Protein lipoylation: mitochondria, cuproptosis, and beyond.

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.

Manipulating Ferroelectric Polarization and Spin Polarization of 2D CuInP2S6 Crystals for Photocatalytic CO2 Reduction.

Manipulating electronic polarizations such as ferroelectric or spin polarizations has recently emerged as an effective strategy for enhancing the efficiency of photocatalytic reactions. This study demonstrates the control of electronic polarizations modulated by ferroelectric and magnetic approaches within a two-dimensional (2D) layered crystal of copper indium thiophosphate (CuInP2S6) to boost the photocatalytic reduction of CO2. We investigate the substantial influence of ferroelectric polarization on the photocatalytic CO2 reduction efficiency, utilizing the ferroelectric-paraelectric phase transition and polarization alignment through electrical poling. Additionally, we explore enhancing the CO2 reduction efficiency by harnessing spin electrons through the synergistic introduction of sulfur vacancies and applying a magnetic field. Several advanced characterization techniques, including piezoresponse force microscopy, ultrafast pump-probe spectroscopy, in situ X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier transformed spectroscopy, are performed to unveil the underlying mechanism of the enhanced photocatalytic CO2 reduction. These findings pave the way for manipulating electronic polarizations regulated through ferroelectric or magnetic modulations in 2D layered materials to advance the efficiency of photocatalytic CO2 reduction.

Intelligent Evacuation Sign Control Mechanism in IoT-Enabled Multi-Floor Multi-Exit Buildings.

In contemporary evacuation systems, the evacuation sign typically points fixedly towards the nearest emergency exit, providing guidance to evacuees. However, this static approach may not effectively respond to the dynamic nature of a rapidly evolving fire situation, in particular if the closest emergency exit is compromised by fire. This paper introduces an intelligent evacuation sign control mechanism that leverages smoke and temperature sensors to dynamically adjust the direction of evacuation signs, ensuring evacuees are guided to the quickest and safest emergency exit. The proposed mechanism is outlined through a rigorous mathematical formulation, and an ESP heuristic is devised to determine temperature-safe, smoke-safe, and congestion-aware evacuation paths for each sign. This algorithm then adjusts the direction light on the evacuation sign to align with the identified evacuation path. To validate the effectiveness of this approach, fire simulations using FDS software 6.7.1 were conducted in the Taipei 101 shopping mall. Temperature and smoke data from sensor nodes were utilized by the ESP algorithm, demonstrating superior performance compared to that of the existing FEL algorithm. Specifically, the ESP algorithm exhibited a notable increase in the probability of evacuation success, surpassing the FEL algorithm by up to 34% in methane fire scenarios and 14% in PVC fire scenarios. The significance of this improvement is more pronounced in densely congested evacuation scenarios.

Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II.

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

Studying the Roles of the Renin-Angiotensin System in Accelerating the Disease of High-Fat-Diet-Induced Diabetic Nephropathy in a db/db and ACE2 Double-Gene-Knockout Mouse Model.

Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.

ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury.

COVID-19 is a highly transmittable respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major complication of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6 and TNF-α) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

Development and psychometric evaluation of the Physical Resilience Instrument for Older Adults (PRIFOR).

BACKGROUND: Physical resilience is known to minimize the adverse outcomes of health stressors for older people. However, validated instruments that assess physical resilience in older adults are rare. Therefore, we aimed to validate the Physical Resilience Instrument for Older Adults (PRIFOR) to fill the literature gap. METHODS: Content analysis with content validity was first carried out to generate relevant items assessing physical resilience for older adults, and 19 items were developed. Psychometric evaluation of the 19 items was then tested on 200 older adults (mean [SD] age = 76.4 [6.6] years; 51.0% women) for item properties, factor structure, item fit, internal consistency, criterion-related validity, and known-group validity. RESULTS: All 19 items had satisfactory item properties, as they were normally distributed (skewness = -1.03 to 0.38; kurtosis = -1.05 to 0.32). However, two items were removed due to substantial ceiling effects. The retained 17 items were embedded in three factors as suggested by the exploratory factor analysis (EFA) results. All items except one had satisfactory item fit statistics in Rasch model; thus, the unidimensionality was supported for the three factors on 16 items. The retained 16 items showed promising properties in known-group validity, criterion-related validity, and internal consistency (α = 0.94). CONCLUSIONS: The 16-item PRIFOR exhibits good psychometric properties. Using this instrument to measure physical resilience would be beneficial to identify factors that could protect older people from negative health consequence. With the use of the PRIFOR, intervention effects could also be evaluated. It is helpful to strengthen resilience and thereby facilitate successful aging.

A novel intervention to reduce noninfectious and infectious complications associated with indwelling urethral catheters in hospitalized older patients: a quasi-experimental study.

BACKGROUND: Indwelling urethral catheters are widely used in clinical settings. Catheter-associated urinary tract infection has been recognized as a common adverse event in older patients. However, noninfectious complications are almost 5 times as common as infectious complications, and insufficient attention has been given to noninfectious complications. Given this importance, a novel intervention related to removing unnecessary catheters in a timely manner to promote, after removal, the recovery of self-voiding function is herein developed to reduce infectious and noninfectious complications associated with indwelling urethral catheters in hospitalized older patients. METHODS: A quasi-experimental study design was adopted. Patients aged 65 and older who had a urinary catheter placed within 24 h of hospital admission were included. All patients were allocated into either an intervention group, in which the novel intervention developed in the study was implemented, or a control group, who received care as usual. The outcomes of this study were to evaluate whether the novel intervention reduced the incidence of the following: catheter-associated urinary tract infections, catheter-associated noninfectious complications, decline in activities of daily living, and new nursing home admissions. RESULTS: Of 106 hospitalized older patients who consented to participate, 92 completed follow-up until discharge, including 49 in the control group and 43 in the intervention group. The patients in the intervention group were significantly older than those in the control group [83.72 ± 9.18 vs. 80.26 ± 7.66, p = 0.038], and no differences were found between the groups in other demographics or present health conditions. Multivariable logistic regression analysis showed that the control group was more likely to develop noninfectious complications [adjusted odds ratio: 3.01, 95% confidence interval: 1.32-6.81] and a decline in ADLs [adjusted odds ratio: 11.20, 95% confidence interval: 3.68-34.00]. CONCLUSIONS: A novel intervention can be effective as a means of reducing noninfectious complications associated with indwelling urethral catheters in hospitalized older patients. This approach will help to standardize urethral catheter care, and it highlights the fact that health care professionals can play a crucial role in preventing harm from urethral catheters.

Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy with an increasing incidence worldwide. Over the past decade, concurrent chemoradiotherapy (CCRT) with or without surgery is an emerging therapeutic approach for locally advanced ESCC. Unfortunately, many patients exhibit poor response or develop acquired resistance to CCRT. Once resistance occurs, the overall survival rate drops down rapidly and without proper further treatment options, poses a critical clinical challenge for ESCC therapy. Here, we utilized lab-created CCRT-resistant cells as a preclinical study model to investigate the association of chemoradioresistantresistance with miRNA-mediated cell plasticity alteration, and to determine whether reversing EMT status can re-sensitize refractory cancer cells to CCRT response. During the CCRT treatment course, refractory cancer cells adopted the conversion of epithelial to mesenchymal phenotype; additionally, miR-200 family members were found significantly down-regulated in CCRT resistance cells by miRNA microarray screening. Down-regulated miR-200 family in CCRT resistance cells suppressed E-cadherin expression through snail and slug, and accompany with an increase in N-cadherin. Rescuing expressions of miR-200 family members in CCRT resistance cells, particularly in miR-200b and miR-200c, could convert cells to epithelial phenotype by increasing E-cadherin expression and sensitize cells to CCRT treatment. Conversely, the suppression of miR-200b and miR-200c in ESCC cells attenuated E-cadherin, and that converted cells to mesenchymal type by elevating N-cadherin expression, and impaired cell sensitivity to CCRT treatment. Moreover, the results of ESCC specimens staining established the clinical relevance that higher N-cadherin expression levels associate with the poor CCRT response outcome in ESCC patients. Conclusively, miR-200b and miR-200c can modulate the conversion of epithelial-mesenchymal phenotype in ESCC, and thereby altering the response of cells to CCRT treatment. Targeting epithelial-mesenchymal conversion in acquired CCRT resistance may be a potential therapeutic option for ESCC patients.

A review of epidemic investigation on cold-chain food-mediated SARS-CoV-2 transmission and food safety consideration during COVID-19 pandemic.

COVID-19 has brought speculations on potential transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the pandemic. It is reported that the main route of virus transmission to be person-to-person by respiratory droplets; however, people have raised concerns on the possible transmission of SARS-CoV-2 to humans via food and packaging and its potential effects on food safety. This review discusses food safety issues in the COVID-19 pandemic and reveals its possible transmission in cold-chain food. The first outbreak of COVID-19 in late 2019 was associated with a seafood market in Wuhan, China, while the second outbreak of COVID-19 in June 2020 was also related to a seafood market in Beijing, China. As of 2020, several frozen seafood products linked with SARS-CoV-2 have been reported in China. According to the current survey and scientific studies, the risk of infection by SARS-CoV-2 from cold-chain food, food products, and food packaging is thought to be very low. However, studies on food cold chain contamination have shown that SARS-CoV-2 remained highly stable under refrigerated (4°C) and even in freezing conditions (-10 to -80°C). Since one mode of SARS-CoV-2 transmission appears to be touching contaminated surfaces, it is important to clean and sanitize food contact surfaces properly. Understanding food safety hazard risks is essential to avoid potential negative health effects and SARS-CoV-2 transmission in the food supply chain during the COVID-19 pandemic.

Time-Aware and Temperature-Aware Fire Evacuation Path Algorithm in IoT-Enabled Multi-Story Multi-Exit Buildings.

Temperature sensors with a communication capability can help monitor and report temperature values to a control station, which enables dynamic and real-time evacuation paths in fire emergencies. As compared to traditional approaches that identify a one-shot fire evacuation path, in this paper, we develop an intelligent algorithm that can identify time-aware and temperature-aware fire evacuation paths by considering temperature changes at different time slots in multi-story and multi-exit buildings. We first propose a method that can map three-dimensional multi-story multi-exit buildings into a two-dimensional graph. Then, a mathematical optimization model is proposed to capture this time-aware and temperature-aware evacuation path problem in multi-story multi-exit buildings. Six fire evacuation algorithms (BFS, SP, DBFS, TABFS, TASP and TADBFS) are proposed to identify the efficient evacuation path. The first three algorithms that do not address human temperature limit constraints can be used by rescue robots or firemen with fire-proof suits. The last three algorithms that address human temperature limit constraints can be used by evacuees in terms of total time slots and total temperature on the evacuation path. In the computational experiments, the open space building and the Taipei 101 Shopping Mall are all tested to verify the solution quality of these six algorithms. From the computational results, TABFS, TASP and TADBF identify almost the same evacuation path in open space building and the Taipei 101 Shopping Mall. BFS, SP DBFS can locate marginally better results in terms of evacuation time and total temperature on the evacuation path. When considering evacuating a group of evacuees, the computational time of the evacuation algorithm is very important in a time-limited evacuation process. Considering the extreme case of seven fires in eight emergency exits in the Taipei 101 Shopping Mall, the golden window for evacuation is 15 time slots. Only TABFS and TADBFS are applicable to evacuate 1200 people in the Taipei 101 Shopping Mall when one time slot is setting as one minute. The computational results show that the capacity limit for the Taipei 101 Shopping Mall is 800 people in the extreme case of seven fires. In this case, when the number of people in the building is less than 700, TADBFS should be adopted. When the number of people in the building is greater than 700, TABFS can evacuate more people than TADBFS. Besides identifying an efficient evacuation path, another significant contribution of this paper is to identify the best sensor density deployment at large buildings like the Taipei 101 Shopping Mall in considering the fire evacuation.

Hepatitis B virus surface gene pre-S2 mutant as a high-risk serum marker for hepatoma recurrence after curative hepatic resection.

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre-S2 region as a high-risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV-related HCC who underwent curative hepatic resection was analyzed for pre-S gene mutations using Pre-S Gene Chip. Results of the multivariate regression analysis showed that the serum pre-S2 mutant level and the American Joint Committee on Cancer stage were the two main independent high-risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence-free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion: Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV-induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre-S2 mutant in serum is, independently of tumor stage, an important high-risk marker for HCC recurrence after primary hepatic resection. (Hepatology 2018).

Huntingtin-Interacting Protein-1 Is an Early-Stage Prognostic Biomarker of Lung Adenocarcinoma and Suppresses Metastasis via Akt-mediated Epithelial-Mesenchymal Transition.

RATIONALE: Non-small cell lung cancer (NSCLC) carries a poor survival rate mainly because of metastasis. However, the molecular mechanisms that govern NSCLC metastasis have not been described. Because huntingtin-interacting protein-1 (HIP1) is known to play a role in tumorigenesis, we tested the involvement of HIP1 in NSCLC progression and metastasis. OBJECTIVES: HIP1 expression was measured in human NSCLC tumors, and correlation with survival outcome was evaluated. Furthermore, we investigated the ability of HIP1 to suppress metastasis. The molecular mechanism by which HIP1 contributes to suppress metastasis was investigated. METHODS: We used tissue arrays containing samples from 121 patients with NSCLC to analyze HIP1 expression by immunohistochemistry. To investigate the role of HIP1 expression on metastasis, we evaluated cellular mobility, migration, and invasion using lung adenocarcinoma (AdCA) cells with modified HIP1 expression levels. The human disease mouse models with the same cells were applied to evaluate the HIP1 suppressing metastasis and its mechanism in vivo. MEASUREMENTS AND MAIN RESULTS: HIP1 expression in AdCA progression was found to be an early-stage prognostic biomarker, with low expression correlated to poor prognosis. We also found HIP1 to be a metastatic suppressor in AdCA. HIP1 significantly repressed the mobility of lung cancer cells in vitro and in vivo and regulated the epithelial-mesenchymal transition by repressing AKT/glycogen synthase kinase-3ß/ß-catenin signaling. CONCLUSIONS: HIP1 serves as an early-stage prognostic biomarker and a metastatic suppressor. Reduced expression during AdCA progression can relieve HIP1 suppression of Akt-mediated epithelial-mesenchymal transition and thereby lead to development of late metastases and poor prognosis.

Castor is required for Hedgehog-dependent cell-fate specification and follicle stem cell maintenance in Drosophila oogenesis.

Asymmetric division of stem cells results in both self-renewal and differentiation of daughters. Understanding the molecules and mechanisms that govern differentiation of specific cell types from adult tissue stem cells is a major challenge in developmental biology and regenerative medicine. Drosophila follicle stem cells (FSCs) represent an excellent model system to study adult stem cell behavior; however, the earliest stages of follicle cell differentiation remain largely mysterious. Here we identify Castor (Cas) as a nuclear protein that is expressed in FSCs and early follicle cell precursors and then is restricted to differentiated polar and stalk cells once egg chambers form. Cas is required for FSC maintenance and polar and stalk cell fate specification. Eyes absent (Eya) is excluded from polar and stalk cells and represses their fate by inhibiting Cas expression. Hedgehog signaling is essential to repress Eya to allow Cas expression in polar and stalk cells. Finally, we show that the complementary patterns of Cas and Eya reveal the gradual differentiation of polar and stalk precursor cells at the earliest stages of their development. Our studies provide a marker for cell fates in this model and insight into the molecular and cellular mechanisms by which FSC progeny diverge into distinct fates.

A general method for growing large area mesoporous silica thin films on flat substrates with perpendicular nanochannels.

Here we introduce a new synthetic approach to grow mesoporous silica thin films with vertical mesochannels on centimeter-sized substrates via an oil-induced co-assembly process. Adding an oil, i.e., decane, into a CTAB-EtOH-TEOS ammonia solution leads to thin-film formation of mesoporous silica of controlled thickness between 20 and 100 nm with vertical mesochannels on various surfaces. The vertical mesoporous channels were evidenced by grazing incidence small-angle X-ray scattering (GISAXS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) characterizations. Decane played two roles: (a) as a pore expansion agent (up to 5.7 ± 0.5 nm) and (b) inducing vertically oriented hexagonal mesophases of micelle-silica composite. The production of periodic and vertical nanochannels is very robust, over many different substrate surfaces (from silicon to polystyrene), various silica precursors (TEOS, fumed silica, or zeolite seed), and many oils (decane, petroleum ether, or ethyl acetate). This wide robustness in the formation of vertical nanophases is attributed to a unique mechanism of confined synthesis of surfactant-silicate between two identical thin layers of oils on a substrate.

Field performance of 15 rain gardens in different cities in Taiwan.

Rain gardens are widely used for low impact development (LID) or as a nature-based solution (NbS). They help to reduce runoff, mitigate hot temperatures, create habitats for plants and insects, and beautify landscapes. Rain gardens are increasingly being established in urban areas. In Taiwan, the Ministry of Environment (MoE) initiated a rain garden project in Taipei city in 2018, and 15 rain gardens have since been constructed in different cities. These Taiwanese-style rain gardens contain an underground storage tank to collect the filtrated rainwater, which can be used for irrigation. Moreover, the 15 rain gardens are equipped with sensors to monitor temperature, rainfall, and underground water levels. The monitoring data were transmitted with Internet of Things (IoT) technology, enabling the capture and export of real-time values. The water retention, temperature mitigation, water quality, and ecological indices of the rain gardens were quantified using field data. The results from the young rain gardens (1-3 years) showed that nearly 100 % of the rainfall was retained onsite and did not flow out from the rain gardens; however, if the stored water was not used and the tanks were full, the rainwater from subsequent storms could not be stored, and the tanks overflowed. The surface temperatures of the rain garden and nearby impermeable pavement differed by an average of 2-4 °C. This difference exceeded 20 °C in summer at noon. The water in the underground storage tanks had very low levels of SS and BOD, with averages of 1.6 mg/L and 5.6 mg/L, respectively. However, the E. coli concentrations were high, and the average was 6283 CFU/100 mL; therefore, washing or drinking water is not recommended. The ecological indices, i.e., the Shannon and Simpson indices, demonstrated the good flora status of the rain gardens after one year. Although the weather differed by city, the performance of the rain gardens in terms of water retention, temperature mitigation, rainwater harvesting, and providing biological habitats was consistent. However, maintenance influences rain garden performance. If the stored water is not frequently used, the stored volume is reduced, and the stored water quality degrades.

A game-based multimedia application to improve the ability of clinical nurses to perform geriatric care: A randomized controlled trial.

BACKGROUND: Given the realities of global aging, maintaining Comprehensive Geriatric Assessment (CGA) abilities among clinical nurses is very important. Newer methods of continuing education are needed to engage nurses in CGA education. Using multimedia and game-based applications in CGA education (CGA APP) may be an effective method for continuing education. OBJECTIVES: To test the effectiveness of CGA APP in improving nurses' confidence in their abilities to perform geriatric care. DESIGN: A randomized, controlled trial were adopted. SETTING: An 1343-bed tertiary-care medical center in southern Taiwan. PARTICIPANTS: A total of 1250 nurses met inclusion criteria in 35 adult wards. We employed stratified sampling to recruit a total of 132 nurses proportional to the number of nurses in each ward, from January to March 2019. METHODS: Based on the Octalysis gamification framework, the CGA APP was developed. Participants were randomly assigned to either an CGA APP or a control group, which received traditional classroom learning of the same content. The main outcome was improvement in confidence in geriatric care ability were measured before and end of the training session, and six months later. RESULTS: There were no differences in baseline characteristics (except years of experience as a registered nurse), knowledge, attitudes or confidence of geriatric care between the two groups. Clinical nurses in the CGA APP group demonstrated significantly higher confidence in their geriatric care abilities than control group immediately after the intervention (75.85 ± 10.71 vs. 65.93 ± 8.49, p < 0.001) and six-months later (71.13 ± 9.69 vs. 63.57 ± 8.78, p < 0.001). After using GEE to control the confounding variable, the CGA APP group remained significantly higher confidence in their geriatric care abilities than control group. CONCLUSIONS: Use of multimedia game-based applications my better engage and teach practicing clinical than traditional learning methods. Our findings suggest that such interventions be further developed and tested for a larger variety of continuing education needs.

Treatment with autophagic inhibitors enhances oligonol­induced apoptotic effects in nasopharyngeal carcinoma cells.

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.