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A novel meta-heuristic algorithm named Egret Swarm Optimization Algorithm (ESOA) is proposed in this paper, which is inspired by two egret species’ hunting behavior (Great Egret and Snowy Egret). ESOA consists of three primary components: a sit-and-wait strategy, aggressive strategy as well as discriminant conditions. The learnable sit-and-wait strategy guides the egret to the most probable solution by applying a pseudo gradient estimator. The aggressive strategy uses random wandering and encirclement mechanisms to allow for optimal solution exploration. The discriminant model is utilized to balance the two strategies. The proposed approach provides a parallel framework and a strategy for parameter learning through historical information that can be adapted to most scenarios and has well stability. The performance of ESOA on 36 benchmark functions as well as 3 engineering problems are compared with Particle Swarm Optimization (PSO), Genetic Algorithm (GA), Differential Evolution (DE), Grey Wolf Optimizer (GWO), and Harris Hawks Optimization (HHO). The result proves the superior effectiveness and robustness of ESOA. ESOA acquires the winner in all unimodal functions and reaches statistic scores all above 9.9, while the scores are better in complex functions as 10.96 and 11.92.

The aim of this paper is to examine cross-cultural differences in body stigmatization between the individualistic Christian culture of guilt (Poland) and the collectivistic Buddhist/Confucian culture of honor and shame (Vietnam). The study included 1290 university students from Poland (n = 586) and Vietnam (n = 704). Subjects filled in the body esteem scale and the perceived stigmatization questionnaire, and body measurements were collected to calculate anthropometric indices. Participants from Vietnam were less satisfied with their appearance than their Polish peers. Men in both countries assessed themselves more favorably. No anthropometric index predicted body esteem in Vietnamese women, while only indices related to fat levels were predictors in Polish women. Men with a V-shaped body assessed themselves as stronger and as having a better physical condition. A possible explanation of the observed cross-cultural differences is that interdependent self-construal makes young adults in collectivistic societies more susceptible to criticism, and the Confucian values of modesty and shame lead to them not perceiving their bodies as sexual objects. The Christian sense of guilt does not influence the perception of sexuality. Absence of friendly behavior mediated the relation between anthropometric indices and body esteem in both cultures.

Background Colorectal cancer (CRC) is a highly prevalent cancer type with limited targeted therapies available and 5-year survival rate, particularly for late-stage patients. There have been numerous attempts to repurpose drugs to tackle this problem. It has been reported that autophagy inducers could augment the effect of certain chemotherapeutic agents by enhancing immunogenic cell death (ICD). Methods In this study, we employed bioinformatics tools to identify thioridazine (THD), an antipsychotic drug, and found that it could induce autophagy and ICD in CRC. Then in vitro and in vivo experiments were performed to further elucidate the molecular mechanism of THD in CRC. Results THD was found to induce endoplasmic reticulum (ER) stress in CRC cells by activating the eIF2α/ATF4/CHOP axis and facilitating the accumulation of secretory autophagosomes, leading to ICD. In addition, THD showed a remarkable ICD-activating effect when combined with oxaliplatin (OXA) to prevent tumor progression in the mouse model. Conclusions Together, our findings suggest that the repurposed function of THD in inhibiting CRC involves the upregulation of autophagosomes and ER stress signals, promoting the release of ICD markers, and providing a potential candidate to enhance the clinical outcome for CRC treatment. 6ZzBeVddzkUiW38NXX-mrK Video Abstract

We examine whether directors on a board who are related to minority shareholders have an effect on bank risk. We use a panel of European banks with a controlling shareholder over the period from 2003 to 2017 and find that these directors result in lower risk. Our results depend crucially on whether or not such directors have reputational concerns or financial expertise, and the level of shareholder protection; the observed decrease in risk does not depend on their position on the board or on the presence of controlling shareholders. To identify the relationship, we use a dynamic generalized method of moments.

PurposeThe authors examine whether the uncertainty avoidance culture and the stringency of government response play a role in shaping the stock market's response to coronavirus disease 2019 (COVID-19). The authors find that investors' response to the pandemic will not only depend on their instinct of uncertainty aversion but also on their expectation about the effectiveness of the government measures. The uncertainty avoidance culture amplifies the irrational actions of investors. However, harsh government responses will weaken this effect. Harsh government responses also send a negative signal to the market about the extent of the pandemic and the economic damage caused by anti-COVID measures. Governments need to be balanced in imposing anti-COVID measurements to preserve market confidence.Design/methodology/approachIn this article, the authors investigate whether the stock market volatility of emerging countries is simultaneously driven by two factors: the uncertainty-aversion culture of investors in a country and the stringency of the government's response to the pandemic. The authors conduct an empirical study on a sample of 20 emerging countries during the period from January 2020 to March 2021.FindingsThe authors find that the national-level uncertainty aversion amplifies the irrational actions of investors during the period of crisis. However, harsh government responses will weaken this effect. The authors’ findings show evidence that investors' response to the pandemic will not only depend on their instinct of uncertainty aversion but also on their expectation about the effectiveness of the government measures. Although harsh government responses can stabilize the investors' sentiment in countries with high levels of uncertainty aversion, they also send a negative signal to the market about the extent of the pandemic as well as the economic damage caused by anti-COVID measures.Originality/valueFirst, the study’s results complement evidence from existing studies on the effect of uncertainty avoidance culture in determining stock market responses to COVID-19. Second, an important difference from previous studies, this paper adds to the behavioral finance literature by showing that investors' investment decisions in the face of economic uncertainty are not driven solely by their cultural values but also by their expectation about the effectiveness of the government policy. During a crisis, when the market has neither rational information nor adequate experience to forecast the future, the government must play an important role in stabilizing investors' sentiment and reactions.

Background Colorectal cancer (CRC) poses a significant clinical challenge because of drug resistance, which can adversely impact patient outcomes. Recent research has shown that abnormalities within the tumor microenvironment, especially hyperglycemia, play a crucial role in promoting metastasis and chemoresistance, and thereby determine the overall prognosis of patients with advanced CRC. Methods This study employs data mining and consensus molecular subtype (CMS) techniques to identify pitavastatin and atorvastatin as potential agents for targeting high glucose-induced drug resistance in advanced CRC cells. CRC cells maintained under either low or high glucose conditions were established and utilized to assess the cytotoxic effects of pitavastatin and atorvastatin, both with and without 5-fluorouracil (5-FU). CRC 3D spheroids cultured were also included to demonstrate the anti-drug resistance of pitavastatin and atorvastatin. Results A bioinformatics analysis identified pitavastatin and atorvastatin as promising drug candidates. The CMS4 CRC cell line SW480 (SW480-HG) was established and cultured under high glucose conditions to simulate hyperglycemia-induced drug resistance and metastasis in CRC patients. Pitavastatin and atorvastatin could inhibit cell proliferation and 3D spheroid formation of CMS4 CRC cells under high glucose conditions. In addition, both pitavastatin and atorvastatin can synergistically promote the 5-FU-mediated cytotoxic effect and inhibit the growth of 5-FU-resistant CRC cells. Mechanistically, pitavastatin and atorvastatin can induce apoptosis and synergistically promote the 5-FU-mediated cytotoxic effect by activating autophagy, as well as the PERK/ATF4/CHOP signaling pathway while decreasing YAP expression. Conclusion This study highlights the biomarker-guided precision medicine strategy for drug repurposing. Pitavastatin and atorvastatin could be used to assist in the treatment of advanced CRC, particularly with CMS4 subtype CRC patients who also suffer from hyperglycemia. Pitavastatin, with an achievable dosage used for clinical interventions, is highly recommended for a novel CRC therapeutic strategy.

Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti–lung cancer and anti–lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.

Background High-resolution anorectal manometry (HRAM) has been developed to improve measurement of anorectal functions. This study aims to identify normal HRAM values in healthy young Vietnamese adults. Methods We conducted a cross-sectional study at the National Hospital of Traditional Medicine (Hanoi, Vietnam) from July through December 2014. Healthy young adults were invited to participate in the study. All anorectal measurement values were performed using the ISOLAB high-resolution manometry system. Differences between groups were analyzed using Student’s t-tests. Results Thirty healthy young adults, including 15 males and 15 females aged 19–26 years, were recruited. Mean functional anal canal length was 3.4 ± 0.5 cm (range: 2.4–4.8 mm). Mean maximum resting pressure, mean maximum squeezing pressure, mean maximum coughing pressure, and mean maximum strain pressure were 65.5, 168.0, 125.9, and 84.2 mm Hg, respectively. All anal pressure values were significantly different between males and females. For rectal sensation measurements, only the volume at first sensation was significantly higher in males than in females. Conclusions This study provides normal HRAM value for healthy young adults in Vietnam. Sex may influence anal pressure and first rectal sensation values in this cohort. Further studies should be conducted in order to improve the quality of HRAM normal values and to confirm the effects of sex.

Background Despite advances in treatment, patients with refractory colorectal cancer (CRC) still have poor long-term survival, so there is a need for more effective therapeutic options. Methods To evaluate the HDAC8 inhibition efficacy as a CRC treatment, we examined the effects of various HDAC8 inhibitors (HDAC8i), including BMX (NBM-T-L-BMX-OS01) in combination with temozolomide (TMZ) or other standard CRC drugs on p53 mutated HT29 cells, as well as wild-type p53 HCT116 and RKO cells. Results We showed that HDAC8i with TMZ cotreatment resulted in HT29 arrest in the S and G2/M phase, whereas HCT116 and RKO arrest in the G0/G1 phase was accompanied by high sub-G1. Subsequently, this combination approach upregulated p53-mediated MGMT inhibition, leading to apoptosis. Furthermore, we observed the cotreatment also enabled triggering of cell senescence and decreased expression of stem cell biomarkers. Mechanistically, we found down-expression levels of β-catenin, cyclin D1 and c-Myc via GSK3β/β-catenin signaling. Intriguingly, autophagy also contributes to cell death under the opposite status of β-catenin/p62 axis, suggesting that there exists a negative feedback regulation between Wnt/β-catenin and autophagy. Consistently, the Gene Set Enrichment Analysis (GSEA) indicated both apoptotic and autophagy biomarkers in HT29 and RKO were upregulated after treating with BMX. Conclusions BMX may act as a HDAC8 eraser and in combination with reframed-TMZ generates a remarkable synergic effect, providing a novel therapeutic target for various CRCs. 12mq7khsyzMPAFsnG-a-Nk Video Abstract

Colorectal cancer (CRC) is one of the primary contributors to cancer-related fatalities, with up to 80% of advanced CRC cases exhibiting mutations in the p53 gene. Unfortunately, the development of new compounds targeting mutant p53 is quite limited. The anticancer effects of Dehydroepiandrosterone (DHEA) on various cancers have been reported. However, the suppressive effect of DHEA on CRC cells harboring wild-type or mutant p53 gene remains controversial. This study emphasized revealing the suppressive mechanism and the effect of DHEA on CRC cell tumorigenesis in the presence of wild-type or mutant p53 gene. We demonstrate that DHEA causes CRC cell death and cell cycle arrest in a dose and time-dependent manner. Notably, DHEA exhibits similar inhibitory effects on CRC cells regardless of the p53 gene status. Further study reveals that DHEA induces endoplasmic reticulum (ER) stress and triggers PERK/eIF2/ATF4/CHOP UPR signaling pathway to activate autophagy followed by apoptosis, which was confirmed by suppression of 4-phenylbutyric acid (an ER stress inhibitor) or knockdown either ATF4 or CHOP. DHEA-induced apoptosis was attenuated by silencing ATG5 gene in either p53 +/+ or p53 −/− CRC cells, indicating autophagy regulation of apoptosis. Furthermore, DHEA treatment accompanied by bafilomycin A1 (a blocker of autophagosome degradation) leads to the accumulation of ATF4, CHOP, DR5, and p21 levels in CRC cells, implying that the degradative autophagy machinery regulates these four molecules. Consistently, DHEA demonstrates its inhibitory effect by suppressing CRC tumor formation in vivo . Altogether, we provide compelling evidence that DHEA is a potential therapeutic candidate for CRC patient treatment regardless of the p53 status through ER stress-PERK-autophagy-apoptosis axis.