Boosting Up Electrosynthesis of Urea with Nitrate and Carbon Dioxide via Synergistic Effect of Metallic Iron Cluster and Single-Atom.

Electrocatalytic conversion of nitrates and carbon dioxide to urea under ambient conditions shows promise as a potential substitute for traditional urea synthesis processes characterized by high consumption and pollution. In this study, a straightforward one-pot method is employed to prepare a highly efficient FeNC-Fe1N4 electrocatalyst, consisting of atomically dispersed Fe1N4 sites and metallic Fe clusters (FeNC) with particle size of 4-7 nm. The FeNC-Fe1N4 catalyst exhibits remarkable electrocatalytic activity for urea synthesis from nitrate anion (NO3 -) and carbon dioxide (CO2), achieving a urea production rate of 38.2 mmol gcat -1 h-1 at -0.9 V (vs RHE) and a Faradaic efficiency of 66.5% at -0.6 V (vs RHE). Both experimental and theoretical results conclusively demonstrate that metallic Fe clusters and Fe1N4 species provide active sites for the adsorption and activation of NO3 - and CO2, respectively, and the synergistic effect between Fe1N4 and metallic Fe clusters significantly enhances the electrochemical efficiency of urea synthesis. In all, this work contributes to the rational design and comprehensive synthesis of a dual-active site iron-based electrocatalyst, facilitating efficient and sustainable urea synthesis.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

A Pt(II) complex bearing N-heterocycle ring induced ferroptotic cell death in ovarian cancer.

Cisplatin is a widely used chemotherapeutic agent which interacts with DNA to form Pt-DNA adducts, leading to DNA double-strand breaks and apoptosis. Resistance is the major obstacle in the clinical application of cisplatin. A quinoline derivative based Pt(II) complex PtQ was synthesized and characterized. As an analogue of cisplatin, PtQ demonstrated a novel anticancer mechanism in ovarian cancer. PtQ caused excessive production of reactive oxygen species (ROS), which triggered ferroptotic cell death in ovarian cancer. Cystine/glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4) which alleviate lipid peroxidation were both downregulated in PtQ-treated SKOV3 cells. Furthermore, PtQ induced DNA single-strand breaks and suppressed the expression of single-strand breaks repair protein PARP1. Mechanism studies demonstrated that PtQ can hopefully bypass the signaling pathways mediated cisplatin resistance in ovarian cancer.

A monofunctional Pt(II) complex combats triple negative breast cancer by triggering lysosome-dependent cell death.

Monofunctional Pt(II) complexes with potent efficacy to overcome the drawbacks of current platinum drugs represent a promising therapeutic approach for triple negative breast cancer (TNBC). A heterocyclic-ligated monofunctional Pt(II) complex PtL with a unique action of mode was designed and investigated. PtL induced DNA single-strand breaks and caused genomic instability in TNBC cells. Mechanism studies demonstrated that PtL disrupted lysosomal acidity and function, which in turn triggered lysosome-dependent cell death. Furthermore, PtL showed convincing suppression in the tube forming and cell migratory abilities against the metastatic potential of TNBC cells. The synthesis and investigation of PtL revealed its potential value as an anti-TNBC drug and extended the family of monofunctional Pt(II) complexes.

Single-molecule characterization of Sen1 translocation properties provides insights into eukaryotic factor-dependent transcription termination.

Sen1 is an essential helicase for factor-dependent transcription termination in Saccharomyces cerevisiae, whose molecular-motor mechanism has not been well addressed. Here, we use single-molecule experimentation to better understand the molecular-motor determinants of its action on RNA polymerase II (Pol II) complex. We quantify Sen1 translocation activity on single-stranded DNA (ssDNA), finding elevated translocation rates, high levels of processivity and ATP affinities. Upon deleting the N- and C-terminal domains, or further deleting different parts of the prong subdomain, which is an essential element for transcription termination, Sen1 displays changes in its translocation properties, such as slightly reduced translocation processivities, enhanced translocation rates and statistically identical ATP affinities. Although these parameters fulfil the requirements for Sen1 translocating along the RNA transcript to catch up with a stalled Pol II complex, we observe significant reductions in the termination efficiencies as well as the factions of the formation of the previously described topological intermediate prior to termination, suggesting that the prong may preserve an interaction with Pol II complex during factor-dependent termination. Our results underscore a more detailed rho-like mechanism of Sen1 and a critical interaction between Sen1 and Pol II complex for factor-dependent transcription termination in eukaryotes.

Synergistic ultrasound pulsed electric field extraction of litchi peel polyphenols and determination of their properties.

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.

Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy.

Nitric oxide (NO), as a gaseous therapeutic agent, shows great potential for the treatment of many kinds of diseases. Although various NO delivery systems have emerged, the immunogenicity and long-term toxicity of artificial carriers hinder the potential clinical translation of these gas therapeutics. Mesenchymal stem cells (MSCs), with the capacities of self-renewal, differentiation, and low immunogenicity, have been used as living carriers. However, MSCs as gaseous signaling molecule (GSM) carriers have not been reported. In this study, human MSCs were genetically modified to produce mutant ß-galactosidase (ß-GALH363A). Furthermore, a new NO prodrug, 6-methyl-galactose-benzyl-oxy NONOate (MGP), was designed. MGP can enter cells and selectively trigger NO release from genetically engineered MSCs (eMSCs) in the presence of ß-GALH363A. Moreover, our results revealed that eMSCs can release NO when MGP is systemically administered in a mouse model of acute kidney injury (AKI), which can achieve NO release in a precise spatiotemporal manner and augment the therapeutic efficiency of MSCs. This eMSC and NO prodrug system provides a unique and tunable platform for GSM delivery and holds promise for regenerative therapy by enhancing the therapeutic efficiency of stem cells.

Animals are made up of cells of different types, with each type of cell specializing on a specific role. But for the body to work properly, the different types of cells must be able to coordinate with each other to respond to internal and external stimuli. This can be achieved through signaling molecules, that is, molecules released by a cell that can elicit a specific response in other cells. There are many types of different molecules, including hormones and signaling proteins. Gases can also be potent signaling molecules, participating in various biological processes. Nitric oxide (NO) is a gas signaling molecule that can freely diffuse through the membranes of cells and has roles in blood vessel constriction and other disease processes, making it a promising therapeutic agent. Unfortunately, using artificial carriers to deliver nitric oxide to the organs and tissues where it is needed can lead to issues, including immune reactions to the carrier and long-term toxicity. One way to avoid these effects is by using cells to deliver nitric oxide to the right place. Huang, Qian, Liu et al. have used mesenchymal stem cells ­ which usually develop to form connective tissues such as bone and muscle ­ to develop a cell-based NO-delivery system. The researchers genetically modified the mesenchymal stem cells to produce a compound called ß-GAL^H363A. On its own ß-GAL^H363A does not do much, but in its presence, a non-toxic, non-reactive compound developed by Huang, Qian, Liu et al., called MGP, can drive the release of NO from cells. To confirm the usefulness of their cells as a delivery system, Huang, Qian, Liu et al. transplanted some of the genetically modified mesenchymal stem cells into the kidneys of mice, and then showed that when these mice were given MGP, the levels of NO increased in the kidneys but not in other organs. This result confirms that the cell-based delivery system provides spatial and temporal control of the production of NO. These findings demonstrate a new delivery system for therapies using gas molecules, which can be controlled spatiotemporally in mice. In the future, these types of systems could be used in the clinic for long-term treatment of conditions where artificial carriers could lead to complications.

Host-derived peptide signals regulate Pseudomonas aeruginosa virulence stress via the ParRS and CprRS two-component systems.

Pseudomonas aeruginosa, a versatile bacterium, has dual significance because of its beneficial roles in environmental soil processes and its detrimental effects as a nosocomial pathogen that causes clinical infections. Understanding adaptability to environmental stress is essential. This investigation delves into the complex interplay of two-component system (TCS), specifically ParRS and CprRS, as P. aeruginosa interprets host signals and navigates stress challenges. In this study, through phenotypic and proteomic analyses, the nuanced contributions of ParRS and CprRS to the pathogenesis and resilience mechanisms were elucidated. Furthermore, the indispensable roles of the ParS and CprS extracellular sensor domains in orchestrating signal perception remain unknown. Structural revelations imply a remarkable convergence of TCS sensors in interacting with host peptides, suggesting evolutionary strategies for bacterial adaptation. This pioneering work not only established links between cationic antimicrobial peptide (CAMP) resistance-associated TCSs and virulence modulation in nosocomial bacteria, but also transcended conventional boundaries. These implications extend beyond clinical resistance, permeating into the realm of soil revitalization and environmental guardianship. As it unveils P. aeruginosa intricacies, this study assumes a mantle of guiding strategies to mitigate clinical hazards, harness environmental advantages, and propel sustainable solutions forward.

Advances in Phytochemistry and Modern Pharmacology of Saposhnikovia Divaricata (Turcz.) Schischk.

Saposhnikovia divaricata (Turcz.) Schischk (S. divaricata, Fangfeng) is a herb in the Apiaceae family, and its root has been used since the Western Han Dynasty (202 B.C.). Chromones and coumarins are the pharmacologically active substances in S. divaricata. Modern phytochemical and pharmacological studies have demonstrated their antipyretic, analgesic, anti-inflammatory, antioxidant, anti-tumor, and anticoagulant activities. Technological and analytical strategy theory advancements have yielded novel results; however, most investigations have been limited to the main active substances-chromones and coumarins. Hence, we reviewed studies related to the chemical composition and pharmacological activity of S. divaricata, analyzed the developing trends and challenges, and proposed that research should focus on components' synergistic effects. We also suggested that, the structure-effect relationship should be prioritized in advanced research.

miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the impaired differentiation and uncontrolled proliferation of myeloid blasts. Tumor suppressor p53 is often downregulated in AML cells via ubiquitination-mediated degradation. While the role of E3 ligase MDM2 in p53 ubiquitination is well-accepted, little is known about the involvement of deubiquitinases (DUBs). Herein, we found that the expression of YOD1, among several DUBs, is substantially reduced in blood cells from AML patients. We identified that YOD1 deubiqutinated and stabilized p53 through interaction via N-terminus of p53 and OTU domain of YOD1. In addition, expression levels of YOD1 were suppressed by elevated miR-221/222 in AML cells through binding to the 3' untranslated region of YOD1, as verified by reporter gene assays. Treatment of cells with miR-221/222 mimics and inhibitors yielded the expected effects on YOD1 expressions, in agreement with the negative correlation observed between the expression levels of miR-221/222 and YOD1 in AML cells. Finally, overexpression of YOD1 stabilized p53, upregulated pro-apoptotic p53 downstream genes, and increased the sensitivity of AML cells to FLT3 inhibitors remarkably. Collectively, our study identified a pathway connecting miR-221/222, YOD1, and p53 in AML. Targeting miR-221/222 and stimulating YOD1 activity may improve the therapeutic effects of FLT3 inhibitors in patients with AML.

Combinational study with network pharmacology, molecular docking and preliminary experiments on exploring common mechanisms underlying the effects of weijing decoction on various pulmonary diseases.

Objective: 'Homotherapy for heteropathy' is a theory by which different diseases with similar pathogenesis can be treated with one Chinese formula. We aimed to explore the key components and core targets of Weijing decoction (WJD) in treating various lung diseases, namely, pneumonia, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), pulmonary fibrosis, pulmonary tuberculosis and non-small cell lung cancer (NSCLC), via network pharmacology, molecular docking and some experiments. Significance: This is the first study on the mechanism of WJD in treating various lung diseases by 'homotherapy for heteropathy'. This study is helpful for the transformation of TCM formula and development of new drugs. Methods: Active components and therapeutic targets of WJD were obtained via TCMSP and UniProt databases. Targets of the six pulmonary diseases were harvested from the GeneCards TTD, DisGeNet, UniProt and OMIM databases. Drug-disease intersection targets, corresponding Venn diagrams, herb-component-target networks and protein-protein interaction networks were established. Furthermore, GO biological function and KEGG enrichment analysis were completed. Moreover, the binding activity between main compounds and core targets was measured through molecular docking. Finally, the xenograft NSCLC mouse model was established. Immune responses were evaluated by flow cytometry and mRNA expression levels of critical targets were measured by real-time PCR. Results: JUN, CASP3 and PTGS2 were the most critical targets in six pulmonary diseases. The active compounds beta-sitosterol, tricin and stigmasterol stably bound to many active sites on target proteins. WJD had extensive pharmacological regulation, involving pathways related to cancer, inflammation, infection, hypoxia, immunity and so on. Conclusions: Effects of WJD against various lung diseases involve lots of compounds, targets and pathways. These findings will facilitate further research as well as clinical application of WJD.

Pulsed electric field improves the EGCG binding ability of pea protein isolate unraveled by multi-spectroscopy and computer simulation.

Understanding molecular mechanisms during protein modification is critical for expanding the application of plant proteins. This study investigated the conformational change and molecular mechanism of pea protein isolate (PPI) under pulsed electric field (PEF)-assisted (-)-Epigallocatechin-Gallate (EGCG) modification. The flexibility of PPI was significantly enhanced after PEF treatment (10 kV/cm) with decrease (23.25 %) in α-helix and increase (117.25 %) in random coil. The binding constant and sites of PEF-treated PPI with EGCG were increased by 2.35 times and 10.00 % (308 K), respectively. Molecular docking verified that PEF-treated PPI had more binding sites with EGCG (from 4 to 10). The number of amino acid residues involved in hydrophobic interactions in PEF-treated PPI-EGCG increased from 5 to 13. PEF-treated PPI-EGCG showed a significantly increased antioxidant activity compared to non-PEF-treated group. This work revealed the molecular level of PEF-assisted EGCG modification of PPI, which will be significant for the application of PPI in food industry.

[Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells].

OBJECTIVE: To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies. METHODS: Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy. RESULTS: After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05). CONCLUSION: The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

BODIPY-Based Multifunctional Nanoparticles for Dual Mode Imaging-Guided Tumor Photothermal and Photodynamic Therapy.

Multifunctional nanoparticles integrating accurate multi-diagnosis and efficient therapy hold great prospects in tumor theranostics. However, it is still a challenging task to develop multifunctional nanoparticles for imaging-guided effective eradication of tumors. Herein, we developed a near-infrared (NIR) organic agent Aza/I-BDP by coupling 2,6-diiodo-dipyrromethene (2,6-diiodo-BODIPY) with aza-boron-dipyrromethene (Aza-BODIPY). Through encapsulating with an amphiphilic biocompatible copolymer DSPE-mPEG5000, well-distributed Aza/I-BDP nanoparticles (NPs) were developed, which exhibited high 1O2 generation, high photothermal conversion efficiency, and excellent photo-stability. Notably, coassembly of Aza/I-BDP and DSPE-mPEG5000 effectively inhibits H-aggregation of Aza/I-BDP in aqueous solution and enhances the brightness simultaneously up to 31-fold. More importantly, in vivo experiments demonstrated that Aza/I-BDP NPs might be used for NIR fluorescent and photoacoustic imaging-guided photodynamic and photothermal therapy.

Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation.

BACKGROUND: Mesenchymal stem cells (MSCs) have demonstrated remarkable therapeutic promise for acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). MSC secretomes contain various immunoregulatory mediators that modulate both innate and adaptive immune responses. Priming MSCs has been widely considered to boost their therapeutic efficacy for a variety of diseases. Prostaglandin E2 (PGE2) plays a vital role in physiological processes that mediate the regeneration of injured organs. METHODS: This work utilized PGE2 to prime MSCs and investigated their therapeutic potential in ALI models. MSCs were obtained from human placental tissue. MSCs were transduced with firefly luciferase (Fluc)/eGFP fusion protein for real-time monitoring of MSC migration. Comprehensive genomic analyses explored the therapeutic effects and molecular mechanisms of PGE2-primed MSCs in LPS-induced ALI models. RESULTS: Our results demonstrated that PGE2-MSCs effectively ameliorated lung injury and decreased total cell numbers, neutrophils, macrophages, and protein levels in bronchoalveolar lavage fluid (BALF). Meanwhile, treating ALI mice with PGE2-MSCs dramatically reduced histopathological changes and proinflammatory cytokines while increasing anti-inflammatory cytokines. Furthermore, our findings supported that PGE2 priming improved the therapeutic efficacy of MSCs through M2 macrophage polarization. CONCLUSION: PGE2-MSC therapy significantly reduced the severity of LPS-induced ALI in mice by modulating macrophage polarization and cytokine production. This strategy boosts the therapeutic efficacy of MSCs in cell-based ALI therapy.

Constructing Selenium Nanoparticles with Enhanced Storage Stability and Antioxidant Activities via Conformational Transition of Curdlan.

Selenium nanoparticles (SeNPs) are among the emerging selenium supplements because of their high bioactivity and low toxicity. However, bare SeNPs are prone to activity loss caused by aggregation and sedimentation. This study aims to stabilize SeNPs with curdlan (CUR), a polysaccharide, to maintain or even enhance their biological activity. Herein, the stable SeNPs were constructed via the unique conformational transition of CUR induced by alkali-neutralization (AN) pretreatment. The physicochemical properties and structures of the prepared SeNPs were characterized by dynamic light scattering (DLS), UV-visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and free-radical-scavenging activity assays. The results show that most SeNPs are stabilized within the triple helix of CUR that has been pretreated with high-intensity AN treatment. These amorphous, small-sized (average size was 53.6 ± 17.7 nm), and stabilized SeNPs have significantly enhanced free-radical-scavenging ability compared to the control and can be well-stabilized for at least 240 days at 4 °C. This work indicates that CUR, as a food additive, can be used to well-stabilize SeNPs by AN pretreatment and provides a facile method to prepare and enhance the stability and bioactivity of SeNPs via triple-helix conformational transition.

Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP pathway.

Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, severely threatening human health. The infinite growth and metastasis of NSCLC cells result in a poor prognosis. Therefore, our study was to investigate the mechanism of Sestrin2 on the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Human embryonic lung fibroblasts, NSCLC cell lines, and nude mice were experimental subjects in this study. qRT-PCR and western blot were performed to evaluate the mRNA and protein expression of genes. CCK-8 and EdU assay were conducted to detect cell proliferation. The scratch test and Transwell assay were applied to examine cell migration and invasion. The bioinformatics analysis and Co-IP assay were employed to predict and consolidate the interaction between YAP and TEAD. We found the expression of Sestrin2 was declined but the expression of YAP was elevated in NSCLC cells. Sestrin2 sufficiency or YAP silencing could effectively impair cell growth and metastasis. Mechanistically, YAP interacted with TEAD to enhance FOXM1 expression. Additionally, the elevation of FOXM1 abolished the inhibitory influences of Sestrin2 sufficiency on NSCLC cell growth, invasion, and EMT process. Eventually, Sestrin2 elevation attenuated tumor growth in mice via modulation of the AMPK/YAP/FOXM1 axis, which was reversed by FOXM1 overexpression. Our consequences suggested Sestrin2 could inhibit the activation of YAP via prompting AMPK phosphorylation and then suppress FOXM1 expression through the interplay between YAP and TEAD to impair the capacities of NSCLC cell proliferation, migration, invasion, and EMT. This study provided a novel mechanism of Sestrin2 in NSCLC.

The cure rate of 10-day bismuth-containing quadruple therapy for Helicobacter pylori eradication is equivalent to 14-day: a systematic review and meta-analysis.

Helicobacter pylori (H. pylori) infection is a major cause of duodenal ulcers, gastric ulcers, and gastric cancer. However, the optimal duration for H. pylori eradication therapy remains controversial. Most studies have mainly focused on triple therapy, and there is insufficient research on bismuth-containing quadruple therapy. The aim of this study was to compare the clinical effect of the 10-day bismuth-containing quadruple treatment regimen with the 14-day regime in eradicating H. pylori. We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials published in English until May 2022 according to the eligibility criteria. Summary risk ratios (RRs) and 95% confidence intervals (CIs) for eradication rates, adverse effects, and compliance were calculated for included studies. Four studies, involving 1173 patients, were eligible for inclusion. The eradication rate was similar in the 10-day treatment group and the 14-day treatment group in the intention-to-treat analysis (RR 0.97, 95% CI 0.93 to 1.01). Meanwhile, the incidence of adverse effects was lower in patients who received 10 days of treatment than in those who received 14 days of treatment and patients' compliance was almost the same between two groups. Compared to the 14-day bismuth-containing quadruple regimens, 10-day regimens had similar efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and well-tolerated and should be recommended for H. pylori infection.

Valorizing protein-polysaccharide conjugates from sugar beet pulp as an emulsifier.

Inspired by the emulsion stability of sugar beet pulp pectin, the hydrophobic protein fraction in sugar beet pulp (SBP) is expected to feature high interfacial activity. This work retrieved alkaline extracted protein-polysaccharide conjugates (AEC) from partially depectinized SBP by hot alkaline extraction. AEC was protein-rich (57.20 %), and the polysaccharide mainly comprised neutral sugar, which adopted a rhamnogalacturonan-I pectin-like structure. The hydrophobic polypeptide chains tangled as a dense 'core' with polysaccharide chains attached as a hydrated 'shell' (hydrodynamic radius of ~110 nm). AEC could significantly decrease the oil-water interfacial tension (11.58 mN/m), featuring superior emulsification performance than three control emulsifiers, especially the excellent emulsifying stability (10 % oil) as the emulsion droplet size of 0.438 and 0.479 µm for fresh and stored (60 °C, 5 d) emulsions, respectively. The relationship of molecular structure to emulsification was investigated by specific enzymic modification, suggesting the intact macromolecular structure was closely related to emulsifying activity and that the NS fraction contributed greatly to emulsifying stability. Moreover, AEC was highly efficient to stabilize gel-like high internal phase emulsions (oil fraction 0.80) with low concentration (0.2 %) and even high ionic strength (0-1000 mM). Altogether, valorizing AEC as an emulsifier is feasible for high-value utilization of SBP.

Network Pharmacology-Based Exploration on the Intervention of Qinghao Biejia Decoction on the Inflammation-Carcinoma Transformation Process of Chronic Liver Disease via MAPK and PI3k/AKT Pathway.

Chronic liver disease(CLD) is a slow-developing and long-term disease that can cause serious damage to the liver. Thus far, it has been associated with viral hepatitis, non-alcoholic fatty liver disease(NAFLD), alcoholic liver disease(ALD), hepatic fibrosis(HF), liver cirrhosis (LC), and liver cancer. Qinghao Biejia Decoction (QBD) is a classic ancient Chinese herbal prescription with strong immune-enhancing, anti-inflammatory, and anti-tumor effects. In this study, we used a network pharmacology approach to investigate the molecular mechanisms of QBD in the inflammation-carcinoma transformation process of chronic liver disease. Two key drug targets, MAPK1 and PIK3CA, were screened using network pharmacology and molecular docking techniques, revealing dihydroartemisinin, artesunate, 12-O-Nicotinoylisolineolone, caffeic acid, and diincarvilone A as active ingredients involved in QBD mechanisms. The main signaling pathways involved were the PI3K-AKT signaling pathway and MAPK signaling pathway. In summary, our results indicated that QBD affects the inflammatory transformation of chronic liver disease through MAPK1 and PIK3CA and signaling pathways MAPK and PI3K/AKT. These data provide research direction for investigating the mechanisms underlying the inflammation-carcinoma transformation process in QBD for chronic liver disease.