Effect of salting and dehydration treatments on the physicochemical and gel properties of hen and duck egg yolks, plasma and granules.

BACKGROUND: Salted hen egg yolks are less oily and less flavorful than salted duck egg yolks. However, hen eggs have a more adequate market supply and have a broader application prospect than duck eggs. In the present study, egg yolks, plasma, and granules were dehydrated by adding 1% NaCl to simulate traditional curing process of salted egg yolk. The changes in the pickling process of hen egg yolks (HEY) and duck egg yolks (DEY) plasma and granules were compared to reveal the gelation mechanism and the underlying causes of quality differences in salted HEY and DEY. Salted HEY can be compared with the changes in DEY during the pickling process to provide a theoretical basis for the quality improvement of salted HEY to salted DEY. RESULTS: The results showed that both plasma and granules were involved in gel formation, but exhibited different aggregation behaviors. Based on the intermolecular forces, the HEY proteins achieved aggregation mainly through hydrophobic interactions and DEY proteins mainly through covalent binding. According to spin-spin relaxation time, HEY gels immobilized a large amount of lipid and interacted strongly with lipids. DEY gels showed much free lipid and had weak interaction with lipid. The microstructure showed that HEY proteins were easily unfolded to form a homogeneous three-dimensional gel network structure after salting, whereas heterogeneous aggregates were formed to hinder the gel development in DEY. Changes in protein secondary structure content showed that pickling can promote the transformation of the α-helices to ß-sheets structure in HEY gels, whereas more α-helices structure was formed in DEY gels. CONCLUSION: The present study has demonstrated that different gelation behaviors of hen and duck egg yolk proteins (especially in plasma) through salting treatment led to the difference in the quality of salted HEY and DEY. © 2024 Society of Chemical Industry.

Omics analyses indicate sdhC/D act as hubs of early response of E. coli to antibiotics.

In recent years, the phenomenon of microbial resistance has become increasingly serious. The generation of reactive oxygen species (ROS) during the bactericidal process of antibiotics has attracted great interest, but little research has been done on the generation of ROS in the early stage of antibiotic action. We confirmed the rapid production of ROS by flow cytometry and transmission electron microscopy (TEM). GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis indicated that the oxidative phosphorylation pathway is the key pathway of ROS production. Protein-protein interaction (PPI) network results indicate that sdhC/D are key genes in the oxidative phosphorylation pathway. The overexpression of sdhC/D resulted in a lower survival rate than the control strain after antibiotic treatments, which might be due to excess ROS induced by sdhC/D overexpression. The production of superoxide anion in the overexpress strain was significantly higher than that in the control strain, which further verified the importance of sdhC/D in the ROS release of bacteria. Current results showed that bacteria produce large amounts of ROS in the early stage of gentamicin and ampicillin action, and the regulation patterns of genes in the key pathway were consistent. sdhC/D are key genes in the early ROS release process of bacteria. Our study provides a basis for the search of ROS-related enhancers of antimicrobial action.

Blood lead levels and their associated risk factors in Chinese adults from 1980 to 2018.

In China, studies on lead exposure to grownup are scarce compared to children, although relevant disease burdens for adults are much severe than that in developed countries. The present study evaluated blood lead levels (BLLs) in Chinese adults by data mining using Monte Carlo simulation. A total of 115 scientific studies published between January 1980 and March 2021 reflecting 45,514 Chinese adults were included in the study. After a continuous increase in Chinese adult BLLs from 1980-1983 (GM 74.84 µg/L) to 1994-1996 (GM 92.27 µg/L), BLLs began to decline from 2000--2002 (GM 80.32 µg/L) to 2016-2018 (GM 21.57 µg/L). This decline implied that the lead phase-out policy in gasoline was effective over the past two decades. The study indicated that North, South, and Southwest China were still relatively high compared to other regions in the past decade. Statistical analysis showed that BLLs of males (GM 68.45 µg/L) were higher than females (GM 56.51 µg/L), smokers (GM 80.96 µg/L) higher than nonsmokers (GM 58.95 µg/L), and populations over 40 (GM 40.43 µg/L) higher than younger populations (GM 40.37 µg/L). The significantly positive correlation between the concentrations of PM2.5 and topsoil lead and BLLs in Chinese adults indicated that air and soil pollution affect adult BLLs. Taken together, our results showed that strict lead control strategies and regular bio-monitoring are needed to maintain low BLLs in the population.

MicroRNA hsa-miR-1301-3p Regulates Human ADH6, ALDH5A1 and ALDH8A1 in the Ethanol-Acetaldehyde-Acetate Metabolic Pathway.

Alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) are vital enzymes involved in the metabolism of a variety of alcohols. Differences in the expression and enzymatic activity of human ADHs and ALDHs correlate with individual variability in metabolizing alcohols and drugs and in the susceptibility to alcoholic liver disease. MicroRNAs (miRNAs) function as epigenetic modulators to regulate the expression of drug-metabolizing enzymes. To characterize miRNAs that target ADHs and ALDHs in human liver cells, we carried out a systematic bioinformatics analysis to analyze free energies of the interaction between miRNAs and their cognate sequences in ADH and ALDH transcripts and then calculated expression correlations between miRNAs and their targeting ADH and ALDH genes using a public data base. Candidate miRNAs were selected to evaluate bioinformatic predictions using a series of biochemical assays. Our results showed that 11 miRNAs have the potential to modulate the expression of two ADH and seven ALDH genes in the human liver. We found that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and blocked their induction by ethanol. In summary, our results revealed that hsa-miR-1301-3p plays an important role in ethanol metabolism by regulating ADH and ALDH gene expression. SIGNIFICANCE STATEMENT: Systematic bioinformatics analysis showed that 11 microRNAs might play regulatory roles in the expression of two alcohol dehydrogenase (ADH) and seven aldehyde dehydrogenase (ALDH) genes in the human liver. Experimental evidences proved that hsa-miR-1301-3p suppressed the expression of ADH6, ALDH5A1, and ALDH8A1 in liver cells and decreased their inducibility by ethanol.

Assembling Defined DNA Nanostructure with Nitrogen-Enriched Carbon Dots for Theranostic Cancer Applications.

DNA nanostructures as scaffolds for drug delivery, biosensing, and bioimaging are hindered by its vulnerability in physiological settings, less favorable of incorporating arbitrary guest molecules and other desirable functionalities. Noncanonical self-assembly of DNA nanostructures with small molecules in an alternative system is an attractive strategy to expand their applications in multidisciplinary fields and is rarely explored. This work reports a nitrogen-enriched carbon dots (NCDs)-mediated DNA nanostructure self-assembly strategy. Given the excellent photoluminescence and photodynamic properties of NCDs, the obtained DNA/NCDs nanocomplex holds great potential for bioimaging and anticancer therapy. NCDs can mediate DNA nanoprism (NPNCD ) self-assembly isothermally at a large temperature and pH range in a magnesium-free manner. To explore the suitability of NPNCD in potential biomedical applications, the cytotoxicity and cellular uptake efficiency of NPNCD are evaluated. NPNCD with KRAS siRNA (NPNCD K) is further conjugated for KRAS-mutated nonsmall cell lung cancer therapy. The NPNCD K shows excellent gene knockdown efficiency and anticancer effect in vitro. The current study suggests that conjugating NCDs with programmable DNA nanostructures is a powerful strategy to endow DNA nanostructures with new functionalities, and NPNCD may be a potential theranostic platform with further fine-tuned properties of CDs such as near-red fluorescence or photothermal activities.

The impact of COPD and smoking history on the severity of COVID-19: A systemic review and meta-analysis.

Comorbidities are associated with the severity of coronavirus disease 2019 (COVID-19). This meta-analysis aimed to explore the risk of severe COVID-19 in patients with pre-existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history. A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases. The languages of literature included English and Chinese. The point prevalence of severe COVID-19 in patients with pre-existing COPD and those with ongoing smoking was evaluated with this meta-analysis. Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study. The pooled OR of COPD and the development of severe COVID-19 was 4.38 (fixed-effects model; 95% CI: 2.34-8.20), while the OR of ongoing smoking was 1.98 (fixed-effects model; 95% CI: 1.29-3.05). There was no publication bias as examined by the funnel plot and Egger's test (P = not significant). The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID-19. COPD and ongoing smoking history attribute to the worse progression and outcome of COVID-19.

Integration of proteomics, lipidomics, and metabolomics reveals novel metabolic mechanisms underlying N, N-dimethylformamide induced hepatotoxicity.

N, N-Dimethylformamide (DMF) is a universal organic solvent which widely used in various industries, and a considerable amount of DMF is detected in industrial effluents. Accumulating animal and epidemiological studies have identified liver injury as an early toxic effect of DMF exposure; however, the detailed mechanisms remain poorly understood. In this study, we systematically integrated the quantitative proteomics, lipidomics, and metabolomics data obtained from the primary human hepatocytes exposed to DMF, to depict the complicated biochemical reactions correlated to liver damage. Eventually, we identified 284 deregulated proteins (221 downregulated and 63 upregulated) and 149 deregulated lipids or metabolites (99 downregulated and 50 upregulated) induced by DMF exposure. Further, the integration of the protein-metabolite (lipid) interactions revealed that N-glycan biosynthesis (involved in the endoplasmic reticulum stress and the unfolded protein response), bile acid metabolism (involved in the lipid metabolism and the inflammatory process), and mitochondrial dysfunction and glutathione depletion (both contributed to reactive oxygen species) were the typical biochemical reactions disturbed by DMF exposure. In summary, our study identified the versatile protein, lipid, and metabolite molecules in multiple signaling and metabolic pathways involved in DMF induced liver injury, and provided new insights to elucidate the toxic mechanisms of DMF.

The malleability of executive function in early childhood: Effects of schooling and targeted training.

Executive function (EF), its importance for scholastic achievement and the question of whether or not EF is malleable, have become a topic of intense interest. Education or schooling is often seen as effective approaches to enhance EF due to the specific school-related requirements as compared to kindergarten or pre-school. However, no study to date has investigated whether targeted training focusing on those domains might be comparable with regular schooling in improving EF and fluid intelligence (Gf). The aim of the present study was to replicate and extend the previously demonstrated schooling effects on EF by using a school-cutoff design, and to further investigate whether a theoretically motivated intervention targeting specific EF, i.e., working memory (WM) or inhibitory control (IC), could achieve comparable effects with schooling in both, WM and IC, as well as Gf. 91 6-year-old kindergarteners and first-graders with similar chronological age participated the study. We compared the performance of a first-grade schooling group with that of two kindergarten training groups as well as a business-as-usual kindergarten control group. Participants were assessed in WM, IC and Gf at baseline, immediately after the intervention (posttest), as well as 3 months after training completion (follow-up). The results showed that the schooling group indeed outperformed the kindergarten groups at baseline in several cognitive tasks. Furthermore, both the WM and IC training showed pronounced gains in the trained tasks, as well as varying degrees of improvement in non-trained outcome measures. Most importantly, both training groups achieved comparable performance with the schooling group, which was especially apparent in Gf at follow-up. Our findings provide further evidence for the malleability of EF demonstrating that both, long-term and short-term interventions can facilitate the acquisition of those important skills, and as such, our work has important implications for educational practice.

Paeoniflorin suppresses TGF-ß mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway.

AIM: Paeoniflorin has shown to attenuate bleomycin-induced pulmonary fibrosis (PF) in mice. Because the epithelial-mesenchymal transition (EMT) in type 2 lung endothelial cells contributes to excessive fibroblasts and myofibroblasts during multiple fibrosis of tissues, we investigated the effects of paeoniflorin on TGF-ß mediated pulmonary EMT in bleomycin-induced PF mice. METHODS: PF was induced in mice by intratracheal instillation of bleomycin (5 mg/kg). The mice were orally treated with paeoniflorin or prednisone for 21 d. After the mice were sacrificed, lung tissues were collected for analysis. An in vitro EMT model was established in alveolar epithelial cells (A549 cells) incubated with TGF-ß1 (2 ng/mL). EMT identification and the expression of related proteins were performed using immunohistochemistry, transwell assay, ELISA, Western blot and RT-qPCR. RESULTS: In PF mice, paeoniflorin (50, 100 mg·kg(-1)·d(-1)) or prednisone (6 mg·kg(-1)·d(-1)) significantly decreased the expression of FSP-1 and α-SMA, and increased the expression of E-cadherin in lung tissues. In A549 cells, TGF-ß1 stimulation induced EMT, as shown by the changes in cell morphology, the increased cell migration, and the increased vimentin and α-SMA expression as well as type I and type III collagen levels, and by the decreased E-cadherin expression. In contrast, effects of paeoniflorin on EMT disappeared when the A549 cells were pretreated with TGF-ß1 for 24 h. TGF-ß1 stimulation markedly increased the expression of Snail and activated Smad2/3, Akt, ERK, JNK and p38 MAPK in A549 cells. Co-incubation with paeoniflorin (1-30 µmol/L) dose-dependently attenuated TGF-ß1-induced expression of Snail and activation of Smad2/3, but slightly affected TGF-ß1-induced activation of Akt, ERK, JNK and p38 MAPK. Moreover, paeoniflorin markedly increased Smad7 level, and decreased ALK5 level in A549 cells. CONCLUSION: Paeoniflorin suppresses the early stages of TGF-ß mediated EMT in alveolar epithelial cells, likely by decreasing the expression of the transcription factors Snail via a Smad-dependent pathway involving the up-regulation of Smad7.

Unique Optical Oxygen-Sensing Performance of [Ru(IP)2(HNAIP)](2+) during the Groove-Binding-Induced B-to-Z DNA Conformational Transition.

The oxygen-sensing performance of [Ru(IP)2(HNAIP)](2+) (Ru1, IP = imidazo[4,5-f][1,10]phenanthroline and HNAIP = 2-(2-hydroxy-1-naphthyl)imidazo [4,5-f][1,10]phenanthroline) in the presence of DNA conformational transition has been investigated by means of absorption spectroscopy, steady-state and time-resolved fluorescence spectroscopies, and circular dichroism spectroscopy. Ru1 shows a good linear response toward oxygen between pure nitrogen and pure oxygen with an on-off emission intensity ratio (I0/I100) of up to 9.3 via a dynamic quenching mechanism. Compared with [Ru(IP)2(DHPIP)](2+) (Ru2, DHPIP = 2-(2,4-dihydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline, I0/I100 = 5.8), the HNAIP ligand endows Ru1 with favorable oxygen binding sites to achieve larger energy and electron transfer rates. Simultaneously, Ru1 can induce the B-to-Z DNA conformational transition via a groove interaction with an intrinsic binding constant (K(b)) of 7.9 × 10(4) M(-1), whereas there is no same phenomenon for Ru2 intercalated into DNA (Kb = 3.3 × 10(5) M(-1)). Furthermore, the B-to-Z DNA conformational transition is interestingly found to decrease the Ru1-based oxygen-sensing rate by about 33%.

Association between dietary inflammatory index and risk of fatty liver disease: A systematic review and meta-analysis.

AIMS: This meta-analysis aimed to investigate the correlation between dietary inflammatory index (DII) and risks of fatty liver disease. METHODS: A comprehensive systematic literature search was conducted to select studies published from database inception to 6 September 2023 from five databases. Observational studies examining the association between elevated DII levels and the prevalence of fatty liver disease/liver fibrosis were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using either random-effects or fixed-effect models. RESULTS: In total, 10 studies comprising 242,006 participants were included in the meta-analysis. Individuals with higher DII had a significantly increased risk of fatty liver disease (OR 1.63; 95% CI 1.08-2.45) and liver fibrosis (OR 1.15; 95% CI 1.09-1.21) compared to those with lower DII. CONCLUSIONS: This meta-analysis demonstrated an association between higher DII and increased odds of fatty liver disease. However, additional prospective studies are required to further address this question.

The insulin-like growth factor binding protein-microfibrillar associated protein-sterol regulatory element binding protein axis regulates fibroblast-myofibroblast transition and cardiac fibrosis.

BACKGROUND AND PURPOSE: Excessive fibrogenesis is associated with adverse cardiac remodelling and heart failure. The myofibroblast, primarily derived from resident fibroblast, is the effector cell type in cardiac fibrosis. Megakaryocytic leukaemia 1 (MKL1) is considered the master regulator of fibroblast-myofibroblast transition (FMyT). The underlying transcriptional mechanism is not completely understood. Our goal was to identify novel transcriptional targets of MKL1 that might regulate FMyT and contribute to cardiac fibrosis. EXPERIMENTAL APPROACH: RNA sequencing (RNA-seq) performed in primary cardiac fibroblasts identified insulin-like growth factor binding protein 5 (IGFBP5) as one of the genes most significantly up-regulated by constitutively active (CA) MKL1 over-expression. IGFBP5 expression was detected in heart failure tissues using RT-qPCR and western blots. KEY RESULTS: Once activated, IGFBP5 translocated to the nucleus to elicit a pro-FMyT transcriptional programme. Consistently, IGFBP5 knockdown blocked FMyT in vitro and dampened cardiac fibrosis in mice. Of interest, IGFBP5 interacted with nuclear factor of activated T-cell 4 (NFAT4) to stimulate the transcription of microfibril-associated protein 5 (MFAP5). MFAP5 contributed to FMyT and cardiac fibrosis by enabling sterol response element binding protein 2 (SREBP2)-dependent cholesterol synthesis. CONCLUSIONS AND IMPLICATIONS: Our data unveil a previously unrecognized transcriptional cascade, initiated by IGFBP5, that promotes FMyT and cardiac fibrosis. Screening for small-molecule compounds that target this axis could yield potential therapeutics against adverse cardiac remodelling.

Studies on the Properties and Stability Mechanism of Double Emulsion Gels Prepared by Heat-Induced Aggregates of Egg White Protein-Oligosaccharides Glycosylation Products.

Multiple emulsions can dissolve some substances with different properties, such as hydrophilicity and lipophilicity, into different phases. They play an important role in protection, controlled release and targeted release of the encapsulated substances. However, it's poor stability has always been one of the main problems restricting its application in the food industry. For this reason, a heat-induced aggregate (HIA) of Maillard graft product of isomalto-oligosaccharides (IMO), as well as egg white protein (EWP), was used as hydrophilic emulsifier to improve the stability of W1/O/W2 emulsions. Moreover, gelatin was added into the internal aqueous phase (W1) to construct W1/O/W2 emulsion-gels system. The encapsulation efficiency of HIA-stabilized W1/O/W2 emulsions remained nearly unaltered, dropping by only 0.86%, significantly outperforming the conjugates and physical mixture of IMO and EWP in terms of encapsulation stability. The emulsion-gels system was constructed by adding 5% gelatin in the W1, and had the highest EE% and good salt and heat stability after 30 days of storage. This experiment provides guidance for improving the stability of W1/O/W2 emulsions system and its application in the package delivery of functional substances in the food field.

Spatio-temporal distribution of cadmium levels in Chinese population and its potential risk factors.

Cadmium (Cd), a ubiquitous heavy metal, exists in numerous environmental matrices and has severe adverse effects on various human organs and tissues. This research evaluates blood and urine Cd levels in the Chinese population through data mining using Monte Carlo simulation (MCS). A total of 168 scientific studies (120 on urine and 48 on blood) published between January 1980 and December 2020, reflecting a population of 109,743 individuals in China, were included in the study. The results indicate that the blood and urine Cd levels in the Chinese population exhibited a peak from 1990 to 1995 and remained stable after 1995, averaging 1.21 µg/L of blood Cd (BCd) and 0.61 µg/L of urine Cd (UCd). The spatial trend of Cd levels varied significantly. Shandong, Zhejiang, Heilongjiang, and Guangdong provinces were identified as the top provinces with high Cd levels, which were related to factors such as tobacco sales, E-waste amounts, and contaminated rice. Additionally, the study highlights that BCd concentrations are highest among preschool-aged individuals, whereas school-age and adolescent groups exhibit the lowest levels. However, no significant difference existed among the different age groups. Males showed significantly higher Cd levels than females in the general population. Moreover, exposure to smoking, drinking, and staple food preferences had an impact on Cd levels. Furthermore, this comprehensive study, using biological monitoring and data mining, provides valuable information on Cd pollution levels in the Chinese population. It presents a statistical analysis that can aid decision-makers in implementing effective measures to control potential Cd pollution and improve the health of vulnerable populations.

Re-examination of the genotoxic activity of water taken from the Songhua River in P. R. China.

The Songhua River, in northeast China, has heavy organic contamination due to domestic sewage and industrial wastewater. Thus, it is important to further determine its genotoxic activity, which is a potential hazard for human health. Short-term genotoxic bioassays using Salmonella, the cytokinesis-block micronucleus cytome assay, and mouse liver cell comet assay were employed to further examine the genotoxic activity of diethyl ether extracts of water samples taken from the Songhua River. Ames test results showed that there were still frame-shift mutagens, both direct and indirect, in water samples at doses of 5.0 or 7.0 L water equivalent/plate. The mutagenicity seems to be less when compared with the results from 2002 to 2003. A dose-response relationship was also obtained between DNA damage in mouse liver cells by comet assay and micronuclei formation by CBMN assay. These results indicate that the water samples showed genotoxic activity with a mutagenic potency. 88 and 104 compounds, respectively, were identified in summer and winter water sample extracts by gas chromatography-mass spectrometry analysis. Four priority pollutants listed by the United States Environmental Protection Agency and six priority pollutants listed by the Chinese Environment Protection Agency were found in summer or winter water samples, respectively. The results indicate that the diethyl ether extracts of surface water samples taken from the Songhua River still show genotoxic activity (≥3.0 L water). The risks of potential carcinogenicity for human health in the Songhua River should be studied further.

The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression.

Currently, cancer has become one of the major public health problems worldwide. Apoptosis is an important anti-cancer defense mechanism, which is used in the development of targeted drugs. Because cancer cells have endogenous resistance to apoptosis,the clinical efficacy of related drugs is not ideal. Therefore, non-apoptotic regulatory cell death may bring new therapeutic strategies for cancer treatment. Cuproptosis is a novel form of regulatory cell death which is copper-dependent, regulated and distinct from other known cell death regulatory mechanisms. FDX1,LIAS,and DLAT named cuproptosis-related genes play an essential role in regulating cuproptosis. Meanwhile, abnormal accumulation of copper can be observed in various malignant tumors. The correlation has been established between elevated copper levels in serum and tissues and the progression of several cancers. Copper transporters, CTR1 and Copper-transporting ATPases(ATP7A and ATP7B), are mainly involved in regulating the dynamic balance of copper concentration to maintain copper homeostasis. Thus,cuproptosis-related genes and copper transporters will be the focus of cancer research in future. This review elaborated the basic functions of cuproptosis-related genes and copper transporters by retrievalling PubMed. And then we analyzed their potential relationship with cancer aiming to provide theoretical support and reference in cancer progression, diagnosis and treatment for future study.

Metabolic associated fatty liver disease and sarcopenia additively increase mortality: a real-world study.

BACKGROUND AND AIMS: Sarcopenia is associated with worse prognosis for non-alcoholic fatty liver disease (NAFLD). However, disease progression in the MAFLD-related sarcopenia is largely unknown. We aimed to clarify the relationship between MAFLD and/or sarcopenia with mortality and liver fibrosis in the real world. METHODS: A total of 13,692 individuals were selected from the third National Health and Nutrition Examination Surveys and linked mortality until December 2019. MAFLD is diagnosed based on a radiologically diagnosed hepatic steatosis and the presence of any one of the following three conditions: overweight/obesity, diabetes mellitus (DM), or metabolic dysregulation. Sarcopenia is defined by weight-adjusted skeletal muscle mass. RESULTS: The mean age was 43.7 ± 15.97 years, and 47.3% of the individuals were male. MAFLD was diagnosed in 4207/13,692 (30.73%) participants, and the proportion of sarcopenic was 19.42% amongst subjects with MAFLD. The mean follow-up duration was of 23.7 ± 7.62 years. MAFLD (aHR 1.152, 95% CI 1.070-1.241) and sarcopenia (aHR 1.123, 95% CI 1.042-1.210) were related to increased all-cause mortality in MAFLD after adjustment for age, sex, race, marital status, education, and smoking. Stratified analysis revealed that MAFLD and sarcopenia additively increased the risk of mortality (aHR 1.247, 95% CI 1.132-1.373) and liver fibrosis (aOR 2.296, 95% CI 1.718-3.069 assessed by NFS score >0.676; aOR 2.218, 95% CI 1.788-2.752 assessed by FIB-4 score >1.3) in fully adjusted models (P < 0.001 for all). CONCLUSION: Sarcopenia in individuals with MAFLD portends increased mortality and significant liver fibrosis. Novel therapeutic strategies targeting at increasing skeletal muscle mass should be explored for patients with MAFLD.

An adhesion-based method for rapid and low-cost isolation of circulating tumor cells.

BACKGROUND: Noninvasive monitoring of cancer through circulating tumor cells (CTCs) is hampered long by unsatisfactory CTCs testing techniques. Efficient isolation of CTCs in a rapid and price-favorable way from billions of leukocytes is crucial for testing. METHODS: We developed a new method based on the stronger adhesive power of CTCs versus leukocytes to sensitively isolate CTCs. Using a BSA-coated microplate and low-speed centrifuge, this method could easily separate cancer cells within 20 min at a very low cost. RESULT: The capture ratio can reach 70.7-86.6% in various cancer cell lines (breast/lung/liver/cervical/colorectal cancer) covering different epithelial-mesenchymal transformation (EMT) phenotypes and cell sizes, demonstrating the potential for efficient pan-cancer CTCs detection. Moreover, the label-free process can well preserve cell viability (∼99%) to fit downstream DNA/RNA sequencing. CONCLUSIONS: A novel technique for non-destructive and rapid enrichment of CTCs has been devised. It has enabled the successful isolation of rare tumor cells in the patient blood sample and pleural effusion, highlighting a promising future of this method in clinical translation.

An MRTF-A-ZEB1-IRF9 axis contributes to fibroblast-myofibroblast transition and renal fibrosis.

Myofibroblasts, characterized by the expression of the matricellular protein periostin (Postn), mediate the profibrogenic response during tissue repair and remodeling. Previous studies have demonstrated that systemic deficiency in myocardin-related transcription factor A (MRTF-A) attenuates renal fibrosis in mice. In the present study, we investigated the myofibroblast-specific role of MRTF-A in renal fibrosis and the underlying mechanism. We report that myofibroblast-specific deletion of MRTF-A, achieved through crossbreeding Mrtfa-flox mice with Postn-CreERT2 mice, led to amelioration of renal fibrosis. RNA-seq identified zinc finger E-Box binding homeobox 1 (Zeb1) as a downstream target of MRTF-A in renal fibroblasts. MRTF-A interacts with TEA domain transcription factor 1 (TEAD1) to bind to the Zeb1 promoter and activate Zeb1 transcription. Zeb1 knockdown retarded the fibroblast-myofibroblast transition (FMyT) in vitro and dampened renal fibrosis in mice. Transcriptomic assays showed that Zeb1 might contribute to FMyT by repressing the transcription of interferon regulatory factor 9 (IRF9). IRF9 knockdown overcame the effect of Zeb1 depletion and promoted FMyT, whereas IRF9 overexpression antagonized TGF-ß-induced FMyT. In conclusion, our data unveil a novel MRTF-A-Zeb1-IRF9 axis that can potentially contribute to fibroblast-myofibroblast transition and renal fibrosis. Screening for small-molecule compounds that target this axis may yield therapeutic options for the mollification of renal fibrosis.