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Abstract 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.

Abstract 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.

Abstract 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

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.

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.

An ingenious thermo-mechanical treatment process was utilized on a Fe-5.95Mn-1.55Si-1.0Al-0.055C medium-Mn steel to investigate the effect of fibrous δ-ferrites on mechanical properties. With a large enough cold-rolling reduction ratio (∼70%), the morphology of coarsened fibrous δ-ferrites is tailored into homogeneous distributed fragments, which provides a precondition to launch the present study. Direct experimental evidence has been obtained that fibrous δ-ferrites are a double-edged sword for mechanical properties: it improves ductility (by 3.5% ± 1.1%) but decreases tensile strength (by 65 ± 11.5 MPa). This can be related to the accommodation effect of dislocations within coarsened fibrous δ-ferrite grains as soft phase, which decreases the degree of dislocation pile-ups in martensitic matrix, resulting in the limited strengthening effect of dislocations. Additionally, despite significant directionality along rolling direction, the fibrous δ-ferrite grains do not result in anisotropic properties.

Breaking the strength-ductility paradox of very-low (≤0.05 wt.%)-C medium (3–12 wt.%)-Mn steels (MMnS) has been a hard-wired topic, since in these steels multi-step heat treatments are usually required to obtain austenite for improved ductility and precipitates for higher strength. In this study, a compact two-step heat treatment comprising short (2 min) annealing and tempering was developed to investigate the synergetic effect of austenite reversion and nano-precipitation on the tensile behavior of a very-low-C MMnS containing 1.5 wt.% Cu and 1.5 wt.% Ni. The annealing step promoted considerable amount of reverted austenite (33 vol.%), and the annealing was short to prevent Cu and Ni from partitioning into austenite, since they were supposed to maintain in the ferrite phase and then promote the nano-precipitation in the subsequent tempering stage. During the subsequent tempering step, the nano-precipitates with Cu concentration of 20–50 at.% in the precipitation core and enriched with Cu, Ni, Al and Mn were observed in the ferrite phase. The volume fraction of reverted austenite reached 38.5 vol.% after tempering, which led to the ultimate tensile strength of 1222 MPa and total elongation of 29% by the transformation induced plasticity during plastic deformation. The current study demonstrates the beneficial influence of the compact two-step heat treatment on the austenite reversion and nano-precipitation behavior of very-low-C MMnS with the addition of Cu and Ni, which subsequently enables an enhanced strain hardening behavior, thereby improving the mechanical property profile of the MMnS.

Developing medium-Mn steels (MMnS) demands a better understanding of the microstructure evolution during thermo-mechanical treatments (TMTs). This study demonstrates the relationship among processing, microstructure, and mechanical properties of a warm-rolled medium-Mn steel (MMnS) containing 1.5 wt. % Cu and 1.5 wt. % Ni. After short-time warm rolling (WR) in an intercritical temperature range, a significant quantity (40.6 vol.%) of austenite was reverted and retained after air cooling. The microstructure and tensile properties of the WR specimens were compared with two typical process routes, namely hot rolling+ cold rolling+ annealing+ tempering (CRAT) and warm rolling+ annealing+ tempering (WRAT). The WR specimen exhibited comparable tensile properties with the CRAT specimens (967 MPa yield strength, 1155 MPa tensile strength, 23% total elongation), with a remarkably shortened process route, which was derived from the dislocation accumulation and austenite reversion during rolling. The WR route stands out among the traditional CRAT and the extended WRAT routes for its excellent tensile properties and compact processing route.