monocytes and induced phenotypic changes with a significantly larger percentage of CD14+ CD16+ monocytes. Finally, we identified exosome-mediated transfer of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) from ER stressed CLL cells into monocytes as a novel mechanism through which ERS-exo regulated monocytes. Exosomal eNAMPT up-regulated nicotinamide adenine dinucleotide (NAD+ ) production which subsequently activated SIRT1-C/EBPß signaling pathway in monocytes. Our results suggest the role of ER stress in mediating immunological dysfunction in CLL.

Biomimetic nanoparticles for tumor immunotherapy.

Currently, tumor treatment research still focuses on the cancer cells themselves, but the fact that the immune system plays an important role in inhibiting tumor development cannot be ignored. The activation of the immune system depends on the difference between self and non-self. Unfortunately, cancer is characterized by genetic changes in the host cells that lead to uncontrolled cell proliferation and evade immune surveillance. Cancer immunotherapy aims to coordinate a patient's immune system to target, fight, and destroy cancer cells without destroying the normal cells. Nevertheless, antitumor immunity driven by the autoimmune system alone may be inadequate for treatment. The development of drug delivery systems (DDS) based on nanoparticles can not only promote immunotherapy but also improve the immunosuppressive tumor microenvironment (ITM), which provides promising strategies for cancer treatment. However, conventional nano drug delivery systems (NDDS) are subject to several limitations in clinical transformation, such as immunogenicity and the potential toxicity risks of the carrier materials, premature drug leakage at off-target sites during circulation and drug load content. In order to address these limitations, this paper reviews the trends and progress of biomimetic NDDS and discusses the applications of each biomimetic system in tumor immunotherapy. Furthermore, we review the various combination immunotherapies based on biomimetic NDDS and key considerations for clinical transformation.

Combination of cellulose and plant oil toward sustainable bottlebrush copolymer elastomers with tunable mechanical performance.

In this work, sustainable cellulose-g-poly(lauryl acrylate-co-acrylamide) [Cell-g-P(LA-co-AM)] bottlebrush copolymer elastomers derived from cellulose and plant oil were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Differential scanning calorimeter (DSC) results indicate that these thermally stable Cell-g-P(LA-co-AM) bottlebrush copolymer elastomers show adjustable melting temperatures. Monotonic and cyclic tensile tests suggest that the mechanical properties, including tensile strength, extensibility, Young's modulus, and elasticity, can be conveniently controlled by changing the LA/AM feed ratio and cellulose content. In such kind of bottlebrush copolymer elastomers, the rigid cellulose backbones act as cross-linking points to provide tensile strength. The incorporated PAM segments can form additional network structure via hydrogen bonding, resulting in enhanced tensile strength but decreased extensibility when more PAM segments are introduced. This versatile strategy can promote the development of sustainable cellulose-based bottlebrush copolymer elastomers from renewable resources.

Isoliquiritin Ameliorates Cisplatin-Induced Renal Proximal Tubular Cell Injury by Antagonizing Apoptosis, Oxidative Stress and Inflammation.

Acute kidney injury (AKI) is a clinical syndrome characterized by morbidity, mortality, and cost. Cis-diamminedichloroplatinum (cisplatin) is a chemotherapeutic agent used to treat solid tumors and hematological malignancies, but its side effects, especially nephrotoxicity, limit its clinical application. Isoliquiritin (ISL), one of the major flavonoid glycoside compounds in licorice, has been reported to have anti-apoptotic, antioxidant, and anti-inflammatory activities. However, the effect and mechanism of ISL on cisplatin-induced renal proximal tubular cell injury remain unknown. In this study, mouse proximal tubular cells (mPTCs) and human proximal tubule epithelial cells (HK2) were administered increasing concentrations of ISL from 7.8125 to 250 µM. Moreover, mPTC and HK2 cells were pretreated with ISL for 6-8 h, followed by stimulation with cisplatin for 24 h. CCK-8 assay was performed to evaluate the cell viability. Apoptosis and reactive oxygen species (ROS) of cells were measured by using flow cytometer and western blotting. Our results showed that ISL had no obvious effect on cell viability. ISL decreased cisplatin-induced cell injury in a dose-dependent manner. ISL also protected against cisplatin-induced cell apoptosis. Meanwhile, the enhanced protein levels of Bax, cleaved caspase-3/caspase-3 ratio, levels of Pp-65/p-65, levels of IL-6, and the production of ROS induced by cisplatin were significantly attenuated by ISL treatment. Moreover, ISL markedly increased the protein levels of Bcl-2 and SOD2, which were reduced by cisplatin stimulation. These results showed that ISL ameliorated cisplatin-induced renal proximal tubular cell injury by antagonizing apoptosis, oxidative stress and inflammation.

Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous "inflammation brake." We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.

Recovery of Iron-Dependent Autotrophic Denitrification Activity from Cell-Iron Mineral Aggregation-Induced Reversible Inhibition by Low-Intensity Ultrasonication.

Iron-dependent autotrophic denitrification (IDAD) has garnered increasing interests as an efficient method for removing nitrogen from wastewater with a low carbon to nitrogen ratio. However, an inevitable deterioration of IDAD performance casts a shadow over its further development. In this work, the hidden cause for such a deterioration is uncovered, and a viable solution to this problem is provided. Batch test results reveal that the aggregation of microbial cells and iron-bearing minerals induced a cumulative and reversible inhibition on the activity of IDAD sludge. Extracellular polymeric substances were found to play a glue-like role in the cell-iron mineral aggregates, where microbial cells were caged, and their metabolisms were suppressed. Adopting low-intensity ultrasound treatment efficiently restored the IDAD activity by disintegrating such aggregates rather than stimulating the microbial metabolism. Moreover, the ultrasonication-assisted IDAD bioreactor exhibited an advantageous nitrogen removal efficiency (with a maximum enhancement of 72.3%) and operational stability compared to the control one, demonstrating a feasible strategy to achieve long-term stability of the IDAD process. Overall, this work provides a better understanding about the mechanism for the performance deterioration and a simple approach to maintain the stability of IDAD.

Methylprednisolone Attenuates Lipopolysaccharide-Induced Sepsis by Modulating the Small Nucleolar RNA Host Gene 5/Copine 1 Pathway.

Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.

Iron Cycle Tuned by Outer-Membrane Cytochromes of Dissimilatory Metal-Reducing Bacteria: Interfacial Dynamics and Mechanisms In Vitro.

The biogeochemical cycle of iron is of great importance to living organisms on Earth, and dissimilatory metal-reducing bacteria (DMRB) with the capability of reducing hematite (α-Fe2O3) by outer-membrane (OM) cytochromes play a great role in the iron cycle. However, the dynamic binding of cytochromes to α-Fe2O3 at the molecular level and the resulting impact on the photon-to-electron conversion of α-Fe2O3 for the iron cycle are not fully understood. To address these issues, two-dimensional IR correlation analysis coupled with molecular dynamics (MD) simulations was conducted for an OmcA-Fe2O3 system as OmcA bonds stronger with hematite in a typical DMRB,Shewanella. The photoelectric response of α-Fe2O3 with the OmcA coating was evaluated at three different potentials. Specifically, the binding groups from OmcA to α-Fe2O3 were in the sequence of carboxyl groups, amide II, and amide I. Further MD analysis reveals that both electrostatic interactions and hydrogen bonds played essential roles in the binding process, leading to the structural changes of OmcA to facilitate iron reduction. Moreover, the OmcA coating could store the photogenerated electrons from α-Fe2O3 like a capacitor and utilize the stored electrons for α-Fe2O3 reduction in dark and anoxic environments, further driving the biogeochemical cycle of iron. These investigations give the dynamic information on the OM protein/hematite interaction and provide fundamental insights into the biogeochemical cycle of iron by taking the photon-induced redox chemistry of iron oxide into consideration.

A narrative review of the roles of muscle segment homeobox transcription factor family in cancer.

Deregulation of many homeobox genes has been observed in various cancers and has caused functional implications in the tumor progression. In this review, we will focus on the roles of the human muscle segment homeobox (MSX) transcription factor family in the process of tumorigenesis. The MSX transcription factors, through complex downstream regulation mechanisms, are promoters or inhibitors of diverse cancers by participating in cell proliferation, cell invasion, cell metastasis, cell apoptosis, cell differentiation, drug resistance of tumors, maintenance of tumor stemness, and tumor angiogenesis. Moreover, their upstream regulatory mechanisms in cancers may include: gene mutation and chromosome aberration; DNA methylation and chromatin modification; regulation by non-coding RNAs; regulation by other transcription factors and post-translational modification. These mechanisms may provide a better understanding of why MSX transcription factors are abnormally expressed in tumors. Notably, intermolecular interactions and post-translational modification can regulate the transcriptional activity of MSX transcription factors. It is also crucial to know what affects the transcriptional activity of MSX transcription factors in tumors for possible interventions in them in the future. This systematic summary of the regulatory patterns of the MSX transcription factor family may help to further understand the mechanisms involved in transcriptional regulation and also provide new therapeutic approaches for tumor progression.

Evaluation of antibacterial activities of silver nanoparticles on culturability and cell viability of Escherichia coli.

Nanoparticles released into the environment are attracting increasing concern because of their potential toxic effects. Conventional methods for assessing the toxicity of nanoparticles are usually confined to cultivable cells, but not applicable to viable but non-culturable (VBNC) cells. However, it remains unknown whether silver nanoparticles (AgNPs), a typical antimicrobial agent, could induce bacteria into a VBNC state in natural environments. In this work, the viability of E. coli, an indicator bacterium widely used for assessing the antibacterial activity of AgNPs, was examined through coupling plate counting, fluorescence staining and adenosine triphosphate (ATP) production. AgNPs were found to have a considerable antibacterial ability, which resulted in less than 0.0004% of culturable cells on plates. However, more than 80% of the cells still maintained their cell membrane integrity under the stress of 80 mg/L AgNPs. Meanwhile, the residue of ATP production (0.6%) was 1500 times higher than that of the culturable cells (< 0.0004%). These results clearly demonstrate that when exposed to AgNPs, most of cells fell into a VBNC state, instead of dying. Environmental factors, e.g., Cl- and illumination, which could change the dissolution, hydrophilicity and zeta potential of AgNPs, eventually influenced the culturability of E. coli. Inhibition of dissolved Ag+ and reactive oxygen species was found to facilitate the mitigation of the strain into a VBNC state. Our findings suggest the necessity of re-evaluating the environmental effects and antibacterial activities of AgNPs.

Roles of cation efflux pump in biomineralization of cadmium into quantum dots in Escherichia coli.

Cadmium (Cd) is a typical and widely present toxic heavy metals in environments. Biomineralization of Cd ions could alleviate the toxicity and produce valuable products in certain waste streams containing selenite. However, the impact of the intrinsic Cd(II) efflux system on the biotransformation process remains unrevealed. In this work, the significance of the efflux system on Cd biomineralization was evaluated by constructing engineered Escherichia coli strains, including ΔzntA with suppressed Cd(II) efflux system and pYYDT-zntA with strengthened Cd(II) efflux system. Compared to the wild type (WT), 20% more Cd ions were accumulated in ΔzntA and 17% less were observed in pYYDT-zntA in the presence of selenite as determined by inductively coupled plasma atomic emission spectrometer. Through combination with X-ray absorption fine structure analysis, it was discovered that 50% higher production of CdSxSe1-x quantum dots (QDs) was achieved in the ΔzntA cells than that in the WT cells. Moreover, the ΔzntA cells exhibited the same viability as the WT cells and the pYYDT-zntA cells because accumulated Cd ions were transformed into biocompatible QDs. In addition, the biosynthesized QDs had a uniform particle size (3.82 ± 0.53 nm) and a long fluorescence lifetime (45.6 ns), which could potentially be utilized for bio-imaging. These results not only elucidate the significance of Cd(II) efflux system in the biotransformation of Cd ions and selenite, but also provide a promising way to recover Cd and Se as valuable products in certain waste streams.