ABSTRACT
The thermal bleaching percentage of coral holobionts shows interspecific differences under heat-stress conditions, which are closely related to the coral-associated microbiome. However, the ecological effects of community dynamics and interactions between Symbiodiniaceae and fungi on coral thermal bleaching susceptibility remain unclear. In this study, we analyzed the diversity, community structure, functions, and potential interaction of Symbiodiniaceae and fungi among 18 coral species from a high thermal bleaching risk atoll using next-generation sequencing. The results showed that heat-tolerant C3u sub-clade and Durusdinium dominated the Symbiodiniaceae community of corals and that there were no core amplicon sequence variants in the coral-associated fungal community. Fungal richness and the abundance of confirmed functional animal-plant pathogens were significantly positively correlated with the coral thermal bleaching percentage. Fungal indicators, including Didymellaceae, Chaetomiaceae, Schizophyllum, and Colletotrichum, were identified in corals. Each coral species had a complex Symbiodiniaceae-fungi interaction network (SFIN), which was driven by the dominant Symbiodiniaceae sub-clades. The SFINs of coral holobionts with low thermal bleaching susceptibility exhibited low complexity and high betweenness centrality. These results indicate that the extra heat tolerance of coral in Huangyan Island may be linked to the high abundance of heat-tolerant Symbiodiniaceae. Fungal communities have high interspecific flexibility, and the increase of fungal diversity and pathogen abundance was correlated with higher thermal bleaching susceptibility of corals. Moreover, fungal indicators were associated with the degrees of coral thermal bleaching susceptibility, including both high and intermediate levels. The topological properties of SFINs suggest that heat-tolerant coral have limited fungal parasitism and strong microbial network resilience.IMPORTANCEGlobal warming and enhanced marine heatwaves have led to a rapid decline in coral reef ecosystems worldwide. Several studies have focused on the impact of coral-associated microbiomes on thermal bleaching susceptibility in corals; however, the ecological functions and interactions between Symbiodiniaceae and fungi remain unclear. We investigated the microbiome dynamics and potential interactions of Symbiodiniaceae and fungi among 18 coral species in Huangyan Island. Our study found that the Symbiodiniaceae community of corals was mainly composed of heat-tolerant C3u sub-clade and Durusdinium. The increase in fungal diversity and pathogen abundance has close associations with higher coral thermal bleaching susceptibility. We first constructed an interaction network between Symbiodiniaceae and fungi in corals, which indicated that restricting fungal parasitism and strong interaction network resilience would promote heat acclimatization of corals. Accordingly, this study provides insights into the role of microorganisms and their interaction as drivers of interspecific differences in coral thermal bleaching.
Subject(s)
Anthozoa , Dinoflagellida , Microbiota , Animals , Anthozoa/microbiology , Coral Reefs , Symbiosis , Fungi/geneticsABSTRACT
OBJECTIVE: This study aimed to construct a nomogram to predict radiation-induced hepatic toxicity in patients with hepatocellular carcinoma treated with intensity-modulated radiotherapy. METHODS: This study reviewed the clinical characteristics and dose-volume parameters of 196 patients with hepatocellular carcinoma. Radiation-induced hepatic toxicity was defined as progression of the Child-Pugh score caused by intensity-modulated radiotherapy. Factors relevant to radiation-induced hepatic toxicity were selected using receiver operating characteristic and univariate logistic analysis. A risk assessment model was developed, and its discrimination was validated. RESULTS: Eighty-eight (44.90%) and 28 (14.29%) patients had radiation-induced hepatic toxicity ≥ 1 (Child-Pugh ≥ 1) and radiation-induced hepatic toxicity ≥ 2 (Child-Pugh ≥ 2). Pre-treatment Child-Pugh, body mass index and dose-volume parameters were correlated with radiation-induced hepatic toxicity ≥ 1 using univariate logistic analysis. V15 had the best predictive effectiveness among the dose-volume parameters in both the training (area under the curve: 0.763, 95% confidence interval: 0.683-0.842, P < 0.001) and validation cohorts (area under the curve: 0.759, 95% confidence interval: 0.635-0.883, P < 0.001). The area under the curve values of the model that was constructed by pre-treatment Child-Pugh, body mass index and V15 for radiation-induced hepatic toxicity ≥1 were 0.799 (95% confidence interval: 0.719-0.878, P < 0.001) and 0.775 (95% confidence interval: 0.657-0.894, P < 0.001) in the training and validation cohorts, respectively. Patients with a body mass index ≤ 20.425, Barcelona clinic liver cancer = C, Hepatitis B Virus-positive, Eastern Cooperative Oncology Group = 1-2 and hepatic fibrosis require lower V15 dose limits. CONCLUSIONS: Risk assessment model constructed from Pre-treatment Child-Pugh, V15 and body mass index can guide individualized patient selection of toxicity minimization strategies.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nomograms , Radiation Injuries , Radiotherapy, Intensity-Modulated , Humans , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Male , Female , Retrospective Studies , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Middle Aged , Aged , Radiation Injuries/etiology , Adult , Aged, 80 and over , Liver/radiation effectsABSTRACT
Sanguisorba officinalis L. possesses detoxifying, analgesic, and hemostatic properties. After charred processing, S. officinalis exhibits significantly enhanced medicinal effects. Currently, most pharmacokinetic studies focus on the chemical constituents of unprocessed S. officinalis. There is limited research on the comparison of chemical constituents before and after processing. This study established a pharmacokinetic method using ultra-high-performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS) to simultaneously determine the levels of four tannin compounds in rat plasma. In negative ion mode, MS/MS detection was performed using an electrospray ionization source. Chromatographic separation was performed using WATERS ACQUITY HSS T3 column (2.1 × 100 mm, 1.8 µm) with a gradient elution of water and acetonitrile as the mobile phase. The pharmacokinetic results indicate that all four compounds reached peak concentrations within 2 h, demonstrating rapid absorption into the bloodstream within the gastrointestinal tract. Notably, the absorption was generally faster in the charred compound of S. officinalis after processing. These four compounds exhibited slower elimination in rat plasma, while in S. officinalis charcoal, the compounds were eliminated more rapidly. The pharmacokinetic results have revealed the pharmacokinetic characteristics of the four analytes in rat plasma which provides valuable reference information for further investigating the in vivo absorption process of S. officinalis after processing.
Subject(s)
Drugs, Chinese Herbal , Sanguisorba , Rats , Animals , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Tannins/analysis , Rats, Sprague-Dawley , Drugs, Chinese Herbal/analysisABSTRACT
The overexpression of inflammatory factors is closely related to the pathogenesis of acute kidney injury (AKI). Additionally, the overproduction of reactive oxygen species (ROS) further exacerbates the inflammatory response. In light of this, monotherapies focused solely on inflammation have proven to be suboptimal. Therefore, this study successfully developed a nanoparticle (SC@Se/GA) that possesses anti-inflammatory and antioxidant properties. The SC@Se/GA has a smaller size, better stability, and kidney-targeting. In vivo experiments showed that the GPx enzyme activity of SC@Se/GA increases by almost 50 % more than SC@Se alone, indicating its efficient ability to scavenge ROS. In the meantime, SC@Se/GA has a longer renal retention period (>24 h) than free drug GA, which can dramatically lower the levels of inflammatory factors TNF-α and IL-6. In summary, SC@Se/GA, through its synergistic anti-inflammatory and antioxidant effects, markedly alleviates CDDP-induced renal injury and restores renal function, providing a new effective strategy for treating AKI.
ABSTRACT
As a real-time fluid biopsy method, the detection of circulating tumor cells (CTCs) provides important information for the early diagnosis, precise treatment, and prognosis of cancer. However, the low density of CTCs in the peripheral blood hampers their capture and detection with high sensitivity and selectivity using currently available methods. Hence, we designed a sandwich-type electrochemical aptasensor that utilizes holothurian-shaped AuPd nanoparticles (AuPd HSs), tetrahedral DNA nanostructures (TDNs), and CuPdPt nanowire networks (NWs) interwoven with a graphdiyne (GDY) sheet for ultrasensitive non-destructive detection of MCF-7 breast cancer cells. CuPdPt NW-GDY effectively enhanced the electron transfer rate and coupled with the loaded TDNs. The TDNs could capture MCF-7 cells with precision and firmness, and the resulting composite complex was combined with AuPd HSs to form a sandwich-type structure. This novel aptasensor showed a linear range between 10 and 106 cells mL-1 and an ultralow detection limit of 7 cells mL-1. The specificity, stability, and repeatability of the measurements were successfully verified. Moreover, we used benzonase nuclease to achieve non-destructive recovery of cells for further clinical studies. According to the results, our aptasensor was more sensitive measuring the number of CTCs than other approaches because of the employment of TDNs, CuPdPt NW-GDY, and AuPd HSs. We designed a reliable sensor system for the detection of CTCs in the peripheral blood, which could serve as a new approach for cancer diagnosis at an early stage.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , DNA , Electrochemical Techniques , Gold , Limit of Detection , Metal Nanoparticles , Neoplastic Cells, Circulating , Palladium , Neoplastic Cells, Circulating/pathology , Humans , MCF-7 Cells , Metal Nanoparticles/chemistry , Electrochemical Techniques/methods , Aptamers, Nucleotide/chemistry , Gold/chemistry , DNA/chemistry , Biosensing Techniques/methods , Palladium/chemistryABSTRACT
An electrochemical platform for signal amplification probing chloride ions (Cl-) is constructed by the composite integrating core-shell structured nitrogen-doped porous carbon@Ag-based metal-organic frameworks (NC@Ag-MOF) with polypyrrole (PPy). It is based on the signal of solid-state AgCl derived from Ag-MOF, since both NC and PPy have good electrical conductivity and promote the electron transport capacity of solid-state AgCl. NC@Ag-MOF was firstly synthesized with NC as the scaffold and then, PPy was anchored on NC@Ag-MOF by chemical polymerization. The composite NC@Ag-MOF-PPy was utilized to modify the electrode, which exhibited a higher peak current and lower peak potential during Ag oxidation compared with those of Ag-MOF and NC@Ag-MOF-modified electrodes. More importantly, in the coexistence of chloride (Cl-) ions in solution, the NC@Ag-MOF-PPy-modified electrode displayed a fairly stable and sharp peak of solid-state AgCl with the peak potentials gradually approaching zero, which might effectively overcome the background interference caused by electroactive substances. The oxidation peak currents of solid-state AgCl increased linearly with the concentration of Cl- ions in a broad range of 0.15 µM-40 mM and 40-250 mM, with detection limits of 0.10 µM and 40 mM, respectively. The practical applicability for Cl- ions determination was demonstrated using human serum and urine samples. The results suggest that NC@Ag-MOF-PPy composite could be a promising candidate for the construction of the electrochemical sensor.
ABSTRACT
BACKGROUND AND OBJECTIVE: Glycyrrhiza glabra L. (GG) and Strychnos nux-vomica L. (NV) are traditional Chinese medicines (TCMs). Changes in the chemical composition may occur before and after the GG-NV compatibility. Ultra-performance liquid chromatography Q-exactive Orbitrap mass spectrometry (UPLC-QE-Orbitrap-MS) was applied here to study the difference in the components of the GG and NV decoctions before and after they were combined. The changes in the chemical composition of GG and NV before and after the combination were determined. METHODS: The precise molecular weight, retention time, and fragment ion peak of the different components of the decoctions before and after compatibility were obtained through UPLC-QE-Orbitrap-MS. Differential analysis methods, such as principal component analysis, were used for comparison. RESULTS: In the positive ion mode, 200 new components were added, whereas six components were lost. In the negative ion mode, 144 new compounds were identified, whereas three components were missing. CONCLUSIONS: The compatibility difference between GG and NV was studied through UPLC-QE-Orbitrap-MS. The chemical composition of GG and NV changed before and after compatibility, and a class of compounds different from GG and NV was identified in the co-decoction. This study provides an experimental basis for subsequent research into detoxification mechanisms of the GG-NV combination and offers a new analytical method for investigating the compatibility of various other TCM pairs.
Subject(s)
Drugs, Chinese Herbal , Glycyrrhiza , Mass Spectrometry , Strychnine , Glycyrrhiza/chemistry , Chromatography, High Pressure Liquid/methods , Strychnine/analysis , Strychnine/chemistry , Mass Spectrometry/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Principal Component AnalysisABSTRACT
Ecosystem services provide the basic elements for global economic development. In the context of the deepening global integration process, countries and regions are increasingly connected, resulting in a series of cross-country, cross-regional, multi-scale socio-economic-environmental impacts, these new situations and changes require a multi-site, two-way, and cross-temporal and spatial scale comprehensive study of "the relationship between ecosystem services and humans". Based on this, we apply a telecoupling synthesis framework to explore the socio-economic and eco-environmental interactions of ecosystem service spillover effects. Results show that (1) the spillover effect of ecosystem services in western China is significant. More than 66% of ecosystem services spillover to eastern China provinces, and more than 40% of ecosystem services spillover to countries in Southeast Asia, South Asia, and Central Asia, resulting in a total of 679 million people benefiting from the spillover effect. (2) There are also multiple telecoupling processes between the ecosystem service spillovers in the ecologically fragile areas in western China and the rest of the world. In combination with the scenario simulation of the InVEST model, the services such as water supply, soil retention, flood mitigation, and food supply have significant impacts on sustainable development and human well-being in Asia and even the world. (3) The positive feedback effect of telecoupling is critical to the protection of the ecological environment as well as the improvement of people's livelihood and well-being in Western China's ecologically fragile areas. Therefore, we propose strengthening ecological compensation cooperation between local governments and implementing compensatory transfer payments between upstream and downstream. Simultaneously, international cooperation must be strengthened, and an ecological compensation transfer mechanism with beneficiary countries must be established, while the cross-regional flow of ecosystem services must be maintained. This study provides an example for the "ecosystem services and human relations" in multiple places, two directions and across time and space scales, and also practical reference significance for China implementation of projects such as the "the Belt and Road" initiative and transnational and cross regional resource allocation.
Subject(s)
Ecosystem , Environment , Humans , China , Asia , Sustainable Development , Conservation of Natural ResourcesABSTRACT
Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.
Subject(s)
Antineoplastic Agents , Xanthones , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Water , Xanthones/chemistry , Xanthones/pharmacologyABSTRACT
Epidermal growth factor receptor (EGFR) mutation status is pivotal in predicting the efficacy of tyrosine kinase inhibitor treatments against tumors. Among EGFR mutations, the E746-A750 deletion is particularly common and accurately quantifying it can guide targeted therapies. This study introduces a novel visual sensing technology using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system guided by ligation-initiated loop-mediated isothermal amplification (LAMP) to detect the del E746-A750 mutation in EGFR. Conventional LAMP primers were simplified by designing a pair of target-specific stem-loop DNA probes, enabling selective amplification of the target DNA. The CRISPR/Cas12a system was employed to identify the target nucleic acid and activate Cas12a trans-cleavage activity, thereby enhancing the specificity of the assay. Furthermore, the biosensor utilized high-performance nanomaterials such as triangular gold nanoparticles and graphdiyne, known for their large specific surface area, to enhance sensitivity effectively as a sensing platform. The proposed biosensor demonstrated outstanding specificity, achieving a low detection limit of 17 fM (S/N = 3). Consequently, this innovative strategy not only expands the application scope of CRISPR/Cas12a technology but also introduces a promising approach for clinical diagnostics in modern medicine.
Subject(s)
Biosensing Techniques , CRISPR-Cas Systems , ErbB Receptors , Nucleic Acid Amplification Techniques , Biosensing Techniques/methods , CRISPR-Cas Systems/genetics , Nucleic Acid Amplification Techniques/methods , Humans , ErbB Receptors/genetics , Electrochemical Techniques/methods , Limit of Detection , Gold/chemistry , Metal Nanoparticles/chemistry , Sequence Deletion , Bacterial Proteins , Endodeoxyribonucleases , Molecular Diagnostic Techniques , CRISPR-Associated ProteinsABSTRACT
Astragalus membranaceus (A. membranaceus) leaves can be used both as a medicine and food material. Their main chemical components are flavonoids and triterpenoid saponins. The pharmacokinetics of A. membranaceus leaves are rarely reported in the literature. This study aimed to investigate the pharmacokinetics of five major bioactive components of A. membranaceus leaves [rhamnocitrin 3-glucoside (RCG), tiliroside (TIL), rhamnocitrin 3-neohesperidoside (RNH), huangqiyenin R (HuR), and huangqiyenin I (HuI)]. Simultaneously using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. The extract of A. membranaceus leaves was administered orally to rats, and the rat plasma was subjected to a fast, sensitive, and specific UHPLC-MS/MS method. Butylparaben served as the internal standard. The plasma samples were pretreated using isopropanol/ethyl acetate (1:1, v/v) liquid-liquid extraction. Chromatographic separations were performed at a flow rate of 0.3â¯mL/min on a Waters ACQUITY HSS T3 Column (2.1â¯mm × 100â¯mm, 1.8 µm) using mobile phases of 0.1â¯% formic acid/water and 0.1â¯% formic acid/acetonitrile. Mass spectrometry detection was performed using an electrospray ionization ion source in the negative-ion mode and the multiple reaction monitoring mode. All analytes had an intraday and interday relative standard deviation of less than 14.10â¯%. The range of accuracy was -11.94-6.920â¯% and -15.22-5.800â¯%. The lower limits of quantification for RCG, TIL, RNH, HuR, HuI was 10.24, 10.27, 10.12, 5.137, and 5.841â¯ng/mL, respectively. The criteria were met by stability, matrix effects, and extraction recovery. The pharmacokinetic parameters of A. membranaceus leaf extract were ultimately obtained using this analytical method. The study provides a theoretical basis for future pharmacological research, clinical application, and development of healthy food from A. membranaceus leaves.
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Background: Hand, foot, and mouth disease (HFMD) has remained a serious public health threat since its first outbreak in China. Analyzing the province-level spatiotemporal distribution of HFMD and mapping the relative risk in mainland China will help determine high-risk provinces and periods of infection outbreaks for use in formulating new priority areas for prevention and control of this disease. Furthermore, our study examined the effect of air pollution on HFMD nationwide, which few studies have done thus far. Methods: Data were collected on the number of provincial monthly HFMD infections, air pollution, meteorological variables, and socioeconomic variables from 2014 to 2017 in mainland China. We used spatial autocorrelation to determine the aggregate distribution of HFMD incidence. Spatiotemporal patterns of HFMD were analyzed, risk maps were developed using the Bayesian spatiotemporal model, and the impact of potential influencing factors on HFMD was assessed. Results: In our study, from 2014 to 2017, the HFMD annual incidence rate in all provinces of mainland China ranged from 138.80 to 203.15 per 100,000 people, with an average annual incidence rate of 165.86. The temporal risk of HFMD for 31 Chinese provinces exhibited cyclical and seasonal characteristics. The southern and eastern provinces had the highest spatial relative risk (RR > 3) from 2014 to 2017. The HFMD incidence risk in provinces (Hunan, Hubei, and Chongqing) located in central China increased over time. Among the meteorological variables, except for the mean two-minute wind speed (RR 0.6878; 95% CI 0.5841, 0.8042), all other variables were risk factors for HFMD. High GDP per capita (RR 0.9922; 95% CI 0.9841, 0.9999) was a protective factor against HFMD. The higher the birth rate was (RR 1.0657; 95% CI 1.0185, 1.1150), the higher the risk of HFMD. Health workers per 1,000 people (RR 1.2010; 95% CI 1.0443, 1.3771) was positively correlated with HFMD. Conclusions: From 2014 to 2017, the central provinces (Hunan, Hubei, and Chongqing) gradually became high-risk regions for HFMD. The spatiotemporal pattern of HFMD risk may be partially attributed to meteorological and socioeconomic factors. The prevalence of HFMD in the central provinces requires attention, as prevention control efforts should be strengthened there.
Subject(s)
Hand, Foot and Mouth Disease , Humans , Hand, Foot and Mouth Disease/epidemiology , Bayes Theorem , Incidence , Risk Factors , China/epidemiologyABSTRACT
Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca2+ influx. However, controllable manipulation of TRPV1 signaling for clinical application has remained elusive due to the challenge in finding a mild and effective method of exerting external stimulus without adverse side effects in living systems. Herein, a TRPV1-targeting near-infrared (NIR) triggered nitric oxide (NO)-releasing nanoplatform (HCuS@PDA-TRPV1/BNN6) based on polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) is developed for specific cancer therapy. Upon NIR irradiation, the NO donor BNN6 encapsulated in NIR-responsive nanovehicles can locally generate NO to activate TRPV1 channels and induce Ca2+ influx. This NIR controlled mode enables the nanoplatform to exert its therapeutic effects below the apoptotic threshold temperature (43°C), minimizing the photothermal damage to normal tissue. Integrating this special NO-mediated therapy with HCuS NPs mediated chemodynamic therapy, the designed nanoplatform exhibits a boosted anticancer activity with negligible systematic toxicity. Together, this study provides a promising strategy for site-specific cancer therapy by spatiotemporally controlled activation of surface ion channels, thus offering a solution to an unmet clinical need in cancer treatment.
Subject(s)
Antineoplastic Agents , Nanoparticles , Neoplasms , Antineoplastic Agents/pharmacology , Infrared Rays , Neoplasms/drug therapy , Nitric Oxide/metabolism , Phototherapy , HumansABSTRACT
The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.
Subject(s)
Anti-Inflammatory Agents , Blood Glucose , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Insulin , Polysaccharides , Animals , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Blood Glucose/drug effects , Blood Glucose/analysis , Administration, Oral , Insulin/administration & dosage , Insulin/pharmacokinetics , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Mice , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/pharmacokinetics , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Male , Vitamin B 12/administration & dosage , Nanoparticles/administration & dosage , Drug Liberation , Drug Carriers/chemistry , HumansABSTRACT
A polarized light microscope (PLM) was utilized to examine the optical textures of mesophase pitch (MP) and MP-derived fibers, which aimed to reveal the arrangement and orientation characteristics of pitch molecules and to clarify the evolution and transformation mechanism of carbonaceous microcrystalline from pitch fibers to graphitized fibers. The results found that there were distinct optical textures in MP, where one side exhibited a transition from a flattening plane to a mountain-like undulating plane. This transition corresponded to the arrangement of pitch molecules, resembling stacked lamellar structures reminiscent of curved paper. Meanwhile, the optical textures of fibers revealed that the blue substance was wrapped around the red grain-like domains in the longitudinal section and confirmed that the red part belonged to the pyridine insoluble fraction of MP and the blue part belonged to its pyridine-soluble fraction. After graphitization, the red part was transformed into graphite sheets and the blue part was transformed into an amorphous carbon layer which was wrapped around the graphite sheets, forming a carbonaceous microcrystalline package-like bag. Therefore, this study provided a comprehensive interpretation of the structural evolution mechanism of MP and MP-derived fibers based on their macro-optical textures and micro-nanostructures.
ABSTRACT
Glioblastoma multiforme (GBM) is the most prevalent and lethal primary intracranial neoplasm in the adult population, with treatments of limited efficacy. Recently, bufotalin has been shown to have anti-cancer activity in a variety of cancers. This investigation aims to investigate the effect of bufotalin on GBM and elucidate its potential underlying mechanism. Our results show that bufotalin not only inhibits the proliferation and epithelial-mesenchymal transition (EMT) but also triggers apoptosis in GBM cells. The result of RNA-seq indicated that bufotalin could induce mitochondrial dysfunction. Moreover, our observations indicate that bufotalin induces an excessive accumulation of intracellular reactive oxygen species (ROS) in GBM cells, leading to mitochondrial dysfunction and the dephosphorylation of AKT. Moreover, bufotalin improved TMZ sensitivity of GBM cells in vitro and in vivo. In conclusion, bufotalin enhances apoptosis and TMZ chemosensitivity of glioblastoma cells by promoting mitochondrial dysfunction via AKT signaling pathway.
Subject(s)
Apoptosis , Bufanolides , Glioblastoma , Mitochondria , Proto-Oncogene Proteins c-akt , Reactive Oxygen Species , Signal Transduction , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Apoptosis/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Bufanolides/pharmacology , Bufanolides/therapeutic use , Cell Line, Tumor , Animals , Reactive Oxygen Species/metabolism , Cell Proliferation/drug effects , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Epithelial-Mesenchymal Transition/drug effectsABSTRACT
Background: In China, bacillary dysentery (BD) is the third most frequently reported infectious disease, with the greatest annual incidence rate of 38.03 cases per 10,000 person-years. It is well acknowledged that temperature is associated with BD and the previous studies of temperature-BD association in different provinces of China present a considerable heterogeneity, which may lead to an inaccurate estimation for a region-specific association and incorrect attributable burdens. Meanwhile, the common methods for multi-city studies, such as stratified strategy and meta-analysis, have their own limitations in handling the heterogeneity. Therefore, it is necessary to adopt an appropriate method considering the spatial autocorrelation to accurately characterize the spatial distribution of temperature-BD association and obtain its attributable burden in 31 provinces of China. Methods: A novel three-stage strategy was adopted. In the first stage, we used the generalized additive model (GAM) model to independently estimate the province-specific association between monthly average temperature (MAT) and BD. In the second stage, the Leroux-prior-based conditional autoregression (LCAR) was used to spatially smooth the association and characterize its spatial distribution. In the third stage, we calculate the attribute BD cases based on a more accurate estimation of association. Results: The smoothed association curves generally show a higher relative risk with a higher MAT, but some of them have an inverted "V" shape. Meanwhile, the spatial distribution of association indicates that western provinces have a higher relative risk of MAT than eastern provinces with 0.695 and 0.645 on average, respectively. The maximum and minimum total attributable number of cases are 224,257 in Beijing and 88,906 in Hainan, respectively. The average values of each province in the eastern, western, and central areas are approximately 40,991, 42,025, and 26,947, respectively. Conclusion: Based on the LCAR-based three-stage strategy, we can obtain a more accurate spatial distribution of temperature-BD association and attributable BD cases. Furthermore, the results can help relevant institutions to prevent and control the epidemic of BD efficiently.
Subject(s)
Dysentery, Bacillary , Temperature , China/epidemiology , Humans , Dysentery, Bacillary/epidemiology , Incidence , Spatial Analysis , Models, StatisticalABSTRACT
Caffeoyl-coenzyme 3 A-O-methyltransferase (CCoAOMT) plays a crucial role in the lignin synthesis in many higher plants. In this study, nine PbCCoAOMT genes in total were identified from pear, and classified into six categories. We treated pear fruits with hormones abscisic acid (ABA) and methyl jasmonate (MeJA) and salicylic acid (SA) and observed differential expression levels of these genes. Through qRT-PCR, we also preliminarily identified candidate PbCCoAOMT gene, potentially involved in lignin synthesis in pear fruits. Additionally, the overexpression of PbCCoAOMT1/2 in Arabidopsis and pear fruits increased in lignin content. Enzymatic assays showed that recombinant PbCCoAOMT1/2 proteins have similar enzymatic activity in vitro. The Y1H (Yeast one-hybrid) and dual luciferase (dual-LUC) experiments demonstrated that PbMYB25 can bind to the AC elements in the promoter region of the PbCCoAOMT1 gene. Our findings suggested that the PbCCoAOMT1 and PbCCoAOMT2 genes may contribute to the synthesis of lignin and provide insights into the mechanism of lignin biosynthesis and stone cell development in pear fruits.
Subject(s)
Arabidopsis , Gene Expression Regulation, Plant , Lignin , Methyltransferases , Pyrus , Lignin/metabolism , Lignin/biosynthesis , Methyltransferases/genetics , Methyltransferases/metabolism , Pyrus/genetics , Pyrus/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Abscisic Acid/metabolism , Fruit/genetics , Fruit/metabolism , Salicylic Acid/metabolism , Promoter Regions, Genetic , Plants, Genetically Modified/genetics , Oxylipins/metabolism , Cyclopentanes/metabolism , Acetates/metabolismABSTRACT
Fungiidae have shown increased thermal adaptability in coral reef ecosystems under global warming. This study analyzes the evolutionary divergence and microbial communities of Fungiidae in the Sanjiao Reef of the southern South China Sea and explores the impact of coral evolution radiation and microbial dynamics on the heat tolerance of Fungiidae. The results found that Cycloseris was an ancient branch of Fungiidae, dating back approximately 147.8953 Mya, and Fungiidae differentiated into two ancestral clades (clades I and II) before 107.0312 Ma. Fungiidae exhibited specific symbioses with the Cladocopium C27 sub-clade. Notably, the Cladocopium C1 sub-clade has a high relative abundance in clade I, whereas the heat-tolerant Cladocopium C40 and C3u sub-clades subdominante in clade II. Regarding bacterial communities, Cycloseris costulata, the earliest divergent species, had higher bacterial ß-diversity, while the latest divergent species, Lithophyllon scabra, displayed lower bacterial α-diversity and higher community stability. Beneficial bacteria dominante Fungiidae's bacterial community (54%). The co-occurrence network revealed that microbial networks in clade II exhibited lower complexity and greater resilience than those in clade I. Our study highlights that host evolutionary radiation and microbial communities shaped Fungiidae's thermal tolerance. The variability in subdominant Symbiodiniaceae populations may contribute to interspecific differences in thermal tolerance along the evolutionary branches of Fungiidae. The presence of abundant beneficial bacteria may further enhance the thermal ability of the Fungiidae. Furthermore, the later divergent species of Fungiidae have stronger heat tolerance, possibly driven by the increased regulation ability of the host on the bacterial community, greater microbial community stability, and interaction network resistance.IMPORTANCECoral reefs are facing significant threats due to global warming. The heat tolerance of coral holobionts depends on both the coral host and its microbiome. However, the association between coral evolutionary radiation and interspecific differences in microbial communities remains unclear. In this study, we investigated the role of evolutionary radiation and microbial community dynamics in shaping the thermal acclimation potential of Fungiidae in the Sanjiao Reef of the southern South China Sea. The study's results suggest that evolutionary radiation enhances the thermal tolerance of Fungiidae. Fungiidae species that have diverged more recently have exhibited a higher presence of heat-tolerant Symbiodiniaceae taxa, more stable bacterial communities, and a robust and resilient microbial interaction network, improving the thermal adaptability of Fungiidae. In summary, this study provides new insights into the thermal adaptation patterns of corals under global warming conditions.
Subject(s)
Anthozoa , Dinoflagellida , Microbiota , Animals , Anthozoa/microbiology , Anthozoa/physiology , Coral Reefs , Acclimatization , Bacteria , China , Dinoflagellida/physiologyABSTRACT
BACKGROUND: Cognitive decline, a heavy burden on middle-aged and older adults as global aging is aggravated, was found to be associated with sleep quality. However, the country-between heterogeneity of the association prevented us from quantifying underlying relationship and identifying potential effect modifiers for vulnerable populations and targeted interventions. METHODS: We collected data from 79,922 eligible adults in five nationwide cohorts, examined the respective relationships between cognitive function and sleep quality, synthesized underlying average relationships by meta-analysis, and explored effect modifiers by meta-regressions. Additionally, we conducted subgroup and interaction analyses to identify vulnerable populations and to determine their disparities in vulnerability. RESULTS: Although country-between disparities exist, cognitive function is robustly associated with sleep quality in middle-aged and older adults worldwide, with an effect (ß) of 0.015 [0.003, 0.027]. Executive function is the subdomain most relevant to sleep quality. Disparities in the effects of sleep quality on subdomains exist in populations with different sexes (orientation: ßfemale/ßmale = 1.615, P = 0.020), marital statuses (orientation: ßunmarried/ßmarried = 2.074, P < 0.001), education levels (orientation:ßuneducated/ßeducated = 2.074, P < 0.001) and chronic disease statuses (memory: ßunhealthy/ßhealthy = 1.560, P = 0.005). CONCLUSIONS: Cognitive function decreases with worsening sleep quality in middle-aged and older adults. Vulnerability to poor sleep generally persists in singles, females, the uneducated and people with chronic diseases. To minimize disparities and achieve health equity, we advocate for targeted interventions, i.e., encouraging socialization in singles, confirming effectiveness of hormone replacement therapy in females, employing compulsory education in middle-aged and older adults.