IMPACT OF CLIMATE CHANGE ON COASTAL ECOSYSTEM AND OUTDOOR ACTIVITIES: A COMPARATIVE ANALYSIS AMONG FOUR LARGEST COASTLINE COVERING COUNTRIES.

Climate change and coastal ecosystems have become challenging subjects for world sustainability. Humans, animals, and other ocean habitats are primarily affected by the harmful changes in climate. Coastal ecosystems support biodiversity and a wide range of species that serve as habitats for many commercially important fish species and enhance human activities in coastal areas. By engaging in coastal outdoor activities, individuals can experience numerous physical and mental health benefits, foster environmental awareness. This study provided valuable insights into the importance of coastal outdoor activities and their potential to improve our quality of life. This study undertook a challenging subject where we graphically and econometrically analyze the relationship and linkages among coastal indicators with other climate-concerning factors. The study comprises the ordinary regression and comparative analysis among the four largest coastline countries in the world. The study took a sample from Canada, Indonesia, Norway, and the Russian Federation from 1990 to 2022. The data is selected on a convenient basis. Results declared that each country has its unique challenges and opportunities in mitigating adverse climate change and retaining a sustainable coastal ecosystem. The study surprisingly revealed that climate change insignificantly affects the coastal ecosystem in Indonesia and the Russian Federation while it inversely affects the coastal ecosystem in Canada and Norway, showed that climate change on average declines coastal production by 0.0041922 and 0.0261104 in Canada and Norway respectively. The detailed review is given in the results section; however, the pooling analysis proved that at the aggregate level, a one percent increase in climate change caused a 0.02266-tonne decline in coastal ecosystems in the four largest coastline nations. There is a need for policies tend to increase CAP activities by implementing practical marine protected areas. Furthermore, scientific research and monitoring will be beneficial in restoring coastal sustainability.

Investigating the efficacy and mechanisms of Jinfu'an decoction in treating non-small cell lung cancer using network pharmacology and in vitro and in vivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfu'an Decoction (JFAD) is a traditional Chinese decoction used in lung cancer treatment to improve patient quality of life and survival. Previous research has established that JFAD has a significant therapeutic effect on non-small cell lung cancer (NSCLC), although the underlying molecular mechanisms have not been largely underexplored. AIM OF THE STUDY: We used network pharmacology to identify the putative active ingredients of JFAD and conducted experimental studies to determine the potential molecular mechanism of JFAD in NSCLC treatment. MATERIALS AND METHODS: The herbal components in JFAD-containing serum were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), and targets associated with the anti-lung cancer metastasis effects of JFAD were retrieved from various databases. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Next, the protein-protein interactions network and the "JFAD-Chemical Component-Target-KEGG Pathway" network were constructed. The network pharmacology findings were confirmed by in vitro and in vivo experiments. In vitro experiments were conducted to assess cell viability by CCK8 assay, cell cycle analysis by propidium iodide (PI) assay, and migration and invasion ability of cells by the transwell assay. In vivo experiments were performed to assess the efficacy of JFAD on the tumor by observing the growth of transplanted tumor models in nude mice and evaluated by in vivo bioluminescence imaging. Moreover, we assessed the effect of JFAD on the PI3K/Akt signaling pathway and proteins of Lumican, p120ctn, and specific RhoGTP enzyme family members (RhoA, Rac1, and RhoC) by Western Blot and immunohistochemistry. RESULTS: 32 herbal components were identified in the JFAD-containing serum, which potentially acted on 229 targets related to lung cancer metastasis. Network pharmacology results suggested that JFAD may treat lung cancer metastasis by targeting the PI3K/Akt pathway via regulating multiple core targets. Our experiments showed that JFAD suppressed the proliferation of A549 cells in vitro, induced cell cycle arrest, and reduced the migration and invasion ability of A549 cells. Our in vivo study revealed that JFAD inhibited tumor growth in a nude mouse model. Additionally, we found that JFAD could downregulate the expression of the PI3K/Akt pathway and affect the expression of Lumican, p120ctn, and specific RhoGTPase family members. CONCLUSIONS: In conclusion, through network pharmacology, we have unveiled the underlying mechanisms that link the various components, targets, and pathways influenced by JFAD in the context of lung cancer metastasis. Our experimental results suggest that the oncostatic effects of JFAD may be achieved by upregulating the expression of Lumican/p120ctn and downregulating the levels of specific RhoGTPase family members, which in turn block the PI3K/Akt signaling pathway.

Endothelial progenitor cells in pregnancy-related diseases.

Placental neovascularization plays a crucial role in fetomaternal circulation throughout pregnancy and is dysregulated in several pregnancy-related diseases, including preeclampsia, gestational diabetes mellitus, and fetal growth restriction. Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that differentiate into mature endothelial cells, which influence vascular homeostasis, neovascularization, and endothelial repair. Since their discovery in 1997 by Asahara et al., the role of EPCs in vascular biology has garnered a lot of interest. However, although pregnancy-related conditions are associated with changes in the number and function of EPCs, the reported findings are conflicting. This review discusses the discovery, isolation, and classification of EPCs and highlights discrepancies between current studies. Overviews of how various diseases affect the numbers and functions of EPCs, the role of EPCs as biomarkers of pregnancy disorders, and the potential therapeutic applications involving EPCs are also provided.

Salvianolic acid F suppresses KRAS-dependent lung cancer cell growth through the PI3K/AKT signaling pathway.

BACKGROUND: KRAS mutation is a common driver of NSCLC, and there is a high proportion of lung cancer patients with KRAS G12C and G12D mutation. KRAS was previously considered an "undruggable" target, but the first KRAS G12C mutation-targeted drug AMG510, entered the market in 2021. However, treatments for G12D mutant tumors remain to be discovered. Salvianolic acid F (SalF), a monomer derived from the traditional Chinese medicine Salvia miltiorrhiza (SM), and KRAS had high binding affinity, especially for KRAS G12D. There is an urgent need to investigate effective and safe novel targeted therapies against KRAS G12D-driven NSCLC. METHODS: To evaluate the anticancer effect of SalF, we used KRAS-overexpressing lung cancer cells in vitro, a subcutaneous transplant tumor model, and KRAS G12D mice model in vivo. Then, the binding effect of SalF and KRAS was investigated using molecular docking, proteolytic assays and protein thermal shift assays. More critically, the PI3K/AKT signaling pathway in the lung was investigated utilizing RT-qPCR and Western Blotting. RESULTS: This is the first study to evaluate the anticancer effect of SalF on KRAS-overexpressing lung cancer cells or KRAS G12D lung tumors in vivo. We demonstrated that SalF inhibits OE-KRAS A549 cell migration, proliferation and promotes apoptosis in vitro. In addition, we used a subcutaneous transplant tumor model to show that SalF suppresses the growth of lung cancer cells in vivo. Interestingly, our group found that SalF was strongly bound to G12D and could decrease the stability and promoted the degradation of the KRAS G12D mutant through molecular docking, proteolytic assays and protein thermal shift assays. Further research demonstrated that in the KrasG12D mice model, after SalF treatment, the number and size of mouse lung tumors were significantly reduced. More importantly, SalF can promote apoptosis by inhibiting downstream PI3K/AKT signaling pathway activation. CONCLUSION: SalF activated apoptosis signaling pathways, suppressed anti-apoptotic genes, and inhibited lung cancer cell growth. These datas suggested that SalF could effectively inhibit the growth of lung tumors with KRAS G12D mutation. SalF may be a novel inhibitor against KRAS G12D, providing a strong theoretical basis for the clinical treatment of lung cancer with KRAS mutations.

Lipid metabolism as a target for cancer drug resistance: progress and prospects.

Cancer is the world's leading cause of human death today, and the treatment process of cancer is highly complex. Chemotherapy and targeted therapy are commonly used in cancer treatment, and the emergence of drug resistance is a significant problem in cancer treatment. Therefore, the mechanism of drug resistance during cancer treatment has become a hot issue in current research. A series of studies have found that lipid metabolism is closely related to cancer drug resistance. This paper details the changes of lipid metabolism in drug resistance and how lipid metabolism affects drug resistance. More importantly, most studies have reported that combination therapy may lead to changes in lipid-related metabolic pathways, which may reverse the development of cancer drug resistance and enhance or rescue the sensitivity to therapeutic drugs. This paper summarizes the progress of drug design targeting lipid metabolism in improving drug resistance, and providing new ideas and strategies for future tumor treatment. Therefore, this paper reviews the issues of combining medications with lipid metabolism and drug resistance.

Modeling the protein binding non-linearity in population pharmacokinetic model of valproic acid in children with epilepsy: a systematic evaluation study.

Background: Several studies have investigated the population pharmacokinetics (popPK) of valproic acid (VPA) in children with epilepsy. However, the predictive performance of these models in the extrapolation to other clinical environments has not been studied. Hence, this study evaluated the predictive abilities of pediatric popPK models of VPA and identified the potential effects of protein binding modeling strategies. Methods: A dataset of 255 trough concentrations in 202 children with epilepsy was analyzed to assess the predictive performance of qualified models, following literature review. The evaluation of external predictive ability was conducted by prediction- and simulation-based diagnostics as well as Bayesian forecasting. Furthermore, five popPK models with different protein binding modeling strategies were developed to investigate the discrepancy among the one-binding site model, Langmuir equation, dose-dependent maximum effect model, linear non-saturable binding equation and the simple exponent model on model predictive ability. Results: Ten popPK models were identified in the literature. Co-medication, body weight, daily dose, and age were the four most commonly involved covariates influencing VPA clearance. The model proposed by Serrano et al. showed the best performance with a median prediction error (MDPE) of 1.40%, median absolute prediction error (MAPE) of 17.38%, and percentages of PE within 20% (F20, 55.69%) and 30% (F30, 76.47%). However, all models performed inadequately in terms of the simulation-based normalized prediction distribution error, indicating unsatisfactory normality. Bayesian forecasting enhanced predictive performance, as prior observations were available. More prior observations are needed for model predictability to reach a stable state. The linear non-saturable binding equation had a higher predictive value than other protein binding models. Conclusion: The predictive abilities of most popPK models of VPA in children with epilepsy were unsatisfactory. The linear non-saturable binding equation is more suitable for modeling non-linearity. Moreover, Bayesian forecasting with prior observations improved model fitness.

Multi-omics analysis reveals the prognostic and tumor micro-environmental value of lumican in multiple cancer types.

Background: Lumican (LUM), a proteoglycan of the extracellular matrix, has been reported to be involved in the regulation of immune escape processes, but the data supporting this phenomenon are not sufficient. In this study, we aimed to explore the links among LUM expression, survival, tumor microenvironment (TME), and immunotherapy in 33 cancer types. Methods: Data from several databases, such as UCSC Xena, GTEx, UALCAN, HPA, GEPIA2, TISIDB, PrognoScan, TIMER2, and GEO, as well as published studies, were used to determine the relationship between LUM expression and clinical features, TME, heterogeneity, and tumor stemness. Results: The expression of LUM was statistically different in most tumors versus normal tissues, both at the RNA and protein expression levels. High expression of LUM was typically associated with a poor prognosis in tumors. Additionally, immune scores, six immune cells, four immunosuppressive cells, cancer-associated fibroblasts (CAFs)-associated and immunosuppressive factors, tumor mutation burden (TMB), microsatellite instability (MSI), DNAss, and RNAss were all significantly associated with LUM. Among them, LUM expression displayed a significant positive correlation with CAFs and their factors, and exhibited immunosuppressive effects in six independent immunotherapy cohorts. Conclusion: Multi-omics analysis suggests that LUM may have been a prognostic marker, contributed to immunosuppression in the TME, and decreased the effectiveness of immune checkpoint inhibitors.

Clinical diagnostic value of amino acids in laryngeal squamous cell carcinomas.

Background: Early diagnosis and treatment can improve the survival rates of patients with laryngeal squamous cell carcinoma (LSCC). Therefore, it is necessary to discover new biomarkers for laryngeal cancer screening and early diagnosis. Methods: We collected fasting plasma from LSCC patients and healthy volunteers, as well as cancer and para-carcinoma tissues from LSCC patients, and performed quantitative detection of amino acid levels using liquid chromatography-mass spectrometry. We used overall analysis and multivariate statistical analysis to screen out the statistically significant differential amino acids in the plasma and tissue samples, conducted receiver operating characteristic (ROC) analysis of the differential amino acids to evaluate the sensitivity and specificity of the differential amino acids, and finally determined the diagnostic value of amino acids for laryngeal cancer. Additionally, we identified amino acids in the plasma and tissue samples that are valuable for the early diagnosis of laryngeal cancer classified according to the tumor-node-metastasis (TNM) classification. Results: Asparagine (Asp) and homocysteine (Hcy) were two amino acids of common significance in plasma and tissue samples, and their specificity and sensitivity analysis showed that they may be new biomarkers for the diagnosis and treatment of LSCC. According to the TNM staging system, phenylalanine (Phe) and isoleucine (Ile) were screened out in the plasma of LSCC patients at early (I and II) and advanced (III and IV) stages; ornithine hydrochloride (Orn), glutamic acid (Glu), and Glycine (Gly) were selected in the tissue. These dysregulated amino acids found in LSCC patients may be useful as clinical biomarkers for the early diagnosis and screening of LSCC.

RBFOX2 confers tumor growth by PI3K/AKT and MAPK signaling in gastric cancer.

RNA-binding Fox (RBFOX)2, a member of a family of RNA-binding proteins, is well known as a regulator of alternative pre-mRNA splicing. However, its possible role in gastric cancer is unknown. In this study, we investigated the biologic role and clinical significance of RBFOX2 in gastric cancer growth and elucidated its underlying molecular mechanisms. We found that RBFOX2 was highly expressed in gastric cancer cell lines and tumor tissue compared with the adjacent nontumor tissue. We also found that RBFOX2 overexpression was correlated with poor overall survival in patients with gastric cancers. Multivariate survival analyses revealed that higher RBFOX2 expression was an independent prognostic factor for the overall survival of patients with gastric cancers. Suppression of RBFOX2 by shRNA inhibited gastric cancer cell proliferation, colony formation and induced apoptosis. Mechanism studies revealed that these effects were achieved through the simultaneous modulation of multiple signaling pathways. Knockdown of RBFOX2 expression by shRNA markedly inhibited the phosphorylation of phosphatidylinositol 3-hydroxy kinase, threonine kinase and extracellular signal-regulated kinase and Jun N-terminal kinases proteins. In contrast, the ectopic expression of RBFOX2 had the opposite effects. Moreover, RBFOX2 knockdown also induced the cleavage of caspase-3 and caspase-9 proteins. Collectively, these results demonstrate that RBFOX2 plays a critical role in regulating gastric cancer cell proliferation and survival and may be a potential prognostic biomarker and therapeutic target for gastric cancer.

Clip-SP1 cleavage activates downstream prophenoloxidase activating protease (PAP) in Plutella xylostella.

Melanization is a component of the humoral immune defense of insects and is induced by serine protease-mediated phenoloxidase (PO) catalysis. Prophenoloxidase (PPO) in the midgut of Plutella xylostella is activated by the CLIP domain serine protease (clip-SP) in response to Bacillus thuringiensis (Bt) infection, but the detailed signaling cascade following this activation is unknown. Here, we report that activation of clip-SP enhances PO activity in the P. xylostella midgut by cleaving three downstream PPO-activating proteases (PAPs). First, the expression level of clip-SP1 was increased in the midgut after Bt8010 infection of P. xylostella. Then, purified recombinant clip-SP1 was able to activate three PAPs - PAPa, PAPb and PAP3 - which in turn enhanced their PO activity in the hemolymph. Furthermore, clip-SP1 showed a dominant effect on PO activity compared to the individual PAPs. Our results indicate that Bt infection induces the expression of clip-SP1, which is upstream of a signaling cascade, to efficiently activate PO catalysis and mediate melanization in the midgut of P. xylostella. And it provides a basis for studying the complex PPO regulatory system in the midgut during Bt infection.

Enhanced resistance to Bacillus thuringiensis Cry1Ac toxin mediated by the activation of prophenoloxidase in a cosmopolitan pest.

Plutella xylostella has evolved resistance to Bacillus thuringiensis Cry1Ac toxin over a long evolutionary period. Enhanced immune response is an important factor in insect resistance to a variety of insecticides, and whether phenoloxidase (PO), an immune protein, is involved in resistance to Cry1Ac toxin in P. xylostella remains unclear. Here, spatial and temporal expression patterns showed that prophenoloxidase (PxPPO1 and PxPPO2) in the Cry1S1000-resistant strain was more highly expressed in eggs, 4th instar, head, and hemolymph than those in G88-susceptible strain. The results of PO activity analysis showed that after treatment with Cry1Ac toxin PO activity was about 3 times higher than that before treatment. Furthermore, knockout of PxPPO1 and PxPPO2 significantly increased the susceptibility to Cry1Ac toxin. These findings were further supported by the knockdown of Clip-SPH2, a negative regulator of PO, which resulted in increased PxPPO1 and PxPPO2 expression and Cry1Ac susceptibility in the Cry1S1000-resistant strain. Finally, the synergistic effect of quercetin showed that larval survival decreased from 100 % to <20 % compared to the control group. This study will provide a theoretical basis for the analysis of immune-related genes (PO) genes involved in the resistance mechanism and pest control of P. xylostella.

Analysis of the Effect of Plutella xylostella Polycalin and ABCC2 Transporter on Cry1Ac Susceptibility by CRISPR/Cas9-Mediated Knockout.

Many insects, including the Plutella xylostella (L.), have developed varying degrees of resistance to many insecticides, including Bacillus thuringiensis (Bt) toxins, the bioinsecticides derived from Bt. The polycalin protein is one of the potential receptors for Bt toxins, and previous studies have confirmed that the Cry1Ac toxin can bind to the polycalin protein of P. xylostella, but whether polycalin is associated with the resistance of Bt toxins remains controversial. In this study, we compared the midgut of larvae from Cry1Ac-susceptible and -resistant strains, and found that the expression of the Pxpolycalin gene was largely reduced in the midgut of the resistant strains. Moreover, the spatial and temporal expression patterns of Pxpolycalin showed that it was mainly expressed in the larval stage and midgut tissue. However, genetic linkage experiments showed that the Pxpolycalin gene and its transcript level were not linked to Cry1Ac resistance, whereas both the PxABCC2 gene and its transcript levels were linked to Cry1Ac resistance. The larvae fed on a diet containing the Cry1Ac toxin showed no significant change in the expression of the Pxpolycalin gene in a short term. Furthermore, the knockout of polycalin and ATP-binding cassette transporter subfamily C2 (ABCC2) genes separately by CRISPR/Cas9 technology resulted in resistance to decreased susceptibility to Cry1Ac toxin. Our results provide new insights into the potential role of polycalin and ABCC2 proteins in Cry1Ac resistance and the mechanism underlying the resistance of insects to Bt toxins.

Correlation of endocrine disrupting chemicals with essential elements in biological samples of children (1-5 years) with different infectious diseases and impact on sustainable outdoor activities.

Endocrine disrupting chemicals (EDCs) have been extensively explored due to their harmful effects on individual health and the environment by interfering with hormone activity and disrupting the endocrine system. However, their relationship with essential trace elements remains uncertain. This research aimed to investigate the possible correlation between essential trace elements and toxic metals, including cadmium (Cd), and lead (Pb) in children aged 1-5 years with various infectious diseases, including gastrointestinal disorders, typhoid fever, and pneumonia. The study was conducted on biological testing and specimen (scalp hair and whole blood) of diseased and non-diseased children of the same residential area and referent/control age-matched children from developed cities consuming domestically treated water. The media of biological samples were oxidized by an acid mixture before being analyzed by atomic absorption spectrophotometry. The accuracy and validity of the methodology were verified through accredited reference material from scalp hair and whole blood sample. The study results revealed that diseased children had lower mean values of essential trace elements (iron, copper, and zinc) in both scalp hair and blood, except for copper, which was found to be higher in blood samples of diseased children. This implies that the deficiency of essential residue and trace elements in children from rural areas who consume groundwater is linked to various infectious diseases. The study highlights the need for more human biomonitoring of EDCs to better comprehend their non-classical toxic properties and their concealed costs on human health. The findings suggest that exposure to EDCs could be associated with unfavorable health outcomes and emphasizes the need for future regulatory policies to minimize exposure and safeguard the health of current and forthcoming generations of children. Furthermore, the study highlights the implication of essential trace elements in maintaining good health and their potential correlation with toxic metals in the environment.

Development and validation of an immune-related gene signature for prognosis in Lung adenocarcinoma.

The most common type of lung cancer tissue is lung adenocarcinoma. The TCGA-LUAD cohort retrieved from the TCGA dataset was considered the internal training cohort, while GSE68465 and GSE13213 datasets from the GEO database were used as the external test cohort. The TCGA-LUAD cohort was classified into two immune subtypes using single-sample gene set enrichment analysis of the immune gene set and unsupervised clustering analysis. The ESTIMATE algorithm, the CIBERSORT algorithm, and HLA family expression levels again validated the reliability of this typing. We performed Venn analysis using immune-related genes from the immport dataset and differentially expressed genes from the subtypes to retrieve differentially expressed immune genes (DEIGs). In addition, DEIGs were used to construct a prognostic model with the least absolute shrinkage and selection operator regression analysis. A reliable risk model consisting of 11 DEIGs, including S100P, INHA, SEMA7A, INSL4, CD40LG, AGER, SERPIND1, CD1D, CX3CR1, SFTPD, and CD79A, was then built, and its reliability was further confirmed by ROC curve and calibration plot analysis. The high-risk score subgroup had a poor prognosis and a lower tumour immune dysfunction and exclusion score, indicating a greater likelihood of anti-PD-1/cytotoxic T lymphocyte antigen 4 benefit.

Do oil, gold and metallic price volatilities prove gold as a safe haven during COVID-19 pandemic? Novel evidence from COVID-19 data.

The spreading COVID-19 outbreak has wreaked havoc on the world's financial system that raises an urgent need for the re-evaluation of the gold as safe haven for their money because of the unprecedented challenges faced by markets during this period. Therefore, the current study investigates whether different asset class volatility indices affect desirability of gold as a safe-haven commodity during COVID-19 pandemic. Long run and the short run relationship of gold prices with gold price volatility, oil price volatility, silver price volatility and COVID-19 (measured by the number of deaths due to COVID) has been analyzed in the current study by applying ARDL Bound testing cointegration and non linear ARDL approach on daily time series data ranging from January 2020 to Dec 2021. Findings of the study suggest that in the long run, oil price volatility and gold price volatility positively affect the gold prices, whereas the effect of silver price volatility on gold prices is negative in the long run. However in the short run, all the three indices negatively impact the gold prices. In contrast, the impact of COVID-19 is positive both in the short run and in the long run that proves the validity of gold as safe haven asset in the time of the deadly pandemic. The findings of this study have significant implications and offer investors with some indications to hedge their investments by considering the gold's ability of safe haven during this era of pandemic.

Pre- and post-COVID-19: The impact of the pandemic and stock market psychology on the growth and sustainability of consumer goods industries.

The objective of this study is to investigate the impact of the COVID-19 pandemic and stock market psychology on investor investment decisions in different business units operating in the Shandong stock market. The sample size of the study consists of 5,000 individuals from six different business units. The study used the event study statistical technique to analyze the market reaction to newly released information from the stock market perspective to assess whether the number of COVID-19 positive cases impacted it. With a Z score value of 40.345 and a P-value of 0.000, the Wilcoxon test indicated that stock prices before and after the pandemic were quite different. The test showed a positive relationship between the pandemic and the stock market. Further, the results indicated that COVID-19 and stock market psychology had a significant positive impact on investor investment decisions in cosmetic and beauty, consumer household, textiles and apparel, and consumer electronics industries; however, in the sporting and consumer appliance industries, it had an insignificant negative impact. This study serves to guide investors to make suitable changes in their stock market trading practices to counter these challenges to increase their required rate of return from their specific stock market investment. The findings have important insights for various stakeholders including governments, regulatory bodies, practitioners, academia, industry, and researchers.

The Potential Role of the Methionine Aminopeptidase Gene PxMetAP1 in a Cosmopolitan Pest for Bacillus thuringiensis Toxin Tolerance.

Methionine aminopeptidases (MetAPs) catalyze the cleavage of the N-terminal initiator methionine (iMet) in new peptide chains and arylamides, which is essential for protein and peptide synthesis. MetAP is differentially expressed in two diamondback moth (DBM; Plutella xylostella) strains: the G88 susceptible strain and the Cry1S1000 strain, which are resistant to the Bt toxin Cry1Ac, implicating that MetAP expression might be associated with Bt resistance. In this study, we identified and cloned a MetAP gene from DBMs, named PxMetAP1, which has a CDS of 1140 bp and encodes a 379 amino acid protein. The relative expression of PxMetAP1 was found to be ~2.2-fold lower in the Cry1S1000 strain compared to that in the G88 strain. PxMetAP1 presents a stage- and tissue-specific expression pattern, with higher levels in the eggs, adults, integument, and fatbody of DBMs. The linkage between PxMetAP1 and Cry1Ac resistance is verified by genetic linkage analysis. The knockout of PxMetAP1 in G88 by CRISPR/Cas9 leads to a ~5.6-fold decrease in sensitivity to the Cry1Ac toxin, further supporting the association between the PxMetAP1 gene and Bt tolerance. Our research sheds light on the role of MetAP genes in the development of Bt tolerance in P. xylostella and enriches the knowledge for the management of such a cosmopolitan pest.

Post-COVID-19 investor psychology and individual investment decision: A moderating role of information availability.

This study aims to investigate the influence of psychological biases on the investment decision of Chinese individual investors after the pandemic of COVID-19 with a moderating role of information availability. A cross-sectional method with a quantitative research approach was employed to investigate the hypothesized relationships among variables. The snowball sampling technique was applied to collect the data through a survey questionnaire from individual investors investing in the Chinese stock market. Smart-PLS statistical software was used to analyze the data and for the estimation of hypotheses. Results indicated that overconfidence, representative bias, and anchoring bias have a significant and positive influence on investment decisions during the post-Covid-19 pandemic; however, the availability bias has insignificant and negative effects on the investment decision during the post-COVID-19 pandemic. Moreover, findings indicated that information availability has a significant moderating role in the relationship of psychological biases with the investment decision during the post-COVID-19 pandemic. This study contributes to the body of knowledge regarding behavior finance, psychological biases, and investment decision in emerging stock markets. The findings of the present study improve the understanding that how investors' psychology affects their investment decisions.

A GLP-1/glucagon (GCG)/CCK2 receptors tri-agonist provides new therapy for obesity and diabetes.

BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptor dual agonist have promising therapeutic effects in the treatment of obesity and diabetes. Moreover, GLP-1 and cholecystokinin 2 (CCK2 ) dual agonists have been shown to restore pancreas function and improve glycaemic control in preclinical studies. We describe, for the first time, the beneficial effects of GLP-1/glucagon receptor and GLP-1/CCK2 dual agonists, which can be integrated into one peptide, resulting in significant anti-diabetes and anti-obesity effectiveness. EXPERIMENTAL APPROACH: The in vitro potency of this novel peptide Xenopus (x) GLP-1/GCG/CCK2 tri-agonist (xGLP/GCG/gastrin) against GLP-1, GCG, CCK1 and CCK2 receptors was determined on cells expressing the corresponding receptors by cAMP accumulation or ERK1/2 phosphorylation assays. The in vivo anti-diabetes and anti-obesity effects of this tri-agonist xGLP/GCG/gastrin were studied in both db/db and diet induced obesity (DIO) mice. KEY RESULTS: xGLP/GCG/gastrin was a potent and selective GLP-1, GCG and CCK2 tri-agonist. In DIO mice, the metabolic benefits of xGLP-1/GCG/gastrin, such as reduction of body weight and hepatic lipid contents were significantly better than those of the peptide ZP3022 (GLP-1/CCK-2 dual agonist) and liraglutide. In a short-term study in db/db mice, xGLP/GCG/gastrin treatment had considerable effects, increasing islet numbers, islet areas and insulin content. In a long-term treatment study using db/db mice, xGLP-1/GCG/gastrin showed a significantly and sustained improvement in glucose tolerance and glucose control compared with that of liraglutide, ZP3022, cotadutide (GLP-1/GCG dual agonist) and xGLP/GCG-15. CONCLUSIONS AND IMPLICATIONS: These results demonstrate the therapeutic potential of xGLP-1/GCG/gastrin for the treatment of obesity and diabetes.

Theory of Mind Among Swedish Children with ASD, Down Syndrome and Typically Developing Group.

The present study examined the role of IQ and the Theory of Mind understanding in children with an autism spectrum disorder and down syndrome. Sixty-six Swedish children with ASD (n = 26), DS (n = 18), and typically developed group (n = 22) ranged between 6 and 12 years old were compared on ToM tasks consisted of standard ToM and IQ tasks. SPSS 25 program was used to analyze data. The results indicated that individuals with ASD reach a better understanding of first-order ToM tasks than children with DS. This picture was the same in the TD group to show better ability than children with ASD and DS on first-order tasks, except one task which was not found significant differences. To employ second-order TD performed better than clinical groups, while, there was no significant difference between ASD and DS. The scores for the third-order task in children with ASD were significantly better than children with DS.