Suppressive Effect Research Articles

The impact of FDA-cleared molecular solutions for BK polyomavirus quantitation.

Accurate detection and monitoring of BK polyomavirus (BKV) infection is of critical importance in the post-transplant period, guiding treatment decisions that balance the anti-rejection effects of immune suppression with host-protective effects of immune defense. Historically, test methods for BKV have been independently developed by laboratories to address this unmet need. However, these assays can suffer from inconsistencies in analytical variability, which in turn have hindered the establishment of commutable and clinically actionable viral load thresholds for clinical management. As a result, the interpretation of viral load quantitation has not been standardized across transplant centers for the purpose of monitoring patients at highest risk for infection-related complications. In this review, we describe challenges that have historically limited widespread adoption of BKV quantitative testing. We then detail how developments in the field, including optimized amplicon selection, the introduction of an international standard, and the availability of Food and Drug Administration (FDA)-cleared methods, have played a role in harmonization of quantitative BKV measurements in the clinical management of transplant recipients.

Discovery of (3-Phenylcarbamoyl-3,4-dihydro-2H-pyrrol-2-yl)phosphonates as Imidazoline I2 Receptor Ligands with Anti-Alzheimer and Analgesic Properties.

Imidazoline I2 receptors (I2-IRs) are altered in Alzheimer's disease (AD) patients and are associated with analgesia. I2-IRs are not structurally described, and their pharmacological characterization relies on their modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2H-pyrrol-2-yl)phosphonates endowed with relevant affinities for I2-IRs in human brain tissues. The optimal ADME and pharmacokinetic profile of a selected compound, 12d, secured its in vivo exploration in a senescence accelerated prone 8 mice revealing improvement in the cognitive impairment and unveiling the mechanism of action by analyzing specific AD biomarkers. The treatment of a capsaicin-induced mechanical hypersensitivity murine model with 12d revealed analgesic properties devoid of motor coordination issues. The target engagement of 12d was demonstrated by suppression of the analgesic effect by pretreatment with idazoxan. Overall, 12d is a putative candidate for advancing preclinical phases and supports the modulation of I2-IRs as an innovative approach for therapeutics.

SYNTHESIS OF VANADIUM GRAPHITIC-CARBON NITRIDE(V/g-C₃N₄) COMPOSITE FOR BIOLOGICAL APPLICATION

The synthesis of vanadium carbon nitride (V/g-C₃N₄) composites has been explored for their potential as antimicrobial and antioxidant agents. These materials were evaluated against Escherichia coli and Staphylococcus aureus using a combination of disc diffusion, well diffusion, and biofilm inhibition assays. Antioxidant properties were assessed through DPPH free radical scavenging analysis. V/g-C₃N₄ composites demonstrated notable antimicrobial activity, exhibiting inhibition zones comparable to ciprofloxacin, the standard antibiotic. In disc and well diffusion assays, the composites significantly inhibited the growth of both bacterial strains, with Staphylococcus aureus exhibiting marginally higher sensitivity. Biofilm inhibition assays revealed effective suppression of bacterial adhesion and biofilm formation, achieving biofilm inhibition percentages of approximately 17% for E. coli and 22.6% for S. aureus. These results underscore the potential of V/g-C₃N₄ in curbing biofilm-associated infections. Antioxidant activity was quantitatively measured using the DPPH assay, with radical scavenging efficiency consistently exceeding 52%. This performance highlights the dual functionality of V/g-C₃N₄ composites as both antimicrobial and antioxidant agents. Comparatively, ciprofloxacin demonstrated superior antibacterial activity but lacked antioxidant properties, emphasizing the multifaceted advantage of V/g-C₃N₄ composites in biomedical applications. The shake-flask method further validated the biocompatibility and antimicrobial effectiveness of V/g-C₃N₄. This study indicates that vanadium carbon nitride composites hold promise as versatile agents in combating oxidative stress and bacterial infections, particularly in environments where biofilm formation exacerbates antimicrobial resistance. Future studies will focus on optimizing the composite synthesis and exploring its efficacy against a broader range of pathogens.

Precise Manipulation on the Structural Defects of Poly (Triazine Imide) Single Crystals for Efficient Photocatalytic Overall Water Splitting

AbstractConjugated polymers, represented by polymeric carbon nitrides (PCNs), have risen to prominence as new‐generation photocatalysts for overall water splitting (OWS). Despite considerable efforts, achieving highly crystalline PCNs with minimal structural defects remains a great challenge, and it is also difficult to examine the exact impact of complex defect states on OWS process, which largely limits their quantum efficiency. Herein, we devise a ‘in‐situ salt flux’ assisted copolymerization protocol by using nitrogen‐rich and nitrogen‐deficient monomers to precisely manipulate the structural defects of poly (triazine imide) (PTI) single crystals. Stoichiometric control between two comonomers enables continuous tunning of carbon‐ and nitrogen‐vacancies within PTI, allowing the construction of a series of PTI crystals with different defect states. Theoretical and experimental results unveil the carbon vacancies are related with the radiative decay of excitons, while the nonradiative decay is mainly derived from the nitrogen vacancies. Owing to the effective suppression of both radiative and nonradiative losses, the as‐synthesized PTI achieves a record apparent quantum efficiency of 37.8 % by one‐step‐excitation OWS. This work highlights the significance of rational control of the structural defects and describes clear structure‐property‐activity relationships in PTI photocatalyst, offering guidance for the development of polymer photocatalysts for solar fuel production.

Interannual Variability of the South Equatorial Current in the Southeast Indian Ocean Associated with El Niño–Southern Oscillation

Abstract Interannual variability of the South Equatorial Current (SEC) in the southeast Indian Ocean is investigated using Archiving, Validation, and Interpretation of Satellite Oceanographic Data (AVISO) and Global Ocean Reanalysis and Simulations (GLORYS) data from January 1993 to December 2022 and a 1.5-layer reduced-gravity model. Interannual variability of the SEC averaged over the upper 200 m in the southeast Indian Ocean is influenced by El Niño–Southern Oscillation (ENSO). The SEC has a significant positive correlation with the Niño-3.4 index and lags the Niño-3.4 index by 12–15 months, with the SEC weakening significantly during the decaying years of El Niño events and vice versa for La Niña events. Mechanistic studies suggest that during the developing years of El Niño events, the northward sea level anomaly (SLA) pressure gradient between the negative SLA off Sumatra–Java coast and the positive SLA of SEC region (90°–115°E, 9°–13°S) strengthens the SEC under geostrophic equilibrium. During the decaying years of El Niño events, the negative SLA in the tropical western Pacific Ocean propagates through the Maritime Continent to the SEC region. The SLA pressure gradient between the Sumatra–Java coast and the SEC region reverses to southward. This induces an eastward geostrophic current anomaly under geostrophic equilibrium, significantly weakening the SEC. The converse holds for La Niña events. Local wind in the southeast Indian Ocean has a suppressive effect on the SLA propagated to this area. The results of the 1.5-layer reduced-gravity model verify these phenomena, and the westward-propagating SLA from the Maritime Continent induced by the Pacific wind plays a dominant role in the SLA variation in the SEC region from model experiment. This study can improve the understanding of the effects of ENSO processes on ocean circulation in the southeast Indian Ocean.

Suppression of Nonlinear Effects in a Whispering Gallery Mode Resonator for the Realization of Resonant Optical Gyroscope

Suppression of Nonlinear Effects in a Whispering Gallery Mode Resonator for the Realization of Resonant Optical Gyroscope

Dust suppression analysis of a new conveying channel using CFD-DEM simulation and experiment test

Dust pollution related to channel discharge has drawn the attention of industries dealing with bulk mate-rial handling. However, this mode of transportation is a complex phenomenon that requires low particle velocity and high airflow control to suppress dust. Thus, it is necessary to develop an accurate double guide plates system to verify the characteristics of the conveying channel. Therefore, in this investigation, the inclination angle of the guide plate (55°, 60°, 65°, 70°) and the spacing from the upper outlet (170 mm, 180 mm, 190 mm, 200 mm, 210 mm) are calculated. The dust suppression characteristics of different guide plate spacing and inclination angles are studied. The fluid medium is air, and viscosity and density of the flow field are 1.8 × 10-5 Pa·s and 1.225 kg/m3, respectively. The calculation results are also synchronized with experimental data of the conveying channel. The results show that the dust suppression effect is the best when the inclination angle of the guide plate is 65° and the spacing is 170 mm. The particle velocity and airflow velocity are further discussed in detail. The particle velocity change and airflow velocity are the smallest with the inclination angle of the guide plate is 65° ∼ 70° and the spacing is 170 mm.

Suppression of MCP-1, IFN-γ and IL-6 production of HNSCC ex vivo by pembrolizumab added to docetaxel and cisplatin (TP) exceeding those of TP alone is linked to improved survival

BackgroundAdding pembrolizumab, an anti-PD-1 antibody approved for treatment of head and neck squamous cell carcinoma (HNSCC) to neoadjuvant (induction-) chemotherapy utilizing docetaxel and cisplatin (TP) followed by radiotherapy may improve outcome in larynx organ-preservation (LOP) that is investigated in the European Larynx-Organ preservation Study (ELOS). As biomarkers for response to TP and pembrolizumab +TP are missing but may include cytokines, this work aims on determining cytokines potentially linked to outcome as prognostic markers sufficient to predict and/or monitor response to successful LOP.MethodsCollagenase IV digests were generated from 47 histopathological confirmed HNSCC tumor samples and seeded in 96-well plates containing pembrolizumab, docetaxel, cisplatin either solely or in binary or ternary combination. According to the FLAVINO protocol, supernatants were collected after 3 days, adherent cells fixed using ethanol, air-dried and pan-cytokeratin positive epithelial cells counted using fluorescence microscopy. The cytokines IL-6, IL-8, IFN-γ, IP-10, MCP-1, TNF-α, and VEGF in the supernatant were quantified by sandwich ELISA.ResultsThe mode of interaction between pembrolizumab and TP was assessed and correlated to outcome (overall, disease-specific and progression-free survival of patients). Suppression of MCP-1, IFN-γ and IL-6 production by pembrolizumab + TP exceeding the suppressive effect of TP was detected in the majority of samples and linked to improved survival. Multivariate Cox proportional hazard regression modeling revealed MCP-1, IFN-γ and IL-6 as independent outcome predictors.ConclusionsComparing response to TP vs. pembrolizumab vs. TP + pembrolizumab may allow for identification of patients with superior outcome independent from treatment applied.

Phosphorylation of Bok at Ser-8 blocks its ability to suppress IP3R-mediated calcium mobilization

BackgroundBok is a poorly characterized Bcl-2 protein family member with roles yet to be clearly defined. It is clear, however, that Bok binds strongly to inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which govern the mobilization of Ca2+ from the endoplasmic reticulum, a signaling pathway required for many cellular processes. Also known is that Bok has a highly conserved phosphorylation site for cAMP-dependent protein kinase at serine-8 (Ser-8). Whether Bok, or phosphorylated Bok, has any direct impact on the Ca2+ mobilizing function of IP3Rs remains to be established.MethodsBok Ser-8 phosphorylation was characterized using purified proteins, G-protein coupled receptor agonists that increase cAMP levels in intact cells, mass spectrometry, and immunoreactivity changes. Also, using mammalian cells that exclusively or predominately express IP3R1, to which Bok binds strongly, and a fluorescent Ca2+-sensitive dye or a genetically-encoded Ca2+ sensor, we explored how endogenous and exogenous Bok controls the Ca2+ mobilizing function of IP3R1, and whether Bok phosphorylation at Ser-8, or replacement of Ser-8 with a phosphomimetic amino acid, is regulatory.ResultsOur results confirm that Ser-8 of Bok is phosphorylated by cAMP-dependent protein kinase, and remarkably that phosphorylation can be detected with Bok specific antibodies. Also, we find that Bok has suppressive effects on IP3R-mediated Ca2+ mobilization in a variety of cell types. Specifically, Bok accelerated the post-maximal decline in G-protein coupled receptor-induced cytosolic Ca2+ concentration, via a mechanism that involves suppression of IP3R-dependent Ca2+ release from the endoplasmic reticulum. These effects were dependent on the Bok-IP3R interaction, as they are only seen with IP3Rs that can bind Bok (e.g., IP3R1). Surprisingly, Bok phosphorylation at Ser-8 weakened the interaction between Bok and IP3R1 and reversed the ability of Bok to suppress IP3R1-mediated Ca2+ mobilization.ConclusionsFor the first time, Bok was shown to directly suppress IP3R1 activity, which was reversed by Ser-8 phosphorylation. We hypothesize that this suppression of IP3R1 activity is due to Bok regulation of the conformational changes in IP3R1 that mediate channel opening. This study provides new insights on the role of Bok, its interaction with IP3Rs, and the impact it has on IP3R-mediated Ca2+ mobilization.

Selective suppression of influenza A/H5N1 virus replication <i>in vitro</i> using nanocomplexes consisting of siRNA and aminopropylsilanol nanoparticles

Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the intracellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The aim of the study is to create nanocomplexes consisting of aminopropylsilanol nanoparticles and short interfering RNA (siRNA) to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in vitro. Materials and methods. MDCK cells, influenza virus A/chicken/Kurgan/05/2005 (A/H5N1), aminopropylsilanol nanoparticles, and native and modified siRNA molecules. Results and discussion. We have prepared unique Si~NH2/siRNA nanocomplexes, which consist of aminopropylsilanol nanoparticles and siRNA molecules, which enable cell penetration and selective interaction with target nucleic acids, respectively. The antiviral activity of the proposed nanocomplexes has been studied on MDCK cells infected with the influenza A/H5N1 virus. It has been shown that the double-stranded siRNA molecules in the nanocomplexes, which act by the RNA interference mechanism, are more efficient in inhibiting the replication of the influenza virus than the corresponding single-stranded RNA fragments. The most effective nanocomplex that contained siRNA targeted at the chosen region of mRNA segment 5 of the viral genome reduced virus replication in the culture by a factor of 630. We have shown that non-agglomerated and water-soluble aminopropylsilanol nanoparticles are low-toxic, capable of delivering siRNA into cells and protecting siRNA in the Si~NH2/siRNA nanocomplexes from hydrolysis by cellular nucleases. Conclusion. The biological activity of the created nanocomplexes has been demonstrated by the example of highly effective selective suppression of influenza A/chicken/Kurgan/05/2005 virus replication in the cellular system.

The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia. Nevertheless, the efficacy of NK cell immunotherapy is less pronounced than expected, which suggests the external conditions that affect NK cell functions after the administration to patients with leukemia. In this study, the effects of humoral components in the bone marrow humoral components of B-ALL patients on healthy NK cells were investigated. Healthy peripheral blood mononuclear cells were cultured with and without bone marrow-derived plasma samples of B-ALL patients. The expression of PD-1 and IL-10 were found to be increased whereas the proliferative capacities of NK cells were found to be decreased at the presence of B-ALL plasma samples. Moreover, high IL-10 versus low IL-18 levels were detected in bone marrow plasma samples of B-ALL patients. These findings indicate that humoral components in the bone marrow of B-ALL patients exert a suppressive effect on NK cell functions.

Targeting CHEK1: Ginsenosides-Rh2 and Cu2O@G-Rh2 nanoparticles in thyroid cancer

Thyroid cancer (THCA) is an increasingly common malignant tumor of the endocrine system, with its incidence rising steadily in recent years. For patients who experience recurrence or metastasis, treatment options are relatively limited, and the prognosis is poor. Therefore, exploring new therapeutic strategies has become particularly urgent. This study confirmed that effective suppression of THCA cell proliferation and stimulation of apoptosis can be achieved through the application of Ginsenosides-Rh2. Through network pharmacology screening, the molecular target of Ginsenosides-Rh2 in THCA was identified as CHEK1, and its inhibitory effect was confirmed by downregulating CHEK1 protein expression. Furthermore, demonstrations conducted both in vitro and in vivo showcased that delivering Ginsenosides-Rh2 using nanoparticle carriers significantly reduced cell viability by approximately 50%, regulated DNA damage levels, apoptosis-related protein expression, and cell cycle control. The IC50 of the nanoparticle formulation was determined (B-CPAP IC50 = 88.24 μM), TPC IC50 = 79.52 μM). This study confirmed that Cu2O@G-Rh2 is effective in suppressing tumors and exhibits a significant inhibitory effect on tumor recurrence and metastasis while maintaining good safety. Cu2O@G-Rh2 nanoparticles possess excellent stability and anti-tumor efficacy. This research offers new perspectives for the treatment of THCA and demonstrates potential clinical applications.

Dynamical suppression of many-body non-Hermitian skin effect in anyonic systems

The non-Hermitian skin effect (NHSE) is a fascinating phenomenon in nonequilibrium systems where eigenstates massively localize at the systems’ boundaries, pumping (quasi-)particles loaded in these systems unidirectionally to the boundaries. Its interplay with many-body effects has been widely explored recently, and inter-particle repulsion or Fermi degeneracy pressure have been shown to limit the boundary accumulation induced by the NHSE both in their eigensolutions and dynamics. However, in this work we find that anyonic statistics can even more profoundly affect the NHSE dynamics, suppressing or even reversing the state dynamics against the localizing direction of the NHSE. This phenomenon is found to be more pronounced when more particles are involved. The spreading of quantum information in this system shows even more exotic phenomena, where NHSE affects only the information dynamics for a thermal ensemble, but not that for a single initial state. Our results open up a new avenue on exploring novel non-Hermitian phenomena arisen from the interplay between NHSE and anyonic statistics, and can potentially be demonstrated in ultracold atomic quantum simulators and quantum computers.

Research on Noise Suppression in High-Speed Optical Communication Systems

With the rapid advancement of optical fiber communication technology, the speed and distance of information transmission have increased unprecedentedly. Multi-core fibers (MCF), which contain multiple cores, enable high-capacity and high-density information transmission. However, during signal transmission, four-wave mixing (FWM) and intercore crosstalk (ICXT) noise are generated, significantly impacting signal propagation quality. Based on the characteristics of FWM and ICXT noise, two effective noise suppression schemes are proposed. The first scheme involves reducing noise power by increasing the wavelength interval or using non-equally spaced wavelengths to mitigate phase-matching conditions. The second scheme focuses on altering the structure of the MCF; in weakly coupled MCFs, longitudinal random bending, torsion, and structural fluctuations randomly affect the power coupling coefficient. According to the noise power formula, reducing the effective fiber length, increasing the cores effective area, and using a band with a low nonlinear effect on the MCF can effectively minimize noise generation. Finally, we evaluate the proposed scheme and analyze and discuss the results.

Degraded products generated by iron stent inhibit the vascular smooth muscle cell proliferation by downregulating AP-1

In-stent restenosis (ISR) following interventional therapy is a fatal clinical complication. Current evidence indicates that neointimal hyperplasia driven by uncontrolled proliferation of vascular smooth muscle cells (VSMC) is a major cause of restenosis. This implies that inhibiting VSMC proliferation may be an attractive approach for preventing in-stent restenosis. In our previous study, we found that the iron stent reduced the neointimal hyperplasia in an atherosclerotic artery stenosis model, and the iron corroded granules generated by the iron stent inhibited neointimal hyperplasia by suppressing the proliferation of VSMCs. However, this observation needs to be validated through in vitro experimentation. In this study, co-culture experiments and flow cytometer assays were performed to qualitatively investigate the effects of iron stent degradation on VSMCs. Moreover, the degraded products resulting generated by the iron stent were collected and used to elucidate the suppressive effect of the iron stents. The underlying mechanism was explored through molecular biology assays. The major findings are as follows: 1) The degraded iron stent inhibited the proliferation of VSMCs; 2) The degraded products of the iron stent downregulated the expression of AP-1. In summary, this study demonstrates the inhibitory effect of degraded iron products on VSMC proliferation, implying that such products have the potential to mitigate in-stent restenosis.Graphical degraded products generated from iron stent inhibit the vascular smooth muscle cell proliferation by downregulating AP-1.

Tailoring pyridine bridged chalcogen-concave molecules for defects passivation enables efficient and stable perovskite solar cells

Suppressing deep-level defects at the perovskite bulk and surface is indispensable for reducing the non-radiative recombination losses and improving efficiency and stability of perovskite solar cells (PSCs). In this study, two Lewis bases based on chalcogen-thiophene (n-Bu4S) and selenophene (n-Bu4Se) having tetra-pyridine as bridge are developed to passivate defects in perovskite film. The uncoordinated Pb2+ and iodine vacancy defects can interact with chalcogen-concave group and pyridine group through the formation of the Lewis acid-base adduct, particularly both the defects can be surrounded by concave molecules, resulting in effective suppression charge recombination. This approach enables a power conversion efficiency (PCE) as high as 25.37% (25.18% certified) for n-i-p PSCs with stable operation at 65 °C and 1-sun illumination for 1300 hours in N2 (ISOS-L-2 protocol), retaining 94% of the initial efficiency. Our work provides insight into the bowl-shaped Lewis base in defects passivation by coordinated strategy for high-performance photovoltaic devices.

The mechanism of corrupt criminal behavior: features and criminological transformation

Relevance. Understanding a corrupt criminal act from the standpoint of the mechanism of its commission requires investigating the stages of its implementation through the prism of criminological transformation in interaction with ongoing processes in society and social prerequisites, which undoubtedly contributes to a more effective fight against corruption in general.Purpose: is to identify the features of the mechanism of corrupt criminal behavior and its transformation.Objectives: to determine the stages of the mechanism of corrupt criminal behavior, to identify their features, taking into account the forms of committing corrupt acts and their transformation in modern conditions, which is the basis for effective prevention, detection and suppression of corruption crimes.Methodology. The research was based on dialectical, logical, system-structural, statistical methods; the method of analysis and comparison; the sociological method used in conducting the survey, the results of which are used in the study.Results. The stages of the mechanism of corrupt behavior in the commission of crimes are analyzed; criminological features, forms of commission and types of corrupt criminal behavior are highlighted; individual aspects of the transformation of the elements of the mechanism under consideration are identified.Conclusions. The results of the study serve to expand scientific knowledge about the mechanism of individual criminal behavior, taking into account the characteristics of a particular type of crime – corruption; at the same time, the author substantiates that the mechanism of corrupt criminal behavior and its transformation are most clearly manifested in the forms and means of committing a crime; in types of corrupt criminal behavior, but the triggering stage is the formation of motivation, it is difficult it is changeable, maturing under the influence of needs, interests, habits, etc., which determines one of the directions of preventing corruption – the impact on this component of the mechanism under consideration.

SP1 activates AKT3 to facilitate the development of diabetic nephropathy.

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and has the complex pathogenesis. The previous study reported that protein kinase Bγ (AKT3) was involved in DN progression. Our aim was to explore the detailed mechanisms of AKT3 in DN development. RT-qPCR was performed to measure the levels of specificity protein 1 (SP1) and AKT3. Mesangial cells were treated with high glucose (30 mM) to form DN cell model in vitro. Western blot was conducted to detect the protein expression of AKT3, SP1, fibrosis-related proteins, and AKT/mTOR pathway-related proteins. Cell proliferation and inflammation were evaluated via MTT, EdU staining, and ELISA assays, respectively. Oxidative stress was determined via measuring ROS and MDA levels. ChIP and dual-luciferase reporter assays were carried out to verify the relationship between SP1 and AKT3. C57BL/6 mice-treated with streptozotocin for 5 days were used to establish DN mouse model in vivo, and HE and Masson staining were conducted to evaluate pathological changes of mouse kidney tissues. AKT3 and SP1 were highly expressed in DN kidney tissues and HG-induced mesangial cells. AKT3 depletion could relieve HG treatment-caused cell damage of mesangial cells through repressing cell proliferation, fibrosis, inflammation and oxidative stress. SP1 can bind to the promoter of AKT3 and serve as a translation regulation factor of AKT3. SP1 overexpression worsened HG treatment-caused cell damage of mesangial cells. Moreover, AKT3 upregulation could block the suppressive effects of SP1 depletion on cell proliferation, fibrosis, inflammation and oxidative stress in HG-induced mesangial cells. SP1 depletion reduced AKT3 expression to inactivate the AKT/mTOR pathway in HG-induced mesangial cells. Besides, AKT3 knockdown inhibited the activation of the AKT/mTOR pathway to hamper the development of DN in mice through alleviating fibrosis and inflammation in vivo. Our results indicated that SP1 activated AKT3 and AKT/mTOR pathway to promote mesangial cell proliferation, fibrosis, inflammation and oxidative stress, thereby facilitating DN development.

CCAAT/Enhancer-Binding Protein Beta Nitration Participates in Hyperhomocysteinemia-Induced Cardiomyocyte Autophagic Flux Blockage by Inhibiting Transcription Factor EB Transcription.

Aims: Autophagy is a protective mechanism of cardiomyocytes. Hyperhomocysteinemia (HHcy) elevates oxidative and nitrosative stress levels, leading to an abnormal increase in nitration protein, possibly leading to abnormal autophagy regulation in cardiomyocytes. However, the regulatory effect of HHcy on autophagy at the post-translational modification level is still unclear. Here, we aimed to explore the regulatory mechanism of HHcy on transcription factor EB (TFEB) and nitration of CCAAT/enhancer-binding protein beta (C/EBPβ), a transcriptional repressor of Tfeb, on autophagy in cardiomyocytes. Results: In this study, we established the HHcy rat model by feeding a 2.5% (w/w) methionine diet. The nitration level of C/EBPβ was increased in HHcy, which promoted the entry of C/EBPβ into the nucleus, enhanced the transcriptional suppressive effect of C/EBPβ on Tfeb, and induced insufficient autophagy in cardiomyocytes. Furthermore, we confirmed that the Tyr 274 site of C/EBPβ could undergo nitration induced by HHcy. Once C/EBPβ was nitrated on the Tyr 274 site, the nuclear translocation of C/EBPβ and transcription suppressor function of C/EBPβ on Tfeb were enhanced. Innovation and Conclusion: We find that C/EBPβ is a transcriptional repressor of Tfeb, and HHcy induces the nitration at the Tyr 274 site of C/EBPβ, leading to autophagic flux blockage in cardiomyocytes. These data indicated that nitrated C/EBPβ might be a potential therapeutic target against HHcy-induced autophagy insufficiency of cardiomyocytes. Antioxid. Redox Signal. 00, 000-000.

MiR-507 Acts as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting STEAP3.

In recent years, there has been a rise in the incidence of renal cell carcinoma (RCC), with metastatic RCC being a prevalent and significant contributor to mortality. While a regulatory role for microRNAs (miRNAs) in the development and progression of RCC has been recognized, their precise functions, molecular mechanisms, and potential clinical implications remain inadequately elucidated. Hence, this study aimed to explore the role of miR-507 in RCC and identify STEAP3 as a downstream target of miR-507. Bioinformatics analysis was used to analyze the expression of miR-507 and STEAP3 in RCC specimens. CCK-8, Transwell, and flow cytometry assays were used to assess the function of miR-507 in RCC cells. The connection between miR-507 and STEAP3 was confirmed through a luciferase reporter assay. The expression level of STEAP3, p53, and xCT was analyzed by western blotting. Bioinformatics analysis showed that miR-507 was expressed at low levels in RCC tissues and was linked to poor overall survival. STEAP3 was found to be significantly upregulated in RCC. Further, STEAP3 was shown to be targeted by miR-507. High levels of miR-507 reduced the expression of STEAP3, leading to stagnant cell viability, apoptosis, and migrative capacity. Whereas miR-507 knockdown reverted such a tendency. The study also discovered that miR-507 exerted its inhibitory effect through the op53/xCT pathway. Within RCC, miR-507 modulates the expression of SETAP3/p53/xCT axis, exhibiting a tumor suppressive effect. These discoveries offer present prospective biomarkers for both surveillance and treatment of RCC.