Impacts of PFOS, PFOA and their alternatives on the gut, intestinal barriers and gut-organ axis.

With the restricted use of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), a number of alternatives to PFOS and PFOA have attracted great interest. Most of the alternatives are still characterized by persistence, bioaccumulation, and a variety of toxicity. Due to the production and use of these substances, they can be detected in the atmosphere, soil and water body. They affect human health through several exposure pathways and especially enter the gut by drinking water and eating food, which results in gut toxicity. In this review, we summarized the effects of PFOS, PFOA and 9 alternatives on pathological changes in the gut, the disruption of physical, chemical, biological and immune barriers of the intestine, and the gut-organ axis. This review provides a valuable understanding of the gut toxicity of PFOS, PFOA and their alternatives as well as the human health risks of emerging contaminants.

The impact on Cd bioavailability and accumulation in rice (Oryza sativa L.) induced by dry direct-seeding cultivation method in field-scale experiments.

Dry direct-seeded rice cultivation has gained popularity and expanded its cultivated area due to reduced labor requirements and water consumption. However, the impact of this cultivation method on cadmium (Cd) bioavailability in soil and the accumulation levels in grains remains uncertain. Field experiments were conducted in acidic soils at two locations in southern China to compare rice varieties and evaluate the dry direct-seeding method alongside the wet direct-seeding and traditional transplanting methods. Dry direct-seeded rice reached significantly higher Cd concentrations in its tissues starting from the heading stage than transplanted rice. Cd accumulation levels by the maturation stage in the brown rice of dry direct-seeded rice were 18.33 %-150.69 % higher than those of wet direct-seeded and transplanted rice, with a considerable ability to translocate Cd into brown rice. Furthermore, dry direct seeding decreased iron plaque formation, particularly in the amorphous Fe form; it resulted in high soil temperature and low moisture content during tillering, elevating Cd availability in the soil. Additionally, the proportion of ions and more labile forms of Cd in the soil solution was high. Moreover, the soil under dry direct seeding had high urease and acid phosphatase enzyme activities. However, low richness and diversity in the bacterial community were characterized by a significant increase in the relative abundance of Actinobacteria and Gammaproteobacteria at the class level, while exhibiting decreased relative abundances of Alphaproteobacteria, Bacilli, and KD4-96, along with fewer biomarkers. Nonetheless, these differences are gradually reduced during the maturation stage. Overall, although dry direct seeding offers several advantages, it is crucial to implement additional measures to mitigate the increased health risks linked to rice cultivation through this approach in Cd-contaminated areas.

Biodegradation characteristics and genomic analysis of a newly isolated indole-degrading strain Pseudomonas aeruginosa Jade-X / Características de biodegradación y análisis genómico de una cepa degradante de indol recientemente aislada Pseudomonas aeruginosa Jade-X

Indole is a typical heterocyclic compound derived from tryptophan widespread in nature. Pseudomonas aeruginosa is one of the most common opportunistic pathogens everywhere in the world. Indole and P. aeruginosa will encounter inevitably; however, the indole transformation process by P. aeruginosa remains unclear. Herein, an indole-degrading strain of P. aeruginosa Jade-X was isolated from activated sludge. Strain Jade-X could degrade 1 mmol/L indole within 48 h with the inoculum size of 1% (v/v). It showed high efficiency in indole degradation under the conditions of 30–42 °C, pH 5.0–9.0, and NaCl concentration less than 2.5%. The complete genome of strain Jade-X was sequenced which was 6508614 bp in length with one chromosome. Bioinformatic analyses showed that strain Jade-X did not contain the indole oxygenase gene. Three cytochrome P450 genes were identified and up-regulated in the indole degradation process by RT-qPCR analysis, while cytochrome P450 inhibitors did not affect the indole degradation process. It suggested that indole oxidation was catalyzed by an unraveled enzyme. An ant gene cluster was identified, among which the anthranilate 1,2-dioxygenase and catechol 1,2-dioxygenase genes were upregulated. An indole-anthranilate-catechol pathway was proposed in indole degradation by strain P. aeruginosa Jade-X. This study enriched our understanding of the indole biodegradation process in P. aeruginosa.(AU)

A deep insight into ferroptosis in lung disease: facts and perspectives.

In the last decade, ferroptosis has received much attention from the scientific research community. It differs from other modes of cell death at the morphological, biochemical, and genetic levels. Ferroptosis is mainly characterized by non-apoptotic iron-dependent cell death caused by iron-dependent lipid peroxide excess and is accompanied by abnormal iron metabolism and oxidative stress. In recent years, more and more studies have shown that ferroptosis is closely related to the occurrence and development of lung diseases. COPD, asthma, lung injury, lung fibrosis, lung cancer, lung infection and other respiratory diseases have become the third most common chronic diseases worldwide, bringing serious economic and psychological burden to people around the world. However, the exact mechanism by which ferroptosis is involved in the development and progression of lung diseases has not been fully revealed. In this manuscript, we describe the mechanism of ferroptosis, targeting of ferroptosis related signaling pathways and proteins, summarize the relationship between ferroptosis and respiratory diseases, and explore the intervention and targeted therapy of ferroptosis for respiratory diseases.

Co-culture of benzalkonium chloride promotes the biofilm formation and decreases the antibiotic susceptibility of a Pseudomonas aeruginosa strain.

Benzalkonium chloride (BAC) is a disinfectant with broad-spectrum antibacterial properties, yet despite its widespread use and detection in the environment, the effects of BAC exposure on microorganisms remain poorly documented. Herein, the impacts of BAC on a Pseudomonas aeruginosa strain Jade-X were systematically investigated. The results demonstrated that the minimum inhibitory concentration (MIC) of BAC against strain Jade-X was 64 mg L-1. Exposure to BAC concentrations of 8, 16, 32, and 64 mg L-1 significantly augmented biofilm formation by 2.03-, 2.43-, 2.96-, and 2.56-fold respectively. The swimming and twitching abilities, along with the virulence factor production, were inhibited. Consistently, quantitative reverse transcription PCR assays revealed significant downregulation of genes related to flagellate- and pili-mediated motilities (flgD, flgE, pilB, pilQ, and motB), as well as phzA and phzB genes involved in pyocyanin production. The results of disk diffusion and MIC assays demonstrated that BAC decreased the antibiotic susceptibility of ciprofloxacin, levofloxacin, norfloxacin, and tetracycline. Conversely, an opposite trend was observed for polymyxin B and ceftriaxone. Genomic analysis revealed that strain Jade-X harbored eleven resistance-nodulation-cell division efflux pumps, with mexCD-oprJ exhibiting significant upregulation while mexEF-oprN and mexGHI-opmD were downregulated. In addition, the quorum sensing-related regulators LasR and RhlR were also suppressed, implying that BAC might modulate the physiological and biochemical behaviors of strain Jade-X by attenuating the quorum sensing system. This study enhances our understanding of interactions between BAC and P. aeruginosa, providing valuable insights to guide the regulation and rational use of BAC.

Unraveling the signaling roles of indole in an opportunistic pathogen Pseudomonas aeruginosa strain Jade-X.

Pseudomonas aeruginosa, which can produce several toxins and form biofilm, is listed among the priority pathogens. Indole is a ubiquitous aromatic pollutant and signaling molecule produced by tryptophanase in bacteria. Herein, the impacts of indole on a newly isolated P. aeruginosa strain Jade-X were systematically investigated. Indole (0.5-2.0 mM) enhanced the biofilm production by 1.33-2.31-fold after 24 h incubation at 30 °C. However, the effects indole on biofilm formation were intricate and closely intertwined with factors such as incubation temperature, bacterial growth stage, and indole concentration. The twitching motility was enhanced by 1.15-1.99-fold by indole, potentially facilitating surface exploration and biofilm development. Indole reduced the production of virulence factors (pyocyanin and pyoverdine) as well as altered the surface properties (zeta potential and hydrophobicity). Transcriptional analysis revealed that indole (1.0 mM) significantly downregulated mexGHI-opmD efflux genes (4.73-6.91-fold) and virulence-related genes (pqs, pch, and pvd clusters, and flagella-related genes), while upregulating pili-related genes in strain Jade-X. The quorum sensing related signal regulators, including RhlR, LasR, and MvfR (PqsR), were not altered by indole, while other six transcriptional regulators (AmrZ, BfmR, PchR, QscR, SoxR, and SphR) were significantly affected, implying that indole effects might be regulated in a complex and delicate manner. This study should provide new insights into our understanding of indole signaling roles.

Biodegradation of chloroxylenol by an aerobic enrichment consortium and a newly identified Rhodococcus strain.

Chloroxylenol is a commonly used antimicrobial agent in antibacterial and disinfection products, which has been detected in various environments, such as wastewater treatment plants, rivers, seawater, and even drinking water, with concentrations ranging from ng/L to mg/L. However, the biodegradation of chloroxylenol received limited attention with only sporadic reports available so far. In this study, an efficient chloroxylenol-degrading consortium, which could degrade 20 mg/L chloroxylenol within two days, was obtained after five months of enrichment. Amplicon sequencing analysis revealed a decrease in the α-diversity (e.g., Shannon index and Inv_Simpson index) of the community during the domestication process. Microbial community dynamics were uncovered, with sequences affiliated to Achromobacter, Pseudomonas, and Rhodococcus identified as the most abundant taxonomic groups. From the consortium, five pure isolates were obtained; however, it was found that only one strain of Rhodococcus could degrade chloroxylenol. Strain Rhodococcus sp. DMU2021 could degrade chloroxylenol efficiently under the conditions of temperature 30-40 °C, and neutral/alkaline conditions. Chloroxylenol was toxic to strain DMU2021 and triggered both enzymatic and non-enzymatic antioxidant systems in response. This study provides novel insights into the biodegradation process of chloroxylenol, as well as valuable bioresources for bioremediation.

Biodegradation characteristics and genomic analysis of a newly isolated indole-degrading strain Pseudomonas aeruginosa Jade-X.

Indole is a typical heterocyclic compound derived from tryptophan widespread in nature. Pseudomonas aeruginosa is one of the most common opportunistic pathogens everywhere in the world. Indole and P. aeruginosa will encounter inevitably; however, the indole transformation process by P. aeruginosa remains unclear. Herein, an indole-degrading strain of P. aeruginosa Jade-X was isolated from activated sludge. Strain Jade-X could degrade 1 mmol/L indole within 48 h with the inoculum size of 1% (v/v). It showed high efficiency in indole degradation under the conditions of 30-42 °C, pH 5.0-9.0, and NaCl concentration less than 2.5%. The complete genome of strain Jade-X was sequenced which was 6508614 bp in length with one chromosome. Bioinformatic analyses showed that strain Jade-X did not contain the indole oxygenase gene. Three cytochrome P450 genes were identified and up-regulated in the indole degradation process by RT-qPCR analysis, while cytochrome P450 inhibitors did not affect the indole degradation process. It suggested that indole oxidation was catalyzed by an unraveled enzyme. An ant gene cluster was identified, among which the anthranilate 1,2-dioxygenase and catechol 1,2-dioxygenase genes were upregulated. An indole-anthranilate-catechol pathway was proposed in indole degradation by strain P. aeruginosa Jade-X. This study enriched our understanding of the indole biodegradation process in P. aeruginosa.

Multicity comparative assessment and optimized management path of sustainability of the economy-energy-environment system: A case study of core cities in China's three major economic circles.

Coordinated and stable development of economy-energy-environment (3E) systems represents a long-term strategy for the sustainable development of humankind. Following the research idea of "indicator system construction-3E system evaluation-obstacles identification-optimization management," this article innovatively constructs a multiangle and comparable methodology system for evaluation and optimized management of the 3E system and considers the core cities of three economic circles in China as cases for empirical research. The results show that all the coordination degree levels were of good or high quality, which was at the highest level in the country. The sustainability degree of the three cities showed an upward trend; of these, Beijing had the highest sustainability degree, followed by Guangzhou and Shanghai. Obstacle degree analysis shows that technology investment and energy factors were common factors hindering sustainable development of the 3E systems of the three cities, and each city also had its own unique factors that acted as obstacles. On this basis, this article formulates region-specific policy recommendations in order to provide a useful reference for top-level design for the government. Integr Environ Assess Manag 2024;20:875-887. © 2023 SETAC.

Cadmium accumulation in brown rice (Oryza sativa L.) depends on environmental factors and nutrient transport: A three-year field study.

Cadmium (Cd) accumulation in brown rice is a complex process in agroecosystems and is influenced by multiple factors, such as climate, soil properties, and nutrient transport. However, during the Cd transport process (soil-root-straw-brown rice), it remains unclear how Cd concentration in brown rice (BCd) is causal relationship to environmental factors and nutrient transport. The differences in precipitation, soil properties, nutrient transport, and Cd transport were studied through a three-year fixed-point field trial and linked them to the standard of Cd and nutrient absorption and transport processes. The results showed that the available Cd concentration (ACd), and BCd in 2020 were lower than those in 2019 and 2021, but monthly precipitation (MP) was higher in 2020 than in 2019 and 2021. The MP and niche metrics were significantly negatively associated with ACd and BCd. However, the relationship between the form and location of different nutrient elements and Cd in roots, Cd in straws, and BCd also varied during the transport of nutrient elements and Cd from soil to root to straw to brown rice. Structural equation modelling analysis showed that nitrogen (N 15.5 %), phosphorus (P 14.1 %), silicon (Si 4.2 %), and iron (Fe 7.6 %) transport were more closely related to BCd than to potassium (K), calcium (Ca), magnesium (Mg), and manganese (Mn). The increase in MP significantly inhibited the increase in BCd, whereas the MP led to a decrease in BCd by affecting the transport of N and Fe. Among them, Si, Fe, and BCd had indirect causal relationships, whereas N, P, and BCd had direct causal relationships. Particularly, P is a crucial nutrient in reducing BCd in the Cd transport process. Our results highlight a strong causal relationship between environmental factors and nutrient transport and BCd, and provide a theoretical basis for fertiliser application in Cd-contaminated agroecosystems.

Is solar heating an appropriate choice in rural areas of northern China? Evidence from numerical simulation and life cycle assessment.

Solar heating is generally regarded as a clean and low-carbon heating method, while its high initial investment hinders its promotion in economically underdeveloped areas. With the implementation of the clean heating policy and the proposal of the carbon neutralization target, rural bulk coal heating in northern China is restricted. The Chinese government proposes to widely adopt solar heating to meet the heating demands of rural residents. In this research, the application of solar assisted heat pump systems in Beijing, Tianjin, Hebei and its surrounding areas in China is numerically simulated. A new evaluation method under the same initial investment constraint is proposed to verify its benefits throughout the entire life cycle. The results indicate that although solar thermal heating has the lowest environmental impact and carbon emissions among various heating methods, it is not the best solution to rural clean heating. The reason is that equal investment in other projects can bring much more benefits, such as roof solar photovoltaic. In contrast to the air source heat pump and photovoltaic panel scheme with the same initial investment, solar heating has obvious negative environmental impact, 53.3 % higher economic cost, 35.9 tons more carbon emissions, and 105.9 % higher roof area occupation. The sensitivity analysis of solar fraction, geographical coordinates, and energy price also supports the above findings. The recommendation is proposed to promote air source heat pumps or solar photovoltaic, rather than solar thermal collectors, so as to reduce the cost of rural clean heating and carbon emission reduction.

Long-term influence of chloroxylenol on anaerobic microbial community: Performance, microbial interaction, and antibiotic resistance gene behaviors.

The use of antibacterial and disinfection products is increasing in recent years. Para-chloro-meta-xylenol (PCMX), a widely used antimicrobial agent, has been detected in various environments. Herein, the impacts of PCMX with long-term exposure on anaerobic sequencing batch reactors were investigated. The high concentration (50 mg/L, GH group) PCMX severely inhibited the nutrient removal process, and the low concentration group (0.5 mg/L, GL group) slightly affected the removal efficiency which was recovered after 120 days of adaptation compared to the control group (0 mg/L, GC group). Cell viability tests indicated that PCMX inactivated the microbes. A significant reduction in bacterial α-diversity was observed in the GH but not the GL group. The microbial communities were shifted upon PCMX exposure, among which Olsenella, Novosphingobium, and Saccharibacteria genera incertae Sedis became the predominant genera in the GH groups. Network analyses showed that PCMX significantly reduced the complexity and interactions of the microbial communities, consistent with the negative impacts on bioreactor performance. Real-time PCR analysis indicated that PCMX affected the behavior of antibiotic resistance genes (ARGs), and the relationship between ARGs and bacterial genera gradually became complicated after long-term exposure. Most detected ARGs decreased on Day 60 but increased on Day 120 especially in the GL group, implying the potential risk of environment-relevant concentration of PCMX in the ecosystems. This study provides new insights into the understanding of the impacts and risks of PCMX on wastewater treatment processes.

[Current status of animal experiment report of acupuncture intervention in chronic fatigue syndrome based on ARRIVE guidelines and GSPC list].

OBJECTIVE: To analyze the current status of animal experiments of acupuncture in intervening chronic fatigue syndrome, so as to search formethods to improve the quality of animal experiment reports. METHODS: From the databases, such as CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, Embase and Cochrane Library, the literature of animal experiment on acupuncture treatment for chronic fatigue syndrome was searched from January 1st, 2011 to April 2nd, 2022. Data were extracted according to the animal research reporting in vivo experiment (ARRIVE) guidelines 2.0 and gold standard publication checklist (GSPC), and statistical analysis was performed using Excel 2019. RESULTS: A total of 16 studies were finally included. The satis-faction rate of essential items in the ARRIVE guidelines 2.0 is 41.76%，while the satisfaction rate of recommended items is only 27.73% and of the GSPC is 25.89%. Out of 16 studies, 13 of them explained the reasons for animal exclusion in the experiment, 8 provided specific randomized methods, 8 described detailed information on animal species, strains, and quantities, 3 basically indicated that they had passed ethical review, 7 explained the limitations of the research. All 16 studies reported the main findings and elucidated their potential clinical or scientific value. CONCLUSION: Current animal studies on acupuncture in intervening the chronic fatigue syndrome are of certain limitation. Descriptions of multiple items are incomplete or missing, which prevents rea-ders from assessing reliability and authenticity of the animal experiment. It is recommended that in future research, experimental design, execution and report should be carried out according to the report guidelines for animal experiment to improve research quality.

First Principles Calculation of Adsorption of Water on MgO (100) Plane.

The hydration reaction seriously affects the quality and performance of MgO-based products. The final analysis showed that the problem is the surface hydration of MgO. By studying the adsorption and reaction of water molecules on the surface of MgO, we can understand the nature of the problem from the root cause. In this paper, first-principles calculations are performed on the crystal plane of MgO (100) to study the influence of the different orientation, sites and coverage of water molecules on the surface adsorption. The results show that the adsorption sites and orientations of monomolecular water has no effect on the adsorption energy and adsorption configuration. The adsorption of monomolecular water is unstable, with almost no charge transfer, belonging to the physical adsorption, which implies that the adsorption of monomolecular water on MgO (100) plane will not lead to the dissociation of water molecule. When the coverage of water molecules exceeds 1, water molecules will dissociate, and the population value between Mg and Os-H will increase, leading to the formation of ionic bond. The density of states of O p orbital electrons changes greatly, which plays an important role in surface dissociation and stabilization.

A 7-Day Decitabine-Included Conditioning Regimen Accelerated Donor Hematopoietic Engraftment while Reduced the Occurrence of Mucositis without Interfering with Prognosis.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard and curative treatment strategy for patients with hematologic malignancies. Recently, decitabine-included regimens have been investigated by several studies including ours, which may prevent relapse of primary malignant diseases. METHODS: This study was to retrospectively evaluate a 7-day decitabine-included regimen with reduced dose of idarubicin for patients with hematologic malignancies who underwent allo-HSCT. RESULTS: A total of 84 patients were enrolled, including 24 cases in 7-day and 60 cases in 5-day decitabine groups, respectively. Patients conditioned with 7-day decitabine regimen showed accelerated neutrophil (12.05 ± 1.97 vs. 13.86 ± 3.15; u = 9.309, p < 0.001) and platelet (16.32 ± 6.27 vs. 21.37 ± 8.57; u = 8.887, p < 0.001) engraftment compared with those treated with 5-day decitabine regimen. Patients in the 7-day decitabine group showed a significantly lower incidence rate of total (50.00% [12/24] versus 78.33% [47/60]; χ2 = 6.583, p = 0.010) and grade III or above (4.17% [1/24] vs. 31.67% [19/60]; χ2 = 7.147, p = 0.008) oral mucositis compared to those in the 5-day decitabine group. However, the occurrence of other major complications post-allo-HSCT and outcomes of patients in these two groups were comparable. CONCLUSION: These results demonstrate that this 7-day decitabine-contained new conditioning regimen seems to be feasible and safe for patients with myeloid neoplasms who receive allo-HSCT, and a large-scale prospective study is needed to confirm the findings of this study.

Research on sustainable development evaluation and improvement path of resource-based cities based on coupling of emergy and system dynamics.

The evaluation of the sustainable development of resource-based cities is still one of the hotspots in today's social research. Taking Jining, Shandong Province, as the research object, this work combines a relevant emergy evaluation index system with system dynamics, establishes a resource-based city emergy flow system dynamics model, and studies sustainable development path in the next planning year. In the work, the key factors affecting the sustainable development of Jining are obtained through the coupling of regression and SD sensitivity analysis, and some scenarios are set up by combining them with the local 14th Five-year plan. Besides, the appropriate scenario (M-L-H-H) for Jining's future sustainable development is chosen in accordance with regional circumstances. That is, during the 14th Five-year Plan period, the appropriate development ranges for the growth rate of social fixed assets investment, the growth rate of raw coal emergy, the growth rate of grain emergy and the reduction rate of solid waste emergy are 17.5-18.3%, - 4.0 to - 3.2%, 1.8-2.6% and 4-4.8%. The methodology system constructed in this article can serve as a reference for similar studies, and the research findings can aid the government in formulating pertinent plans for resource-based cities.

Efficient Removal of Heavy Metals from Contaminated Sunflower Straw by an Acid-Assisted Hydrothermal Process.

The removal of heavy metals is crucial to the utilization of contaminated biomass resources. In this study, we report an efficient process of hydrothermal conversion (HTC) of sunflower straw (Helianthus annuus L.) to remove heavy metals. The effect of different HTC temperatures and concentrations of HCl additives on heavy metal removal efficiency was investigated. The results revealed that increasing the temperature or concentration of HCl promoted the transfer of heavy metals from hydrochar to liquid products during HTC. The heavy metals removed to the liquid products included up to 99% of Zn and Cd, 94% of Cu, and 87% of Pb after hydrothermal conversion with a temperature of 200 °C and HCl 2%. The species of heavy metals in hydrochars converted from unstable to stable with an increase in temperature from 160 °C to 280 °C. The stable fractions of heavy metals in the acidic condition decreased as the acid concentration increased. This aligns well with the high transfer efficiency of heavy metals from the solid phase to the liquid phase under acidic conditions. The FTIR indicated that the carboxy and hydroxy groups decreased significantly as the temperature increased and the concentration of HCl increased, which promoted the degradation of sunflower straw. A scan electron microscope showed that the deepening of the destruction of the initial microstructure promotes the transfer of heavy metals from hydrochars to liquid phase products. This acid-assisted hydrothermal process is an efficient method to treat biomass containing heavy metals.

The effect of optimizing chemical fertilizers consumption structure to promote environmental protection, crop yield and reduce greenhouse gases emission in China.

To ensure food security, simultaneously achieving environmental protection and greenhouse gas (GHG) emission reduction has become a significant challenge in the sustainable development of China's chemical fertilizers (CFs) industry. Hence, this work attempt to construct a multi-objective optimization model (MOOM) based on crop yield, environment protection, and GHG emissions to adjust and optimize China's CFs structure (nitrogen, phosphate, potash, and compound fertilizers). The findings revealed that it's impossible to achieve the coordinated development of the three objectives only through the adjustment of CFs structure. Different optimization measures were sequentially integrated with the MOOM to innovatively obtain the most suitable optimization schemes and the quantitative adjustment interval (which was compared with those in 2018) of the CFs structure. The following are the specific conclusions. First, compared with 2018, the appropriate increase interval for the total CFs consumption was 9 %-21 %, in which the proportion intervals of nitrogen, phosphate, potash, and compound fertilizers were 18 %-25 %, 12 %-18 %, 7 %-12 %, 48 %-60 %, respectively. Second, the reduction ranges of environmental impact and GHG emissions were 1.1 %-12 % and 12.2 %-16.4 %, respectively, under the optimal scheme (combination of the synergy of organic fertilizer substitution and technology improvement with the MOOM), and the growing range of crop yield was 0.2 %-52 %. The main contribution of this work is to build a methodology system for the adjustment and optimization of CFs consumption structure. The findings of the study could be used by the government to develop relevant policies and by other sectors to perform multi-objective optimization.

Unraveling the skatole biodegradation process in an enrichment consortium using integrated omics and culture-dependent strategies.

3-Methylindole (skatole) is regarded as one of the most offensive compounds in odor emission. Biodegradation is feasible for skatole removal but the functional species and genes responsible for skatole degradation remain enigmatic. In this study, an efficient aerobic skatole-degrading consortium was obtained. Rhodococcus and Pseudomonas were identified as the two major and active populations by integrated metagenomic and metatranscriptomic analyses. Bioinformatic analyses indicated that the skatole downstream degradation was mainly via the catechol pathway, and upstream degradation was likely catalyzed by the aromatic ring-hydroxylating oxygenase and flavin monooxygenase. Genome binning and gene analyses indicated that Pseudomonas, Pseudoclavibacter, and Raineyella should cooperate with Rhodococcus for the skatole degradation process. Moreover, a pure strain Rhodococcus sp. DMU1 was successfully obtained which could utilize skatole as the sole carbon source. Complete genome sequencing showed that strain DMU1 was the predominant population in the consortium. Further crude enzyme and RT-qPCR assays indicated that strain DMU1 degraded skatole through the catechol ortho-cleavage pathway. Collectively, our results suggested that synergistic degradation of skatole in the consortium should be performed by diverse bacteria with Rhodococcus as the primary degrader, and the degradation mainly proceeded via the catechol pathway.

Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation.

OBJECTIVE: To investigate the mechanism of the effect of Astragalus membranaceus (A. membranaceus) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach. METHODS: The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of "ingredient-target" and "ingredient-target-pathway-disease" were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus. RESULTS: A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus, kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot. CONCLUSION: Our finding unraveled that an active ingredient of A. membranaceus, quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.