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The rapid development of insecticide resistance reinforces the urgent need to develop eco-friendly strategies for controlling Nilaparvata lugens (brown planthopper, BPH), the most destructive insect pest of rice. Both entomopathogens and RNA interference (RNAi) provide attractive alternatives to chemical insecticides. In this study, we demonstrated the synergistic potential of the combination use of entomopathogen- and RNAi-mediated approaches to control BPH. The β-1, 3-glucan recognition protein (βGRP) encoding gene NlGRP3 was identified and its potential role in immune defense was characterized in BPH. The open reading frame (ORF) of NlGRP3 is 1740 bp in length, encoding a 65.8 kDa protein with conserved CBM39 and GH16 domains that typically existed in the βGRP family members. NlGRP3 was shown to be differentially expressed across developmental stages and highly transcribed in the immune responsive tissues haemolymph and fat body. Topical infection with a fungal entomopathogen Metarhizium anisopliae could significantly up-regulate its expression level. RNAi-mediated silencing of NlGRP3 resulted in significantly decreased survival rate and increased susceptibility to fungal challenge in the fifth-instar BPH nymphs. The greatly enhanced mortality of NlGRP3-silenced BPH following fungal infection might be in part directly due to the immune suppression by down-regulating expressions of antimicrobial peptide genes and the imbalance of the bacterial community harboring in BPH body. Our results highly demonstrated that suppressing the insect innate immune defense through RNAi targeting the immune-related genes could effectively strengthen the biocontrol efficacy of fungal entomopathogens, providing clues to the combination use of RNAi and entomopathogens as a promising approach for BPH control., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Alizarin (AZ) is a natural anthraquinone with anti-inflammatory and moderate antioxidant properties., Purpose: In this study, we characterized the role of AZ in a rat model of vascular dementia (VaD) and explored its underlying mechanisms., Methods: VaD was induced by bilateral common carotid artery occlusion., Results: We found that AZ attenuated oxidative stress and improved mitochondrial structure and function in VaD rats, which led to the improvement of their learning and memory function. Mechanistically, AZ reduced transient receptor potential melastatin 2 (TRPM2) expression and activation of the Janus-kinase and signal transducer activator of transcription (JAK-STAT) pathway in VaD rats. In particular, the reduction in the expression of TRPM2 channels was the key to the attenuation of the oxidative stress-induced mitochondrial damage, which may be achieved by increasing the expression of the E3 ubiquitin ligase, Smad-ubiquitination regulatory factor 2 (Smurf2); thereby increasing the ubiquitination and degradation levels of TRPM2., Conclusion: Our results suggest that AZ is an effective candidate drug for ameliorating VaD and provide new insights into the current clinical treatment of VaD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To compare the differences in low-level physical activity (PA) and related influencing factors in patients with diabetes mellitus in China and the United Kingdom (UK). Methods: Using baseline survey data from the China Kadoorie Biobank and the UK Biobank, we analyzed the association between diabetes mellitus and low-level PA using logistic regression, with the participants' self-reported whether they had diabetes mellitus as the independent variable, and low-level PA as the dependent variable. Results: We included 509 254 Chinese adults and 359 763 British adults in the analysis. After adjusting for multiple factors, we found that both Chinese and British patients with diabetes mellitus were at elevated risk for low-level PA, with corresponding ORs (95% CIs ) of 1.15 (1.12-1.19) and 1.37 (1.32-1.41), respectively. Patients with diabetes mellitus with longer disease duration and poorer glycemic control were at greater risk of having low-level of PA. Female, rural-distributed, employed, never-smoking Chinese diabetics, and male, urban-distributed, retired/unemployed, quit-smoking British diabetics were more likely to have low-level PA. Conclusions: Chinese and British patients with diabetes mellitus were more likely to have low-level PA compared with the general population, but the risk of low-level PA for patients in both countries varied by population characteristics. Therefore, PA guidelines and intervention measures should be based on the characteristics of individuals in the target countries and regions, which could improve PA levels among patients with diabetes mellitus.

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV 1 /FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate OR s and 95% CI s for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95% CI ) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P <0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

Low-cost fish species are often used to adulterate or substitute for Atlantic salmon products, posing a serious threat to market order and public health. Hence, reliable techniques are urgently needed to detect Atlantic salmon adulteration. In this study, a precise method for identifying and quantifying adulterated Atlantic salmon with rainbow trout based on droplet digital PCR (ddPCR) testing was developed. Species-specific primers and probes were designed targeting the single-copy nuclear gene myoglobin of two salmonids. A quantitative formula for calculating the mass fraction of adulterated Atlantic salmon with rainbow trout was established based on a one-step conversion strategy, in which the DNA copy number ratios were directly transformed to meat mass fractions by introducing a fixed constant (the transfer coefficient). The dynamic range of the established ddPCR method was from 1% to 90%, with a limit of detection (LOD) of 0.2% and a limit of quantification (LOQ) of 0.8% for rainbow trout in Atlantic salmon, respectively. The quantification method demonstrated an acceptable level of repeatability and reproducibility, as the values of the relative standard deviation (RSD) for the tested meat mixtures with the known fractions were all less than 5%. Thermal and freezing treatments, as well as adding food additives within the recommended dosage limits, had no significant effect on the quantification accuracy. The method was successfully applied to detect rainbow trout adulteration in commercial raw and processed Atlantic salmon products. In comparison to real-time quantitative PCR (qPCR) testing, the established ddPCR method exhibited a higher level of stability and accuracy. Overall, the ddPCR-based quantitative method exhibited high levels of accuracy, stability, sensitivity, and practicability, suitable for applications in the routine surveillance and quality assurance of salmon products.

Diabetic cardiomyopathy (DCM) is part of the most important causes of death from cardiovascular disease. Perillaldehyde (PAE), a major component of the herb perilla, has been shown to ameliorate doxorubicin-induced cardiotoxicity, but it is unclear whether PAE exerts beneficial effects on DCM. Exploring the potential molecular mechanisms of PAE for the treatment of DCM through network pharmacology and molecular docking. The SD rat type 1 diabetes model was established by a single intraperitoneal injection of streptozotocin (60 mg/kg), the cardiac function indexes of each group were detected by echocardiography; the morphological changes, apoptosis, protein expression of P-GSK-3β (S9), collagen I (Col-Ⅰ), collagen III (Col-Ⅲ) and alpha-smooth muscle actin (α-SMA), and miR-133a-3p expression levels were detected. An DCM model of H9c2 cells was established in vitro and transfected with Mimic and Inhibitor of miR-133a-3p. The results showed that PAE ameliorated cardiac dysfunction, reduced fasting glucose and cardiac weight index, and improved myocardial injury and apoptosis in DCM rats. It reduced high glucose-induced apoptosis, promoted migration and improved mitochondrial division injury in H9c2 cells. PAE decreased P-GSK-3β (S9), Col-Ⅰ, Col-Ⅲ and α-SMA protein expression and upregulated miR-133a-3p expression levels. After miR-133a-3p Inhibitor treatment, the expression of P-GSK-3β (S9) and α-SMA expression were significantly increased; after miR-133a-3p Mimic treatment, the expression of P-GSK-3β (S9) and α-SMA decreased significantly in H9c2 cells. It suggests that the mechanism of action of PAE to improve DCM may be related to the upregulation of miR-133a-3p and inhibition of P-GSK-3β expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) remains challenging due to the lack of efficient therapy. Promoting degradation of certain cancer drivers has become an innovative therapy. The nuclear transcription factor sine oculis homeobox 1 (SIX1) is a key driver for the progression of HCC. Here, we explored the molecular mechanisms of ubiquitination of SIX1 and whether targeting SIX1 degradation might represent a potential strategy for HCC therapy. Through detecting the ubiquitination level of SIX1 in clinical HCC tissues and analyzing TCGA and GEPIA databases, we found that ubiquitin specific peptidase 1 (USP1), a deubiquitinating enzyme, contributed to the lower ubiquitination and high protein level of SIX1 in HCC tissues. In HepG2 and Hep3B cells, activation of EGFR-AKT signaling pathway promoted the expression of USP1 and the stability of its substrates, including SIX1 and ribosomal protein S16 (RPS16). In contrast, suppression of EGFR with gefitinib or knockdown of USP1 restrained EGF-elevated levels of SIX1 and RPS16. We further revealed that SNS-023 (formerly known as BMS-387032) induced degradation of SIX1 and RPS16, whereas this process was reversed by reactivation of EGFR-AKT pathway or overexpression of USP1. Consequently, inactivation of the EGFR-AKT-USP1 axis with SNS-032 led to cell cycle arrest, apoptosis, and suppression of cell proliferation and migration in HCC. Moreover, we showed that sorafenib combined with SNS-032 or gefitinib synergistically inhibited the growth of Hep3B xenografts in vivo. Overall, we identify that both SIX1 and RPS16 are crucial substrates for the EGFR-AKT-USP1 axis-driven growth of HCC, suggesting a potential anti-HCC strategy from a novel perspective., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: Accumulating evidence suggests an association between beta-cell apoptosis and the ASK1/JNK/BAX pathway. The aim of this study was to investigate the effects of a combined therapy of liraglutide and human umbilical cord mesenchymal stem cells (hUC-MSCs) on the glucose metabolism and islet beta-cell apoptosis, and further explore its relationship to the ASK1/JNK/BAX pathway., Method: Type 2 diabetes mellitus (T2DM) rat model was induced by a high-sugar and high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ) (30 mg/kg). Three days after STZ injection, diabetic rats were randomly treated with subcutaneous injection of liraglutide (200 μg/kg/12 h) for 8 weeks and or hUC-MSCs (1 × 10 6 /rat) at the first and fifth weeks. Diabetes-related physical and biochemical parameters, pancreatic histopathological changes, immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blot were used to measure the expression of apoptosis signal-regulating kinase 1 (ASK1), Jun N-terminal kinase (JNK), Bcl-2 associated X protein (BAX), and B-cell lymphoma-2 (Bcl-2)., Results: Eight weeks after liraglutide or human umbilical cord mesenchymal stem cell administration, FPG, HbA 1c , glucagon, body weight, and pancreatic ASK1, JNK, and BAX mRNA and proteins were significantly decreased, and the levels of serum C-p, INS and GLP-1, ratio of insulin positive area, and Bcl-2 expression were significantly increased in three treatment groups compared with T2DM group (P<.05)., Conclusion: Liraglutide combined with hUC-MSCs improve glucose metabolism and inhibit islet beta-cell apoptosis in a ASK1/JNK/BAX pathway-dependent manner., (© 2019 John Wiley & Sons, Ltd.)

It is of great significance to analyze habitable suitability of genuine medicinal materials for Chinese herbal medicine planting according to local environment,for medicinal resources protecting and for reasonable planning introduction. Based on GIS technology,the analytic hierarchy process was applied to analyze the spatial differentiation of habitat suitability of Angelica dahurica in Yanting county of Sichuan province. The evaluation combined local geographical environment characteristics and habitat requirements for A. dahurica planting and adopted the expert experience method to screen out the evaluation index for establishing evaluation system.With the established evaluation system,the index weight of evaluating index was determined by analytic hierarchy process and their grouping values were assigned by Delphi method. The all evaluating index were translated into index distribution maps using Arc GIS software. Using the comprehensive factor weighted evaluating model and spatial index distribution map,the evaluation was obtained by means of the overlay analysis function of Arc GIS 10. 3 software. RESULTS:: showed that A. dahurica had a wide range of suitable planting areas in Yanting county. Highly suitable areas amounted to 165. 01 km2,and mainly distributed in the low hilly area with moderate elevation and fertile soil. Moderately suitable areas amounted to 798. 92 km2 which had extensive distribution in middle and west part of the county. Marginally suitable areas amounted to 0. 33 km2,where the soil was highly viscous with high altitude and low temperature that was not conducive to the growth and development of A. dahurica. Adapting to local conditions and scientific planning plays an important role in the development of local characteristic planting industry of genuine medicinal materials.

Objective: To observe the effect of liraglutide (LIRA) in combination of umbilical cord mesenchymal stem cells (hUC-MSCs) in treating type 2 diabetes mellitus., Methods: Eligibility criteria for subjects includes: type 2 diabetes mellitus with more than 10 years duration; having been treated with secretagogues, metformin and insulin in combination with LIRA for at least 6 months; poor glycemic control [glycosylated hemoglobin A1c(HbA1c) 7%-10%]. Totally, twelve patients were enrolled and randomly divided into two groups: the group A (LIRA group, n=6) and the group B (LIRA+ hUC-MSCs group, n=6). The hUC-MSCs were transplanted through infusing of 1×10(6) cells /kg via pancreatic artery directed by interventional radiology on the first day, and followed by infusing 1×10(6) cells /kg through peripheral vein on the eighth, the fifteenth and the twenty-second day sequentially. The control subjects were infused with saline. Both groups were treated with LIRA for 24 weeks at the same period. Fasting plasma glucose(FPG), 2h postprandial plasma glucose(2hPG) and HbA1c were measured. A 75 g oral glucose tolerance test(OGTT)was performed. The early phase of C peptide(CP) secretion function(ΔCP30/ΔG30), the total amount of C peptide secretion function(AUCCP180)and Homeostasis model assessment of insulin resistance (HOMA-IR) were calculated., Results: (1) The baseline FPG, 2hPG, HbA1c, ΔCP30/ΔG30, AUCCP180 and HOMA-IR were comparable between the two groups(P>0.05). (2) Compared with subjects in group A, FPG, 2hPG and HbA1c levels were significantly decreased in subjects in group B [(8.33±0.99) mmol/L vs (6.64±0.79)mmol/L, (13.85±0.86) mmol/L vs (8.65±1.12) mmol/L, (7.82±0.31)% vs (6.82±0.53)%, P<0.05]. (3) Compared with group A, ΔCP30/ΔG30 and AUCCP180 were significantly increased, and HOMA-IR was significantly decreased in group B(0.22±0.13 vs 0.70±0.38, 12.52±5.30 vs 21.16±3.17, 9.46±4.88 vs 4.30±2.68, P<0.05)., Conclusion: LIRA treatment in combination with hUC-MSCs improves glucose metabolism and the β cell function in type 2 diabetic patients. (ClinicalTrials.gov NCT01954147).

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis and low therapeutic efficacy. Recent studies have demonstrated the therapeutic prospect of peroxisome proliferator-activated receptor-γ (PPARγ) cancer angiogenesis. However, the action mechanisms remain elusive. In the present study, by using mass spectrometry, we found that PPARγ ligand rosiglitazone (RGZ) could regulate HCC cell growth by influencing various downstream factors and pathways. Among the altered proteins, septin 2 (SEPT2) was found to exhibit oncogenic function. PPARγ overexpression could inhibit the expression of SEPT2, thus blocking the promoting effects of SEPT2 on HCC cell proliferation, invasion and its inhibitory effect on cell apoptosis. Further studies also indicated that SEPT2 promoted HCC cell growth via upregulation of matrix metalloproteinase (MMP)-2 and -9, and simultaneously inhibited the cleavage of caspase-3, -7, and -9. Interestingly, the effects of SEPT2 on the above factors could be suppressed by PPARγ overexpression, suggesting that PPARγ could inhibit HCC cell growth via regulating the expression and blocking the oncogenic function of SEPT2. Taken together, these results provide new evidence for the action mechanisms of PPARγ in carcinogenesis of HCC, and upon further investigation, PPARγ could be developed as a new target for the treatment of liver cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Objective: Rosiglitazone is a peroxisome proliferators-activated receptor gamma (PPARgamma) ligand, which inhibits tumor growth by activating PPARgamma signaling pathways. Fluorouracil (5-FU) is one of the commonly used chemotherapeutic drugs. However, patients develop drug resistance of 5-FU over time. The aim of this study was to investigate whether rosiglitazone can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms., Methods: Cell viability was measured using MTT assay. Protein expression levels were detected by Western blot analysis. Small interference RNA was utilized to knockout PPARgamma and PTEN in Hep3B cells., Results: After 48 h of treatment with 10, 20, and 40 µmol/L rosiglitazone, the viability of Hep3B cells was (78.0 ± 2.7)%, (37.3 ± 8.1)%, and (19.8 ± 2.2)%, respectively (compared with control group, P values were all < 0.001). After 48 h of treatment with 10 µmol/L 5-FU, the viability of Hep3B cells was about (82.6 ± 3.9)%. When cells were treated with 10 µmol/L 5-FU in combination with either 10, 20 or 40 µmol/L rosiglitazone, the cell viability was (51.6 ± 5.4)%, (14.8 ± 4.2)%, and (8.5 ± 0.9)%, with corresponding q value of 1.36, 1.23, and 1.19, respectively. These data suggested that the two drugs had synergic effect in inhibiting Hep3B cell growth, which was further confirmed in an in vivo mice model. Subsequent investigations showed that rosiglitazone activated PPARgamma signaling pathways and increased the expression of PTEN., Conclusions: Rosiglitazone enhances 5-FU-induced cell growth inhibition of Hep3B cells.