Palladium-catalyzed amidation of carbazole derivatives via hydroamination of isocyanates.

The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole-N-carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.

HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis.

INTRODUCTION: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. METHODS: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components. RESULTS: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. CONCLUSIONS: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

{ScnGdn} Heterometallic Rings: Tunable Ring Topology for Spin-Wave Excitations.

Data carriers using spin waves in spintronic and magnonic logic devices offer operation at low power consumption and free of Joule heating yet requiring noncollinear spin structures of small sizes. Heterometallic rings can provide such an opportunity due to the controlled spin-wave transmission within such a confined space. Here, we present a series of {ScnGdn} (n = 4, 6, 8) heterometallic rings, which are the first Sc-Ln clusters to date, with tunable magnetic interactions for spin-wave excitations. By means of time- and temperature-dependent spin dynamics simulations, we are able to predict distinct spin-wave excitations at finite temperatures for Sc4Gd4, Sc6Gd6, and Sc8Gd8. Such a new model is previously unexploited, especially due to the interplay of antiferromagnetic exchange, dipole-dipole interaction, and ring topology at low temperatures, rendering the importance of the latter to spin-wave excitations.

Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms.

BACKGROUND: No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. RESULTS: In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. CONCLUSION: These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy.

An Epidemiologic Survey and Violent Behavior Analysis of Antisocial Personality Disorder in Young Men in Chengdu.

OBJECTIVES: To investigate the epidemiological characteristics of antisocial personality disorder (ASPD) in young men in Chengdu and explore the characteristics and risks of violence. METHODS: Stratified random sampling was used to conduct a self-assessment questionnaire survey in 4 108 males aged from 18 to 34 in Chengdu, including general demographic characteristics, structured clinical interview for the diagnostic and statistical manual of mental disorders-Ⅳ axis Ⅱ disorders (SCID-Ⅱ) personality disorder screen questionnaire, violence questionnaire, psychosis screening questionnaire (PSQ), Alcohol Use Disorders Identification Test (AUDIT) and drug use. χ2 test, univariate and multivariate logistic regression were used for analysis and odds ratio (OR) was calculated. RESULTS: The positive rate of ASPD was 5.91%, which was associated with young age, unmarried, unemployment state, low educational level, violent behavior, psychotic symptoms, alcohol and drug use (P<0.05). Young men with ASPD also had a risk (P<0.05) of violence (OR was 8.51), multiple violence (OR was 16.57), injury (OR was 6.68), intentional violence (OR was 11.41), etc., the risk decreased after controlling for psychotic symptoms and substance abuse, but was still statistically significant. CONCLUSIONS: The risk of violence, severe violence and intentional violence in young men in Chengdu is high, and psychotic symptoms and substance abuse increase the risk of ASPD violence and relate characteristics.

Folate-Targeted and Oxygen/Indocyanine Green-Loaded Lipid Nanoparticles for Dual-Mode Imaging and Photo-sonodynamic/Photothermal Therapy of Ovarian Cancer in Vitro and in Vivo.

We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells and subcutaneous xenograft models. FA-OINPs were demonstrated to have great potential as superb contrast agents to enhance ultrasound and photoacoustic (US/PA) imaging We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells and subcutaneous xenograft models. FA-OINPs were demonstrated to have great potential as superb contrast agents to enhance ultrasound and photoacoustic (US/PA) imaging in vitro and in vivo. Confocal laser scanning microscopy and flow cytometry analysis verified that FA-OINPs could specifically target SKOV3 ovarian cancer cells and be endocytosed with a remarkable efficiency. Compared with other therapeutic options, FA-OINPs exhibited an excellent therapeutic outcome after exposure to laser and ultrasound. The MTT assay and flow cytometry analysis confirmed that cytotoxicity effects and apoptosis/necrosis rates were significantly increased. The fluorescence microscopy and fluorescence microplate reader detection validated that the generation of intracellular reactive oxygen species (ROS) was dramatically improved. Immunohistochemical analyses of tumor tissues demonstrated the enhanced tumor apoptosis, the decreased vascular endothelial growth factor (VEGF) and microvascular density (MVD) expression, and the decreased expression of CD68 after treatment. The presented results suggest that photo-sonodynamic/photothermal mediated FA-OINPs could provide a promising strategy for synergistic therapy in ovarian cancer with the guidance of US/PA dual-mode imaging.

Study on the levels of glycosylated lipoprotein in patients with coronary artery atherosclerosis.

BACKGROUND: The main risk factors for atherosclerosis patients are not fully explicated. The aim of this study was to analyze the levels of blood lipid and glycosylated lipoprotein in patients with coronary artery atherosclerosis and healthy individuals and to study the relationship between the glycosylated lipoprotein and atherosclerosis. METHODS: The study involved 200 patients diagnosed with myocardial infarction caused by coronary atherosclerosis as case group and 230 healthy individuals as control group. We analyzed and contrasted the levels of blood lipid and glycosylated lipoprotein between the different groups. In addition, we investigated the correlation between glycosylated low-density lipoprotein (G-LDL) and glucose levels. RESULTS: There is no statistical difference between the level of TG in case group and control group. The level of CHOL, HDL-C, and LDL-C in case group is significantly lower than that in control group (3.90 [3.23, 4.42] vs 5.16 [4.86, 5.77] [mmol/L]; 1.09 [0.83, 1.38] vs 1.46 [1.15, 1.80] [mmol/L]; 2.22 [1.68, 2.81] vs 2.95 [2.60, 3.27] [mmol/L]) (P < 0.05). The level of GLU, HbA1c, G-HDL, and G-LDL in case group is significantly higher than that in control group (7.10 [5.68, 9.27] vs 4.84 [4.68, 5.07] [mmol/L]; 6.8 [6.3, 7.4] vs 5.9 [5.6, 6.1] [%]; 30.08 [25.04, 40.17] vs 22.95 [18.14, 27.06] [ng/mL], 6.26 [4.95, 7.50] vs 3.61 [2.66, 5.15] [ng/mL]) (p < 0.05). The level of G-LDL in patients with coronary atherosclerosis was relevant with the level of GLU and HbA1c (r = 0.625, 0.706, P < 0.05), and there was no relevance with LDL-C (r = 0.331, P > 0.05). CONCLUSION: Hyperlipidemia is not an important cause of coronary atherosclerosis. High glucose levels and glycosylated lipoprotein are of high importance in the development and progression of coronary atherosclerosis.

NIR-responsive nanoplatform for pre/intraoperative image-guided carcinoma surgery and photothermal ablation of residual tumor tissue.

Local recurrence is common among patients with advanced cancer who have undergone surgery. Here, we developed a new surgical treatment for cancer based on a nanoparticle that loaded a near-infrared dye (IR780 iodide) and perfluorooctyl bromide into liposomes (NP-IR780). In an orthotopic breast cancer mouse model, NP-IR780 was demonstrated to have excellent tumor-targeting ability due to the selective tumor accumulation of IR780 iodide and the enhanced permeation and retention effect of the nanoparticle. With the excellent targeting ability, concurrent computed tomography and photoacoustic imaging were achieved for preoperative planning. In particular, NP-IR780 could serve as a tumor indicator for near-infrared fluorescence image-guided precise resection of lesions during surgery. Importantly, residual tumors could be ablated through intraoperative photothermal therapy without obvious recurrence. This work provides a theranostic strategy that significantly improved the survival of mice through pre/intraoperative image-guided tumor resection and subsequent photothermal therapy of residual lesions.

Deficiency of unc-51 like kinase 1 (Ulk1) protects against mice traumatic brain injury (TBI) by suppression of p38 and JNK pathway.

Unc-51 like autophagy activating kinase 1 (Ulk1) is a serine/threonine kinase that plays a key role in regulating autophagy processes. We attempted to investigate the effects of Ulk1 on traumatic brain injury (TBI) progression by using wild type (WT) mice and Ulk1-knockout (KO) mice suffered with or not TBI. The results were verified using LPS-treated primary astrocyte (AST). Here, Ulk1 was over-expressed in hippocampus of WT mice after TBI, as well as in lipopolysaccharide (LPS)-stimulated AST. Ulk1-deletion improved cognitive ability and hippocampus histological changes in TBI mice. Nissl and neuronal nuclei (NeuN) staining indicated that Ulk1-deletion increased the number of surviving neurons in hippocampus of TBI mice. Ulk1-ablation alleviated neuroinflammation, as evidenced by the reduced expression of hippocampus pro-inflammatory cytokines in TBI mice. TBI-induced apoptosis was also ameliorated by Ulk1-ablation, as proved by the reduced number of TUNEL-staining cells, and cleaved Caspase-3 and poly (ADP-ribose) polymerase (PARP) expressions. Moreover, Ulk1-knockout suppressed TBI-stimulated activation of astrocytes and microglia cells. Additionally, hippocampus autophagy induced by TBI was attenuated by Ulk1-knockout. Further, TBI-activated p38/c-Jun N-terminal Kinase (JNK) pathway was repressed by Ulk1-deletion in hippocampus of mice. The findings above were confirmed in LPS-stimulated AST with or without Ulk1 siRNA transfection. Intriguingly, pre-treatment of p38 or JNK activator markedly abolished the anti-inflammation, anti-apoptosis and anti-autophagy effects of Ulk1-knockdown on LPS-incubated AST. In conclusion, our results demonstrated that Ulk1 might be a potential target for developing therapeutic strategy against TBI in future.

A preliminary study of photoacoustic/ultrasound dual-mode imaging in melanoma using MAGE-targeted gold nanoparticles.

Nanoprobes are small enough to circulate within the vasculature and can reach tumour tissues through the endothelial gap, providing a new strategy for accurate tumour monitoring and imaging-guided antitumour therapy at the molecular level. Both photoacoustic and ultrasonic imaging are noninvasive tools for cancer detection via the application of nanoprobes. In this study, a polymeric multifunctional nanoparticle probe loaded with gold nanorods (Au-NRs) and liquid perfluorocarbon (perfluorinated hexane/PFH) and conjugated to a monoclonal antibody (MAGE-1 antibody) to melanoma-associated antigens (MAGE) targeting melanoma was successfully prepared by the double emulsion and carbodiimide methods as a targeted photoacoustic/ultrasound dual-mode imaging contrast agent (MAGE-Au-PFH-NPs). Cell-targeting experiments in vitro showed large amounts of MAGE-Au-PFH-NPs surrounding B16 melanoma cells in the targeted group. The photoacoustic signal in the targeted group was significantly increased, and the duration was longer than that in the untargeted group in vivo. The photoacoustic signal of the nanoprobes was enhanced with increased Au-NR concentration in the photoacoustic experiment in vitro. The enhanced signal was observed by ultrasound after 808-nm laser irradiation. A cytotoxicity and biocompatibility test showed that MAGE-Au-PFH-NPs exhibited good biological safety. The MAGE-Au-PFH-NPs can be used as a photoacoustic/ultrasound dual-mode contrast agent to lay the foundation for a promising new approach for the noninvasive targeting, monitoring and treatment of tumours.

Prognostic impact of absolute lymphocyte count/absolute monocyte count ratio and prognostic score in patients with nasal-type, extranodal natural killer/T-cell lymphoma.

Nasal-type, extranodal natural killer/T-cell lymphoma is a heterogeneous disorder with poor prognosis, requiring risk stratification in this population. The combined value of baseline absolute lymphocyte count and absolute monocyte count provided prognostic information in some malignancies. However, the evidence requires validation in extranodal natural killer/T-cell lymphoma. Aiming to investigate the prognostic significance of absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score for extranodal natural killer/T-cell lymphoma, a retrospective research was carried out. A total of 264 patients with newly diagnosed extranodal natural killer/T-cell lymphoma were analyzed in this study. The patients' absolute lymphocyte count and absolute monocyte count tested at initial diagnosis were collected. Receiver operating curve analysis showed that the optimal cut-off values for absolute lymphocyte count and absolute monocyte count were 1.0 × 109 and 0.5 × 109L-1, respectively, and for absolute lymphocyte count/absolute monocyte count ratio was 2.85. After a median follow-up of 27 months (range 1-87 months), the 3-year overall survival and progression-free survival was 75.4% and 67.6%, respectively. Patients with absolute lymphocyte count/absolute monocyte count ratio ≥ 2.85 had better 3-year overall survival and progression-free survival than those with absolute lymphocyte count/absolute monocyte count ratio <2.85 (p < 0.001). According to absolute lymphocyte count/absolute monocyte count prognostic score, significant difference has been noticed in 3-year overall survival and progression-free survival (p < 0.001) and high absolute lymphocyte count/absolute monocyte count prognostic score was associated with poorer survival. The International Prognostic Index and Korean Prognostic Index were used for prognosis and showed no significant difference. When adding absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score to the International Prognostic Index and Korean Prognostic Index model, additional prognostic information was found. These results suggest that absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score might be useful prognostic factors in extranodal natural killer/T-cell lymphoma.

[Assessing Cardiac Function of Patients with Chronic Kidney Disease using N-Terminal Pro-brain Natriuretic Peptide Precursor (NT-proBNP)].

OBJECTIVE: To determine the plasma level of N-terminal brain natriuretic peptide precursor (NT-proBNP) in patients with chronic kidney disease (CKD) and its association with cardiac function. METHODS: A total of 567 CKD patients admitted to the hospital from January 2013 to December 2014 were divided into six groups according to their estimated glomerular filtration rate. Their plasma level of NT-proBNP, renal function, and cardiac function were determined. RESULTS: The worse patients cardiac function, and the lower eGFR, the higher concentration of plasma NT-proBNP. Plasma level of NT-proBNP was negatively correlated with glomerular filtration rate (=-0.529, P<0.01). The receiver operating characteristic curves generated a cutoff NT-proBNP value of 119.5 ng/L, 168.5 ng/L, 300.5 ng/L, 1 019.5 ng/L, 2 777.5 ng/L, and 3 640.5 ng/L, respectively, for diagnosing cardiac failure in the six groups, respectively. CONCLUSION: NT-proBNP is affected by renal function, which can be used for diagnosing cardiac failure in patients with CKD.

[The Targeted Regulating Role of Has-miR-577 and Has-miR-583 on Gene FGF-21 Detected by the Dual Luciferase Reporter System.]

OBJECTIVES: To determine the targeted regulating role of has-miR-577 and has-miR-583 on the expression of fibroblast growth factor 21 (FGF-21) based on a constructed luciferase reporter FGF-21 gene vector. METHODS: The site of has-miR-577 and has-miR-583 target genes FGF-21 were predicted by the bioinformatics analyzing tools online.FGF-21 gene fragments,combined with has-miR-577 or has-miR-583 sequences and mutant sequences,were designed and synthesized.The wild type (psiCHECK2-FGF-21) and mutant (psiCHECK2-FGF-21-mut) luciferase reporter gene carriers were constructed.The relevant plasmids [hsa-miR-577mimics,hsa-miR-583 mimics or miR negative control (miR-NC)] and luciferase reporter gene carrier (wild type or mutant ) were co-transfected into 293T cells.The luciferase reporter system was used to detect the luciferase activity.The effects of has-miR-577 and has-miR-583 on the expression of FGF-21 were observed. RESULTS: The double enzyme electrophoresis and sequencing results showed that the gene fragment size and sequences of the wild type (psiCHECK2-FGF-21) and mutant (psiCHECK2-FGF-21-mut) carriers met expectations of the experiment.The luciferase assays revealed that has-miR-577 and has-miR-583 significantly diminished luciferase activity from the reporter vector containing 3'UTR of FGF-21 (P<0.05),whereas no suppression of luciferase activity was found in the mutant (psiCHECK2-FGF-21-mut). CONCLUSIONS: FGF-21 gene can be targeted by has-miR-577 and has-miR-583.

[Risk stratification of diabetic chronic kidney disease using eGFR equations].

OBJECTIVE: To compare different eGFR equations for risk stratification of diabetic chronic kidney disease. METHODS: A total of 601 diabetic patients participated in the study. Data about the patient serum cystatin C (Cys-C), blood urea nitrogen (BUN), creatinine (Scr), uric acid (UA), glycosylated hemoglobin (HbAlc), and urinary albumin creatinine ratio (ACR) were extracted. Simplified MDRD formula were used for calculating glomerular filtration rate (eGFR) using eGFR-EPlcrea, eGFR-EPIcys and eGFR-EPIcrea-cys. The patients were divided into three groups according to their urine ACR. Comparisons were made between the groups of patients in Cys-C, BUN, UA, eGFR and Scr. RESULTS: There were significant differences (P < 0.05) in Cys-C, eGFR-MDRD, eGFR EPIcrea, eGFR-EPIcys, and eGFR-EPIcrea-cys among the groups of patients. The different equations for risk stratification produced different distributions of patients among the three groups. Significant differences appeared among the groups in the distribution of patients using eGFR-MDRD (P < 0.05), eGFR-EPIcrea (P = 0.000) and eGFR-EPIcys (P < 0.05) and indication for stratification. No significant differences were found in the distribution of patient among the three groups (P > 0.05) using GFR-MDRD, eGFR-EPIcrea and eGFR-EPIcrea-cys as an indication for stratification. In low risk patients, eGFR-MDRD was higher than other eGFR (P < 0.05). In medium and high-risk patients, eGFR-MDRD and eGFR-EPIcrea were higher than eGFR-EPIcys and eGFR-EPIcrea-cys. In very high-risk patients, the four eGFR did not show differences. CONCLUSION: The performance of different eGFR equations differs in risk stratification of diabetic chronic kidney disease. In low-risk patients, MDRD equation may overestimate GFR level.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice.

Introduction: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR. Methods: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition. Results: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group. Discussion: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

Ginkgo biloba extract and ginkgolide antiarrhythmic potential by targeting hERG and ICa-L channel.

We investigated the effects of Ginkgo biloba extract (GBE) and ginkgolide (GLD) on human ether-a-go-go-related gene (hERG)-encoded K(+) channels and its underlying mechanisms in the hERG-HEK293 cell line by determining GBE- and GLD-induced changes in action potential duration (APD), L-type calcium currents (ICa-L), and the intracellular calcium concentration ([Ca(2+)]i) in guinea-pig ventricular myocytes. hERG currents, APD and ICa-L were recorded using the whole-cell patch clamp technique, the [Ca(2+)]i was examined by an immunofluorescence experiment. In the present study, we found that a low concentration of GBE (0.005 mg/ml) increased hERG currents, but the high concentration of GBE (from 0.05 to 0.25 mg/ml) reduced hERG currents. GLD reduced hERG currents in a concentration-dependent manner (from 0.005 to 0.25 mg/ml). Both GBE and GLD altered kinetics of the hERG channel. GBE accelerated the activation of hERG channels without changing the inactivation curve, but reduced the time constant of inactivation; GLD did not shift the activation or the inactivation curve, but only reduced the time constant of inactivation. Both GBE and GLD shortened the APD, inhibited the ICa-L currents, and decreased the [Ca(2+)]i in isolated guinea-pig ventricular myocytes. The results indicate that GBE and GLD can prevent ischemic arrhythmias and have an antiarrhythmic effect potential via inhibition of IKr and ICa-L currents.