Targeting CD73 with flavonoids inhibits cancer stem cells and increases lymphocyte infiltration in a triple-negative breast cancer mouse model.

Introduction: Chemotherapy remains the mainstay treatment for triple-negative breast cancer (TNBC) due to the lack of specific targets. Given a modest response of immune checkpoint inhibitors in TNBC patients, improving immunotherapy is an urgent and crucial task in this field. CD73 has emerged as a novel immunotherapeutic target, given its elevated expression on tumor, stromal, and specific immune cells, and its established role in inhibiting anti-cancer immunity. CD73-generated adenosine suppresses immunity by attenuating tumor-infiltrating T- and NK-cell activation, while amplifying regulatory T cell activation. Chemotherapy often leads to increased CD73 expression and activity, further suppressing anti-tumor immunity. While debulking the tumor mass, chemotherapy also enriches heterogenous cancer stem cells (CSC), potentially leading to tumor relapse. Therefore, drugs targeting both CD73, and CSCs hold promise for enhancing chemotherapy efficacy, overcoming treatment resistance, and improving clinical outcomes. However, safe and effective inhibitors of CD73 have not been developed as of now. Methods: We used in silico docking to screen compounds that may be repurposed for inhibiting CD73. The efficacy of these compounds was investigated through flow cytometry, RT-qPCR, CD73 activity, cell viability, tumorsphere formation, and other in vitro functional assays. For assessment of clinical translatability, TNBC patient-derived xenograft organotypic cultures were utilized. We also employed the ovalbumin-expressing AT3 TNBC mouse model to evaluate tumor-specific lymphocyte responses. Results: We identified quercetin and luteolin, currently used as over-the-counter supplements, to have high in silico complementarity with CD73. When quercetin and luteolin were combined with the chemotherapeutic paclitaxel in a triple-drug regimen, we found an effective downregulation in paclitaxel-enhanced CD73 and CSC-promoting pathways YAP and Wnt. We found that CD73 expression was required for the maintenance of CD44highCD24low CSCs, and co-targeting CD73, YAP, and Wnt effectively suppressed the growth of human TNBC cell lines and patient-derived xenograft organotypic cultures. Furthermore, triple-drug combination inhibited paclitaxel-enriched CSCs and simultaneously improved lymphocyte infiltration in syngeneic TNBC mouse tumors. Discussion: Conclusively, our findings elucidate the significance of CSCs in impairing anti-tumor immunity. The high efficacy of our triple-drug regimen in clinically relevant platforms not only underscores the importance for further mechanistic investigations but also paves the way for potential development of new, safe, and cost-effective therapeutic strategies for TNBC.

Crab microRNA-381-5p regulates prophenoloxidase activation and phagocytosis to promote intracellular bacteria Spiroplasma eriocheiris infection by targeting mannose-binding protein.

Mannose-binding lectin plays an essential role in bacteria or virus-triggered immune response in mammals. Previous proteomic data revealed that in Eriocheir sinensis, the mannose-binding protein was differentially expressed after Spiroplasma eriocheiris infection. However, the function of mannose-binding protein against pathogen infection in invertebrates is poorly understood. In this study, a crab mannose-binding protein (EsMBP) was characterized and enhanced the host resistance to S. eriocheiris infection. The application of recombinant C-type carbohydrate recognition domain (CTLD) of EsMBP led to increased crab survival and decreased S. eriocheiris load in hemocytes. Meanwhile, the overexpression of CTLD of EsMBP in Raw264.7 cells inhibited S. eriocheiris intracellular replication. In contrast, depletion of EsMBP by RNA interference or antibody neutralization attenuated phenoloxidase activity and hemocyte phagocytosis, rendering host more susceptible to S. eriocheiris infection. Furthermore, miR-381-5p in hemocytes suppressed EsMBP expression and negatively regulated phenoloxidase activity to exacerbate S. eriocheiris invasion of hemocytes. Taken together, our findings revealed that crab mannose-binding protein was involved in host defense against S. eriocheiris infection and targeted by miR-381-5p, providing further insights into the control of S. eriocheiris spread in crabs.

Exposure to nanopolystyrene and phoxim at ambient concentrations causes oxidative stress and inflammation in the intestines of the Chinese mitten crab (Eriocheir sinensis).

Nanopolystyrene (NP) and phoxim (PHO) are common environmental pollutants in aquatic systems. We evaluated the toxic effects of exposure to ambient concentrations of NP and/or PHO in the intestines of the Chinese mitten crab (Eriocheir sinensis). Our study showed that histopathological changes were observed in the intestines. Specifically, NP and/or PHO exposure increased intraepithelial lymphocytes. Furthermore, NP and/or PHO exposure induced oxidative stress, as evidenced by a significant decrease in superoxide dismutase activity (SOD), peroxidase activity (POD), and total antioxidant capacity (T-AOC). Pro-inflammatory gene expression and transcriptome analysis demonstrated that NP and/or PHO exposure induced the intestinal inflammatory response. Transcriptome results showed that NP and/or PHO exposure upregulated the NF-κB signaling pathway, which is considered a key pathway in the inflammatory response. Additionally, the expression of pro-inflammatory genes significantly increased after a single exposure to NP or PHO, but it exhibited a significant decrease after the co-exposure. The downregulation of these genes in the co-exposure group likely suggested that the co-exposure mitigated intestinal inflammation response in E. sinensis. Collectively, our findings mainly showed that NP and/or PHO exposure at ambient concentrations induces oxidative stress and inflammatory response in the intestines of E. sinensis.

Toward Predicting Interfacial Tension of Impure and Pure CO2-Brine Systems Using Robust Correlative Approaches.

In the context of global climate change, significant attention is being directed toward renewable energy and the pivotal role of carbon capture and storage (CCS) technologies. These innovations involve secure CO2 storage in deep saline aquifers through structural and capillary processes, with the interfacial tension (IFT) of the CO2-brine system influencing the storage capacity of formations. In this study, an extensive data set of 2811 experimental data points was compiled to model the IFT of impure and pure CO2-brine systems. Three white-box machine learning (ML) methods, namely, genetic programming (GP), gene expression programming (GEP), and group method of data handling (GMDH) were employed to establish accurate mathematical correlations. Notably, the study utilized two distinct modeling approaches: one focused on impurity compositions and the other incorporating a pseudocritical temperature variable (Tcm) offering a versatile predictive tool suitable for various gas mixtures. Among the correlation methods explored, GMDH, employing five inputs, exhibited exceptional accuracy and reliability across all metrics. Its mean absolute percentage error (MAPE) values for testing, training, and complete data sets stood at 7.63, 7.31, and 7.38%, respectively. In the case of six-input models, the GEP correlation displayed the highest precision, with MAPE values of 9.30, 8.06, and 8.31% for the testing, training, and total data sets, respectively. The sensitivity and trend analyses revealed that pressure exerted the most significant impact on the IFT of CO2-brine, showcasing an adverse effect. Moreover, an impurity possessing a critical temperature below that of CO2 resulted in an elevated IFT. Consequently, this relationship leads to higher impurity concentrations aligning with lower Tcm values and subsequently elevated IFT. Also, monovalent and divalent cation molalities exhibited a growing influence on the IFT, with divalent cations exerting approximately double the influence of monovalent cations. Finally, the Leverage approach confirmed both the reliability of the experimental data and the robust statistical validity of the best correlations established in this study.

Identification of Six Pathogenic Genes for Tibetan Familial Ventricular Septal Defect by Whole Exome Sequencing.

INTRODUCTION: Ventricular septal defect (VSD) is the most common congenital heart malformation in children. This study aimed to investigate potential pathogenic genes associated with Tibetan familial VSD. METHODS: Whole genomic DNA was extracted from eight Tibetan children with VSD and their healthy parents (a total of 16 individuals). Whole-exome sequencing was performed using the Illumina HiSeq platform. After filtration, detection, and annotation, single nucleotide variations and insertion-deletion markers were examined. Comparative evaluations using the Sorting Intolerant from Tolerant, PolyPhen V2, Mutation Taster, and Combined Annotation Dependent Depletion databases were conducted to predict harmful mutant genes associated with the etiology of Tibetan familial VSD. RESULTS: A total of six missense mutations in genetic disease-causing genes associated with the development of Tibetan familial VSD were identified: activin A receptor type II-like 1 (c.652 C > T: p.R218 W), ATPase cation transporting 13A2 (c.1363 C > T: p.R455 W), endoplasmic reticulum aminopeptidase 1 (c.481 G > A: p.G161 R), MRI1 (c.629 G > A: p.R210Q), tumor necrosis factor receptor-associated protein 1 (c.224 G > A: p.R75H), and FBN2 (c.2260 G > A: p.G754S). The Human Gene Mutation Database confirmed activin A receptor type II-like 1, MRI1, and tumor necrosis factor receptor-associated protein 1 as pathogenic mutations, while FBN2 was classified as a probable pathogenic mutation. CONCLUSIONS: This novel study directly screens genetic variations associated with Tibetan familial VSD using whole-exome sequencing, providing new insights into the pathogenesis of VSD.

Impact of missense TSBP1 variants on the susceptibility to coronary heart disease.

BACKGROUND: A genome-wide association study has recognized C6orf10-BTNL2 polymorphism in coronary artery disease. The goal of this study was to explore the potential correlation of nine missense TSBP1 variants with coronary heart disease (CHD) risk in the Chinese Han population. METHODS: Nine TSBP1 missense single nucleotide polymorphisms (SNPs) were selected for genotyping by the Agena MassARRAY platform. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to analyze the contribution of TSBP1 SNPs to CHD predisposition by logistic regression models adjusted by age, sex, drinking, and smoking. The correlation of TSBP1 variants with clinical data in CHD patients was examined by Kruskal-Wallis test. RESULTS: rs9268368-C (p = 0.039, OR = 1.18, 95 % CI: 1.01-1.38) was related to an increased risk of CHD, while rs3749966-C (p = 0.032, OR = 0.49, 95 % CI: 0.25-0.96) and rs3129941-A (p = 0.011, OR = 0.74, 95 % CI: 0.59-0.93) might be protective factors against CHD occurrence in the Chinese Han population. We also observed the effects of demographic characteristics (age, sex, alcohol consumption, and smoking) and complications (hypertension and diabetes) on the interactive association of TSBP1 polymorphisms with CHD susceptibility. rs139993810 was related to the levels of high-density lipoprotein cholesterol (HDL-C, p = 0.030). CONCLUSIONS: Our findings determined the association of TSBP1 rs9268368, rs3749966, and rs3129941 with CHD occurrence in the Chinese Han population, and highlighted the influence of demographic characteristics and complications on the interactive association of TSBP1 polymorphisms with CHD risk.

Transcriptome and metabolomics analysis of adaptive mechanism of Chinese mitten crab (Eriocheir sinensis) to aflatoxin B1.

Aflatoxin B1 (AFB1), with the strong toxicity and carcinogenicity, has been reported to great toxicity to the liver and other organs of animals. It cause huge economic losses to breeding industry, including the aquaculture industry. Chinese mitten crabs (Eriocheir sinensis), as one of important species of freshwater aquaculture in China, are deeply disturbed by it. However, the molecular and metabolic mechanisms of hepatopancreas and ovary in crabs underlying coping ability are still unclear. Hence, we conducted targeted injection experiment with or without AFB1, and comprehensively analyzed transcriptome and metabolomics of hepatopancreas and ovary. As a result, 210 and 250 DEGs were identified in the L-C vs. L-30 m and L-C vs. L-60 m comparison, among which 14 common DEGs were related to six major functional categories, including antibacterial and detoxification, ATP energy reaction, redox reaction, nerve reaction, liver injury repair and immune reaction. A total of 228 and 401 DAMs in the ML-C vs. ML-30 m and ML-C vs. ML-60 m comparison both enriched 12 pathways, with clear functions of cutin, suberine and wax biosynthesis, tyrosine metabolism, purine metabolism, nucleotide metabolism, glycine, serine and threonine metabolism, ABC transporters and tryptophan metabolism. Integrated analysis of metabolomics and transcriptome in hepatopancreas discovered three Co-enriched pathways, including steroid biosynthesis, glycine, serine and threonine metabolism, and sphingolipid metabolism. In summary, the expression levels and functions of related genes and metabolites reveal the regulatory mechanism of Chinese mitten crab (Eriocheir sinensis) adaptability to the Aflatoxin B1, and the findings contribute to a new perspective for understanding Aflatoxin B1 and provide some ideas for dealing with it.

Robust memory humoral immune response to SARS-CoV-2 in the tonsils of adults and children.

Background: Adaptive humoral immunity against SARS-CoV-2 has mainly been evaluated in peripheral blood. Human secondary lymphoid tissues (such as tonsils) contain large numbers of plasma cells that secrete immunoglobulins at mucosal sites. Yet, the role of mucosal memory immunity induced by vaccines or natural infection against SARS-CoV-2 and its variants is not fully understood. Methods: Tonsillar mononuclear cells (TMNCs) from adults (n=10) and children (n=11) were isolated and stimulated using positive SARS-CoV-2 nasal swabs. We used endpoint enzyme-linked immunosorbent assays (ELISAs) for the measurement of anti-S1, -RBD, and -N IgG antibody levels and a pseudovirus microneutralization assay to assess neutralizing antibodies (nAbs) in paired serum and supernatants from stimulated TMNCs. Results: Strong systemic humoral response in previously SARS-CoV-2 infected and vaccinated adults and children was observed in accordance with the reported history of the participants. Interestingly, we found a significant increase in anti-RBD IgG (305 and 834 folds) and anti-S1 IgG (475 and 443 folds) in the stimulated TMNCs from adults and children, respectively, compared to unstimulated cells. Consistently, the stimulated TMNCs secreted higher levels of nAbs against the ancestral Wuhan strain and the Omicron BA.1 variant compared to unstimulated cells by several folds. This increase was seen in all participants including children with no known history of infection, suggesting that these participants might have been previously exposed to SARS-CoV-2 and that not all asymptomatic cases necessarily could be detected by serum antibodies. Furthermore, nAb levels against both strains were significantly correlated in adults (r=0.8788; p = 0.0008) and children (r = 0.7521; p = 0.0076), and they strongly correlated with S1 and RBD-specific IgG antibodies. Conclusion: Our results provide evidence for persistent mucosal humoral memory in tonsils from previously infected and/or vaccinated adults and children against recent and old variants upon re-exposure. They also highlight the importance of targeting mucosal sites with vaccines to help control infection at the primary sites and prevent potential breakthrough infections.

Maize Dek407 Encodes the Nitrate Transporter 1.5 and Is Required for Kernel Development.

The kernel serves as the storage organ and harvestable component of maize, and it plays a crucial role in determining crop yield and quality. Understanding the molecular and genetic mechanisms of kernel development is of considerable importance for maize production. In this study, we obtained a mutant, which we designated defective kernel 407 (dek407), through ethyl methanesulfonate mutagenesis. The dek407 mutant exhibited reduced kernel size and kernel weight, as well as delayed grain filling compared with those of the wild type. Positional cloning and an allelism test revealed that Dek407 encodes a nitrate transporter 1/peptide transporter family (NPF) protein and is the allele of miniature 2 (mn2) that was responsible for a poorly filled defective kernel phenotype. A transcriptome analysis of the developing kernels showed that the mutation of Dek407 altered the expression of phytohormone-related genes, especially those genes associated with indole-3-acetic acid synthesis and signaling. Phytohormone measurements and analysis indicated that the endogenous indole-3-acetic acid content was significantly reduced by 66% in the dek407 kernels, which may be the primary cause of the defective phenotype. We further demonstrated that natural variation in Dek407 is associated with kernel weight and kernel size. Therefore, Dek407 is a potential target gene for improvement of maize yield.

The impact of the new acute respiratory distress syndrome (ARDS) criteria on Berlin criteria ARDS patients: a multicenter cohort study.

OBJECTIVE: The European Society of Intensive Care Medicine (ESICM) recently recommended changes to the criteria of acute respiratory distress syndrome (ARDS), patients with high-flow oxygen were included, however, the effect of these changes remains unclear. Our objectives were to evaluate the performance of these new criteria and to compare the outcomes of patients meeting the new ARDS criteria with those meeting the Berlin ARDS criteria. METHODS: This was a retrospective cohort. The patients admitted to the intensive care unit (ICU) were diagnosed with ARDS. Patients were classified as meeting Berlin criteria ARDS (n = 4279), high-flow nasal oxygen (HFNO) criteria ARDS (n = 559), or new criteria ARDS (n = 4838). RESULTS: In comparison with HFNO criteria ARDS and new criteria ARDS, patients with Berlin criteria ARDS demonstrated lower blood oxygen levels assessed by PaO2/FiO2, SpO2/FiO2, and ROX (SpO2/FiO2/respiratory rate) (p < 0.001); and higher severity of illness assessed by the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology And Chronic Health Evaluations (APACHE II), Simplified Acute Physiology Score (SAPS II) (p < 0.001), (p < 0.001), and longer ICU and hospital stays (p < 0.001). In comparison with the HFNO criteria, patients meeting Berlin criteria ARDS had higher hospital mortality (10.6% vs. 16.9%; p = 0.0082), 28-day mortality (10.6% vs. 16.5%; p = 0.0079), and 90-day mortality (10.7% vs. 17.1%; p = 0.0083). ARDS patients with HFNO did not have severe ARDS; Berlin criteria ARDS patients with severe ARDS had the highest mortality rate (approximately 33%). PaO2/FiO2, SpO2/FiO2, and ROX negatively correlated with the SOFA and APACHE II scores. The SOFA and APACHE II scores had high specificity and sensitivity for prognosis in patients with new criteria ARDS. CONCLUSION: The new criteria of ARDS reduced the severity of illness, length of stay in the ICU, length of hospital stays, and overall mortality. SOFA and APACHE II scores remain important in assessing the prognosis of patients with new criteria ARDS. TRIAL REGISTRATION: Registration number: ChiCTR2200067084.

Relationship between Nonhepatic Serum Ammonia Levels and Sepsis-Associated Encephalopathy: A Retrospective Cohort Study.

Objectives: Nonhepatic hyperammonemia often occurs in patients with sepsis. Ammonia plays an essential role in the occurrence of hepatic encephalopathy. However, the relationship between nonhepatic serum ammonia levels and sepsis-associated encephalopathy (SAE) remains unclear. Thus, we aimed to evaluate the association between serum ammonia levels and patients with SAE. Methods: Data of critically ill adults with sepsis who were admitted to the intensive care unit were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) between 2008 and 2019 and retrospectively analyzed. Data of patients with sepsis patients and serum ammonia not related to acute or chronic liver disease were not included. Results: Data from 720 patients with sepsis were included. SAE was found to have a high incidence (64.6%). After adjusting for other risk factors, a serum ammonia level of ≥45 µmol/L (odds ratio (OR): 3.508, 95% confidence interval (CI): 2.336-5.269, p < 0.001) was found to be an independent risk factor for patients with SAE; moreover, as the serum ammonia level increased, the hospital mortality of SAE gradually increased in a certain range (serum ammonia <150 µmol/L). Serum ammonia levels of ≥45 µmol/L were associated with higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment (SOFA) scores in patients with SAE. Besides, our study found that patients with SAE used opioid analgesics (OR:3.433, 95% CI: 1.360-8.669, p = 0.009) and the SOFA scores of patients with SAE (OR: 1.126, 95% CI: 1.062-1.194, p < 0.001) were significantly higher than those without SAE. Conclusions: Nonhepatic serum ammonia levels of ≥45 µmol/L evidently increased the incidence of SAE. Serum ammonia levels should be closely monitored in patients with sepsis.

The Expression Kinetics and Immunogenicity of Lipid Nanoparticles Delivering Plasmid DNA and mRNA in Mice.

In recent years, lipid nanoparticles (LNPs) have emerged as a revolutionary technology for vaccine delivery. LNPs serve as an integral component of mRNA vaccines by protecting and transporting the mRNA payload into host cells. Despite their prominence in mRNA vaccines, there remains a notable gap in our understanding of the potential application of LNPs for the delivery of DNA vaccines. In this study, we sought to investigate the suitability of leading LNP formulations for the delivery of plasmid DNA (pDNA). In addition, we aimed to explore key differences in the properties of popular LNP formulations when delivering either mRNA or DNA. To address these questions, we compared three leading LNP formulations encapsulating mRNA- or pDNA-encoding firefly luciferase based on potency, expression kinetics, biodistribution, and immunogenicity. Following intramuscular injection in mice, we determined that RNA-LNPs formulated with either SM-102 or ALC-0315 lipids were the most potent (all p-values < 0.01) and immunogenic (all p-values < 0.05), while DNA-LNPs formulated with SM-102 or ALC-0315 demonstrated the longest duration of signal. Additionally, all LNP formulations were found to induce expression in the liver that was proportional to the signal at the injection site (SM102: r = 0.8787, p < 0.0001; ALC0315: r = 0.9012, p < 0.0001; KC2: r = 0.9343, p < 0.0001). Overall, this study provides important insights into the differences between leading LNP formulations and their applicability to DNA- and RNA-based vaccinations.

Fluorinated High-Voltage Electrolytes To Stabilize Nickel-Rich Lithium Batteries.

As state-of-the-art (SOA) lithium-ion (Li-ion) batteries approach their specific energy limit (∼250 Wh kg-1), layer-structured, nickel-rich (Ni-rich) lithium transition metal oxide-based cathode materials, e.g., LiNi0.8Mn0.1Co0.1O2 (NMC811), have attracted great interest owing to their practical high specific capacities (>200 mAhg-1). Coupled with their high average discharge voltages (∼4 V vs Li/Li+), Ni-rich cathode-based lithium batteries possess a great potential to achieve much higher specific energies (>350 Wh kg-1 at the cell level) than the SOA Li-ion counterparts. In addition, Ni-rich oxides are low-cost battery cathode materials due to their low cobalt contents. However, Ni-rich cathode-based lithium batteries suffer quick capacity degradations upon cycling, particularly at high upper cutoff voltages (e.g., ≥4.5 V vs Li/Li+), due to crystal structure changes of the active cathode materials and parasitic side reactions at the electrolyte/electrode interfaces. In this study, a fluorinated-solvent-based, high-voltage stable electrolyte (HVE), i.e., 1 M Li bis(trifluoromethanesulfonyl)imide (LiTFSI) in fluoroethylene carbonate (FEC), bis(2,2,2-trifluoroethyl) carbonate (FDEC), and methyl (2,2,2-trifluoroethyl) carbonate (FEMC) with Li difluoro(oxalate)borate (LiDFOB) additive, was formulated and evaluated in Li/NMC811 battery cells. To the best of our knowledge, this class of electrolyte has not been investigated for Ni-rich cathode-based lithium batteries. Li/NMC811 cells with HVE exhibited a superior long-term cycle performance stability, maintaining ∼80% capacity after ∼500 cycles at a high cutoff voltage of 4.5 V (vs Li/Li+) than a baseline carbonate-solvent-based electrolyte (BE). The superior cycle stability of the Li/NMC811 cells is attributed to the inherently high-voltage stability of HVE, supported by the physical and electrochemical analyses. This conclusion is supported by our density functional theory (DFT) modeling where HVE shows a less tendency of deprotonation/oxidation than BE, leading to the observed cycle stability. The findings in this study are important to help tackle the technical challenges facing Ni-rich cathode-based lithium batteries to realize their high energy density potentials with a long cycle life.

The Epigenetic Legacy of Maternal Protein Restriction: Renal Ptger1 DNA Methylation Changes in Hypertensive Rat Offspring.

Nutrient imbalances during gestation are a risk factor for hypertension in offspring. Although the effects of prenatal nutritional deficiency on the development of hypertension and cardiovascular diseases in adulthood have been extensively documented, its underlying mechanisms remain poorly understood. In this study, we aimed to elucidate the precise role and functional significance of epigenetic modifications in the pathogenesis of hypertension. To this end, we integrated methylome and transcriptome data to identify potential salt-sensitive hypertension genes using the kidneys of stroke-prone spontaneously hypertensive rat (SHRSP) pups exposed to a low-protein diet throughout their fetal life. Maternal protein restriction during gestation led to a positive correlation between DNA hypermethylation of the renal prostaglandin E receptor 1 (Ptger1) CpG island and high mRNA expression of Ptger1 in offspring, which is consistently conserved. Furthermore, post-weaning low-protein or high-protein diets modified the Ptger1 DNA hypermethylation caused by fetal malnutrition. Here, we show that this epigenetic variation in Ptger1 is linked to disease susceptibility established during fetal stages and could be reprogrammed by manipulating the postnatal diet. Thus, our findings clarify the developmental origins connecting the maternal nutritional environment and potential epigenetic biomarkers for offspring hypertension. These findings shed light on hypertension prevention and prospective therapeutic strategies.

Recent Progress of Layered Double Hydroxide-Based Materials in Wastewater Treatment.

Layered double hydroxides (LDHs) can be used as catalysts and adsorbents due to their high stability, safety, and reusability. The preparation of modified LDHs mainly includes coprecipitation, hydrothermal, ion exchange, calcination recovery, and sol-gel methods. LDH-based materials have high anion exchange capacity, good thermal stability, and a large specific surface area, which can effectively adsorb and remove heavy metal ions, inorganic anions, organic pollutants, and oil pollutants from wastewater. Additionally, they are heterogeneous catalysts and have excellent catalytic effect in the Fenton system, persulfate-based advanced oxidation processes, and electrocatalytic system. This review ends with a discussion of the challenges and future trends of the application of LDHs in wastewater treatment.

Boosting interfacial solar steam generation by three-dimensional bilayer cellulose aerogels.

Interfacial solar steam generation (ISSG) provides a sustainable approach of clean water production through desalination and water purification. It is still needed to pursue a fast evaporation rate, high-quality freshwater production, and low-cost evaporators. Herein, a three-dimensional (3D) bilayer aerogel was fabricated using cellulose nanofiber (CNF) as a skeleton filled with polyvinyl alcohol phosphate ester (PVAP), and carbon nanotubes (CNT) as a light absorbing material in the top layer. The CNF/PVAP/CNT aerogel (CPC) had broadband light absorption ability and exhibited an ultrafast water transfer rate. The lower thermal conductivity of CPC effectively confined the convert heat in the top surface and minimized heat loss. Additionally, a large amount of intermediate water caused by water activation decreased the evaporation enthalpy. Under 1 sun irradiation, the CPC-3 (3.0 cm height of CPC) achieved a high evaporation rate of 4.02 kg m-2 h-1 with an energy conversion efficiency of 125.1%. The additional convective flow and environmental energy made CPC achieve an ultrahigh evaporation rate of 11.37 kg m-2 h-1, surpassing 673% of the solar input energy. More importantly, the continuous solar desalination and higher evaporation rate (10.70 kg m-2 h-1) in seawater revealed that CPC was a promising candidate for practical desalination. Outdoor cumulative evaporation was up to 73.2 kg m-2 d-1 in weak sunlight and lower temperature, which would meet the daily drinking water demands of 20 people. The excellent cost-effectiveness of 1.085 L h-1 $-1 presented its potential for a wide range of practical applications, such as solar desalination, wastewater treatment, and metal extractions.

Postnatal nutrition environment reprograms renal DNA methylation patterns in offspring of maternal protein-restricted stroke-prone spontaneously hypertensive rats.

Maternal malnutrition hampers the offspring health by manipulating the epigenome. Recent studies indicate that the changes in DNA methylation could be reversed by afterbirth nutrition supplementation. In this study, we used DNA methylation arrays to comprehensively investigate the DNA methylation status of the renal promoter regions and the effects of postnatal protein intake on DNA methylation. We fed stroke-prone spontaneously hypertensive (SHRSP) rat dams a normal diet or a low-protein diet during pregnancy, and their 4-week-old male offspring were fed a normal diet or a high-/low-protein diet for 2 weeks. We found that the methylation status of 2,395 differentially methylated DNA regions was reprogrammed, and 34 genes were reset by different levels of postnatal protein intake in the offspring. Among these genes, Adora2b, Trpc5, Ar, Xrcc2, and Atp1b1 are involved in renal disease and blood pressure regulation. Our findings indicate that postnatal nutritional interventions can potentially reprogram epigenetic changes, providing novel therapeutic and preventive epigenetic targets for salt-sensitive hypertension.

NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing.

Background: Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients in the Chinese Tibetan population, and to provide a theoretical basis for the genetic mechanism of VSD. Methods: Peripheral venous blood was collected from 20 VSD subjects, and whole-genome DNA was extracted. High-throughput sequencing was performed on qualified DNA samples using whole-exome sequencing (WES) technology. After filtering, detecting, and annotating qualified data, single nucleotide variations (SNVs) and insertion-deletion (InDel) markers were analyzed, and data processing software such as GATK, SIFT, Polyphen, and MutationTaster were used for comparative evaluation and prediction of pathogenic deleterious variants associated with VSD. Results: A total of 4793 variant loci, including 4168 SNVs, 557 InDels and 68 unknown loci and 2566 variant genes were obtained from 20 VSD subjects through bioinformatics analysis. According to the screening of the prediction software and database, the occurrence of VSD was predicted to be associated with five inherited pathogenic gene mutations, all of which were missense mutations, including NOTCH2 (c.1396C >A:p.Gln466Lys), ATIC (c.235C >T:p.Arg79Cys), MRI1 (c.629G >A:p.Arg210Gln), SLC6A13 (c.1138G >A:p.Gly380Arg), ATP13A2 (c.1363C >T:p.Arg455Trp). Conclusion: This study demonstrated that NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 gene variants were potentially associated with VSD in Chinese Tibetan population.

(NH4)2Mo3S13/MnFe2O4 hybrid with multiple active sites boosted activation of peroxymonosulfate for removal of tetracycline.

Advanced oxidation processes (AOPs) based on peroxymonosulfate (PMS) activation have attracted much attention in wastewater treatment. Here, a series of (NH4)2Mo3S13/MnFe2O4 (MSMF) composites were prepared and used as PMS activators to remove tetracycline (TC) for the first time. When the mass ratio of (NH4)2Mo3S13 to MnFe2O4 was 4.0 (MSMF4.0), the composite showed remarkable catalytic efficiency for activating PMS to remove TC. Over 93% of TC was removed in MSMF4.0/PMS system in 20 min. The aqueous •OH as well as the surface SO4•- and •OH were the primary reactive species for TC degradation in MSMF4.0/PMS system, and the comprehensive experimental results excluded the contributions of aqueous SO4•-, O2•-, and 1O2, high-valent metal-oxo species, and surface-bound PMS. The Mn(II)/Mn(III), Fe(II)/Fe(III), Mo(IV)/Mo(VI), and S2-/SOx2- all contributed to the catalytic process. MSMF4.0 also showed excellent activity and stability after five cycles and significant degradation efficiency for a variety of pollutants. This work will provide theoretical basis for applying MnFe2O4-based composites in PMS-based AOPs.

DNA lipid nanoparticle vaccine targeting outer surface protein C affords protection against homologous Borrelia burgdorferi needle challenge in mice.

Introduction: The incidence of Lyme disease (LD) in Canada and the United States has risen over the last decade, nearing 480,000 cases each year. Borrelia burgdorferi sensu lato, the causative agent of LD, is transmitted to humans through the bite of an infected tick, resulting in flu-like symptoms and often a characteristic bull's-eye rash. In more severe cases, disseminated bacterial infection can cause arthritis, carditis and neurological impairments. Currently, no vaccine is available for the prevention of LD in humans. Methods: In this study, we developed a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding outer surface protein C type A (OspC-type A) of B. burgdorferi. Results: Vaccination of C3H/HeN mice with two doses of the candidate vaccine induced significant OspC-type A-specific antibody titres and borreliacidal activity. Analysis of the bacterial burden following needle challenge with B. burgdorferi (OspC-type A) revealed that the candidate vaccine afforded effective protection against homologous infection across a range of susceptible tissues. Notably, vaccinated mice were protected against carditis and lymphadenopathy associated with Lyme borreliosis. Discussion: Overall, the results of this study provide support for the use of a DNA-LNP platform for the development of LD vaccines.