Mitochondrial Mechanisms in Temozolomide Resistance: Unraveling the Complex Interplay and Therapeutic Strategies in Glioblastoma.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor, with temozolomide (TMZ) being the standard chemotherapeutic agent for its treatment. However, TMZ resistance often develops, limiting its therapeutic efficacy and contributing to poor patient outcomes. Recent evidence highlights the crucial role of mitochondria in the development of TMZ resistance through various mechanisms, including alterations in reactive oxygen species (ROS) production, metabolic reprogramming, apoptosis regulation, biogenesis, dynamics, stress response, and mtDNA mutations. This review article aims to provide a comprehensive overview of the mitochondrial mechanisms involved in TMZ resistance and discuss potential therapeutic strategies targeting these mechanisms to overcome resistance in GBM. We explore the current state of clinical trials targeting mitochondria or related pathways in primary GBM or recurrent GBM, as well as the challenges and future perspectives in this field. Understanding the complex interplay between mitochondria and TMZ resistance will facilitate the development of more effective therapeutic strategies and ultimately improve the prognosis for GBM patients.

Impact of a pyridazine derivative on tripartite synapse ultrastructure in hippocampus: a three-dimensional analysis.

Introduction: We previously discovered a pyridazine derivative compound series that can improve cognitive functions in mouse models of Alzheimer's disease. One of the advanced compounds from this series, LDN/OSU-0215111-M3, was selected as the preclinical development candidate. This compound activates local protein translation at the perisynaptic astrocytic process (PAP) and enhances synaptic plasticity sequentially. While biochemical evidence supports the hypothesis that the compound enhances the structural plasticity of the tripartite synapse, its direct structural impact has not been investigated. Methods: Volume electron microscopy was used to study the hippocampal tripartite synapse three-dimensional structure in 3-month-old wild-type FVB/NJ mice after LDN/OSU-0215111-M3 treatment. Results: LDN/OSU-0215111-M3 increased the size of tertiary apical dendrites, the volume of mushroom spines, the proportion of mushroom spines containing spine apparatus, and alterations in the spine distribution across the surface area of tertiary dendrites. Compound also increased the number of the PAP interacting with the mushroom spines as well as the size of the PAP in contact with the spines. Furthermore, proteomic analysis of the isolated synaptic terminals indicated an increase in dendritic and synaptic proteins as well as suggested a possible involvement of the phospholipase D signaling pathway. To further validate that LDN/OSU-0215111-M3 altered synaptic function, electrophysiological studies showed increased long-term potentiation following compound treatment. Discussion: This study provides direct evidence that pyridazine derivatives enhance the structural and functional plasticity of the tripartite synapse.

Dysregulated lipid metabolism in TMZ-resistant glioblastoma: pathways, proteins, metabolites and therapeutic opportunities.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM.

Update on Regulation of Regenerative Medicine in Taiwan.

Due to rapid development of biotechnology in recent years, the field of regenerative medicine has attracted considerable attention. Regenerative medicine-related regulations have been established in several countries to ensure the quality, safety, and efficacy of innovative treatments. Considering the diversity of regenerative medicine, the regulatory framework in Taiwan has been adjusted in response to global trend and local demand. Before 2010, cell and gene therapies were regarded as "new medical practice" under the "Medical Care Act." Along with the establishment of Taiwan Food and Drug Administration (TFDA) in 2010, regenerative medicine was regulated as "medicinal products" under the "Pharmaceutical Affairs Act." Then, the Ministry of Health and Welfare (MOHW) established a new dual-track regulatory pathway for regenerative medicine in 2016. The dual-track pathway divided regenerative medicine into medical practices and medicinal products, aiming to improve the accessibility of new treatments to patients and maintain the flexibility for clinical operations. In order to refine the regulation, the MOHW proposed two draft Acts for regenerative medicine in 2022. The two draft Acts are currently under legislative process. It is expected that the research and development of regenerative medicine can be further accelerated, thus providing early access to innovative therapies for patients in the future.

Eradication therapy may decrease the risk of immune thrombocytopenia after Helicobacter pylori infection: a retrospective cohort study in Taiwan.

BACKGROUND: Helicobacter pylori (HP) eradication therapy (HPE) is recommended for patients with unexplained immune thrombocytopenia (ITP); however, the role of HPE in preventing ITP in patients with HP infection remains unclear. Therefore, this study was designed to clarify it. METHODS: This study was conducted at a tertiary medical center and included all adult patients with HP infection between January 1, 2016 and December 31, 2018. We compared the risk of developing ITP between patients with and without HPE. All patients were followed up until December 31, 2020. RESULTS: After excluding patients with thrombocytopenia, 1995 adult patients with HP infection, including 1188 patients with HPE and 807 patients without HPE, were included in this study. The mean age of the patients with HPE was 57.9 years, whereas that of those without HPE was 61.6 years. The percentage of males was 56% in patients with HPE and 59% in those without HPE. Patients without HPE had a higher risk of ITP than those with HPE after adjusting for age, sex, the Charlson Comorbidity Index, and comorbidities [adjusted odds ratio (OR) 1.76; 95% confidence interval (CI) 1.16-2.68]. Stratified analyses showed that the higher risk was found only in males (adjusted OR: 1.70; 95% CI 1.03-2.80). In addition to HPE, male sex and anemia were independent predictors of ITP in patients with HP infection. CONCLUSION: This study showed that adult patients with HP infection not receiving HPE had a higher risk of developing ITP. We suggest that HPE should be considered, particularly in males and those who have anemia, to prevent ITP.

Plumbagin induces the apoptosis of drug-resistant oral cancer in vitro and in vivo through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction.

BACKGROUND: Oral cancer is one of the leading causes of cancer-related deaths worldwide. Chemotherapy is widely used in the treatment of oral cancer, but its clinical efficacy is limited by drug resistance. Hence, novel compounds capable of overcoming drug-resistance are urgently needed. PURPOSE: Plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, has been used to treat various cancers. In this study, we investigated the anticancer effects of PG on drug-resistant oral cancer (CR-SAS) cells, as well as the underlying mechanism. METHODS: MTT assays were used to evaluate the effect of PG on the viability of CR-SAS cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined using flow cytometry. Protein expression levels were detected by western blotting. RESULTS: The results show that PG reduces the viability and causes the apoptosis of CR-SAS cells. PG is able to induce intracellular and mitochondrial ROS generation that leads to mitochondrial dysfunction. Furthermore, endoplasmic reticulum (ER) stress was triggered in PG-treated CR-SAS cells. The inhibition of ROS using N-acetylcysteine (NAC) abrogated the PG-induced ER stress and apoptosis, as well as the reduction in cell viability. Meanwhile, similar results were observed both in zebrafish and in murine models of drug-resistant oral cancer. CONCLUSION: Our results indicate that PG induces the apoptosis of CR-SAS cells via the ROS-mediated ER stress pathway and mitochondrial dysfunction. It will be interesting to develop the natural compound PG for the treatment of drug-resistant oral cancer.

Bibliometric-Based Evaluation of the Neuromarketing Research Trend: 2010-2021.

Neuromarketing has become a new and important topic in the field of marketing in recent years. Consumer behavior research has received increasing attention. In the past decade, the importance of marketing has also been recognized in many fields such as consumer behavior, advertising, information systems, and e-commerce. Neuromarketing uses neurological methods to determine the driving forces behind consumers' choices. Various neuroscience tools, such as eye movements, have been adopted to help reveal how consumers react to particular advertisements or objects. This information can be used as the basis for new advertising campaigns and brand promotions. To effectively explore the research trends in this field, we must understand the current situation of neuromarketing. A systematic bibliometric analysis can solve this problem by providing publishing trends and information on various topics. In this study, journals that focused on neuromarketing in the field of marketing between 2010 and 2021 were analyzed. These journals were core journals rated by the Association of Business Schools with three or more stars. According to the data analysis results, neuromarketing has 15 main journals with relevant papers. Based on the data collected by the Web of Science (WOS), this study mainly collected 119 references and analyzed the most productive countries, universities, authors, journals, and prolific publications in the field of neuromarketing via Citespace. Through the analysis of knowledge maps, this study explored the mapping of co-citation, bibliographic coupling (BC), and co-occurrence (CC). Moreover, the strongest citation bursts were used to study popular research at different time stages and analyze the research trends of neuromarketing research methods and tools. This study provides an overview of the trends and paths in neuromarketing, which can help researchers understand global trends and future research directions.

Roles and Research Trends of Neuroscience on Major Information Systems Journal: A Bibliometric and Content Analysis.

Over the past decade, neuroscience has been integrated into information systems as a new methodology and perspective to study and solve related problems. Therefore, NeuroIS has emerged as a new cutting-edge research field. This review aimed to identify, summarize, and classify existing NeuroIS publications through knowledge mapping and bibliometric analysis. To effectively understand the development trend of NeuroIS, this study referred to the journal selection index of the Association of Business Schools in 2021 and journals above three stars in the field of information management as the main selection basis. A total of 99 neuroscience papers and their citation data were included from 19 major information systems journals of SCI/SSCI. This study analyzed bibliometric data from 2010 to 2021 to identify the most productive countries, universities, authors, journals, and prolific publications in NeuroIS. To this end, VOSviewer was used to visualize mapping based on co-citation, bibliographic coupling, and co-occurrence. Keywords with strong citation bursts were also identified in this study. This signifies the evolution of this research field and may reveal potential research directions in the near future. In selecting research methods and analysis tools for NeuroIS, content analysis was used to further conclude and summarize the relevant trends. Moreover, a co-citation network analysis was conducted to help understand how the papers, journals, and authors in the field were connected and related, and to identify the seminal or pioneering major literature. For researchers, network maps visualized mainstream research and provided a structural understanding of NeuroIS. The review concludes by discussing potential research topics in this field.

Safe-Sex Behavioral Intention of Chinese College Students: Examining the Effect of Sexual Knowledge Using the Theory of Planned Behavior.

Numerous contemporary studies have examined safe sexual behavior among college students. In China, families are reluctant to discuss sexual behavior, thus understanding and exploring the sexual knowledge of college students and the promotion of safe sexual behavior is essential. On the basis of the theory of planned behavior (TPB), a cognitive behavioral theory that is widely used to predict human social behavior, we conducted an in-depth investigation of the factors influencing the sexual behavioral intentions of Chinese college students. We referenced the relevant literature to develop a TPB-based model for analyzing differences in sexual knowledge. Our statistical analysis revealed the following: (1) subjective norms and behavior control are key variables that influence the safe sexual behavior of college students; (2) attitudes and safe-sex behavioral intentions are influential in groups with extensive sexual knowledge; (3) behavioral control and subjective norms influence the differences in the comparative sexual knowledge of students. On the basis of the present results, we propose research recommendations and directions for the development of sex education in China.

Role of high ubiquitin-conjugating enzyme E2 expression as a prognostic factor in nasopharyngeal carcinoma.

The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile (GSE12452 and GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.

Research Landscape of Artificial Intelligence and e-Learning: A Bibliometric Research.

While an increasing number of organizations have introduced artificial intelligence as an important facilitating tool for learning online, the application of artificial intelligence in e-learning has become a hot topic for research in recent years. Over the past few decades, the importance of online learning has also been a concern in many fields, such as technological education, STEAM, AR/VR apps, online learning, amongst others. To effectively explore research trends in this area, the current state of online learning should be understood. Systematic bibliometric analysis can address this problem by providing information on publishing trends and their relevance in various topics. In this study, the literary application of artificial intelligence combined with online learning from 2010 to 2021 was analyzed. In total, 64 articles were collected to analyze the most productive countries, universities, authors, journals and publications in the field of artificial intelligence combined with online learning using VOSviewer through WOS data collection. In addition, the mapping of co-citation and co-occurrence was explored by analyzing a knowledge map. The main objective of this study is to provide an overview of the trends and pathways in artificial intelligence and online learning to help researchers understand global trends and future research directions.

The Impact of Career Competence on Career Sustainability Among Chinese Expatriate Managers Amid Digital Transformation in Vietnam: The Role of Lifelong Learning.

Digitalization and advanced technologies are replacing human jobs. Around the world, many people have lost their jobs due to increasing digitalization. Similarly, Chinese expatriates associated with the manufacturing sector in emerging countries such as Vietnam face similar challenges. Therefore, Chinese expatriates need to bring competitiveness in their competencies. This competitiveness brings sustainability to their career. The aim of this study is to investigate the impact of career competencies on career sustainability. Moreover, we test the mediating effect of lifelong learning in the relationship between career competencies and career sustainability. A questionnaire survey approach was used in this study. The target population was the Chinese expatriate managers working at China-invested manufacturing multinational organizations in Vietnam. To estimate the proposed relationships, we use structural equation modeling. The results are confirmed that in the direct relationship career competence has a positive impact on career sustainability. The findings of this study also indicate that career competencies have a positive impact on lifelong learning. Furthermore, outcomes confirmed that lifelong learning has a positive impact on career sustainability. Similarly, results are also confirmed that lifelong learning is positively mediating between career competencies and career sustainability. Therefore, the empirical results of this article identify that lifelong learning has a critical impact on sustainable careers. Specifically, this study is useful for mid-level managers who are associated with multinational organizations. At the end of this article, we also explained the practical implications, limitations, and future research directions.

Effect of diabetes mellitus comorbidity on outcomes in stages II and III colorectal cancer.

AIM: The effects of diabetes mellitus (DM) on the outcomes of colorectal cancer (CRC) are controversial. This retrospective study evaluated the effects of DM on American Joint Committee on Cancer (AJCC, 7th) Stages II and III CRC patients who received curative surgery. METHODS: We reviewed the records of CRC patients who were treated from January 2008 to December 2014 and identified the presence of DM and hypertension prior to CRC diagnosis. Cox proportional hazards analyses were used for prognostic factor determination, and survival was analyzed using the Kaplan-Meier method with the log-rank test. RESULTS: Total of 1066 consecutive eligible patients with stage II/III CRC were enrolled. There were 326 (30.6%) patients diagnosed with DM, and 311 (29.2%) CRC patients had recurrence. Patients with DM did not have a higher recurrence risk (p = 0.183) but had higher mortality (adjusted hazard ratio [aHR] = 1.381; 95% conference interval [CI], 1.069-1.782). In addition, HbA1c (≥7 vs. <7) was not associated with recurrence (p = 0.365). Patients with DM had more hypertension than patients without DM (69.1% vs. 37.6%, p < 0.001). A lower recurrence risk was noted in patients with hypertension (p = 0.002), but the overall survival (OS) did not reach statistical significance (aHR = 0.910; 95% CI, 0.707-1.169). CONCLUSION: In our study, DM was a poor prognostic factor for survival in curative CRC patients. More studies are required to elucidate the effects that DM and other metabolic disorders, such as hypertension, have on the prognosis of patients with CRC.

Risk of dementia in colorectal cancer patients receiving chemotherapy: A nationwide cohort study.

BACKGROUND: Studies have reported conflicting evidence regarding whether chemotherapy leads to dementia. This study aimed to determine whether chemotherapy increases dementia risk in Taiwanese patients with colorectal cancer (CRC). METHODS: Data from the Taiwan Cancer Registry and National Health Insurance Research Database were used. Patients newly diagnosed as having CRC between 2007 and 2015 without prior history of dementia or neurodegenerative disorders were identified. Based on whether they underwent chemotherapy, patients were divided into chemotherapy and non-chemotherapy groups. Those who later developed dementia were identified using validated diagnostic codes. The Fine and Gray subdistribution hazard model for all-cause dementia with competing risk of death was applied for all patients or each stratified group. RESULTS: A total of 76,130 patients with CRC were included, with 45,872 (60.25%) in the chemotherapy group and 30,258 (39.75%) in the non-chemotherapy group. A higher incidence of dementia was observed in the non-chemotherapy group compared with the chemotherapy group (3.75% vs. 2.40%, p < 0.0001), but the risk of dementia did not differ between the groups (adjusted subdistribution hazard ratio [HRSD] = 0.97, 95% confidence interval [CI]: 0.88-1.06, p = 0.492). In the stratified analysis, chemotherapy was a risk factor for dementia in patients aged > 80 years (adjusted HRSD = 1.20, 95% CI: 1.03-1.40, p = 0.0190), whereas gender, clinical cancer stage, comorbidities, surgery, and radiation therapy had no impact on the risk of dementia. CONCLUSION: Chemotherapy increased the risk of dementia in elderly patients with CRC, highlighting the necessity to monitor their cognitive function after chemotherapy.

Safe Sexual Behavior Intentions among College Students: The Construction of an Extended Theory of Planned Behavior.

Sexual health education is an essential part of quality-oriented education for college students. It aims to help these students to acquire knowledge of sexual physiology, sexual psychology, and sexual social norms that is consistent with the maturity of the students. Along with college students'attitudes toward sex, their perceptions regarding sexual behavior have also undergone profound changes. The importance of safe sexual behavior, sexual taboos, and sexual autonomy are gaining increasing attention as Chinese society is becoming more open. For college students who have just reached adulthood and have full autonomy of themselves, however, are they really going to have sexual behavior without careful consideration? Or is it something they have planned to do in the first place? To answer the above questions, this study was conducted to understand the relationship between college students' attitudes toward sex, subjective norms, and behavioral control of their sexual behavior intentions by applying the Theory of Planned Behavior. In this study, 460 valid questionnaires were collected from Chinese college students and analyzed with partial least squares structural equation modeling (PLS-SEM). This study analyzes the relationship of multiple factors, including those influencing college students' sexual behavior intentions. Meanwhile, it also compares the differences in factors affecting sexual behavior intentions between college students with or without sexual experience and those of different genders. Based on the results of the study, it was found that, first, subjective norms and perceived behavioral control of college students had a significant effect on safe sexual behavior intentions, while attitudes did not have a significant effect on safe sexual behavior intentions. Second, the gender and sexual experience of college students had a significant effect on safe sexual behavior intentions. Third, non-sexually experienced college students were more likely to be influenced by external factors. Relevant future research suggestions will be proposed based on the results of this study. Finally, this study helps to provide substantive suggestions for enhancing safe sexual behavior among college students in the context of universal higher education, as well as strengthening the self-protection of college students and providing practical advice for the development of sex education in China.

Age as a modifier of the effects of chemoradiotherapy with infusional 5-fluorouracil after D2 dissection in gastric cancer.

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, p = 0.002) and gastrointestinal (46.9% vs. 14.3%, p = 0.027) toxicities and death (12.5% vs. 0.0%, p = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.

Inclusive Leadership and Career Sustainability: Mediating Roles of Supervisor Developmental Feedback and Thriving at Work.

Career sustainability is a well-researched issue in academics and other sectors. Technology advancements and COVID-19 have jeopardized career sustainability. Numerous studies have explored the influence of individual characteristics on career sustainability, but few have focused on leadership. In addition, cultural factors must be considered because leadership is rooted in culture. In particular, inclusive leadership reflects traditional Chinese culture. Therefore, based on self-determination social exchange theories, we analyzed the effects of inclusive leadership on career sustainability as well as the roles of thriving at work and supervisor developmental feedback (SDF) in career sustainability. In total, 363 samples were collected from China. The results revealed that inclusive leadership improves career sustainability through SDF and thriving at work. Theoretically, our study fills the research gap and establishes a mechanism and theoretical framework for inclusive leadership and career sustainability. Practically, we offer guidance for enterprises to cultivate inclusive leadership and improve career sustainability.