A critical review of improving mainstream anammox systems: Based on macroscopic process regulation and microscopic enhancement mechanisms.

Full-scale anaerobic ammonium oxidation (anammox) engineering applications are vastly limited by the sensitivity of anammox bacteria to the complex mainstream ambience factors. Therefore, it is of great necessity to comprehensively summarize and overcome performance-related challenges in mainstream anammox process at the macro/micro level, including the macroscopic process variable regulation and microscopic biological metabolic enhancement. This article systematically reviewed the recent important advances in the enrichment and retention of anammox bacteria and main factors affecting metabolic regulation under mainstream conditions, and proposed key strategies for the related performance optimization. The characteristics and behavior mechanism of anammox consortia in response to mainstream environment were then discussed in details, and we revealed that the synergistic nitrogen metabolism of multi-functional bacterial genera based on anammox microbiome was conducive to mainstream anammox nitrogen removal processes. Finally, the critical outcomes of anammox extracellular electron transfer (EET) at the micro level were well presented, carbon-based conductive materials or exogenous electron shuttles can stimulate and mediate anammox EET in mainstream environments to optimize system performance from a micro perspective. Overall, this review advances the extensive implementation of mainstream anammox practice in future as well as shedding new light on the related EET and microbial mechanisms.

Exploring the Potential of ChatGPT-4 in Responding to Common Questions About Abdominoplasty: An AI-Based Case Study of a Plastic Surgery Consultation.

BACKGROUND: With the increasing integration of artificial intelligence (AI) in health care, AI chatbots like ChatGPT-4 are being used to deliver health information. OBJECTIVES: This study aimed to assess the capability of ChatGPT-4 in answering common questions related to abdominoplasty, evaluating its potential as an adjunctive tool in patient education and preoperative consultation. METHODS: A variety of common questions about abdominoplasty were submitted to ChatGPT-4. These questions were sourced from a question list provided by the American Society of Plastic Surgery to ensure their relevance and comprehensiveness. An experienced plastic surgeon meticulously evaluated the responses generated by ChatGPT-4 in terms of informational depth, response articulation, and competency to determine the proficiency of the AI in providing patient-centered information. RESULTS: The study showed that ChatGPT-4 can give clear answers, making it useful for answering common queries. However, it struggled with personalized advice and sometimes provided incorrect or outdated references. Overall, ChatGPT-4 can effectively share abdominoplasty information, which may help patients better understand the procedure. Despite these positive findings, the AI needs more refinement, especially in providing personalized and accurate information, to fully meet patient education needs in plastic surgery. CONCLUSIONS: Although ChatGPT-4 shows promise as a resource for patient education, continuous improvements and rigorous checks are essential for its beneficial integration into healthcare settings. The study emphasizes the need for further research, particularly focused on improving the personalization and accuracy of AI responses. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CFTR Modulates Hypothalamic Neuron Excitability to Maintain Female Cycle.

Cystic fibrosis transmembrane conductance regulator (CFTR), known as an epithelial Cl- channel, is increasingly noted to be expressed in the nervous system, although whether and how it plays a role in neuronal excitability is unclear. Given the association of CFTR with fertility, we tested here possible involvement of CFTR in regulating hypothalamic neuron excitability. Patch-clamp and Ca2+ imaging showed that pharmacological inhibition of CFTR evoked electrical pulses and Ca2+ spikes in primary rat hypothalamic neurons, which was dependent on extracellular Cl-. Hypothalamic neurons in brain-slice preparations from adult female mice with CFTR mutation (DF508) exhibited significantly reduced electrical pulses as compared to the wild-type controls. Removal of extracellular Cl- eliminated hypothalamic electrical pulses in the wild-type brain slices, which was reversible by subsequent addition of Cl-. In adult female mice, Ca2+ indicator (GCaMP6s)-based fiber-photometry showed that hypothalamic Ca2+ activities in vivo were enhanced at the proestrus/estrus phase as compared to the diestrus phase of the female cycle. Such estrus-associated hypothalamic activities were largely diminished in DF508 female mice, together with delayed puberty and disturbed female cycles. Therefore, these findings suggest a critical role of CFTR in modulating hypothalamic neuron excitability, which may account for the disturbed female cycles and reduced female fertility associated with CFTR mutations.

Direction of plant-soil feedback determines plant responses to drought.

Droughts exarcerbate Plant-soil feedbacks (PSFs) making positive PSFs more positive and negative PSFs more negative. Alterations in PSFs that droughts induce could relate to the rooting depth of the tested plants. We present some rare evidence on how a driver of global change will alter a biotic interaction.

Development of a droplet digital PCR method for detection of Streptococcus agalactiae.

BACKGROUND: Streptococcus agalactiae (GBS) is the causative pathogen of puerperal sepsis in pregnant women and pneumonia, sepsis and meningitis in infants. Infection of GBS is responsible for the increased morbidity in pregnant women and the elderly, and bring challenges to clinical diagnosis and treatment. However, culture-based approaches to detect S.agalactiae is time-consuming with limited sensitivity. Besides, real-time quantitative PCR demands expensive instruments with tedious steps. Thus, we aim to establish a new detection method for more accurate and rapid detection of S.agalactiae. RESULTS: The ddPCR primer targeted the CpsE gene showed better amplified efficiency in the reaction. The limit of detection for GBS DNA with ddPCR was able to reach 5 pg/µL. Moreover, no positive amplified signals could be detected in the reactions which served 11 non-GBS strains DNA as templates. Furthermore, the coefficient of variation of this method was 4.5%, indicating excellent repeatability of ddPCR assay. CONCLUSIONS: In our study, ddPCR was performed as a rapid detection of S.agalactiae with high sensitivity and specificity. This technique can promote the accuracy of the diagnosis of GBS infection and provide a scientific basis for clinical treatment.

Retracted: Mechanisms of Action of MicroRNAs in Infantile Hemangioma Tissue and Vascular Endothelial Cells in Different Periods.

The article is withdrawn by the authors request.

Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124.

Increasing evidences have revealed the important role of circular RNAs (circRNAs) in cardiovascular system disease. Whereas, the expression profiles and in-depth regulation of circRNAs on vascular smooth muscle cells (VSMCs) is still undetermined. In present study, our research team performed circRNAs microarray analysis to present the circRNAs expression profiles in high glucose induced VSMCs in vitro. Results showed that total of 983 circRNAs were discovered to be differentially expressed, and of these, 458 were upregulated and 525 were downregulated. Moreover, 31 circRNAs were up-regulated and 22 circRNAs were down-regulated with 2 fold change (P < 0.05). One of an up-regulated circRNA, circWDR77, was identified. In vitro cell assay, circWDR77 silencing significantly inhibited the proliferation and migration. Bioinformatics methods discovered that miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of circWDR77. The RNA sequence complementary binding was validated by RNA immunoprecipitation (RIP) and/or luciferase reporter assay. Further function validation experiments revealed that circWDR77 regulated VSMCs proliferation and migration via targeting miR-124/FGF2. Taken together, present study firstly reveals the circRNAs expression profiles in high glucose induced VSMCs and identifies the role of circWDR77-miR-124-FGF2 regulatory pathway in VSMCs proliferation and migration, which might provide a new theoretical basis for diabetes mellitus correlated vasculopathy.

The Dual Role of the NFATc2/galectin-9 Axis in Modulating Tumor-Initiating Cell Phenotypes and Immune Suppression in Lung Adenocarcinoma.

Tumor-initiating cells (TICs) resilience and an immunosuppressive microenvironment are aggressive oncogenic phenotypes that contribute to unsatisfactory long-term outcomes in lung adenocarcinoma (LUAD) patients. The molecular mechanisms mediating the interaction between TICs and immune tolerance have not been elucidated. The role of Galectin-9 in oncogenesis and immunosuppressive microenvironment is still unknown. This study explored the potential role of galectin-9 in TIC regulation and immune modulation in LUAD. The results show that galectin-9 supports TIC properties in LUAD. Co-culture of patient-derived organoids and matched peripheral blood mononuclear cells showed that tumor-secreted galectin-9 suppressed T cell cytotoxicity and induced regulatory T cells (Tregs). Clinically, galectin-9 is upregulated in human LUAD. High expression of galectin-9 predicted poor recurrence-free survival and correlated with high levels of Treg infiltration. LGALS9, the gene encoding galectin-9, is found to be transcriptionally regulated by the nuclear factor of activated T cells 2 (NFATc2), a previously reported TIC regulator, via in silico prediction and luciferase reporter assays. Overall, the results suggest that the NFATc2/galectin-9 axis plays a dual role in TIC regulation and immune suppression.

Metagenomics insights into high-rate nitrogen removal from municipal wastewater by integrated nitrification, partial denitrification and Anammox at an extremely short hydraulic retention time.

To achieve high-rate nitrogen removal in municipal wastewater treatment through anaerobic ammonia oxidation (Anammox), the nitrification, partial denitrification, and Anammox processes were integrated by a step-feed strategy. An exceptional nitrogen removal load of 0.224 kg N/(m3·d) was achieved by gradient-reducing the hydraulic retention time (HRT) to 5 h. Metagenomic analysis demonstrated that Nitrosospira could express all genes encoding ammonia oxidation under low nitrogen and dissolved oxygen conditions (less than 0.5 mg/L), enabling complete nitrification. With the short of HRT, the relative abundance of Thauera increased from 2.8 % to 6.4 %. Frequent substrate exchanges at such extremely short HRT facilitated enhanced synergistic interactions among Nitrosospira, Thauera, and Candidatus Brocadia. These findings provide a comprehensive understanding of the utilization of Anammox combined processes for high-speed nitrogen removal in municipal wastewater treatment and the microbial interactions involved.

Thermally and Photothermally Triggered Cytocompatible Triple-Shape-Memory Polymer Based on a Graphene Oxide-Containing Poly(ε-caprolactone) and Acrylate Composite.

Triple-shape-memory polymers (triple-SMPs) are a class of polymers capable of fixing two temporary shapes and recovering sequentially from the first temporary shape to the second temporary shape and, last, to the permanent shape. To accomplish a sequential shape change, a triple-SMP must have two separate shape-fixing mechanisms triggerable by distinct stimuli. Despite the biomedical potential of triple-SMPs, a triple-SMP that with cells present can undergo two different shape changes via two distinct cytocompatible triggers has not previously been demonstrated. Here, we report the design and characterization of a cytocompatible triple-SMP material that responds separately to thermal and light triggers to undergo two distinct shape changes under cytocompatible conditions. Tandem triggering was achieved via a photothermally triggered component, comprising poly(ε-caprolactone) (PCL) fibers with graphene oxide (GO) particles physically attached, embedded in a thermally triggered component, comprising a tert-butyl acrylate-butyl acrylate (tBA-BA) matrix. The material was characterized in terms of thermal properties, surface morphology, shape-memory performance, and cytocompatibility during shape change. Collectively, the results demonstrate cytocompatible triple-shape behavior with a relatively larger thermal shape change (an average of 20.4 ± 4.2% strain recovered for all PCL-containing groups) followed by a smaller photothermal shape change (an average of 3.5 ± 0.8% strain recovered for all PCL-GO-containing groups; samples without GO showed no recovery) with greater than 95% cell viability on the triple-SMP materials, establishing the feasibility of triple-shape memory to be incorporated into biomedical devices and strategies.

Efficient nitrogen removal from municipal wastewater by an autotrophic-heterotrophic coupled anammox system: The up-regulation of key functional genes.

The metabolic pathways based on key functional genes were innovatively revealed in the autotrophic-heterotrophic coupled anammox system for real municipal wastewater treatment. The nitrogen removal performance of the system was stabilized at 88.40 ± 3.39 % during the treatment of real municipal wastewater. The relative abundances of the nitrification functional genes ammonia oxidase (amoA/B/C), hydroxylamine oxidoreductase (hao), and nitrite oxidoreductases (nxrA/B) were increased by 1.2-2.4 times, and these three nitrification functional genes were mostly contributed by Nitrospira that dominated the efficient nitrification of the system. The relative abundance of anammox bacteria Candidatus Brocadia augmented from 0.35 % to 0.75 %, accompanied with the increased expression of hydrazine synthase (hzs) and hydrazine dehydrogenase (hdh), resulting in the major role of anammox (81.24 %) for nitrogen removal. The expression enhancement of the functional genes nitrite reductase (narG/H, napA/B) that promoted partial denitrification (PD) of the system weakened the adverse effects of the sharp decline in the population of PD microbe Thauera (from 5.7 % to 2.2 %). The metabolic module analysis indicated that the carbon metabolism pathways of the system mainly included CO2 fixation and organic carbon metabolism, and the stable enrichment of autotrophic bacteria ensured stable CO2 fixation. Furthermore, the enhanced expression of the glucokinases (glk, GCK, HK, ppgk) and the abundant pyruvate kinase (PK) achieved stable hydrolysis ability of organic carbon metabolism function of the system. This study offers research basics to practical application of the mainstream anammox process.

Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors.

Glutathione S-transferase pi (GSTP1), a phase II detoxification enzyme, is known to be overexpressed and mediates chemotherapeutic resistance in lung cancer. However, whether GSTP1 supports cancer stem cells (CSCs) and the underlying mechanisms in lung adenocarcinoma (LUAD) remain largely unknown. This study unveiled that GSTP1 is upregulated in lung CSCs and supports tumor self-renewal, metastasis, and resistance to targeted tyrosine kinase inhibitors of LUAD both in vitro and in vivo. Mechanistically, CaMK2A (calcium/calmodulin-dependent protein kinase 2 isoform A)/NRF2 (nuclear factor erythroid 2-related factor 2)/GSTP1 is uncovered as a regulatory axis under hypoxia. CaMK2A increased GSTP1 expression through phosphorylating the Sersine558 residue of NRF2 and promoting its nuclear translocation, a novel mechanism for NRF2 activation apart from conventional oxidization-dependent activation. Upregulation of GSTP1 in turn suppressed reactive oxygen species levels and supported CSC phenotypes. Clinically, GSTP1 analyzed by immunohistochemistry is upregulated in a proportion of LUAD and serves as a prognostic marker for survival. Using patient-derived organoids from an ALK-translocated LUAD, the therapeutic potential of a specific GSTP1 inhibitor ezatiostat in combination treatment with the ALK inhibitor crizotinib is demonstrated. This study demonstrates GSTP1 to be a promising therapeutic target for long-term control of LUAD through targeting CSCs.

PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter.

Phosphodiesterase type 5 (PDE5) inhibitors are widely used in the treatment of male erectile dysfunction and pulmonary hypertension. Recently, several groups have evaluated the ability of PDE5 inhibitors for their anticancer activities. Previously, we had shown that sildenafil, vardenafil and tadalafil could reverse P-glycoprotein (ATP-binding cassette B1)-mediated MDR. In the present study, we determined whether these PDE5 inhibitors have the potential to reverse multidrug resistance protein 7 (MRP7; ATP-binding cassette C10)-mediated MDR. We found that sildenafil and vardenafil dose-dependently enhanced the sensitivity of MRP7-transfected HEK293 cells to paclitaxel, docetaxel and vinblastine, while tadalafil had only a minimal effect. Accumulation and efflux experiments demonstrated that sildenafil and vardenafil increased the intracellular accumulation of [(3)H]-paclitaxel by inhibiting the efflux of [(3 H]-paclitaxel in HEK/MRP7 cells. In addition, immunoblot and immunofluorescence analyses indicated that no significant alterations of MRP7 protein expression and localization in plasma membranes were found after treatment with sildenafil, vardenafil or tadalafil. These results demonstrate that sildenafil and vardenafil reverse MRP7-mediated a MDR through inhibition of the drug efflux function of MRP7. Our findings indicate a potentially novel use of PDE5 inhibitors as an adjuvant chemotherapeutic agent in clinical practice.

Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production.

Drug resistance remains a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug-resistance related proteins, increased drug metabolism, decreased apoptosis, and impairment of signal transduction pathway can contribute multidrug resistance (MDR). Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug-resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/chemokines screened, IL-6, IL-8, and 13 other proteins were found to be markedly increased in drug-resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drug-resistant MCF-7/R cells. Neutralizing antibodies against IL-6 and IL-8 partially reversed the drug resistance of MCF-7/R to paclitaxel and doxorubicin, while a neutralizing antibody against MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. Furthermore, overexpression of IL-6 or IL-8 expression by transfection increased the ADM resistance in MCF-7/S cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to MDR in human breast cancer cells.

BBA, a derivative of 23-hydroxybetulinic acid, potently reverses ABCB1-mediated drug resistance in vitro and in vivo.

23-O-(1,4'-Bipiperidine-1-carbonyl)betulinic acid (BBA), a synthetic derivative of 23-hydroxybetulinic acid (23-HBA), shows a reversal effect on multidrug resistance (MDR) in our preliminary screening. Overexpression of ATP-binding cassette (ABC) transporters such as ABCB1, ABCG2, and ABCC1 has been reported in recent studies to be a major factor contributing to MDR. Our study results showed that BBA enhanced the cytotoxicity of ABCB1 substrates and increased the accumulation of doxorubicin or rhodamine123 in ABCB1 overexpressing cells, but had no effect on non ABCB1 substrate, such as cisplatin; what's more, BBA slightly reversed ABCG2-mediated resistance to SN-38, but did not affect the ABCC1-mediated MDR. Further studies on the mechanism indicated that BBA did not alter the expression of ABCB1 at mRNA or protein levels, but affected the ABCB1 ATPase activity by stimulating the basal activity at lower concentrations and inhibiting the activity at higher concentrations. In addition, BBA inhibited the verapamil-stimulated ABCB1 ATPase activity and the photolabeling of ABCB1 with [(125)I] iodoarylazidoprazosin in a concentration-dependent manner, indicating that BBA directly interacts with ABCB1. The docking study confirmed this notion that BBA could bind to the drug binding site(s) on ABCB1, but its binding position was only partially overlapping with that of verapamil or iodoarylazidoprazosin. Importantly, BBA increased the inhibitory effect of paclitaxel in ABCB1 overexpressing KB-C2 cell xenografts in nude mice. Taken together, our findings suggest that BBA can reverse ABCB1-mediated MDR by inhibiting its efflux function of ABCB1, which supports the development of BBA as a novel potential MDR reversal agent used in the clinic.

Enhancing chemosensitivity in ABCB1- and ABCG2-overexpressing cells and cancer stem-like cells by an Aurora kinase inhibitor CCT129202.

Imidazopyridine CCT129202 is an inhibitor of Aurora kinase activity and displays a favorable antineoplastic effect in preclinical studies. Here, we investigated the enhanced effect of CCT129202 on the cytotoxicity of chemotherapeutic drugs in multidrug resistant (MDR) cells with overexpression of ATP-binding cassette (ABC) transporters and cancer stem-like cells. CCT129202 of more than 90% cell survival concentration significantly enhanced the cytotoxicity of substrate drugs and increased the intracellular accumulations of doxorubicin and rhodamine 123 in ABCB1 and ABCG2 overexpressing cells, while no effect was found on parental sensitive cells. Interestingly, CCT129202 also potentiated the sensitivity of cancer stem-like cells to doxorubicin. Importantly, CCT129202 increased the inhibitory effect of vincristine and paclitaxel on ABCB1 overexpressing KBv200 cell xenografts in nude mice and human esophageal cancer tissue overexpressing ABCB1 ex vivo, respectively. Furthermore, the ATPase activity of ABCB1 was inhibited by CCT129202. Homology modeling predicted the binding conformation of CCT129202 within the large hydrophobic cavity of ABCB1. On the other hand, CCT129202 neither apparently altered the expression levels of ABCB1 and ABCG2 nor inhibited the activity of Aurora kinases in MDR cells under the concentration of reversal MDR. In conclusion, CCT129202 significantly reversed ABCB1- and ABCG2-mediated MDR in vitro, in vivo and ex vivo by inhibiting the function of their transporters and enhanced the eradication of cancer stem-like cells by chemotherapeutic agents. CCT129202 may be a candidate as MDR reversal agent for antineoplastic combination therapy and merits further clinical investigation.

Deep Neural Network for Automatic Classification of Pathological Voice Signals.

OBJECTIVES: Computer-aided pathological voice detection is efficient for initial screening of pathological voice, and has received high academic and clinical attention. This paper proposes an automatic diagnosis method of pathological voice based on deep neural network (DNN). Other two classification models (support vector machines and random forests) were used to verify the effectiveness of DNN. METHODS: In this paper, we extracted 12 Mel frequency cepstral coefficients of each voice sample as row features. The constructed DNN consists a two-layer stacked sparse autoencoders network and a softmax layer. The stacked sparse autoencoders layer can learn high-level features from raw Mel frequency cepstral coefficients features. Then, the softmax layer can diagnose pathological voice according to high-level features. The DNN and the other two comparison models used the same train set and test set for the experiment. RESULTS: Experimental results reveal that the value of sensitivity, specificity, precision, accuracy, and F1 score of the DNN can reach 97.8%, 99.4%, 99.4%, 98.6%, and 98.4%, respectively. The five indexes of DNN classification results are at least 6.2%, 5%, 5.6%, 5.7%, and 6.2% higher than the comparison models (support vector machine and random forest). CONCLUSIONS: The proposed DNN can learn advanced features from raw acoustic features, and distinguish pathological voice from healthy voice. To the extent of this preliminary study, future studies can further explore the application of DNN in other experiments and clinical practice.