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IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a leading cause of end-stage renal disease globally. Although mesangial IgA deposition defines its pathology, this alone does not predict disease progression. Current biomarkers lack specificity for forecasting outcomes or guiding early intervention. Recent advances have highlighted the potential of exosome-derived tRNA-derived small RNAs (tsRNAs) as novel diagnostic tools and mediators of disease processes, but their role in IgAN remains insufficiently explored. In this study, serum exosomes were isolated from patients with progressive or non-progressive IgAN and healthy controls. tsRNA expression profiles were obtained using small RNA sequencing and validated by qRT-PCR. Bioinformatic analyses were conducted to identify target pathways. Functional effects of candidate tsRNAs were evaluated using luciferase reporter assays, tsRNA mimic/antago transfections, and co-culture of B cell-derived exosomes with collecting duct epithelial cells (CDECs). Among 566 identified exosomal tsRNAs, tRNA-Pro-TGG was significantly upregulated in patients with progressive IgAN. It was enriched in B lymphocytes and correlated with serum soluble TNFR1 levels. Functional assays revealed that exosomal tRNA-Pro-TGG suppressed MAPK translation and activated proinflammatory responses in CDECs, including increased secretion of TNF-α, IL-6, and CCL2. ROC analysis demonstrated its robust diagnostic power for distinguishing progressive from non-progressive disease (AUC = 0.9618). This study identifies exosomal tRNA-Pro-TGG as a novel, non-invasive biomarker for IgAN progression and implicates it as a mediator of immune-driven renal inflammation. These findings offer valuable insights into IgAN pathogenesis and support the potential clinical utility of tsRNA-based diagnostics in nephrology.

Background Among the Mangifera species, mango ( Mangifera indica ) is an important commercial fruit crop. However, very few studies have been conducted on the Mangifera mitochondrial genome. This study reports and compares the newly sequenced mitochondrial genomes of three Mangifera species. Results Mangifera mitochondrial genomes showed partial similarities in the overall size, genomic structure, and gene content. Specifically, the genomes are circular and contain about 63–69 predicted functional genes, including five ribosomal RNA (rRNA) genes and 24–27 transfer RNA (tRNA) genes. The GC contents of the Mangifera mitochondrial genomes are similar, ranging from 44.42–44.66%. Leucine (Leu) and serine (Ser) are the most frequently used, while tryptophan (Trp) and cysteine (Cys) are the least used amino acids among the protein-coding genes in Mangifera mitochondrial genomes. We also identified 7–10 large chloroplast genomic fragments in the mitochondrial genome, ranging from 1407 to 6142 bp. Additionally, four intact mitochondrial tRNAs genes ( tRNA-Cys, tRNA-Trp, tRNA-Pro, and tRNA-Met ) and intergenic spacer regions were identified. Phylogenetic analysis based on the common protein-coding genes of most branches provided a high support value. Conclusions We sequenced and compared the mitochondrial genomes of three Mangifera species. The results showed that the gene content and the codon usage pattern of Mangifera mitochondrial genomes is similar across various species. Gene transfer from the chloroplast genome to the mitochondrial genome were identified. This study provides valuable information for evolutionary and molecular studies of Mangifera and a basis for further studies on genomic breeding of mango.

Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC 50 and EC 50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins.

Amaranthus retroflexus L. is one of the main broad-leaved weeds in soybean fields in Heilongjiang Province and is an important factor affecting soybean yield. It is becoming increasingly resistant to herbicides. However, studies on the transcriptome level and the molecular mechanism of secondary metabolite accumulation of resistant varieties of Amaranthus retroflexus L. have not been reported. Therefore, comprehensive analysis of transcriptome and metabolome is needed to determine the key metabolic pathways and key genes of Amaranthus retroflexus L. The biosynthetic pathway of resistance to Amaranthus retroflexus L. was studied by transcriptome and metabolome analysis. Transcriptome analysis showed that in the three comparison groups, compared with untreated (CK) group, there were 979 Differentially expressed genes (DEGs) in resistant (RY) group and 15731 DEGs in sensitive (SY) group; The RY group had 13822 DEGs compared to the SY group. Fluorescent quantitative PCR detection found that two gene tables related to Cytochrome P450 Monooxygenase (P450), Glutathione S-transferase (GST) and other enzyme systems such as peroxidase (POD), polyphenol oxidase (PPO), Catalase (CAT) and Superoxide dismutase (SOD) were significantly reached. Using Venn analysis for metabolomics analysis (VIP>1 and P<0.05), 239 Differentially expressed metabolites (DEMs) were selected. There are 15 common DEMs in the three control groups, and 8 unique DEMs in the RY group. This study detected 76 cases of DEMs and 139 cases of DEMs in the CK, RY, and SY control groups, respectively. More metabolites were detected in the CK and SY control groups. This viewpoint provides evidence for the genetic and metabolic differences between resistance and sensitivity in Amaranthus retroflexus L.. The KEGG in the RY vs SY group is mainly enriched in cysteine and methlonine metabololism, glycine, serine and threonine metabololism, aminoacyl-tRNA biosynthesis, biosynthesis of variant plant secondary metabololites, biosynthesis of amino acids, arginine and proline metabololism, biosynthesis of cofactors. Therefore, the resistance mechanism of Amaranthus retroflexus L. may be mainly generated by the metabolic pathway mechanism of amino acids. In this study, DEGs and DEMs were identified by de novo Transcriptome assembly and metabonomic analysis, and an important metabolic pathway of resistance was found. It was found that the resistance mechanism of Amaranthus retroflexus L. might be mainly produced by amino acid metabolic pathway. This discovery laid the foundation for further research on the molecular mechanism and functional characteristics of the resistance of Amaranthus retroflexus L..

Nascent polypeptide chains can induce translational stalling to regulate gene expression. This is exemplified by the E. coli secretion monitor (SecM) arrest peptide that induces translational stalling to regulate expression of the downstream encoded SecA, an ATPase that co-operates with the SecYEG translocon to facilitate insertion of proteins into or through the cytoplasmic membrane. Here we present the structure of a ribosome stalled during translation of the full-length E. coli SecM arrest peptide at 2.0 Å resolution. The structure reveals that SecM arrests translation by stabilizing the Pro-tRNA in the A-site, but in a manner that prevents peptide bond formation with the SecM-peptidyl-tRNA in the P-site. By employing molecular dynamic simulations, we also provide insight into how a pulling force on the SecM nascent chain can relieve the SecM-mediated translation arrest. Collectively, the mechanisms determined here for SecM arrest and relief are also likely to be applicable for a variety of other arrest peptides that regulate components of the protein localization machinery identified across a wide range of bacteria lineages. Stalling of ribosomes by the nascent polypeptide chain is widely used to regulate gene expression. Here, Gersteuer et al determine cryo-EM structures of SecM-stalled ribosomes revealing the mechanism by which the SecM peptide arrests translation.

The prolyl-tRNA synthetase (PRS) is a validated drug target for febrifugine and its synthetic analog halofuginone (HFG) against multiple apicomplexan parasites including Plasmodium falciparum and Toxoplasma gondii . Here, a novel ATP-mimetic centered on 1-(pyridin-4-yl) pyrrolidin-2-one (PPL) scaffold has been validated to bind to Toxoplasma gondii PRS and kill toxoplasma parasites. PPL series exhibited potent inhibition at the cellular ( T . gondii parasites) and enzymatic ( Tg PRS) levels compared to the human counterparts. Cell-based chemical mutagenesis was employed to determine the mechanism of action via a forward genetic screen. Tg- resistant parasites were analyzed with wild-type strain by RNA-seq to identify mutations in the coding sequence conferring drug resistance by computational analysis of variants. DNA sequencing established two mutations, T477A and T592S, proximal to terminals of the PPL scaffold and not directly in the ATP, tRNA, or L-pro sites, as supported by the structural data from high-resolution crystal structures of drug-bound enzyme complexes. These data provide an avenue for structure-based activity enhancement of this chemical series as anti-infectives.

The paddy frog (Fejervarya multistriata) belonging to the family Dicroglossidae, is a species widely distributed in temperate and tropical Asia. In this study, the complete mitochondrial genome of F. multistriata was sequenced. The mitogenome was 17 677 bp in size, consisting of 13 protein-coding genes (PCGs), 23 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a non-coding control region (D-loop). Like in other vertebrates, most mitochondrial genes of the species are encoded on the heavy (H) strand, except for ND6 and eight tRNA genes which are encoded on the light (L) strand. The overall base composition contained 28.03% A, 29.90% T, 26.91% C and 15.16% G. The alignment of the Fejervarya and related species' control regions exhibited high genetic variability and rich A + T content. In addition, we found that the tRNA-Leu2 rearrangement occurred in the LTPF gene cluster in the mitochondrial genome of the F. multistriata, resulting in a new arrangement (T-PL-F). There was a tandem duplication of the tRNA-Met gene between tRNA-Gln and ND2, and the similarity rate of the two genes reached 74.6%. The phylogenetic relationships based on nucleotide sequences of 13 PCGs was analysed by re-establishing phylogenetic trees (ML and BI). The results indicated that F. multistriata was more closely related to F. limnocharis than to F. cancrivora and F. manoharani, the two latter showing a new gene rearrangement (ND6-tRNA-Glu-Cytb-D-loop-ND5-tRNA-Thr-tRNA-Pro-tRNA-Leu-tRNA-Phe). Our results indicate that F. limnocharis sample found in Yancheng, and F. multistriata from Mojia, Santai and Ji'an, are possible conspecifics. This study on the mitochondrial genome of F. multistriata provides an important reference for the future studies on phylogenetic relationship and the taxonomic status of Fejervarya and related Dicroglossidae species.

The mitochondrial genome (mitogenome) of (Anura: Megophryidae) was sequenced by the Illumina platform. The assembled circular mitogenome of had a total length of 17,040 bp, with a GC content of 41.25%. It consisted of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes, and a D-loop region. The majority of the PCGs were encoded by the H-strand, while one PCG ( ) and eight tRNA genes (tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser2, tRNA-Glu, and tRNA-Pro) were encoded in the L-strand. Phylogenetic analysis revealed that the newly sequenced species formed a clade with other species, while the genus itself formed a sister group with the genus .

In this study, we sequenced and reported the complete mitochondrial genomes of Kusala populi for the first time. The complete mitochondrial genome was registered in GenBank with accession number NC_064377 as the first complete mitogenome of the genus Kusala. The circular mitochondrial genome length is 15,402 bp, with nucleotide composition A (41.8%), C (11.4%), G (9.2%), T (37.6%), A + T (79.4%), and C + G (20.6%), comprising 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a D-loop region. All protein-coding genes were encoded by the H-strand, except for 4 genes (nad5, nad4, nad4L, nad1). 8 tRNA genes (tRNA-Gln, tRNA-Cys, tRNA-Tyr, tRNA-Phe, tRNA-His, tRNA-Pro, tRNA-Leu, tRNA-Val) and 2 rRNA genes (16S, 12S) were encoded in the L-strand. Phylogenetic analysis indicated that the newly sequenced species had a close relationship with Mitjaevia, another widespread Old-World genus of Erythroneurini.

We aimed to determine the metabolomic profile of kidney cells under high glucose conditions and following sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in kidney cells stimulated with high glucose (25 and 50 mM) and treated with SGLT2 inhibitor, dapagliflozin (2 µM). Primary cultured human tubular epithelial cells and podocytes were used to identify the metabolomic profile in high glucose conditions following dapagliflozin treatment. The levels of asparagine, PC ae C34:1, and PC ae C36:2 were elevated in tubular epithelial cells stimulated with 50 mM glucose and were significantly decreased after 2 µM dapagliflozin treatment. The level of PC aa C32:0 was significantly decreased after 50 mM glucose treatment compared with the control, and its level was significantly increased after dapagliflozin treatment in podocytes. The metabolism of glutathione, asparagine and proline was significantly changed in tubular epithelial cells under high-glucose stimulation. And the pathway analysis showed that aminoacyl-tRNA biosynthesis, arginine and proline metabolism, glutathione metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, beta-alanine metabolism, phenylalanine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism were altered in tubular epithelial cells after dapagliflozin treatment following 50 mM glucose compared to those treated with 50 mM glucose.