ABSTRACT
Nitraria tangutorum Bobrov., belonging to the family Nitrariaceae, is a drought-tolerant and salt-loving plant and has drawn attention for its good economic and ecological value. As one of the main group species and dominant species in China's desert and semi-desert regions, N. tangutorum possesses superior tolerance to drought, high temperature, cold, barren, high salinity and alkalinity and wind and sand. Its root system is well developed, with many branches and a strong germination capacity. Once buried in sandy soil, N. tangutorum can quickly produce a large number of adventitious roots, forming new plants and continuously expanding the shrubs, forming fixed and semi-fixed shrub sand dunes. Sand dune shrubs can trap and fix a large amounts of quicksand, prevent desert expansion and erosion, and play an important role in maintaining regional ecosystem balance and improving ecological environmental quality. In addition, the phytochemical screening studies report that N. tangutorum contains an abundance of various compounds including flavonoids, alkaloids, phenolic acids and polysaccharides. These compounds confer a range of beneficial bioactivities such as antioxidant, anti-inflammatory, anti-tumor, anti-fatigue, liver protection, neuroprotection, cardiovascular protection, lowering blood lipid, regulating blood sugar level and immunoregulation. The fruits of N. tangutorum also contain vitamin C, amino acids, minerals and microelements. It has been traditionally used as a nutritional food source and in folk medicine to treat diseases of the spleen and stomach, abnormal menstruation, indigestion, and hyperlipidemia. N. tangutorum, as a wild plant with medicinal and edible homology, possesses remarkable economic and medicinal values. This detailed, comprehensive review gathers and presents all the information related to the morphological structure, propagation characteristics, resistance physiology and exploitation and utilization of N. tangutorum, providing a theoretical basis for the researchers to conduct future in-depth research on N. tangutorum.
Subject(s)
Plant Roots , China , EcosystemABSTRACT
Selective catalytic reduction using CO as a reducing agent (CO-SCR) has exhibited its application potential in coal-fired, steel, and other industrial sectors. In comparison to NH3-SCR, CO-SCR can achieve synergistic control of CO and NO pollutants, making it a powerful denitrification technology that treats waste with waste. Unfortunately, the competitive adsorption of O2 and NO on CO-SCR catalysts inhibits efficient conversion of NOx under O2-containing conditions. In this work, we obtained two Ir sites with different electron densities, Ir1 single atoms in the oxidized Irδ+ state and Ir0 nanoparticles in the metallic state, by controlled pretreatment of the Ir/ZSM-5 catalyst with H2 at 200 °C. The coexistence of Ir1 single atoms and Ir0 nanoparticles on ZSM-5 creates a synergistic effect, which facilitates the reduction of NO through CO in the presence of O2, following the Langmuir-Hinshelwood mechanism. The ONNO dimer is formed on the Ir1 single atom sites and then spills over to the neighboring Ir0 nanoparticles for subsequent reduction to N2 by CO. Specifically, this tandem reaction enables 83% NO conversion and 100% CO conversion on an Ir-based catalyst at 250 °C under 3% O2.
Subject(s)
Carbon Monoxide , Catalysis , Carbon Monoxide/chemistry , Nitric Oxide/chemistry , Oxidation-Reduction , AdsorptionABSTRACT
Developing solid-state hydrogen storage materials is as pressing as ever, which requires a comprehensive understanding of the dehydrogenation chemistry of a solid-state hydride. Transition state search and kinetics calculations are essential to understanding and designing high-performance solid-state hydrogen storage materials by filling in the knowledge gap that current experimental techniques cannot measure. However, the ab initio analysis of these processes is computationally expensive and time-consuming. Searching for descriptors to accurately predict the energy barrier is urgently needed, to accelerate the prediction of hydrogen storage material properties and identify the opportunities and challenges in this field. Herein, we develop a data-driven model to describe and predict the dehydrogenation barriers of a typical solid-state hydrogen storage material, magnesium hydride (MgH2), based on the combination of the crystal Hamilton population orbital of Mg-H bond and the distance between atomic hydrogen. By deriving the distance energy ratio, this model elucidates the key chemistry of the reaction kinetics. All the parameters in this model can be directly calculated with significantly less computational cost than conventional transition state search, so that the dehydrogenation performance of hydrogen storage materials can be predicted efficiently. Finally, we found that this model leads to excellent agreement with typical experimental measurements reported to date and provides clear design guidelines on how to propel the performance of MgH2 closer to the target set by the United States Department of Energy (US-DOE).
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Two new mealybug species, Paracoccusgillianwatsonae Zhang, sp. nov. and P.wui Zhang, sp. nov., collected from Jiangxi, South China, are described and illustrated based on the morphology of adult females. Paracoccusgillianwatsonae is similar to P.burnerae (Brain, 1915), but it differs in having fewer pairs of cerarii, and in lacking both ventral oral collar tubular ducts on the margins of the head and translucent pores on the hind femur. Paracoccuswui resembles P.keralae Williams, 2004 and P.neocarens (Lit, 1992), but it differs in lacking ventral oral collar tubular ducts on the margins of the head and in having multilocular disc-pores usually in double rows at the posterior edges of abdominal segments V and VI. A key to the Paracoccus species found in China is provided.
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Reversible solid-state hydrogen storage of magnesium hydride, traditionally driven by external heating, is constrained by massive energy input and low systematic energy density. Herein, a single phase of Mg2Ni(Cu) alloy is designed via atomic reconstruction to achieve the ideal integration of photothermal and catalytic effects for stable solar-driven hydrogen storage of MgH2. With the intra/inter-band transitions of Mg2Ni(Cu) and its hydrogenated state, over 85% absorption in the entire spectrum is achieved, resulting in the temperature up to 261.8 °C under 2.6 W cm-2. Moreover, the hydrogen storage reaction of Mg2Ni(Cu) is thermodynamically and kinetically favored, and the imbalanced distribution of the light-induced hot electrons within CuNi and Mg2Ni(Cu) facilitates the weakening of Mg-H bonds of MgH2, enhancing the "hydrogen pump" effect of Mg2Ni(Cu)/Mg2Ni(Cu)H4. The reversible generation of Mg2Ni(Cu) upon repeated dehydrogenation process enables the continuous integration of photothermal and catalytic roles stably, ensuring the direct action of localized heat on the catalytic sites without any heat loss, thereby achieving a 6.1 wt.% H2 reversible capacity with 95% retention under 3.5 W cm-2.
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In this paper, we present a novel Secure Clustering Routing Method based on Blockchain and Swarm Intelligence (BS-SCRM) for Wireless Sensor Networks (WSNs), which serves as a cornerstone in the Internet of Things (IoT) infrastructure. Recognizing the limitations of existing clustering routing methods in addressing security threats, our approach integrates blockchain technology to fortify WSNs against vulnerabilities such as man-in-the-middle attacks. The proposed BS-SCRM method is structured in two phases: (1) an enhanced cluster head (CH) election utilizing an elite strategy-enhanced Whale Optimization Algorithm (WOA) that considers node energy and proximity to the base station, and (2) a secure data on-chain phase where blockchain comes into play, encrypting and validating cluster data to safeguard integrity and prevent tampering. We further tackle the challenge of implementing blockchain in resource-constrained WSNs by assigning distinct roles to devices, i.e., ordinary nodes with data viewing permissions and accounting nodes entrusted with both data viewing and consensus algorithm execution. Extensive simulations confirm that BS-SCRM not only improves clustering quality but also provides a more secure and energy-efficient routing solution compared to contemporary methods. More specifically, simulation results in different scenarios demonstrate that BS-SCRM enhances network lifetime by 24-73% compared to other clustering methods when facing attacks.
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Uncontrollability could lead to behavioral adjustment or even giving up when facing repeated failure. Here, we detail a protocol to study the behavioral transition from action to no-action induced by prolonged uncontrollable experiences in mice. We describe the behavioral devices, video analysis, and the exponential learning curve fitting for mathematical assessment. We perform further validation experiments evaluating locomotor, social, and anxiety-/depression-like behaviors. This approach helps study neural mechanisms underlying adaptive decision-making when facing repeated failure. For complete details on the use and execution of this protocol, please refer to Li et al.1.
Subject(s)
Behavior, Animal , Animals , Mice , Behavior, Animal/physiology , Male , Decision Making/physiology , Mice, Inbred C57BL , Anxiety/physiopathologyABSTRACT
Aspirin, also named acetylsalicylate, can directly acetylate the side-chain of lysine in protein, which leads to the possibility of unexplained drug effects. Here, the study used isotopic-labeling aspirin-d3 with mass spectrometry analysis to discover that aspirin directly acetylates 10 HDACs proteins, including SIRT1, the most studied NAD+-dependent deacetylase. SIRT1 is also acetylated by aspirin in vitro. It is also identified that aspirin directly acetylates lysine 408 of SIRT1, which abolishes SIRT1 deacetylation activity by impairing the substrates binding affinity. Interestingly, the lysine 408 of SIRT1 can be acetylated by CBP acetyltransferase in cells without aspirin supplement. Aspirin can inhibit SIRT1 to increase the levels of acetylated p53 and promote p53-dependent apoptosis. Moreover, the knock-in mice of the acetylation-mimic mutant of SIRT1 show the decreased production of pro-inflammatory cytokines and maintain intestinal immune homeostasis. The study indicates the importance of the acetylated internal functional site of SIRT1 in maintaining intestinal immune homeostasis.
Subject(s)
Aspirin , Homeostasis , Sirtuin 1 , Sirtuin 1/metabolism , Sirtuin 1/genetics , Animals , Aspirin/pharmacology , Acetylation/drug effects , Mice , Homeostasis/drug effects , Humans , Intestines/drug effects , Mice, Inbred C57BLABSTRACT
Albendazole (ABZ) is the primary treatment for alveolar echinococcosis (AE); however, its limited solubility impacts oral bioavailability, affecting therapeutic outcomes. In this study, various ABZ-solubilizing formulations, including albendazole crystal dispersion system (ABZ-CSD), albendazole hydrochloride-hydroxypropyl methylcellulose phthalate composite (TABZ-HCl-H), and albendazole hydroxyethyl sulfonate-hydroxypropyl methylcellulose phthalate composite (TABZ-HES-H), were developed and evaluated. Physicochemical properties as well as liver enzyme activity were analyzed and their pharmacodynamics in an anti-secondary hepatic alveolar echinococcosis (HAE) rat model were investigated. The formulations demonstrated improved solubility, exhibiting enhanced inhibitory effects on microcysts in HAE model rats compared to albendazole tablets. However, altered hepatic drug-metabolizing enzymes in HAE model rats led to increased ABZ levels and reduced ABZ-SO production, potentially elevating drug toxicity. These findings emphasize the importance of dose adjustments in patient administration, considering the impact of alveolar echinococcosis on rat hepatic drug metabolism.
Subject(s)
Albendazole , Disease Models, Animal , Echinococcosis, Hepatic , Animals , Albendazole/pharmacology , Albendazole/pharmacokinetics , Albendazole/therapeutic use , Rats , Echinococcosis, Hepatic/drug therapy , Echinococcosis, Hepatic/parasitology , Male , Rats, Sprague-Dawley , Liver/parasitology , Liver/drug effects , Liver/metabolism , SolubilityABSTRACT
BACKGROUND: An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM: To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization. METHODS: Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS: The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM. CONCLUSION: Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.
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OBJECTIVE: Scutellaria baicalensis (SB) and Polygonatum Rhizoma (PR), two traditional Chinese medicines, are both known to suppress cancer. However, the mechanism and effect of combined treatment of them for lung cancer are rarely known. Investigating the combined effect of SB and PR (hereafter referred to as SP) in potential mechanism of lung cancer is required. This study was to evaluate the inhibitory effects of SP on A549 cell growth and to explore the underlying molecular mechanisms. METHODS: According to the theory of Chinese medicine and network pharmacology, in the in vivo experiment, a mouse model of carcinoma in situ was constructed, and lung carcinoma in situ tissues were collected for proteomics analysis, hematoxylin-eosin staining, and CK19 immunohistochemistry. In the in vitro experiment, lung cancer A549 cells at logarithmic growth stage were taken, and the inhibitory effect of SP on the proliferation of A549 cells was detected by CCK8 method. The expression of PON3 was detected by quantitative polymerase chain reaction and western blot. In addition, the effect of SP on the induction of apoptosis in A549 cells and the changes of membrane potential and reactive oxygen species (ROS) content were detected by flow cytometry. The changes of PON3 content in endoplasmic reticulum (ER) are observed by laser confocal microscopy, whereas the effects of SP on the expression of apoptosis-related proteins and ER stress-related proteins in A549 cells were examined by western blot. RESULT: By searching the Traditional Chinese Medicines of Systems Pharmacology (TCMSP) (https://www.tcmspe.com/index.php) database and SymMap database, the respective target genes of PR and SB were mapped into protein network interactions, and using Venn diagrams to show 38 genes in common between PR and SB and lung cancer, SP was found to play a role in the treatment of lung cancer. In vivo experiments showed that in a lung carcinoma in situ model, lung tumor tissue was significantly lower in the SP group compared with the control group, and PON3 was shown to be downregulated by lung tissue proteomics analysis. The combination of SP was able to inhibit the proliferation of A549 cells in a concentration-dependent manner (p < .0001). The expression levels of apoptosis-related proteins and ER stress proteins were significantly increased and the expression levels of PON3 and anti-apoptosis-related proteins were decreased in A549 cells. At the same time, knockdown of PON3 could inhibit tumor cell proliferation (p < .0001). The combination of different concentrations of SP significantly induced apoptosis in A549 cells (p < .05; p < .0001), increased ROS content (p < .01), and damaged mitochondrial membrane potential of A549 cells (p < .05; p < .0001), and significantly increased the expression levels of apoptosis-related proteins and ER stress proteins in lung cancer A549 cells. CONCLUSION: SP inhibits proliferation of lung cancer A549 cells by downregulating PON3-induced apoptosis in the mitochondrial and ER pathways.
Subject(s)
Carcinoma in Situ , Lung Neoplasms , Polygonatum , Animals , Mice , Humans , A549 Cells , Polygonatum/metabolism , Scutellaria baicalensis/metabolism , Reactive Oxygen Species/metabolism , Down-Regulation , Lung Neoplasms/pathology , Apoptosis , Cell Proliferation , Endoplasmic Reticulum Stress , Heat-Shock Proteins/metabolism , Cell Line, TumorABSTRACT
During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.
Subject(s)
Neoplasms , Humans , Neoplasms/drug therapy , Cholesterol/metabolism , Carcinogenesis , Cell Transformation, Neoplastic , Cell Proliferation , Tumor MicroenvironmentABSTRACT
Due to molecular forces, biomacromolecules assemble into liquid condensates or solid aggregates, and their corresponding formation and dissolution processes are controlled. Protein homeostasis is disrupted by increasing age or environmental stress, leading to irreversible protein aggregation. Hypoxic pressure is an important factor in this process, and uncontrolled protein aggregation has been widely observed in hypoxiarelated conditions such as neurodegenerative disease, cardiovascular disease, hypoxic brain injury and cancer. Biomolecular condensates are also highorder complexes assembled from macromolecules. Although they exist in different phase from protein aggregates, they are in dynamic balance under certain conditions, and their activation or assembly are considered as important regulatory processes in cell survival with hypoxic pressure. Therefore, a better understanding of the relationship between hypoxic stress, protein aggregation and biomolecular condensation will bring marked benefits in the clinical treatment of various diseases. The aim of the present review was to summarize the underlying mechanisms of aggregate assembly and dissolution induced by hypoxic conditions, and address recent breakthroughs in understanding the role of aggregates in hypoxicrelated diseases, given the hypotheses that hypoxia induces macromolecular assemblage changes from a liquid to a solid phase, and that adenosine triphosphate depletion and ATPdriven inactivation of multiple protein chaperones play important roles among the process. Moreover, it is anticipated that an improved understanding of the adaptation in hypoxic environments could extend the overall survival of patients and provide new strategies for hypoxicrelated diseases.
Subject(s)
Cardiovascular Diseases , Neurodegenerative Diseases , Humans , Protein Aggregates , Hypoxia , Adenosine TriphosphateABSTRACT
The gregarious ectoparasitic beetle Dastarcus helophoroides (Fairmaire) is considered a primary biocontrol agent for controlling several cerambycid pests in East Asian countries. A thorough study of reproductive behavior is a prerequisite for the mass production of natural insect predators. Nonetheless, little attention has been given to this ectoparasitic beetle. We performed a series of trials to assess whether the adult copulation duration, a key behavioral trait, is differentially influenced by physiological and ecological factors, including body size, mating history, kinship, sex ratio, mating sequence, feeding status, ambient temperature, photoperiod, and time of day. Additionally, the effect of the copulation duration on the reproductive output of this beetle was also investigated. The results indicated that the copulation duration varied considerably, ranging from 1.12 min to 16.40 min and lasting for an average of 9.11 ± 0.12 min. Females with longer copulations laid more eggs and had a greater proportion of eggs hatched. Medium-sized individuals copulated significantly longer than small- and large-sized individuals. The copulation durations were significantly longer when both sexes experienced an asymmetric mating history than when both sexes experienced a symmetric mating history. Inbred couples copulated significantly longer than outbred couples. In terms of the adult sex ratio, increasing the density of females (polygamous group) or males (polyandrous group) led to significantly longer copulation durations than those in the monogamous group. The copulation durations gradually decreased with increasing the mating sequence and temperature. Food-absence couples copulated significantly longer than food-presence couples. The mean copulation duration of the scotophase was significantly longer than that of the photophase. These results demonstrate that all of the analyzed factors emerge as important factors influencing the copulation duration, ultimately affecting the reproductive outputs in this ectoparasitic beetle.
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The allosteric modulation of the homodimeric H10-03-6 protein to glycan ligands L1 and L2, and the STAB19 protein to glycan ligands L3 and L4, respectively, has been studied by molecular dynamics simulations and free energy calculations. The results revealed that the STAB19 protein has a significantly higher affinity for L3 (-11.38 ± 2.32 kcal/mol) than that for L4 (-5.51 ± 1.92 kcal/mol). However, the combination of the H10-03-6 protein with glycan L2 (1.23 ± 6.19 kcal/mol) is energetically unfavorable compared with that of L1 (-13.96 ± 0.35 kcal/mol). Further, the binding of glycan ligands L3 and L4 to STAB19 would result in the significant closure of the two CH2 domains of the STAB19 conformation with the decrease of the centroid distances between the two CH2 domains compared with the H10-03-6/L1/L2 complex. The CH2 domain closure of STAB19 relates directly to the formation of new hydrogen bonds and hydrophobic interactions between the residues Ser239, Val240, Asp265, Glu293, Asn297, Thr299, Ser337, Asp376, Thr393, Pro395, and Pro396 in STAB19 and glycan ligands L3 and L4, which suggests that these key residues would contribute to the specific regulation of STAB19 to L3 and L4. In addition, the distance analysis revealed that the EF loop in the H10-03-6/L1/L2 model presents a high flexibility and partial disorder compared with the stabilized STAB19/L3/L4 complex. These results will be helpful in understanding the specific regulation through the asymmetric structural characteristics in the CH2 and CH3 domains of the H10-03-6 and STAB19 proteins.
Subject(s)
Immunoglobulin Fc Fragments , Molecular Dynamics Simulation , Immunoglobulin Fc Fragments/chemistry , Immunoglobulin Fc Fragments/metabolism , Immunoglobulin Isotypes , Molecular Conformation , PolysaccharidesABSTRACT
BACKGROUND: Intermittent hypoxia intervention (IHI) has been shown to reduces blood glucose and improves insulin resistance in type 2 diabetes (T2D) and has been suggested as a complementary or alternative intervention to exercise for individuals with limited mobility. Previous research on IHI has assessed cellular glucose uptake rather than utilization. The purpose of this study was to determine the effect of a 4-week IHI, with or without an aerobic exercise, on skeletal muscle glucose utilization as indicated by the changes in pyruvate, lactate, NAD+, and NADH, using a mouse model of diet-induced T2D. In addition, the effects of one exposure to hypoxia (acute) and of a 4-week IHI (chronic) were compared to explore their relationship. METHODS: C57BL/6J mice were randomly assigned to normal control and high-fat-diet groups, and the mice that developed diet-induced diabetes were assigned to diabetes control, and intervention groups with 1 hour (acute) or 4 weeks (1 hour/day, 6 days/week) exposure to a hypoxic envrionment (0.15 FiO2), exercise (treadmill run) in normoxia, and exercise in hypoxia, respectively, with N = 7 in each group. The effects of the interventions on concentrations of fasting blood glucose, muscle glucose, GLUT4, lactate, pyruvate, nicotinamide adenine dinucleotide (NAD+), and NADH were measured, and statistically compared between the groups. RESULTS: Compared with diabetes control group, the mice treated in the hypoxic environment for 4 weeks showed a significantly higher pyruvate levels and lower lactate/pyruvate ratios in the quadriceps muscle, and the mice exposed to hypoxia without or with aerobic exercise for either for 4 weeks or just 1 hour showed higher NAD+ levels and lower NADH/NAD+ ratios. CONCLUSIONS: Exposure to moderate hypoxia for either one bout or 4 weeks significantly increased the body's mitochondrial NAD cyclethe in diabetic mice even in the absence of aerobic exercise. The hypoxia and exercise interventions exhibited synergistic effects on glycolysis. These findings provide mechanistic insights into the effects of IHI in respect of the management of hyperglycemia.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Animals , Mice , Glucose , Blood Glucose , NAD , Mice, Inbred C57BL , Muscle, Skeletal , Insulin Resistance/physiology , Disease Models, Animal , Hypoxia , Lactates , PyruvatesABSTRACT
Petrocosmea qinlingensis is a protected wild plant endemic in China, inhabiting low-light limestone cliffs but the complete chloroplast genome has not been reported. In this study, we first sequenced and assembled the complete chloroplast genome of P. qinlingensis. The total size of this genome was 153,865 bp, including a large single-copy (LSC) region (84,737 bp), a small single-copy (SSC) region (18,244 bp), and two inverted repeats (IRs) regions (25,442 bp). This genome encoded 111 uniquegenes, consisted of 77 protein-coding genes, four ribosomal RNA genes, and 30 transfer RNA genes. Phylogenomic analysis based on the chloroplast protein-coding genes and showed that the genus Petrocosmea was the closest relative to Raphiocarpus. Our results will support further phylogeographic, population genetic studies of this species.
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BACKGROUND: The exact cause of intracranial aneurysms (IA) is still unclear. However, pro-inflammatory factors are known to contribute to IA progression. The specific changes in the immune microenvironment of IAs remain largely unexplored. METHODS: This study analyzed single-cell sequencing data from a male mouse model of brain aneurysm, focusing on samples before and after elastase-induced Willis aneurysms. The data helped identify eight distinct cell subpopulations: fibroblasts, macrophages, NK cells, endothelial cells, B cells, granulocytes, and monocytes. The study also involved bulk RNA sequencing of 97 IA samples, utilizing ssGSEA and CIBERSORT algorithms for analysis. Intercellular communication among these cells was inferred to understand the immune dynamics in IA. RESULTS: The study found that fibroblasts and macrophages are predominant in various disease states of IA. Notably, the onset of IA was marked by a significant increase in fibroblasts and a decrease in macrophages. There was a marked increase in cellular interactions, especially involving macrophages, at the onset of the disease. Through enrichment analysis, 12 potential immunogenic biomarkers were identified. Of these, Rgs1 emerged as a critical molecule in IA formation, confirmed through secondary validation in a single-cell sequencing dataset. CONCLUSION: This comprehensive analysis of immune cell composition and intercellular communication in IA tissues highlights the significant roles of macrophages and the molecule Rgs1. These findings shed light on the physiological and pathological conditions of IA, offering new insights into its immune microenvironment.
Subject(s)
Intracranial Aneurysm , Mice , Animals , Male , Intracranial Aneurysm/genetics , Intracranial Aneurysm/pathology , Endothelial Cells/pathology , Multiomics , Disease Models, Animal , BiomarkersABSTRACT
Mitochondrial malic enzyme 2 (ME2), which catalyzes the conversion of malate to pyruvate, is frequently upregulated during tumorigenesis and is a potential target for cancer therapy. However, the regulatory mechanism underlying ME2 activity is largely unknown. In this study, we demonstrate that ME2 is highly expressed in human colorectal cancer (CRC) tissues, and that ME2 knockdown inhibits the proliferation of CRC cells. Furthermore, we reveal that ME2 is succinylated and identify Sirtuins 5 (SIRT5) as an ME2 desuccinylase. Glutamine deprivation directly enhances the interaction of SIRT5 with ME2 and thus promotes SIRT5-mediated desuccinylation of ME2 at lysine 346, activating ME2 enzymatic activity. Activated ME2 significantly enhances mitochondrial respiration, thereby counteracting the effects of glutamine deprivation and supporting cell proliferation and tumorigenesis. Additionally, the levels of succinylated ME2 at K346 and SIRT5 in CRC tissues, which are negatively correlated, are associated with patient prognosis. These observations suggest that SIRT5-catalyzed ME2 desuccinylation is a key signaling event through which cancer cells maintain mitochondrial respiration and promote CRC progression under glutamine deficiency conditions, offering the possibility of targeting SIRT5-mediated ME2 desuccinylation for CRC treatment.
Subject(s)
Glutamine , Sirtuins , Humans , Cell Proliferation , Mitochondria , Carcinogenesis , Respiration , Sirtuins/geneticsABSTRACT
Aerobic glycolysis is a hallmark property of cancer metabolism. Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate into phosphoenolpyruvate. In mammals, enolases exist in three isoforms, encoded by the genes ENO1, ENO2, and ENO3. The altered expression of enolases is a common occurrence in various types of cancer. Although most published studies on enolases have predominantly focused on the role of ENO1 in cancer, ENO2 and ENO3 have recently emerged as crucial regulatory molecules in cancer development. Significant progress has been made in understanding their multifaceted roles in oncogenesis. In this comprehensive review, we provide an overview of the structure, subcellular localization, diagnostic and prognostic significance, biological functions, and molecular mechanisms of ENO2 and ENO3 in cancer progression. The importance of enolase in cancer development makes it a novel therapeutic target for clinical applications. Furthermore, we discuss anticancer agents designed to target enolases and summarize their anticancer efficacy in both in vitro and in vivo studies.