Under xenon lamps, ZnFe2O4 (ZFO) has been shown to be effective in removing uranium through photocatalysis. However, its performance is still inadequate in low-light environments due to low photon utilization and high electron-hole complexation. Herein, S-doped hollow ZnFe2O4 microcubes (Sx-H-ZFO, x = 1, 3, 6, 9) were synthesized using the MOF precursor template method. The hollow morphology improves the utilization of visible light by refracting and reflecting the incident light multiple times within the confined domain. S doping narrows the band gap and shifts the conduction band position negatively, which enhances the separation, migration, and accumulation of photogenerated charges. Additionally, S doping increases the number of adsorption sites, ultimately promoting efficient surface reactions. Consequently, Sx-H-ZFO is capable of removing U(VI) in low-light environments. Under cloudy and rainy weather conditions, the photocatalytic rate of S3-H-ZFO was 100.31 µmol/(g·h), while under LED lamps (5000 Lux) it was 72.70 µmol/(g·h). More interestingly, a systematic mechanistic investigation has revealed that S doping replaces some of the oxygen atoms to enhance electron transfers and adsorption of O2. This process initiates the formation of hydrogen peroxide, which reacts directly with UO22+ to form solid studtite (UO2)O2·2H2O. Additionally, the promising magnetic separation capability of Sx-H-ZFO facilitates the recycling and reusability of the material. This work demonstrates the potential of ZnFe2O4 extraction uranium from nuclear wastewater.
Background: The effect of drug-drug interaction between tacrolimus and caspofungin on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies. Objectives: To investigate the effect of caspofungin on the blood concentration and dose of tacrolimus under different CYP3A5 genotypes. Design: We conducted a retrospective cohort study in The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital from January 2015 to December 2022. All kidney transplant patients were divided into the combination or non-combination group based on whether tacrolimus was combined with caspofungin or not. Patients were subdivided into CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3). Methods: Data from the combination and the non-combination groups were matched with propensity scores to reduce confounding by SPSS 22.0. A total of 200 kidney transplant patients receiving tacrolimus combined with caspofungin or not were enrolled in this study. Statistical analysis was conducted on the dose-corrected trough concentrations (C0/D) and dose requirements (D) of tacrolimus using independent sample two-sided t-test and nonparametric tests to investigate the impact on patients with different. Results: In this study, the C0/D values of tacrolimus were not significantly different between the combination and non-combination groups (p = 0.054). For CYP3A5 expressers, there was no significant difference in tacrolimus C0/D or D values between the combination and non-combination groups (p = 0.359; p = 0.851). In CYP3A5 nonexpressers, the C0/D values of tacrolimus were significantly lower in the combination than in the non-combination groups (p = 0.039), and the required daily dose of tacrolimus was increased by 11.11% in the combination group. Conclusion: Co-administration of caspofungin reduced tacrolimus blood levels and elevated the required daily dose of tacrolimus. In CYP3A5 non-expressers, co-administration of caspofungin had a significant effect on tacrolimus C0/D values. An approximate 10% increase in the weight-adjusted daily dose of tacrolimus in CYP3A5 non-expressers is recommended to ensure the safety of tacrolimus administration.
Differential drug interactions of caspofungin on tacrolimus in Chinese kidney transplant patients with different CYP3A5 genotypes Why was the study done? Currently, there have been studies reporting the effect of caspofungin on tacrolimus blood concentrations, but the conclusions are conflicting, and no study has focused on the effect of CYP3A5 genotypes on the drug-drug interaction. We explored a number of research questions: 1. Does caspofungin have an effect on the pharmacokinetics of the immunosuppressant tacrolimus? 2. How does CYP3A5*3, which affects tacrolimus metabolism significantly, affect tacrolimus blood concentration levels? 3. How should the dose of tacrolimus be adjusted when combined with caspofungin? What did the researchers do? By reviewing literature, we understood the problems related with the kidney transplant patients better, which led to the development of strict inclusion and exclusion criteria. The patients (from January 2015 to December 2022) were categorized into combination and non-combination groups according to whether they were co-administered with caspofungin or not. The results of the study were analyzed using SPSS 22.0. What did the researchers find? The study finally included 200 patients. We found no statistically significant differences in the dose-corrected trough concentrations (C0/D) and dose requirements (D) of tacrolimus between the combination and non-combination groups. However, in patients with CYPA5*3/*3 genotype, tacrolimus C0/D values were significantly lower in the combination group than in the non-combination group, and the required daily tacrolimus dose was increased. What do the findings mean? This study has found that co-administration of caspofungin in patients with CYP3A5*3/*3 genotype resulted in a significant decrease in the C0/D value of tacrolimus, therefore, an appropriate increase in the daily dose of tacrolimus is recommended. The implication is that it is important and necessary to monitor the concentrations of tacrolimus and the CYP3A5 genotypes, and adjust the dose when combined or discontinuing with caspofungin in kidney transplant patients.
Piezoelectric-photocatalysis is distinguished by its piezoelectricity as an external force that induces deformation within the catalyst to engender a polarized electric field compared to conventional photocatalysis. Herein, the piezoelectric photocatalyst BiOBr has been expertly synthesized via a plasma process and applied for piezoelectric-photocatalysis removal of uranium(VI) for the first time. The abundant surface oxygen vacancies (OVs) could induce a dipole moment and built-in electric field, which endows BiOBr with excellent separation and transport efficiency of photogenerated charges to actuate more charges to participate in the piezoelectric-photocatalytic reduction process. Consequently, under visible light and ultrasound (150 W and 40 kHz), the removal rate constant of OVs-BiOBr-30 (0.0306 min-1) was 2.4, 30.6, and 6 times higher than those of BiOBr (0.01273 min-1), ultrasound, or photocatalysis, respectively. The piezoelectric-photocatalytic synergy is also universal for BiOX (X = Cl, Br, or I) to accelerate the reduction rate of uranium(VI). This work highlights the role of piezoelectric-photocatalysis in the treatment of uranium-containing wastewater, which is of great significance for resource conservation and environmental remediation.
Inspired by its large specific surface area, and tunable chemical and physical properties, a hollow carbon-based mater8ial derived from ZIF-8 with phosphate groups (HCM-PO4) was prepared for the elimination of U(VI). The structural and surface features of HCM and HCM-PO4 were thoroughly examined using techniques such as SEM, TEM, and XRD. The resulting carbon material, HCM-PO4, exhibits a higher BET surface area of 571.2 m2·g-1, featuring a hollow structure. The removal procedure of HCM-PO4 for U(VI) aligns with the quasi-secondary kinetic model. Furthermore, the theoretical sorption capacity of HCM-PO4 was found to be 482.30 mg·g-1 at 298.15 K. The results obtained from XPS, FT-IR, and EDS analysis of HCM-PO4 after adsorption revealed the coordination of the phosphate group for U(VI), contributing significantly to the adsorption process. In brief, the HCM-PO4 demonstrates excellent adsorptive ability, positioning it as a hopeful expectant to remove U(VI) from wastewater.
Carbon , Phosphates , Adsorption , Spectroscopy, Fourier Transform Infrared , Kinetics
BACKGROUND: The effect of drug-drug interaction (DDI) between tacrolimus and voriconazole on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies. OBJECTIVE: The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-voriconazole DDI in Chinese kidney transplant patients. METHODS: All kidney transplant patients were divided into combination and non-combination groups based on whether tacrolimus was combined with or without voriconazole. Each group was subdivided into CYP3A5 expresser (CYP3A5*1/*1 or CYP3A5*1/*3) and CYP3A5 nonexpresser (CYP3A5*3/*3). A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between combination and non-combination groups, respectively. Tacrolimus C0/D was also compared between CYP3A5 expresser and nonexpresser in both groups. RESULTS: The C0/D values of tacrolimus were significantly different between CYP3A5 expresser and nonexpresser in combination group (378.20 [219.38, 633.48] ng/mL/[mg/kg/d] vs 720.00 [595.35, 1681.50] ng/mL/[mg/kg/d], P = 0.0010). Either in CYP3A5 expresser or nonexpresser, we found a statistically significant difference in tacrolimus C0/D between combination and non-combination group (P < 0.0001). The increase in CYP3A5 nonexpresser was 1.38 times higher than that in CYP3A5 expresser (320.93% vs 232.19%). CONCLUSION AND RELEVANCE: The median C0/D values were 90.38% higher in kidney transplant recipients with CYP3A5*3/*3 genotype than in those with CYP3A5*1/*1 or CYP3A5*1/*3 genotype when treated with both tacrolimus and voriconazole. A CYP3A5 genotype-dependent DDI was found between tacrolimus and voriconazole. Therefore, personalized therapy accounting for CYP3A5 genotype detection and therapeutic drug monitoring is necessary for kidney transplant patients when treating with tacrolimus and voriconazole.
IMPORTANCE: Aspergillus flavus is a model filamentous fungus that can produce aflatoxins when it infects agricultural crops. This study evaluated the protein phosphatase 2C (PP2C) family as a potential drug target with important physiological functions and pathological significance in A. flavus. We found that two redundant PP2C phosphatases, Ptc1 and Ptc2, regulate conidia development, aflatoxin synthesis, autophagic vesicle formation, and seed infection. The target protein phosphoglycerate kinase 1 (PGK1) that interacts with Ptc1 and Ptc2 is essential to regulate metabolism and the autophagy process. Furthermore, Ptc1 and Ptc2 regulate the phosphorylation level of PGK1 S203, which is important for influencing aflatoxin synthesis. Our results provide a potential target for interdicting the toxicity of A. flavus.
Aflatoxins , Aspergillus flavus , Aspergillus flavus/metabolism , Protein Phosphatase 2C/genetics , Protein Phosphatase 2C/metabolism , Phosphoric Monoester Hydrolases/metabolism , Aflatoxins/metabolism , Autophagy
Lignin is an important cell wall component that provides plants with mechanical support and improved tolerance to pathogen attacks. Previous studies have shown that plants rich in S-lignin content or with a higher S/G ratio always exhibit higher efficiency in the utilization of lignocellulosic biomass. Ferulate 5-hydroxylase, or coniferaldehyde 5-hydroxylase (F5H, or CAld5H), is the critical enzyme in syringyl lignin biosynthesis. Some F5Hs have been characterized in several plant species, e.g., Arabidopsis, rice, and poplar. However, information about F5Hs in wheat remains unclear. In this study, a wheat F5H gene, TaF5H1, together with its native promoter (pTaF5H1), was functionally characterized in transgenic Arabidopsis. Gus staining results showed that TaF5H1 could be expressed predominantly in the highly lignified tissues in transgenic Arabidopsis plants carrying pTaF5H1:Gus. qRT-PCR results showed that TaF5H1 was significantly inhibited by NaCl treatment. Ectopic expression of TaF5H1 driven by pTaF5H1 (i.e., pTaF5H1:TaF5H1) could increase the biomass yield, S-lignin content, and S/G ratio in transgenic Arabidopsis plants, which could also restore the traces of S-lignin in fah1-2, the Arabidopsis F5H mutant, to an even higher level than the wild type (WT), suggesting that TaF5H1 is a critical enzyme in S lignin biosynthesis, and pTaF5H1:TaF5H1 module has potential in the manipulation of S-lignin composition without any compromise on the biomass yield. However, expression of pTaF5H1:TaF5H1 also led to decreased salt tolerance compared with the WT. RNA-seq analysis showed that many stress-responsive genes and genes responsible for the biosynthesis of cell walls were differentially expressed between the seedlings harboring pTaF5H1:TaF5H1 and the WT, hinting that manipulation of the cell wall components targeting F5H may also affect the stress adaptability of the modified plants due to the interference to the cell wall integrity. In summary, this study demonstrated that the wheat pTaF5H1: TaF5H1 cassette has the potential to modulate S-lignin composition without any compromise in biomass yield in future engineering practice. Still, its negative effect on stress adaptability to transgenic plants should also be considered.
Arabidopsis , Arabidopsis/metabolism , Plants, Genetically Modified/metabolism , Lignin/metabolism , Triticum/genetics , Triticum/metabolism , Salt Tolerance , Mixed Function Oxygenases/genetics , Cell Wall/metabolism , Gene Expression Regulation, Plant
In order to deal with the sudden nuclear leakage event to suppress the spread of radioactive contaminants in a short period of time, it is extremely urgent needed to explore an adsorbent that could be capable of in-situ remedial actions to rapidly capture the leaked radionuclides in split second. An adsorbent was developed that MoS2 via ultrasonic to expose more surface defects afterwards functionalized by phosphoric acid resulting in more active sites being endowed on the edge S atoms of Mo-vacancy defects, while simultaneously increased the hydrophilicity and interlayer spacing. Hence, an overwhelming fast adsorption rates (adsorption equilibrium within 30 s) are presented and place the MoS2-PO4 at the top of performing sorbent materials. Moreover, the maximum capacity calculated from Langmuir model is as high as 354.61 mg·g-1, the selective adsorption capacity (SU) achieving 71.2% in the multi-ion system and with more than 91% capacity retention after 5 cycles of recycling. Finally, XPS and DFT insight into the adsorption mechanism, which can be explained as interaction of UO22+ on the surface of MoS2-PO4 by forming U-O and U-S bonds. The successful fabrication of such a material may provide a promising solution for emergency treatment of radioactive wastewater during nuclear leakage events.
Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery and development. New opportunities are emerging in target identification owing to improved disease understanding through cell subtyping, and highly multiplexed functional genomics screens incorporating scRNA-seq are enhancing target credentialling and prioritization. ScRNA-seq is also aiding the selection of relevant preclinical disease models and providing new insights into drug mechanisms of action. In clinical development, scRNA-seq can inform decision-making via improved biomarker identification for patient stratification and more precise monitoring of drug response and disease progression. Here, we illustrate how scRNA-seq methods are being applied in key steps in drug discovery and development, and discuss ongoing challenges for their implementation in the pharmaceutical industry.
Gene Expression Profiling , Single-Cell Analysis , Humans , Sequence Analysis, RNA , Genomics , Drug Discovery , RNA/genetics
Effective spatial separation and utilization of photogenerated charges are critical for photocatalysis process. Herein, novel Co3O4 @TiO2 @CdS@Au double-shelled nanocage (CTCA) with spatially separated redox centers was synthesized by loading Co3O4 and Au NP cocatalysts on the inner and outer surfaces of Z-scheme heterojunction (TiO2 @CdS). The reduction rate constant of U(VI) by CTCA reached 0.218 min-1 under simulated sunlight irradiation, which was 6.6, 3.2 and 36.3 times than that of monolayer CTCA (0.033 min-1), CTC (0.068 min-1) and CT (0.006 min-1). The full-spectrum light-assisted photothermal catalytic performance can enable CTCA to remove 98.8% of U(VI) and degrade nearly 90% of five organic pollutants simultaneously. Detailed characterizations and theory calculations revealed that the photogenerated holes and electrons in CTCA flow inward and outward. More importantly, Co3O4 acts as a "nano heater" to generate the photothermal effect for further enhancing the charge transfer and accelerating the surface reaction kinetics. Meanwhile, the photogenerated electrons and superoxide radicals play a dominant role in reducing the adsorbed U(VI) to insoluble (UO2)O2·2H2O(s). This work provides valuable input toward a novel double-shelled hollow nanocage reactor with excellent photothermal catalysis ability for efficient recovery U(VI) from uranium mine wastewater to address environmental contamination issues.
Designing highly efficient photocatalysts with rapid migration of photogenerated charges and surface reaction kinetics for the photocatalytic removal of uranium (U(VI)) from uranium mine wastewater remains a significant challenge. Inspired by natural photosynthesis, a biomimetic photocatalytic system is assembled by designing a novel hollow nanosphere MnOx @TiO2 @CdS@Au (MTCA) with loading MnOx and Au nano particles (Au NPs) cocatalysts on the inner and outer surfaces of the TiO2 @CdS. The spatially separated cocatalysts efficiently drive the photogenerated charges to migrate in opposite directions, while the Z-scheme heterogeneous shell further separates the interfacial charges. Theoretical calculation identifies multiple consecutive forward charge transfers without charge recombination within MTCA. Thus, MTCA could efficiently remove 99.61% of U(VI) after 15 min of simulated sunlight irradiation within 3 mmol L-1 NaHCO3 with 0.231 min-1 of the reduction rate constant, outperforming most previously reported photocatalysts. MTCA further significantly removes 91.83% of U(VI) from the natural uranium mining wastewater under sunlight irradiation. This study provides a novel approach to designing an ideal biomimetic photocatalyst for remediating environmental pollution.
BACKGROUND: Janus kinase (JAK) 1 inhibitor upadacitinib and IL-23 inhibitor risankizumab are efficacious in inflammatory bowel disease (IBD) patients who are antitumor necrosis factor (anti-TNF)-α inadequate responders (TNF-IRs). We aimed to understand the mechanisms mediating the response of upadacitinib and risankizumab. METHODS: Eight tissue transcriptomic data sets from IBD patients treated with anti-TNF-α therapies along with single-cell RNAseq data from ulcerative colitis were integrated to identify TNF-IR mechanisms. The RNAseq colon tissue data from clinical studies of TNF-IR Crohn's disease patients treated with upadacitinib or risankizumab were used to identify TNF-IR mechanisms that were favorably modified by upadacitinib and risankizumab. RESULTS: We found 7 TNF-IR upregulated modules related to innate/adaptive immune responses, interferon signaling, and tissue remodeling and 6 TNF-IR upregulated cell types related to inflammatory fibroblasts, postcapillary venules, inflammatory monocytes, macrophages, dendritic cells, and cycling B cells. Upadacitinib was associated with a significant decrease in the expression of most TNF-IR upregulated modules in JAK1 responders (JAK1-R); in contrast, there was no change in these modules among TNF-IR patients treated with a placebo or among JAK1 inadequate responders (JAK1-IR). In addition, 4 of the 6 TNF-IR upregulated cell types were significantly decreased after upadacitinib treatment in JAK1-R but not among subjects treated with a placebo or among JAK1-IR patients. We observed similar findings from colon biopsy samples from TNF-IR patients treated with risankizumab. CONCLUSIONS: Collectively, these data suggest that upadacitinib and risankizumab affect TNF-IR upregulated mechanisms, which may account for their clinical response among TNF-IR IBD patients.
We identified molecular and cellular mechanisms associated with and potentially mediating the response of upadacitinib and risankizumab for IBD patients that inadequately responded to anti-TNF-α treatment.
Inflammatory Bowel Diseases , Tumor Necrosis Factor Inhibitors , Humans , Tumor Necrosis Factor-alpha
Arrhythmias are perceived as a complication of pituitrin. However, injecting a standard dose of pituitrin via vein causes different arrhythmias. In our case, a 35-year-old female patient was admitted to the hospital due to a productive cough with sputum for 5 days and two occasions of massive hemoptysis. After 1 day of treatment using 500 ml normal saline with 10u pituitrin, the sputum was filled with small amounts of kermesinus bloodstains. When pituitrin was stopped without any other treatment, all presenting symptoms gradually subsided after half an hour, and the ECG returned to normal. Therefore, when treating massive hemoptysis by administering pituitrin intravenously, it is necessary to exercise great precaution and therapeutic measures.
Hemoptysis , Pituitary Hormones, Posterior , Female , Humans , Adult , Hemoptysis/drug therapy , Electrocardiography , Pituitary Hormones, Posterior/therapeutic use , Arrhythmias, Cardiac/therapy , Arrhythmias, Cardiac/drug therapy
Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal epithelial barrier leading to breach of barrier immunity. Here we identified similar protein expression changes between IBD and Citrobacter rodentium-infected FVB mice with respect to dysregulation of solute transporters as well as components critical for intestinal barrier integrity. We attribute the disease associated changes in the model to the emergence of undifferentiated intermediate intestinal epithelial cells. Prophylactic treatment with IL-22.Fc in C. rodentium-infected FVB mice reduced disease severity and rescued the mice from lethality. Multi-omics and solute analyses revealed that IL-22.Fc treatment prevented disease-associated changes including disruption of the solute transporter machinery and restored proper physiological functions of the intestine, respectively. Taken together, we established the disease relevance of the C. rodentium-induced colitis model to IBD, demonstrated the protective role of IL-22 in amelioration of epithelial dysfunction and elucidated the molecular mechanisms with IL-22's effect on intestinal epithelial cells.
Colitis , Enterobacteriaceae Infections , Inflammatory Bowel Diseases , Interleukins , Animals , Mice , Citrobacter rodentium/physiology , Colitis/drug therapy , Colitis/microbiology , Enterobacteriaceae Infections/drug therapy , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/microbiology , Intestinal Mucosa/metabolism , Intestines , Mice, Inbred C57BL , Interleukins/pharmacology , Interleukin-22
Our purpose of this study was to analyze the application value of the information-based nursing quality evaluation model in improving the daily work quality of the PICC room in the outpatient department. From January 2020 to December 2020, 465 patients who received PICC treatment were selected as the research objects and divided into the observation group (265 cases, July 2020-December 2020, information-based nursing quality evaluation model after implementation) and the control group (200 cases, January 2020-June 2020, before the implementation of the information-based nursing quality assessment model). Compared with the control group, the children and their families in the observation group had higher PICC health knowledge and compliance scores, longer mean time for catheter placement, lower overall complication rate, and higher overall satisfaction rate after the intervention. The information-based nursing quality evaluation model can improve the daily work quality of the PICC room in the outpatient clinic, improve the clinical efficacy of PICC in patients, and reduce the incidence of complications such as catheter shedding. It is worthy of clinical application.
Catheterization, Central Venous , Catheterization, Peripheral , Ambulatory Care Facilities , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Child , Humans , Treatment Outcome
BACKGROUND: Research shows that the clinical learning environment can affect medical learners' levels of empathy and formation of professional identity. However, few studies examined the impacts of early exposure to the clinical learning environment on first-year nursing students' empathy levels and professional identity perceptions. AIM: This study aimed to explore effects of initial contact with the clinical learning environment on first-year nursing students' empathy levels and perceptions of professional identity. METHODS: This is a mixed-methods study conducted in a medical university and its affiliated hospital in Northeast China. For quantitative analysis, 220 first-year nursing students finished Interpersonal Reactivity Index (IRI) twice before and after their five-day clinical placement in the hospital in June, 2021. Paired samples t tests were used to explore the changes in first-year nursing students' cognitive empathy, affective empathy and total empathy levels as measured by IRI before and after the clinical placement. For qualitative analysis, 15 first-year nursing students' diary recording their clinical learning experiences were analyzed. An inductive thematic analysis approach was adopted to extract themes from the content on professional identity in nursing students' diary. RESULTS: After the five-day clinical placement, first-year nursing students' cognitive empathy, affective empathy and total empathy levels all increased. Five themes emerged regarding nursing students' perceptions of professional identity: (1) Love for the nursing profession; (2) Multiple roles nurses play; (3) Personal characteristics a good nurse needs to have; (4) Deeper understanding of the nursing profession; (5) New understanding of the relationships between patients and nurses, between patients and doctors, and between doctors and nurses. CONCLUSIONS: First-year nursing students' initial contact with the clinical learning environment helped them enhance empathy levels and shape professional identity. Nursing educators may consider providing nursing students with opportunities of early exposure to the clinical learning setting to cultivate their empathy and develop their professional identity.
Cadmium (Cd) is an environmental endocrine-disrupting pollutant which mainly occurs in pulsed manner in natural waters, while traditional toxicology experiments have less examined the effects of pulsed exposure. Here, we studied the effects of short-term (7 days) continuous and pulse exposure to 100 µg/L Cd on gut morphology and microbiota of frogs (Pelophylax nigromaculatus) during pre-hibernation. Compared to continuous exposure, Cd pulse exposure significantly increased individual mortality and decreased the villi height and the ratio of villi height to crypt depth of the gut. Cd continuous and pulse exposure both changed the community structure and relative abundance of intestinal microbiota. Compared to continuous exposure, Cd pulse exposure significantly decreased the relative abundance of beneficial bacteria (e.g., Cetobacterium and Aeromonas genus), and significantly increased the relative abundance of harmful bacteria (e.g., Parabacteroides, Odoribacter, and Acinetobacter genus). This study shows that the gut histology and microbiota of amphibians during pre-hibernation are more susceptible to Cd pulse exposure than continuous exposure.
Gastrointestinal Microbiome , Hibernation , Microbiota , Animals , Anura , Cadmium/toxicity , Male , Ranidae
Background: Sevoflurane exposure at brain developmental stages has been reported to induce neurotoxicity and, subsequently, results in learning deficits at the juvenile age. In this study, we aimed to investigate the effects of prior early-age sevoflurane exposure on locomotor activity, anxiety, CA1-dependent learning, and spatial memory, as well as synapse changes in mice. Methods: Totally, 3% sevoflurane was given to neonatal mice at postnatal day 7 for 4 h. These sevoflurane-treated mice were later subjected to open field and Morris water maze tests at their adult age (postnatal days 60-90) to assess their motor activity and spatial learning ability, respectively. The brain slices of sevoflurane-treated and control mice were examined for dendritic spine density and long-term potentiation (LTP) features following behavior tests (postnatal day 60). Protein levels of N-methyl-D-aspartate (NMDA) receptor subtypes and PSD95 in brain lysate were measured by using immunoblotting at the same age (postnatal day 60). Results: Prior early-age sevoflurane exposure increased the overall moving distance, prolonged the central-area lingering time, and increased the central-area entries of adult mice. Sevoflurane-treated mice spent more time in the target quadrant during the probe test. An increase of the spine density of pyramidal neurons in the CA1 region was observed in sevoflurane-treated mice. NMDA receptor GluN2A subunit, but not the GluN2B or PSD95, was increased in the brain lysate of sevoflurane-treated mice compared with that of control mice. LTP in the hippocampus did not significantly differ between sevoflurane-treated and control mice. Conclusion: Exposure to sevoflurane for mice during an early brain developmental stage (P7) induces later-on hyperactivity, anxiety-free, and enhancement of memory retention. These observations shed light on future investigations on the underlying mechanisms of sevoflurane's effect on neuronal development.
OBJECTIVE: This study was undertaken to understand the mechanistic basis of response to anti-tumor necrosis factor (anti-TNF) therapies and to determine whether transcriptomic changes in the synovium are reflected in peripheral protein markers. METHODS: Synovial tissue from 46 rheumatoid arthritis (RA) patients was profiled with RNA sequencing before and 12 weeks after treatment with anti-TNF therapies. Pathway and gene signature analyses were performed on RNA expression profiles of synovial biopsies to identify mechanisms that could discriminate among patients with a good response, a moderate response, or no response, according to the American College of Rheumatology (ACR)/EULAR response criteria. Serum proteins encoded by synovial genes that were differentially expressed between ACR/EULAR response groups were measured in the same patients. RESULTS: Gene signatures predicted which patients would have good responses, and pathway analysis identified elevated immune pathways, including chemokine signaling, Th1/Th2 cell differentiation, and Toll-like receptor signaling, uniquely in good responders. These inflammatory pathways were correspondingly down-modulated by anti-TNF therapy only in good responders. Based on cell signature analysis, lymphocyte, myeloid, and fibroblast cell populations were elevated in good responders relative to nonresponders, consistent with the increased inflammatory pathways. Cell signatures that decreased following anti-TNF treatment were predominately associated with lymphocytes, and fewer were associated with myeloid and fibroblast populations. Following anti-TNF treatment, and only in good responders, several peripheral inflammatory proteins decreased in a manner that was consistent with corresponding synovial gene changes. CONCLUSION: Collectively, these data suggest that RA patients with robust responses to anti-TNF therapies are characterized at baseline by immune pathway activation, which decreases following anti-TNF treatment. Understanding mechanisms that define patient responsiveness to anti-TNF treatment may assist in development of predictive markers of patient response and earlier treatment options.
Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/metabolism , Tumor Necrosis Factor Inhibitors/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Synovial Membrane/metabolism , Tumor Necrosis Factor-alpha/metabolism
The separation of magnetic adsorbents from aqueous solutions is made simple by using an external magnetic field. Herein, magnetic Zr(IV)-ethylenediamine tetramethylene phosphonic acid (EDTMPA) hybrids (MZrOP-x-T, x, and T were the different quality of Fe3O4@C and temperature in the synthesis process, respectively). A study was conducted on the uses of MZrOP-x-T in the capture of U(VI). The influences of pH, adsorption period, initial concentration, and temperature were all investigated. Furthermore, the desorption and reusability of the materials were explored. The optimal values of x and T were 0.2 g and 100 °C, respectively. At 298.15 K, the maximum adsorption capacity of MZrOP-0.2-100 was 330.30 mg·g-1. The current research demonstrates that MZrOP-0.2-100 is a potentially effective material in removing U(VI) from radioactive solution.
