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Abstract Differentiating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) without a kidney biopsy remains a major challenge, often leading to missed opportunities for targeted treatments that could greatly improve NDRD outcomes. To reform the traditional biopsy-all diagnostic paradigm and avoid unnecessary biopsy, we developed a transformer-based deep learning (DL) system for detecting DN and NDRD upon non-invasive multi-modal data of fundus images and clinical characteristics. Our Trans-MUF achieved an AUC of 0.980 (95% CI: 0.979 to 0.980) over the internal retrospective set and also had superior generalizability over a prospective dataset (AUC: 0.989, 95% CI: 0.987 to 0.990) and a multicenter, cross-machine and multi-operator dataset (AUC: 0.932, 95% CI: 0.931 to 0.939). Moreover, the nephrologists‘ diagnosis accuracy can be improved by 21%, through visualization assistance of the DL system. This paper lays a foundation for automatically differentiating DN and NDRD without biopsy. (Registry name: Correlation Study Between Clinical Phenotype and Pathology of Type 2 Diabetic Nephropathy. ID: NCT03865914. Date: 2017-11-30).

Abstract Dry eye disease (DED) is a prevalent inflammatory condition significantly impacting quality of life, yet lacks effective pharmacological therapies. Herein, we proposed a novel approach to modulate the inflammation through metabolic remodeling, thus promoting dry eye recovery. Our study demonstrated that co-treatment with mesenchymal stem cells (MSCs) and thymosin beta-4 (Tβ4) yielded the best therapeutic outcome against dry eye, surpassing monotherapy outcomes. In situ metabolomics through matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased glutamine levels in cornea following MSC + Tβ4 combined therapy. Inhibition of glutamine reversed the anti-inflammatory, anti-apoptotic, and homeostasis-preserving effects observed with combined therapy, highlighting the critical role of glutamine in dry eye therapy. Clinical cases and rodent model showed elevated expression of glutaminase (GLS1), an upstream enzyme in glutamine metabolism, following dry eye injury. Mechanistic studies indicated that overexpression and inhibition of GLS1 counteracted and enhanced, respectively, the anti-inflammatory effects of combined therapy, underscoring GLS1’s pivotal role in regulating glutamine metabolism. Furthermore, single-cell sequencing revealed a distinct subset of pro-inflammatory and pro-fibrotic corneal epithelial cells in the dry eye model, while glutamine treatment downregulated those subclusters, thereby reducing their inflammatory cytokine secretion. In summary, glutamine effectively ameliorated inflammation and the occurrence of apoptosis by downregulating the pro-inflammatory and pro-fibrotic corneal epithelial cells subclusters and the related IκBα/NF-κB signaling. The present study suggests that glutamine metabolism plays a critical, previously unrecognized role in DED and proposes an attractive strategy to enhance glutamine metabolism by inhibiting the enzyme GLS1 and thus alleviating inflammation-driven DED progression.

IntroductionMitochondria are essential organelles that provide energy for plants. They are semi-autonomous, maternally inherited, and closely linked to cytoplasmic male sterility (CMS) in plants. Lonicera macranthoides, a widely used medicinal plant from the Caprifoliaceae family, is rich in chlorogenic acid (CGA) and its analogues, which are known for their antiviral and anticancer properties. However, studies on the mitogenome of L. macranthoides still remain limited.MethodsThe mitochondrial DNA contained in the whole genome DNA was extracted from a male sterile cultivar of L. macranthoides, named ‘Yulei 1’. Next-generation sequencing (NGS) and third-generation sequencing (TGS) technologies were combined to obtain the mitogenome. RNA editing events were identified by integrating the mitogenome data with RNA sequencing data from leaf, stem, and flower tissues. The potential causes of male sterility in ‘Yulei 1’ were analyzed based on the loss of functional genes, mitogenome rearrangements, RNA editing events, and open reading frames (ORFs).Results and discussionThe complete mitogenome of L. macranthoides ‘Yulei 1’ was obtained for the first time, with a length of 1,002,202 bp. It contains 48 protein-coding genes (PCGs), 26 tRNA genes, and 3 rRNA genes. Additionally, 79 simple sequence repeats (SSRs), 39 tandem repeats, and 99 dispersed repeats were identified. Among these, two direct repeats (RP1a/1b, RP2a/2b) and two inverse repeats (RP3a/b, RP4a/b) may facilitate mitogenome recombination. Gene transfer analysis revealed that 4.36% and 21.98% of mitogenomic sequences mapped to the chloroplast and nuclear genomes, respectively. Phylogenetic analysis indicated that L. macranthoides is closest to L. japonica at the mitogenome level. Notably, RNA editing events varied across different plant tissues, with 357 editing sites in 30 PCGs in leaves, 138 sites in 24 PCGs in flowers, and 68 sites in 13 PCGs in stems. Finally, all indications of CMS in the mitogenome were screened, including the detection of ORFs, and the findings showed no mutations in the mitogenome that would explain the sterility of ‘Yulei 1’. Overall, our study provides a complete mitogenome of L. macranthoides, which will aid in its genetic marker exploration, evolutionary relationship analysis, and breeding programs.

Metamaterials have garnered significant interest in recent years due to their unprecedented properties unattainable by natural substances and potential applications in various fields. In this review, we provide an in-depth analysis of a novel class of three-dimensional (3D) disordered alloy metamaterials, including metallic glasses and high/medium entropy alloys metamaterials, which offer a promising platform for the integration of structure and function. These materials are characterized by their unique including disordered atomic structures and alloy compositions modulation, enabling the manipulation of electromagnetic, thermal, and mechanical properties. We begin by discussing the underlying principles and synthesis methods of 3D disordered alloy metamaterials, followed by a comprehensive examination of their distinctive properties and potential applications in the realms of engineering, energy harvesting, and sensing. Furthermore, we delve into the existing challenges and future directions of this burgeoning field, encompassing aspects such as scalability, precision in fabrication, and the evolution of multi-functional materials. 3D disordered alloy metamaterials represent a promising avenue for the advancement of structure-function integration, with potential implications for a broad range of scientific and technological disciplines.