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The interplay between gut microbiota and host is crucial for maintaining host health. When this balance is broken, various diseases can arise, including colorectal cancer (CRC). However, the mechanism by which gut microbiota and host interactions mediate CRC development remains unclear. Here, we found that Gasdermin D (GSDMD), an inflammasome effector responsible for forming membrane pores to mediate cell pyroptosis, was upregulated in both human and mouse intestinal tumor samples. GSDMD deficiency significantly suppressed intestinal tumor development in Apc min/+ mice, a spontaneous CRC mouse model. Apc min/+ Gsdmd -/- mice exhibited reduced IL-1β release in the intestine, and the administration of recombinant mouse IL-1β partially restored intestinal tumor development in Apc min/+ Gsdmd -/- mice. Moreover, 16s rRNA sequencing showed a substantial increase in Lactobacillus abundance in the feces of Apc min/+ Gsdmd -/- mice compared to Apc min/+ mice. Concurrently, Kynurenine (Kyn), a metabolite derived from host tryptophan (Trp) metabolism, was significantly decreased in the feces of Apc min/+ Gsdmd -/- mice, as shown by metabolite analysis. Additionally, Kyn levels were inversely correlated with Lactobacillus abundance. Furthermore, the administration of exogenous Kyn also promoted intestinal tumor development in Apc min/+ Gsdmd -/- mice. Thus, GSDMD promotes spontaneous CRC development through increasing IL-1β release and Kyn production. Our data suggest an association between GSDMD, gut microbiota, the host Trp/Kyn pathway, and CRC development., (© 2024. The Author(s).)

Autoimmune related kidney diseases (ARKDs), including minimal change nephropathy (MCN), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN), significantly affect renal function. These diseases are characterized by the formation of local immune complexes and the subsequent activation of the complement system, leading to kidney damage and proteinuria. Despite the known patterns of glomerular injury, the specific molecular mechanisms that contribute to renal tubular damage across ARKDs remain underexplored. Laser capture microdissection and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to conduct a comparative proteomic analysis of renal tubular tissues from formalin-fixed paraffin-embedded samples. The cohort comprised of 10 normal controls (NC), 5 MCN, 4 MN, 17 IgAN, and 21 LN patients. Clinical parameters and histopathological assessments were integrated with proteomic findings to comprehensively investigate underlying pathogenic processes. Clinical evaluation indicated significant glomerular damage, as reflected by elevated urinary protein levels and reduced plasma albumin levels in patients with ARKD. Histological analyses confirmed varying degrees of tubular damage and deposition of immune complexes. Proteomic analyses identified significant changes in protein expression, particularly in complement components (C3, C4A, C4B, C8G, CFB, and SERPINA1) and mitochondrial proteins (ATP5F1E and ATP5PD), highlighting the common alterations in the complement system and mitochondrial proteins across ARKDs. These alterations suggest a novel complement-mitochondrial-epithelial-mesenchymal transition (EMT) pathway axis that contributes to tubular damage in ARKDs. Notably, significant alterations in CFB in tubular ARKD patients were revealed, implicating it as a therapeutic target. This study underscores the importance of complement activation and mitochondrial dysfunction in the pathogenesis of ARKDs, and proposes CFB as a potential therapeutic target to inhibit complement activation and mitigate tubular damage. Future research should validate the complement-mitochondrial-EMT pathway axis and explore the effects and mechanisms of CFB inhibitors in alleviating ARKD progression., (© 2024. The Author(s).)

Research on the flexible hybrid epidermal electronic system (FHEES) has attracted considerable attention due to its potential applications in human-machine interaction and healthcare. Through material and structural innovations, FHEES combines the advantages of traditional stiff electronic devices and flexible electronic technology, enabling it to be worn conformally on the skin while retaining complex system functionality. FHEESs use multimodal sensing to enhance the identification accuracy of the wearer's motion modes, intentions, or health status, thus realizing more comprehensive physiological signal acquisition. However, the heterogeneous integration of soft and stiff components makes balancing comfort and performance in designing and implementing multimodal FHEESs challenging. Herein, multimodal FHEESs are first introduced in 2 types based on their different system structure: all-in-one and assembled, reflecting totally different heterogeneous integration strategies. Characteristics and the key design issues (such as interconnect design, interface strategy, substrate selection, etc.) of the 2 multimodal FHEESs are emphasized. Besides, the applications and advantages of the 2 multimodal FHEESs in recent research have been presented, with a focus on the control and medical fields. Finally, the prospects and challenges of the multimodal FHEES are discussed., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ding Li et al.)

Background: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis., Methods: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves., Results: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds., Conclusions: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis., (© 2024. The Author(s).)

Background: N-glycosylation is one of the most common posttranslational modifications in humans, and these alterations are associated with kidney diseases., Methods: A novel technological approach, single-cell N-acetyllactosamine sequencing (scLacNAc-seq), was applied to simultaneously detect N-glycosylation expression and the transcriptome at single-cell resolution in three human kidney tissues from zero-time biopsy. Cell clusters, glycation abundance in each cell cluster, functional enrichment analysis, cell-cell crosstalk, and pseudotime analysis were applied., Results: Using scLacNAc-seq, 24,247 cells and 22 cell clusters were identified, and N-glycan abundance in each cell was obtained. Transcriptome analysis revealed a close connection between capillary endothelial cells (CapECs) and parietal epithelial cells (PECs). PECs and CapECs communicate with each other through several pairs of ligand receptors (e.g., TGFB1-EGFR, GRN-EGFR, TIMP1-FGFR2, VEGFB-FLT1, ANGPT2-TEK, and GRN-TNFRSF1A). Finally, a regulatory network of cell-cell crosstalk between PECs and CapECs was constructed, which is involved in cell development., Conclusions: We here, for the first time, constructed the glycosylation profile of 22 cell clusters in the human kidney from zero-time biopsy. Moreover, cell-cell communication between PECs and CapECs through the ligand-receptor system may play a crucial regulatory role in cell proliferation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Spatial distribution perception has become an important trend for flexible pressure sensors, which endows wearable health devices, bionic robots, and human-machine interactive interfaces (HMI) with more precise tactile perception capabilities. Flexible pressure sensor arrays can monitor and extract abundant health information to assist in medical detection and diagnosis. Bionic robots and HMI with higher tactile perception abilities will maximize the freedom of human hands. Flexible arrays based on piezoresistive mechanisms have been extensively researched due to the high performance of pressure-sensing properties and simple readout principles. This review summarizes multiple considerations in the design of flexible piezoresistive arrays and recent advances in their development. First, frequently used piezoresistive materials and microstructures are introduced in which various strategies to improve sensor performance are presented. Second, pressure sensor arrays with spatial distribution perception capability are discussed emphatically. Crosstalk is a particular concern for sensor arrays, where mechanical and electrical sources of crosstalk issues and the corresponding solutions are highlighted. Third, several processing methods are also introduced, classified as printing, field-assisted and laser-assisted fabrication. Next, the representative application works of flexible piezoresistive arrays are provided, including human-interactive systems, healthcare devices, and some other scenarios. Finally, outlooks on the development of piezoresistive arrays are given.

The oral microbiota are closely related to human health. Nonetheless, to the best of our knowledge, their relationship with membranous nephropathy (MN) remains unstudied. The saliva microbiota collected from 22 patients with MN and 15 healthy controls were analyzed by next‑generation sequencing, and bioinformatics analysis of the 16S ribosomal RNA gene was subsequently carried out. The Chao1 and Shannon indices in patients with MN were higher than those in healthy controls. Analysis of similarities revealed that the oral microbiota in the patient group were significantly different from those in the healthy controls. At the genus level, the abundance of Alloprevotella , Granulicatella , Prevotella , Streptococcus and Prevotella&#95;7 was markedly higher in patients with MN than in healthy controls. Six operational taxonomic units (OTUs; OTU5, OTU28, OTU9, OTU15, OTU33 and OTU38) were found to be markedly correlated with the clinical factors creatinine, proteinuria in 24 h, estimated glomerular filtration rate and systolic blood pressure. A total of 28 Kyoto Encyclopedia of Genes and Genomes pathways were obtained from the significant OTUs. The oral microbiota of patients with MN were investigated and it was found that OTU5, OTU28, OTU9, OTU15, OTU33 and OTU38 may be used as biomarkers. The present findings may assist in the diagnosis of patients with MN.