High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host-phage activity associations in human gut microbiome.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications in health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve comprehensive understanding of complex microbial communities together with their hosts is therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive responses states among species in Prevotella and Roseburia genus and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated the smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-word situations and promises new perspectives in the understanding of human microbiomes.

Bimetallic MOFs-Derived NiFe2O4/Fe2O3 Enabled Dendrite-free Lithium Metal Anodes with Ultra-High Area Capacity Based on An Intermittent Lithium Deposition Model.

In practical operating conditions, the lithium deposition behavior is often influenced by multiple coupled factors and there is also a lack of comprehensive and long-term validation for dendrite suppression strategies. Our group previously proposed an intermittent lithiophilic model for high-performance three-dimensional (3D) composite lithium metal anode (LMA), however, the electrodeposition behavior was not discussed. To verify this model, this paper presents a modified 3D carbon cloth (CC) backbone by incorporating NiFe2O4/Fe2O3 (NFFO) nanoparticles derived from bimetallic NiFe-MOFs. Enhanced Li adsorption capacity and lithiophilic modulation were achieved by bimetallic MOFs-derivatives which prompted faster and more homogeneous Li deposition. The intermittent model was further verified in conjunction with the density functional theory (DFT) calculations and electrodeposition behaviors. As a result, the obtained Li-CC@NFFO||Li-CC@NFFO symmetric batteries exhibit prolonged lifespan and low hysteresis voltage even under ultra-high current and capacity conditions (5 mA cm-2, 10 mAh cm-2), what's more, the full battery coupled with a high mass loading (9 mg cm-2) of LiFePO4 cathode can be cycled at a high rate of 5C, the capacity retention is up to 95.2% before 700 cycles. This work is of great significance to understand the evolution of lithium dendrites on the 3D intermittent lithiophilic frameworks.

Van der Waals Transition Metal Carbo-Chalcogenides: Theoretical Screening and Charge Storage.

High-rate lithium/sodium ion batteries or capacitors are the most promising functional units to achieve fast energy storage that highly depends on charge host materials. Host materials with lamellar structures are a good choice for hybrid charge storage hosts (capacitor or redox type). Emerging layered transition metal carbo-chalcogenides (TMCC) with homogeneous sulfur termination are especially attractive for charge storage. Using density functional theory calculations, six of 30 potential TMCC are screened to be stable, metallic, anisotropic in electronic conduction and mechanical properties due to the lamellar structures. Raman, infrared active modes and frequencies of the six TMCC are well assigned. Interlayer coupling, especially binding energies predict that the bulk layered materials can be easily exfoliated into 2D monolayers. Moreover, Ti2S2C, Zr2S2C are identified as the most gifted Li+/Na+ anode materials with relatively high capacities, moderate volume expansion, relatively low Li+/Na+ migration barriers for batteries or ion-hybrid capacitors. This work provides a foundation for rational materials design, synthesis, and identification of the emerging 2D family of TMCC.

On the role of asymmetric molecular geometry in high-performance organic solar cells.

Although asymmetric molecular design has been widely demonstrated effective for organic photovoltaics (OPVs), the correlation between asymmetric molecular geometry and their optoelectronic properties is still unclear. To access this issue, we have designed and synthesized several symmetric-asymmetric non-fullerene acceptors (NFAs) pairs with identical physical and optoelectronic properties. Interestingly, we found that the asymmetric NFAs universally exhibited increased open-circuit voltage compared to their symmetric counterparts, due to the reduced non-radiative charge recombination. From our molecular-dynamic simulations, the asymmetric NFA naturally exhibits more diverse molecular interaction patterns at the donor (D):acceptor (A) interface as compared to the symmetric ones, as well as higher D:A interfacial charge-transfer state energy. Moreover, it is observed that the asymmetric structure can effectively suppress triplet state formation. These advantages enable a best efficiency of 18.80%, which is one of the champion results among binary OPVs. Therefore, this work unambiguously demonstrates the unique advantage of asymmetric molecular geometry, unveils the underlying mechanism, and highlights the manipulation of D:A interface as an important consideration for future molecular design.

Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii.

Ribose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis; however, the importance and homeostasis of R5P in the intracellular parasite Toxoplasma gondii remain enigmatic. Here, we show that the cytoplasmic sedoheptulose-1,7-bisphosphatase (SBPase) is dispensable. Still, its co-deletion with transaldolase (TAL) impairs the double mutant's growth and increases 13C-glucose-derived flux into pentose sugars via the transketolase (TKT) enzyme. Deletion of the latter protein affects the parasite's fitness but is not lethal and is correlated with an increased carbon flux via the oxidative pentose phosphate pathway. Further, loss of TKT leads to a decline in 13C incorporation into glycolysis and the TCA cycle, resulting in a decrease in ATP levels and the inability of phosphoribosyl-pyrophosphate synthetase (PRPS) to convert R5P into 5'-phosphoribosyl-pyrophosphate and thereby contribute to the production of AMP and IMP. Likewise, PRPS is essential for the lytic cycle. Not least, we show that RuPE-mediated metabolic compensation is imperative for the survival of the ΔsbpaseΔtal strain. In conclusion, we demonstrate that multiple routes can flexibly supply R5P to enable parasite growth and identify catalysis by TKT and PRPS as critical enzymatic steps. Our work provides novel biological and therapeutic insights into the network design principles of intracellular parasitism in a clinically-relevant pathogen.

A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury.

Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.

Protein Allostery Study in Cells Using NMR Spectroscopy.

Protein allostery is commonly observed in vitro. But how protein allostery behaves in cells is unknown. In this work, a protein monomer-dimer equilibrium system was built with the allosteric effect on the binding characterized using NMR spectroscopy through mutations away from the dimer interface. A chemical shift linear fitting method was developed that enabled us to accurately determine the dissociation constant. A total of 28 allosteric mutations were prepared and grouped to negative allosteric, nonallosteric, and positive allosteric modulators. ∼ 50% of mutations displayed the allosteric-state changes when moving from a buffered solution into cells. For example, there were no positive allosteric modulators in the buffered solution but eight in cells. The change in protein allostery is correlated with the interactions between the protein and the cellular environment. These interactions presumably drive the surrounding macromolecules in cells to transiently bind to the monomer and dimer mutational sites and change the free energies of the two species differently which generate new allosteric effects. These surrounding macromolecules create a new protein allostery pathway that is only present in cells.

The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection.

During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.

Defining a TFAP2C-centered transcription factor network during murine peri-implantation.

Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.

Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification.

Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c's function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.

Acetylated KHSRP impairs DNA-damage-response-related mRNA decay and facilitates prostate cancer tumorigenesis.

Androgen-regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone-sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)-homology splicing regulatory protein known as far upstream element-binding protein 2 (KHSRP) is an RNA-binding protein that can attach to AU-rich elements in the 3' untranslated region (3'-UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen-regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP-regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA-seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD-dependent protein deacetylase sirtuin-7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP-regulated mRNA decay of the DDR-related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration-resistant PCa.

Correlational analysis of PLIN1 with inflammation in diabetic foot ulcer wounds.

BACKGROUND: The persistent presence of inflammation is a recognized pathogenic mechanisms of diabetic foot ulcers (DFUs). We aimed to investigate the expression of PLIN1 in tissues from DFU patients and assess its potential association with inflammation-induced damage. METHODS: We performed transcriptome sequencing and correlation analysis of the foot skin from patients with or without DFUs. Additionally, we examined the correlation between PLIN1 and related inflammatory indicators by analyzing PLIN1 expression in tissue and serum samples and through high-glucose stimulation of keratinocytes (HaCaT cells). RESULTS: PLIN1 is upregulated in the tissue and serum from DFU patients. Additionally, PLIN1 shows a positive correlation with leukocytes, neutrophils, monocytes, C-reactive protein, and procalcitonin in the serum, as well as IL-1ß and TNF-α in the tissues. Experiments with Cells demonstrated that reduced expression of PLIN1 leads to significantly decreased expression of iNOS, IL-1ß, IL-6, IL-18, and TNF-α. PLIN1 may mediate wound inflammatory damage through the NF-κB signaling pathway. CONCLUSION: Our findings suggest that PLIN1 mediates the inflammatory damage in DFU, offering new prospects for the treatment of DFU.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins inhibit intestinal glucose transport in human Caco-2 cells.

Background: The hypoglycemic effects of Chinese bayberry leaves proanthocyanidins (BLPs) have been demonstrated. It is unclear, nevertheless, whether BLPs reduced postprandial blood glucose levels by regulating glucose uptake and glucose transport. Method: This study investigated the effect of BLPs (25, 50, and 100 µg/mL) on glucose uptake and glucose transport in human intestinal epithelial cells (Caco-2 cells). The uptake of 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) and disaccharidases activity in Caco-2 cells were measured. The glucose transport ability across the cell membrane was determined using the established Caco-2 monolayer model. The transcript and protein levels of key glucose transporters were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Results: The results showed that BLPs significantly decreased glucose uptake and disaccharidases activity (p < 0.05). Otherwise, BLPs treatment obviously inhibited glucose transport across the Caco-2 monolayer in both simulated-fast (5 mM glucose) and simulated-fed (25 mM glucose) conditions. It was attributed to the suppression of glucose transporter2 (GLUT2) and sodium-dependent glucose cotransporter 1 (SGLT1) by BLPs. BLPs were found to significantly downregulated the transcript level and protein expression of glucose transporters (p < 0.05). Meanwhile, the mRNA expression of phospholipase C (PLC) and protein kinase C (PKC) involved in the signaling pathway associated with glucose transport were decreased by BLPs. Conclusion: These results suggested that BLPs inhibited intestinal glucose transport via inhibiting the expression of glucose transporters. It indicated that BLPs could be potentially used as a functional food in the diet to modulate postprandial hyperglycemia.

Postbiotics from Lactobacillus delbrueckii Alleviate Intestinal Inflammation by Promoting the Expansion of Intestinal Stem Cells in S. Typhimurium-Induced Mice.

Previous studies have demonstrated that L. delbrueckii plays beneficial roles in modulating the gut microbiota, enhancing the intestinal barrier, and promoting animal growth. Postbiotics have a similar or even superior effect in protecting intestinal health compared to probiotics due to their excellent stability, extended shelf life, and safety. However, the protective effects and underlying mechanism of postbiotics from L. delbrueckii in intestinal inflammation remain unclear. In this study, we demonstrated the beneficial impact of postbiotics from L. delbrueckii on intestinal health by establishing a S. Typhimurium-induced intestinal inflammation model in mice, which included inactivated bacteria and supernatant. The results revealed that the probiotics and postbiotics from L. delbrueckii increased the survival rate and body weight of S. Typhimurium-induced mice, increased the level of IL-10, and decreased the levels of TNF-α and IL-6, thereby alleviating intestinal inflammation. Meanwhile, treatment with postbiotics decreased the levels of D-LA, DAO, and LPS and promoted the expression of Occludin, ZO-1, and Claudin-1 in the serum and jejunum, suggesting an improvement in intestinal barrier function by postbiotics. Additionally, the postbiotics modulated gut microbial diversity, increased the ratio of Firmicutes and Bacteroidetes, and restored the abundance of Muribaculaceae, Lachnospiraceae_NK4a136_groups, and Alloprevotella in S. Typhimurium-infected mice. Moreover, postbiotics from L. delbrueckii promoted the expansion of intestinal stem cells (ISCs) and increased the numbers of Paneth and Goblet cells. Taken together, these data revealed the beneficial role of postbiotics from L. delbrueckii in protecting against intestinal inflammation by promoting the expansion of ISCs.

Local Chemical Environment Dependent Nitrate-Reduction-to-Ammonia Performance on Cu-Based Electrocatalysts.

The active component of copper-based materials for electrocatalytic nitrate reduction to ammonia (NRA) remains unclear due to the susceptibility of oxidation of copper. Using density functional theory calculations, NRA pathways are evaluated on low-index crystal surfaces Cu2O (111), CuO (111), and Cu (111) at different pH. Cu2O (111), with abundant undercoordinated Cu atoms on the surface, shows easier adsorption of NO3- than Cu (111) or CuO (111). NRA on CuO (111) is hindered by the large ΔG of adsorption of NO3- and hydrogenation of *NO. Thus, Cu (111) and Cu2O (111) contribute most to the NRA activity while CuO (111) is inert. Three key steps of NRA on copper-based catalysts are identified: adsorption of NO3-, *NO → *NOH/*NHO, and *NH3 desorption, as the three can be rate-determining steps depending on the local environment. Moreover, previous experimentally detected NH2OH on copper-based catalysts may come from the NRA on Cu2O (111) as the most probable pathway on Cu2O (111) is NO3- → *NO3 → *NO2 → *NO → *NHO → *NHOH → *NH2OH → *NH2 → *NH3 → *NH3(g). At high reduction potential, CuOx would be reduced into Cu, so the effective active substance for NRA in a strong reduction environment is Cu.

Self-Assembled Interlayer Enables High-Performance Organic Photovoltaics with Power Conversion Efficiency Exceeding 20.

Interfacial layers (ILs) are prerequisites to form the selective charge transport for high-performance organic photovoltaics (OPVs) but mostly result in considerable parasitic absorption loss. Trimming the ILs down to a mono-molecular level via the self-assembled monolayer is an effective strategy to mitigate parasitic absorption loss. However, such a strategy suffers from inferior electrical contact with low surface coverage on rough surfaces and poor producibility. To address these issues, here, the self-assembled interlayer (SAI) strategy is developed, which involves a thin layer of 2-6 nm to form a full coverage on the substrate via both covalent and van der Waals bonds by using a self-assembled molecule of 2-(9H-carbazol-9-yl) (2PACz). Via the facile spin coating without further rinsing and annealing process, it not only optimizes the electrical and optical properties of OPVs, which enables a world-record efficiency of 20.17% (19.79% certified) but also simplifies the tedious processing procedure. Moreover, the SAI strategy is especially useful in improving the absorbing selectivity for semi-transparent OPVs, which enables a record light utilization efficiency of 5.34%. This work provides an effective strategy of SAI to optimize the optical and electrical properties of OPVs for high-performance and solar window applications.

Petaloid bimetallic metal-organic frameworks derived ZnCo2O4/ZnO nanosheets enabled intermittent lithiophilic model for dendrite-free lithium metal anode.

The application of lithium metal anode (LMA) is hindered by its poor cycle life which could be caused by lithium dendrite and critical volume change during cycling. Our group previously proposed an intermittent lithiophilic model for three-dimensional (3D) composite LMA, however, the lithium electrodeposition behavior was not discussed. To verify this model, this work proposed a facile design of a petaloid bimetallic metal-organic frameworks (MOFs) derived ZnCo2O4/ZnO (ZZCO) nanosheets modified carbon cloth (CC), i.e. CC@ZZCO, as a 3D host to achieve the intermittent deposition of lithium (Li). The material characterizations, density functional theory (DFT) calculations, lithium electrodeposition behaviors, and the electrochemical tests were investigated and the intermittent lithium deposition behavior was firstly confirmed. Thanks to the intermittent lithiophilic model, the composite LMA enabled a prolonged lifespan of 1500 h in a symmetrical cell under challenging conditions of 5 mA h cm-2 and 5 mA cm-2, and can maintain stable at 10C with an ultrahigh specific capacity of 110 mAh/g. Furthermore, it can also be coupled with a LiNi0.5Co0.2Mn0.3O2 (NCM523) and a high surface load of LiFePO4 (LFP) cathode (11.5 mg cm-2). This research might open a window for the understanding of the Li deposition behavior and pave the way to develop other alkali-metal-ion batteries.

Relationships between Size-specific Dose Estimate and Signal to Noise Ratio under Chest CT Examinations with Tube Current Modulation.

PURPOSE: Exploring the relationship between the signal-to-noise ratio (SNR) of organs and size-specific dose estimate (SSDE) in tube current modulation (TCM) chest CT examination. METHODS: Forty patients who received TCM chest CT scanning were retrospectively collected and divided into four groups according to the tube voltage and sexes. We chose to set up the region of interest (ROI) at the tracheal bifurcation and its upper and lower parts in slice images of the heart, aorta, lungs, paracranial muscles, and female breast, and the SNR of each organ was calculated. We also calculated the corresponding axial volume CT dose index (CTDIvolz) and axial size-specific dose estimate (SSDEz). RESULTS: The correlation analysis showed that the correlation between the SNR of the slice images of most organs and SSDEz was more significant than 0.8, and that between the SNR and CTDIvol was more significant than 0.7. The simple linear regression analysis results showed that when the sex is the same, the SNR of the same organ at 100kVp was higher than 120kVp, except for the lung. In multiple regression analysis, the result indicated that the determination coefficients of the SNR and SSDEz of the four groups were 0.934, 0.971, 0.905, and 0.709, respectively. CONCLUSION: In chest CT examinations with TCM, the correlation between the SNR of each organ in slice images and SSDEz was better than that of CTDIvolz. And when the SSDEz was the same, the SNR at 100 kVp was better than that at 120 kVp.

Corin deficiency alleviates mucosal lesions in a mouse model of colitis induced by dextran sulfate sodium.

AIMS: High dietary salt consumption is a risk factor for inflammatory bowel disease (IBD). Corin is a protease that activates atrial natriuretic peptide (ANP), thereby regulating sodium homeostasis. Corin acts in multiple tissues, including the intestine. In mice, corin deficiency impairs intestinal sodium excretion. This study aims to examine if reduced intestinal sodium excretion alters the pathophysiology of IBD. MAIN METHODS: Wild-type (WT), Corin knockout (KO), and Corin kidney conditional KO (kcKO) mice were tested in a colitis model induced by dextran sulfide sodium (DSS). Effects of ANP on DSS-induced colitis were tested in WT and Corin KO mice. Body weight changes in the mice were monitored. Necropsy, histological analysis, and immunostaining studies were conducted to examine colon length and mucosal lesions. Fecal sodium levels were measured. RT-PCR was done to analyze proinflammatory genes in colon samples. KEY FINDINGS: DSS-treated Corin KO mice had an ameliorated colitis phenotype with less body weight loss, longer colon lengths, smaller mucosal lesions, lower disease scores, more preserved goblet cells, and suppressed proinflammatory genes in the colon. In longitudinal studies, the DSS-treated Corin KO mice had delayed onset of colon mucosal lesions. ANP administration lessened the colitis in WT, but not Corin KO, mice. Analyses of WT, Corin KO, and Corin kcKO mice indicated that fecal sodium excretion, controlled by intestinal corin, may regulate inflammatory responses in DSS-induced colitis in mice. SIGNIFICANCE: Our findings indicate a role of corin in intestinal pathophysiology, suggesting that reduced intestinal sodium level may offer protective benefits against IBD.