A Rat Model of Middle Cerebral Artery Occlusion/Reperfusion without Damaging the Anatomical Structure of Cerebral Vessels.

Ischemic stroke stands as the primary cause of long-term disability and mortality among adults worldwide. Animal models of ischemic stroke have significantly contributed to our understanding of its pathological mechanisms and the development of potential treatments. Presently, there are two common methods involving filament (endovascular suture) techniques to induce animal models of cerebral ischemia. However, these methods have inherent limitations, such as reduced blood perfusion to the brain, damage to the external carotid artery system, impaired food and/or water intake, and sensory dysfunction of the face. This article introduces a new method for inducing a rat ischemic stroke model without compromising the cerebral vascular anatomy. In this study, the common carotid artery (CCA) of Sprague-Dawley rats was exposed, and an incision was made. A filament was then inserted through the incision into the internal carotid artery to occlude the middle cerebral artery. After 1.5 h of induced ischemia, the occluding filament was fully removed from both the internal carotid artery and the CCA. The incision in the CCA was subsequently sutured using 11-0 microsurgical sutures under a microscope (magnification 4x). Through the utilization of microsurgical techniques to repair the CCA, this study successfully developed a unique method to induce an ischemic stroke model in rats while preserving the anatomical integrity of cerebral blood vessels.

Effect of out-of-school visual art activities on academic performance. The mediating role of socioeconomic status.

The application of visual art and other extracurricular activities to children's sustainable development is predominantly discussed in Western countries. Consequently, non-Western society could not cherish the benefit of visual art on their children's cognitive and non-cognitive skill development due to a lack of evidence that would revive the community, educators, and policy-makers' impressions about visual art activities, in addition to its amusement use. Thus, the present study adopted a cross-sectional study comprised of a large-scale survey (N = 1624) taken from the southwest part of China to assess the impact of out-of-school visual art activities on children's academic attainment across economically advantaged and disadvantaged children. Astonishingly, the study's findings shed light on current Chinese parents' dedication to purchasing out-of-school activities regardless of their social class difference; notwithstanding, lower-class parents ought to learn that spending time with their children during their activities is more beneficial. The study's implication calls for curriculum policy reform involving aesthetic education and expanding community youth centers for different extracurricular activities.

Unveiling the absorption, translocation, and metabolism of penthiopyrad in pakchoi under hydroponic and soil-cultivated conditions.

The efficient use of pesticides has long been a topic of public concern, necessitating a thorough understanding of their movement in plants. This study investigates the translocation and distribution of penthiopyrad in pakchoi plants cultivated both in hydroponic and soil-cultivated conditions. Results indicate that penthiopyrad predominantly accumulates in the roots, with concentrations of 11.3-53.9 mg/kg following root application, and in the leaves, with concentrations of 2.0-17.1 mg/kg following foliar application. The bioconcentration factor exceeded 1, with values ranging from 1.2 to 23.9 for root application and 6.4 to 164.0 for foliar application, indicating a significant role in the absorption and accumulation processes. The translocation factor data, which were <1, suggest limited the translocations within pakchoi plants. The limitation may be attributed to the hydrophobic properties of penthiopyrad (log Kow = 3.86), as evidenced by its predominant distribution in the subcellular solid fractions of pakchoi tissues, accounting for 93.1% to 99.5% of the total proportion. Six metabolites (753-A-OH, M12, 754-T-DO, M11, PCA, and PAM) were identified in this study as being formed during this process. These findings provide valuable insights into the absorption, translocation, and metabolism of penthiopyrad in pakchoi.

Optimal timing for early mobilization initiatives in intensive care unit patients: A systematic review and network meta-analysis.

OBJECTIVES: Analyse the effect of varying start times for early exercise interventions on the prevention of intensive care unit-acquired weakness. RESEARCH METHODOLOGY: We conducted a comprehensive search on PubMed, Cochrane Library, Web of Science, Embase, China Biology Medicine Disc, China National Knowledge Infrastructure, Wan Fang Database, and reference lists up to May 2023. SETTING: We systematically searched the literature for all randomized controlled trials on the effect of early mobilization in patients with critical illness. MAIN OUTCOME MEASURES: The primary outcome assessed was the incidence of intensive care unit-acquired weakness. The secondary outcomes included: the Medical Research Council Score, the Barthel Index, duration of mechanical ventilation, length of intensive care unit stay, total length of hospital stay, mortality and incidence of intensive care unit-related complications. RESULTS: The results of meta-analysis showed that compared with routine care, less than 24 hours after admission (RR = 0.44, 95 %CI: 0.28-0.68), more than 24 hours (RR = 0.33, 95 %CI: 0.16-0.67), less than 72 hours after admission (RR = 0.33, 95 %CI: 0.20-0.52) may lead to a lower incidence of intensive care unit-acquired weakness. The results of under surface cumulative ranking showed that early mobilization within 72 hours may have the lowest incidence of intensive care unit-acquired weakness (SUCRA = 81.9 %). CONCLUSIONS: The current empirical evidence from intensive care unit patients suggests that initiating mobilization protocols within 24-72 hours timeframe following admission to the intensive care unit could potentially be the most beneficial strategy to reduce the incidence of intensive care unit-acquired weakness and the related medical complications. Moreover, this strategy seems to significantly improve rehabilitation and treatment outcomes for these patients. IMPLICATIONS FOR CLINICAL PRACTICE: According to this study, medical and nursing staff in the intensive care unit have the chance to identify the most suitable timing for the implementation of early rehabilitative measures for patients. This can potentially prevent intensive care unit-acquired weakness and enhance various clinical outcomes for patients.

Combined analysis of inorganic elements and flavonoid metabolites reveals the relationship between flower quality and maturity of Sophora japonica L.

Flos Sophorae (FS), or the dried flower buds of Sophora japonica L., is widely used as a food and medicinal material in China. The quality of S. japonica flowers varies with the developmental stages (S1-S5) of the plant. However, the relationship between FS quality and maturity remains unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) and ultra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry (UPLC-ESI-Q TRAP-MS/MS) were used to analyze inorganic elements and flavonoid metabolites, respectively. A combined analysis of the inorganic elements and flavonoid metabolites in FS was conducted to determine the patterns of FS quality formation. Sixteen inorganic elements and 173 flavonoid metabolites that accumulated at different developmental stages were identified. Notably, 54 flavonoid metabolites associated with the amelioration of major human diseases were identified, and Ca, P, K, Fe, and Cu were postulated to influence flavonoid metabolism and synthesis. This study offers a novel perspective and foundation for the further exploration of the rules governing the quality of plant materials.

PE (0:0/14:0), an endogenous metabolite of the gut microbiota, exerts protective effects against sepsis-induced intestinal injury by modulating the AHR/CYP1A1 pathway.

Sepsis is known to cause damage to the intestinal mucosa, leading to bacterial translocation, and exacerbation of both local and remote organ impairments. In the present study, fecal samples were collected from both septic and healthy individuals. Analysis through 16s rRNA sequencing of the fecal microbiota revealed that sepsis disrupts the balance of the gut microbial community. Recent research has highlighted the association of lipid metabolism with disease. By analyzing the fecal metabolome, four lipid metabolites that showed significant differences between the two groups were identified: PE (O-16:0/0:0), PE (17:0/0:0), PE (0:0/14:0), and PE (12:0/20:5 (5Z, 8Z, 11Z, 14Z, 17Z)). Notably, the serum levels of PE (0:0/14:0) were higher in the healthy group. Subsequent in vitro and in vivo experiments demonstrated the protective effects of this compound against sepsis-induced intestinal barrier damage. Label-free proteomic analysis showed significant differences in the expression levels of the aryl hydrocarbon receptor (AHR), a protein implicated in sepsis pathogenesis, between the LPS-Caco-2 and LPS-Caco-2 + PE (0:0/14:0) groups. Further analysis, with the help of Discovery Studio 3.5 software and co-immunoprecipitation assays, confirmed the direct interaction between AHR and PE (0:0/14:0). In the cecal ligation and puncture (CLP) model, treatment with PE (0:0 /14:0) was found to up-regulate the expression of tight junction proteins through the AHR/Cytochrome P450, family 1, subfamily A, and polypeptide 1 (CYP1A1) pathway. This highlights the potential therapeutic use of PE (0:0/14:0) in addressing sepsis-induced intestinal barrier damage.

Establishment of health related physical fitness evaluation system for school adolescents aged 12-16 in Pakistan: a cross-sectional study.

Background: The decline in adolescent physical fitness is a significant global public health concern, and Pakistan is no exception. The country's absence of a health-related physical fitness (HRPF) evaluation system has compounded this issue. To bridge this gap, this study aims to develop a scientifically-based HRPF evaluation system for the adolescent population that meets international standards. The evaluation system identifies at-risk children and improves adolescent health outcomes, including obesity, cardiovascular and musculoskeletal disorders, chronic diseases, and psychological illnesses, through crucial physical fitness evaluation. This study specifically aims to establish an HRPF evaluation system for school adolescents aged 12-16 in Pakistan. Methods: A cross-sectional study was conducted among 2,970 school adolescents aged 12-16 years in the South Punjab, Pakistan. The study used a stratified sampling technique to select participants. The HRPF evaluation system included four components: cardiorespiratory endurance, core muscular endurance, muscular strength, and body composition. Data were collected through standardized tests and anthropometric measurements. Results: The study's results indicated that the HRPF evaluation scoring system was feasible and valid for evaluating the HRPF of school adolescents in the South Punjab region of Pakistan. The results of the evaluation system categorized participants into five groups based on their performance: excellent (6.2%), good (24.9%), medium (50.7%), poor (17%), and very poor (1.2%). Conclusion: The study establishes an HRPF evaluation system for Pakistani school adolescents. This system lays the foundation for implementing effective strategies to improve their physical health. The findings offer valuable insights to policymakers, health professionals, and educators, enabling them to promote fitness and devise impactful interventions for enhancing HRPF in this population.

Research on the integral forming process of thin walled and thick mouth seamless gas cylinders.

There is a considerable difference in wall thickness between the mouth and the cavity of thin-walled and thick-mouthed seamless gas cylinders, and the existing manufacturing processes are unable to effectively meet product requirements. To overcome such issue, a step-by-step boring-necking-spinning solution for gas cylinders was proposed, in which sufficient wall thickness is reserved for the mouth area of the cylinder blank, followed by necking-spinning to realize the overall forming of thin-walled, thick-mouthed seamless gas cylinders. The stress-strain distribution and geometric dimensional changes of gas cylinders during the spinning process were investigated by means of finite element simulation, and the effects of different process parameters on the stress and wall thickness of the bottle mouth were analyzed. Further, multi-objective optimization of the response surface model was performed using the NSGA-II algorithm to derive a set of optimal process parameters. Finally, the correctness of the simulation and optimization results was verified experimentally, and the expected geometry and optimal strain state of the gas cylinder were obtained. The newly developed processing solution represents a groundbreaking advancement in the manufacturing of thin-walled and thick-mouthed gas cylinders.

Antinociceptive effects of carbidopa levodopa on normal rats and Parkinson's disease mice.

Carbidopa levodopa is widely used to ameliorate motor symptoms of Parkinson's disease (PD) patients. Pain is one of common symptoms of PD. The aim of this experiment is to study antinociceptive effects of carbidopa levodopa on normal rats and PD mice. Rats were intragastrically treated with carbidopa levodopa and the hind paw withdrawal latency (HWL) was investigated. PD mouse model was prepared with MPTP and then the antinociceptive effects of carbidopa levodopa on PD mice were evaluated. In normal rats, the HWL to thermal stimulus was augmented after carbidopa levodopa administration (p<0.05 or p<0.01) and carbidopa levodopa increased the HWL (p<0.05 or p<0.01) to mechanical stimulus. In PD mice, carbidopa levodopa elevated the HWL of the thermal stimulus in PD mice (p<0.05). Furthermore, the HWL in the inflammatory pain of PD mice was also increased by carbidopa levodopa treatmet (p<0.01). The current findings indicate that carbidopa levodopa has an antinociceptive effects in normal rats and PD mice. The analgesic effect of carbidopa levodopa on patients with or without PD is worth studying in further research.

Responses of Zooplankton Community Pattern to Environmental Factors along the Salinity Gradient in a Seagoing River in Tianjin, China.

As the primary consumers in aquatic organisms, zooplankton play an important role in aquatic ecosystems. It is valuable for management and researchers to have an insight into the responses of zooplankton community patterns to environmental factors. In this study, RDA and variation partitioning analysis were adopted to determine the important environmental factors affecting zooplankton abundance and biomass, as well as the relative importance of different environmental factors. The findings reveal that TN (total nitrogen), WD (water depth), pH, and SAL (salinity) were all important abiotic factors shaping the zooplankton community pattern in the study area. TN affected protozoa by influencing Stentor amethystinus, while the effects of WD on copepods may have been mainly induced by the responses of Calanus sinicus and Paracyclopina nana. By inhibiting Stentor amethystinus and Vorticella lutea, pH significantly affected protozoa. In addition, Rotifera and copepods were affected by SAL mainly through the responses of Brachionus calyciflorus, Calanus sinicus, and Ectocyclops phaleratus. Importantly, fundamental alternations in the variation trends of zooplankton abundance and biomass along the salinity gradient were found when the salinity was approximately 4-5. By combining these results with the findings on phytoplankton responses to salinity in previous studies, it can be concluded that salinity may influence the river ecosystem by influencing zooplankton abundance and biomass rather than phytoplankton.

Clinical outcomes of an olive wire and external fixator versus a metallic screw in the treatment of inferior tibiofibular syndesmosis injuries in ankle fractures.

BACKGROUND: Metal screws are the most widely used in treating syndesmotic injuries, but failure and the rigidity of the screws can threaten the success of the treatment and increase the cost of care. We have provided an alternative with an olive wire and external fixator(OWEF) used for syndesmotic fixation. METHODS: A retrospective longitudinal follow-up study was conducted. From February 2011 to January 2018, 58 of 72 patients with ankle fractures and associated syndesmotic disruption were treated with either screw or OWEF fixation. The costs, complications, and clinical outcomes using Olerud-Molander score and Visual Analog score in screw and OWEF fixation group were compared. RESULTS: We found the severity of the injury, BMI of the patients and the different fixation methods were determinants of the complications and clinical outcomes. But if no malreduction of the syndesmosis was present, no difference in clinical result was detected. CONCLUSION: The OWEF method appeared to be at least equally functional and effective to screw fixation while maintaining possible lower complication rate. LEVELS OF CLINICAL EVIDENCE: Level 3.

Fabrication of Transferable and Micro/Nanostructured Superhydrophobic Surfaces Using Demolding and iCVD Processes.

Superhydrophobic surfaces possess enormous potential in various applications on account of their versatile functionalities. However, artificial superhydrophobic surfaces with ultralow solid/liquid adhesion often require complicated structure fabrication and surface fluorination processes. Here, we designed a superhydrophobic surface possessed of micro/nanoscale structures by employing facile and low-cost demolding and initiated chemical vapor deposition (iCVD) processes. The achieved micro/nanostructured superhydrophobic surface has a maximum static contact angle of ∼170°, a roll-off angle and contact angle hysteresis below 1°, ultralow solid/liquid adhesion for water droplets, and maintains excellent superhydrophobicity after exposure to strongly corrosive species, like strong acid/base and salt solutions, for 60 h. This reasonability-designed method of creating the superhydrophobic surface could provide valuable guidelines for the manufacture of transferable superhydrophobic surfaces and facilitate potential applications extending from optoelectronic devices to self-cleaning materials, such as solar cells, windows, and electronic displays.

Analysis on the stability of plankton in a food web with empirical organism body mass distribution.

The mechanism supporting the stability of complex food webs is an important, yet still controversial issue in ecology. Integrating the bioenergetic model with a natural plankton food web with empirical organism body mass distribution, we studied the effects of taxa diversity, nutrient enrichment simulation and connectance on the stability of plankton, and the underlying mechanisms. The behavior and functions of plankton with different body masses in the system were also explored. The results showed that genus richness promoted the temporal stability of community but reduced that of population. Meanwhile, the effects of taxon extinction on community biomass and temporal stability depended on the body masses of those lost taxa. Enrichment decreased phytoplankton and zooplankton community stability directly by increasing the temporal variability of biomass and indirectly by reducing taxa diversity. Enrichment preferentially caused phytoplankton taxa with the highest individual biomass to go extinct and the ones with smaller to increase in biomass. The effects, as well as the underlying mechanisms of connectance on phytoplankton and zooplankton stability were different. High connectance promoted the persistence and biomasses of both zooplankton and small-bodied phytoplankton but reduced those of larger-bodied phytoplankton. The results and methodology in this research will be helpful in understanding and analyzing the stability of plankton communities.

Clinical features and prognosis analysis of 31 cases of extramedullary plasmacytoma of the head and neck / 中华放射肿瘤学杂志

Objective:To investigate the clinical features, treatment options and prognostic factors of extramedullary plasmacytoma of the head and neck.Methods:Clinical data of 31 cases of extramedullary plasmacytoma of the head and neck treated in Eye Ear Nose and Throat Hospital of Fudan University from January 2005 to January 2020 were retrospectively analyzed. According to the involvement sites, the lesions were divided into the Waldeyer's ring involvement and non-involvement groups. The differences between two groups were compared by one-way ANOVA. The overall survival (OS) was analyzed by Kaplan-Meier method. The OS rate and local recurrence free survival (LRFS) rate between two groups were compared by log-rank test.Results:All 31 patients received radiotherapy. The median follow-up time was 98 months (7-192 months). Among them, 16 patients received radiotherapy and surgery, 10 patients received radiochemotherapy, and 2 patients received surgery and radiochemotherapy. Waldeyer's ring involvement was found in 15 patients, and Waldeyer's ring was not involved in 16 patients. The 10-year OS rate was 84.8%. Two cases showed local recurrence and 2 cases progressed to multiple myeloma. The 10-year OS rate in patients ≤55 years old was 100% vs. 67% in those >55 years old ( P=0.039). The 10-year OS rates in patients with and without Waldeyer's ring involvement were 93.3% vs. 75.2% ( P=0.031). The 10-year LRFS rate in patients with Waldeyer's ring involvement was 100% vs. 66.7% in those without Waldeyer's ring involvement ( P=0.022). The 10-year OS rate was 95% and 35.7% for patients with longest diameter of tumor ≤5 cm and >5 cm before radiotherapy, respectively ( P=0.02). Conclusions:Extramedullary plasmacytoma of the head and neck patients with longest diameter of tumor ≤5 cm obtain higher 10-year OS rate. Those with Waldeyer's ring involvement have better 10-year OS and LRFS rates.

Construction of a risk warning model for acute lung injury caused by Staphylococcus aureus infection / 中华传染病杂志

Objective:To investigate the risk factors of acute lung injury (ALI) caused by Staphylococcus aureus infection, and to construct a risk warning model. Methods:Patients with Staphylococcus aureus infection confirmed by sputum or blood culture admitted to the Affiliated Hospital of Jiangnan University from January 1, 2020 to May 10, 2022 were enrolled and divided into ALI group and non-ALI group. The age, smoking status, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), albumin, oxygenation index and other clinical data were compared between the two groups. Univariate analysis was performed by using independent sample t test and chi-square test. Binary logistic regression analysis was used to screen the independent risk factors of ALI caused by Staphylococcus aureus infection, and a risk warning model was constructed. The receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the model. Results:There were 96 cases of Staphylococcus aureus infection, including 68 cases (70.8%) in ALI group, of which 41 cases (60.3%) were positive in sputum culture and 27 cases (39.7%) were positive in blood culture. Compared with the non-ALI group, the proportion of patients aged ≥60 years in ALI group was lower (58.8%(40/68) vs 64.3%(18/28)), the proportion of smoking was higher (58.8%(40/68) vs 35.7%(10/28)), and the differences were both statistically significant ( χ2=0.76 and 0.03, respectively, both P<0.05). The levels of CRP, PCT and NLR in the ALI group were all higher than those in non-ALI group, while oxygenation index and albumin level were both lower, and the differences were all statistically significant ( t=-5.28, -3.46, -9.87, 12.83 and 3.08, respectively, all P<0.05). Binary logistic regression analysis showed that CRP (odds ratio ( OR)=1.973, 95% confidence interval (95% CI) 0.956 to 2.989), PCT ( OR=3.734, 95% CI 1.014 to 13.746), NLR ( OR=1.152, 95% CI 1.058 to 2.254) and albumin ( OR=1.527, 95% CI 1.110 to 2.102) were independent risk factors for ALI caused by Staphylococcus aureus infection. The areas under the ROC curve of CRP, PCT, NLR, albumin and the risk warning model constructed from the combination of four risk factors were 0.69, 0.81, 0.83, 0.78 and 0.93, respectively. The sensitivities were 65.14%, 89.91%, 84.40%, 56.88% and 98.17%, respectively. The specificities were 62.37%, 60.22%, 65.59%, 80.64% and 93.55%, respectively. The accuracy of the effectiveness test of the risk warning model was 84.97%. Conclusions:CRP, PCT, NLR and albumin are the independent risk factors for ALI caused by Staphylococcus aureus infection. The risk warning model based on the above factors has a good early warning effect on ALI caused by Staphylococcus aureus infection.

Mechanism of quercetin regulating p38 MAPK/NF-kB/NLRP3 signaling pathway in rats with secretory otitis media / 中国药理学通报

Aim To investigate the effect of quercetin (Que) on secretory otitis media (SOM) rats and its mechanism. Methods Forty-eight male SD rats were selected and randomly divided into control group (control), model group (model), Que group (100 mg • kg

SuanZaoRen decoction amliorates mitochondrial dysfunction of APP/PS1 mice via activating AMPK/SIRT1/PGC-1α signaling pathway / 中国药理学通报

Aim To explore the effect of Suanzaoren decoction(SZRD) on mitochondrial dysfunction in AD model of APP/PS1 mice via AMPK/SIRT1/PGC-1α signaling pathway and to reveal the possible mechanism. Methods Thirty APP/PS1 mice were randomly divided into app /PS1 group, low-dose SZRD group(L-SZRD) and high-dose SZRD group(H-SZRD). Ten C57BL/6JNju mice were set as control group(WT). Morris water maze test was used to detect the learning and memory ability of mice. Thioflavin T staining was used to observe senile plaques hippocampus. Immunohistochemistry was performed to detect the expression level of Aβ in hippocampus. Transmission electron microscope was used to observe the mitochondrial morph hology in hippocampus. Kits were employed to detect the contents of ATP and ROS in hippocampus; Western blot was employed to detect the expression levels of AMPK, p-AMPKThrK172, SIRT1, PGC-1α, NRF1, NRF2 and TFAM in hippocampus. Results Compared to the APP/PS1 group, L-SZRD and H-SZRD induced mouse cognitive impairment, reduced the deposition of senile plaques, inhibited the expression of Aβ, improved the damage of mitochondrial structure, increased the content of ATP in the hippocampus, reduced the expression level of ROS in hippocampus and increased the expression of p-AMPK-ThrK172, SIRT1, PGC-1α, NRF1, NRF2, TFAM Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.

A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice / 中国天然药物

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.