Pan-cancer analysis of polo-like kinase family genes reveals polo-like kinase 1 as a novel oncogene in kidney renal papillary cell carcinoma.

Background: Polo-like kinases (PLKs) are a kinase class of serine/threonine with five members that play crucial roles in cell cycle regulation. However, their biological functions, regulation, and expression remain unclear. This study revealed the molecular properties, oncogenic role, and clinical significance of PLK genes in pan-cancers, particularly in kidney renal papillary cell carcinoma (KIRP). Methods: We evaluated the mutation landscape, expression level, and prognostic values of PLK genes using bioinformatics analyses and explored the association between the expression level of PLK genes and tumor microenvironment (TME), immune subtype, cancer immunotherapy, tumor stemness, and drug sensitivity. Finally, we verified the prognostic value in patients with KIRP through univariate and multivariate analyses and nomogram construction. Results: PLK genes are extensively altered in pan-cancer, which may contribute to tumorigenesis. These genes are aberrantly expressed in some types of cancer, with PLK1 being overexpressed in 31 cancers. PLK expression is closely associated with the prognosis of various cancers. The expression level of PLK genes is related with sensitivity to diverse drugs and cancer immunity as well as cancer immunotherapy. Importantly, we verified that PLK1 was overexpressed in KIRP tissues and could be an unfavorable prognostic biomarker in patients with KIRP. Hence, PLK1 may serve as an oncogenic gene in KIRP and should be explored in future studies. Conclusions: Our study comprehensively reports the molecular characteristics and biological functions of PLK family gens across human cancers and recommends further investigation of these genes as potential biomarkers and therapeutic targets, especially in KIRP.

S100P facilitates LUAD progression via PKA/c-Jun-mediated tumor-associated macrophage recruitment and polarization.

S100P, a member of the S100 calcium-binding protein family, is closely associated with abnormal proliferation, invasion, and metastasis of various cancers. However, its role in the lung adenocarcinoma (LUAD) tumor microenvironment (TME) remains unclear. In this study, we observed specific expression of S100P on tumor cells in LUAD patients through tissue immunofluorescence analysis. Furthermore, this expression was strongly correlated with the recruitment and polarization of tumor-associated macrophages (TAMs). Bioinformatics analysis revealed that high S100P expression is associated with poorer overall survival in LUAD patients. Subsequently, a subcutaneous mouse model demonstrated that S100P promotes recruitment and polarization of TAMs towards the M2 type. Finally, in vitro studies on LUAD cells revealed that S100P enhances the secretion of chemokines and polarizing factors by activating the PKA/c-Jun pathway, which is implicated in TAM recruitment and polarization towards the M2 phenotype. Moreover, inhibition of c-Jun expression impedes the ability of TAMs to infiltrate and polarize towards the M2 phenotype. In conclusion, our study demonstrates that S100P facilitates LUAD cells growth by recruiting M2 TAMs through PKA/c-Jun signaling, resulting in the production of various cytokines. Considering these findings, S100P holds promise as an important diagnostic marker and potential therapeutic target for LUAD.

Reprogramming the Metabolism of Yeast for High-Level Production of Miltiradiene.

Miltiradiene serves as a crucial precursor in the synthesis of various high-value abietane-type diterpenes, exhibiting diverse pharmacological activities. Previous efforts to enhance miltiradiene production have primarily focused on the mevalonate acetate (MVA) pathway. However, limited emphasis has been placed on optimizing the supply of acetyl-CoA and NADPH. In this study, we constructed a platform yeast strain for miltiradiene production by reinforcing the biosynthetic pathway of geranylgeranyl diphosphate (GGPP) and acetyl-CoA, and addressing the imbalance between the supply and demand of the redox cofactor NADPH within the cytoplasm, resulting in an increase in miltiradiene yield to 1.31 g/L. Furthermore, we conducted modifications to the miltiradiene synthase fusion protein tSmKSL1-CfTPS1. Finally, the comprehensive engineering strategies and protein modification strategies culminated in 1.43 g/L miltiradiene in the engineered yeast under shake flask culture conditions. Overall, our work established efficient yeast cell factories for miltiradiene production, providing a foothold for heterologous biosynthesis of abietane-type diterpenes.

Investigating the impact of regulatory B cells and regulatory B cell-related genes on bladder cancer progression and immunotherapeutic sensitivity.

BACKGROUND: Regulatory B cells (Bregs), a specialized subset of B cells that modulate immune responses and maintain immune tolerance in malignant tumors, have not been extensively investigated in the context of bladder cancer (BLCA). This study aims to elucidate the roles of Bregs and Breg-related genes in BLCA. METHODS: We assessed Breg infiltration levels in 34 pairs of BLCA and corresponding paracancerous tissues using immunohistochemical staining. We conducted transwell and wound healing assays to evaluate the impact of Bregs on the malignant phenotype of SW780 and T24 cells. Breg-related genes were identified through gene sets and transcriptional analysis. The TCGA-BLCA cohort served as the training set, while the IMvigor210 and 5 GEO cohorts were used as external validation sets. We employed LASSO regression and random forest for feature selection and developed a risk signature using Cox regression. Primary validation of the risk signature was performed through immunohistochemical staining and RT-qPCR experiments using the 34 local BLCA samples. Additionally, we employed transfection assays and flow cytometry to investigate Breg expansion ability and immunosuppressive functions. RESULTS: Breg levels in BLCA tissues were significantly elevated compared to paracancerous tissues (P < 0.05) and positively correlated with tumor malignancy (P < 0.05). Co-incubation of SW780 and T24 cells with Bregs resulted in enhanced invasion and migration abilities (all P < 0.05). We identified 27 Breg-related genes, including CD96, OAS1, and CSH1, which were integrated into the risk signature. This signature demonstrated robust prognostic classification across the 6 cohorts (pooled HR = 2.25, 95% CI = 1.52-3.33). Moreover, the signature exhibited positive associations with advanced tumor stage (P < 0.001) and Breg infiltration ratios (P < 0.05) in the local samples. Furthermore, the signature successfully predicted immunotherapeutic sensitivity in three cohorts (all P < 0.05). Knockdown of CSH1 in B cells increased Breg phenotype and enhanced suppressive ability against CD8 + T cells (all P < 0.05). CONCLUSIONS: Bregs play a pro-tumor role in the development of BLCA. The Breg-related gene signature established in this study holds great potential as a valuable tool for evaluating prognosis and predicting immunotherapeutic response in BLCA patients.

Simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction: initial experience.

BACKGROUND: Simultaneous transcatheter mitral valve in valve (VIV) replacement and aortic valve replacement experience is limited. We report our initial experience with simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction. METHODS: A total of 8 patients had simultaneous transcatheter heart valve implants for severe mitral bioprosthesis failure (VIV), with a second valve procedure that included native aortic regurgitation (n = 3) or degenerated bioprostheses in the aortic position (n = 5). All patients were treated with a self-expandable J-valve transcatheter valve, using the transapical approach. RESULTS: The mean age of the patients was 73.1 ± 6.2 years. The mean Society of Thoracic Surgeons score was 13.8 ± 6.3%. Device success was 100% according to Valve Academic Research Consortium-2 criteria. No other procedure-associated complications occurred, including left ventricular outflow tract obstruction and valve migration. The mean hospital lengths of stay after the procedure were 11.5 ± 8.0 days. No deaths occurred at 30 days. At a median follow-up period of 28.7 ± 22.3 months, no patients died. All patients were in New York Heart Association functional classes I-II. Echocardiographic parameters at follow-up showed a normofunctioning J valve in the mitral position and a mean max mitral flow velocity of 2.0 ± 0.5 m/s; the J valve in the aortic position was also normofunctioning, and the mean max aortic flow velocity was 2.3 ± 0.5 m/s. CONCLUSION: Simultaneous transapical transcatheter aortic and mitral valve replacement using the self-expandable J valve appears to be a feasible and effective alternative to redo surgery.

Reduced Monocular Luminance Promotes Fusion But Not Mixed Perception in Amblyopia.

Purpose: The purpose of this study was to understand how monocular luminance reduction affects binocular balance and examine whether it differentially influences fusion and mixed perception in amblyopia. Methods: Twenty-three normally sighted observers and 12 adults with amblyopia participated in this study. A novel binocular rivalry task was used to measure the phase duration of four perceptual responses (right- and left-tilts, fusion, and mixed perception) before and after a neutral density (ND) filter was applied at various levels to the dominant eye (DE) of controls and the fellow eye (FE) of patients with amblyopia. Phase durations were analyzed to assess whether the duration of fusion or mixed perception shifted after monocular luminance reduction. Moreover, we quantified ocular dominance and adjusted monocular contrast and luminance separately to investigate the relationship between changes in ocular dominance induced by the two manipulations. Results: In line with previous studies, binocular balance shifted in favor of the brighter eye in both normal adults and patients with amblyopia. As a function of the ND filter's density, the duration of fusion and mixed perception decreased in normal controls, whereas that of fusion but not mixed perception increased significantly in patients with amblyopia. In addition, changes in binocular balance from luminance reduction were more significant in more balanced amblyopes or normal observers. Furthermore, shifts in binocular balance after contrast and luminance modulation were correlated in both normal and amblyopic observers. Conclusions: The duration of fusion but not mixed perception increased in amblyopia after monocular luminance reduction in the FE. Moreover, our findings demonstrate that changes in ocular dominance from contrast-modulation and luminance-modulation are correlated in both normal and amblyopic observers.

CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.

OBJECTIVE: This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. METHODS: Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. RESULTS: This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. CONCLUSION: As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

Carbon Fiber Film with Multi-Hollow Channels to Expedite Oxygen Electrocatalytic Reaction Kinetics for Flexible Zn-Air Battery.

The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.

Abnormal energy metabolism, oxidative stress, and polyunsaturated fatty acid metabolism in depressed adolescents associated with childhood maltreatment: A targeted metabolite analysis.

The purpose of this study was to explore the metabolomic differences between Major depressive disorder (MDD) and healthy individuals among adolescents and the association between childhood maltreatment (CM) and differentially abundant metabolites. The exploratory study included 40 first-episode drug-naïve adolescents with MDD and 20 healthy volunteers. We used the Beck Depression Inventory (BDI-13) to assess the severity of depression and the Childhood Trauma Questionnaire (CTQ) to assess the presence of childhood maltreatment. The plasma samples from all participants were collected for targeted metabolomics analysis using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS) methods. Spearman correlation was applied to analyse the correlations between clinical variables and metabolites. We found 11 increased metabolites and 37 decreased metabolites that differed between adolescents with MDD and healthy individuals. Pathway enrichment analysis of differentially abundant metabolites showed abnormalities in energy metabolism and oxidative stress in MDD. Importantly, we found that creatine, valine, isoleucine, glutamic acid and pyroglutamic acid were negatively correlated with the BDI-13, while isocitric acid, fatty acid and acylcarnitine were negatively associated with CTQ, and 4-hydroxyproline was positively related to CTQ in adolescents with MDD. These studies provide new ideas for the pathogenesis and potential treatment of adolescents with MDD.

Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs.

BACKGROUND: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3). However, the underlying mechanism remains largely unknown. METHODS: BCa-derived exosomes was isolated and used for a series of experiments. RNA sequencing was used to identify the differentially expressed circRNAs. Western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, ELISA and Flow cytometry were performed to reveal the potential mechanism of circRNA_0013936 promoting the immunosuppressive activity of PMN-MDSC. RESULTS: CircRNA_0013936 enriched in BCa-derived exosomes could promote the expression of FATP2 and inhibit the expression of RIPK3 in PMN-MDSCs. Mechanistically, circRNA_0013936 promoted the expression of FATP2 and inhibited the expression of RIPK3 expression via sponging miR-320a and miR-301b, which directly targeted JAK2 and CREB1 respectively. Ultimately, circRNA_0013936 significantly inhibited the functions of CD8+ T cells by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway, and down-regulating RIPK3 through the circRNA_0013936/miR-301b/CREB1 pathway in PMN-MDSCs. CONCLUSIONS: BCa-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway and down-regulating RIPK3 through the circRNA_0013936/miR-301b-3p/CREB1 pathway in PMN-MDSCs. These findings help to find new targets for clinical treatment of human bladder cancer.

Phenotypic switching as a non-genetic mechanism of resistance predicts antibody therapy regimens.

Despite the specificity and effectiveness of antibody therapy, resistance to treatment remains a major barrier for their broad clinical applications. While genetic mutations are known to be critical, the impact of non-genetic mechanisms, such as epigenetic changes and phenotypic adaptations, on resistance to antibody-dependent cellular cytotoxicity (ADCC) is not fully understood. Our study investigated the non-genetic resistance mechanisms that colorectal cancer cells develop against cetuximab and the resulting ADCC pressure. Resistance clones exhibited decreased EGFR/HER2 expressions, enriched interferon-related pathways, and lower NK cell activation. Interestingly, these resistance clones regained sensitivity upon the withdrawal of therapeutic pressure, implying phenotypic plasticity and reversibility. To counter resistance, we developed a mathematical model recapitulating the phenotypic switching dynamics. The model predicted that intermittent dosing strategy outperforms continuous regimen in delaying treatment resistance. Our findings have implications for improving efficacy and circumventing resistance to targeted antibody therapies.

Understanding formation processes of calcareous nephrolithiasis in renal interstitium and tubule lumen.

Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi-step and long-term process involving the transformation of stone-forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen.

Comparative evaluation of SPE methods for biotoxicity assessment of water and wastewater: Linkage between chemical extracting efficiency and biotoxicity outcome.

Biotoxicity assessment results of environmental waters largely depend on the sample extraction protocols that enrich pollutants to meet the effect-trigger thresholds of bioassays. However, more chemical mixture does not necessarily translate to higher combined biotoxicity. Thus, there is a need to establish the link between chemical extracting efficiency and biotoxicity outcome to standardize extraction methods for biotoxicity assessment of environmental waters. This study compares the performance of five different extraction phases in solid phase extraction (SPE), namely HLB, HLB+Coconut, C18 cartridge, C18 disk and Strata-X, and evaluated their chemical extracting efficiencies and biotoxicity outcomes. We quantitatively assessed cytotoxicity, acute toxicity, genotoxicity, estrogenic activity, and neurotoxicity of the extracts using in vitro bioassays and characterized the chemical extracting efficiencies of the SPE methods through chemical recoveries of 23 model compounds with different polarities and total organic carbon. Using Pareto ranking, we identified HLB+Coconut as the optimal SPE method, which exhibited the highest level of water sample biotoxicity and recovered the most chemicals in water samples. We found that the biotoxicity outcomes of the extracted water samples significantly and positively correlated with the chemical extracting efficiencies of the SPE methods. Moreover, we observed synchronous changing patterns in biotoxicity outcome and chemical extracting efficiencies in response to increasing sample volumes per cartridge (SVPC) during SPE. Our findings underscore that higher chemical extracting efficiency of SPE corresponds to higher biotoxicity outcome of environmental water samples, providing a scientific basis for standardization of SPE methods for adequate assessment of biotoxicities of environmental waters.

The application of HER2-ADC in future: More than expression.

We analyzed the potential of HER2-targeted antibody-drug conjugates (ADCs) in treating NSCLC with activating HER2 mutations. We identified specific mutations, notably G776delinsVC, that are associated with higher therapeutic response rates, suggesting a refined approach for precision treatment. Further validation and exploration are crucial for potential breakthroughs in ADC therapy.

GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. METHODS: We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. RESULTS: Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. CONCLUSIONS: This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD.

Effects of Monocular Flicker on Binocular Imbalance in Amblyopic and Nonamblyopic Adults.

Purpose: This study aimed to evaluate the effects of monocular flicker stimulation on binocular imbalance in both amblyopic and nonamblyopic adults. Methods: Seven amblyopic patients (28.3 ± 3.3 years; four females) and seven normally sighted participants (27.3 ± 4.1 years; five females) participated in the study. We used liquid crystal spectacles to create externally-generated monocular flicker (4, 7, 10, 15, or 20 Hz) and used the metric of log balance point (logBP) to determine whether imposed flicker could change the eyes' equilibrium interocular contrast ratio. Flicker was applied to either the fellow eye vs. the amblyopic eye or dominant eye (DE) vs. non-DE (non-DE) of amblyopic and nonamblyopic participants, respectively. We defined a logBP of 0 to indicate complete binocular balance and an increase in logBP relative to baseline to indicate a relative strengthening of the non-DE or amblyopic eye. Results: Monocular flicker applied to the DE or fellow eye increased logBP, whereas when applied to the non-DE or amblyopic eye, reduced the logBP. These effects were more pronounced at low temporal frequencies than that at high temporal frequencies. The interaction between eye and temporal frequency was significant in both normals, F(4, 24) = 58.082, P < 0.001, η2 = 0.906, and amblyopes, F(1.923, 11.538) = 60.555, P < 0.001, η2 = 0.91. Conclusions: Monocular flicker diminishes the contribution of the flickered eye in binocular combination, resulting in a relative dominance of the nonflickered eye in interocular interactions. Furthermore, a more pronounced temporally modulated effect was observed at lower temporal frequencies.

Chemical-toxicological insights and process comparison for estrogenic activity mitigation in municipal wastewater treatment plants.

Efforts in water ecosystem conservation require an understanding of causative factors and removal efficacies associated with mixture toxicity during wastewater treatment. This study conducts a comprehensive investigation into the interplay between wastewater estrogenic activity and 30 estrogen-like endocrine disrupting chemicals (EEDCs) across 12 municipal wastewater treatment plants (WWTPs) spanning four seasons in China. Results reveal substantial estrogenic activity in all WWTPs and potential endocrine-disrupting risks in over 37.5 % of final effluent samples, with heightened effects during colder seasons. While phthalates are the predominant EEDCs (concentrations ranging from 86.39 %) for both estrogenic activity and major EEDCs (phthalates and estrogens), with the secondary and tertiary treatment segments contributing 88.59 ± 8.12 % and 11.41 ± 8.12 %, respectively. Among various secondary treatment processes, the anaerobic/anoxic/oxic-membrane bioreactor (A/A/O-MBR) excels in removing both estrogenic activity and EEDCs. In tertiary treatment, removal efficiencies increase with the inclusion of components involving physical, chemical, and biological removal principles. Furthermore, correlation and multiple liner regression analysis establish a significant (p < 0.05) positive association between solid retention time (SRT) and removal efficiencies of estrogenic activity and EEDCs within WWTPs. This study provides valuable insights from the perspective of prioritizing key pollutants, the necessity of integrating more efficient secondary and tertiary treatment processes, along with adjustments to operational parameters like SRT, to mitigate estrogenic activity in municipal WWTPs. This contribution aids in managing endocrine-disrupting risks in wastewater as part of ecological conservation efforts.

Daily dose-response from short-term monocular deprivation in adult humans.

Short-term monocular deprivation (MD) shifts sensory eye balance in favour of the previously deprived eye. The effect of MD on eye balance is significant but brief in adult humans. Recently, researchers and clinicians have attempted to implement MD in clinical settings for adults with impaired binocular vision. Although the effect of MD has been studied in detail in single-session protocols, what is not known is whether the effect of MD on eye balance deteriorates after repeated periods of MD (termed 'perceptual deterioration'). An answer to this question is relevant for two reasons. Firstly, the effect of MD (i.e., dose-response) should not decrease with repeated use if MD is to be used therapeutically (e.g., daily for weeks). Second, it bears upon the question of whether the neural basis of the effects of MD and contrast adaptation, a closely related phenomenon, is the same. The sensory change from contrast adaptation depends on recent experience. If the observer has recently experienced the same adaptation multiple times for consecutive days, then the adaptation effect will be smaller because contrast adaptation exhibits perceptual deterioration, so it is of interest to know if the effects of MD follow suit. This study measured the effect of 2-h MD for seven consecutive days on binocular balance of 15 normally sighted adults. We found that the shift in eye balance from MD stayed consistent, showing no signs of deterioration after subjects experienced multiple periods of MD. This finding shows no loss of effectiveness of repeated daily doses of MD if used therapeutically to rebalance binocular vision in otherwise normal individuals. Furthermore, ocular dominance plasticity, which is the basis of the effects of short-term MD, does not seem to share the property of 'perceptual deterioration' with contrast adaptation, suggesting different neural bases for these two related phenomena.

Binocular balance across spatial frequency in anisomyopia.

Purpose: Anisomyopia is prevalent in myopia and studies have reported it exhibits impaired binocular function. We investigated the binocular balance across spatial frequency in adults with anisomyopia and compared it to in individuals with less differences in refractive error, and examined whether ocular characteristics can predict binocular balance in anisomyopia. Methods: Fifteen anisomyopes, 15 isomyopes and 12 emmetropes were recruited. Binocular balance was quantitatively measured at 0.5, 1, 2 and 4 c/d. The first two groups of the observers were tested with and without optical correction with contact lenses. Emmetropes were tested without optical correction. Results: Binocular balance across spatial frequency in optically corrected anisomyopes and isomyopes, as well as emmetropes were found to be similar. Their binocular balance nevertheless still got worse as a function of spatial frequency. However, before optical correction, anisomyopes but not isomyopes showed significant imbalance at higher spatial frequencies. There was a significant correlation between the dependence on spatial frequency of binocular imbalance in uncorrected anisomyopia and interocular difference in visual acuity, and between the dependence and interocular difference in spherical equivalent refraction. Conclusion: Anisomyopes had intact binocular balance following correction across spatial frequency compared to those in isomyopes and emmetropes. Their balance was weakly correlated with their refractive status after optical correction. However, their binocular balance before correction and binocular improvement following optical correction were strongly correlated with differences in ocular characteristics between eyes.