Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.
Introduction: Pedicle screw instrumentation (PSI) serves as the widely accepted surgical treatment for adolescent idiopathic scoliosis (AIS). The accuracy of screw positioning has remarkably improved with robotic assistance. Nonetheless, its impact on radiographic and clinical outcomes remains unexplored. This study aimed to investigate the radiographic and clinical outcomes of robot-assisted PSI vs. conventional freehand method in AIS patients. Methods: Data of AIS patients who underwent PSI with all pedicle screws between April 2013 and March 2022 were included and retrospectively analyzed; those with hybrid implants were excluded. Recruited individuals were divided into the Robot-assisted or Freehand group according to the technique used. Radiographic parameters and clinical outcome measures were documented. Results: In total, 50 patients (19, Freehand group; 31, Robot-assisted group) were eligible, with an average age and follow-up period of 17.6 years and 60.2 months, respectively, and female predominance (40/50, 80.0%). The correction rates of Cobb's angles for both groups were significant postoperatively. Compared to freehand, the robot-assisted technique achieved a significantly reduced breech rate and provided better trunk shift and radiographic shoulder height correction with preserved lumbar lordosis, resulting in significantly improved visual analog scale scores for back pain from the third postoperative month. Conclusion: Overall, robot-assisted PSI provides satisfactory radiographic and clinical outcomes in AIS patients.
Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways.
Magnetic resonance-diffusion tensor imaging (MR-DTI) has been used in the microvascular decompression and gamma knife radiosurgery in trigeminal neuralgia (TN) patients; however, use of percutaneous stereotactic radiofrequency rhizotomy (PSR) to target an abnormal trigeminal ganglion (ab-TG) is unreported. Fractional anisotropy (FA), mean and radial diffusivity (MD and RD, respectively), and axial diffusivity (AD) of the trigeminal nerve (CNV) were measured in 20 TN patients and 40 healthy control participants immediately post PSR, at 6-months, and at 1 year. Longitudinal alteration of the diffusivity metrics and any correlation with treatment effects, or prognoses, were analyzed. In the TN group, either low FA (value < 0.30) or a decreased range compared to the adjacent FA (dFA) > 17% defined an ab-TG. Two-to-three days post PSR, all 15 patients reported decreased pain scores with increased FA at the ab-TG (P < 0.001), but decreased MD and RD (P < 0.01 each). Treatment remained effective in 10 of 14 patients (71.4%) and 8 of 12 patients (66.7%) at the 6-month and 1-year follow-ups, respectively. In patients with ab-TGs, there was a significant difference in treatment outcomes between patients with low FA values (9 of 10; 90%) and patients with dFA (2 of 5; 40%) (P < 0.05). MR-DTI with diffusivity metrics correlated microstructural CNV abnormalities with PSR outcomes. Of all the diffusivity metrics, FA could be considered a novel objective quantitative indicator of treatment effects and a potential indicator of PSR effectiveness in TN patients.
Diffusion Tensor Imaging , Rhizotomy , Trigeminal Neuralgia , Humans , Trigeminal Neuralgia/surgery , Trigeminal Neuralgia/diagnostic imaging , Male , Female , Rhizotomy/methods , Middle Aged , Diffusion Tensor Imaging/methods , Aged , Treatment Outcome , Adult , Trigeminal Nerve/surgery , Trigeminal Nerve/diagnostic imaging , Trigeminal Nerve/pathology , Radiosurgery/methods , Anisotropy , Prognosis
It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and ß-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.
Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.
OBJECTIVE: The primary objective of this study is to address the reconstruction time challenge in Magnetic Particle Imaging (MPI) by introducing a novel approach named SNR-Peak-Based Frequency Selection (SPFS). The focus is on improving spatial resolution without compromising reconstruction speed, thereby enhancing the clinical potential of MPI for real-time imaging. APPROACH: To overcome the trade-off between reconstruction time and spatial resolution in MPI, the researchers propose SPFS as an innovative frequency selection method. Unlike conventional SNR-based selection, SPFS prioritizes frequencies with Signal-to-Noise Ratio (SNR) peaks that capture crucial system matrix information. This adaptability to varying quantities of selected frequencies enhances versatility in the reconstruction process. The study compares the spatial resolution of MPI reconstruction using both SNR-based and SPFS frequency selection methods, utilizing simulated and real device data. MAIN RESULTS: The research findings demonstrate that the SPFS approach substantially improves image resolution in Magnetic Particle Imaging, especially when dealing with a limited number of frequency components. By focusing on SNR peaks associated with critical system matrix information, SPFS mitigates the spatial resolution degradation observed in conventional SNR-based selection methods. The study validates the effectiveness of SPFS through the assessment of MPI reconstruction spatial resolution using both simulated and real device data, highlighting its potential to address a critical limitation in the field. SIGNIFICANCE: The introduction of SNR-Peak-Based Frequency Selection (SPFS) represents a significant breakthrough in MPI technology. The method not only accelerates reconstruction time but also enhances spatial resolution, thus expanding the clinical potential of MPI for various applications. The improved real-time imaging capabilities of MPI, facilitated by SPFS, hold promise for advancements in drug delivery, plaque assessment, tumor treatment, cerebral perfusion evaluation, immunotherapy guidance, and in vivo cell tracking.
Till now, microplastics/nano-plastics(M/NPs) have received a lot of attention as emerging contaminant. As a typical but complex porous medium, soil is not only a large reservoir of M/NPs but also a gateway for M/NPs to enter groundwater. Therefore, the review of the factors controlling the transport behavior of M/NPs in porous media can provide important guidance for the risk assessment of M/NPs in soil and groundwater. In this study, the key factors controlling the transport behavior of M/NPs in porous media are systematically divided into three groups: (1) nature of M/NPs affecting M/NPs transport in porous media, (2) nature of flow affecting M/NPs transport in porous media, (3) nature of porous media affecting M/NPs transport. In each group, the specific control factors for M/NPs transport in porous media are discussed in detail. In addition to the above factors, some substances (colloids or pollutants) present in natural porous media (such as soil or sediments) will co-transport with M/NPs and affect its mobility. According to the different properties of co-transported substances, the mechanism of promoting or inhibiting the migration behavior of M/NPs in porous media was discussed. Finally, the limitations and future research directions of M/NPs transport in porous media are pointed out. This review can provide a useful reference for predicting the transport of M/NPs in natural porous media.
Valvular endothelial cells (VECs) derived from human induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for tissue engineering heart valves (TEHVs); however, they are limited by their low differentiation efficiency and immature function. In our study, we applied unidirectional shear stress to promote hiPSCs differentiation into valvular endothelial-like cells (VELs). Compared to the static group, shear stress efficiently promoted the differentiation and functional maturation of hiPSC-VELs, as demonstrated by the efficiency of endothelial differentiation reaching 98.3% in the high shear stress group (45 dyn/cm2). Furthermore, we found that Piezo1 served as a crucial mechanosensor for the differentiation and maturation of VELs. Mechanistically, the activation of Piezo1 by shear stress resulted in the influx of calcium ions, which in turn initiated the Akt signaling pathway and promoted the differentiation of hiPSCs into mature VELs. Moreover, VELs cultured on decellularized heart valves (DHVs) exhibited a notable propensity for proliferation, robust adhesion properties, and antithrombotic characteristics, which were dependent on the activation of the Piezo1 channel. Overall, our study demonstrated that proper shear stress activated the Piezo1 channel to facilitate the differentiation and maturation of hiPSC-VELs via the Akt pathway, providing a potential cell source for regenerative medicine, drug screening, pathogenesis, and disease modeling. STATEMENT OF SIGNIFICANCE: This is the first research that systematically analyzes the effect of shear stress on valvular endothelial-like cells (VELs) derived from human induced pluripotent stem cells (hiPSCs). Mechanistically, unidirectional shear stress activates Piezo1, resulting in an elevation of calcium levels, which triggers the Akt signaling pathway and then facilitates the differentiation of functional maturation VELs. After exposure to shear stress, the VELs exhibited enhanced proliferation, robust adhesion capabilities, and antithrombotic characteristics while being cultured on decellularized heart valves. Thus, it is of interest to develop hiPSCs-VELs using shear stress and the Piezo1 channel provides insights into the functional maturation of valvular endothelial cells, thereby serving as a catalyst for potential applications in the development of therapeutic and tissue-engineered heart valves in the future.
Induced Pluripotent Stem Cells , Humans , Endothelial Cells , Calcium/metabolism , Fibrinolytic Agents , Proto-Oncogene Proteins c-akt/metabolism , Cell Differentiation/physiology , Endothelium
The photocatalytic environmental decontamination ability of carbon nitride (g-C3 N4 , CN) typically suffers from their inherent structural defects, causing rapid recombination of photogenerated carriers. Conjugating CN with tailored donor-acceptor (D-A) units to counteract this problem through electronic restructuring becomes a feasible strategy, where confirmation by density functional theory (DFT) calculations becomes indispensable. Herein, DFT is employed to predirect the copolymerization modification of CN by benzene derivatives, screening benzaldehyde as the optimal electron-donating candidate for the construction of reoriented intramolecular charge transfer path. Experimental characterization and testing corroborate the formation of a narrowed bandgap as well as high photoinduced carrier separation. Consequently, the optimal BzCN-2 exhibited superior photocatalytic capacity in application for tetracycline hydrochloride degradation, with 3.73 times higher than that of CN. Besides, the BzCN-2-based photocatalytic system is determined to have a toxicity-mitigating effect on TC removal via T.E.S.T and prefers the removal of dissociable TC2- species under partial alkalinity. This work provides insight into DFT guidance for the design of D-A conjugated polymer and its application scenarios in photocatalytic decontamination.
Calcium-containing biochar ï¼ES-BCï¼ was prepared by pyrolyzing eggshell and kitchen wastesï¼ and the ES-BC composite was used to remove phosphate ï¼marked as ES-BC/Pï¼. Based on the high affinity of phosphate and carbonate to leadï¼ the ES-BC/P was then used to remove lead from the water. The results showed thatï¼ in the appropriate dosageï¼ ES-BC/P could remove lead efficiently at different initial concentrations ï¼1-100 mg·L-1ï¼ï¼ and the removal efficiency could reach to 99%. Meanwhileï¼ the release of phosphorus could be ignored after the reaction. As ES-BC/P was alkalineï¼ and the lead-containing solution was weakly acidicï¼ the addition of ES-BC/P could adjust the pH of the system automatically. The reaction kinetics and isotherm experiments showed that the lead removal by ES-BC/P was mainly monolayer chemisorption with a maximum adsorption capacity of 493.12 mg·g-1 ï¼318 Kï¼. The characterization results showed that lead was mainly removed through the ion exchanges of Pb2+ in the solution with Ca2+ in ES-BC/P. Thenï¼ the Pb2+ combined with CO32- and PO42- to form many precipitatesï¼ including Pb5ï¼PO4ï¼3OHï¼ Pb10ï¼PO4ï¼6ï¼OHï¼2ï¼ PbCO3ï¼ and Pb3ï¼CO3ï¼2ï¼OHï¼2. In summaryï¼ the ES-BC/P material could achieve the efficient removal of lead from the waterï¼ thereby realizing the resource utilization of the wastes.
In this work, a new use of mixed Ti-6Al-4V powder, consisting of the retained powder after screening for additive manufacturing and the recycled powder after multiple printing, has been exploited. The powder mixture has been hot-isostatically-pressed (HIPed) at 930 °C/120 MPa for 3 h to reach full density. The hot deformation behavior of the as-HIPed powder compacts were investigated through isothermal compression tests, kinetic analyses, and hot processing maps. Finally, the optimized hot working parameters were validated using upsetting tests. The results show that the as-HIPed Ti-6Al-4V alloy has a fine and homogeneous microstructure. The activation energies were calculated to be 359 kJ/mol in the α + ß phase regime and 463 kJ/mol in the ß phase regime, respectively. The optimal hot working parameters are a deformation temperature above 950 °C and strain rate higher than 0.1 s-1. The hot workability of as-HIPed powder compacts is better than the as-cast billets. The deformed microstructure can be finer than that of as-HIPed state, and the mechanical performance can be further improved by the optimal thermo-mechanical processing treatment.
Methamphetamine (MA) use disorder poses significant challenges to both the affected individuals and society. Current non-drug therapies like transcranial direct-current stimulation and transcranial magnetic stimulation have limitations due to their invasive nature and limited reach to deeper brain areas. Transcranial focused ultrasound (FUS) is gaining attention as a noninvasive option with precise spatial targeting, able to affect deeper areas of the brain. This research focused on assessing the effectiveness of FUS in influencing the infralimbic cortex (IL) to prevent the recurrence of MA-seeking behavior, using the conditioned place preference (CPP) method in rats. The study involved twenty male Sprague-Dawley rats. Neuronal activation by FUS was first examined via electromyography (EMG). Rats received alternately with MA or saline, and confined to one of two distinctive compartments in a three compartment apparatus over a 4-day period. After CPP test, extinction, the first reinstatement, and extinction again, FUS was applied to IL prior to the second MA priming-induced reinstatement. Safety assessments were conducted through locomotor and histological function examinations. EMG data confirmed the effectiveness of FUS in activating neurons. Significant attenuation of reinstatement of MA CPP was found, along with successful targeting of the IL region, confirmed through acoustic field scanning, c-Fos immunohistochemistry, and Evans blue dye staining. No damage to brain tissue or impaired locomotor activity was observed. The results of the study indicate that applying FUS to the IL markedly reduced the recurrence of MA seeking behavior, without harming brain tissue or impairing motor skills. This suggests that FUS could be a promising method for treating MA use disorder, with the infralimbic cortex being an effective target for FUS in preventing MA relapse.
Extinction, Psychological , Methamphetamine , Rats, Sprague-Dawley , Animals , Male , Methamphetamine/pharmacology , Rats , Extinction, Psychological/drug effects , Ultrasonic Therapy/methods , Central Nervous System Stimulants/pharmacology , Prefrontal Cortex/drug effects , Proto-Oncogene Proteins c-fos/metabolism
Peptidomics analysis was conducted using high-resolution tandem mass spectrometry (MS2) to determine the peptide profile of snail-derived mucin extract (SM). The study was also aimed to identify an indicator peptide and validate a quantification method for this peptide. The peptide profiling and identification were conducted using discovery-based peptidomics analysis employing data-dependent acquisition, whereas the selected peptides were verified and quantified using parallel reaction monitoring acquisition. Among the 16 identified peptides, the selected octapeptide (TEAPLNPK) was quantified via precursor ion ionization (m/z 435.2400), followed by quantification of the corresponding quantifier ion fragment (m/z 639.3824) using MS2. The quantification method was optimized and validated in terms of specificity, linearity, accuracy, precision, and limit of detection/quantification. The validated method accurately quantified the TEAPLNPK content in the SM as 7.5 ± 0.2 µg/g. Our study not only identifies an indicator peptide from SM but also introduces a novel validation method, involving precursor ion ionization and quantification of specific fragments. Our findings may serve as a comprehensive workflow for the monitoring, selection, and quantification of indicator peptides from diverse food resources.
Mucins , Tandem Mass Spectrometry , Tandem Mass Spectrometry/methods , Workflow , Peptides/chemistry
Cancer is an abnormal proliferation of cells that is stimulated by cyclin-dependent kinases (CDKs) and defective cell cycle regulation. The essential agent that drive the cell cycle, CDK4/6, would be activated by proliferative signals. Activated CDK4/6 results in the phosphorylation of the neuroblastoma protein (RB) and the release of the transcription factor E2F, which promotes the cell cycle progression. CDK4/6 inhibitor (CDK4/6i) has been currently a research focus, which inhibits the CDK4/6-RB-E2F axis, thereby reducing the cell cycle transition from G1 to S phase and mediating the cell cycle arrest. This action helps achieve an anti-tumor effect. Recent research has demonstrated that CDK4/6i, in addition to contributing to cell cycle arrest, is also essential for the interaction between the tumor cells and the host immune system, i.e., activating the immune system, strengthening the tumor antigen presentation, and reducing the number of regulatory T cells (Treg). Additionally, CDK4/6i would elevate the level of PD-L1, an immunosuppressive factor, in tumor cells, and CDK4/6i in combination with anti-PD-L1 therapy would more effectively reduce the tumor growth. Our results showed that CDK4/6i caused autophagy and senescence in tumor cells. Herein, the impact of CDK4/6i on the immune microenvironment of malignant tumors was mainly focused, as well as their interaction with immune checkpoint inhibitors in affecting anti-tumor immunity.
Cyclin-Dependent Kinase 6 , Neoplasms , Humans , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 4/pharmacology , Cyclin-Dependent Kinase 6/metabolism , Cyclin-Dependent Kinase 6/pharmacology , Phosphorylation , Cell Cycle Checkpoints , Cell Cycle , Neoplasms/metabolism , Protein Kinase Inhibitors/pharmacology , Tumor Microenvironment
Cardiovascular Disease (CVD) is the leading cause of morbidity and death worldwide and has become a global public health problem. Traditional Chinese medicine (TCM) has been used in China to treat CVD and achieved promising results. Therefore, TCM has aroused significant interest among pharmacologists and medical practitioners. Previous research showed that TCM can regulate the occurrence and development of atherosclerosis (AS), ischemic heart disease, heart failure, myocardial injury, and myocardial fibrosis by inhibiting vascular endothelial injury, inflammation, oxidant stress, ischemia-reperfusion injury, and myocardial remodeling. It is well-known that TCM has the characteristics of multi-component, multi-pathway, and multitarget. Here, we systematically review the bioactive components, pharmacological effects, and clinical application of TCM in preventing and treating CVD.
BACKGROUND: Allopurinol, a xanthine inhibitor that lowers uric acid concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modiï¬cation in acute coronary syndromes (ACS). This study aimed to investigate whether allopurinol could improve coronary plaque stabilization using coronary computed tomography angiography (CCTA). METHODS: This was a prospective, single-center, randomized, double-blind clinical trial began in March 2019. A total of 162 ACS patients aged 18-80 years with a blood level of high-sensitivity C-reactive protein (hsCRP) â> â2 âmg/L were included. The subjects were randomly assigned in a 1:1 ratio to receive either allopurinol sustained-release capsules (at a dose of 0.25 âg once daily) or placebo for 12 months. The plaque analysis was performed at CCTA. The primary efficacy endpoint was the change in low-attenuation plaque volume (LAPV) from baseline to the 12-month follow-up. RESULTS: Among 162 patients, 54 in allopurinol group and 51 in placebo group completed the study. The median follow-up duration was 14 months in both groups. Compared with placebo, allopurinol therapy did not signiï¬cantly alter LAPV (-13.4 â± â3.7 â% vs. -17.8 â± â3.6 â%, p â= â0.390), intermediate attenuation plaque volume (-16.1 â± â3.0 â% vs. -16.2 â± â2.9 â%, p â= â0.992), dense calciï¬ed plaque volume (12.2 â± â13.7 â% vs. 9.7 â± â13.0 â%, p â= â0.894), total atheroma volume (-15.2 â± â3.2 â% vs. -16.4 â± â3.1 â%, p â= â0.785), remodeling index (2.0 â± â3.9 â% vs. 5.4 â± â3.8 â%, p â= â0.536) or hsCRP levels (-73.6 [-91.6-17.9] % vs. -81.2 [-95.4-47.7] %, p â= â0.286). CONCLUSIONS: Our ï¬ndings suggest that allopurinol does not improve atherosclerotic plaque stability or inï¬ammation in ACS.
Acute Coronary Syndrome , Allopurinol , Plaque, Atherosclerotic , Humans , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/drug therapy , Allopurinol/therapeutic use , C-Reactive Protein , Coronary Angiography/methods , Inflammation , Predictive Value of Tests , Prospective Studies , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over
As one of the most important diatomic molecules in the universe, the spectroscopic characterizations of C2 have attracted wide attention in various fields, such as interstellar chemistry, planetary atmospheric chemistry, and combustion. In recent years, a systematic spectroscopic study of C2 in the vacuum ultraviolet (VUV) region has been carried out in our laboratory by using the (1VUV+1'UV) resonance-enhanced multiphoton ionization method based on the combination of a tunable VUV laser source and a time-of-flight mass spectrometer. Two new electronic transition band systems have been reported, following the pioneering work of Herzberg and co-workers in 1969. In the current study, a total of 18 vibronic transition bands of C2 from the lower a3Πu state are experimentally observed in the VUV photon energy range 72000-81000 cm-1, and 6 new upper vibronic levels of 3Δg symmetry are identified, which are assigned as the v' = 0-5 vibrational levels of the 33Δg state of C2. The term energy Te of the 33Δg state is determined to be in the range of 78425-78475 cm-1 (9.724-9.730 eV) with respect to the ground X1Σg+ state, and the molecular constants such as vibrational and rotational constants are also determined, which are in reasonable agreement with those predicted by high-level ab initio theoretical calculations. Irregular vibrational energy level spacings in the 33Δg state are observed, which is tentatively attributed to the strong perturbations between the 33Δg and 23Δg states, as previously predicted by theory.
The pathogenesis of acute lung injury (ALI) is complex and it is a common critical illness in clinical practice, seriously threatening the lives of critically ill patients, for which no specific molecular marker exists and there is a lack of effective methods for the treatment of ALI. The present study aimed to investigate the mechanism of action of honeysuckle and forsythia in treatment of acute lung injury (ALI) based on network pharmacology and in vitro modeling. The active ingredients and targets of honeysuckle and forsythia were predicted using traditional Chinese medicine systems pharmacology, PubChem and Swiss Target Prediction databases, and the Cytoscape 3.7.2 software was used to construct a drug-component-potential target network. The potential targets were imported into the Search tool for recurring instances of neighboring genes) database to obtain protein-protein interactions and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Targets analysis using Database for Annotation, Visualization, and Integrated Discovery. AutoDock Vina 1.1.2 software was used for docking between key active ingredients and the target proteins to analyze the binding ability of the active ingredients to the primary targets in honeysuckle and forsythia. A total of 64 male BALB/c mice were randomly divided into control, model, positive drug (Lianhua-Qingwen capsule), honeysuckle, forsythia, honeysuckle + forsythia high-, medium- and low-dose groups. Lipopolysaccharide (LPS) was used to induced an ALI model. The lung tissues of the mice were stained with hematoxylin-eosin and the serum levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured 4 h after the LPS administration. Reverse transcription-quantitative PCR and western blotting were used to detect NF-κB mRNA and protein expression, respectively. Active ingredients of honeysuckle and forsythia acted on 265 common targets in ALI, which regulated NF-κB, tumor necrosis factor-α (TNF-α) and PI3K-AKT signaling pathway, HIF-1 signalling pathway to slow the inflammatory response in treatment of ALI. In the positive drug group, honeysuckle, forsythia group, honeysuckle + forsythia high-, medium- and low-dose groups, lung tissue damage were significantly decrease compared with the model group, and inflammatory cell infiltration was reduced. Compared with the model group, honeysuckle + forsythia groups experienced decreased damage caused by the LPS and inflammation in the lung tissues and significantly decreased TNF-α and NF-κB and MDA concentration and significantly increased the SOD and GSH-Px activities. The mechanism of the effect of honeysuckle and forsythia on ALI may be mediated by inhibition of TNF-α and NF-κB expression and the activation of antioxidant mechanisms to decrease production of pro-inflammatory cytokines in lung tissue, thus treating ALI.
Impervious surface area, due to its high energy storage and low permeability, hinders the cycles of material and energy between soil and atmosphere, thus affecting the sustainable supply of ecosystem services. It is of great practical significance to explore the influence of impervious surface areas on ecosystem services for territorial spatial planning and ecological construction projects. Correlation analysis and decoupling are used to explore the spatiotemporal variation and interaction between impervious surface areas and six ecosystem services in Hangzhou Bay from 1996 to 2018. The results show that different abundance levels of impervious surface areas are negatively correlated with ecosystem services, and with the increase of the impervious surface areas, the correlation coefficients with ecosystem services gradually decrease; there are mostly weak decoupling (79.2%) and strong decoupling (11.9%) between impervious surface areas and ecosystem services from 2007 to 2018, and the central areas that have achieved urbanization are mostly dominated by strong and weak decoupling, while the peripheral areas of the central cities are dominated by expansive recoupling and expansive connection. These results indicate that the loss of ecosystem services can be mitigated with the continuous advancement of urbanization and the enhancement of land use intensification. Finally, based on the aforementioned results, differentiated control suggestions are proposed, in order to provide insights for the sustainability of the urbanization of Hangzhou Bay and other cities with similar characteristics around the world.
Ecosystem , Urbanization , Cities , Soil , Atmosphere , China , Conservation of Natural Resources
