Genome-wide CRISPR screenings identified SMCHD1 as a host-restricting factor for AAV transduction.

AAV-mediated gene therapy typically requires a high dose of viral transduction, risking acute immune responses and patient safety, part of which is due to limited understanding of the host-viral interactions, especially post-transduction viral genome processing. Here, through a genome-wide CRISPR screen, we identified SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain 1), an epigenetic modifier, as a critical broad-spectrum restricting host factor for post-entry AAV transgene expression. SMCHD1 knock-down by RNAi and CRISPRi or knock-out by CRISPR all resulted in significantly enhanced transgene expression across multiple viral serotypes, as well as for both single-strand and self-complementary AAV genome types. Mechanistically, upon viral transduction, SMCHD1 effectively repressed AAV transcription by the formation of an LRIF1-HP1-containing protein complex and directly binding with the AAV genome to maintain a heterochromatin-like state. SMCHD1-KO or LRIF1-KD could disrupt such a complex and thus result in AAV transcriptional activation. Together, our results highlight the host factor-induced chromatin remodeling as a critical inhibitory mechanism for AAV transduction and may shed light on further improvement in AAV-based gene therapy.

ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.

Massive GGGGCC (G4C2) repeat expansion in C9orf72 and the resulting loss of C9orf72 function are the key features of ~50% of inherited amyotrophic lateral sclerosis and frontotemporal dementia cases. However, the biological function of C9orf72 remains unclear. We previously found that C9orf72 can form a stable GTPase activating protein (GAP) complex with SMCR8 (Smith-Magenis chromosome region 8). Herein, we report that the C9orf72-SMCR8 complex is a major negative regulator of primary ciliogenesis, abnormalities in which lead to ciliopathies. Mechanistically, the C9orf72-SMCR8 complex suppresses the primary cilium as a RAB8A GAP. Moreover, based on biochemical analysis, we found that C9orf72 is the RAB8A binding subunit and that SMCR8 is the GAP subunit in the complex. We further found that the C9orf72-SMCR8 complex suppressed the primary cilium in multiple tissues from mice, including but not limited to the brain, kidney, and spleen. Importantly, cells with C9orf72 or SMCR8 knocked out were more sensitive to hedgehog signaling. These results reveal the unexpected impact of C9orf72 on primary ciliogenesis and elucidate the pathogenesis of diseases caused by the loss of C9orf72 function.

High-Performance Blue Perovskite Light-Emitting Diodes Enabled by Synergistic Effect of Additives.

While quasi-two-dimensional (quasi-2D) perovskites have good properties of cascade energy transfer, high exciton binding energy, and high quantum efficiency, which will benefit high-efficiency blue PeLEDs, inefficient domain distribution management and unbalanced carrier transport impede device performance improvement. Herein, (2-(9H-carbazol-9-yl)ethyl)phosphonic acid (2PACz) and methyl 2-aminopyridine-4-carboxylate (MAC) were simultaneously introduced to a blue quasi-2D perovskite film. Relying on the synergistic effect of 2PACz and MAC, it not only modulates the phase distribution inhibiting the n = 2 phase but also greatly improves the electrical property of the quasi-2D perovskite film. As a result, the as-modified blue quasi-2D PeLED demonstrated an external quantum efficiency (EQE) of 17.08% and a luminance of 10142 cd m-2. This study exemplifies the synergistic effect among dual additives and offers a new effective additive strategy modulating phase distribution and building balanced carrier transport, which paves the way for the fabrication of highly efficient blue PeLEDs.

NIR-Triggered Multifunctional NO Nanoplatform for Conquering Thermal Resistance in Biofilms.

Photothermal treatment (PTT) has emerged as a promising avenue for biofilm elimination, yet its potential drawbacks, such as local hyperpyrexia and bacterial heat resistance, have posed challenges. To address these concerns, an innovative nanoplatform (Au@mSiO2-arg/ICG) is devised that integrates phototherapeutic and gas therapeutic functionalities. This multifaceted nanoplatform is composed of mesoporous silica-coated Au nanorods (Au@mSiO2), supplemented with l-arginine (l-arg) and indocyanine green (ICG), and is engineered for mild temperature PTT aimed at biofilm eradication. Au@mSiO2-arg/ICG nanoparticles (NPs) show excellent antibacterial effects through the generation of nitric oxide (NO) gas, heat, and reactive oxygen species (ROS) under 808 nm light irradiation. The ROS generated by ICG initiates a cascade reaction with l-arg, ultimately yielding NO gas molecules. This localized release of NO not only effectively curbs the expression of heat shock proteins 70 mitigating bacterial thermoresistance, but also reduces extracellular polymeric substance allowing better penetration of the therapeutic agents. Furthermore, this nanoplatform achieves an outstanding biofilm elimination rate of over 99% in an abscess model under 808 nm light irradiation (0.8 W·cm-2), thereby establishing its potential as a dependable strategy for NO-enhanced mild PTT and antibacterial photodynamic therapy (aPDT) in clinical settings.

A superior heterologous prime-boost vaccination strategy against COVID-19: A bivalent vaccine based on yeast-derived RBD proteins followed by a heterologous vaccine.

Various vaccines have been challenged by SARS-CoV-2 variants. Here, we reported a yeast-derived recombinant bivalent vaccine (Bivalent wild-type [Wt]+De) based on the wt and Delta receptor-binding domain (RBD). Yeast derived RBD proteins based on the wt and Delta mutant were used as the prime vaccine. It was found that, in the presence of aluminium hydroxide (Alum) and unmethylated CpG-oligodeoxynucleotides (CpG) adjuvants, more cross-protective immunity against SARS-CoV-2 prototype and variants were elicited by bivalent vaccine than monovalent wtRBD or Delta RBD. Furthermore, a heterologous boosting strategy consisting of two doses of bivalent vaccines followed by one dose adenovirus vectored vaccine exhibited cross-neutralization capacity and specific T cell responses against Delta and Omicron (BA.1 and BA.4/5) variants in mice, superior to a homologous vaccination strategy. This study suggested that heterologous prime-boost vaccination with yeast-derived bivalent protein vaccine could be a potential approach to address the challenge of emerging variants.

Species pool, local assembly processes: Disentangling the mechanisms determining bacterial α- and ß-diversity during forest secondary succession.

Across ecology, and particularly within microbial ecology, there is limited understanding how the generation and maintenance of diversity. Although recent work has shown that both local assembly processes and species pools are important in structuring microbial communities, the relative contributions of these mechanisms remain an important question. Moreover, the roles of local assembly processes and species pools are drastically different when explicitly considering the potential for saturation or unsaturation, yet this issue is rarely addressed. Thus, we established a conceptual model that incorporated saturation theory into the microbiological domain to advance the understanding of mechanisms controlling soil bacterial diversity during forest secondary succession. Conceptual model hypotheses were tested by coupling soil bacterial diversity, local assembly processes and species pools using six different forest successional chronosequences distributed across multiple climate zones. Consistent with the unsaturated case proposed in our conceptual framework, we found that species pool consistently affected α-diversity, even while local assembly processes on local richness operate. In contrast, the effects of species pool on ß-diversity disappeared once local assembly processes were taken into account, and changes in environmental conditions during secondary succession led to shifts in ß-diversity through mediation of the strength of heterogeneous selection. Overall, this study represents one of the first to demonstrate that most local bacterial communities might be unsaturated, where the effect of species pool on α-diversity is robust to the consideration of multiple environmental influences, but ß-diversity is constrained by environmental selection.

Strong nonlinear optical limiting of resin composed by carbon nanotubes.

The development of solid-state nonlinear optical limiting (NOL) materials is crucial for advancing the practicality in the field of optical limiting. In this paper, we innovatively prepare a new solid NOL material which is spiral carbon nanotubes doped epoxy resin (SCNTs-doped ER, SER) with a simple physical mixing method, and achieve an excellent nonlinear optical limiting performance. We experimentally measured optical limiting of SER with different SCNTs concentrations (0.14, 0.28, and 0.43 mg/mL) and obtained the nonlinear absorption coefficient, nonlinear refractive index, and third-order nonlinear susceptibility at the wavelength 1064 nm. Z-scan experiment results show that the SER exhibits a large nonlinear absorption coefficient (5.07 ± 0.38) × 10-9 m/W. We also measure the transmittance of the SER to evaluate its nonlinear optical limiting performance. For the SER with 0.43 mg/mL concentration, the linear transmittance and minimum transmittance with NOL effects at 1064 nm are 54.8% and 26.2%, respectively. In addition, the SER also has prominent features such as a high damage threshold and easy fabrication, indicating that the SER is a promising solid material for nonlinear optical limiting.

Polarizability inversion suspension for nonlinear optical limiting with a low limiting threshold.

We propose what we believe to be a novel nonlinear optical limiting (NOL) method with a low limiting threshold based on a light intensity-controlled polarizability inversion suspension (PIS). This suspension has negative polarizability under weak light, allowing stable propagation of weak light with a low loss. Nevertheless, the suspension reverses into positive polarizability due to the optical Kerr effect under strong light, resulting in enhanced scattering that rapidly attenuates the intense light. In a proof-of-concept experiment, PS (polystyrene)-CS2-CCl4 suspension is used as the example suspension. We experimentally verify the NOL performance of several samples. Among them, 4 g/L PS-CS2-CCl4 suspension with a volume ratio of 0.15 has the best optical limiting effect, with a high limiting capacity coefficient of 0.48 and a very low limiting threshold of 14.80 kW/cm2, which is an order magnitude lower than that of most common NOL materials. Therefore, the proposed method provides a new promising approach to achieve NOL of continuous wave laser with a low limiting threshold.

Tau suppresses microtubule-regulated pancreatic insulin secretion.

Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.

Synthesis, Structure and Luminescence Properties of Mn-doped MgAl2O4 Red-Emitting Phosphors with Varying Sintering Temperature.

Oxide matrix red-emitting phosphors are deemed as excellent color converters for white light emitting diodes (WLEDs) and laser diodes (LDs). Manganese-doped MgAl2O4 powder was synthesized by a solid-state reaction method at different sintering temperatures. Microstructure shows that grain size is mainly in the range of 0.2-5 µm, and grain agglomeration occurs with increased sintering temperature. XPS analysis indicates that the doped Mn ion exhibits a valence state of + 4 within the MgAl2O4 matrix. The diffraction peak of the phosphors is shifted by the sintering temperature, which affects lattice constant. Upon excitation by 300 nm ultraviolet light, the samples emit asymmetric broadband red light within the range of 620-720 nm, attributed to Mn4+ ion's transition from 2Eg to 4A2g states. With the increasing temperature, the main emission peak shifts from 677 nm to 650 nm, ascribed to the change in energy level (2Eg) resulting from the reduction of Al2O3 phase. Crystal field theory confirmed that Mn4+ ions are within a strong crystal field environment created by MgAl2O4 matrix. By affecting particle size and crystallinity, the sintering temperature influences the fluorescence lifetime of the Mn4+ ion. Notably, these red-emitting phosphors exhibits remarkable thermal stability as their emission intensity remains approximately at 58% of initial intensity even at elevated temperature (435 K). Consequently, Mn4+: MgAl2O4 red-emitting phosphors with high thermal stability render them promising candidates for WLED applications.

Machine Learning Developed a MYC Expression Feature-Based Signature for Predicting Prognosis and Chemoresistance in Pancreatic Adenocarcinoma.

MYC has been identified to profoundly influence a wide range of pathologic processes in cancers. However, the prognostic value of MYC-related genes in pancreatic adenocarcinoma (PAAD) remains unclarified. Gene expression data and clinical information of PAAD patients were obtained from The Cancer Genome Atlas (TCGA) database (training set). Validation sets included GSE57495, GSE62452, and ICGC-PACA databases. LASSO regression analysis was used to develop a risk signature for survival prediction. Single-cell sequencing data from GSE154778 and CRA001160 datasets were analyzed. Functional studies were conducted using siRNA targeting RHOF and ITGB6 in PANC-1 cells. High MYC expression was found to be significantly associated with a poor prognosis in patients with PAAD. Additionally, we identified seven genes (ADGRG6, LINC00941, RHOF, SERPINB5, INSYN2B, ITGB6, and DEPDC1) that exhibited a strong correlation with both MYC expression and patient survival. They were then utilized to establish a risk model (MYCsig), which showed robust predictive ability. Furthermore, MYCsig demonstrated a positive correlation with the expression of HLA genes and immune checkpoints, as well as the chemotherapy response of PAAD. RHOF and ITGB6, expressed mainly in malignant cells, were identified as key oncogenes regulating chemosensitivity through EMT. Downregulation of RHOF and ITGB6 reduced cell proliferation and invasion in PANC-1 cells. The developed MYCsig demonstrates its potential in enhancing the management of patients with PAAD by facilitating risk assessment and predicting response to adjuvant chemotherapy. Additionally, our study identifies RHOF and ITGB6 as novel oncogenes linked to EMT and chemoresistance in PAAD.

Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

Research on Food Preservation Based on Antibacterial Technology: Progress and Future Prospects.

The nutrients present in food are not only prone to a series of physicochemical reactions but also provide conditions for the growth and reproduction of foodborne microorganisms. In recent years, many innovative methods from different fields have been introduced into food preservation, which extends the shelf life while maximizing the preservation of the original ingredients and properties of food. In this field, there is a lack of a systematic summary of new technologies emerging. In view of this, we overview the innovative methods applied to the field of food preservation in recent 3 years, focusing on a variety of technological approaches such as antimicrobial photodynamic therapy based on nanotechnology, electromagnetic radiation sterilization based on radiation technology, and antimicrobial peptides based on biomolecules. We also discuss the preservation mechanism and the application of the different methods to specific categories of products. We evaluated their advantages and limitations in the food industry, describing their development prospects. In addition, as microorganisms are the main causes of food spoilage, our review also has reference significance for clinical antibacterial treatment.

Revisiting the Surface Brightness Profile of the Stellar Disk with the Statistical Mechanics of the Self-Gravitating System with the Central Body.

We have explored the exponential surface brightness profile (SBP) of stellar disks, a topic extensively discussed by many authors yet seldom integrated with the study of correlations between black holes, bulges, and entire disks. Building upon our prior work in the statistical mechanics of disk-shaped systems and aligning with methodologies from other research, we analyze the influence of the central body. This analysis reveals analytical relationships among black holes, bulges, and the entire stellar disk. Additionally, we incorporate a specific angular momentum distribution (SAMD) that aligns more closely with observational data, showing that for the self-gravitating disk, with the same surface density, a reduction in its spin results in only a slight decrease in its radius, whereas with the same SAMD, an increment in its spin significantly limits its extent. A key feature of our model is its prediction that the surface density profile of an isolated disk will invariably exhibit downbending at a sufficient distance, a hypothesis that future observations can test. Our refined equations provide a notably improved fit for SBPs, particularly in the central regions of stellar disks. While our findings underscore the significance of statistical mechanics in comprehending spiral galaxy structures, they also highlight areas in our approach that warrant further discussion and exploration.

Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

Pathogen-Activated Macrophage Membrane Encapsulated CeO2 -TCPP Nanozyme with Targeted and Photo-Enhanced Antibacterial Therapy.

Nanozymes with peroxidase-mimic activity have recently emerged as effective strategies for eliminating infections. However, challenges in enhancing catalytic activities and the ability to target bacteria have hindered the broader application of nanozymes in bacterial infections. Herein, a novel nanozyme based on mesoporous CeO2 nanosphere and meso-tetra(4-carboxyphenyl)porphine (TCPP) encapsulated within pathogen-activated macrophage membranes, demonstrates photodynamic capability coupled with photo-enhanced chemodynamic therapy for selective and efficient antibacterial application against infected wounds. Interestingly, the expression of Toll-like receptors accordingly upregulates when macrophages are co-cultured with specific bacteria, thereby facilitating to recognition of the pathogen-associated molecular patterns originating from bacteria. The CeO2 not only serve as carriers for TCPP, but also exhibit intrinsic peroxidase-like catalytic activity. Consequently, Staphylococcus aureus (S. aureus)-activated macrophage membrane-coated CeO2 -TCPP (S-MM@CeO2 -TCPP) generated singlet oxygen, and simultaneously promoted photo-enhanced chemodynamic therapy, significantly boosting reactive oxygen species (ROS) to effectively eliminate bacteria. S-MM@CeO2 -TCPP specifically targeted S. aureus via Toll-like receptor, thereby directly disrupting bacterial structural integrity to eradicate S. aureus in vitro and relieve bacteria-induced inflammation to accelerate infected wound healing in vivo. By selectively targeting specific bacteria and effectively killing pathogens, such strategy provides a more efficient and reliable alternative for precise elimination of pathogens and inflammation alleviation in microorganism-infected wounds.

A Novel Z-Scheme Heterostructured Bi2 S3 /Cu-TCPP Nanocomposite with Synergistically Enhanced Therapeutics against Bacterial Biofilm Infections in Periodontitis.

Porphyrin-based antibacterial photodynamic therapy (aPDT) has found widespread applications in treating periodontitis. However, its clinical use is limited by poor energy absorption, resulting in limited reactive oxygen species (ROS) generation. To overcome this challenge, a novel Z-scheme heterostructured nanocomposite of Bi2 S3 /Cu-TCPP is developed. This nanocomposite exhibits highly efficient light absorption and effective electron-hole separation, thanks to the presence of heterostructures. The enhanced photocatalytic properties of the nanocomposite facilitate effective biofilm removal. Theoretical calculations confirm that the interface of the Bi2 S3 /Cu-TCPP nanocomposite readily adsorbs oxygen molecules and hydroxyl radicals, thereby improving ROS production rates. Additionally, the photothermal treatment (PTT) using Bi2 S3 nanoparticles promotes the release of Cu2+ ions, enhancing the chemodynamic therapy (CDT) effect and facilitating the eradication of dense biofilms. Furthermore, the released Cu2+ ions deplete glutathione in bacterial cells, weakening their antioxidant defense mechanisms. The synergistic effect of aPDT/PTT/CDT demonstrates potent antibacterial activity against periodontal pathogens, particularly in animal models of periodontitis, resulting in significant therapeutic effects, including inflammation alleviation and bone preservation. Therefore, this design of semiconductor-sensitized energy transfer represents an important advancement in improving aPDT efficacy and the treatment of periodontal inflammation.

Raman laser induced self-organization with topology in a dipolar condensate.

We investigate the ground states of a dipolar Bose-Einstein condensate (BEC) subject to Raman laser induced spin-orbit coupling with mean-field theory. Owing to the interplay between spin-orbit coupling and atom-atom interactions, the BEC presents remarkable self-organization behavior and thus hosts various exotic phases including vortex with discrete rotational symmetry, stripe with spin helix, and chiral lattices with C4 symmetry. The peculiar chiral self-organized array of square lattice, which spontaneously breaks both U(1) and rotational symmetries, is observed when the contact interaction is considerable in comparison with the spin-orbit coupling. Moreover, we show that the Raman-induced spin-orbit coupling plays a crucial role in forming rich topological spin textures of the chiral self-organized phases by introducing a channel for atoms to turn on spin flipping between two components. The self-organization phenomena predicted here feature topology owing to spin-orbit coupling. In addition, we find long-lived metastable self-organized arrays with C6 symmetry in the case of strong spin-orbit coupling. We also present a proposal to observe these predicted phases in ultracold atomic dipolar gases with laser-induced spin-orbit coupling, which may stimulate broad theoretical as well as experimental interest.

Erythropoietin prevented the decreased expression of aquaporin1-3 in ureteral obstructive kidneys in juvenile rats.

BACKGROUND: Urinary tract obstruction is associated with impaired renal urinary concentration; even after the release of the obstruction, patients still suffer from polyuria. It has been reported that the decreased expression of aquaporins (AQPs) is associated with postobstructive polyuria, and erythropoietin (EPO) can promote the recovery of decreased AQP2 expression induced by bilateral ureteral obstruction. However, whether EPO can promote the recovery of the expression of AQP1-3 after the release of unilateral ureteral obstruction (UUO) has not yet been reported. AIMS: To investigate the effects of EPO treatment on the expression of renal AQP1-3 after the release of UUO. METHODS: UUO was established in rats by 24-h temporary unilateral obstruction of renal ureters. Three days following EPO treatment, the kidneys were removed to determine the expression levels of AQP1-3, NLRP3, caspase-1, and IL-1ß via semiquantitative immunoblotting and immunohistochemistry. RESULTS: EPO inhibited the expression of NLRP3, caspase-1, and IL-1ß; reduced plasma creatinine and urea; and promoted the recovery of AQP1-3 expression in UUO rats. CONCLUSIONS: EPO treatment prevented the decreased expression of renal AQPs and the development of impaired urinary concentration capacity after the release of UUO, which may partially occur by way of anti-inflammasome effects. IMPACT: EPO treatment could prevent the decreased expression of renal water transporter proteins AQP1-3 and the development of impaired renal functions, which may be associated with its anti-inflammasome effects. EPO regulated the expression of renal water transporter proteins AQP1-3, which could provide the potential for the treatment of postobstructive polyuresis. EPO treatment could be one of the effective methods by participating in multiple dimensions for patients with obstructive nephropathy.

Alteration of N6-methyladenosine epitranscriptome profiles in bilateral ureteral obstruction-induced obstructive nephropathy in juvenile rats.

BACKGROUND: Urinary tract obstruction is a common cause of renal failure in children and infants, and the pathophysiological mechanisms of obstructive nephropathy are largely unclear. It has been reported that m6A modulation is involved in renal injury. However, whether m6A RNA modulation is associated with obstructive nephropathy has not yet been reported. The aim of this study was to investigate the m6A epitranscriptome profiles in the kidneys of bilateral ureteral obstruction (BUO) in young rats. METHODS: The total level of m6A in the kidneys was measured by liquid chromatography-tandem mass spectrometry. The mRNAs of related genes were detected by real-time PCR. Methylated RNA immunoprecipitation sequencing was performed to map the epitranscriptome-wide m6A profile. RESULTS: Global m6A levels were increased after BUO, and the mRNA expression levels of m6A methyltransferases and demethylases were significantly decreased in BUO group rat kidneys; the expression levels of EGFR and Brcal were significantly upregulated, while the mRNA expression levels of Notch1 were downregulated (P < 0.05). A total of 154 genes associated with 163 m6A peaks were identified. CONCLUSION: The m6A epitranscriptome was significantly altered in BUO rat kidneys, which is potentially implicated in the pathophysiological processes of obstructive nephropathy. IMPACT: The m6A RNA modification was associated with the process of renal injury in ureteral obstructive nephropathy by participating in multiple dimensions. The dysregulation of m6A methyltransferases and demethylases may be related to the pathophysiological changes of BUO-induced obstructive nephropathy. The m6A RNA modulation of the genes EGFR, Brca1, and Notch1 that were related to the regulation of aquaporin2 might be the potential mechanism for the polyuresis after ureteral obstruction.