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Uremic cardiomyopathy (UC) represents a leading cause of mortality in patients with chronic kidney disease (CKD), characterized by left ventricular hypertrophy (LVH) and fibrosis. The underlying mechanisms of UC pathogenesis remain incompletely understood. This study developed two methods to simulate human UC – modified nephrectomy (MNx) and adenine-normal combinational diet – and compared these approaches across several rodent strains. Transcriptomic analysis was performed on left ventricular tissues from these models. The analysis revealed global changes in UC, including dysregulated cell cycle processes, enhanced extracellular matrix remodeling and metabolic abnormalities, while also highlighting molecular distinctions between MNx- and adenine-induced UC. Notably, this study identified C-C-motif receptor 2 (CCR-2) as a novel potential antifibrotic target in UC. CCR-2 blockade substantially reversed fibrosis without affecting LVH. The mechanism through which CCR-2 inhibition suppresses cardiac fibrosis development in UC appears to involve the promotion of cardiac residual macrophage expansion. These findings establish a central role for CCR-2 in cardiac fibrosis and suggest CCR-2 inhibition as a promising therapeutic target for UC.

The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

Background The symbiotic nitrogen-fixing system formed between alfalfa ( Medicago sativa L.) and rhizobia requires precise regulation of carbohydrate and lipid metabolism to sustain their high-energy-demand system. However, metabolic divergence between roots and nodules remains poorly characterized. Results Using comparative transcriptomics, we analyzed gene expression profiles in pink nodules (PN), white nodules (WN), Pink nodule roots (PNR), white nodule roots (WNR), non-nodule roots (NNR) and control roots (CKR) from rhizobia-inoculated plants at 35 days post-inoculation. Key findings revealed metabolic specialization between tissues: PN exhibited elevated expression of lipid catabolism genes ( MsECHIA , MsACX ) and key genes of the TCA cycle regulators, driving direct energy supply for nitrogenase activity. PNR, WNR preferentially expressed glycolysis ( MsPKP2 ) and pentose phosphate pathway ( MsG6PD5 ) genes to convert photoassimilates into dicarboxylic acids via a directional transport system to nodules. WN showed enriched fatty acid elongation genes ( MsKCR1 , MsHACD2 ), suggesting compensatory synthesis of structural lipid to maintain symbiotic interfaces under carbon limitation. NNR, CKR retained starch metabolism dominance. Weighted geneco-expression network analysis revealed that symbiotic signaling synchronizes nodule lipid degradation with root carbon repartitioning to prioritize photoassimilate allocation to nodules. Nodulated roots may supplement nodule energetics through lipid precursor synthesis or storage lipid hydrolysis, thereby forming a “root-nodule metabolic relay” mechanism. Our results demonstrate that the alfalfa-rhizobia symbiosis establishes a hierarchical energy distribution network through tissue-specific regulation of metabolic genes, coordinating nitrogen fixation efficiency with energy supply homeostasis. Conclusions This study elucidates metabolic coordination mechanisms underlying legume-rhizobial symbiosis, providing a theoretical framework for optimizing symbiotic energy economics through targeted gene editing approaches.

Infection following rhino-prosthesis surgery poses a significant challenge, with primary treatment strategies centered on identifying specific pathogenic bacteria through bacterial culture and administering effective antibiotics. This study aimed to investigate whether conducting bacterial cultures that specifically target the nasal prosthesis could provide more objective guidance for clinical decision-making. We included patients who developed infections subsequent to prosthesis rhinoplasty in this investigation. The clinical significance of bacterial cultures obtained from nasal prostheses was assessed by comparing the culture results with those derived from the nasal mucosa or secretions from disrupted wounds. Notably, the bacterial detection rate in samples taken from prosthetic devices was significantly higher than that observed in conventional specimens from the same patients, exhibiting a statistically significant difference. Within the prosthetic group, no statistically significant difference was identified in bacterial detection rates between patients who received antibiotics 3 days prior to surgery and those who did not. In contrast, in the conventional control group, there was a marked decrease in bacterial detection rates among patients following antibiotic administration. Among patients treated with antibiotics, the detection rate of bacteria cultured from prosthetic specimens was significantly higher compared to that in the control group; however, there were no statistical differences found regarding bacterial detection rates for those not treated with antibiotics. In analyzing materials within the prosthesis group: silicone implants showed a bacterial detection rate of 80%, expanded polytetrafluoroethylene materials had a rate of 79.2%, and other materials demonstrated a 90.9%rate. No statistically significant differences were noted among these three material types within this cohort. In contrast, within the control group: silicone implants exhibited a bacterial detection rate of 66.7%, expanded polytetrafluoroethylene materials registered at 73.6%, while other materials maintained a lower count at 63.6%. Similarly, no statistically significant differences prevailed among these groups. Culturing prosthetic specimens can enhance the detection rate of bacteria, particularly in patients who have received antibiotic therapy prior to surgery, offering distinct advantages. Therefore, we advocate for the implementation of prosthetic specimen cultures as an adjunctive measure for detecting infections post-nasal prosthesis reconstruction. Among patients treated with antibiotics, the rate of bacteria detected from cultured prosthetic specimens was significantly higher compared to that in the control group. However, no statistically significant differences were observed regarding bacterial detection rates in patients not receiving antibiotic treatment. When analyzing materials within the prosthesis group: silicone implants exhibited a bacterial detection rate of 80%, expanded polytetrafluoroethylene (ePTFE) materials had a detection rate of 79.2%, and other materials demonstrated a higher rate of 90.9%. Notably, there were no statistically significant differences among these three material types within this cohort. In contrast, within the control group: silicone implants displayed a bacterial detection rate of 66.7%, ePTFE materials showed a rate of 73.6%, while other materials recorded a lower count at 63.6%. Similarly, no statistically significant differences emerged among these groups. Culturing prosthetic specimens can enhance the detection rates of bacteria, particularly in patients who have undergone antibiotic therapy prior to surgery, thereby offering distinct advantages for infection diagnosis. Therefore, we advocate for incorporating cultures of prosthetic specimens as an adjunctive measure for detecting infections following nasal prosthesis reconstruction. Level of evidence: Level 4.

To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted. qRT-PCR was used to verify the significantly expressed genes-HLA-DRB1, HLA-DRB5, CXCL5 and IGFL1. There were 2441 significantly up-regulated and 3904 significantly down-regulated genes in the postoperative group. The qRT-PCR results showed the expression of HLA-DRB1, HLA-DRB5 and CXCL5 was consistent with the transcriptional sequencing results. CXCL5 and CXCL6 differentially up-regulated genes are involved in the process of neovascularization, and HLA-DRB1 is involved in the improvement of the degree of diabetic peripheral nerve degeneration. Pathway analysis showed that differential genes were most significantly enriched in Adherens junction, Inflammatory mediator regulation of TRP channels and Wnt signaling pathway. Inflammatory mediator regulation of TRP channels is involved in the improvement of peripheral neurodegeneration, VEGF signaling pathway is involved in the process of neovascularization, and Wnt signaling pathway is involved in the process of bone healing. Significantly up-regulated CXCL5 and CXCL6 and enriched VEGF signaling pathway analyzed are involved in postoperative lower limb neovascularization. The HLA-DRB1 and the enriched Inflammatory mediator regulation of TRP channels may be related to the improvement of postoperative peripheral neurodegeneration. The differentially expressed genes and related pathways can provide objective basis for further mechanism study.

Sexual development in Toxoplasma gondii is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro. Wang et al. discovered that AP2XI-2 and AP2XII-1 negatively regulate merozoite-primed pre-sexual commitment in Toxoplasma gondii, and parasites depleted of either AP2XI-2 or AP2XII-1 can serve as a valuable in vitro model for studying merogony.

The G allele of rs4702 polymorphism has been reported to reduce the production of mature BDNF and FURIN, both of which were closely associated with cognitive functions. Real‐time PCR, ELISA and luciferase assay were performed to explore the interactions between miR‐338‐3p, FURIN and BDNF. T‐RFLP was used to assess the intestinal flora in the stool samples of glioma patients after radiotherapy. We grouped the 106 glioma patients recruited according to the rs4702 polymorphism. The results showed no obvious correlation between rs4702 polymorphism and the expression of miR‐338‐3p. However, rs4702‐A was associated with increased expression of FURIN and BDNF in the serum and PBMC of glioma patients after radiotherapy. Besides, the study found that rs4702‐A was remarkably associated with increased enterotype I and decreased enterotype III in the stool of glioma patients after radiotherapy. Rs4702‐A was also proved to be closely associated with increased MMSE, role functioning and social functioning at three months after radiotherapy. Furthermore, miR‐338‐3p repressed the expression of FURIN‐G. Compared with G allele, the presence of A allele of rs4702 polymorphism in FURIN could obstruct the suppressive effect of miR‐338‐3p upon the expression of FURIN and BDNF in intestinal flora. Therefore, the carriers of A allele will be challenged with less risk of radiotherapy‐induced cognitive impairment.

Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T . gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite’s daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T . gondii .

Background Amoebiasis is caused by the protozoan Entamoeba histolytica , which is a rare infectious disease in developed countries. If the trophozoites enter the blood, it can spread through the body, such as brain, and lungs. Cases of simultaneous infection of multiple organs are extremely rare. Case presentation Here we report a case of simultaneous infection of amoeba in pulmonary pleura, urinary system and central nervous system. Although the patient received anti amoeba treatment, the prognosis of the patient was poor. Conclusions In this patient, multiple extraintestinal amebic infections in the absence of clinically confirmed intestinal amebiasis or amebic liver abscess are rare and pose diagnostic challenges. The disseminated amebiasis has significantly increased the mortality. Early diagnosis and appropriate treatment may reduce the mortality of disseminated amebiasis.