Xenotransplantation - a shortcut to construct tissue complexity in organoids.

Our knowledge of human biology is mainly originated from studies using animal models. However, interspecies differences between human and model organisms may lead to imprecise extrapolation of results obtained from model organisms. Organoids are three-dimensional cell clusters derived from pluripotent or adult stem cells that self-organize into organ-like structures reminiscent of the cognate organ. The establishment of human organoids makes it possible to study organ or tissue pathophysiology that is specific to human beings. However, most organoids do not have organ-specific vasculature, neurons, and immune cells, hence limiting their utility in emulating complex pathophysiological phenotypes. Among the various approaches to address these limitations, xenotransplantation represents a promising 'shortcut'. We will discuss recent advance in constructing tissue complexity in organoids, with a special focus on xenotransplantation.

[Effect of total saponins from Panacis Majoris Rhizoma on proliferation, apoptosis and autophagy of human cervical carcinoma HeLa cells].

This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.

Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

Delta magnetic resonance imaging radiomics features­based nomogram predicts long­term efficacy after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.

Preliminary study on the active substances and cellular pathways of lactic acid bacteria for colorectal cancer treatment.

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

Noviherbaspirillum album sp. nov., an airborne bacteria isolated from an urban area of Beijing, China.

A Gram-negative, ellipsoidal to short-rod-shaped, motile bacterium was isolated from Beijing's urban air. The isolate exhibited the closest kinship with Noviherbaspirillum aerium 122213-3T, exhibiting 98.4 % 16S rRNA gene sequence similarity. Phylogenetic analyses based on 16S rRNA gene sequences and genomes showed that it clustered closely with N. aerium 122213-3T, thus forming a distinct phylogenetic lineage within the genus Noviherbaspirillum. The average nucleotide identity and digital DNA-DNA hybridization values between strain I16B-00201T and N. aerium 122213-3T were 84.6 and 29.4 %, respectively. The respiratory ubiquinone was ubiquinone 8. The major fatty acids (>10 %) were summed feature 3 (C16:1ω6c/C16:1ω7c, 43.3 %), summed feature 8 (C18:1ω7c/C18:1ω6c, 15.9 %) and C12:0 (11.0 %). The polyamine profile showed putrescine as the predominant compound. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, unknown lipids and unknown phosphatidylaminolipids. The phenotypic, phylogenetic and chemotaxonomic results consistently supported that strain I16B-00201T represented a novel species of the genus Noviherbaspirillum, for which the name Noviherbaspirillum album sp. nov. is proposed, with I16B-00201T (=CPCC 100848T=KCTC 52095T) designated as the type strain. Its DNA G+C content is 59.4 mol%. Pan-genome analysis indicated that some Noviherbaspirillum species possess diverse nitrogen and aromatic compound metabolism pathways, suggesting their potential value in pollutant treatment.

A Facile Approach to Construct Novel Polyesters as Soft Midblock for Thermoplastic Elastomers.

The development of innovative synthetic strategies to create functional polycaprolactones is highly demanded for advanced material applications. In this contribution, we reported a facile synthetic strategy to prepare a class of CL-based monomers (R-TO) derived from epoxides. They readily polymerize via well-controlled ring-opening polymerization (ROP) to afford a series of polyesters P(R-TO) with high molecular weight (Mn up to 350 kDa). Sequential addition copolymerization of MTO and L-lactide (L-LA) allowed to access of a series of ABA triblock copolymers with composition-dependent mechanical properties. Notably, P(L-LA)100-b-P(MTO)500-b-P(L-LA)100 containing the amorphous P(MTO) segment as a soft midblock and crystalline P(L-LA) domain as hard end block behaved as an excellent thermoplastic elastomer (TPE) with high elongation at break (1438±204 %), tensile strength (23.5±1.7 MPa), and outstanding elastic recovery (>88 %).

EDA Complex-Enabled Annulation to Access CF2-Containing Tetralones and Quinazolinones Using Persulfates as Electron Donors.

A photocatalyst-free and EDA complex-enabled radical cascade cyclization reaction of inactive alkenes with bromodifluoroacetamides was reported for the divergent synthesis of fluorine-containing tetralones and quinazolinones. In this transformation, persulfates as electron donors and difluoro bromamide as electron acceptors generate the EDA complex. This is a promising photochemical method with advantages such as mild reaction conditions, simple operation, being metal-free, and excellent functional group tolerance.

Assessing catchment-scale groundwater discharge: Optimal tracers and factors analysis.

Identifying streamwater-groundwater interactions (SGI) is crucial for effective water resource management, especially in arid and semi-arid regions. Despite the effectiveness of tracers in detecting these interactions, their large-scale application is challenged by the variability in tracer characteristics and natural conditions. This study addresses these challenges through extensive research across seven watersheds (7636-60,916 km2) in China's Loess Plateau (CLP). We utilized multiple physicochemical and stable isotope tracers (δ2H and δ18O) to elucidate the spatiotemporal variations and controlling factors of SGI, and to estimate uncertainties in quantifying SGI using various indicators during unidirectional water exchange periods. Our findings indicated that groundwater discharge into streamwater dominates SGI in the CLP, with mean discharge ratios (the percentage of river flow that originates from groundwater discharge) varying from 10% to 57%. Significant spatial variability was observed both across and within watersheds. The central watersheds exhibited lower discharge ratios (23 ± 11%) compared to the northern (29 ± 12%) and southern (25 ± 13%) watersheds. The upper reaches showed higher discharge ratios (28 ± 12%) compared to the middle and lower reaches (22 ± 8%). Loess thickness and vegetation primarily limit groundwater discharge by affecting groundwater storage and water flow velocity. The utilization of individual isotopic or hydrochemical indicators introduces large uncertainties in quantifying groundwater discharge ratios due to isotope fractionation or water-rock interaction, while the combination of these two indicators can reduce uncertainties in quantifying SGI. This study provides valuable insights for selecting environmental tracers to quantify SGI, contributing to sustainable water resource management in arid and semi-arid regions.

Relationship of inflammatory indices with left atrial appendage thrombus or spontaneous echo contrast in patients with atrial fibrillation.

BACKGROUND: Inflammatory indices derived from complete blood tests have been reported to be associated with poor outcomes in patients with atrial fibrillation (AF). The data about the relationship between inflammatory indices and left atrial appendage thrombus (LAAT) or dense spontaneous echo contrast (SEC) are limited. AIM: To explore the value of inflammatory indices for predicting the presence of LAAT or dense SEC in nonvalvular AF patients. METHODS: A total of 406 patients with nonvalvular AF who underwent transesophageal echocardiography were included and divided into two groups based on the presence (study group) or absence (control group) of LAAT or dense SEC. Inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), were calculated from complete blood analysis. The associations of inflammatory indices with LAAT/dense SEC were analyzed using logistic regression. RESULTS: LAAT and dense SEC were detected in 11 (2.7%) and 42 (10.3%) patients, respectively. The PLR only showed an association with LAAT/dense SEC in the univariate model. Elevated NLR (odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.11-1.98, P = 0.007) and reduced LMR (OR = 0.59, 95%CI: 0.41-0.83, P = 0.003) were found to be independent risk factors for the presence of LAAT/dense SEC. The areas under the NLR and LMR curves for predicting LAAT/dense SEC were 0.73 (95%CI: 0.66-0.80, P < 0.001) and 0.73 (95%CI: 0.65-0.81, P < 0.001), respectively, while the cutoff values were 2.8 (sensitivity: 69.8%; specificity: 64.0%) and 2.4 (sensitivity: 71.7%; specificity: 60.6%), respectively. CONCLUSION: Increased NLR and decreased LMR may predict LAAT/dense SEC in patients with nonvalvular AF.

Antimicrobial susceptibilities, resistance mechanisms and molecular characteristics of toxigenic Clostridioides difficile isolates in a large teaching hospital in Chongqing, China.

OBJECTIVES: Clostridioides difficile ranks among the primary sources of healthcare-related infections and diarrhoea in numerous nations. We evaluated the drug susceptibility and resistance mechanisms of C. difficile isolates from a hospital in Chongqing, China, and identified resistance rates and resistance mechanisms that differed from previous findings. METHODS: The toxin genes and drug resistance genes of clinical strains were detected using Polymerase Chain Reaction (PCR), and these strains were subjected to Multilocus Sequence Typing (MLST). The agar dilution technique was employed for assessing susceptibility of antibiotics. Clinical data collection was completed through a review of electronic medical records. RESULTS: A total of 67 strains of toxin-producing C. difficile were detected. All C. difficile isolates demonstrated susceptibility to both metronidazole and vancomycin. However, resistance was observed in 8.95%, 16.42%, 56.72%, 56.72%, 31.34% and 5.97% of the isolates for tigecycline, tetracycline, clindamycin, erythromycin, moxifloxacin and rifampin, respectively. Among the strains with toxin genotypes A + B + CDT - and belonging to the ST3, six strains exhibited reduced susceptibility to tigecycline (MIC=0.5mg/L) and tetracycline (MIC=8mg/L). The tetA(P) and tetB(P) genes were present in these six strains, but were absent in tetracycline-resistant strains. Resistance genes (ermB, tetM, tetA(P) and tetB(P)) and mutations (in gyrA, gyrB, and rpoB) were identified in resistant strains. CONCLUSIONS: In contrast to prior studies, we found higher proportions of ST3 isolates with decreased tigecycline sensitivity, sharing similar resistance patterns and resistance genes. In the resistance process of tigecycline and tetracycline, the tetA(P) and tetB(P) genes may play a weak role.

Effects of two fillers and process conditions on the water treatment efficiency of a continuous packed bed biofilm reactor.

This study evaluated the treatment efficiency of two selected fillers and their combination for improving the water quality of aquaculture wastewater using a packed bed biofilm reactor (PBBR) under various process conditions. The fillers used were nanosheet (NS), activated carbon (AC), and a combination of both. The results indicated that the use of combined fillers and the hydraulic retention time (HRT) of 4 h significantly enhanced water quality in the PBBR. The removal rates of chemical oxygen demand, NO2-─N, total suspended solids（TSS）, and chlorophyll a were 63.55%, 74.25%, 62.75%, and 92.85%, respectively. The microbiota analysis revealed that the presence of NS increased the abundance of microbial phyla associated with nitrogen removal, such as Nitrospirae and Proteobacteria. The difference between the M1 and M2 communities was minimal. Additionally, the microbiota in different PBBR samples displayed similar preferences for carbon sources, and carbohydrates and amino acids were the most commonly utilized carbon sources by microbiota. These results indicated that the combination of NS and AC fillers in a PBBR effectively enhanced the treatment efficiency of aquaculture wastewater when operated at an HRT of 4 h. The findings provide valuable insights into optimizing the design of aquaculture wastewater treatment systems.

Homology in Sex Determination in Two Distant Spiny Frogs, Nanorana quadranus and Quasipaa yei.

Sex determination is remarkably diverse, with frequent transitions between sex chromosomes, in amphibians. Under these transitions, some chromosomes are more likely to be recurrently co-opted as sex chromosomes, as they are often observed across deeply divergent taxa. However, little is known about the pattern of sex chromosome evolution among closely related groups. Here, we examined sex chromosome and sex determination in two spiny frogs, Nanorana quadranus and Quasipaa yei. We conducted an analysis of genotyping-by-sequencing (GBS) data from a total of 34 individuals to identify sex-specific makers, with the results verified by PCR. The results suggest that chromosome 1 is a homologous sex chromosome with an XY pattern in both species. This chromosome has been evolutionarily conserved across these closely related groups within a period of time. The DMRT1 gene is proposed to be implicated in homology across two distantly related spiny frog species as a putative candidate sex-determining gene. Harboring the DMRT1 gene, chromosome 1 would have been independently co-opted for sex determination in deeply divergent groups of anurans.

Applying Kumpfer's resilience framework to understand the social adaptation process of the trailing parents in China.

BACKGROUND: Trailing parents, a distinct group emerging from China's rapid social change and urbanization, are experiencing migration in old age, posing challenges for their social adaptation. Existing research has mainly focused on the hardships faced by this group, but few studies have focused on how they cope with change and achieve some degree of successful social adaptation. This study aimed to understand the coping and social adaptation process of trailing parents in China. METHODS: This study used a qualitative research approach. A total of 24 trailing parents were invited to participate in a semi-structured interview and share their experiences and efforts to cope with the many challenges. Kumpfer's resilience framework was used as the theoretical framework for the study design, data collection, and data analysis. RESULTS: This study identified several intra-family and community stressors that trailing parents may face when moving to a new environment and uncovered five key resilience characteristics that may be triggered or fostered in the presence of these stressors, including physical fitness, psychological stability, open-mindedness, learning ability, and nurturing hobbies. Individuals with resilience traits have been observed to engage in positive cognitive processing and transform the new environment. Consistent with Kumpfer's resilience framework, this study revealed the dynamics of the stressors faced by trailing parents in the new environments, the role of resilience characteristics, and the critical influence of social support in shaping the interplay between the individual and the environment that enabled them to adapt positively. CONCLUSIONS: This study highlights the importance of fostering resilience traits and leveraging positive coping mechanisms to facilitate a smoother adaptation process for trailing parents. Meanwhile, there is an urgent need to focus on creating opportunities that strengthen their social support networks.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.

The Role and Mechanism of Ambra1-Mediated Mitophagy in TDCPP-Exposed Mouse Hippocampal Neurons.

Tri(1,3-dichloro-2-propyl)phosphate (TDCPP) is one of the most widely used organophosphorus flame retardants in consumer products. TDCPP has been confirmed to be neurotoxic, but its mechanism has not been clarified and may be related to mitophagy. AMBRA1 can promote neurological autophagy, but whether AMBRA1 is involved in the mechanism of TDCPP-induced neurotoxicity has not been elucidated. In this study, the optimal neuronal damage model was established by exposing mice hippocampal neurons to TDCPP. Furthermore, on the basis of this model, siRNA was used to knock down AMBRA1. Combined with qRT-PCR and Western blot techniques, we identified AMBRA1-mediated mitophagy-induced neuronal damage in vitro mechanism. The experimental results indicated that TDCPP treatment for 24 h led to a decrease in the cell viability of mouse hippocampal neurons, causing neuronal damage. Meanwhile, TDCPP exposure increased autophagy marker proteins p62 and LC3B, and down-regulated mitochondrial DNA ND1 damage and TOMM20 protein, suggesting that TDCPP exposure promoted mitophagy. In addition, TDCPP exposure led to changes in the expression of AMBRA1 and the key factors of mitophagy, FUNDC1, PINK1, and PARKIN, whereas mitophagy was inhibited after knockdown of AMBRA1. The research results indicated that exposure to TDCPP induced neuronal damage and promoted mitophagy. The mechanism may be that AMBRA1 promoted mitophagy in neuronal cells through the PARKIN-dependent/non-dependent pathway. This study revealed the toxic effects of TDCPP on the nervous system and its potential molecular mechanisms, which provided important clues for further understanding the mechanism of action of AMBAR1-mediated mitophagy.

Modulation of the gut microbiota by processed food and natural food: evidence from the Siniperca chuatsi microbiome.

Habitual dietary changes have the potential to induce alterations in the host's gut microbiota. Mandarin fish (Siniperca chuatsi), an aquatic vertebrate species with distinct feeding habits, were fed with natural feeds (NF) and artificial feeds (AF) to simulate the effects of natural and processed food consumption on host gut microbiota assemblages. The results showed that the alpha diversity index was reduced in the AF diet treatment, as lower abundance and diversity of the gut microbiota were observed, which could be attributed to the colonized microorganisms of the diet itself and the incorporation of plant-derived proteins or carbohydrates. The ß-diversity analysis indicated that the two dietary treatments were associated with distinct bacterial communities. The AF diet had a significantly higher abundance of Bacteroidota and a lower abundance of Actinomycetota, Acidobacteriota, and Chloroflexota compared to the NF group. In addition, Bacteroidota was the biomarker in the gut of mandarin fish from the AF treatment, while Acidobacteriota was distinguished in the NF treatments. Additionally, the increased abundance of Bacteroidota in the AF diet group contributed to the improved fermentation and nutrient assimilation, as supported by the metabolic functional prediction and transcriptome verification. Overall, the present work used the mandarin fish as a vertebrate model to uncover the effects of habitual dietary changes on the evolution of the host microbiota, which may provide potential insights for the substitution of natural foods by processed foods in mammals.

Hold the salt for kidney regeneration.

The macula densa (MD) is a distinct cluster of approximately 20 specialized kidney epithelial cells that constitute a key component of the juxtaglomerular apparatus. Unlike other renal tubular epithelial cell populations with functions relating to reclamation or secretion of electrolytes and solutes, the MD acts as a cell sensor, exerting homeostatic actions in response to sodium and chloride changes within the tubular fluid. Electrolyte flux through apical sodium transporters in MD cells triggers release of paracrine mediators, affecting blood pressure and glomerular hemodynamics. In this issue of the JCI, Gyarmati and authors explored a program of MD that resulted in activation of regeneration pathways. Notably, regeneration was triggered by feeding mice a low-salt diet. Furthermore, the MD cells showed neuron-like properties that may contribute to their regulation of glomerular structure and function. These findings suggest that dietary sodium restriction and/or targeting MD signaling might attenuate glomerular injury.