An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders.

The adverse use of alcohol is a serious global public health problem. Maternal alcohol consumption during pregnancy usually causes prenatal alcohol exposure (PAE) in the developing fetus, leading to a spectrum of disorders known as fetal alcohol spectrum disorders (FASD) and even fetal alcohol syndrome (FAS) throughout the lifelong sufferers. The prevalence of FASD is approximately 7.7 per 1,000 worldwide, and is even higher in developed regions. Generally, Ethanol in alcoholic beverages can impair embryonic neurological development through multiple pathways leading to FASD. Among them, the leading mechanism of FASDs is attributed to ethanol-induced neuroinflammatory damage to the central nervous system (CNS). Although the underlying molecular mechanisms remain unclear, the remaining multiple pathological mechanisms is likely due to the neurotoxic damage of ethanol and the resultant neuronal loss. Regardless of the molecular pathway, the ultimate outcome of the developing CNS exposed to ethanol is almost always the destruction and apoptosis of neurons, which leads to the reduction of neurons and further the development of FASD. In this review, we systematically summarize the current research progress on the pathogenesis of FASD, which hopefully provides new insights into differential early diagnosis, treatment and prevention for patents with FASD.

Plant-Derived Caffeic Acid and Its Derivatives: An Overview of Their NMR Data and Biosynthetic Pathways.

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.

Triglyceride-glucose index predicts postoperative delirium in elderly patients with type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is more prevalent among elderly patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR) can be assessed using the triglyceride-glucose (TyG) index, a novel biomarker. This study aims to investigate the predictive potential of the TyG index for POD in elderly patients with T2DM. MATERIALS AND METHODS: Elderly patients (≥ 65) with T2DM who underwent non-neurosurgery and non-cardiac surgery were enrolled. Univariate and multivariate logistic regression analyses were conducted to assess the association between the TyG index and POD. Additionally, subgroup analyses were performed to compare the sex-specific differences in the predictive ability of the TyG index for POD. RESULTS: A total of 4566 patients were included in this retrospective cohort. The receiver operating characteristic (ROC) curve analysis determined the optimal cut-off value for the TyG index to be 8.678. In the univariate model, a TyG index > 8.678 exhibited an odds ratio (OR) of 1.668 (95% CI: 1.210-2.324, P = 0.002) for predicting POD. In the multivariate regression models, the ORs were 1.590 (95% CI: 1.133-2.252, P < 0.008), 1.661 (95% CI: 1.199-2.325, P < 0.003), and 1.603 (95% CI: 1.137-2.283, P = 0.008) for different models. Subgroup analyses demonstrated that the predictive ability of the TyG index was more pronounced in females compared to males. CONCLUSION: The TyG index shows promise as a novel biomarker for predicting the occurrence of POD in elderly surgical patients with T2DM.

Organic-Inorganic Hybrid Materials: Tailoring Carbon Dioxide-Based Polycarbonate with POSS-SH Crosslinking.

A novel functional polycarbonate (PAGC), characterized by the presence of double bonds within its side chain, was successfully synthesized through a ternary copolymerization of propylene oxide (PO), allyl glycidyl ether (AGE), and carbon dioxide (CO2). Polyhedral oligomeric silsesquioxanes octamercaptopropyl (POSS-SH) was employed as a crosslinking agent, contributing to the formation of organic-inorganic hybrid materials. This incorporation was facilitated through thiol-ene click reactions, enabling effective interactions between the POSS molecules and the double bonds in the side chains of the polycarbonate. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) confirmed a homogeneous distribution of silicon (Si) and sulfur (S) in the polycarbonate matrix. The thiol-ene click reaction between POSS-SH and the polycarbonate led to a micro-crosslinked structure. This enhancement significantly increased the tensile strength of the polycarbonate to 42 MPa, a notable improvement over traditional poly (propylene carbonate) (PPC). Moreover, the cross-linked structure exhibited enhanced solvent resistance, expanding the potential applications of these polycarbonates in various plastic materials.

Current understanding of circular RNAs in preeclampsia.

Preeclampsia (PE) is a multiple organ and system disease that seriously threatens the safety of the mother and infant during pregnancy, and has a profound impact on the morbidity and mortality of the mother and new babies. Presently, there are no remedies for cure of PE as to the mechanisms of PE are still unclear, and the only way to eliminate the symptoms is to deliver the placenta. Thus, new therapeutic targets for PE are urgently needed. Approximately 95% of human transcripts are thought to be non-coding RNAs, and the roles of them are to be increasingly recognized of great importance in various biological processes. Circular RNAs (circRNAs) are a class of non-coding RNAs, with no 5' caps and 3' polyadenylated tails, commonly produced by back-splicing of exons. The structure of circRNAs makes them more stable than their counterparts. Increasing evidence shows that circRNAs are involved in the pathogenesis of PE, but the biogenesis, functions, and mechanisms of circRNAs in PE are poorly understood. In the present review, we mainly summarize the biogenesis, functions, and possible mechanisms of circRNAs in the development and progression of PE, as well as opportunities and challenges in the treatment and prevention of PE.

Jiawei Dachaihu decoction protects against mitochondrial dysfunction in atherosclerosis (AS) mice with chronic unpredictable mild stress (CUMS) via SIRT1/PGC-1α/TFAM/LON signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: JiaWei DaChaiHu is composed of Bupleurum chinense, Scutellaria baicalensis, Pinellia ternata, Paeonia lactiflora, Zingiber officinale Roscoe, Poncirus tuifoliata, Rheum palmatum L., Curcumae Radix, Herba Lysimachiae, Ziziphus. JiaWei DaChaiHu one of the most common traditional Chinese medicines for the treatment of depression. AIM OF THE STUDY: The chronic unpredictable mild stress (CUMS) has been shown to promote atherosclerosis (AS). Dachaihu has been widely used in traditional Chinese medicine and has been known to exert distinct pharmacological effects. This investigation aims to examine the therapeutic effect of Jiawei Dachaihu extract on AS animal models with CUMS. METHODS: AS-CUMS mice model was established by Apoe-/- mice. Mice were treated with Jiawei Dachaihu. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) levels were measured using ELISA kits. Aortic tissue pathologic changes detected by oil red O staining. Mice behavioral changes detected by sucrose preference test and sucrose preference test. The relative mRNA expression levels of CRH, ND1, and TFAM were determined by qRT-PCR. 5-HT1A, BDNF, LON, TFAM, PGC-1α, and SIRT1 protein expression determined by western blotting. ATP content detected by ATP kits. RESULTS: The treatment with Jiawei Dachaihu extract alleviated the veins plaque and reduced stress signs in vitro and in vivo. It increased the ATP and HDL-C levels while decreased the TC, TG, LDL-C levels. Jiawei Dachaihu extract treatment upregulated Lon, SIRT1, TFAM, PGC-1α, BDNF, and 5-HT1A protein expression and regained mitochondrial function. CONCLUSION: Jiawei Dachaihu extract could alleviate AS and reduce CUMS by upregulating the SIRT1/PGC-1α signaling and promoted its crosstalk with Lon protein to maintain mitochondrial stability.

Role of integrin ß1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel.

Cartilage defects may lead to severe degenerative joint diseases. Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair. However, the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified. Herein, we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis. Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-ß signaling pathway, and integrin-ß1 (ITGB1), a receptor of collagen, was highly expressed in bone marrow mesenchymal stem cells (BMSCs). Further analysis showed genes such as COL2A1 and Tenascin C (TNC) that interacted with ITGB1 were significantly enriched in extracellular matrix (ECM) structural constituents in the chondrogenic induction group. Knockdown of ITGB1 led to the downregulation of cartilage-specific genes (SOX9, ACAN, COL2A1), SMAD2 and TNC, as well as the downregulation of phosphorylation of SMAD2/3. Knockdown of TNC also resulted in the decrease of cartilage markers, ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend. Finally, in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration. In summary, we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel. It can activate TGF-SMAD2/3 signaling, followed by impacting TNC expression, which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance chondrogenesis. These may provide concernful support for cartilage tissue engineering and biomaterials development.

Construction of Cobalt Porphyrin-Modified Cu2 O Nanowire Array as a Tandem Electrocatalyst for Enhanced CO2 Reduction to C2 Products.

Here, the molecule-modified Cu-based array is first constructed as the self-supporting tandem catalyst for electrocatalytic CO2 reduction reaction (CO2 RR) to C2 products. The modification of cuprous oxide nanowire array on copper mesh (Cu2 O@CM) with cobalt(II) tetraphenylporphyrin (CoTPP) molecules is achieved via a simple liquid phase method. The systematical characterizations confirm that the formation of axial coordinated Co-O-Cu bond between Cu2 O and CoTPP can significantly promote the dispersion of CoTPP molecules on Cu2 O and the electrical properties of CoTPP-Cu2 O@CM heterojunction array. Consequently, as compared to Cu2 O@CM array, the optimized CoTPP-Cu2 O@CM sample as electrocatalyst can realize the 2.08-fold C2 Faraday efficiency (73.2% vs 35.2%) and the 2.54-fold current density (-52.9 vs -20.8 mA cm-2 ) at -1.1 V versus RHE in an H-cell. The comprehensive performance is superior to most of the reported Cu-based materials in the H-cell. Further study reveals that the CoTPP adsorption on Cu2 O can restrain the hydrogen evolution reaction, improve the coverage of * CO intermediate, and maintain the existence of Cu(I) at low potential.

Microbial diversity in camel milk from Xinjiang, China as revealed by metataxonomic analysis.

The quality of raw camel milk is affected by its bacterial composition and diversity. However, few studies have investigated the bacterial composition and diversity of raw camel milk. In this study, we obtained 20 samples of camel milk during spring and summer in Urumqi and Hami, Xinjiang, China. Single-molecule real-time sequencing technology was used to analyze the bacterial community composition. The results revealed that there were significant seasonal differences in the bacterial composition and diversity of camel milk. Overall, Epilithonimonas was the most abundant bacterial genus in our samples. Through the annotated genes inferred by PICRUSt2 were mapped against KEGG database. Non-parametric analysis of the bacterial community prediction function revealed a strong bacterial interdependence with metabolic pathways (81.83%). There were clear regional and seasonal differences in level 3 metabolic pathways such as fat, vitamins, and amino acids in camel milk. In addition, we identified lactic acid bacteria in camel milk with antibacterial and anti-tumor activities. Our findings revealed that camel milk from Xinjiang had serious risk of contamination by psychrophilic and pathogenic bacteria. Our research established a crucial theoretical foundation for ensuring the quality and safety of camel milk, thereby contributing significantly to the robust growth of China's camel milk industry.

Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf.

Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.

Nanofluidic memristor based on the elastic deformation of nanopores with nanoparticle adsorption.

The memristor is the building block of neuromorphic computing. We report a new type of nanofluidic memristor based on the principle of elastic strain on polymer nanopores. With nanoparticles absorbed at the wall of a single conical polymer nanopore, we find a pinched hysteresis of the current within a scanning frequency range of 0.01-0.1 Hz, switching to a diode below 0.01 Hz and a resistor above 0.1 Hz. We attribute the current hysteresis to the elastic strain at the tip side of the nanopore, caused by electrical force on the particles adsorbed at the inner wall surface. Our simulation and analytical equations match well with experimental results, with a phase diagram for predicting the system transitions. We demonstrate the plasticity of our nanofluidic memristor to be similar to a biological synapse. Our findings pave a new way for ionic neuromorphic computing using nanofluidic memristors.

Protection of Ndrg2 deficiency on renal ischemia-reperfusion injury via activating PINK1/Parkin-mediated mitophagy.

BACKGROUND: Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 (Ndrg2) in R-I/R injury. METHODS: We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient (Ndrg2-/-) mice and wild type (Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion injury (OGD-R) in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2-/- mice after R-I/R injury or HK-2 cells in OGD-R injury. RESULTS: We found that Ndrg2 was primarily expressed in renal proximal tubules and significantly decreased its expression 24 h after R-I/R injury. Ndrg2-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. CONCLUSION: Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

Alzheimer's therapeutic development: shifting neurodegeneration to neuroregeneration.

Alzheimer's disease (AD), similar to AD-related dementias, is characterized by impaired/lost neuronal structures and functions due to a long progression of neurodegeneration. Derailed endogenous signal pathways and disease processes have critical roles in neurodegeneration and are pharmacological targets in inducing neuroregeneration. Pharmacologically switching/shifting the brain status from neurodegeneration to neuroregeneration is emerging as a new therapeutic concept, one that is not only achievable, but also essential for effective therapy for AD. The results of the pharmacological-induced shift from neurodegeneration to neuroregeneration are twofold: arresting cognitive deterioration (and directing the brain toward cognitive recovery) in established AD, and preventing neurodegeneration through building up cognitive resilience in patients with preclinical or probable AD. In this review, we discuss these new developments in AD pharmacology and relevant clinical trials.

Development and characterization of a novel nanobody with SRMV neutralizing activity.

Peste des petits ruminants (PPR) is an acute, contact infectious disease caused by the small ruminant morbillivirus (SRMV), and its morbidity in goats and sheep can be up to 100% with significant mortality. Nanobody generated from camelid animals such as alpaca has attracted wide attention because of its unique advantages compared with conventional antibodies. The main objective of this study was to produce specific nanobodies against SRMV and identify its characteristics. To obtain the coding gene of SRMV-specific nanobodies, we first constructed an immune phage-displayed library from the VHH repertoire of alpaca that was immunized with SRMV-F and -H proteins. By using phage display technology, the target antigen-specific VHHs can be obtained after four consecutive rounds of biopanning. Results showed that the size of this VHH library was 2.26 × 1010 CFU/mL and the SRMV-F and -H specific phage particles were greatly enriched after four rounds of biopanning. The positive phage clones were selected and sequenced, and total of five independent different sequences of SRMV-specific nanobodies were identified. Subsequently, the DNA fragments of the five nanobodies were cloned into E. coli BL21(DE3), respectively, and three of them were successfully expressed and purified. Specificity and affinity towards inactivated SRMV of these purified nanobodies were then evaluated using the ELISA method. Results demonstrated that NbSRMV-1-1, NbSRMV-2-10, and NbSRMV-1-21 showed no cross-reactivity with other antigens, such as inactivated BTV, inactivated FMDV, His-tag labeled protein, and BSA. The ELISA titer of these three nanobodies against inactivated SRMV was up to 1:1000. However, only NbSRMV-1-21 displayed SRMV neutralizing activity at a maximum dilution of 1:4. The results indicate that the nanobodies against SRMV generated in this study could be useful in future applications. This study provided a novel antibody tool and laid a foundation for the treatment and detection of SRMV.

Constructing the Polymer Molecules to Regulate the Electrode/Electrolyte Interface to Enhance Lithium-Metal Battery Performance.

Lithium-ion batteries, with high energy density and long cycle life, have become the battery of choice for most vehicles and portable electronic devices; however, energy density, safety and cycle life require further improvements. Single-functional group electrolyte additives are very limited in practical applications, a ternary polymer bifunctional electrolyte additive copolymer (acrylonitrile-butyl hexafluoro methacrylate- poly (ethylene glycol) methacrylate- methyl ether) (PMANHF) was synthesized by free radical polymerization of acrylonitrile, 2, 2, 3, 4, 4, 4-hexafluorobutyl methacrylate and poly (ethylene glycol) methyl ether methacrylate. A series of characterizations show that in Li metal anodes, the preferential reduction of PMANHF is conducive to the formation of a uniform and stable solid electrolyte interphase layer, and Li deposition is uniform and dense. At the NCM811 cathode, a film composed of LiF- and Li3N-rich is formed at the cathode-electrolyte interface, mitigating the side reaction at the interface. At 1.0 mA cm-2, the Li/Li cell can be stabilized for 1000 cycles. In addition, the Li/NCM811 cell can stabilize 200 cycles with a cathode capacity of 153.7 mAh g-1, with the capacity retention of 89.93 %, at a negative/positive capacity ratio of 2.5. This study brings to light essential ideas for the fabrication of additives for lithium-metal batteries.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.

Genome-wide analysis and characterization of the TaTLP gene family in wheat and functional characterization of the TaTLP44 in response to Rhizoctonia cerealis.

Wheat sharp eyespot is a soil-borne disease caused by Rhizoctonia cerealis, which occurs in many countries worldwide and significantly reduces the yield. Thaumatin-like protein (TLP), also known as PR5, is a member of the pathogen response protein family and plays an essential role in plant resistance to pathogen infection. In this study, 131 TaTLP genes were identified from the wheat genome, of which 38 TaTLPs were newly discovered. The TaTLP gene family contains many tandem duplications and fragment duplications, which is a major pathway for gene amplification. Besides, we also analyzed the physicochemical properties, gene structure and promoter cis-acting regulatory elements of all the TaTLP genes. In addition, the expression patterns of nine TaTLPs in response to R. cerealis were analyzed by RT-qPCR. Six TaTLP proteins expressed in vitro had no significant inhibitory effect on R. cerealis, suggesting that these TaTLP proteins may function in other ways. Finally, we performed gene silencing of TaTLP44 in wheat, which increased the expression of some defense-associated genes and improved resistance to R. cerealis. In summary, we systematically analyzed TaTLP family members and demonstrated that TaTLP44 negatively regulates the resistance to R. cerealis by controlling expression of defense-associated genes. These results provide new insights into the functional mechanism of TaTLP proteins.

Differentiation Potential of Hypodifferentiated Subsets of Nephrogenic Rests and Its Relationship to Prognosis in Wilms Tumor.

Background Wilms tumor (WT) is highly curable, although anaplastic histology or relapse imparts a worse prognosis. Nephrogenic rests (NR) associated with a high risk of developing WT are abnormally retained embryonic kidney precursor cells. Methods After pseudo-time analysis using single-cell RNA sequencing (scRNA-seq) data, we generated and validated a WT differentiation-related gene (WTDRG) signature to predict overall survival (OS) in children with a poor OS. Results A differentiation trajectory from NR to WT was identified and showed that hypodifferentiated subsets of NR could differentiate into WT. Classification of WT children with anaplastic histology or relapse based on the expression patterns of WTDRGs suggested that patients with relatively high levels of hypodifferentiated NR presented a poorer prognosis. A WTDRG-based risk model and a clinically applicable nomogram was developed. Conclusions These findings may inform oncogenesis of WT and interventions directed toward poor prognosis in WT children of anaplastic histology or relapse.

YTHDF3 modulates the Cbln1 level by recruiting BTG2 and is implicated in the impaired cognition of prenatal hypoxia offspring.

The "Fetal Origins of Adult Disease (FOAD)" hypothesis holds that adverse factors during pregnancy can increase the risk of chronic diseases in offspring. Here, we investigated the effects of prenatal hypoxia (PH) on brain structure and function in adult offspring and explored the role of the N6-methyladenosine (m6A) pathway. The results suggest that abnormal cognition in PH offspring may be related to the dysregulation of the m6A pathway, specifically increased levels of YTHDF3 in the hippocampus. YTHDF3 interacts with BTG2 and is involved in the decay of Cbln1 mRNA, leading to the down-regulation of Cbln1 expression. Deficiency of Cbln1 may contribute to abnormal synaptic function, which in turn causes cognitive impairment in PH offspring. This study provides a scientific clues for understanding the mechanisms of impaired cognition in PH offspring and provides a theoretical basis for the treatment of cognitive impairment in offspring exposed to PH.