Bilevel positive airway pressure ventilation in patients susceptible to hypoxemia during procedural sedation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIMS: Hypoxemia is one of the most common adverse events during colonoscopy, particularly among patients who are diagnosed with obstructive sleep apnea (OSA) or are overweight. Consequently, the objective of this study was to evaluate the effectiveness of bilevel positive airway pressure (BPAP) ventilation for patients with high-risk hypoxemia during colonoscopy with sedation. METHODS: In this trial, 127 patients who met the eligibility criteria were randomly assigned to the BPAP oxygen group and nasal cannula (NC) group. The primary endpoint was the incidence of hypoxemia. RESULTS: Compared with the use of NC, BPAP ventilation exhibited a significant reduction in the incidence of hypoxemia, decreasing it from 23.8% to 6.3% (absolute risk difference, 17.5%; 95% confidence interval, 5.4-29.6; P = .006). Importantly, BPAP ventilation prevented the occurrence of severe hypoxemia (9.5% vs 0%; absolute risk difference, 9.5%; 95% confidence interval, 2.3-16.7; P = .035). In addition, the BPAP group required fewer airway interventions (P < .05). CONCLUSIONS: In individuals with OSA or overweight status, the use of BPAP ventilation during colonoscopy significantly reduced the incidence of hypoxemia. (Clinical trial registration number: ChiCTR2300073193.).

Altered functional connectivity of resting-state networks and the correlation with clinical characteristics in intermittent exotropia adult patients: a resting-state magnetic resonance imaging study.

BACKGROUND: The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms. METHODS: Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. RESULTS: Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P < 0.05). The FNC analysis between different RSNs also provides evidence on visual-motor cortical plasticity. CONCLUSIONS: IXT patients showed widespread changes of brain activity within RSNs related to binocular fusion, stereopsis, oculomotor control, emotional processes, and social cognition. These findings extend our current understanding of the neuropathological mechanisms of IXT. TRIAL REGISTRATION: Beginning date of the trial: 2021-09-01. Date of registration:2021-07-18. Trial registration number: ChiCTR 2,100,048,852. Trial registration site: http://www.chictr.org.cn/index.aspx .

Association of Accommodation and Convergence with Axial Length Elongation in Children with Basic Intermittent Exotropia: A 12-Month Observational Study.

INTRODUCTION: The aim of the study was to investigate the association of parameters related to accommodation and convergence and axial elongation in basic intermittent exotropia (IXT) patients and the potential clinical predictors of axial length (AL) growth. METHODS: A total of 140 basic IXT patients were recruited in this study. The medians of AL growth in different age brackets were chosen to divide the subjects into group A (slower axial elongation group, n = 69) and group B (faster axial elongation group, n = 71). Parameters of dominant and nondominant eyes were compared and analyzed during the 12-month follow-up period. The parameters, including baseline refraction, angle of deviation, Newcastle control score (NCS), accommodative amplitude (AMP), accommodative facility (AMF), accommodative response, positive or negative relative accommodation (PRA/NRA), and near point of convergence (NPC), were analyzed via univariate and multivariate regression. RESULTS: Subjects in the faster axial elongation group tended to have more myopic spherical equivalents (t = 3.956, p < 0.001), greater AMPs of dominant eyes (t = -2.238, p = 0.027), and fewer near points of convergence (t = 2.347, p = 0.020) than in the slower axial elongation group. For dominant eyes, logistic and linear regression analysis revealed that more negative spherical equivalents (OR = 0.603, p < 0.001; ß = -0.045, p < 0.001), greater AMPs (OR = 1.201, p = 0.027; ß = 0.023, p = 0.010), and less near points of convergence (OR = 0.883, p = 0.021; ß = -0.012, p = 0.019) were correlated with the faster axial elongation. For nondominant eyes, a more myopic spherical equivalent (OR = 0.682; p = 0.001; ß = -0.029, p = 0.005) was the only parameter correlated with faster axial elongation through regression analysis. CONCLUSION: In children with basic IXT, faster axial elongation in the dominant eyes was associated with more myopic spherical equivalents, greater AMPs, and lower NPCs. These accommodative parameters can serve as potential clinical indicators for monitoring myopia progression in addition to AL.

Endogenous IAA affected fluoranthene accumulation by regulating H+-ATPase and SOD activity in ryegrass.

This study explores the role of endogenous indole-3-acetic acid (IAA) in modulating plant responses to pollution stress and its effect on pollutant accumulation, with a focus on fluoranthene (Flu) in ryegrass. To elucidate the mechanism, we employed an IAA promoter (α-aminobutyric acid [α-AB]) and an IAA inhibitor (naphthylphthalamic acid [NPA]) to regulate IAA levels and analyze Flu uptake characteristics. The experimental setup included a Flu treatment group (ryegrass with Flu addition) and a control group (ryegrass without Flu). Our findings demonstrate that Flu treatment enhanced IAA content and plant growth in ryegrass compared to the control. The Flu+AB treatment further enhanced these effects, while the Flu+NPA treatment exhibited a contrasting trend. Moreover, Flu+AB treatment led to increased Flu accumulation, in contrast to the inhibitory effect observed with Flu+NPA treatment. Flu treatment also enhanced the activities of key antioxidant enzymes (SOD, POD, CAT) and increased soluble sugar and protein levels, indicative of enzymatic and nonenzymatic defense responses, respectively. The Flu+AB treatment amplified these responses, whereas the Flu+NPA treatment attenuated them. Significantly, Flu treatment raised H+-ATPase activity compared to the control, an effect further elevated by Flu+AB treatment and diminished by Flu+NPA treatment. A random forest analysis suggested that Flu accumulation dependency varied under different treatments: it relied more on H+-ATPase activity under Flu+AB treatment and more on SOD activity under Flu+NPA treatment. Additionally, Flu+AB treatment boosted the transpiration rate in ryegrass, thereby increasing the Flu translocation factor, a trend reversed by Flu+NPA treatment. This research highlights crucial factors influencing Flu accumulation in ryegrass, offering potential new avenues for controlling the gathering of contaminants within plant systems.

Arabidopsis thaliana YUC1 reduced fluoranthene accumulation by modulating IAA content and antioxidant enzyme activities.

Indole-3-acetic acid (IAA) can regulate plant growth and thus modulate the accumulation of polycyclic aromatic hydrocarbons (PAHs). However, the effect of endogenous IAA on PAHs accumulation and its influencing factors remains unclear. To unravel this, two different IAA expression genotypes of Arabidopsis thaliana, i.e., IAA-underproducing yucca1D [YUC1] mutant and wild type [WT]) were selected and treated with different fluoranthene (Flu) concentrations (0 mg/L [CK], 5 mg/L [Flu5], and 20 mg/L [Flu20]) to reveal the impact mechanism of endogenous IAA on Flu uptake by plants. The results indicated that under Flu5 treatment, the bioconcentration factors (BCF) and translocation factors (TF) of Flu in WT were 41.4 % and 14.3 % higher than those in YUC1. Similarly, under Flu20 treatment, the BCF and TF of Flu in WT were also 42.2 % and 8.2 % higher than those in YUC1. In addition, the BCF and TF were 72.5 % and 35.8 % higher under Flu5 treatment compared to Flu20 treatment for WT, and 73.4 % and 28.6 % higher respectively for YUC1. Moreover, WT exhibited higher plant growth (biomass, root morphology indicators [root length, root area and number of tips]) and IAA content compared to YUC1 under identical Flu treatments. Plant growth and IAA content declined with the increase of Flu concentration in both YUC1 and WT leaves compared with CK treatment. Conversely, in WT roots, root biomass and morphology indicators promoted followed by a decrease as the concentration of Flu increased. Additionally, the antioxidant enzyme activities (SOD, POD, and CAT) of WT were 11.1 %, 16.7 %, and 28.9 % higher than those of YUC1 under Flu5 treatment, and 13.6 %, 12.9 %, and 26.5 % higher under Flu20 treatment. Compared with CK treatment, SOD and POD activities promoted with increasing Flu concentration, whereas CAT activities decreased. Variability separation analysis revealed that level of IAA primarily influenced Flu accumulation in WT or under Flu5 treatments, whereas antioxidant enzyme activity primarily affected Flu accumulation in YUC1 or under Flu20 treatments. Exploring the relationship between the IAA synthesis gene YUCCA and IAA levels, alongside Flu accumulation, could yield novel insights into the regulation of PAH accumulation in plants.

Bilateral Embedded Anchoring via Tailored Polymer Brush for Large-Area Air-Processed Blue Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

New Insights into the Roles of p53 in Central Nervous System Diseases.

The transcription factor p53, a widely accepted tumor suppressor, regulates the expression of many oncogenes and their downstream signaling pathways, resulting in a series of biological outcomes. Mutations and deletions of the p53 gene often occur in tumor tissues and are involved in their development. In addition to its role in tumors, p53 has a widespread expression in the brain and participates in most cell processes, such as dendrite formation, oxidative stress, apoptosis, autophagy, DNA repair, and cell cycle arrest. Therefore, abnormalities in p53 and its related signaling pathways play an important role in the diagnosis and treatment of central nervous system diseases. This review mainly discusses the latest findings regarding the role of p53 in some central nervous system diseases, such as brain tumors, Alzheimer disease, Parkinson disease, autism, epilepsy, spinocerebellar ataxia, and so on, to provide a comprehensive interpretation of the treatment of neurological diseases from a new perspective.

Diversity of fungus-mediated synthesis of gold nanoparticles: properties, mechanisms, challenges, and solving methods.

Fungi-mediated synthesis of Gold nanoparticles (AuNPs) has advantages in: high efficiency, low energy consumption, no need for extra capping and stabilizing agents, simple operation, and easy isolation and purification. Many fungi have been found to synthesize AuNPs inside cells or outside cells, providing different composition and properties of particles when different fungi species or reaction conditions are used. This is good to produce AuNPs with different properties, but may cause challenges to precisely control the particle shape, size, and activities. Besides, low concentrations of substrate and fungal biomass are needed to synthesize small-size particles, limiting the yield of AuNPs in a large scale. To find clues for the development methods to solve these challenges, the reported mechanisms of the fungi-mediated synthesis of AuNPs were summarized. The mechanisms of intracellular AuNPs synthesis are dependent on gold ions absorption by the fungal cell wall via proteins, polysaccharides, or electric absorption, and the reduction of gold ions via enzymes, proteins, and other cytoplasmic redox mediators in the cytoplasm or cell wall. The extracellular synthesis of AuNPs is mainly due to the metabolites outside fungal cells, including proteins, peptides, enzymes, and phenolic metabolites. These mechanisms cause the great diversity of the produced AuNPs in functional groups, element composition, shapes, sizes, and properties. Many methods have been developed to improve the synthesis efficiency by changing: chloroauric acid concentrations, reaction temperature, pH, fungal mass, and reaction time. However, future studies are still required to precisely control the: shape, size, composition, and properties of fungal AuNPs.

A new PEDV strain CH/HLJJS/2022 can challenge current detection methods and vaccines.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) variant strains cause great economic losses to the global swine industry. However, vaccines do not provide sufficient protection against currently circulating strains due to viral mutations. This study traced the molecular characteristics of the most recent isolates in China and aimed to provide a basis for the prevention and treatment of PEDV. METHODS: We obtained samples from a Chinese diarrheal swine farm in 2022. Reverse transcription polymerase chain reaction and immunofluorescence were used to determine the etiology, and the full-length PEDV genome was sequenced. Nucleotide similarity was calculated using MEGA to construct a phylogenetic tree and DNASTAR. Mutant amino acids were aligned using DNAMAN and modeled by SWISS-MODEL, Phyre2 and FirstGlance in JMOL for protein tertiary structure simulation. Additionally, TMHMM was used for protein function prediction. RESULTS: A PEDV virulent strain CH/HLJJS/2022 was successfully isolated in China. A genome-wide based phylogenetic analysis suggests that it belongs to the GII subtype, and 96.1-98.9% homology existed in the whole genomes of other strains. For the first time, simultaneous mutations of four amino acids were found in the highly conserved membrane (M) and nucleocapsid (N) proteins, as well as eight amino acid mutations that differed from the vast majority of strains in the spike (S) protein. Three of the mutations alter the S-protein spatial structure. In addition, typing markers exist during strain evolution, but isolates are using the fusion of specific amino acids from multiple variant strains to add additional features, as also demonstrated by protein alignments and 3D models of numerous subtype strains. CONCLUSION: The newly isolated prevalent strain CH/HLJJS/2022 belonged to the GII subtype, and thirteen mutations different from other strains were found, including mutations in the highly conserved m and N proteins, and in the S1° and COE neutralizing epitopes of the S protein. PEDV is breaking through original cognitions and moving on a more complex path. Surveillance for PEDV now and in the future and improvements derived from mutant strain vaccines are highly warranted.

Gut microbiota as a potential target for developing anti-fatigue foods.

Fatigue has many negative effects on human health. As such, it is desirable to develop anti-fatigue foods and understand the mechanisms of their action. Based on a comprehensive review of the literature, this article discusses the important roles of gut microbiota in fatigue and anti-fatigue. Studies have shown that an increase in pathogenic bacteria and a decrease in beneficial bacteria co-exist when fatigue is present in both rodents and humans, whereas changes in gut microbiota were reported after intervention with anti-fatigue foods. The roles of gut microbiota in the activities of anti-fatigue foods can also be explained in the causes and the effects of fatigue. Among the causes of fatigue, the accumulation of lactic acid, decrease of energy, and reduction of central nervous system function were related to gut microbiota metabolism. Among the harmful effects of fatigue, oxidative stress, inflammation, and intestinal barrier dysfunction were related to gut microbiota dysbiosis. Furthermore, gut microbiota, together with anti-fatigue foods, can inhibit pathogen growth, convert foods into highly anti-oxidative or anti-inflammatory products, produce short-chain fatty acids, maintain intestinal barrier integrity, inhibit intestinal inflammation, and stimulate the production of neurotransmitters that regulate the central nervous system. Therefore, it is believed that gut microbiota play important roles in the activities of anti-fatigue foods and may provide new insights on the development of anti-fatigue foods.

Concentration-dependent mechanisms of fluoranthene uptake by ryegrass.

Fluoranthene (Flu) uptake by plants is affected by plant growth and environmental concentration. Although plant growth processes, including substance synthesis and antioxidant enzyme activities, have been reported to regulate Flu uptake, their contributions have been poorly evaluated. Moreover, the effect of Flu concentration is little known. Here, low concentrations (0, 1, 5, and 10 mg/L) and high concentrations (20, 30, and 40 mg/L) of Flu were set to compare the changes in Flu uptake by ryegrass (Lolium multiflorum Lam.). Indices of plant growth (biomass, root length, root area, root tip number, and photosynthesis and transpiration rates), substance synthesis (indole acetic acid [IAA] content), and antioxidant enzyme activities (superoxide dismutase [SOD], peroxidase [POD], and catalase [CAT]) were recorded to unravel the mechanism of Flu uptake. Findings suggested that the Langmuir model fitted Flu uptake by ryegrass well. Flu absorption capacity in the root was stronger than that that in the leaf. Flu bioconcentration and translocation factors increased then reduced with the increase in Flu concentration and reached the maximum value under 5 mg/L Flu treatment. Plant growth and IAA content had the same pattern as before bioconcentration factor (BCF). SOD and POD activities increased then decreased with Flu concentration and reached their highest levels under 30 and 20 mg/L Flu treatments, respectively, whereas CAT activity decreased continuously and reached its lowest level under 40 mg/L Flu treatment. Variance partitioning analysis indicated that IAA content had the greatest significant effect on Flu uptake under low-concentration Flu treatments, whereas antioxidant enzyme activities had the greatest significant effect on Flu uptake under high-concentration Flu treatments. Revealing the concentration-dependent mechanisms of Flu uptake could provide a basis for regulating pollutant accumulation in plants.

Constructing In2S3/CdS/N-rGO Hybrid Nanosheets via One-Pot Pyrolysis for Boosting and Stabilizing Visible Light-Driven Hydrogen Evolution.

The construction of hybrid junctions remains challenging for the rational design of visible light-driven photocatalysts. Herein, In2S3/CdS/N-rGO hybrid nanosheets were successfully prepared via a one-step pyrolysis method using deep eutectic solvents as precursors. Benefiting from the surfactant-free pyrolysis method, the obtained ultrathin hybrid nanosheets assemble into stable three-dimensional self-standing superstructures. The tremella-like structure of hybrid In2S3/N-rGO exhibits excellent photocatalytic hydrogen production performance. The hydrogen evolution rate is 10.9 mmol·g-1·h-1, which is greatly superior to CdS/N-rGO (3.7 mmol·g-1·h-1) and In2S3/N-rGO (2.6 mmol·g-1·h-1). This work provides more opportunities for the rational design and fabrication of hybrid ultrathin nanosheets for broad catalytic applications in sustainable energy and the environment.

Role of Xihuang capsule combined with albumin-bound paclitaxel on the treatment of stage III breast cancer and T cell subsets, survival rate and adverse reactions.

To investigate the impact of Xihuang Capsule combined with albumin-bound paclitaxel on the treatment of stage III breast cancer and T cell subsets, survival rate and adverse reactions. Totally 200 patients with stage III breast cancer were evenly randomized into control group (albumin-bound paclitaxel for chemotherapy) and observation group (Xihuang Capsules for adjuvant therapy based on the treatment of the control group). The RR and DCR of the observation group was markedly higher as compared to the control group (66.7% vs 28.6%; 80.9% VS 47.6%) (all P <0.05). After 4 weeks of treatment, the CD8+ in the two groups decreased, while CD3+ and CD4+ increased, and the change in observation group was more significant (all P<0.05). The observation group exhibited a better half-year, 1-year, 1.5-year and 2-year survival rates compared to the control group (81.0% vs 71.4%, 71.4% vs 57.1%, 57.1% vs 33.3% and 42.9%vs 19.0%) (all P<0.05). Adding Xihuang Capsule to adjuvant therapy with albumin paclitaxel chemotherapy benefits the patient's immunity and survival rate, with good efficacy and safety profiles.

Management effects on soil nematode abundance differ among functional groups and land-use types at a global scale.

Anthropogenic land use is threatening global biodiversity. As one of the most abundant animals on Earth, nematodes occupy several key positions in belowground food webs and contribute to many ecosystem functions and services. However, the effects of land use on nematode abundance and its determinants remain poorly understood at a global scale. To characterize nematodes' responses to land use across trophic groups, we used a dataset of 6,825 soil samples globally to assess how nematode abundance varies among regional land-use types (i.e. primary vegetation, secondary vegetation, pasture, cropland and urban) and local land-use intensities (i.e. human-managed or not). We also quantified the interactive effects of land use and environmental predictors (i.e. mean annual temperature, annual precipitation, soil organic carbon, soil pH, global vegetation biomass and global vegetation productivity) on nematode abundance. We found that total nematode abundance and the abundance of bacterivores, fungivores, herbivores, omnivores and predators generally increased or were not affected under management across land-use types. Specifically, the most numerically abundant bacterivores were higher in managed than in unmanaged secondary vegetation habitats and urban areas, and herbivores were more abundant in managed than in unmanaged primary and secondary vegetation habitats. Furthermore, the numbers of significant environmental predictors of nematode abundance were reduced and the magnitude and the direction of the predictors were changed under management. We also found that nematode abundance was more variable and less determined by environmental factors in urban than in other land-use types. These findings challenge the view that human land use decreases animal abundance across trophic groups, but highlight that land use is altering the trophic composition of soil nematodes and its relationships with the environment at the global scale.

The capability of Bacillus pseudomycoides from soil to remove Cu(II) in water and prevent it from entering plants.

AIMS: Copper ion is widespread in wastewater and threatens the condition and human health. Micro-organisms have unique advantages to remove heavy-metal ions from water, but are rarely reported in the removal of copper ion. This aims to develop micro-organisms that can remove copper ion in water, characterize their properties and analyse their potential application in practice. METHODS AND RESULTS: Sewage sludge was used as the source to isolate wild bacteria that can remove copper ion in water. The most efficient strain was screened out from 23 obtained isolates, identified as Bacillus pseudomycoides and coded as C6. The properties of C6 in the removal of copper ion in water were investigated in the aspects of reaction conditions, reaction groups, reaction dynamic and the application in oat planting. The reaction at pH 7 within 10 min yielded the highest removal rate of copper ion, 83%. The presence of lead ion in the reaction system could promote the removal rate of copper ion. Carboxyl groups and amidogen of C6 biomass were mainly involved in the removal of copper ion. The removal of copper ion was in accord with single-layer adsorption and Langmuir adsorption isotherm model. In application, C6 biomass reduced the copper content in the oat seedlings grown in copper ion containing water by more than seven times. CONCLUSIONS: B. pseudomycoides C6 can efficiently remove copper ion in water and inhibit it from entering plants. SIGNIFICANCE AND IMPACT OF STUDY: This is the first time to report the capability of B. pseudomycoides to remove copper ion in water, which is also more efficient than the currently reported chemical and biological methods.

Highland adaptation of birds on the Qinghai-Tibet Plateau via gut microbiota.

Highland birds evolve multiple adaptive abilities to cope with the harsh environments; however, how they adapt to the high-altitude habitats via the gut microbiota remains understudied. Here we integrated evidences from comparative analysis of gut microbiota to explore the adaptive mechanism of black-necked crane, a typical highland bird in the Qinghai-Tibet Plateau. Firstly, the gut microbiota diversity and function was compared among seven crane species (one high-altitude species and six low-altitude species), and then among three populations of contrasting altitudes for the black-necked crane. Microbiota community diversity in black-necked crane was significantly lower than its low-altitude relatives, but higher microbiota functional diversity was observed in black-necked crane, suggesting that unique bacteria are developed and acquired due to the selection pressure of high-altitude environments. The functional microbial genes differed significantly between the low- and high-altitude black-necked cranes, indicating that altitude significantly impacted microbial communities' composition and structure. Adaptive changes in microbiota diversity and function are observed in response to high-altitude environments. These findings provide us a new insight into the adaptation mechanism to the high-altitude environment for birds via the gut microbiota. KEY POINTS: • The diversity and function of gut microbiota differed significantly between the low- and high-altitude crane species. • Black-necked crane adapts to the high-altitude environment via specific gut microbiota. • Altitude significantly impacted microbial communities' composition and structure.

The Plasmid pEX18Gm Indirectly Increases Caenorhabditis elegans Fecundity by Accelerating Bacterial Methionine Synthesis.

Plasmids are mostly found in bacteria as extrachromosomal genetic elements and are widely used in genetic engineering. Exploring the mechanisms of plasmid-host interaction can provide crucial information for the application of plasmids in genetic engineering. However, many studies have generally focused on the influence of plasmids on their bacterial hosts, and the effects of plasmids on bacteria-feeding animals have not been explored in detail. Here, we use a "plasmid-bacteria-Caenorhabditis elegans" model to explore the impact of plasmids on their host bacteria and bacterivorous nematodes. First, the phenotypic responses of C. elegans were observed by feeding Escherichia coli OP50 harboring different types of plasmids. We found that E. coli OP50 harboring plasmid pEX18Gm unexpectedly increases the fecundity of C. elegans. Subsequently, we found that the plasmid pEX18Gm indirectly affects C. elegans fecundity via bacterial metabolism. To explore the underlying regulatory mechanism, we performed bacterial RNA sequencing and performed in-depth analysis. We demonstrated that the plasmid pEX18Gm upregulates the transcription of methionine synthase gene metH in the bacteria, which results in an increase in methionine that supports C. elegans fecundity. Additionally, we found that a pEX18Gm-induced increase in C. elegans can occur in different bacterial species. Our findings highlight the plasmid-bacteria-C. elegans model to reveal the mechanism of plasmids' effects on their host and provide a new pattern for systematically studying the interaction between plasmids and multi-species.

Development of a microecologic product from Lactobacillus rhamnosus based on silica.

BACKGROUND: Probiotics are primarily made into microecologic products for use in the food and feed industries. The freeze-drying technique is widely used in their preparation to maintain their high level of bioactivity. This causes high costs in terms of the energy and time needed. In this study, we developed a method to produce a highly active microecologic product from Lactobacillus rhamnosus using heating and silica. RESULTS: A microecologic product was made successfully from L. rhamnosus using the whole bacterial culture broth, without waste, and using food-grade silica (4.5 mL g-1 ) to absorb water before drying at 37 °C for 8 h. The activity of L. rhamnosus cells was increased significantly by adding water extracts of green tea to the culture medium. The viable amount of L. rhamnosus in the obtained microecologic product was 9.80 × 1010 cfu g-1 with a survival rate of 224.67% in simulated gastric juice for 3 h and 68.2% in simulated intestinal juice for 3 h. The microecologic product treated an intestinal infection by multi-drug-resistant Staphylococcus aureus in mice very efficiently. CONCLUSION: The study developed an economic, eco-friendly, and efficient method for preparing highly active microecologic agents using heating and without waste. © 2022 Society of Chemical Industry.

Ketamine suppresses proliferation and induces ferroptosis and apoptosis of breast cancer cells by targeting KAT5/GPX4 axis.

Breast cancer (BC) serves as a prevalent and mortal malignancy among female globally. Ferroptosis, as an oxidative cell death that characterized by abnormal iron accumulation, plays critical role in cancer development. Ketamine is a rapid-acting anesthetic agent and has presented potential anti-tumor properties. However, the effect of Ketamine on breast cancer is still obscure. Here, we aimed to explore the function of Ketamine in the modulation of proliferation and ferroptosis of breast cancer cells. The cell viability of breast cancer cells was repressed by the treatment of Ketamine, while ferroptosis inhibitor ferrostatin 1 and apoptosis inhibitor ZVAD-FMK could restore the cell viability. The treatment of Ketamine significantly decreased the Edu-positive breast cancer cells and the colony formation numbers, and the treatment of ferrostatin 1 reversed the effect of Ketamine. We observed that the levels of ferroptosis markers, such as MDA, lipid ROS, and Fe2+ were increased by the treatment of Ketamine in breast cancer cells. Regarding to the mechanism, we found that Ketamine inhibited the expression of GPX4, an anti-ferroptosis factor, by attenuating KAT5 on the promoter region of GPX4, repressing the enrichment of histone H3 lysine 27 acetylation (H3K27ac) and RNA polymerase II (RNA pol II). The treatment of Ketamine reduced the cell viability and proliferation of breast cancer cells, in which the overexpression of KAT5 or GPX4 was able to restore the phenotypes. The treatment of Ketamine induced the levels of MDA, lipid ROS, and Fe2+, while KAT5 or GPX4 overexpression could reverse this effect in breast cancer cells. Thus, we concluded that Ketamine suppressed proliferation and induced ferroptosis of breast cancer cells by targeting KAT5/GPX4 axis. Ketamine may serve as a potential therapeutic strategy for breast cancer.

Platinum-Containing Supramolecular Drug Self-Delivery Nanomicelles for Efficient Synergistic Combination Chemotherapy.

Supramolecular drug self-delivery systems (SDSDSs) involving active drugs as building blocks linked by supramolecular interactions have been well defined as an advanced chemotherapy strategy. However, the lack of detecting release of drugs from SDSDSs at specific tumor sites inevitably leads to unsatisfactory therapeutic effects, owing to the lack of information regarding the administration of these drugs. In this work, predesigned platinum-containing supramolecular drug self-delivery nanomicelles (SDSDNMs) were employed to synchronously realize drug monitoring by computed tomography imaging, immediately reflecting the evolution of drug release and real-time treatment at the tumor site. The appropriate administration dosage (1.2 mg mL-1,100 µL) and the injection interval (once every 3 days) needed to guide the antitumor activity of SDSDNMs were then defined, thereby attaining the aim of efficient synergistic combination chemotherapy. In vivo tumor inhibition and histological analyses showed that SDSDNMs exhibited a strong tumor inhibition effect and good safety with respect to normal organs. Such a supramolecular drug self-delivery strategy with monitored functions may offer new potential opportunities for application in the field of synergistic combination chemotherapy.