Predicting potential distribution of the Rhinoncus sibiricus under climatic in China using MaxEnt.

In recent years, buckwheat (Fagopyrum spp.) is being increasingly damaged by the Siberian tortoise beetle (Rhinoncus sibiricus Faust). Adults and nymphs feed on leaf tissues and caulicles, thus damaging its stems and leaves. In this study, we investigated the habits, distribution, and environmental impact of R. sibiricus using MaxEnt, an ecological niche model. Geographic information about the infestation site from previous field surveys and climatic data from 2013 to 2018 were organized and optimized using R. The impact factors were calculated using MaxEnt software. The results indicate that population fluctuations in R. sibiricus are related to changes in temperature, humidity, and their spatial distribution. Under current climatic conditions, R. sibiricus is mainly distributed in northern China, with sporadic distribution in south-western China. The values for a survival probability threshold > 0.3 were: precipitation during the wettest month (bio13), 70.31-137.56 mm; mean temperature of the coldest quarter (bio11), -15.00-0.85°C; mean temperature of the warmest quarter (bio10), 11.88-23.16°C; precipitation during the coldest quarter (biol9), 0-24.39 mm. The main factors contributing > 70% to the models were precipitation during the wettest month and coldest quarter, and mean temperature during the warmest and coldest quarters. Under both future climate models, the center of the fitness zone moves northward. Our results will be useful in guiding administrative decisions and support farmers interested in establishing control and management strategies for R. sibiricus. This study could also serve as a reference for future research on other invasive pests.

[Cell metabolomics study of ginkgo flavone aglycone combined with doxorubicin against liver cancer in synergy].

Ultra-high-performance liquid chromatography-Q exactive orbitrap tandem mass spectrometry(UHPLC-QEOrbitrap-MS/MS) was used to explore the inhibitory effect and mechanism of ginkgo flavone aglycone(GA) combined with doxorubicin(DOX) on H22 cells. The effects of different concentrations of GA and DOX on the viability of H22 cells were investigated, and combination index(CI) was used to evaluate the effects. In the experiments, control(CON) group, DOX group, GA group, and combined GA and DOX(GDOX) group were constructed. Then the metabolomics strategy was employed to explore the metabolic markers that were significantly changed after combination therapy on the basis of single medication treatment, and by analyzing their biological significance, the effect and mechanism of the anti-tumor effect of GA combined with DOX were explained. The results revealed that when 30 µg·mL~(-1) GA and 0.5 µmol·L~(-1) DOX was determined as the co-administration concentration, the CI value was 0.808, indicating that the combination of GA and DOX had a synergistic anti-tumor effect. Metabolomics analysis identified 23 metabolic markers, including L-arginine, L-tyrosine and L-valine, mostly amino acids. Compared with the CON group, 22 and 17 metabolic markers were significantly down-regulated after DOX treatment and GA treatment, respectively. Compared with the DOX and GA groups, the treatment of GA combined with DOX further down-regulated the levels of these metabolic markers in liver cancer, which might contribute to the synergistic effect of the two. Five key metabolic pathways were found in pathway enrichment analysis, including glutathione metabolism, phenylalanine metabolism, arginine and proline metabolism, ß-alanine metabolism, and valine, leucine and isoleucine degradation. These findings demonstrated that the combination of GA and DOX remarkably inhibited the viability of H22 cells and exerted a synergistic anti-tumor effect. The mechanism might be related to the influence of the energy supply of tumor cells by interfering with the metabolism of various amino acids.

The effect of intestinal flora intervention on bone development in children: A systematic review and meta-analysis.

BACKGROUND: The intestinal flora is involved in the bone development of children through a variety of mechanisms, but it remains unclear whether intervention of the intestinal flora can enhance children's bone development. METHODS: Six databases (PubMed, Web of Science, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health, and China National Knowledge Infrastructure) were searched for all English and Chinese studies published up to August 2021. Stata version 16.0 (StataCorp, College Station, TX, USA) was used. Bone mass density and biochemical markers related to bone metabolism were reported as the primary outcome, and the secondary outcomes were anthropometric parameters such as height, height Z score for age, and height velocity. Intergroup differences were determined by standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: A total of 3245 participants from 20 RCTs and 370 participants from 8 crossover trials were included in the study. Significant differences were found in bone mineral density (SMD 0.47; 95% CI, 0.28 to 0.66; p < 0.001; I2 = 0.00%) and total serum calcium (SMD 1.07; 95% CI, 0.39 to 1.74; p < 0.001; I2 = 61.9%), as well as in height Z score for age (SMD = 0.11; 95% CI, 0.00 to 0.22; P = 0.044; I2 = 0%). The overall quality of evidence ranged from moderate to very low. CONCLUSIONS: This systematic review and meta-analysis suggested that intestinal flora intervention was an effective method of improving bone mineral density, serum calcium, and height in infants, children, and adolescents. Future studies with a larger sample size and longer intervention period are needed. The protocol of this systematic review was registered in PROSPERO and the registered number was CRD42021282606.

Pharmacokinetic herb-drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma.

BACKGROUND: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. METHODS: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. CONCLUSIONS: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Effects of berberine on the growth performance, antioxidative capacity and immune response to lipopolysaccharide challenge in broilers.

This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response-related genes in lipopolysaccharide (LPS)-challenged broilers. We assigned 120 one-day-old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T-SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS-induced decreases in the mRNA expression of nuclear factor-kappa B (NF-κB), TNF-α, IL-1ß, inducible nitrite synthase and cyclooxygenase-2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF-κB signalling and the expression of inflammatory mediators.

An Incremental Version of L-MVU for the Feature Extraction of MI-EEG.

Due to the nonlinear and high-dimensional characteristics of motor imagery electroencephalography (MI-EEG), it can be challenging to get high online accuracy. As a nonlinear dimension reduction method, landmark maximum variance unfolding (L-MVU) can completely retain the nonlinear features of MI-EEG. However, L-MVU still requires considerable computation costs for out-of-sample data. An incremental version of L-MVU (denoted as IL-MVU) is proposed in this paper. The low-dimensional representation of the training data is generated by L-MVU. For each out-of-sample data, its nearest neighbors will be found in the high-dimensional training samples and the corresponding reconstruction weight matrix be calculated to generate its low-dimensional representation as well. IL-MVU is further combined with the dual-tree complex wavelet transform (DTCWT), which develops a hybrid feature extraction method (named as IL-MD). IL-MVU is applied to extract the nonlinear features of the specific subband signals, which are reconstructed by DTCWT and have the obvious event-related synchronization/event-related desynchronization phenomenon. The average energy features of α and ß waves are calculated simultaneously. The two types of features are fused and are evaluated by a linear discriminant analysis classifier. Based on the two public datasets with 12 subjects, extensive experiments were conducted. The average recognition accuracies of 10-fold cross-validation are 92.50% on Dataset 3b and 88.13% on Dataset 2b, and they gain at least 1.43% and 3.45% improvement, respectively, compared to existing methods. The experimental results show that IL-MD can extract more accurate features with relatively lower consumption cost, and it also has better feature visualization and self-adaptive characteristics to subjects. The t-test results and Kappa values suggest the proposed feature extraction method reaches statistical significance and has high consistency in classification.

Dietary leonurine hydrochloride supplementation attenuates lipopolysaccharide challenge-induced intestinal inflammation and barrier dysfunction by inhibiting the NF-κB/MAPK signaling pathway in broilers.

This study was performed to evaluate the beneficial effects of dietary leonurine hydrochloride (LH) supplementation on intestinal morphology and barrier integrity and further illuminate its underlying antioxidant and immunomodulatory mechanisms in lipopolysaccharide (LPS)-treated broilers. A total of 120 1-d-old male broilers (Ross 308) were assigned to 4 treatment groups with 6 replicates of 5 birds per cage. The experiment was designed in a 2 × 2 factorial arrangement with LH (0 or 120 mg/kg) and LPS (injection of saline or 1.5 mg/kg body weight) as treatments. On days 14, 16, 18, and 20 of the trial, broilers were intraperitoneally injected with LPS or physiological saline. Compared with the control group, LPS-challenged broilers showed impaired growth performance (P < 0.05) from day 15 to day 21 of the trial, increased serum diamine oxidase (DAO) and D-lactic acid (D-LA) levels coupled with reduced glutathione (GSH) content and total superoxide dismutase (T-SOD) activity (duodenal and jejunal mucosa), reduced malondialdehyde (MDA) content (duodenal, jejunal, and ileal mucosa), and compromised morphological structure of the duodenum and jejunum. Additionally, LPS challenge increased (P < 0.05) the mRNA expression of proinflammatory cytokine genes and reduced tight junction (TJ) protein expression in the jejunum. However, dietary LH prevented LPS-induced reductions in average daily gain (ADG) and average daily feed intake (ADFI) in broilers. It also alleviated LPS challenge-induced increases in serum DAO levels, MDA content (duodenal and jejunal mucosa), and jejunal crypt depth (P < 0.05) but reduced villus height, GSH content (jejunal mucosa), and T-SOD activity (duodenal and jejunal mucosa) (P < 0.05). Additionally, LH supplementation significantly downregulated the mRNA expression of nuclear factor (NF)-κB, cyclooxygenase-2 (COX-2), and proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and upregulated the mRNA expression of zonula occludens-1 (ZO-1) and Occludin in the jejunal mucosa induced by LPS (P < 0.05). On the other hand, LH administration prevented LPS-induced activation of the p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) and attenuated IkB alpha (IκBα) phosphorylation and nuclear translocation of NF-κB (p65) in the jejunal mucosa. In conclusion, dietary LH supplementation attenuates intestinal mucosal disruption mainly by accelerating the expression of TJ proteins and inhibiting activation of the NF-κB/MAPK signaling pathway.

The anti-inflammatory and antioxidant effects of leonurine hydrochloride after lipopolysaccharide challenge in broiler chicks.

This study was carried out to investigate the protective effects of leonurine hydrochloride (LH, from Leonurus sibiricus) on lipopolysaccharide (LPS)-stimulated broiler chicks. A total of 120 one-day-old male Ross broilers were randomly divided into 4 treatment groups with 6 replicates of 5 birds per cage. The experiment was designed as a 2 × 2 factorial arrangement with LH (0 or 120 mg/kg) and LPS (injection of saline or 1.5 mg/kg body weight) levels as treatments. On days 14, 16, 18, and 20 of the trial, broilers were intraperitoneally injected with LPS or saline. Blood, spleen, and liver samples were collected on days 21 and 28 for analysis. The results showed that dietary LH had no effect on growth performance or immunoglobulin concentrations in the serum. However, dietary LH prevented LPS-induced reductions in average daily gain and average daily feed intake in the broilers on days 15-21 of the trial (P > 0.05). Dietary LH supplementation dramatically attenuated the LPS-induced increases in the spleen index, reduced glutathione (GSH) activity (serum and liver) and total superoxide dismutase (T-SOD) activity (serum and spleen), and significantly reduced malondialdehyde (MDA) levels (serum, spleen, and liver) on days 21 and 28 (P < 0.05). Additionally, LH supplementation significantly mitigated the LPS-induced increases in the tumor necrosis factor (TNF)-α (serum and spleen), interleukin (IL)-1ß (serum, spleen and liver), IL-2 (liver), IL-6 (serum, spleen and liver), toll-like receptor 4 (TLR4) (spleen and liver), and nuclear factor (NF)-κB (spleen and liver) levels on days 21 and 28 (P < 0.05). Therefore, this study revealed that LH could downregulate the expression of proinflammatory factors, mainly by inhibiting the expression of TLR4 and the activation of NF-κB. LH may be a potential feed additive with dual efficacy as an anti-inflammatory and antioxidant agent.

Effects of Senegenin against hypoxia/reoxygenation-induced injury in PC12 cells.

OBJECTIVE: To investigate the effect and the potential mechanism of Senegenin (Sen) against injury induced by hypoxia/reoxygenation (H/R) in highly differentiated PC12 cells. METHODS: The cultured PC12 cells were treated with H/R in the presence or absence of Sen (60 µmol/L). Four groups were included in the experiment: control group, H/R group, H/R+Sen group and Sen group. Cell viability of each group and the level of lactate dehydrogenase (LDH) in culture medium were detected for the pharmacological effect of Sen. Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate. Moreover, mitochondrial membrane potential (△Ψm), reactive oxygen species (ROS) and intracellular free calcium ([Ca(2+)]i) were measured by fluorescent staining and flow cytometry. Cleaved caspase-3 and activity of NADPH oxidase (NOX) were determined by colorimetric protease assay and enzyme linked immunosorbent assay, respectively. RESULTS: Sen significantly elevated cell viability (P<0.05), decreased the leakage of LDH (P<0.05) and apoptosis rate (P<0.05) in H/R-injured PC12 cells. Sen maintained the value of △Ψm (P<0.05) and suppressed the activity of caspase-3 (P<0.05). Moreover, Sen reduced ROS accumulation P<0.05) and [Ca(2+)]i increment (P<0.05) by inhibiting the activity of NOX (P<0.05). CONCLUSION: Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and [Ca(2+)]i, thereby suppressing the mitochondrial pathway of cellular apoptosis.

Enhancing ergosterol production in Pichia pastoris GS115 by overexpressing squalene synthase gene from Glycyrrhiza uralensis.

The present study was designed to determine the effects of copy number variations (CNVs) of squalene synthase 1(SQS1) gene on the mevalonate (MVA) pathway. SQS1 gene from G. uralensis (GuSQS1) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy number of GuSQS1 were constructed. HPLC was used to assay the level of ergosterol in all transgenic P. pastoris strains containing GuSQS1. HPLC analysis showed that the contents of ergosterol in all of the transgenic P. pastoris containing GuSQS1 were higher than that in the negative control. And with the increase of copy number of GuSQS1, the content of ergosterol showed an increasing-decreasing-increasing pattern. The contents of ergosterol in 10-copy-GuSQS1 P. pastoris and 47-copy-GuSQS1 P. pastoris were significantly higher than that in the rest recombinant P. pastoris strains. In conclusion, the CNVs of GuSQS1 influence the content of secondary metabolites in the MVA pathway. The present study provides a basis for over-expressing GuSQS1 and increasing the content of glycyrrhizin in G. uralensis cultivars.

Senegenin Inhibits Hypoxia/Reoxygenation-Induced Neuronal Apoptosis by Upregulating RhoGDIα.

Neuronal apoptosis is an important event in hypoxia/reoxygenation (H/R)-induced neuronal injury. Senegenin (Sen), the predominant and most active component in Radix Polygalae root extracts, displays anti-apoptotic and anti-oxidative properties. Sen protects against H/R-induced neuronal apoptosis of highly differentiated PC12 cells and primary cortical neurons. Sen has also been investigated as a source of potential therapeutic targets. In this study, a proteomic approach was used to identify Sen-regulated proteins in PC12 cells. We found that Sen protected against H/R-induced neuronal apoptosis by upregulating RhoGDIα protein expression. The regulatory functions of RhoGDIα were investigated by knocking down RhoGDIα expression in PC12 cells using small interfering RNA (siRNA), followed by quantification of apoptosis and then altering the expression levels of apoptosis-related proteins. Our data show that after silencing RhoGDIα, the neuroprotective effects of Sen on H/R-induced PC12 cell apoptosis were absent. Furthermore, RhoGDIα silencing alleviated the Sen-mediated inhibition of the JNK pathway. Therefore, these findings indicated that Sen attenuates H/R-induced neuronal apoptosis by upregulating RhoGDIα expression and inhibiting the JNK pathway. In addition to the mechanism underlying neuroprotective effects of Sen, RhoGDIα was identified as a putative target of Sen based on a primary rat cortical neuron model of H/R-induced injury.

Refining cortical representation of sound azimuths by auditory discrimination training.

Although training-based auditory cortical plasticity in the adult brain has been previously demonstrated in multiparametric sound domains, neurochemical mechanisms responsible for this form of plasticity are not well understood. In this study, we trained adult rats to identify a target sound stimulus at a specific azimuth angle by using a reward-contingent auditory discrimination task. We found that auditory spatial discrimination training significantly enhanced representation of sound azimuths in the primary auditory cortex, as shown by sharper azimuth-selective curves and more evenly distributed best angles of cortical neurons. Training also facilitated long-term potentiation of field potentials in the primary auditory cortex induced by theta burst stimulation of the white matter. In parallel, there were significant alterations in expression levels of certain cortical GABA(A) and NMDA receptor subunits, resulting in a marked decrease in the level of GABA(A) relative to NMDA receptors. These changes in the expression profile of inhibitory and excitatory neurotransmitter receptor subunits might enhance synaptic transmission, thereby facilitating training-induced cortical plasticity in the spatial domain.

Low-power transpupillary thermotherapy combined with intravitreal triamcinolone acetonide for subfoveal choroidal neovascularization.

PURPOSE: To examine transpupillary thermotherapy combined with intravitreal triamcinolone for treatment of subfoveal choroidal neovascularization. METHODS: The clinical interventional, noncomparative, case series study included 14 patients (14 eyes) with choroidal neovascularization (age-related macular degeneration, n = 11; high myopia, n = 2; unknown reason, n = 1), who underwent transpupillary thermotherapy (75-150 mW, 60 s, 500-3,000 microm), followed by an intravitreal triamcinolone injection (10 mg). Follow-up was at least 6 months. RESULTS: Visual acuity increased by 3 lines in 3 (21%) eyes at 3 months, and in 3 (21%) eyes at 6 months of follow-up. None of the patients experienced a visual acuity loss of 3 or more lines. At the 6-month follow-up, mean visual acuity was improved by 1.36 +/- 1.16 lines. Retreatment by transpupillary thermotherapy was performed for 3 (21%) eyes at 3 months, and for 1 (7%) eye at 6 months of follow-up. CONCLUSIONS: Transpupillary thermotherapy combined with intravitreal triamcinolone may be a therapeutic option for choroidal neovascularization particularly if other treatment modalities are not available.

[The effect of retrobulbar injection with anisodamine on ocular blood velocity in anterior ischemic optic neuropathy].

OBJECTIVE: To study the effect of retrobulbar injection with anisodamine on ocular blood velocity in anterior ischemic optic neuropathy (AION). METHODS: 15 minutes before injection, 15 minutes and 1 hour after injection, the blood flow velocity in 39 cases (39 eyes) diagnosed as AION was measured and analyzed by CDI, timed average maximum velocity, peak systolic velocity, end diastolic velocity, resistance index and pulsatility index of OA, CRA and PCA were recorded. RESULTS: Compared with the normal eyes, each parameter of SPCA was statistically significant. 15 minutes and 1 hour after post ocular injection of anisodamine, every parameter examined in the experiment was increased except resistance index compared with pre-injection (P < 0.01). CONCLUSIONS: retrobulbar injection with anisodamine can effectively improve flow velocity of nasal and tempo short posterior ciliary artery and central retinal artery.