OsEIL2 balances rice immune responses against (hemi)biotrophic and necrotrophic pathogens via the salicylic acid and jasmonic acid synergism.

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.

Sluggish and Ion-Resilient Behavior of Interfacial Aqueous Layer on Single-Layer Graphene Oxide: Insights from In Situ Atomic Force Microscopy.

Understanding interfacial interactions of graphene oxide (GO) is important to evaluate its colloidal behavior and environmental fate. Single-layer GO is the fundamental unit of GO colloids, and its interfacial aqueous layers critically dictate these interfacial interactions. However, conventional techniques like X-ray diffraction are limited to multilayer systems and are inapplicable to single-layer GO. Therefore, our study employed atomic force microscopy to precisely observe the in situ dynamic behaviors of interfacial aqueous layers on single-layer GO. The interfacial aqueous layer height was detected at the subnanometer level. In real-time monitoring, the single-layer height increased from 1.17 to 1.70 nm within 3 h immersion. This sluggish process is different from the rapid equilibration of multilayer GO in previous studies, underscoring a gradual transition in hydration kinetics. Ion strength exhibited negligible influence on the single-layer height, suggesting a resilient response of the interfacial aqueous layer to ion-related perturbations due to intricate ion interactions and electrical double-layer compression. Humic acid led to a substantial increase in the interfacial aqueous layers, improving the colloidal stability of GO and augmenting its potential for migration. These findings hold considerable significance regarding the environmental behaviors of the GO interfacial aqueous layer in ion- and organic-rich water and soil.

Natural Disinfection-like Process Unveiled in Soil Microenvironments by Enzyme-Catalyzed Chlorination.

Substantial natural chlorination processes are a growing concern in diverse terrestrial ecosystems, occurring through abiotic redox reactions or biological enzymatic reactions. Among these, exoenzymatically mediated chlorination is suggested to be an important pathway for producing organochlorines and converting chloride ions (Cl-) to reactive chlorine species (RCS) in the presence of reactive oxygen species like hydrogen peroxide (H2O2). However, the role of natural enzymatic chlorination in antibacterial activity occurring in soil microenvironments remains unexplored. Here, we conceptualized that heme-containing chloroperoxidase (CPO)-catalyzed chlorination functions as a naturally occurring disinfection process in soils. Combining antimicrobial experiments and microfluidic chip-based fluorescence imaging, we showed that the enzymatic chlorination process exhibited significantly enhanced antibacterial activity against Escherichia coli and Bacillus subtilis compared to H2O2. This enhancement was primarily attributed to in situ-formed RCS. Based on semiquantitative imaging of RCS distribution using a fluorescence probe, the effective distance of this antibacterial effect was estimated to be approximately 2 mm. Ultrahigh-resolution mass spectrometry analysis showed over 97% similarity between chlorine-containing formulas from CPO-catalyzed chlorination and abiotic chlorination (by sodium hypochlorite) of model dissolved organic matter, indicating a natural source of disinfection byproduct analogues. Our findings unveil a novel natural disinfection process in soils mediated by indigenous enzymes, which effectively links chlorine-carbon interactions and reactive species dynamics.

Safety analysis of therapeutic drugs for breast cancer patients and construction of a predictive model for serious adverse drug reactions.

OBJECTIVES: To explore the characteristics of the occurrence of antineoplastic drug adverse reactions (ADRs) in breast cancer and to utilize a computerized tool to identify early warning indicators of potentially serious ADRs. METHODS: We conducted descriptive statistical analyses of the demographic features, medication use characteristics, and clinical manifestations of suspected ADRs in ADR-exposed patients using data from the Shaanxi Provincial Adverse Drug Reaction Monitoring Center, China, from 2017 to 2021. Using disproportionality methods (reporting odds ratio, proportional reporting ratio, and comprehensive standard method), the relationship between drugs and ADRs was measured. Finally, a web-based clinical prediction model for serious ADRs based on binary logistic regression was developed to estimate individual event probabilities numerically. RESULTS: We developed a new computer-mineable breast cancer-ADR system. In total, 1119 ADR reports were received between 2017 and 2021, with an increasing trend in the number. Antineoplastic medications of natural sources made up the greatest portion of the drug category (530, 38.10%) while targeted drugs' part increased with time. The medicine with the greatest number of ADR cases was docetaxel. Bone marrow failure was the most reported ADR. The disproportionality methods produced 19 signals of disproportionate reporting, two signals of disproportionate reporting were unknown ADRs. The occurrence of serious ADRs was shown to be substantially correlated with gender, platinum drugs, and blood and lymphatic system disorders. The clinical prediction model for serious ADRs had above-moderate discriminatory power (C-index was 0.775). CONCLUSIONS: The number of ADRs to breast cancer antineoplastic drugs was constantly increasing, with docetaxel ranking first, with the majority of ADRs presenting as bone marrow suppression, nausea, and vomiting. Data mining identified 19 signals of disproportionate reporting.

An inferior vena cava-priority approach in laparoscopic isolated hepatic caudate lobectomy.

PURPOSE: Laparoscopic isolated caudate lobectomy is still a challenging operation for surgeons. The access route of the operation plays a vital role during laparoscopic caudate lobectomy. There are few references regarding this technique. Here, we introduce a preferred inferior vena cava (IVC) approach in laparoscopic caudate lobectomy. METHODS: Twenty-one consecutive patients with caudate hepatic tumours between June 2016 and December 2021 were included in this study. All of them received laparoscopic caudate lobectomy involving an IVC priority approach. The IVC priority approach refers to prioritizing the dissection of the IVC from the liver parenchyma before proceeding with the conventional left or right approach. It emphasizes the importance of the IVC dissection during process. Clinical data, intraoperative parameters and postoperative results were evaluated. Sixteen patients were performed pure IVC priority approach, while 5 patients underwent a combined approach. We subsequently compared the intraoperative and postoperative between the two groups. RESULTS: All 21 patients were treated with laparoscopic technology. The operative time was 190.95 ± 92.65 min. The average estimated blood loss was 251.43 ± 247.45 ml, and four patients needed blood transfusions during the perioperative period. The average duration of hospital stay was 8.43 ± 2.64 (range from 6.0 to 16.0) days. Patients who underwent the pure inferior vena cava (IVC) approach required a shorter hepatic pedicle clamping time (26 vs. 55 min, respectively; P < 0.001) and operation time (150 vs. 380 min, respectively; P = 0.002) than those who underwent the combined approach. Hospitalization (7.0 vs. 9.0 days, respectively; P = 0.006) was shorter in the pure IVC group than in the combined group. CONCLUSIONS: Laparoscopic caudate lobectomy with an IVC priority approach is safe and feasible for patients with caudate hepatic tumours.

Association between sleep disorders and physical activity in middle-aged Americans: a cross-sectional study from NHANES.

BACKGROUND: Among the numerous studies on physical activity and sleep disorders, few have focused on physical activity and sleep disorders in middle-aged people who are particularly stressed. A restricted cubic web (RCS) technique was applied to determine whether physical activity and the self-rated prevalence of sleep disorders exhibit a dose-response relationship in middle-aged adults. METHODS: This study analyzed 8880 middle-aged adults aged 40-65 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) between physical activity and sleep disorders in middle-aged adults. Thereafter, the dose-response connection was examined using RCS. RESULTS: After adjusting for potential confounders, subjects with MET values in the first quartile (Q1) had odds ratios (OR) for sleep disturbance of 0.851 (95% CI = 0.745-0.973), 0.800 (95% CI = 0.698-0.917), and 0.780 (95% CI = 0.680-0.895) compared to subjects with MET values in the second, third, and fourth quartiles respectively. RCS regression showed a non-linear association between physical activity and sleep disorders in middle-aged adults (non-linearity P = 0.0382). Furthermore, the prevalence of sleep disorders in middle-aged adults decreased with increasing physical activity, reaching a minimum when weekly physical activity was around 166.27MET*h (OR = 0.885, 95% CI = 0.799-0.981). CONCLUSION: Our research demonstrates that physical activity was negatively associated with sleep disorders.

Efficacy, immunogenicity and safety of respiratory syncytial virus prefusion F vaccine: systematic review and meta-analysis.

OBJECTIVE: A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine. METHODS: We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills. CONCLUSIONS: Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.

The short- and long-term effects of community-family-doctor-based type 2 diabetes self-management interventions.

OBJECTIVES: The popularity of contracted family doctor services in China has been growing in recent years, but community-family-doctor-based type 2 diabetes mellitus (T2DM) intervention programs have yet to be adequately studied. This study was to evaluate the short- and long-term effects of community-family-doctor-based self-management interventions for T2DM and to explore strategies for long-term glycemic control. STUDY DESIGN: This was a randomized controlled trial. METHODS: A total of 144 eligible participants were randomly assigned to intervention and control groups. The control group received only routine community diabetes care, and the intervention group received community-family-doctor-based interventions involving the same standard of care. The interventions lasted for 3 months, and the follow-up was continued for 15 months. Intention-to-treat analysis and generalized estimation equations were then used to determine the short- and long-term effects of the interventions on glycated hemoglobin (HbA1c), diabetes self-management, and medication adherence. RESULTS: There were statistically significantly greater improvements in all aspects of the intervention group after 3 months of intervention. Compared with baseline, changes in the attitude (ß = 0.384, 95% confidence interval [CI; 0.194, 0.574], P < 0.001), practice (ß = 1.751, 95% CI [0.762, 2.739], P = 0.001), and knowledge, attitudes, practice total scores (ß = 2.338, 95% CI [0.682, 3.995], P = 0.006) of patients in the intervention group were statistically significant after 15 months, and the HbA1c (8.19 ± 1.73%), knowledge (16.42 ± 3.21), and medication adherence (5.53 ± 1.76) scores were slightly better than those at baseline, although not statistically significant (P > 0.05). CONCLUSIONS: T2DM self-management interventions based on community family doctors improved patients' HbA1c, diabetes self-management, and medication adherence, did not do so significantly in the long term.

Mercury pollution risks of agricultural soils and crops in mercury mining areas in Guizhou Province, China: effects of large mercury slag piles.

The historical large mercury slag piles still contain high concentrations of mercury and their impact on the surrounding environment has rarely been reported. In this study, three different agricultural areas [the area with untreated piles (PUT), the area with treated piles (PT), and the background area with no piles (NP)] were selected to investigate mercury slag piles pollution in the Tongren mercury mining area. The mercury concentrations of agricultural soils ranged from 0.42 to 155.00 mg/kg, determined by atomic fluorescence spectrometry of 146 soil samples; and mercury concentrations in local crops (rice, maize, pepper, eggplant, tomato and bean) all exceeded the Chinese food safety limits. Soil and crop pollution trends in the three areas were consistent as PUT > PT > NP, indicating that mercury slag piles have exacerbated pollution. Mercury in the slag piles was adsorbed by multiple pathways of transport into soils with high organic matter, which made the ecological risk of agricultural soils appear extremely high. The total hazard quotients for residents from ingesting mercury in these crops were unacceptable in all areas, and children were more likely to be harmed than adults. Compared to the PT area, treatment of slag piles in the PUT area may decrease mercury concentrations in paddy fields and dry fields by 46.02% and 70.36%; further decreasing health risks for adults and children by 47.06% and 79.90%. This study provided a scientific basis for the necessity of treating large slag piles in mercury mining areas.

Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours.

BACKGROUND: The vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC). METHODS: Immunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases. RESULTS: Among 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively. CONCLUSION: Claudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

The Composition and Diversity of the Rhizosphere Bacterial Community of Ammodendron bifolium Growing in the Takeermohuer Desert Are Different from Those in the Nonrhizosphere.

Soil microorganisms play important roles in vegetation establishment and soil biogeochemical cycling. Ammodendron bifolium is a dominant sand-fixing (i.e., stabilizing sand dunes) and endangered plant in the Takeermohuer Desert, and the bacterial community associated with this plant rhizosphere is still unclear. In this study, we investigated the composition and diversity of the bacterial community from the A. bifolium rhizosphere and bulk soil at different soil depths (i.e., 0-40 cm, 40-80 cm, 80-120 cm) using culture and high-throughput sequencing methods. We preliminarily analyzed the edaphic factors influencing the structure of bacterial communities. The results showed that the high-salinity Takeermohuer Desert has an oligotrophic environment, while the A. bifolium rhizosphere exhibited a relatively nutrient-rich environment due to higher contents of soil organic matter (SOM) and soil alkaline nitrogen (SAN) than bulk soil. The dominant bacterial groups in the desert were Actinobacteria (39.8%), Proteobacteria (17.4%), Acidobacteria (10.2%), Bacteroidetes (6.3%), Firmicutes (6.3%), Chloroflexi (5.6%), and Planctomycetes (5.0%) at the phylum level. However, the relative abundances of Proteobacteria (20.2%) and Planctomycetes (6.1%) were higher in the rhizosphere, and those of Firmicutes (9.8%) and Chloroflexi (6.9%) were relatively higher in barren bulk soil. A large number of Actinobacteria were detected in all soil samples, of which the most abundant genera were Streptomyces (5.4%) and Actinomadura (8.2%) in the bulk soil and rhizosphere, respectively. The Chao1 and PD_whole_tree indices in the rhizosphere soil were significantly higher than those in the bulk soil at the same soil depth and tended to decrease with increasing soil depth. Co-occurrence network analyses showed that the keystone species in the Takeermohuer Desert were the phyla Actinobacteria, Acidobacteria, Proteobacteria, and Chloroflexi. Furthermore, the major edaphic factors affecting the rhizosphere bacterial community were electrical conductivity (EC), SOM, soil total nitrogen (STN), SAN, and soil available potassium (SAK), while the major edaphic factors affecting the bacterial community in bulk soil were distance and ratio of carbon to nitrogen (C/N). We concluded that the A. bifolium rhizosphere bacterial community is different from that of the nonrhizosphere in composition, structure, diversity, and driving factors, which may improve our understanding of the relationship between plant and bacterial communities and lay a theoretical foundation for A. bifolium species conservation in desert ecosystems.

Composition and Distribution Characteristics of Rhizosphere Bacterial Community of Ammodendron bifolium Growing in Takeermohuer Desert Are Different from Those in Non-rhizosphere.

Soil microorganisms play important roles in vegetation establishment and soil biogeochemical cycling. Ammodendron bifolium is a dominant sand-fixing and endangered plant in Takeermohuer Desert, and bacterial community associated with this plant rhizosphere is still unclear. In this study, we studied the composition and diversity of bacterial community from A. bifolium rhizosphere and bulk soil at different soil depths (i.e., 0-40 cm, 40-80 cm, 80-120 cm) using traditional bacterial isolation and high-throughput sequencing approaches, and preliminarily analyzed the edaphic factors influencing the structure of bacterial communities. Results showed that Takeermohuer Desert with high salinity has been an oligotrophic environment, while the rhizosphere exhibited eutrophication resulting from high content SOM (soil organic matter) and SAN (soil alkaline nitrogen) compared with bulk soil. The dominant bacterial groups in the desert were Actinobacteria (39.8%), Proteobacteria (17.4%), Acidobacteria (10.2%), Bacteroidetes (6.3%), Firmicutes (6.3%), Chloroflexi (5.6%), and Planctomycetes (5.0%) at the phyla level. However, the relative abundances of Proteobacteria (20.2%) and Planctomycetes (6.1%) were higher in eutrophic rhizosphere, and Firmicutes (9.8%) and Chloroflexi (6.9%) relatively higher in barren bulk soil. A large number of Actinobacteria were detected in all soil samples, of which the most abundant genus was Streptomyces (5.4%) and Actinomadura (8.2%) in the bulk soil and rhizosphere, respectively. The Chao1 and PD indexes in rhizosphere were significantly higher than those in bulk soil at the same soil depth, and tended to decrease with increasing soil depth. Co-occurrence network analyses showed that the keystone species in Takeermohuer Desert were Actinobacteria, Acidobacteria, Proteobacteria, and Chlorofexi. Furthermore, the major environmental factors affecting rhizosphere bacterial community were EC (electrical conductivity), SOM, STN (soil total nitrogen), SAN, and SAK (soil available potassium), while bulk soil were distance and C/N (STC/STN). We concluded that A. bifolium rhizosphere bacterial community is different from non-rhizosphere in composition, distribution, and environmental influencing factors, which will have important significances for understanding their ecological functions and maintaining biodiversity.

Optimized Water Supply in a Solar Evaporator for Simultaneous Freshwater Production and Salt Recycle.

Solar desalination has shown great potential in alleviating global water scarcity. However, the trade-off between energy efficiency and salt rejection remains a challenge, restricting its practical applications. In this study, we report a three-dimensional nitrocellulose membrane-based evaporator featuring a high evaporation rate (1.5 kg m-2 h-1) and efficient salt precipitation at the edges. Additionally, the salt is isolated from the photothermal area of the evaporator and falls automatically with a salt recovery rate of 97 g m-2 h-1 in brine with 10 wt % salt content. The distinctive performance is attributed to the precise water supply control, which was adjusted by changing the resistance force and driven force in the evaporator. With a high evaporation rate, stable performance, and specific salt recovery ability, this solar evaporation structure holds great potential in water desalination and resource recovery.

Probing Molecular-Level Dynamic Interactions of Dissolved Organic Matter with Iron Oxyhydroxide via a Coupled Microfluidic Reactor and an Online High-Resolution Mass Spectrometry System.

The interactions between dissolved organic matter (DOM) and iron (Fe) oxyhydroxide are crucial in regulating the biogeochemical cycling of nutrients and elements, including the preservation of carbon in soils. The mechanisms of DOM molecular assembly on mineral surfaces have been extensively studied at the mesoscale with equilibrium experiments, yet the molecular-level evolution of the DOM-mineral interface under dynamic interaction conditions is not fully understood. Here, we designed a microfluidic reactor coupled with an online solid phase extraction (SPE)-LC-QTOF MS system to continually monitor the changes in DOM composition during flowing contact with Fe oxyhydroxide at circumneutral pH, which simulates soil minerals interacting with constant DOM input. Time-series UV-visible absorption spectra and mass spectrometry data showed that after aromatic DOM moieties were first preferentially sequestered by the pristine Fe oxyhydroxide surface, the adsorption of nonaromatic DOM molecules with greater hydrophobicity, lower acidity, and lower molecular weights (<400) from new DOM solutions was favored. This is accompanied by a transition from mineral surface chemistry-dominated adsorption to organic-organic interaction-dominated adsorption. These findings provide direct molecular-level evidence to the zonal model of DOM assembly on mineral surfaces by taking the dynamics of interfacial interactions into consideration. This study also shows that coupled microfluidics and online high-resolution mass spectrometry (HRMS) system is a promising experimental platform for probing microscale environmental carbon dynamics by integrating in situ reactions, sample pretreatment, and automatic analysis.

Long-Term Exposure of Graphene Oxide Suspension to Air Leading to Spontaneous Radical-Driven Degradation.

Understanding the environmental transformation and fate of graphene oxide (GO) is critical to estimate its engineering applications and ecological risks. While there have been numerous investigations on the physicochemical stability of GO in prolonged air-exposed solution, the potential generation of reactive radicals and their impact on the structure of GO remain unexplored. In this study, using liquid-PeakForce-mode atomic force microscopy and quadrupole time-of-flight mass spectroscopy, we report that prolonged exposure of GO to the solution leads to the generation of nanopores in the 2D network and may even cause the disintegration of its bulk structure into fragment molecules. These fragments can assemble themselves into films with the same height as the GO at the interface. Further mediated electrochemical analysis supports that the electron-donating active components of GO facilitate the conversion of O2 to •O2- radicals on the GO surface, which are subsequently converted to H2O2, ultimately leading to the formation of •OH. We experimentally confirmed that attacks from •OH radicals can break down the C-C bond network of GO, resulting in the degradation of GO into small fragment molecules. Our findings suggest that GO can exhibit chemical instability when released into aqueous solutions for prolonged periods of time, undergoing transformation into fragment molecules through self-generated •OH radicals. This finding not only sheds light on the distinctive fate of GO-based nanomaterials but also offers a guideline for their engineering applications as advanced materials.

A universal approach for sensitive and rapid detection of different pathogenic bacteria based on aptasensor-assisted SERS technique.

An assembled-aptasensor based on Fe3O4@Au@Ag nanocomposites grafting onto the gold foil was prepared, which can be developed into a universal approach for sensitive and rapid detection of various pathogenic bacteria, such as Escherichia coli (E. coli), Salmonella typhimurium (S. typhimurium), Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Pseudomonas aeruginosa (P. aeruginosa), and Shigella flexneri (S. flexneri). Firstly, the gold foil paper was modified with thiolated capture probe and SERS tag in proportion, and at the same time, the specific thiolated aptamer probe for corresponding pathogenic bacteria was fixed with Fe3O4@Au@Ag nanocomposites. An obvious Raman signal can be subsequently increased about 106 times by the external electromagnetic field enhancement at the "hot spots" caused by the hybridization of aptamer and capture probe. But in the presence of target pathogenic bacteria, Raman intensity will decrease as Fe3O4@Au@Ag nanocomposites are dissociated from gold foil. Thus, all of the concentrations of the six kinds of pathogenic bacteria both in PBS and liquorice extract showed an obvious negative linear correlation with the Raman intensity of SERS tag in the range of 10-107 CFU/mL with detection limits were all lower than 10 CFU/mL. And there was no significant difference between our method and the plate counting method. Besides, the assembled-aptasensor had superior specific recognition ability even in the mixed interfering bacteria. Our study showed that this assembled-aptasensor had good specific detection ability to a variety of foodborne pathogens based on magnetic field-assisted SERS technique, which can be used for rapid and sensitive detection of a variety of pathogens in complex substrates.

Evaluating the effect of ginsenoside Rg1 on CPF-induced brain injury in mice via PI3k/AKT pathway.

Organophosphorus pesticides (OPs) have long been used extensively on agricultural land and can lead to significant improvements in crop yields. Due to occupational exposure, humans are exposed to pesticides through dermal contact, inhalation, and ingestion. The effects of OPs on the organism are currently studied for their effects on livers, kidneys, hearts, blood indicators, neurotoxicity, and teratogenic, carcinogenic, and mutagenic effects, while studies in the direction of brain tissue damage have not been reported in detail. Previous reports have confirmed that ginsenoside Rg1 is a prominent and representative tetracyclic triterpenoid derivative rich in ginseng and has good neuroprotective activity. Considering that, the aim of this study was to establish a mouse model of brain tissue injury by using the OP-type pesticide chlorpyrifos (CPF) and to explore the therapeutic effects and possible molecular mechanisms of Rg1. Mice in the experimental group were pre-protected with Rg1 by gavage for 1 week, and brain tissue damage was induced using CPF (5 mg/kg for 1 week) to assess the effect of Rg1 (80 and 160 mg/kg for 3 weeks) in alleviating brain damage. Morris water maze and histopathological analysis were performed to assess cognitive function and pathological changes in the mouse brain, respectively. Protein expression levels of Bax, Bcl-2, Caspase-3, Cl-Cas-3, Caspase-9, Cl-Cas-9, phosphoinositide 3-kinase (PI3K), phosphorylated-PI3K, protein kinase B (AKT), and phosphorylated-AKT were quantified by protein blotting analysis. Rg1 obviously restored CPF-induced oxidative stress damage in mouse brain tissue, increased the levels of antioxidant parameters (total superoxide dismutase, total antioxidative capacity, and glutathione) in the brain, and significantly reduced the overexpression of apoptosis-related proteins induced by CPF. At the same time, Rg1 also markedly attenuated the histopathological changes in the brain induced by CPF exposure. Mechanistically, Rg1 could effectively activate the phosphorylation of PI3K/AKT. Furthermore, molecular docking studies revealed a stronger binding capacity between Rg1 and PI3K. Rg1 attenuated neurobehavioural alterations and reduced lipid peroxidation in the mouse brain to a great extent. Apart from that, Rg1 administration improved brain histopathology in CPF-induced rats. All results suggest that ginsenoside Rg1 has potential antioxidant effects on CPF-induced oxidative brain injury, and it is evident that Rg1 could be used as a promising therapeutic strategy for the study of brain injury from OP poisoning.

Aluminum exposure induces central nervous system impairment via activating NLRP3-medicated pyroptosis pathway.

PURPOSE: Aluminum is an environmental toxicant whose long-term exposure is closely associated with nervous system impairment. This study mainly investigated neurological impairment induced by subchronic aluminum exposure via activating NLRP3-medicated pyroptosis pathway. METHODS: In vivo, Kunming mice were exposed to AlCl3 (30.3 mg/kg, 101 mg/kg and 303 mg/kg) via drinking water for 3 months, and administered with Rsv (100 mg/kg) by gavage for 1 month. Cognitive impairment was assessed by Morris water maze test, and pathological injury was detected via H&E staining. BBB integrity, pyroptosis and neuroinflammation were evaluated through western blotting and immunofluorescence methods. In vitro, BV2 microglia was treated with AlCl3 (0.5 mM, 1 mM and 2 mM) to sensitize pyroptosis pathway. The protein interaction was verified by co-immunoprecipitation, and neuronal damage was estimated via a conditioned medium co-culture system with BV2 and TH22 cells. RESULTS: Our results showed that AlCl3 induced mice memory disorder, BBB destruction, and pathological injury. Besides, aluminum caused glial activation, sensitized DDX3X-NLRP3 pyroptosis pathway, released cytokines IL-1ß and IL-18, initiating neuroinflammation. BV2 microglia treated with AlCl3 emerged hyperactivation and pyroptotic death, and Ddx3x knockdown inhibited pyroptosis signaling pathway. DDX3X acted as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome and G3BP1 stress granules. Furthermore, aluminum-activated microglia had an adverse effect on co-cultured neurons and destroyed nervous system homeostasis. CONCLUSION: Aluminum exposure could induce pyroptosis and neurotoxicity. DDX3X determined live or die via selectively regulating pro-survival stress granules or pro-death NLRP3 inflammasome. Excessive activation of microglia might damage neurons and aggravate nerve injury.

Aluminum induces neuroinflammation via P2X7 receptor activating NLRP3 inflammasome pathway.

INTRODUCTION: Aluminum is everywhere in nature and is a recognized neurotoxicant closely associated with various neurodegenerative diseases. Neuroinflammation occurs in the early stage of neurodegenerative diseases, but the underlying mechanism by which aluminum induces neuroinflammation remains unclear. MATERIAL AND METHODS: A 3-month subchronic aluminum exposure mouse model was established by drinking water containing aluminum chloride (AlCl3). Microglia BV2 cells and hippocampal neuron HT22 cells were treated with AlCl3 in vitro. BBG and YC-1 were used as intervention agents. RESULTS: Aluminum could activate microglia and increase the level of extracellular ATP, stimulate P2X7 receptor, HIF-1α, activate NLRP3 inflammasome and CASP-1, release more cytokine IL-1ß, and induce an inflammatory response in nerve cells. There was a mutual regulatory relationship between P2X7 and HIF-1α at mRNA and protein levels. The co-culture system of BV2-HT22 cells observed that conditioned medium from microglia treated with aluminum could aggravate neuronal morphological damage, inflammatory response and death. While BBG and YC-1 intervention could rescue these injuries to some extent. CONCLUSION: The P2X7-NLRP3 pathway was involved in aluminum-induced neuroinflammation and injury. P2X7 and HIF-1α might mutually regulate and promote the progression of neuroinflammation, both BBG and YC-1 could relieve it.

CD26 CAR-T cells have attenuated mitochondrial and glycolytic metabolic profiling.

BACKGROUND: Multiple targets of chimeric antigen receptor T cells (CAR-T cells) are shared expressed by tumor cells and T cells, these self-antigens may stimulate CAR-T cells continuously during the expansion. Persistent exposure to antigens is considered to cause metabolic reprogramming of T cells and the metabolic profiling is critical in determining the cell fate and effector function of CAR-T cells. However, whether the stimulation of self-antigens during CAR-T cell generation could remodel the metabolic profiling is unclear. In this study, we aim to investigate the metabolic characteristics of CD26 CAR-T cells, which expressed CD26 antigens themselves. METHODS: The mitochondrial biogenesis of CD26 and CD19 CAR-T cells during expansion was evaluated by the mitochondrial content, mitochondrial DNA copy numbers and genes involved in mitochondrial regulation. The metabolic profiling was investigated by the ATP production, mitochondrial quality and the expression of metabolism-related genes. Furthermore, we assessed the phenotypes of CAR-T cells through memory-related markers. RESULTS: We reported that CD26 CAR-T cells had elevated mitochondrial biogenesis, ATP production and oxidative phosphorylation at early expansion stage. However, the mitochondrial biogenesis, mitochondrial quality, oxidative phosphorylation and glycolytic activity were all weakened at later expansion stage. On the contrary, CD19 CAR-T cells did not exhibit such characteristics. CONCLUSION: CD26 CAR-T cells showed distinctive metabolic profiling during expansion that was extremely unfavorable to cell persistence and function. These findings may provide new insights for the optimization of CD26 CAR-T cells in terms of metabolism.