Cytotoxic withanolides from the leaves of Datura stramonium L.

Six novel withanolides, along with nine known related compounds were isolated from the leaves of Datura stramonium L. The structures and absolute configurations of the new withanolides were elucidated by employing various spectral techniques and comparing them with those previously reported in the literature. In addition, four withanlides demonstrated interesting cytotoxic activity on LN229 cells with IC50 <20 µM.

Seeds Act as Vectors for Antibiotic Resistance Gene Dissemination in a Soil-Plant Continuum.

Though the evidence for antibiotic resistance spread via plant microbiome is mounting, studies regarding antibiotic resistome in the plant seed, a reproductive organ and important food resource, are still in their infancy. This study investigated the effects of long-term organic fertilization on seed bacterial endophytes, resistome, and their intergenerational transfer in the microcosm. A total of 99 antibiotic resistance genes (ARGs) and 26 mobile genetic elements (MGEs) were detected by high-throughput quantitative PCR. The amount of organic fertilizer applied was positively correlated to the number and relative abundance of seed-associated ARGs and MGEs. Moreover, the transmission of ARGs from the rhizosphere to the seed was mainly mediated by the shared bacteria and MGEs. Notably, the rhizosphere of progeny seedlings derived from seeds harboring abundant ARGs was found to have a higher relative abundance of ARGs. Using structural equation models, we further revealed that seed resistome and MGEs were key factors affecting the ARGs in the progeny rhizosphere, implying the seed was a potential resistome reservoir for rhizosphere soil. This study highlights the overlooked role of seed endophytes in the dissemination of resistome in the soil-plant continuum, and more attention should be paid to plant seeds as vectors of ARGs within the "One-Health" framework.

Environmental epigenetic interaction of gametes and early embryos†.

In recent years, the developmental origins of diseases have been increasingly recognized and accepted. As such, it has been suggested that most adulthood chronic diseases such as diabetes, obesity, cardiovascular disease, and even tumors may develop at a very early stage. In addition to intrauterine environmental exposure, germ cells carry an important inheritance role as the primary link between the two generations. Adverse external influences during differentiation and development can cause damage to germ cells, which may then increase the risk of chronic disease development later in life. Here, we further elucidate and clarify the concept of gamete and embryo origins of adult diseases by focusing on the environmental insults on germ cells, from differentiation to maturation and fertilization.

Bufadienolides from the Eggs of the Toad Bufo bufo gargarizans and Their Antimelanoma Activities.

Toads produce potent toxins, named bufadienolides, to defend against their predators. Pharmacological research has revealed that bufadienolides are potential anticancer drugs. In this research, we reported nine bufadienolides from the eggs of the toad Bufo bufo gargarizans, including two new compounds (1 and 3). The chemical structures of 1 and 3, as well as of one previously reported semisynthesized compound (2), were elucidated on the basis of extensive spectroscopic data interpretation, chemical methods, and X-ray diffraction analysis. Compound 1 is an unusual 19-norbufadienolide with rearranged A/B rings. A biological test revealed that compounds 2 and 4-8 showed potent cytotoxic activities toward human melanoma cell line SK-MEL-1 with IC50 values less than 1.0 µM. A preliminary mechanism investigation revealed that the most potent compound, 8, could induce apoptosis via PARP cleavage, while 5 and 6 significantly suppressed angiogenesis in zebrafish. Furthermore, an in vivo biological study showed that 5, 6, and 8 inhibit SK-MEL-1 cell growth significantly.

α-Expansin EXPA4 Positively Regulates Abiotic Stress Tolerance but Negatively Regulates Pathogen Resistance in Nicotiana tabacum.

Since they function as cell wall-loosening proteins, expansins can affect plant growth, developmental processes and environmental stress responses. Our previous study demonstrated that changes in Nicotiana tabacum α-expansin 4 (EXPA4) expression affect the sensitivity of tobacco to Tobacco mosaic virus [recombinant TMV encoding green fluorescent protein (TMV-GFP)] infection by Agrobacterium-mediated transient expression. In this study, to characterize the function of tobacco EXPA4 further, EXPA4 RNA interfernce (RNAi) mutants and overexpression lines were generated and assayed for their tolerance to abiotic stress and resistance to pathogens. First, the differential phenotypes and histomorphology of transgenic plants with altered EXPA4 expression indicated that EXPA4 is essential for normal tobacco growth and development. By utilizing tobacco EXPA4 mutants with abiotic stress, it was demonstrated that RNAi mutants have increased hypersensitivity to salt and drought stress. In contrast, the overexpression of EXPA4 in tobacco conferred greater tolerance to salt and drought stress, as indicated by less cell damage, higher fresh weight, higher soluble sugar and proline accumulation, and higher expression levels of several stress-responsive genes. In addition, the overexpression lines were more susceptible to the viral pathogen TMV-GFP when compared with the wild type or RNAi mutants. The induction of the antioxidant system, several defense-associated phytohormones and gene expression was down-regulated in overexpression lines but up-regulated in RNAi mutants when compared with the wild type following TMV-GFP infection. In addition, EXPA4 overexpression also accelerated the disease development of Pseudomonas syringae DC3000 on tobacco. Taken together, these results suggested that EXPA4 appears to be important in tobacco growth and responses to abiotic and biotic stress.

Integrated Eu3+ loaded covalent organic framework with smartphone for ratiometric fluorescence detection of tetracycline.

Developing rapid tetracycline sensing system is of great significance to monitor the illegal addition to drugs and pollution to food and ecosystem. By loading covalent organic frameworks (COFs) with Eu3+, a new hybridized material (COF@Eu3+) was prepared for tetracycline determination. Based on the Schiff base reaction, the COFs were by synthesized through solvent evaporation in 30 min at room temperature. Thereafter, Eu3+ was modified into COFs to develop the COF@Eu3+ sensing platform by adsorption and coordination. In presence of tetracycline, tetracycline can displace water molecules and coordinate with Eu3+ through the antenna effect. As a result, the red fluorescence of Eu3+ was enhanced by tetracycline with green fluorescence of COF as a reference. The developed ratiometric fluorescence sensor exhibits a linear range of 0.1-20 µM for detecting tetracycline with a detection limit of 30 nM. Integrated with a smartphone, the rapid tetracycline detection can be realized in situ, which is potential for high-throughput screening of tetracycline contaminated samples. Furthermore, the COF@Eu3+ fluorescence sensor has been successfully applied to the detection of tetracycline in traditional Chinese medicine compound preparation with satisfied recoveries. Therefore, a smartphone-assisted device was successfully developed based on Eu3+-functionalized COF, which is an attractive candidate for further applications of fluorescence sensing and visual detection.

Current state and influencing factors in airbag management among emergency department nurses: A multicenter study.

BACKGROUND: The emergency department (ED) plays a critical role in establishing artificial airways and implementing mechanical ventilation. Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia. Nonetheless, existing research has largely overlooked the understanding, beliefs, and practical dimensions of airway airbag management among ED nurses, with a predominant focus on intensive care unit nurses. AIM: To investigate the current status of ED nurses' knowledge, beliefs, and practical behaviors in airway airbag management and their influencing factors. METHODS: A survey was conducted from July 10th to August 10th, 2023, using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai. Pathway analysis was utilized to analyze the influencing factors. RESULTS: The scores for ED nurses' airway airbag management knowledge were 60.26 ± 23.00, belief was 88.65 ± 13.36, and behavior was 75.10 ± 19.84. The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training, department, and work experience in the department. Influencing factors of airbag management belief comprised knowledge, department, and participation in specialized nurse or mechanical ventilation training. Primary influencing factors of airbag management behavior included knowledge, belief, department, participation in specialized nurse or mechanical ventilation training, and professional title. The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior, with a total effect value of 0.513, and an indirect effect of 0.085, constituting 16.6% of the total effect. CONCLUSION: ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices, yet there remains room for improvement in their knowledge levels. Nursing managers should implement interventions tailored to the characteristics of ED nurses' airbag management knowledge, beliefs, and practices to enhance their airbag management proficiency.

Concurrent manipulation of competitive mechanisms to construct glutathione-stabilized gold nanocluster-based dual-channel molecular classifier for metal ions detection and information steganography.

Understanding charge transport in metal ion-mediated glutathione-stabilized gold nanoclusters (GSH-Au NCs) has proved difficult due to the presence of various competitive mechanisms, such as electron transfer (ET) and aggregation induction effect (AIE). In this paper, we present a dual-channel fluorescence (FL) and second-order Rayleigh scattering (SRS) sensing method for high-throughput classification of metal ions, relying on the competition between ET and AIE using GSH-Au NCs. The SRS signals show significant enhancement when Pb2+, Ag+, Al3+, Cu2+, Fe3+, and Hg2+ are present, as a result of the aggregation of GSH-Au NCs. Notably, the fluorescence signal exhibits the opposite trend. The FL intensities of GSH-Au NCs are enhanced by Pb2+, Ag+, and Al3+ through the AIE mechanism, while they are quenched by Cu2+, Fe3+, and Hg2+, which is dominated by the ET mechanism. By employing principal component analysis and hierarchical cluster analysis, these signals are transformed into unique fingerprints and Euclidean distances, respectively, enabling successful distinction of six metal ions and their mixtures with a low detection limit of 30 nM. This new strategy has successfully addressed interference from impurities in the testing of real water samples, demonstrating its strong ability to detect multiple metal ions. Impressively, we have achieved molecular cryptosteganography, which involves encoding, storing, and concealing information by transforming the selective response of GSH-Au NCs to binary strings. This research is anticipated to advance utilization of nanomaterials in logic sensing and information safety, bridging the gap between molecular sensors and information systems.

Nitrogen fertilization modulates rice phyllosphere functional genes and pathogens through fungal communities.

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.

Cytotoxicity phenylpropanoid amides from the seed of Cannabis sativa L.

Two novel phenylpropanoid amides, namely huomarenamide A (1) and huomarenamide B (2), along with twelve known compounds (3-14), were isolated from the seeds of Cannabis sativa L. The structures with absolute configurations of new compounds were unequivocally determined by spectroscopic analyses and the ECD method. The identification of the known compounds was based on a comparison of their 1D NMR data with literature references. All compounds were assessed for cytotoxic activity against LN229 cells, revealing that compounds 2, 13, and 14 exhibited significant cytotoxicity with IC50 values ranging from 9.02 to 21.26 µM.

Fourteen undescribed steroidal saponins from Solanum capsicoides leaves and their neuroprotective effects.

A total of 14 previously undescribed steroidal saponins named capsicsaponins A-N were isolated from the leaves of Solanum capsicoides, encompassing various types, including cholesterol derivatives and pseudospirostanol saponins. The structures of all compounds were determined through comprehensive analysis of spectroscopic data (1D NMR and 2D NMR), along with physicochemical analysis methods (acid hydrolysis, OR, and UV). Moreover, in the H2O2-induced pheochromocytoma cell line model, compounds 1-14 were screened for their neuroprotective effects on cells. The bioassay results demonstrated compounds 8-14 were able to revive cell viability compared to the positive control edaravone. The damage neuroprotection of the most active compound was further explored.

Identification of glycogen phosphorylase L as a potential target for lung cancer.

Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.

Identification of a novel therapeutic target for lung cancer: Mitochondrial ribosome protein L9.

Lung cancer has a high fatality rate and incidence rate. At present, the initial and progress mechanism of lung cancer has not been completely elucidated and new therapeutic targets still need to be developed. In this study, the screening process was based on lung cancer expression profile data and survival analysis. Mitochondrial ribosome protein L9 (MRPL9) was upregulated in lung cancer tissues and related to the poor overall survival rate and recurrence-free survival rate of lung cancer patients. Knockdown of MRPL9 inhibited the proliferation, sphere-formation, and migration ability of lung cancer cells. MRPL9 was associated with the c-MYC signaling pathway, and lung cancer patients with high expression of both MRPL9 and MYC had a poor prognosis. Furthermore, c-MYC was associated with the epithelial-mesenchymal transition (EMT) regulatory protein zinc finger E-box binding homeobox 1 (ZEB1) by bioinformatics analysis. The relationship between ZEB1 and c-MYC was further confirmed by interfering with c-MYC expression. MRPL9 is a potential therapeutic target for lung cancer and exerts its biological functions by affecting the transcription factor c-MYC thereby regulating the EMT regulator ZEB1.

Uncorrected Preoperative Infection Causing the Death of a Patient with a Thoracic Aortic Aneurysm.

Background: A thoracic aortic aneurysm (TAA) is a known condition seen in cardiovascular practice. A TAA rupture and postoperative infection may result in death. Preoperative infections leading to death are extremely rare. Case Study: A 62-year-old Chinese female was admitted to The First Hospital of Hebei Medical University with a two-day history of abdominal pain. She was diagnosed with a TAA rupture and underwent immediate surgery. The preoperative urine analysis indicated that the positive bacteria and white blood cell count suggested a urinary tract bacterial infection. The patient was administered the empiric antibiotics, cefazolin; however, her blood pressure continued to drop during the perioperative period and she died of uncorrectable acidosis 8 h after the operation. On the second day after death, both the blood and urine cultures were positive for Pseudomonas aeruginosa. Conclusion: Given that this patient with a TAA rupture died of uncorrected acidosis caused by preoperative infection, it is important to evoke the diagnosis in the context of TAA. Routine laboratory indicators are valuable factors for surgeons and physicians in assessing a patient's condition and improving their prognosis.

Method for quantitative extraction of copper hydroxide nanoparticles from farmland soil.

With the development of nanotechnology, nano-pesticides have been developed and show better application effects than traditional pesticides, which have a good development prospect. Copper hydroxide nanoparticles (Cu(OH)2 NPs) are one of the specific fungicides. However, there is still no reliable method to evaluate their environmental processes, which is essential for the broad application of new pesticides. Since soil is a vital link between pesticides and crops, this study took linear and slightly soluble Cu(OH)2 NPs as the research object and established a method to quantitatively extract Cu(OH)2 NPs from the soil. Five essential parameters in the extraction process were optimized first, and then the extraction effect of this optimal method was further tested under different nanoparticles and soil conditions. The optimal extraction method was determined, including (i) Dispersant: 0.2 % carboxymethyl cellulose (CMC) with a molecular weight of 250,000; (ii) Mixing conditions of soil and dispersant: water bath shaking for 30 min, water bath ultrasonication for 10 min (energy of the ultrasonication = 6 kJ/ml); (iii) Phase separation conditions: settlement for 60 min; (iv) Solid-to-liquid ratio: 1:20; (v) 1 extraction cycle. After optimization, 81.5 % of the supernatant was Cu(OH)2 NPs, and 2.6 % was dissolved copper ions (Cu2+). This method showed good applicability to different concentrations of Cu(OH)2 NPs and different farmland soils. It also showed significant differences in the extraction rates of copper oxide nanoparticles (CuO NPs), Cu2+, and other copper sources. The addition of a small amount of silica was confirmed to improve the extraction rate of Cu(OH)2 NPs. The establishment of this method lays the foundation for the quantitative analysis of nano-pesticides and other non-spherical and slightly soluble nanoparticles.

Continuous exposure to isoprenaline reduced myotube size by delaying myoblast differentiation and fusion through the NFAT-MEF2C signaling pathway.

We aimed to explore whether superfluous sympathetic activity affects myoblast differentiation, fusion, and myofiber types using a continuous single-dose isoprenaline exposure model in vitro and to further confirm the role of distinct NFATs in ISO-mediated effects. Compared with delivery of single and interval single, continuous single-dose ISO most obviously diminished myotube size while postponing myoblast differentiation/fusion in a time- and dose-dependent pattern, accompanied by an apparent decrease in nuclear NFATc1/c2 levels and a slight increase in nuclear NFATc3/c4 levels. Overexpression of NFATc1 or NFATc2, particularly NFATc1, markedly abolished the inhibitory effects of ISO on myoblast differentiation/fusion, myotube size and Myh7 expression, which was attributed to a remarkable increase in the nuclear NFATc1/c2 levels and a reduction in the nuclear NFATc4 levels and the associated increase in the numbers of MyoG and MEF2C positive nuclei within more than 3 nuclei myotubes, especially in MEF2C. Moreover, knockdown of NFATc3 by shRNA did not alter the inhibitory effect of ISO on myoblast differentiation/fusion or myotube size but partially recovered the expression of Myh7, which was related to the slightly increased nuclear levels of NFATc1/c2, MyoG and MEF2C. Knockdown of NFATc4 by shRNA prominently increased the number of MyHC +, MyoG or MEF2C + myoblast cells with 1 ~ 2 nuclei, causing fewer numbers and smaller myotube sizes. However, NFATc4 knockdown further deteriorated the effects of ISO on myoblast fusion and myotube size, with more than 5 nuclei and Myh1/2/4 expression, which was associated with a decrease in nuclear NFATc2/c3 levels. Therefore, ISO inhibited myoblast differentiation/fusion and myotube size through the NFAT-MyoG-MEF2C signaling pathway.

Association study of ACE polymorphisms and systemic lupus erythematosus in Northern Chinese Han population.

Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involving in its etiology. Angiotensin converting enzyme (ACE) gene was reported to have important roles in the development and progression of SLE. In this study, a case-control study was carried out to investigate the effects of seven SNPs and I/D in ACE gene in the development of SLE in Northern China. Seven SNPs including A5466C, T3892C, A240T, C1237T, G2215A, A2350G and C3409T were genotyped by PCR-RFLP method, and I/D was examined by agarose gel electrophoresis followed PCR directly. 314 SLE patients were compared to 320 normal controls in the study. Data were analyzed by SPSS 13.0 and HaploView software. The frequency distribution of SNP A2350G and Alu I/D and five haplotypes (AAAACCCI, AGAACCTD, AAAATCTI, TAAATTTI and TAAATCTI) were demonstrated to be different between case and control groups significantly. Whereas other SNPs and haplotypes had no differences in two cohorts. The results revealed that variations of ACE gene had association with SLE, which indicated ACE gene may play an important role in pathogenesis of SLE in Northern Chinese Han population.

Evaluation of nano-silver concentrations using multi-media fate and transport models with different spatial resolutions.

Due to the complexity of the environmental matrix and the limitation of the detection level, it is important to use models to evaluate environmental exposure to nanomaterials. Based on this, this research established two multi-media fate and transport models of silver nanoparticles (AgNPs) with respective coarse and fine spatial resolutions. Using the case of the spatial distribution of AgNPs in the Xiangjiang River, China, we compared how the spatial resolution of a model impacts modeling results. The results show that the process of heterogeneous aggregation has the greatest impact on the modeled concentration of AgNPs in water, and the heterogeneous aggregation of free AgNPs with natural colloids and settling down to sediments is the dominant mechanism responsible for the loss of AgNPs. In addition, the use of different spatial resolutions gives similar trends in the modeled AgNPs concentration, despite the difference in absolute levels. Our work also shows that the reliability and accuracy of the rate constant of heterogeneous aggregation has a great influence on the modeled AgNPs concentrations.

Cloud point extraction (CPE) combined with single particle -inductively coupled plasma-mass spectrometry (SP-ICP-MS) to analyze and characterize nano-silver sulfide in water environment.

Silver Nanoparticles (Ag-NPs), an emerging type of pollutant, might occur various physical and chemical transformations, which would affect its environmental fate, transformation and biological effects. Sulfurization is the most common conversion of Ag-NPs, accompanied by the formation of nano-silver sulfide (Ag2S-NPs). The method of Ag2S-NPs analysis and characterization is of great significance for assessing the environmental risks of Ag. In this study, cloud point extraction (CPE) and Single Particle-Inductively Coupled Plasma-Mass Spectrometry (SP-ICP-MS) were used in combination to establish a simple and reliable analysis method to quantify Ag2S-NPs in water, with the morphology unchanged. Non-Ag2S-NPs were dissociated into Ag+ firstly, and Ag2S-NPs and Ag+ were separated by CPE, followed by SP-ICP-MS analysis. The extraction rate based on particle number concentration was between (76.19 ± 0.56) % to (106.35 ± 0.00) % in environmental waters. Compared with the (76.96 ± 2.18) nm Ag2S-NPs spiked, the particle size extracted increased slightly with (94.19 ± 2.72) nm- (97.25 ± 0.22) nm as the large-size Ag2S-NPs originally presented in waters, instead of agglomeration. This method could be generally applicable to the analysis of Ag2S-NPs in waters, and provide ideas for other metal sulfide nanoparticles (MS-NPs), which has certain significance.

Integrating Lipidomics and Transcriptomics Reveals the Crosstalk Between Oxidative Stress and Neuroinflammation in Central Nervous System Demyelination.

Multiple sclerosis (MS) is an incurable and progressive neurodegenerative disease that affects more than 2.5 million people worldwide and brings tremendous economic pressures to society. However, the pathophysiology of MS is still not fully elucidated, and there is no effective treatment. Demyelination is thought to be the primary pathophysiological alteration in MS, and our previous study found abnormal lipid metabolism in the demyelinated corpus callosum. Growing evidence indicates that central nervous system (CNS) demyelinating diseases never result from one independent factor, and the simultaneous participation of abnormal lipid metabolism, oxidative stress, and neuroinflammation could potentiate each other in the pathogenesis of MS. Therefore, a single omics analysis cannot provide a full description of any neurodegenerative disease. It has been demonstrated that oxidative stress and neuroinflammation are two reciprocal causative reasons for the progression of MS disease. However, the potential crosstalk between oxidative stress and neuroinflammation remains elusive so far. With an integrated analysis of targeted lipidomics and transcriptomics, our research presents the potential interaction between abnormalities of lipid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in CNS demyelinating diseases. The findings of this paper may be used to identify possible targets for the therapy of CNS demyelinating diseases.