IL-4 polymorphisms (rs2227284, rs2243267, and rs2243270) are associated with reduced risk of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, and understanding its genetic and molecular basis is crucial for early diagnosis, treatment, and prevention. OBJECTIVE: This study aims to explore the association between IL-4 polymorphisms (rs2227284, rs2243267, rs2243270, and rs2243283) and RA risk. METHODS: The four IL-4 polymorphisms were genotyped in 493 RA patients and 493 healthy controls using Agena MassARRAY. Logistic regression analysis calculated odds ratio (OR) and 95% confidence interval (CI) to estimate the relationship between IL-4 polymorphisms and RA risk. RESULTS: Overall analysis revealed that rs2243267 (GG vs. CC: OR = 0.26, FDR-p = .032; Recessive: OR = 0.27, FDR-p = .048) and rs2243270 (AA vs. GG: OR = 0.26, FDR-p = .024; Recessive: OR = 0.27, FDR-p = .024) were associated with a decreased risk of RA. Stratified analysis indicated that rs2243267 and rs2243270 were correlated with reduced RA risk in female, smoking, BMI <24, and drinking population; rs2227284 was associated with a decreased RA risk in BMI <24 and drinking population. Moreover, rs2243267 and rs2243270 were significantly associated with reduced ACPA positivity. CONCLUSIONS: Our findings suggest that IL-4 polymorphisms (rs2227284, rs2243267, and rs2243270) act as protective factors for RA in the Chinese Han population.

Novel insight into the genetic signatures of altitude adaptation related body composition in Tibetans.

Background: The Tibetan population residing in high-altitude (HA) regions has adapted to extreme hypoxic environments. However, there is limited understanding of the genetic basis of body compositions in Tibetan population adapted to HA. Methods: We performed a genome-wide association study (GWAS) to identify genetic variants associated with HA and HA-related body composition traits. A total of 755,731 single nucleotide polymorphisms (SNPs) were genotyped using the precision medicine diversity array from 996 Tibetan college students. T-tests and Pearson correlation analysis were used to estimate the association between body compositions and altitude. The mixed linear regression identified the SNPs significantly associated with HA and HA-related body compositions. LASSO regression was used to screen for important SNPs in HA and body compositions. Results: Significant differences were observed in lean body mass (LBW), muscle mass (MM), total body water (TBW), standard weight (SBW), basal metabolic rate (BMR), total protein (TP), and total inorganic salt (Is) in different altitudes stratification. We identified three SNPs in EPAS1 (rs1562453, rs7589621 and rs7583392) that were significantly associated with HA (p < 5 × 10-7). GWAS analysis of 7 HA-related body composition traits, we identified 14 SNPs for LBM, 11 SNPs for TBW, 15 SNPs for MM, 16 SNPs for SBW, 9 SNPs for BMR, 12 SNPs for TP, and 26 SNPs for Is (p < 5.0 × 10-5). Conclusion: These findings provide insight into the genetic basis of body composition in Tibetan college students adapted to HA, and lay the foundation for further investigation into the molecular mechanisms underlying HA adaptation.

Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma: A case report.

BACKGROUND: Lymphangiomas in the gastrointestinal tract are extremely rare in adults. As a benign lesion, small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis. However, lymphangiomas can give rise to complications such as abdominal pain, bleeding, volvulus, and intussusception. Here, we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult. CASE SUMMARY: A 66-year-old man presented with intermittent melena, fatigue and refractory anemia nine months prior. Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding. Conservative management, including transfusion, hemostasis, gastric acid secretion inhibition and symptomatic treatment, was performed, but the lesions tended to recur shortly after surgery. Ultimately, the patient underwent capsule endoscopy, which revealed a more than 10 cm lesion accompanied by active bleeding. After single-balloon enteroscopy and biopsy, a diagnosis of jejunal cavernous lymphangioma was confirmed, and the patient underwent surgical resection. No complications or recurrences were observed postoperatively. CONCLUSION: Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding. Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis. Surgical resection is an effective management method.

Hybrid Filtering Compensation Algorithm for Suppressing Random Errors in MEMS Arrays.

To solve the high error phenomenon of microelectromechanical systems (MEMS) due to their poor signal-to-noise ratio, this paper proposes an online compensation algorithm wavelet threshold back-propagation neural network (WT-BPNN), based on a neural network and designed to effectively suppress the random error of MEMS arrays. The algorithm denoises MEMS and compensates for the error using a back propagation neural network (BPNN). To verify the feasibility of the proposed algorithm, we deployed it in a ZYNQ-based MEMS array hardware. The experimental results showed that the zero-bias instability, angular random wander, and angular velocity random wander of the gyroscope were improved by about 12 dB, 10 dB, and 7 dB, respectively, compared with the original device in static scenarios, and the dispersion of the output data was reduced by about 8 dB in various dynamic environments, which effectively verified the robustness and feasibility of the algorithm.

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.

Association Between CYP24A1 Polymorphisms and Bladder Cancer Risk in the Chinese Han Population.

In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.

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.

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.

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.

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.

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.

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.

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.