Gut microbiome for predicting immune checkpoint blockade-associated adverse events.

BACKGROUND: The impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies. METHODS: We performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms. RESULTS: We identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymes menH and menC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group. CONCLUSIONS: Our study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed. RESULTS: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6, 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred. CONCLUSION: Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.

A Straightforward Bifurcation Pattern-Based Fundus Image Registration Method.

Fundus image registration is crucial in eye disease examination, as it enables the alignment of overlapping fundus images, facilitating a comprehensive assessment of conditions like diabetic retinopathy, where a single image's limited field of view might be insufficient. By combining multiple images, the field of view for retinal analysis is extended, and resolution is enhanced through super-resolution imaging. Moreover, this method facilitates patient follow-up through longitudinal studies. This paper proposes a straightforward method for fundus image registration based on bifurcations, which serve as prominent landmarks. The approach aims to establish a baseline for fundus image registration using these landmarks as feature points, addressing the current challenge of validation in this field. The proposed approach involves the use of a robust vascular tree segmentation method to detect feature points within a specified range. The method involves coarse vessel segmentation to analyze patterns in the skeleton of the segmentation foreground, followed by feature description based on the generation of a histogram of oriented gradients and determination of image relation through a transformation matrix. Image blending produces a seamless registered image. Evaluation on the FIRE dataset using registration error as the key parameter for accuracy demonstrates the method's effectiveness. The results show the superior performance of the proposed method compared to other techniques using vessel-based feature extraction or partially based on SURF, achieving an area under the curve of 0.526 for the entire FIRE dataset.

Decoding SEC24 Homolog D, COPII coat complex component accuracy as a signature gene in three human cancers.

Although an increasing body of evidence supports the crucial role of the SEC24 Homolog D, COPII Coat Complex Component (SEC24D) gene in the initiation and progression of cancer, a comprehensive pan-cancer analysis of this gene is still lacking. In this study, we conducted an extensive investigation of SEC24D, aiming to elucidate its potential role and underlying mechanisms across multiple human tumors. Our analysis relied on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To validate our findings, we employed RNA sequencing (RNA-seq), targeted bisulfite sequencing (bisulfite-seq) molecular techniques. Our findings revealed elevated mRNA (Messenger RNA) and protein levels of SEC24D in different tumor tissues. However, the up-regulation of SEC24D was significantly correlated with shorter overall survival (OS), metastasis, and various clinical parameters in esophageal cancer (ESCA), lung adenocarcinoma (LUAD), and kidney renal papillary cell carcinoma (KIRP). Expression validation analysis via RNA-seq and targeted bisulfite-seq analyses, further confirmed the higher expression of SEC24D in LUAD cancer cell lines as compared to normal controls. The DNA methylation level of SEC24D was found to be decreased in ESCA, LUAD, and KIRP samples. DNA methylation analysis via bisulfite-seq analysis also validate the lower promoter methylation level of SE24D in LUAD cell lines relative to controls. Moreover, we observed a significant association between the elevated expression of SEC24D and the levels of infiltrating cells, such as B cells, neutrophils, macrophages, CD8+ T cells, and CD4+ T cells. Analysis of SEC24-related genes revealed that "Protein processing in endoplasmic reticulum, SNARE interaction in vesicular transport, Legionellosis, Pathogenic Escherichia coli infection" were mainly involved in the functional mechanism of SEC24D in ESCA, LUAD, and KIRP. Moreover, we also suggested a few valuable drugs (Acetaminophen, Acteoside, Cyclosporine, Polydatin, Estradiol, Estradiol, Quercetin) for treating ESCA, LUAD, and KIRP patients with respect to overexpressed SEC24D. To summarize, this comprehensive pan-cancer study investigated the association between SEC24D expression and clinical parameters in ESCA, LUAD, KIRP. The study provides valuable insights for further exploring the functional and therapeutic aspects of SEC24D and underscores its predictive significance in the carcinogenesis and prognosis of these specific cancer types.

Lineage switch in a pediatric patient with KMT2A-MLLT3 from acute megakaryoblastic leukemia to T cell acute lymphoblastic leukemia at the fourth relapse after allo-HSCT: with literature review.

We present a patient with acute megakaryoblastic leukemia (AMKL) harboring KMT2A-MLLT3 that converted to T cell acute lymphoblastic leukemia (T-ALL) at her fourth relapse. A 4-year-old girl developed AMKL with multiple swollen lymph nodes. She exhibited several recurrences in the bone marrow and died of septic shock after her fourth relapse. Bone marrow cells at the initial diagnosis and at all four relapses had the same KMT2A-MLLT3 fusion transcript. She also developed a somatic mutation (c.7177C > T p.Q2393X) of NOTCH1 at the fourth relapse. This sequential phenotypic and cytogenetic study may yield valuable insights into the mechanism of AMKL to T-ALL lineage switch and possible implications for treatment selection.

Multiple Preprocessing Hybrid Level Set Model for Optic Disc Segmentation in Fundus Images.

The accurate segmentation of the optic disc (OD) in fundus images is a crucial step for the analysis of many retinal diseases. However, because of problems such as vascular occlusion, parapapillary atrophy (PPA), and low contrast, accurate OD segmentation is still a challenging task. Therefore, this paper proposes a multiple preprocessing hybrid level set model (HLSM) based on area and shape for OD segmentation. The area-based term represents the difference of average pixel values between the inside and outside of a contour, while the shape-based term measures the distance between a prior shape model and the contour. The average intersection over union (IoU) of the proposed method was 0.9275, and the average four-side evaluation (FSE) was 4.6426 on a public dataset with narrow-angle fundus images. The IoU was 0.8179 and the average FSE was 3.5946 on a wide-angle fundus image dataset compiled from a hospital. The results indicate that the proposed multiple preprocessing HLSM is effective in OD segmentation.

Quantitative and direct serum albumin detection by label-free SERS using tunable hydroxyapatite nanostructure for prostate cancer detection.

With the aid of good biocompatibility and stability with hydroxyapatite (HAp) in protein separation and adsorption fields, we developed a novel extraction-isolation albumin analysis method by relying on the specific adsorption capacity of HAp, combining with surface-enhanced Raman spectroscopy (SERS) for prostate cancer screening. Two different nanostructures of HAp particles, including the HAp flower and HAp sphere, were synthesized with a hydrothermal method, and the targeted binding and extraction abilities of serum albumin of these two HAp particles were compared. By changing the morphology of the nanostructure, the albumin-adsorption capacity of HAp varied significantly. Compared with spherical HAp particles, HAp flower particles have more albumin binding sites per unit area. Thus, the HAp flower displayed the superior capacity for adsorption-release of albumin, which was further employed for clinical prostate cancer screening. Based on the superior adsorption-extraction ability of albumin of HAp flower, serum albumin was adsorbed and extracted by HAp flower from serum samples of prostate cancer patients (n = 30) and healthy volunteers (n = 30), and mixed with silver colloids to perform SERS spectral analysis. The partial least square-support vector machines (PLS-SVM) model is used to analyze the obtained serum albumin SERS spectra and establish the diagnostic model, the diagnostic accuracy was up to 95.00% for differentiating the normal volunteer from prostate patient groups. The results demonstrate that the PLS-SVM model provides superior performance in the classification of a prostate cancer diagnosis. Due to the advantages of simplicity and rapidness, the HAp flower-adsorbed-released albumin combined with SERS was expected to become a promising tool for prostate cancer detection.

[Efficacy of Chimeric Antigen Receptor T Cell in the Treatment of Refractory/Recurrent B Acute Lymphocytic Leukemia in Children].

OBJECTIVE: To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL). METHODS: Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T. RESULTS: The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis. CONCLUSION: CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.

Label-free detection of bladder cancer and kidney cancer plasma based on SERS and multivariate statistical algorithm.

In this study, we mainly aimed to investigate the diagnostic potential of surface-enhanced Raman spectroscopy for bladder cancer and kidney cancer which are the most common cancers of the urinary system, and evaluate the classification ability of three statistical algorithms: principal component analysis-linear discriminate analysis (PCA-LDA), partial least square-random forest (PLS-RF), and partial least square-support vector machine (PLS-SVM). The plasma of 26 bladder cancer patients, 38 kidney cancer patients and 39 normal subjects was mixed with the same volume of silver nanoparticles, respectively, and then high-quality SERS signal was obtained. The SERS spectra in the range of 400-1800 cm-1 were compared and analyzed. There were some significant differences in SERS peak intensity, which may reflect the changes in the content of some biomacromolecules in the plasma of cancer patients. Based on the three algorithms of PCA-LDA, PLS-RF and PLS-SVM, the classification accuracy of SERS spectra of plasma from cancer patients and normal subjects was 98.1%, 100% and 100%, respectively. In addition, the classification accuracy of the three diagnostic algorithms to classify the SERS spectra of bladder cancer and kidney cancer was 81.3%, 91.7%, and 98.4%, respectively. This exploratory work demonstrates that SERS combined with PLS-SVM algorithm has superior performance for clinical screening of bladder cancer and kidney cancer through peripheral plasma.

Analysis of the interaction between A1 R and A2A R proteins in living cells based on FRET imaging and batch processing method.

The quantitative FRET analysis of living cells is a tedious and time-consuming task for freshman lacks technical training. In this study, FRET imaging and batch processing method were combined to analyze reagents-induced interactions of A1 R and A2A R on cell membranes. Results showed that the method had taken less time than if cell-by-cell was analyzed. The accuracy and repeatability of FRET efficiency values were likewise improved by removing the interference from anthropogenic factors. Then this method was applied to rapidly analyze acetaldehyde-induced interactions, which analyzed hundreds of single-cell trends by one operation, and the results revealed that interactions were consistently attenuated in LX-2 cells, and statistical differences appeared after 30 min. Combined with batch processing method, procedures of cells FRET analysis have been greatly simplified without additional technical work, which has broad prospects in large-scale analysis of cellar protein interaction.

Design, synthesis, and LFA-1/ICAM-1 antagonist activity evaluation of Lifitegrast analogues.

The interaction between Lymphocyte function-associated antigen 1 (LFA-1) and intercellular-adhesion molecule-1 (ICAM-1) plays important roles in the cell-mediated immune response and inflammation associated with dry eye disease. LFA-1/ICAM-1 antagonists can be used for the treatment of dry eye disease, such as Lifitegrast which has been approved by the FDA in 2016 as a new drug for the treatment of dry eye disease. In this study, we designed and synthesized some new structure compounds that are analogues to Lifitegrast, and their biological activities were evaluated by in vitro cell-based assay and also by in vivo mouse dry eye model. Our results demonstrated that one of these analogues of Lifitegrast (compound 1b) showed good LFA-1/ICAM-1 antagonist activity in in vitro assay; meanwhile, it also significantly reduced ocular surface epithelial cells damage, increased goblet cell density in dry eye mouse and highly improved the symptoms of dry eye mouse. Graphical abstract.

Submucosal protuberance caused by a fish bone in the absence of preoperative positive signs: A case report.

BACKGROUND: Submucosal protuberance caused by fish bone insertion into the digestive tract has rarely been reported. These cases usually include patients with clear signs such as a history of fish intake, pain, and dysphagia, as well as positive findings on endoscopy and imaging. Here, we report a case of a fish bone hidden in the submucosal protuberance of the gastric antrum during endoscopic submucosal dissection without preoperative obvious positive signs. CASE SUMMARY: A 58-year-old woman presented with epigastric pain for the past 20 d and a submucosal protuberance. Abdominal computed tomography and endoscopic ultrasonography did not indicate the presence of a fish bone. We assumed the cause to be an ordinary submucosal eminence and performed an endoscopic submucosal dissection to confirm its essence. During the operation, a fish bone approximately 20 mm in length was found incidentally. CONCLUSION: Our report could potentially prevent the oversight of embedded fish bones and associated adverse effects in patients with similar presentation.

Exposure parameters and health risk of Cryptosporidium and Giardia in the recreational water activities for urban residents in China.

Knowledge gaps in the exposure parameters for recreational water activities make quantitative risk assessment related to water recreation difficult. Therefore, the annual exposure frequency and single exposure duration for the recreational water activities of residents from ten cities in the North and South of China were investigated. Questionnaire interviews were carried on recreational water activities comprising swimming (SW), boating (BA), playing in interactive fountains (PF), and watching fountains (WF). Quantitative microbial risk assessment for the exposure of urban residents to Cryptosporidium and Giardia was also performed. For the four recreational water activities, the participation rates of urban residents in SW and WF were higher than the others. For SW and BA, the mean annual exposure frequency and single exposure duration for males were significantly higher than those for females. PF and WF showed the opposite. The annual exposure frequency for above 35-year-old residents was higher than that for young residents (18-35 years). However, the single exposure duration for young residents was highest in SW, BA, and PF. The mean annual exposure frequency and single exposure duration for North China residents were higher than those for South China residents in all recreational water activities, except for SW. Overall, the annual exposure frequency and single exposure duration in recreational water activities for all urban residents followed a lognormal distribution. In the four recreational water activities, the total annual infection risk of male exposure to Cryptosporidium was 1.0 × 10-2, with the confidence intervals between 95 and 5% of [4.3 × 10-4, 3.7 × 10-2], whereas that for females was 6.8 × 10-3 and [4.2 × 10-4, 2.4 × 10-2]. Also, the annual infection risk of males to Giardia was 8.8 × 10-3 and [5.1×10-4, 3.2×10-2], and that of females was 5.3 × 10-3 and [4.0 × 10-4, 1.8 × 10-2]. These results demonstrated that SW and PF made the highest contribution to the total annual infection risk. Sensitivity analysis highlighted that the characterization of exposure parameters plays a critical role in health risk assessment, which may provide a scientific basis for recreational water quality standards formulation.

Evaluation of the Effect of PDCA in Hospital Health Management.

PDCA plays a very important role in the hygienic management of hospital operating rooms. Before the PDCA management from February 2018 to February 2019, routine hygiene management in the operating room was adopted; after the PDCA management from February 2018 to February 2019, PDCA cycle management was adopted. 500 surgical patients were randomly selected from both groups. We compare the quality control checklist scores of hand hygiene management, environmental hygiene management, medical waste management, and disinfection and isolation management in the routine group and the PDCA group. We also compared the detection rate of pathogenic bacteria in surgical incisions of the routine group and the PDCA group and the infection rate of various surgical incisions, air samples, surface samples, disinfectants, and sterilization rates of sterile items. The PDCA group's hand hygiene management score, environmental hygiene management score, medical waste management score, and disinfection and isolation management score were higher than those in the conventional group (P < 0.05). The detection rate of pathogenic bacteria in the PDCA group, the infection rate of type I, type II, and type III incisions, and the total infection rate of surgical incisions were lower than those in the conventional group, and the difference was statistically significant (P < 0.05). The qualified rate of air samples and surface samples in the PDCA group was higher than that in the conventional group (P < 0.05), and the difference in the qualified rate of disinfectants and sterile items between the two groups was not statistically significant (P > 0.05). The hygiene management of the operating room adopts PDCA sustainable improvement management measures to effectively increase the qualification rate of disinfection and sterilization, reduce the detection rate of pathogenic bacteria and infection rate of surgical incisions, and strengthen the management quality of hand hygiene, environmental hygiene, medical waste, and disinfection and isolation.

Vapor-Phase Molecular Doping in Covalent Organosiloxane Network Thin Films Via a Lewis Acid-Base Interaction for Enhanced Mechanical Properties.

Incorporating inorganic components in organosiloxane polymer thin films for enhanced mechanical properties could enable better durability and longevity of functional coatings for a multitude of applications. However, molecularly dispersing the inorganic dopants while preserving the cyclosiloxane rings represents a challenge for cross-linked organosiloxane networks. Here, we report a molecular doping strategy using vapor-phase infiltration. On the basis of the proper Lewis acid-base interaction between diethyl zinc (DEZ) and cyclotrisiloxane rings, we achieved a complete infiltration of the organometallic precursors and well-distributed Zn-OH terminal groups formed in the initiated chemical vapor deposited poly(1,3,5-trimethyl-1,3,5-trivinylcyclotrisiloxane) (PV3D3) films. X-ray photoelectron spectroscopy and nanoscale infrared spectroscopy together with density functional theory simulation reveal that the formation of a Lewis acid-base adduct rather than a ring-opening process is possibly involved in anchoring DEZ in the cross-linked network of PV3D3. Because of the incorporation of Zn-OH components, the organic-inorganic hybrid films obtained via our vapor-phase molecular doping exhibit a 10.2% larger elastic modulus and 67.0% higher hardness than the pristine PV3D3. Unveiling the reaction mechanisms between organometallic precursors and cross-linked organic networks provides new insights for expanding the vapor-phase processing strategies for engineering hybrid materials at the nanoscale.

Enhancing biological nitrogen removal for a retrofit project using wastewater with a low C/N ratio-a model-based study.

Anaerobic ammonium oxidation (anammox) has the merit of saving the carbon source and aeration energy for nitrogen (N) removal, but it is normally a challenge to achieve mainstream anammox. In this study, the potential to enhance the N-removal capability of an existing University of Cape Town membrane bioreactor system (UCT-MBR) system is evaluated through process modeling. In addition to external carbon addition, the UCT-MBR system is proposed to be converted into an anoxic-oxic (AO) configuration with two operation plans: one is single-sludge (suspended sludge) and the other is double-sludge (suspended sludge and biofilm). The choice between pushing anammox and enhancing conventional heterotrophic denitrification is assessed. The simulation result indicates it is feasible to strategically adjust the spatial-temporal balance between electron donors and electron acceptors to achieve enhanced N-removal by utilizing the influent organic carbon other than adding external carbon. Although anammox can be promoted in the double-sludge-based AO under low-DO conditions, pushing anammox will weaken the system's resilience to influent fluctuations and carries no economic advantage over the single-sludge-based AO. Overall, this study concurs with the United Nations Sustainable Development Goal that the wastewater industry should seek more energy-efficient measures for wastewater treatment.

Lung Nodule Segmentation with a Region-Based Fast Marching Method.

When dealing with computed tomography volume data, the accurate segmentation of lung nodules is of great importance to lung cancer analysis and diagnosis, being a vital part of computer-aided diagnosis systems. However, due to the variety of lung nodules and the similarity of visual characteristics for nodules and their surroundings, robust segmentation of nodules becomes a challenging problem. A segmentation algorithm based on the fast marching method is proposed that separates the image into regions with similar features, which are then merged by combining regions growing with k-means. An evaluation was performed with two distinct methods (objective and subjective) that were applied on two different datasets, containing simulation data generated for this study and real patient data, respectively. The objective experimental results show that the proposed technique can accurately segment nodules, especially in solid cases, given the mean Dice scores of 0.933 and 0.901 for round and irregular nodules. For non-solid and cavitary nodules the performance dropped-0.799 and 0.614 mean Dice scores, respectively. The proposed method was compared to active contour models and to two modern deep learning networks. It reached better overall accuracy than active contour models, having comparable results to DBResNet but lesser accuracy than 3D-UNet. The results show promise for the proposed method in computer-aided diagnosis applications.

Tribulus terrestris Ameliorates Oxidative Stress-Induced ARPE-19 Cell Injury through the PI3K/Akt-Nrf2 Signaling Pathway.

Oxidative stress on retinal pigment epithelial (RPE) cells has been confirmed to play a crucial role in the development and progression of age-related macular degeneration (AMD) or other retinal degenerative diseases. Tribulus terrestris (TT) is a Chinese traditional herb medicine, which has been used for the treatment of ocular diseases for many centuries. In this study, we investigated the underlying mechanisms of TT and examined its ability to protect and restore the human retinal pigment epithelial cells (ARPE-19) against H2O2-induced oxidative stress. Our data show that 200 µg/mL of ethanol extract of Tribulus terrestris (EE-TT) significantly increased the cell viability and prevented the apoptosis of H2O2-treated ARPE-19 cells through the regulation of Bcl2, Bax, cleaved caspase-3, and caspase-9. Treatment with EE-TT also significantly decreased the upregulated reactive oxygen species (ROS) activities and increased the downregulated superoxide dismutase (SOD) activities induced by H2O2 in ARPE-19 cells. Additionally, H2O2 at 1 mM significantly decreased the mRNA expression levels of Nrf2, CAT, SOD1, SOD2, HO-1, GST-pi, NQO1, and GLCM in ARPE-19 cells; however, treatment with EE-TT reversed the downregulated mRNA expression levels of all these genes induced by H2O2. Furthermore, treatment with 200 µg/mL EE-TT alone for 24 h significantly increased Nrf2, HO-1, NQO1, and GCLM mRNA expressions in ARPE-19 cells when compared with untreated control cells. Pretreatment with the inhibitor of PI3K/Akt signaling (LY294002) completely blocked these EE-TT-upregulated mRNA expressions and abolished the improvement of cell viability in H2O2-treated ARPE-19 cells. These findings all suggest that Tribulus terrestris has significant antioxidant effects on oxidative stressed ARPE-19 cells through regulating PI3K/Akt-Nrf2 signaling pathway.

Nitrite-shunt and biological phosphorus removal at low dissolved oxygen in a full-scale high-rate system at warm temperatures.

This study presents results from the City of St. Petersburg's (Florida) Southwest Water Reclamation Facility. This high-rate BNR plant (SRT ~ 5 days; HRT < 8 hr) achieves combined bioP and shortcut simultaneous nitrification and denitrification (SND) via nitrite in a simple BNR configuration-an anaerobic-aerobic (A/O) process without mixed liquor recycle and a 25% unaerated fraction. N removal to low effluent and nitrate and nitrite ( NO 3 -  +  NO 2 - ) concentrations occurs mainly via SND by operating the aerated zone at low DO, but still achieving near-complete ammonium ( NH 4 + ) removal. Despite the low DO operation, very good bioP performance is achieved. Full-scale performance data and detailed bench-scale testing were conducted to assess the nitrogen and phosphorus removal at low DO conditions. Full-scale results showed that the plant achieves effluent total inorganic nitrogen (TIN) and total phosphorus (TP) concentrations of approximately 2.0 mgN/L and 0.5 mgP/L, respectively, at an average influent C:N ratio of 7:1 mgCOD:mgN. PRACTITIONER POINTS: Simple anaerobic-aerobic (A/O) process demonstrated combined N and P removal Ammonia oxidation was not hampered by low DO (<0.5 mg/L) operation Low DO (<0.5 mg/L) operation sustained SND via nitrite pathway in a high-rate process (HRT < 6 hr) P uptake was demonstrated at low DO which counters to the widely held understanding that high DO (>1.5 mg/L) is necessary Heterotrophic consumption of nitrite at low DO was the key to the out-selection of nitrite-oxidizing bacteria.

Alternative polyadenylation coordinates embryonic development, sexual dimorphism and longitudinal growth in Xenopus tropicalis.

RNA alternative polyadenylation contributes to the complexity of information transfer from genome to phenome, thus amplifying gene function. Here, we report the first X. tropicalis resource with 127,914 alternative polyadenylation (APA) sites derived from embryos and adults. Overall, APA networks play central roles in coordinating the maternal-zygotic transition (MZT) in embryos, sexual dimorphism in adults and longitudinal growth from embryos to adults. APA sites coordinate reprogramming in embryos before the MZT, but developmental events after the MZT due to zygotic genome activation. The APA transcriptomes of young adults are more variable than growing adults and male frog APA transcriptomes are more divergent than females. The APA profiles of young females were similar to embryos before the MZT. Enriched pathways in developing embryos were distinct across the MZT and noticeably segregated from adults. Briefly, our results suggest that the minimal functional units in genomes are alternative transcripts as opposed to genes.