Protective effect of theaflavins on neuron against 6-hydroxydopamine-induced apoptosis in SH-SY5Y cells

Theaflavins, the oxidation products of tea polyphenols are important biologically active components of black tea. 6-hydroxydopamine is a pro-parkinsonian neurotoxin. Theaflavins could inhibit the auto-oxidation of 6-hydroxydopamine in a dose-dependent manner from 0.5 µg/ml to 25 µg/ml. Here we investigated the protective effect of theaflavins on 6-hydroxydopamine induced SH-SY5Y cells against apoptosis (within this concentration range). It was found that pretreating SH-SY5Y cells with 0.5 µg/ml of theaflavins prevented 6-hydroxydopamine-induced loss of cell viability, condensed nuclear morphology, attenuated 6-hydroxydopamine-induced apoptosis, decrease of mitochondrial membrane potential and the increase of intracellular nitric oxide levels. Our results indicated that theaflavins had protective effect against 6-hydroxydopamine induced apoptosis at low concentrations, possibly through inhibition of reactive oxygen species and nitric oxide production

Pharmacokinetics, tissue distribution, and antitumor activity of a novel compound, NY-2, in non-small cell lung cancer

Introduction: ZLDI-8, which has a relatively strong antitumor activity, is an inhibitor of ADAM-17 and acts on the Notch signaling pathway. To further optimize its structure and improve its activity, a series of derivatives of ZLDI-8 was synthesized. NY-2 was the most effective derivative based on preliminary activity screening in vitro, with no obvious toxicity after administration in vivo.Method: The study aimed to determine the pharmacokinetics, tissue distribution, hepatotoxicity, nephrotoxicity, and antitumor activity of compound NY-2 on non-small cell lung cancer (NSCLC) in vitro and in vivo.Results: The in vivo pharmacokinetics parameters of NY-2 were better than those of ZLDI-8. The tissue distribution analysis showed that tail vein injection of 6 mg/kg of NY-2 in rats resulted in the highest concentration in the lung, so we hypothesized that NY-2 might be effective in the treatment of non-small cell lung cancer. In vitro assays showed that NY-2 significantly inhibited tumor colony formation, invasion, and migration and increased LDH activity and apoptosis in a concentration-dependent manner in non-small cell lung cancer cells. NY-2 also inhibited the formation of lung metastases without significant toxicity to major organs in nude mice.Conclusion: Compared with the parent compound, ZLDI-8, the activity and safety of NY-2 were higher. NY-2 acts on ADAM17 and simultaneously affects the downstream Notch1 and integrinβ1 signaling pathways resulting in antitumor activity. Thus, NY-2 could be a potential antitumor agent, inhibiting the organization and development of non-small cell lung cancer

Impacts of climate change on climatically suitable regions of two invasive Erigeron weeds in China

IntroductionErigeron philadelphicus and Erigeron annuus are two ecologically destructive invasive plants from the Asteraceae family. Predicting the potential distribution pattern of two invasive alien Erigeron weeds can provide a scientific basis for prevent the further spread of these two weeds in China under climate change.MethodsBased on historical occurrence datasets and environmental variables, we optimized a MaxEnt model to predict the potential suitable habitats of E. philadelphicus and E. annuus. We also analyzed the shifts of distribution centroids and patterns under climate change scenarios.ResultsThe key variables that affect the potential geographical distribution of E. annuus and E. philadelphicus, respectively, are temperature seasonality and precipitation of the driest month. Moreover, topsoil sodicity and topsoil salinity also influence the distribution of E. philadelphicus. Under climate change, the overall suitable habitats for both invasive alien Erigeron weeds are expected to expand. The potential geographical distribution of E. annuus exhibited the highest expansion under the SSP245 climate scenario (medium forcing scenarios), whereas E. philadelphicus had the highest expansion under the SSP126 climate scenario (lower forcing scenarios) globally. The future centroid of E. annuus is projected to shift to higher latitudes specifically from Hubei to Hebei, whereas E. philadelphicus remains concentrated primarily in Hubei Province. The overlapping suitable areas of the two invasive alien Erigeron plants mainly occur in Jiangsu, Zhejiang, Fujian, Jiangxi, Hunan, Guizhou, and Chongqing, within China.DiscussionClimate change will enable E. annuus to expand into northeastern region and invade Yunnan Province whereas E. philadelphicus was historically the only suitable species. E. annuus demonstrates a greater potential for invasion and expansion under climate change, as it exhibits higher environmental tolerance. The predictive results obtained in this study can serve as a valuable reference for early warning systems and management strategies aimed at controlling the spread of these two invasive plants

Analysis of Genomic and Immune Intratumor Heterogeneity in Linitis Plastica via Multiregional Exome and T-Cell Receptor Sequencing

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi-cancers. IHC using antibodies against CD4, CD8, and PD-L1 demonstrated scant T-cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T-cell clones shared across tumor regions in any of the patients, while over 94% of T-cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi-regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T-cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma

The harlequin ladybird, Harmonia axyridis: global perspectives on invasion history and ecology

The harlequin ladybird, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), is native to Asia but has been intentionally introduced to many countries as a biological control agent of pest insects. In numerous countries, however, it has been introduced unintentionally. The dramatic spread of H. axyridis within many countries has been met with considerable trepidation. It is a generalist top predator, able to thrive in many habitats and across wide climatic conditions. It poses a threat to biodiversity, particularly aphidophagous insects, through competition and predation, and in many countries adverse effects have been reported on other species, particularly coccinellids. However, the patterns are not consistent around the world and seem to be affected by many factors including landscape and climate. Research on H. axyridis has provided detailed insights into invasion biology from broad patterns and processes to approaches in surveillance and monitoring. An impressive number of studies on this alien species have provided mechanistic evidence alongside models explaining large-scale patterns and processes. The involvement of citizens in monitoring this species in a number of countries around the world is inspiring and has provided data on scales that would be otherwise unachievable. Harmonia axyridis has successfully been used as a model invasive alien species and has been the inspiration for global collaborations at various scales. There is considerable scope to expand the research and associated collaborations, particularly to increase the breadth of parallel studies conducted in the native and invaded regions. Indeed a qualitative comparison of biological traits across the native and invaded range suggests that there are differences which ultimately could influence the population dynamics of this invader. Here we provide an overview of the invasion history and ecology of H. axyridis globally with consideration of future research perspectives. We reflect broadly on the contributions of such research to our understanding of invasion biology while also informing policy and people

Population mixing mediates the intestinal flora composition and facilitates invasiveness in a globally invasive fruit fly

Abstract Background Changes in population heterozygosity and genetic diversity play important roles in mediating life history traits of organisms; these changes often lead to phenotypic evolution in offspring, which become superior to their parents. In the present study, we examined phenotypic differentiation, the intestinal microbiome composition, and metabolism shift in the oriental fruit fly (Bactrocera dorsalis) by comparing an inbred (monophyletic) original population and an outbred (mixed) invasive population. Results The results showed that the outbred population of B. dorsalis had significantly higher biomass, adult longevity, and fecundity than the inbred population. Additionally, intestinal microflora analysis revealed that both Diutina rugosa and Komagataeibacter saccharivorans were significantly enriched in the outbred population with higher genetic heterozygosity. D. rugosa enrichment altered amino acid metabolism in the intestinal tract, and supplementing essential amino acids (e.g. histidine and glutamine) in the diet led to an increase in pupal weight of the outbred population. Additionally, transcriptome analysis revealed that the HSPA1S gene was significantly downregulated in the outbred population. HSPA1S was involved in activation of the JNK-MAPK pathway through negative regulation, caused the upregulation of juvenile hormone (JH), and led to an increase in biomass in the outbred flies. Conclusion In conclusion, the outbred population had an altered intestinal microbe composition, mediating metabolism and transcriptional regulation, leading to phenotypic differentiation; this may be a potential mechanism driving the global invasion of B. dorsalis. Thus, multiple introductions could lead to invasiveness enhancement in B. dorsalis through population mixing, providing preliminary evidence that changes in the intestinal microbiome can promote biological invasion. Video Abstrac