Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A2 and mitochondrial respiration.

Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1), which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid ß-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize ETO to etomoxir-carnitine (ETO-carnitine) prior to nearly complete ETO-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine structure. On the basis of these data, ETO-carnitine was successfully differentiated from isobaric structures (e.g., 3-hydroxy-C18:0 carnitine and 3-hydroxy-C18:1 carnitine). Mechanistically, generation of ETO-carnitine from mitochondria required exogenous Mg2+, ATP or ADP, CoASH, and L-carnitine, indicating that thioesterification by long-chain acyl-CoA synthetase to form ETO-CoA precedes its conversion to ETO-carnitine by CPT1. CPT1-dependent generation of ETO-carnitine was substantiated by an orthogonal approach using ST1326 (a CPT1 inhibitor), which effectively inhibits mitochondrial ETO-carnitine production. Surprisingly, purified ETO-carnitine potently inhibited calcium-independent PLA2γ and PLA2ß as well as mitochondrial respiration independent of CPT1. Robust production and release of ETO-carnitine from HepG2 cells incubated in the presence of ETO was also demonstrated. Collectively, this study identifies the chemical mechanism for the biosynthesis of a novel pharmaco-metabolite of ETO, ETO-carnitine, that is generated by CPT1 in mitochondria and likely impacts multiple downstream (non-CPT1 related) enzymes and processes in multiple subcellular compartments.

Establishment and application of a rapid visualization method for detecting Vibrio parahaemolyticus nucleic acid.

Background: Swift and accurate detection of Vibrio parahaemolyticus, which is a prominent causative pathogen associated with seafood contamination, is required to effectively combat foodborne disease and wound infections. The toxR gene is relatively conserved within V. parahaemolyticus and is primarily involved in the expression and regulation of virulence genes with a notable degree of specificity. The aim of this study was to develop a rapid, simple, and constant temperature detection method for V. parahaemolyticus in clinical and nonspecialized laboratory settings. Methods: In this study, specific primers and CRISPR RNA were used to target the toxR gene to construct a reaction system that combines recombinase polymerase amplification (RPA) with CRISPR‒Cas13a. The whole-genome DNA of the sample was extracted by self-prepared sodium dodecyl sulphate (SDS) nucleic acid rapid extraction reagent, and visual interpretation of the detection results was performed by lateral flow dipsticks (LFDs). Results: The specificity of the RPA-CRISPR/Cas13a-LFD method was validated using V. parahaemolyticus strain ATCC-17802 and six other non-parahaemolytic Vibrio species. The results demonstrated a specificity of 100%. Additionally, the genomic DNA of V. parahaemolyticus was serially diluted and analysed, with a minimum detectable limit of 1 copy/µL for this method, which was greater than that of the TaqMan-qPCR method (102 copies/µL). The established methods were successfully applied to detect wild-type V. parahaemolyticus, yielding results consistent with those of TaqMan-qPCR and MALDI-TOF MS mass spectrometry identification. Finally, the established RPA-CRISPR/Cas13a-LFD method was applied to whole blood specimens from mice infected with V. parahaemolyticus, and the detection rate of V. parahaemolyticus by this method was consistent with that of the conventional PCR method. Conclusions: In this study, we describe an RPA-CRISPR/Cas13a detection method that specifically targets the toxR gene and offers advantages such as simplicity, rapidity, high specificity, and visual interpretation. This method serves as a valuable tool for the prompt detection of V. parahaemolyticus in nonspecialized laboratory settings.

A Programmable Microfluidic Paper-Based Analytical Device for Simultaneous Colorimetric and Photothermal Visual Sensing of Multiple Enzyme Activities.

New strategies for the simultaneous and portable detection of multiple enzyme activities are highly desirable for clinical diagnosis and home care. However, the methods developed thus far generally suffer from high costs, cumbersome procedures, and heavy reliance on large-scale instruments. To satisfy the actual requirements of rapid, accurate, and on-site detection of multiple enzyme activities, we report herein a smartphone-assisted programmable microfluidic paper-based analytical device (µPAD) that utilizes colorimetric and photothermal signals for simultaneous, accurate, and visual quantitative detection of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Specifically, the operation of this µPAD sensing platform is based on two sequential steps. Cobalt-doped mesoporous cerium oxide (Co-m-CeO2) with remarkable peroxidase-like activities under neutral conditions first catalytically decomposes H2O2 for effectively converting colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB). The subsequent addition of ALP or BChE to their respective substrates produces a reducing substance that can somewhat inhibit the oxTMB transformation for compromised colorimetric and photothermal signals of oxTMB. Notably, these two-step bioenzyme-nanozyme cascade reactions strongly support the straightforward and excellent processability of this platform, which exhibit lower detection limits for ALP and BChE with a detection limit for BChE an order of magnitude lower than those of the other reported paper-based detection methods. The practicability and efficiency of this platform are further demonstrated through the analysis of clinical serum samples. This innovative platform exhibits great potential as a facile yet robust approach for simultaneous, accurate, and on-site visual detection of multiple enzyme activities in authentic samples.

DNA-based ForceChrono probes for deciphering single-molecule force dynamics in living cells.

Understanding cellular force transmission dynamics is crucial in mechanobiology. We developed the DNA-based ForceChrono probe to measure force magnitude, duration, and loading rates at the single-molecule level within living cells. The ForceChrono probe circumvents the limitations of in vitro single-molecule force spectroscopy by enabling direct measurements within the dynamic cellular environment. Our findings reveal integrin force loading rates of 0.5-2 pN/s and durations ranging from tens of seconds in nascent adhesions to approximately 100 s in mature focal adhesions. The probe's robust and reversible design allows for continuous monitoring of these dynamic changes as cells undergo morphological transformations. Additionally, by analyzing how mutations, deletions, or pharmacological interventions affect these parameters, we can deduce the functional roles of specific proteins or domains in cellular mechanotransduction. The ForceChrono probe provides detailed insights into the dynamics of mechanical forces, advancing our understanding of cellular mechanics and the molecular mechanisms of mechanotransduction.

Growth of Scenedesmus obliquus in anaerobically digested swine wastewater from different cleaning processes for pollutants removal and biomass production.

Anaerobically digested swine wastewater (ASW) purification by microalgae provides a promising strategy for nutrients recovery, biomass production and CO2 capture. However, the characteristics of ASW from different cleaning processes vary greatly. At present, the cultivation of microalgae in ASW from different manure cleaning processes is rarely investigated and compared. That may bring uncertainty for microalgae growth using different ASW in large-scale application. Thus, the ASW from three cleaning processes were tested for cultivating microalgae, including manure dry collection (I), water flushing (II) and water submerging processes (III). The characteristics of ASW from three manure cleaning processes varied greatly such as nutrient and heavy metals levels. High concentration of ammonia and copper in ASW significantly inhibited microalgae growth. Fortunately, the supply of high CO2 (10%) effectively alleviated negative influences, ensuring microalgal growth at low dilution ratio. The characteristics of three ASW resulted in significant differences in microalgae growth and biomass components. The maximal biomass production in optimal diluted ASW-I, II and III reached 1.46 g L-1, 2.19 g L-1 and 2.47 g L-1, respectively. The removal of organic compounds, ammonia and phosphorus by optimal microalgae growth in diluted ASW-I, II and III was 50.6%/94.2%/64.7%, 63.7%/82.3%/57.6% and 83.2%/91.7%/59.7%, respectively. The culture in diluted ASW-I, II and III obtained the highest lipids production of 12.1 mg L-1·d-1, 16.5 mg L-1·d-1 and 19.4 mg L-1·d-1, respectively. The analysis of lipids compositions revealed that the proportion of saturated fatty acids accounted for 36.4%, 32.4% and 27.9 % in optimal diluted ASW-I, II and III, as ideal raw materials for biodiesel production.

Changes in Microbial Composition During the Succession of Biological Soil Crusts in Alpine Hulun Buir Sandy Land, China.

Biological soil crusts (biocrusts) are considered "desert ecosystem engineers" because they play a vital role in the restoration and stability maintenance of deserts, including those cold sandy land ecosystems at high latitudes, which are especially understudied. Microorganisms participate in the formation and succession of biocrusts, contributing to soil properties' improvement and the stability of soil aggregates, and thus vegetation development. Accordingly, understanding the composition and successional characteristics of microorganisms is a prerequisite for analyzing the ecological functions of biocrusts and related applications. Here, the Hulun Buir Sandy Land region in northeastern China-lying at the highest latitude of any sandy land in the country-was selected for study. Through a field investigation and next-generation sequencing (Illumina MiSeq PE300 Platform), our goal was to assess the shifts in diversity and community composition of soil bacteria and fungi across different stages during the succession of biocrusts in this region, and to uncover the main factors involved in shaping their soil microbial community. The results revealed that the nutrient enrichment capacity of biocrusts for available nitrogen, total nitrogen, total phosphorus, total content of water-soluble salt, available potassium, soil organic matter, and available phosphorus was progressively enhanced by the succession of cyanobacterial crusts to lichen crusts and then to moss crusts. In tandem, soil bacterial diversity increased as biocrust succession proceeded but fungal diversity decreased. A total of 32 bacterial phyla and 11 fungal phyla were identified, these also known to occur in other desert ecosystems. Among those taxa, the relative abundance of Proteobacteria and Cyanobacteria significantly increased and decreased, respectively, along the cyanobacterial crust-lichen-moss crust successional gradient. However, for Actinobacteria, Chloroflexi, and Acidobacteria their changed relative abundance was significantly hump-shaped, increasing in the shift from cyanobacterial crust to lichen crust, and then decreasing as lichen crust shifted to moss crust. In this process, the improved soil properties effectively enhanced soil bacterial and fungal community composition. Altogether, these findings broaden our understanding about how soil microbial properties can change during the succession of biocrusts in high-latitude, cold sandy land ecosystems.

Current advances in modulating tumor hypoxia for enhanced therapeutic efficacy.

Hypoxia is a common feature of most solid tumors, which promotes the proliferation, invasion, metastasis, and therapeutic resistance of tumors. Researchers have been developing advanced strategies and nanoplatforms to modulate tumor hypoxia to enhance therapeutic effects. A timely review of this rapidly developing research topic is therefore highly desirable. For this purpose, this review first introduces the impact of hypoxia on tumor development and therapeutic resistance in detail. Current developments in the construction of various nanoplatforms to enhance tumor treatment in response to hypoxia are also systematically summarized, including hypoxia-overcoming, hypoxia-exploiting, and hypoxia-disregarding strategies. We provide a detailed discussion of the rationale and research progress of these strategies. Through a review of current trends, it is hoped that this comprehensive overview can provide new prospects for clinical application in tumor treatment. STATEMENT OF SIGNIFICANCE: As a common feature of most solid tumors, hypoxia significantly promotes tumor progression. Advanced nanoplatforms have been developed to modulate tumor hypoxia to enhanced therapeutic effects. In this review, we first introduce the impact of hypoxia on tumor progression. Current developments in the construction of various nanoplatforms to enhance tumor treatment in response to hypoxia are systematically summarized, including hypoxia-overcoming, hypoxia-exploiting, and hypoxia-disregarding strategies. We discuss the rationale and research progress of the above strategies in detail, and finally introduce future challenges for treatment of hypoxic tumors. By reviewing the current trends, this comprehensive overview can provide new prospects for clinical translatable tumor therapy.

Konjac glucomannan-based aerogels with excellent thermal stability and flame retardancy for thermal insulation application.

Biomass aerogels are a promising kind of environment-friendly thermal insulation material. However, the flammability, poor water resistance, and thermal instability of biomass aerogels limit their applications. Herein, freeze-drying and thermal imidization were used to create konjac glucomannan (KGM), boron nitride (BN), and polyimide (PI)-based aerogels with a semi-interpenetrating network structure. The introduction of BN was beneficial to improve the mechanical properties and thermal stability of aerogels. The imidization process of PI improved the hydrophobicity, mechanical property, and flame retardancy of the aerogels. The synergistic effect of PI and BN reduced the peak heat release rate and total heat release rate of KGM-based aerogel by 55.8 % and 35 %, respectively, and endowed aerogel with good self-extinguishing performance. Moreover, the results of thermal conductivity and infrared thermal imaging demonstrated that the aerogels had excellent thermal insulation properties, and could effectively manage thermal energy over a wide range of temperatures. This study provides a simple method for the preparation of heat-insulating aerogel with high fire safety, which has broad application prospects in the field of energy saving and emission reduction.

Multifunctional Nanoparticles for Enhanced Chemodynamic/Photodynamic Therapy through a Photothermal, H2O2-Elevation, and GSH-Consumption Strategy.

Chemodynamic therapy (CDT) has witnessed significant advancements in recent years due to its specific properties. Its association with photodynamic therapy (PDT) has also garnered increased attention due to its mutually reinforcing effects. However, achieving further enhancement of the CDT/PDT efficacy remains a major challenge. In this study, we have developed an integrated nanosystem comprising a Fenton catalyst and multifunctional photosensitizers to achieve triply enhanced CDT/PDT through photothermal effects, H2O2 elevation, and GSH consumption. We prepared nano-ZIF-8 vesicles as carriers to encapsulate ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) and photosensitizers IR825. Subsequently, cinnamaldehyde-modified hyaluronic acid (HA-CA) was coated onto ZIF-8 through metal coordination interactions, resulting in the formation of active targeting nanoparticles (NPs@Fc-BE&IR825). Upon cellular internalization mediated by CD44 receptors, HA-CA elevated H2O2 levels, while released Fc-BE consumed GSH and catalyzed H2O2 to generate highly cytotoxic hydroxyl radicals (·OH). Furthermore, NIR irradiation led to increased ·OH production and the generation of singlet oxygen (1O2), accompanied by a greater GSH consumption. This accelerated and strengthened amplification of oxidative stress can be harnessed to develop highly effective CDT/PDT nanoagents.

Rapid visual nucleic acid detection of Vibrio alginolyticus by recombinase polymerase amplification combined with CRISPR/Cas13a.

Vibrio alginolyticus (V. alginolyticus) is a common pathogen in the ocean. In addition to causing serious economic losses in aquaculture, it can also infect humans. The rapid detection of nucleic acids of V. alginolyticus with high sensitivity and specificity in the field is very important for the diagnosis and treatment of infection caused by V. alginolyticus. Here, we established a simple, fast and effective molecular method for the identification of V. alginolyticus that does not rely on expensive instruments and professionals. The method integrates recombinase polymerase amplification (RPA) technology with CRISPR system in a single PCR tube. Using this method, the results can be visualized by lateral flow dipstick (LFD) in less than 50 min, we named this method RPA-CRISPR/Cas13a-LFD. The method was confirmed to achieve high specificity for the detection of V. alginolyticus with no cross-reactivity with similar Vibrio and common clinical pathogens. This diagnostic method shows high sensitivity; the detection limit of the RPA-CRISPR/Cas13a-LFD is 10 copies/µL. We successfully identified 35 V. alginolyticus strains from a total of 55 different bacterial isolates and confirmed their identity by (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS). We also applied this method on infected mice blood, and the results were both easily and rapidly obtained. In conclusion, RPA-CRISPR/Cas13a-LFD offers great potential as a useful tool for reliable and rapid diagnosis of V. alginolyticus infection, especially in limited conditions.

Indole Diterpenes from Mangrove Sediment-Derived Fungus Penicillium sp. UJNMF0740 Protect PC12 Cells against 6-OHDA-Induced Neurotoxicity via Regulating the PI3K/Akt Pathway.

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.

Manufacturer invasion and online sales mode strategy considering the level of service quality.

This study investigates the decision process of own-brand intrusion by contract manufacturers and their selection of invasion sales modes under the consideration of service quality disparities between brand manufacturers and contract manufacturers. Specifically, the study constructs a three-tier supply chain system comprising a brand manufacturer, a contract manufacturer, and an e-commerce platform. The equilibrium profits under different sales mode combinations are determined by using reverse induction methodology, and the optimal sales mode combinations are analyzed and compared. The study reveals that the decision process of contract manufacturers' own-brand invasion depends on the potential market demand. Furthermore, when brand manufacturers adopt the reselling mode, the service quality level does not affect the decision process of invasion sales modes. However, when brand manufacturers adopt the agency mode, contract manufacturers with low service quality levels are more suitable for invasion through the agency mode, whereas contract manufacturers with high service quality levels are better suited for invasion through the reselling mode. Additionally, for the equilibrium sales mode combination among members of the supply chain, it is observed that with lower commission rates, both brand manufacturers and contract manufacturers choose the agency mode, while with higher commission rates, both choose the reselling mode. When commission rates are moderate, brand manufacturers prefer the agency mode, whereas contract manufacturers prefer the reselling mode.

Three-Component Ring-Expansion Reaction of Indoles Leading to Synthesis of Pyrrolo[2,3-c]quinolines.

Herein, we have developed an atom- and step-economic three-component cascade reaction that enables a modular platform for the synthesis of pyrrolo[2,3-c]quinoline compounds through ring-expansion/cyclization by way of novel N1-C2 cleavage of indoles. The metal-free catalytic system exhibits a broad functional group tolerance.

Asymmetric pre-growing season warming may jeopardize seed reproduction of the sand-stabilizing shrub Caragana microphylla.

Our current understanding of the processes and mechanisms by which seasonal asymmetric warming affects seed reproduction in semiarid regions, which are essential in preserving the stability of both vegetation ecosystem structure and function, remains poorly understood. Here, we conducted a field warming experiment, including pre-growing season warming (W1), in-growing season warming (W2), and combined pre- and in-growing season warming (W3) treatments, to investigate the seed reproductive strategy of Caragana microphylla, an important sand-stabilizing shrub, from the perspective of reproductive phenology, reproductive effort, and reproductive success. Results show that the warming treatments advanced the initial stages of reproductive phenology, prolonged its duration, and decreased its synchrony (magnitude = W3 > W2 > W1). Additionally, flowering phenology was more sensitive to warming than podding phenology. The W1 treatment inclined seed reproduction towards the conservative strategy with low reproductive effort and success. The W3 treatment tended to increase seed reproductive effort and success. While the W2 treatment did not affect reproductive success, it did increase reproductive effort. Changes in reproductive phenology explained 20 % of the variation in reproductive effort and 38 % of the variation in reproductive success. However, these changes also directly hindered reproductive success (direct effect = -0.57) while indirectly promoting reproductive success (indirect effect = 0.27) by increasing reproductive efforts. Our results reveal that the seasonal asymmetry of warming altered the seed reproduction strategy of sand-stabilizing shrubs, with warmer winters and springs before the growing season decreasing seed fecundity.

Nanoparticles-mediated ion channels manipulation: From their membrane interactions to bioapplications.

Ion channels are transmembrane proteins ubiquitously expressed in all cells that control various ions (e.g. Na+, K+, Ca2+ and Cl- etc) crossing cellular plasma membrane, which play critical roles in physiological processes including regulating signal transduction, cell proliferation as well as excitatory cell excitation and conduction. Abnormal ion channel function is usually associated with dysfunctions and many diseases, such as neurodegenerative disorders, ophthalmic diseases, pulmonary diseases and even cancers. The precise regulation of ion channels not only helps to decipher physiological and pathological processes, but also is expected to become cutting-edge means for disease treatment. Recently, nanoparticles-mediated ion channel manipulation emerges as a highly promising way to meet the increasing requirements with respect to their simple, efficient, precise, spatiotemporally controllable and non-invasive regulation in biomedicine and other research frontiers. Thanks the advantages of their unique properties, nanoparticles can not only directly block the pore sites or kinetics of ion channels through their tiny size effect, and perturb active voltage-gated ion channel by their charged surface, but they can also act as antennas to conduct or enhance external physical stimuli to achieve spatiotemporal, precise and efficient regulation of various ion channel activities (e.g. light-, mechanical-, and temperature-gated ion channels etc). So far, nanoparticles-mediated ion channel regulation has shown potential prospects in many biomedical fields at the interfaces of neuro- and cardiovascular modulation, physiological function regeneration and tumor therapy et al. Towards such important fields, in this typical review, we specifically outline the latest studies of different types of ion channels and their activities relevant to the diseases. In addition, the different types of stimulation responsive nanoparticles, their interaction modes and targeting strategies towards the plasma membrane ion channels will be systematically summarized. More importantly, the ion channel regulatory methods mediated by functional nanoparticles and their bioapplications associated with physiological modulation and therapeutic development will be discussed. Last but not least, current challenges and future perspectives in this field will be covered as well.

Orthogonal light-triggered multiple effects based on photochromic nanoparticles for DNA cleavage and beyond.

Efficient and spatiotemporally controllable cleavage of deoxyribonucleic acid (DNA) is of great significance for both disease treatment (e.g. tumour, bacterial infection, etc) and molecular biology applications (e.g. gene editing). The recently developed light-induced cleavage strategy based on catalytic nanoparticles has been regarded as a promising strategy for DNA controllable cleavage. Although the regulation based on orthogonal light in biomedical applications holds more significant advantages than that based on single light, nanoparticle-mediated DNA cleavage based on orthogonal light has yet to be reported. In this article, for the first time, we demonstrated an orthogonal light-regulated nanosystem for efficient and spatiotemporal DNA cleavage. In this strategy, tungsten oxide (WO3) nanoparticles with photochromic properties were used as nano-antennae to convert the photoenergy from the orthogonal visible light (405 nm) and near-infrared light (808 nm) into chemical energy for DNA cleavage. We verified that only the orthogonal light can trigger high cleavage efficiency on different types of DNA. Moreover, such an orthogonal light-response nano-system can not only induce significant apoptosis of tumour cells, but also effectively eliminate bacterial biofilms.

Construction and Activity Study of a Natural Antibacterial Patch Based on Natural Active Substance-Green Porous Structures.

Bacterial infections are a serious threat to human health, and the rapid emergence of bacterial resistance caused by the abuse of antibiotics exacerbates the seriousness of this problem. Effectively utilizing natural products to construct new antimicrobial strategies is regarded as a promising way to suppress the rapid development of bacterial resistance. In this paper, we fabricated a new type of natural antibacterial patch by using a natural active substance (allicin) as an antibacterial agent and the porous structure of the white pulp of pomelo peel as a scaffold. The antibacterial activity and mechanisms were systematically investigated by using various technologies, including the bacteriostatic circle, plate counting, fluorescence staining, and a scanning electron microscope. Both gram-positive and negative bacteria can be effectively killed by this patch. Moreover, this natural antibacterial patch also showed significant anti-skin infection activity. This study provides a green approach for constructing efficient antibacterial patches.

[Analysis of Microbial Interaction Law of Mud Membrane in IFAS Process for Treating Low Carbon Source Sewage in South China].

To assess the problem of sewage treatment under the condition of low carbon sources, we carried out a study of activated sludge and a biofilm symbiosis system (IFAS). The occurrence characteristics and interaction law of microorganisms in two phases of sludge membrane under low carbon source conditions were discussed, and their niche and influence on treatment efficiency were clarified. Through a pilot-scale experiment in actual water plants, the biofilm characteristics, sludge membrane activity, and succession law of flora were analyzed, and the microbial structure and interaction in sludge membrane in two phases under the control of different activated sludge ages were compared. The results showed that the sludge concentration in the reactor increased with the increase in SRT under variable SRT. Because the microbial concentration in SRT-H was much higher than that in SRT-L, the competition between mud films in SRT-H was more intense than that in SRT-L, and the pollutant removal efficiency in SRT-H was lower than that in SRT-L. Under the condition of low-carbon feed water, the sludge activity in the IFAS process decreased with the increase in SRT. Under the condition of low SRT(5 d), the nitrification, denitrification, phosphorus accumulation, and phosphorus absorption rate of activated sludge increased by 122%, 88%, 34%, and 44%, respectively, compared with that of high SRT (25 d). However, SRT had little effect on biofilm activity, and there was little difference in nitrification activity and denitrification activity between the two SRTs. Microbial sequencing analysis showed that the functional bacteria of the IFAS process were enriched and transferred with the change in SRT between the two phases of mud membrane. In SRT-L, the functional bacteria that were enriched and transferred between the two phases of mud film owing to the "seeding" effect were mainly unclassified_g__Enterobacteriaceae, whereas in SRT-H, Acinetobacter was mainly used. At the same time, by analyzing the distribution of dominant functional bacteria, it was found that there was some competition between denitrifying bacteria and phosphorus-accumulating bacteria in activated sludge. Under the condition of a lack of organic substrate in the influent, the relative abundance of denitrifying bacteria was obviously higher than that of phosphorus-accumulating bacteria, which indicated that denitrifying bacteria could better adapt to low-carbon source conditions. Thus, they could occupy a dominant competition position, which was mainly reflected in the increase in the relative abundance of aerobic denitrifying bacteria. In addition, the SRT change in the mud phase reacted in the membrane phase, making the residence time of biofilm change correspondingly, thus changing the flora structure, screening out different dominant bacteria genera, and further increasing the difference.

Cardiac immune cell infiltration associates with abnormal lipid metabolism.

CD36 mediates the uptake of long-chain fatty acids (FAs), a major energy substrate for the myocardium. Under excessive FA supply, CD36 can cause cardiac lipid accumulation and inflammation while its deletion reduces heart FA uptake and lipid content and increases glucose utilization. As a result, CD36 was proposed as a therapeutic target for obesity-associated heart disease. However, more recent reports have shown that CD36 deficiency suppresses myocardial flexibility in fuel preference between glucose and FAs, impairing tissue energy balance, while CD36 absence in tissue macrophages reduces efferocytosis and myocardial repair after injury. In line with the latter homeostatic functions, we had previously reported that CD36-/- mice have chronic subclinical inflammation. Lipids are important for the maintenance of tissue homeostasis and there is limited information on heart lipid metabolism in CD36 deficiency. Here, we document in the hearts of unchallenged CD36-/- mice abnormalities in the metabolism of triglycerides, plasmalogens, cardiolipins, acylcarnitines, and arachidonic acid, and the altered remodeling of these lipids in response to an overnight fast. The hearts were examined for evidence of inflammation by monitoring the presence of neutrophils and pro-inflammatory monocytes/macrophages using the respective positron emission tomography (PET) tracers, 64Cu-AMD3100 and 68Ga-DOTA-ECL1i. We detected significant immune cell infiltration in unchallenged CD36-/- hearts as compared with controls and immune infiltration was also observed in hearts of mice with cardiomyocyte-specific CD36 deficiency. Together, the data show that the CD36-/- heart is in a non-homeostatic state that could compromise its stress response. Non-invasive immune cell monitoring in humans with partial or total CD36 deficiency could help evaluate the risk of impaired heart remodeling and disease.

Annual Herbaceous Plants Exhibit Altered Morphological Traits in Response to Altered Precipitation and Drought Patterns in Semiarid Sandy Grassland, Northern China.

The frequency and intensity of extreme precipitation events and severe drought are predicted to increase in semiarid areas due to global climate change. Plant morphological traits can reflect plant responses to a changing environment, such as altered precipitation or drought patterns. In this study, we examined the response of morphological traits of root, stem, leaf and reproduction meristems of annual herbaceous species to altered precipitation and drought patterns in a semiarid sandy grassland. The study involved a control treatment (100% of background precipitation) and the following six altered precipitation treatments: (1) P(+): precipitation increased by 30%, (2) P(++): precipitation increased by 60%, (3) P(-): precipitation decreased by 30%, (4) P(--): precipitation decreased by 60%, (5) drought 1 (D1): 46-day drought from May 1st to June 15th, and (6) drought 2 (D2): 46-day drought from July 1st to August 15th. P(++) significantly increased root length, flower length-to-width ratio, both P(+) and P(++) significantly increased stem length and flower number in the plant growing seasons, while all of them decreased under P(-) and P(--). The annual herbaceous plants marginally increased the number of second-level stem branches and stem diameter in order to better resist the severe drought stress under P(--). P(+) and P(++) increased the root, stem, leaf, and flower dry weight, with the flower dry weight accounting for a larger proportion than the other aboveground parts. Under D2, the plants used the limited water resources more efficiently by increasing the root-to-shoot ratio compared with P(-), P(--) and D1, which reflects biomass allocation to belowground increased. The linear mixed-effects models and redundancy analysis showed that the root-to-shoot ratio and the dry weight of various plant components were significantly affected by morphological traits and altered precipitation magnitude. Our results showed that the herbaceous species have evolved morphological trait responses that allow them to adapt to climate change. Such differences in morphological traits may ultimately affect the growing patterns of annual herbaceous species, enhancing their drought-tolerant capacity in semiarid sandy grassland during the ongoing climate change.