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Hyperosmolarity of the renal medulla is essential for urine concentration and water homeostasis. However, how renal medullary collecting duct (MCD) cells survive and function under harsh hyperosmotic stress remains unclear. Using RNA-Seq, we identified SLC38A2 as a novel osmoresponsive neutral amino acid transporter in MCD cells. Hyperosmotic stress-induced cell death in MCD cells occurred mainly via ferroptosis, and it was significantly attenuated by SLC38A2 overexpression but worsened by Slc38a2 -gene deletion or silencing. Mechanistic studies revealed that the osmoprotective effect of SLC38A2 is dependent on the activation of mTORC1. Moreover, an in vivo study demonstrated that Slc38a2 -knockout mice exhibited significantly increased medullary ferroptosis following water restriction. Collectively, these findings reveal that Slc38a2 is an important osmoresponsive gene in the renal medulla and provide novel insights into the critical role of SLC38A2 in protecting MCD cells from hyperosmolarity-induced ferroptosis via the mTORC1 signalling pathway.

Background: GAP43, a membrane phosphoprotein with high expression level in the developing brains, plays an important role in higher integrative functions of the brain. Materials and Methods: To explore the association of GAP43 with schizophrenia, 11 single-nucleotide polymorphisms (SNPs) were examined in a Northeast Chinese Han sample set consisting of 741 schizophrenia patients and 1330 healthy controls. Results: The results showed that three SNPs were associated with schizophrenia (rs2028248, rs6790048, and rs2164930). Haplotype analysis also revealed a significant association of a strong linkage disequilibrium block (rs2164930-rs11926976-rs16823991) with schizophrenia. Conclusion: The current findings suggested that the human GAP43 gene may be a susceptibility gene for schizophrenia.

Air-stability is one of the most important considerations for the practical application of electrode materials in energy-harvesting/storage devices, ranging from solar cells to rechargeable batteries. The promising P2-layered sodium transition metal oxides (P2-Na x TmO 2 ) often suffer from structural/chemical transformations when contacted with moist air. However, these elaborate transitions and the evaluation rules towards air-stable P2-Na x TmO 2 have not yet been clearly elucidated. Herein, taking P2-Na 0.67 MnO 2 and P2-Na 0.67 Ni 0.33 Mn 0.67 O 2 as key examples, we unveil the comprehensive structural/chemical degradation mechanisms of P2-Na x TmO 2 in different ambient atmospheres by using various microscopic/spectroscopic characterizations and first-principle calculations. The extent of bulk structural/chemical transformation of P2-Na x TmO 2 is determined by the amount of extracted Na + , which is mainly compensated by Na + /H + exchange. By expanding our study to a series of Mn-based oxides, we reveal that the air-stability of P2-Na x TmO 2 is highly related to their oxidation features in the first charge process and further propose a practical evaluating rule associated with redox couples for air-stable Na x TmO 2 cathodes. Air-stability is a critical challenge faced by layered sodium transition metal oxide cathodes. Here, the authors depict a general and in-depth model of the structural/chemical evolution of P2-type layered oxides in air and propose an evaluation rule for the air-stability of layered sodium cathodes.

Layered transition metal oxides are the most important cathode materials for Li/Na/K ion batteries. Suppressing undesirable phase transformations during charge-discharge processes is a critical and fundamental challenge towards the rational design of high-performance layered oxide cathodes. Here we report a shale-like Na x MnO 2 (S-NMO) electrode that is derived from a simple but effective water-mediated strategy. This strategy expands the Na + layer spacings of P2-type Na 0.67 MnO 2 and transforms the particles into accordion-like morphology. Therefore, the S-NMO electrode exhibits improved Na + mobility and near-zero-strain property during charge-discharge processes, which leads to outstanding rate capability (100 mAh g −1 at the operation time of 6 min) and cycling stability (>3000 cycles). In addition, the water-mediated strategy is feasible to other layered sodium oxides and the obtained S-NMO electrode has an excellent tolerance to humidity. This work demonstrates that engineering the spacings of alkali-metal layer is an effective strategy to stabilize the structure of layered transition metal oxides. Suppressing phase transitions is crucial for the layered lithium/sodium transition metal oxide cathodes in batteries. Here, the authors report a water-mediated strategy to mitigate the phase transitions and boost electrochemical performances of manganese-based layered cathodes for cost-effective Na-ion batteries.

A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-β and tau pathologies, and improved the animals’ memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational–experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis. Two potent mitophagy inducers, identified and characterized via unsupervised machine learning and a cross-species screening approach, ameliorated the pathology of Alzheimer’s disease in worms and mice.

In this study, a novel poly (vinyl alcohol) (PVA)/poly (ethylene glycol) (PEG) scaffold was carefully designed via thermal processing and subsequent supercritical fluid (SCF) foaming. Interestingly, a bimodal open-celled structure with interconnected networks was successfully created in the plasticized PVA (WPVA)/PEG scaffold. Large cells were produced from the nucleation sites generated in the PVA phase during rapid depressurization, while plenty of small pores generate in the cell walls of the big cells. The formation mechanism of this cellular structure was studied by considering the various phase morphologies and the diffusion behaviour of the carbon dioxide (CO 2 ) in individual phases. In addition, the intermolecular interactions of the WPVA/PEG blend were studied using X-ray diffraction and FTIR analysis. The results demonstrate that various types of hydrogen bonds among the hydroxyl groups on the PVA chains, PEG and water molecules are formed in the blend system. The realization of thermoplastic foaming of the PVA/PEG blend benefits from the interactions of complexation and plasticization between water and PEG molecules. The SEM images also revealed that L929 fibroblast cells were able to attach and spread on surfaces of the WPVA/PEG samples. Thus the WPVA/PEG scaffold with unique bimodal cellular structure is nontoxic and favours the attachment and proliferation of cells, making it promising for use as the candidate for tissue engineering applications.

Grain boundary controlling is an effective approach for manipulating the electronic structure of electrocatalysts to improve their hydrogen evolution reaction performance. However, probing the direct effect of grain boundaries as highly active catalytic hot spots is very challenging. Herein, we demonstrate a general water-assisted carbothermal reaction strategy for the construction of ultrathin Mo 2 C nanosheets with high-density grain boundaries supported on N-doped graphene. The polycrystalline Mo 2 C nanosheets are connected with N-doped graphene through Mo–C bonds, which affords an ultra-high density of active sites, giving excellent hydrogen evolution activity and superior electrocatalytic stability. Theoretical calculations reveal that the d z 2 orbital energy level of Mo atoms is controlled by the MoC 3 pyramid configuration, which plays a vital role in governing the hydrogen evolution activity. The d z 2 orbital energy level of metal atoms exhibits an intrinsic relationship with the catalyst activity and is regarded as a descriptor for predicting the hydrogen evolution activity. Probing the direct effect of grain boundaries as active catalytic sites is very challenging. Here, the authors reveal that the d z 2 orbital energy level of Mo atoms in grain boundaries exhibits an intrinsic relationship with the hydrogen evolution activity.

Background: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration.Methods: The population-based sample of adults in Guangzhou, China (baseline: 40–83 years old; n = 5,118) was followed up about every 3 years. All are tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-day real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome.Results: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5,118 participants aged 40–83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3,628 (71%) completed at least one on-site follow-up, with a median duration of 9.48 years.Conclusion: The cohort will provide data that will be influential in establishing the role of nutrition in metabolic diseases with multi-omics.

This study aimed to develop a PANoptosis-related gene prognostic index (PANGPI) to explore its potential value in predicting the prognosis and immunotherapy response of diffuse large B-cell lymphoma (DLBCL). Differentially expressed genes of DLBCL from GEO databases were analyzed and mapped to the PANoptosis gene set. The independent prognostic value of the PANGPI signature was evaluated using LASSO Cox regression and multivariate Cox regression. Additionally, the tumor infiltrating lymphocyte (TIL) characteristics and mutation landscape of both subgroups were evaluated, and drug sensitivity was predicted using the GDSC database. Furthermore, in silico docking and molecular dynamic simulation studies were presented to elucidate the mode of interaction of these predicted drugs. The PANGPI risk score was an independent risk factor for the prognosis of patients with DLBCL and exhibited good prognostic predictive performance. Furthermore, the cytolytic activity of the TILs was positively correlated with the PANGPI scores. Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group. We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL.

Background Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. Methods This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008–2013). Fecal samples were collected at follow-up (2015–2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. Results In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake ( p  < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71–0.97). The FMI-fruit association ( p  = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84–0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51–0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13–1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09–1.54), oleylcarnitine (OR 1.77, 95%CI 1.45–2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37–2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33–2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25–1.72) were positively associated with T2D risk. Conclusions Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.