Mind the gap in kidney care: translating what we know into what we do / Atenção às lacunas no cuidado renal: traduzindo o que sabemos em ações

Abstract Historically, it takes an average of 17 years for new treatments to move from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. Now is the time to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from the patient to the clinician to the health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Resumo Historicamente, são necessários, em média, 17 anos para que novos tratamentos passem da evidência clínica para a prática diária. Considerando os tratamentos altamente eficazes disponíveis atualmente para prevenir ou retardar o início e a progressão da doença renal, esse período é demasiadamente longo. Agora é o momento de reduzir a lacuna entre o que sabemos e aquilo que fazemos. Existem diretrizes claras para a prevenção e o manejo dos fatores de risco comuns para doenças renais, como hipertensão e diabetes, mas apenas uma fração das pessoas com essas condições é diagnosticada mundialmente, e um número ainda menor recebe tratamento adequado. Da mesma forma, a grande maioria das pessoas que sofrem de doença renal não têm conhecimento de sua condição, pois ela costuma ser silenciosa nos estágios iniciais. Mesmo entre pacientes que foram diagnosticados, muitos não recebem tratamento adequado para a doença renal. Levando em consideração as graves consequências da progressão da doença renal, insuficiência renal ou óbito, é imperativo que os tratamentos sejam iniciados precocemente e de maneira adequada. As oportunidades para diagnosticar e tratar precocemente a doença renal devem ser maximizadas, começando no nível da atenção primária. Existem muitas barreiras sistemáticas, que vão desde o paciente até o médico, passando pelos sistemas de saúde e por fatores sociais. Para preservar e melhorar a saúde renal para todos em qualquer lugar, cada uma dessas barreiras deve ser reconhecida para que soluções sustentáveis sejam desenvolvidas e implementadas sem mais demora.

Bibliometric analysis of electroencephalogram research in Parkinson's disease from 2004 to 2023.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients' quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses. Methods: The data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions. Results: A total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments. Conclusion: This bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration.

Comparisons between In-Check DIAL® and PF810® in evaluation and training inspiratory capacity for using dry powder inhalers.

BACKGROUND: Dry powder inhalers (DPIs) rely on both internal resistance and patients' inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. METHODS: The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland-Altman graphical analysis. RESULTS: PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland-Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients. CONCLUSIONS: In-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.

In-Sensor Organic Electrochemical Transistor for the Multimode Neuromorphic Olfactory System.

The olfactory system is one of the six basic sensory nervous systems. Developing artificial olfactory systems is challenging due to the complexity of chemical information decoding and memory. Conventional chemical sensors can convert chemical signals into electric signals to decode gas information but they lack memory functions. Additional storage and processing units would significantly increase the complexity and power consumption of the devices, especially for portable and wearable devices. Here, an olfactory-inspired in-sensor organic electrochemical transistor (OI-OECT) is proposed, with the integrated functions of chemical information decoding, tunable memory level, and selectivity of vapor sensing. The ion-gel electrolyte endows the OI-OECT with the function of tunable memory levels and a low operating voltage. Typical synaptic behaviors, including inhibitory postsynaptic current and paired-pulse facilitations, are successfully achieved. Importantly, the gas memory level can be effectively modulated by the gate voltages (0 and -1 V), which realized the transformation of volatile and nonvolatile memory. Furthermore, benefiting from the recognition of multiple gases and ability to detect cumulative damage caused by gases, the OI-OECT is demonstrated for early warning system targeting leakage detection of two gases (NH3 and H2S). This work achieves the integrated functions of chemical gas information decode, tunable gas memory level, and selectivity of gas in a single device, which provides a promising pathway for the development of future artificial olfactory systems.

IL-32 regulates trophoblast invasion through miR-205-NFκB-MMP2/9 axis contributing to the pregnancy-induced hypertension.

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

Revealing the crucial roles of suppressive immune microenvironment in cardiac myxoma progression.

Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition of this condition is still not well understood. To fill this gap, we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing. We defined a population of myxoma cells, which exhibited a resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, and adhesion. The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration, along with their enhanced spatial interaction, were found to significantly contribute to the occurrence of embolism. The immune cells surrounding the myxoma exhibit inhibitory characteristics, with impaired function of T cells characterized by the expression of GZMK and TOX, along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC. Furthermore, in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly. In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.

Ultrahigh carbon utilization in symbiotic biofilm-sludge denitrification systems using polymers as sole electron donors.

The polymer-based denitrification system is an effective nitrate removal process for treating low carbon/nitrogen wastewater. However, in polymer denitrification systems, carbon used for the denitrification reaction is weakly targeted. Improving the efficiency of carbon utilization in denitrification is important to reduce carbon wastage. In this study, a symbiotic biofilm-sludge denitrification system was constructed using polycaprolactone as electron donors. Results show that the carbon release amount in 120 days was 85.32±0.46 g, and the unit mass of polycaprolactone could remove 1.55±0.01 g NO3--N. Meaningfully, the targeted carbon utilization efficiency for denitrification could achieve 79%-85%. The quantitative results showed that the release of electron donors can be well matched to the demand for electron acceptors in the biofilm-sludge denitrification system. Overall, the symbiotic system can improve the nitrate removal efficiency and reduce the waste of carbon source.

Identification of Coupled Landau and Anomalous Resonances in Space Plasmas.

Wave-particle resonance, a ubiquitous process in the plasma universe, occurs when resonant particles observe a constant wave phase to enable sustained energy transfer. Here, we present spacecraft observations of simultaneous Landau and anomalous resonances between oblique whistler waves and the same group of protons, which are evidenced, respectively, by phase-space rings in parallel-velocity spectra and phase-bunched distributions in gyrophase spectra. Our results indicate the coupling between Landau and anomalous resonances via the overlapping of the resonance islands.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Influencing factors and risk prediction model for emergence agitation after general anesthesia for primary liver cancer.

BACKGROUND: General anesthesia is commonly used in the surgical management of gastrointestinal tumors; however, it can lead to emergence agitation (EA). EA is a common complication associated with general anesthesia, often characterized by behaviors, such as crying, struggling, and involuntary limb movements in patients. If treatment is delayed, there is a risk of incision cracking and bleeding, which can significantly affect surgical outcomes. Therefore, having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia, which is beneficial for improving patient prognosis. AIM: To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer. METHODS: Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital (January 2020 to December 2023) was conducted. Post-surgery, the Richmond Agitation-Sedation Scale was used to evaluate EA presence, noting EA incidence after general anesthesia. Patients were categorized by EA presence postoperatively, and the influencing factors were analyzed using logistic regression. A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves. RESULTS: EA occurred in 51 (25.5%) patients. Multivariate analysis identified advanced age, American Society of Anesthesiologists (ASA) grade III, indwelling catheter use, and postoperative pain as risk factors for EA (P < 0.05). Conversely, postoperative analgesia was a protective factor against EA (P < 0.05). The area under the curve of the nomogram was 0.972 [95% confidence interval (CI): 0.947-0.997] for the training set and 0.979 (95%CI: 0.951-1.000) for the test set. Hosmer-Lemeshow test showed a good fit (χ 2 = 5.483, P = 0.705), and calibration curves showed agreement between predicted and actual EA incidence. CONCLUSION: Age, ASA grade, catheter use, postoperative pain, and analgesia significantly influence EA occurrence. A nomogram constructed using these factors demonstrates strong predictive accuracy.

Evaluation of immune and pyroptosis status in a model of sepsis-induced secondary pneumonia.

In recent years, researchers have focused on studying the mechanism of sepsis-induced immunosuppression, but there is still a lack of suitable animal models that accurately reflect the process of sepsis-induced immunosuppression. The aim of this study was to evaluate the immune status at various stages in a model of sepsis-induced secondary pneumonia and to demonstrate whether pyroptosis is one of the modes of immune cell death in sepsis. Firstly, we established a sepsis model in C57BL/6J mice using cecal ligation and puncture (CLP). The surviving mice were treated with a 40 µL suspension of P.aeruginosa (Pa) under anesthesia on day 4 post-CLP to establish a sepsis-induced secondary pneumonia model. Secondly, routine blood tests, serum ALT and PCT levels, gross lung specimens, and H&E staining of the lung and liver tissues were used to assess the successful establishment of this model. Serum levels of TNF-α and IL-6, the CD4+/CD8+ratio in blood, H&E staining of the spleen, and immunohistochemistry of CD4 and CD8 in the spleen were detected to evaluate the immune status of the model mice. Finally, the expression levels of pyroptosis-related proteins in the spleen were detected by Western blot. The expression of GSDMD was assessed using immunohistochemistry, and pyroptosis was directly observed through transmission electron microscopy. The experimental results above confirmed the successful construction of the model for sepsis-induced secondary pneumonia, demonstrating its ability to reflect sepsis-induced immunosuppression. Moreover, the expression of pyroptosis-related proteins, immunohistochemical GSDMD, and transmission electron microscopy of the spleen showed that pyroptosis was one of the modes of immune cell death in sepsis.

Enhanced electrocatalytic activity in MOFs-derived 3D hollow NiCo-LDH nanocages decorated porous biochar for simultaneously ultra-sensitive electrochemical sensing of Cu2+ and Hg2.

Layered double hydroxides (LDHs) have attracted significant attention due to their compositional and structural flexibility. However, it is challenging but meaningful to design and fabricate hierarchical mixed-dimensional LDHs with synergistic effects to increase the electrical conductivity of LDHs and promote the intrinsic activity. Herein, 3D hollow NiCo-LDH nanocages decorated porous biochar (3D NiCo-LDH/PBC) has been synthesized by using ZIF-67 as precursor, which was utilized for constructing electrochemical sensing platform to realize simultaneous determination of Cu2+ and Hg2+. The 3D NiCo-LDH/PBC possessed the characteristics of hollow material and three-dimensional porous material, revealing a larger surface area, more exposed active sites, and faster electron transfer, which is beneficial to enhancing its electrochemical performance. Consequently, the developed sensor displayed good performance for simultaneously detecting Cu2+ and Hg2+ with ultra-low limit of detection (LOD) of 0.03 µg L-1 and 0.03 µg L-1, respectively. The proposed sensor also demonstrated excellent stability, repeatability and reproducibility. Furthermore, the sensor can be successfully used for the electrochemical analysis of Cu2+ and Hg2+ in lake water sample with satisfactory recovery, which is of great feasibility for practical application.

Treating waste with waste: adsorption behavior and mechanism of phosphate in water by modified phosphogypsum biochar.

The use of green methods to treat industrial waste and waste reuse has become a key environmental issue. In order to achieve this goal, this study treated waste phosphogypsum (PG) and produced modified PG biochar to adsorb and remove phosphorus from PG leachate, so that the PG pollution problem was controlled. In this study, PG was modified with sodium carbonate (Na2CO3) to prepare a modified PG biochar that was used for the removal of phosphorus-containing wastewater. An X-ray diffraction (XRD) analysis of the modified PG revealed that the main component was calcium carbonate (CaCO3), and a suitable amount of modified PG could load calcium oxide (CaO) onto the biochar and improve its physical properties. The experimental results showed that the modified PG biochar had a maximum phosphorus adsorption capacity of 132 mg/g. A further investigation of the mechanism of adsorption revealed the importance of electrostatic attraction and chemical precipitation, and it was found that the CaO in the modified PG biochar could effectively facilitate the conversion of phosphate to hydroxylapatite (Ca5(PO4)3OH) in water. The phosphorus removal rate from leachate obtained from a landfill containing PG was 99.38% for a specific dose of the modified PG biochar. In this study, a PG pollution control technology was developed to realize the goal of replacing waste with waste.

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

Preoperative Prediction of Axillary Lymph Node Metastasis in Patients With Breast Cancer Through Multimodal Deep Learning Based on Ultrasound and Magnetic Resonance Imaging Images.

RATIONALE AND OBJECTIVES: Deep learning can enhance the performance of multimodal image analysis, which is known for its noninvasive attributes and complementary efficacy, in predicting axillary lymph node (ALN) metastasis. Therefore, we established a multimodal deep learning model incorporating ultrasound (US) and magnetic resonance imaging (MRI) images to predict ALN metastasis in patients with breast cancer. MATERIALS AND METHODS: A retrospective cohort of patients with histologically confirmed breast cancer from two hospitals composed of the primary cohort (n = 465) and the external validation cohort (n = 123). All patients had undergone both preoperative US and MRI scans. After data preprocessing, three convolutional neural network models were used to analyze the US and MRI images, respectively. After integrating the US and MRI deep learning prediction results (DLUS and DLMRI, respectively), a multimodal deep learning (DLMRI+US+Clinical parameter) model was constructed. The predictive ability of the proposed model was compared to that of the DLUS, DLMRI, combined bimodal (DLMRI+US), and clinical parameter models. Evaluation was performed using the area under the receiver operating characteristic curves (AUCs) and decision curves. RESULTS: A total of 588 patients with breast cancer participated in this study. The DLMRI+US+Clinical parameter model outperformed the alternative models, achieving the highest AUCs of 0.819 (95% confidence interval [CI] 0.734-0.903) and 0.809 (95% CI 0.723-0.895) on the internal and external validation sets, respectively. The decision curve analysis confirmed its clinical usefulness. CONCLUSION: The DLMRI+US＋Clinical parameter model demonstrates the feasibility and reliability of its performance for ALN metastasis prediction in patients with breast cancer.

Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway.

OBJECTIVES: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss. METHODS: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes. RESULTS: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis. DISCUSSION: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.

Pokemon inhibits Bim transcription to promote the proliferation, anti-anoikis, invasion, histological grade, and dukes stage of colorectal neoplasms.

PURPOSE: This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis. METHODS: Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined. RESULTS: Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects. CONCLUSION: These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.

Multigenerational effects of disperse blue 79 at environmentally relevant concentrations on zebrafish (Danio rerio) fecundity: An integrated approach.

The brominated azo dye (BAD) Disperse Blue (DB79) is a widespread environmental pollutant. The long-term toxicological effects of DB79 and the mechanisms thereof must be understood to allow assessment of the risks of DB79 pollution. A dual-omics approach employing in silico analysis, bioinformatics, and in vitro bioassays was used to investigate the transgenerational (F0-F2) toxicity of DB79 in zebrafish at environmentally relevant concentrations and identify molecular initiating events and key events associated with DB79-induced fertility disorders. Exposure to 500 µg/L DB79 decreased fecundity in the F0 and F1 generations by > 30 % and increased the condition factor of the F1 generation 1.24-fold. PPARα/RXR and PXR ligand binding activation were found to be critical molecular initiating events associated with the decrease in fecundity. Several key events (changes in fatty acid oxidation and uptake, lipoprotein metabolism, and xenobiotic metabolism and transport) involved in lipid dysregulation and xenobiotic disposition were found to be induced by DB79 through bioinformatic annotation using dual-omics data. The biomolecular underpinnings of decreased transgenerational fertility in zebrafish attributable to BAD exposure were elucidated and novel biomolecular targets in the adverse outcome pathway framework were identified. These results will inform future studies and facilitate the development of mitigation strategies.