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1.
Angew Chem Int Ed Engl ; : e202410442, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993065

ABSTRACT

Renewable electricity driven electrosynthesis of cyclohexanone oxime (C6H11NO) from cyclohexanone (C6H10O) and nitrogen oxide (NOx) is a promising alternative to traditional environment-unfriendly industrial technologies for green synthesis of C6H11NO. Precisely controlling the reaction pathway of the C6H10O/NOx-involved electrochemical reductive coupling reaction is crucial for selectively producing C6H11NO, which is yet still challenging. Herein, we report a porous high-entropy alloy PdCuAgBiIn metallene (HEA-PdCuAgBiInene) to boost the electrosynthesis of C6H11NO from C6H10O and nitrite, achieving a high Faradaic efficiency (47.6%) and almost 100% yield under ambient conditions. In situ Fourier transform infrared spectroscopy and theoretical calculations demonstrate that unconventional orbital hybridization between d-block metals and p-block metals could regulate the local electronic structure of active sites and induce electron localization of electron-rich Pd sites, which tunes the active hydrogen supply and facilitates the generation and enrichment of key intermediates NH2OH* and C6H10O*, and efficiently promotes their C-N coupling to selectively produce C6H11NO.

2.
Bioresour Technol ; : 131083, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972430

ABSTRACT

Algae-mediated nitrogen removal from low carbon vs. nitrogen (C/N) wastewater techniques has garnered significant attention due to its superior autotrophic assimilation properties. This study investigated the ammonium-N removal potential of four algae species from low C/N synthetic wastewater. Results showed that 95 % and 99 % of ammonium-N are eliminated at initial concentrations of 11.05 ±â€¯0.98 mg/L and 42.51 ±â€¯2.20 mg/L with little nitrate and nitrite accumulation. The compositions of secreted algal-derived dissolved organic matter varied as C/N decreased and showed better bioavailability for nitrate-N removal by Pseudomonas sp. SZF15 without pre-oxidation, achieving an efficiency of 99 %. High-throughput sequencing revealed that the aquatic microbial communities, dominated by Scenedesmus, Kalenjinia, and Micractinium, remain relatively stable across different C/N, aligning with the underlying metabolic pathways. These findings may provide valuable insights into the sustainable elimination of multiple nitrogen contaminants from low C/N wastewater.

3.
Article in English | MEDLINE | ID: mdl-38976328

ABSTRACT

BACKGROUND: Several studies have reported the role of Helicobacter pylori (H. pylori) eradication in gastric cancer (GC) prevention. However, for individuals with unsatisfactory management of their H. pylori infection status after eradication, the risk of GC remains unclear. METHODS: An exhaustive search strategy of the incidence of GC (including primary gastric cancer [PGC] and metachronous gastric cancer [MGC]) incidence in patients with unsuccessful eradication or H. pylori reinfection was implemented in the PubMed, Embase, Cochrane Library, and Web of Science. The Hazard ratios (HRs) and cumulative incidence of total GC in patients with failed eradication or H. pylori reinfection (FE-Hp (+)) group were compared with that in patients with successful eradication and no H. pylori reinfection (SE-Hp (-)) group and patients with noneradication (NE) group. RESULTS: Seven eligible studies (including 8767 H. pylori infection patients) were identified. In the FE-Hp (+) group, the total GC risk was 1.86-fold of that in the SE-Hp (-) group (HR=1.86, 95% CI: 1.14-3.04, P=0.013). The total GC risk in the NE group was also higher than that in the FE-Hp (+) group (HR= 1.98,95% CI: 1.11-3.52, P=0.002). On further analysis with different endpoints showed that the pooled GC risk increased over time (5-year follow-up: HR=2.92, 1.34-6.34; 10-year follow-up: HR=4.04, 2.56-6.37). CONCLUSION: Compared with the SE-Hp (-) group, the FE-Hp (+) group had a higher risk of gastric carcinoma. Long-term monitoring of H. pylori infection status could consolidate the benefit of eradicating H. pylori for preventing GC prevention in patients after eradication.

4.
World J Gastrointest Oncol ; 16(6): 2697-2715, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994159

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.

5.
Adv Healthc Mater ; : e2401120, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888501

ABSTRACT

Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan-catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.

6.
Nat Commun ; 15(1): 5287, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902231

ABSTRACT

Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.


Subject(s)
Anti-Bacterial Agents , Bacteriophages , Nanoparticles , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Nanoparticles/chemistry , Drug Delivery Systems/methods , Viral Proteins/metabolism , Viral Proteins/chemistry , Animals , Mice , Rifampin/pharmacology , Rifampin/administration & dosage , Humans , Ampicillin , Bacterial Infections/drug therapy
7.
Int J Biol Macromol ; 273(Pt 1): 133008, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38852736

ABSTRACT

The mucosal barrier and scavenging effect of the mucosal layer are two main obstacles in inducing mucosal immunization. To overcome these obstacles, we synthesized a bio-inspired mucoadhesive material, chitosan-catechol (ChiC), for surface modification of inactive porcine epidemic diarrhea virus (PEDV). Studies have revealed that PEDV particles can be facilely and mildly modified by Chi-C forming Chi-C-PEDV nanoparticles (Chic-Ps) through the covalent and electrostatic bond, which effectively prolongs the retention time of PEDV in the nasal mucosa. The cell co-culture model demonstrated that Chic-Ps exhibit enhanced recruitment of dendritic cells via the secretion of stimulating chemokine CCL20 and improving antigen permeability by disruption the distribution of ZO-1 protein in epithelial cells. Additionally, the flow cytometry (FCM) analysis revealed that Chic-Ps facilitate trafficking to lymph nodes and induce stronger cellular and humoral immune responses compared to unmodified PEDV. Notably, Chic-Ps induced a higher level of PEDV neutralizing antibody was induced by Chic-Ps in the nasal washes, as confirmed by a plaque reduction neutralization test. These results demonstrate that Chi-C is a promising nasal delivery system for vaccines. Proof of principle was obtained for inactivated PEDV, but similar delivery mechanisms could be applied in other vaccines when intranasal administration is needed.


Subject(s)
Administration, Intranasal , Catechols , Chitosan , Chitosan/chemistry , Animals , Catechols/chemistry , Mice , Immunization , Swine , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Nanoparticles/chemistry , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Chlorocebus aethiops , Drug Delivery Systems , Vero Cells
8.
Food Chem ; 454: 139744, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38797096

ABSTRACT

The long-term and excessive use of glyphosate (GLY) in diverse matrices has caused serious hazard to the human and environment. However, the ultrasensitive detection of GLY still remains challenging. In this study, the smartphone-assisted dual-signal mode ratiometric fluorescent and paper sensors based on the red-emissive gold nanoclusters (R-AuNCs) and blue-emissive carbon dots (B-CDs) were ingeniously designed accurate and sensitive detection of GLY. Upon the presence of GLY, it would quench the fluorescence of B-CDs through dynamic quenching effect, and strengthen the fluorescence response of R-AuNCs due to aggregation-induced enhancement effect. Through calculating the GLY-induced fluorescence intensity ratio of B-CDs to R-AuNCs by using a fluorescence spectrophotometer, low to 0.218 µg/mL of GLY could be detected in lab in a wide concentration range of 0.3-12 µg/mL with high recovery of 94.7-103.1% in the spiked malt samples. The smartphone-assisted ratiometric fluorescent sensor achieved in the 96-well plate could monitor 0-11 µg/mL of GLY with satisfactory recovery of 94.1-107.0% in real edible malt matrices for high-throughput analysis. In addition, a portable smartphone-assisted ratiometric paper sensor established through directly depositing the combined B-CDs/R-AuNCs probes on the test strip could realize on-site measurement of 2-8 µg/mL of GLY with good linear relationship. This study provides new insights into developing the dual-signal ratiometric sensing platforms for the in-lab sensitive detection, high-throughput analysis, and on-site portable measurement of more trace contaminants in foods, clinical and environmental samples.


Subject(s)
Food Contamination , Glycine , Glyphosate , Herbicides , Smartphone , Glycine/analogs & derivatives , Glycine/analysis , Food Contamination/analysis , Herbicides/analysis , Spectrometry, Fluorescence/methods , Paper , Quantum Dots/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Fluorescence , Edible Grain/chemistry , Limit of Detection
9.
Nature ; 629(8013): 937-944, 2024 May.
Article in English | MEDLINE | ID: mdl-38720067

ABSTRACT

QS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host's native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families-a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases-from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure-activity relationship, and will thus enable the rational design of potent vaccine adjuvants.


Subject(s)
Adjuvants, Immunologic , Metabolic Engineering , Saccharomyces cerevisiae , Saponins , Adjuvants, Immunologic/biosynthesis , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/genetics , Adjuvants, Immunologic/metabolism , Biosynthetic Pathways/genetics , Drug Design , Enzymes/genetics , Enzymes/metabolism , Metabolic Engineering/methods , Plants/enzymology , Plants/genetics , Plants/metabolism , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saponins/biosynthesis , Saponins/chemistry , Saponins/genetics , Saponins/metabolism , Structure-Activity Relationship
10.
ACS Omega ; 9(19): 21035-21041, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38764623

ABSTRACT

A robust and versatile dual-signal enhanced fluorescent aptasensor was developed for ochratoxin A (OTA) detection based on fluorescence resonance energy transfer between 5-carboxyfluorescein (FAM) and Super Green I (SG) fluorophores as the donor and graphene oxide (GO) nanosheet as the acceptor. Abundant SG probes were adsorbed into the FAM-complementary DNA (cDNA)-aptamer double-stranded structure to achieve remarkably enhanced fluorescence responses. Without OTA, the FAM-cDNA-SG conjugates coexisted with GO nanosheets, exhibiting strong fluorescence signals. In the presence of OTA, it was captured by the aptamers to release cDNA-FAM and SG probes, which were adsorbed by GO, leading to OTA-dependent fluorescence quenching. The changed fluorescence intensity was measured for accurate quantitation of OTA. Under optimum conditions, the dual-signal enhanced fluorescent aptasensor realized fascinating sensitivity with a limit of detection of 0.005 ng/mL and a wide concentration range of 0.02-20 ng/mL, as well as high selectivity for OTA over other interfering substances, excellent accuracy with average recoveries of 91.37-116.83% in the fortified malt matrices, and superior reliability and practicability in actual samples. This FAM-cDNA-aptamer-SG/GO nanosheet-based aptasensing platform could be extended to monitor other contaminants or trace molecules in food, environmental, and diagnostic fields by altering the corresponding aptamers.

11.
Antioxidants (Basel) ; 13(5)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38790630

ABSTRACT

Chickens are a major source of meat and eggs in human food and have significant economic value. Cadmium (Cd) is a common environmental pollutant that can contaminate feed and drinking water, leading to kidney injury in livestock and poultry, primarily by inducing the generation of free radicals. It is necessary to develop potential medicines to prevent and treat Cd-induced nephrotoxicity in poultry. Luteolin (Lut) is a natural flavonoid compound mainly extracted from peanut shells and has a variety of biological functions to defend against oxidative damage. In this study, we aimed to demonstrate whether Lut can alleviate kidney injury under Cd exposure and elucidate the underlying molecular mechanisms. Renal histopathology and cell morphology were observed. The indicators of renal function, oxidative stress, DNA damage and repair, NAD+ content, SIRT1 activity, and autophagy were analyzed. In vitro data showed that Cd exposure increased ROS levels and induced oxidative DNA damage and repair, as indicated by increased 8-OHdG content, increased γ-H2AX protein expression, and the over-activation of the DNA repair enzyme PARP-1. Cd exposure decreased NAD+ content and SIRT1 activity and increased LC3 II, ATG5, and particularly p62 protein expression. In addition, Cd-induced oxidative DNA damage resulted in PARP-1 over-activation, reduced SIRT1 activity, and autophagic flux blockade, as evidenced by reactive oxygen species scavenger NAC application. The inhibition of PARP-1 activation with the pharmacological inhibitor PJ34 restored NAD+ content and SIRT1 activity. The activation of SIRT1 with the pharmacological activator RSV reversed Cd-induced autophagic flux blockade and cell injury. In vivo data demonstrated that Cd treatment caused the microstructural disruption of renal tissues, reduced creatinine, and urea nitrogen clearance, raised MDA content, and decreased the activities or contents of antioxidants (GSH, T-SOD, CAT, and T-AOC). Cd treatment caused oxidative DNA damage and PARP-1 activation, decreased NAD+ content, decreased SIRT1 activity, and impaired autophagic flux. Notably, the dietary Lut supplement observably alleviated these alterations in chicken kidney tissues induced by Cd. In conclusion, the dietary Lut supplement alleviated Cd-induced chicken kidney injury through its potent antioxidant properties by relieving the oxidative DNA damage-activated PARP-1-mediated reduction in SIRT1 activity and repairing autophagic flux blockade.

12.
Heliyon ; 10(9): e30343, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707325

ABSTRACT

Adhesions are the most common complication of abdominal or pelvic surgery and remain a challenging problem. To better understand the development tendency of abdominal adhesions, we performed a comprehensive bibliometric analysis of the field of abdominal adhesions. In total, 2219 articles regarding abdominal adhesions were screened and analyzed from 3410 manuscripts indexed in the Web of Science-indexed manuscripts regarding abdominal adhesion from 2004 to 2023. A bibliometric analysis was performed, and CiteSpace [version 6.2. R3 (64-bit)] and VOSviewer (version 1.6.19) were used to visualize the results. The number of annual publications showed slight growth before 2019, and the USA contributed the most publications. The most prolific author in this domain was Diamond, while the publications from Ten Broek had the strongest influence. The most popular journal in this field was the Journal of Surgical Research, and the most frequently co-cited journal was Fertility and Sterility. After analyzing the keywords, "prevention", "surgery" and "peritoneal adhesion" were the 3 most co-cited keywords, while "adhesive small bowel obstruction" was the strongest keyword in the citation burst. Here, for the first time, we used bibliometric methods to study abdominal adhesions over the past ten years. By summarizing the characteristics of publications and predicting future research prospects, we established a framework for researchers and provided a basis for subsequent research.

13.
Nanoscale ; 16(17): 8546-8562, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38596837

ABSTRACT

Improving the mechanical properties of wound dressings and achieving personalized automatic real-time in situ deposition are important for accelerating wound management and repair. In this study, we report a self-designed automatic in situ deposition device based on solution blow spinning (SBS) to prepare poly(lactic-co-glycolic acid) (PLGA) and poly-L-lactic acid (PLLA) composite (PLGA/PLLA) nanofibrous membranes for wound dressing at a short distance. Polymer solution and in situ deposition conditions, including air pressure, spinning distance, solvent extrusion rate, and spinning rate, were optimized using orthogonal experiments and characterized via dynamic mechanical analysis. The microscopic morphology and physical properties of the prepared PLGA/PLLA composite nanofibrous membranes show that their strength, adhesion, water vapor transmission rate (WVTR), water retention, water absorption, degradation, and other properties were sufficient for wound-dressing applications. To investigate the possibility of a biomedical wound-dressing material, tannic acid (TA) was incorporated into the PLGA/PLLA composite nanofibrous membranes. The resultant PLGA/PLLA/TA composite nanofibrous membranes exhibited good biocompatibility and exceptional antibacterial properties against both Escherichia coli and Staphylococcus aureus. A pilot animal study illustrated the potential of this in situ deposition of PLGA/PLLA/TA composite nanofibrous membranes across multiple applications in wound healing/repair by reducing wound scar tissue formation and fibroblast overactivation.


Subject(s)
Anti-Bacterial Agents , Bandages , Escherichia coli , Nanofibers , Polyesters , Polylactic Acid-Polyglycolic Acid Copolymer , Staphylococcus aureus , Wound Healing , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Nanofibers/chemistry , Staphylococcus aureus/drug effects , Animals , Escherichia coli/drug effects , Polyesters/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Wound Healing/drug effects , Membranes, Artificial , Mice , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Humans
14.
Article in English | MEDLINE | ID: mdl-38578884

ABSTRACT

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

15.
Acta Pharmacol Sin ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627462

ABSTRACT

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

16.
ChemSusChem ; : e202400624, 2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38616165

ABSTRACT

Glycerol oxidation-assisted water electrolysis has emerged as a cost-effective way of co-producing green hydrogen and HCOOH. Still, preparing highly selective and stable nickel-based metal electrocatalysts remains a challenge. Herein, heterostructure Ni3N/WO3 nanosheet arrays of bifunctional catalysts with large specific surface areas loaded on nickel foam (denoted as Ni3N/WO3/NF) were synthesized. This catalyst was for glycerol oxidation reaction (GOR) and hydrogen evolution reaction (HER) with excellent catalytic performance, a voltage saving of 267 mV compared to oxygen evolution reaction (OER), and a HER overpotential of 104 mV at 100 mA cm-2. The cell voltage in the assembled GOR//HER hybrid electrolysis system reaches 100 mA cm-2 at 1.50 V, 296 mV lower than the potential required for overall water splitting. This work demonstrates that replacing GOR with OER using a cost-effective and highly active Ni-based bifunctional electrocatalyst can make hybrid water electrolysis an energy-efficient, sustainable, and green strategy for hydrogen production.

17.
Sci Total Environ ; 930: 172702, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38657810

ABSTRACT

Exogenous Si mitigates the mobility and bioavailability of Cd in the soil, thereby alleviating its phytotoxicity. This study focused on specific Si-induced immobilisation effects within the rhizosphere (S1), near-rhizosphere (S2), and far-rhizosphere (S3) zones. Based on the rhizobox experiment, we found that applying Si significantly elevated soil pH, and the variation amplitudes in the S3 soil exceeded those in the S1 and S2 soils. Si-induced changes in the rhizosphere also included enhanced dissolved organic carbon and diminished soil Eh, particularly in the Si400 treatment. Meanwhile, the introduction of Si greatly enhanced the Fe2+ and Mn2+ concentrations in the S1 soil, but reduced them in the S2 soil. The rhizosphere effect of Si which enriched Fe2+ and Mn2+ subsequently promoted the formation of Fe and Mn oxides/hydro-oxides near the rice roots. Consequently, the addition of Si significantly reduced the available Cd concentrations in S1, surpassing the reductions in S2 and S3. Moreover, Si-treated rice exhibited increased Fe plaque generation and fixation on soil Cd, resulting in decreased Cd concentrations in rice tissues, accompanied by reduced Cd translocation from roots to shoots and shoots to grains. Structural equation modelling further highlighted that Si is essential in Cd availability in S1 and Fe plaque development, ultimately mitigating Cd accumulation in rice. Si-treated rice also exhibited higher biomass and grain yield than those of control groups. These findings provide valuable insights into Si-based strategies for addressing the Cd contamination of agricultural soils.


Subject(s)
Cadmium , Oryza , Rhizosphere , Silicon , Soil Pollutants , Soil , Cadmium/analysis , Soil Pollutants/analysis , Soil/chemistry , Biological Availability , Plant Roots , Fertilizers
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 411-417, 2024 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-38645840

ABSTRACT

Objective: To analyze the effect of additional surgery on the survival and prognosis of high-risk T1 colorectal cancer patients who have undergone endoscopic resection. Methods: The clinical data of patients with high-risk T1 colorectal cancer were retrospectively collected. The patients were divided into the endoscopic resection (ER) plus additional surgical resection (SR) group, or the ER+SR group, and the ER group according to whether additional SR were performed after ER. Baseline data of the patients and information on the location, size, and postoperative pathology of the lesions were collected. Patient survival-related information was obtained through the medical record system and patient follow-up. The primary outcome indicators were the overall survival and the colorectal cancer-specific survival. Univariate Cox regression analysis was used to screen survival-related risk factors and hazard ratio (HR) was calculated. Multivariate Cox regression analysis was used to analyze the independent influencing factors. Results: The data of 109 patients with T1 high-risk colorectal cancer were collected, with 52 patients in the ER group and 57 patients in the ER+SR group. The mean age of patients in the ER group was higher than that in the ER+SR group (65.21 years old vs. 60.54 years old, P=0.035), and the median endoscopic measurement of the size of lesions in the ER group was slightly lower than that in the ER+SR group (2.00 cm vs. 2.50 cm, P=0.026). The median follow-up time was 30.00 months, with the maximum follow-up time being 119 months, in the ER+SR group and there were 4 patients deaths, including one colorectal cancer-related death. Whereas the median follow-up time in the ER group was 28.50 months, with the maximum follow-up time being 78.00 months, and there were 4 patient deaths, including one caused by colorectal cancer. The overall 5-year cumulative survival rates in the ER+SR group and the ER group were 94.44% and 81.65%, respectively, and the cancer-specific 5-year cumulative survival rates in the ER+SR group and the ER group were 97.18% and 98.06%, respectively. The Kaplan-Meier analysis showed no significant difference in the overall cumulative survival or cancer-specific cumulative survival between the ER+SR and the ER groups. Univariate Cox regression analysis showed that age and the number of reviews were the risk factors of overall survival (HR=1.16 and HR=0.27, respectively), with age identified as an independent risk factor of overall survival in the multivariate Cox regression analysis (HR=1.10, P=0.045). Conclusion: For T1 colorectal cancer patients with high risk factors after ER, factors such as patient age and their personal treatment decisions should not be overlooked. In clinical practice, additional caution should be exercised in decision-making concerning additional surgery.


Subject(s)
Colorectal Neoplasms , Humans , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Retrospective Studies , Female , Male , Prognosis , Aged , Middle Aged , Risk Factors , Survival Rate , Proportional Hazards Models
19.
Clin Chim Acta ; 558: 119675, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38631604

ABSTRACT

BACKGROUND: Gastric cancer (GC) is characterized by high morbidity, high mortality and low early diagnosis rate. Early diagnosis plays a crucial role in radically treating GC. The aim of this study was to identify plasma biomarkers for GC and early GC diagnosis. METHODS: We quantified 369 protein levels with plasma samples from discovery cohort (n = 88) and validation cohort (n = 50) via high-throughput proximity extension assay (PEA) utilizing the Olink-Explore-384-Cardiometabolic panel. The multi-protein signatures were derived from LASSO and Ridge regression models. RESULTS: In the discovery cohort, 13 proteins (GDF15, ITIH3, BOC, DPP7, EGFR, AMY2A, CCDC80, CD163, GPNMB, LTBP2, CTSZ, CCL18 and NECTIN2) were identified to distinguish GC (Stage I-IV) and early GC (HGIN-I) groups from control group with AUC of 0.994 and AUC of 0.998, severally. The validation cohort yielded AUC of 0.930 and AUC of 0.818 for GC and early GC, respectively. CONCLUSIONS: This study identified a multi-protein signature with the potential to benefit clinical GC diagnosis, especially for Asian and early GC patients, which may contribute to the development of a less-invasive, convenient, and efficient early screening tool, promoting early diagnosis and treatment of GC and ultimately improving patient survival.


Subject(s)
Biomarkers, Tumor , Early Detection of Cancer , Proteomics , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/blood , Biomarkers, Tumor/blood , Female , Male , Proteomics/methods , Middle Aged , Cohort Studies , Aged
20.
Virol J ; 21(1): 97, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671522

ABSTRACT

BACKGROUND: Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted. METHODS: In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection. RESULTS: We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes. CONCLUSIONS: These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.


Subject(s)
CD4-Positive T-Lymphocytes , DNA Methylation , HIV Infections , HIV-1 , vpr Gene Products, Human Immunodeficiency Virus , Humans , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , HIV-1/genetics , HIV-1/physiology , HIV-1/immunology , vpr Gene Products, Human Immunodeficiency Virus/genetics , vpr Gene Products, Human Immunodeficiency Virus/metabolism , HIV Infections/virology , HIV Infections/immunology , HIV Infections/genetics , Promoter Regions, Genetic , Gene Expression Regulation
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