Clinical Characteristics of Children With Foreign Bodies in the Digestive Tract and Analysis of Risk Factors for Serious Complications.

Foreign bodies (FBs) in the digestive tract are common in children, we analyzed the clinical characteristics of children with FBs in the digestive tract and discuss the risk factors for serious complications. We retrospectively reviewed clinical data of 139 children with FBs in the digestive tract. Based on the severity of complications caused by FBs, the patients were divided into risk and general groups for analysis and comparison. Significant differences were observed in the retention sites of FBs, the diameter of FBs retained in the esophagus, FBs retention time exceeding 24 h, and the absence of witnesses between the 2 groups. Inadequate care, button batteries (BBs), ingested mmFBs, FBs retained in the esophagus, long-term retention, and giant gastric bezoars may cause serious complications. In addition to treating FBs and the complications, clinicians should emphasize the importance of childcare to prevent the ingestion of FBs.

The Prognostic Value of D-Dimer in Patients with Acute Myocardial Infarction: A Retrospective Longitudinal Cohort Study in Taiwan.

Background: Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. Methods: We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Results: Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). Conclusions: This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.

DIPAN: Detecting personalized intronic polyadenylation derived neoantigens from RNA sequencing data.

Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.

Translation, adaptation, and validation of a Chinese version of the Hypertension Self-Care Activity Level effects (H-SCALE) for patients with hypertension.

BACKGROUND: Lifestyle modification is an essential component of prevention and management of hypertension. Existing instruments in Taiwan focus on assessing lifestyle modifications by evaluating medication adherence or confidence in controlling blood pressure. However, other self-care activities, such as diet, physical activity, weight management, smoking, and alcohol consumption are also important. The Hypertension Self-Care Activity Level Effects (H-SCALE) is one such instrument, but there are no similar tools available in Taiwan. AIM: This study aimed to translate the H-SCALE into Chinese and test its validity, and reliability in a sample of adults with hypertension. METHODS: The English version of the 31-item H-SCALE was translated into Chinese using the forward-backward method. The content validity index (CVI) of the translated scale was determined by five experts in hypertension. Item analysis was conducted with a pilot sample of 20 patients with hypertension. Cronbach's α was used to establish the internal consistency reliability for the Chinese version of the H-SCALE (H-SCALE-C). Exploratory factor analysis (EFA) explored the structure of the H-SCALE-C. Additionally, construct validity was examined with confirmatory factor analysis (CFA). Patients with hypertension were recruited by convenience sampling from a cardiovascular outpatient clinic of a medical center in northern Taiwan. A total of 318 patients met the inclusion criteria and participated in factor analysis in the study. RESULTS: Pilot testing of the scale items indicated most patients could not accurately estimate the number of days of alcohol consumption for the previous week. Therefore, three alcohol-related items were removed. The adaptation resulted in a 28-item H-SCALE-C. EFA revealed a 4-factor solution with 13 items that explained 63.93% of the total variance. CFA indicated a good fit for a 4-factor model and construct validity was acceptable. Internal consistency reliability was acceptable (Cronbach's alpha for the four subscales ranged from 0.65 to 0.94). Convergent validity was acceptable, and discriminant validity was significant. CONCLUSIONS: The H-SCALE-C is a valid, reliable tool for promptly assessing life-style activities for patients with hypertension in Taiwan. The instrument is suitable for assisting healthcare providers in evaluating self-care activities, which could be used to facilitate lifestyle modifications for patients with hypertension.

Mediating Effect of Heart Rate Variability on the Relationship Between Anxiety Symptoms and Blood Pressure in Patients with Primary Hypertension.

Patients with hypertension (HTN) are at increased risk of developing cardiovascular disease, which can be reduced with blood pressure (BP) control. Anxiety can contribute to high BP and low heart rate variability (HRV). Although relationships between social support, self-rated health-status (SRHS), anxiety and measures of HRV and BP have been suggested, they have not been clearly established. This cross-sectional correlational study aimed to 1) examine relationships between social support, SRHS, and anxiety; and 2) examine if HRV mediated relationships between anxiety symptoms and BP. Patients with primary HTN were recruited from a cardiovascular outpatient clinic using convenience sampling (N = 300). Data included scale scores for SRHS, social support, and anxiety (Hospital Anxiety and Depression Scale). A handheld limb-lead electrocardiogram monitor measured HRV, using the ratio of low-frequency bands to high-frequency bands; an automatic sphygmomanometer measured systolic and diastolic blood pressure (SBP and DBP, respectively). Path analysis of structural equation models examined relationships between variables; the bootstrap method examined the mediating effects of HRV. Analysis showed scores for SRHS and social support had a direct effect on anxiety scores. Scores for anxiety directly affected HRV and BP. HRV also had a direct effect on BP. Bootstrapping indicated HRV mediated the relationship between anxiety symptoms and BP. The final model indicated SRHS, social support, and anxiety symptoms together explained 80% of SBP and 33% of DBP. These findings suggest HRV could be used to measure the effectiveness of strategies aimed at reducing anxiety and improving control of BP.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

Enhancing extracellular monascus pigment production in submerged fermentation with engineered microbial consortia.

In this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.

Comprehensive characterization of somatic mutations associated with chimeric RNAs in human cancers.

Chimeric RNAs, which can arise from gene recombination at the DNA level or non-canonical splicing events at the RNA level, have been identified as important roles in human tumors. Dysregulated gene expression caused by somatic mutations and altered splicing patterns of oncogenes or tumor suppressor genes can contribute to the development of tumors. Therefore, investigating the formation mechanism of chimeric RNAs via somatic mutations is critical for understanding tumor pathogenesis. This project is the first to propose studying the association between somatic single nucleotide variants and chimeric RNAs, identifying around 2900 somatic SNVs affecting chimeric RNAs in pan-cancer level. The somatic SNVs on chimeric RNAs were commonly observed in various types of tumor tissues, providing a valuable resource for future study. Additionally, these SNVs show distinct tumor specificity, and those with high frequency had a significant impact on the survival time of patients with tumors. Further research revealed that somatic SNVs associated with chimeric RNA (chiR-SNVs) were typically found within 10 nt of the junction site of chimeric RNAs and had a particularly significant effect on chimeric RNAs from different chromosomes. The enrichment analysis revealed that chiR-SNVs were significantly overrepresented in oncogenes and genes related to RNA binding proteins involved in RNA splicing, which could imply that chiR-SNVs may disrupt the process of RNA splicing and induce the occurrence of chimeric RNAs. This study sheds light on the potential molecular interaction mechanism between somatic SNVs and chimeric RNAs, which opens up a new avenue for researching disease pathway and tumorigenesis development.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

An atlas of cell-type-specific interactome networks across 44 human tumor types.

BACKGROUND: Biological processes are controlled by groups of genes acting in concert. Investigating gene-gene interactions within different cell types can help researchers understand the regulatory mechanisms behind human complex diseases, such as tumors. METHODS: We collected extensive single-cell RNA-seq data from tumors, involving 563 patients with 44 different tumor types. Through our analysis, we identified various cell types in tumors and created an atlas of different immune cell subsets across different tumor types. Using the SCINET method, we reconstructed interactome networks specific to different cell types. Diverse functional data was then integrated to gain biological insights into the networks, including somatic mutation patterns and gene functional annotation. Additionally, genes with prognostic relevance within the networks were also identified. We also examined cell-cell communications to investigate how gene interactions modulate cell-cell interactions. RESULTS: We developed a data portal called CellNetdb for researchers to study cell-type-specific interactome networks. Our findings indicate that these networks can be used to identify genes with topological specificity in different cell types. We also found that prognostic genes can deconvolved into cell types through analyzing network connectivity. Additionally, we identified commonalities and differences in cell-type-specific networks across different tumor types. Our results suggest that these networks can be used to prioritize risk genes. CONCLUSIONS: This study presented CellNetdb, a comprehensive repository featuring an atlas of cell-type-specific interactome networks across 44 human tumor types. The findings underscore the utility of these networks in delineating the intricacies of tumor microenvironments and advancing the understanding of molecular mechanisms underpinning human tumors.

The Angiotensin II Receptor Neprilysin Inhibitor LCZ696 Inhibits the NLRP3 Inflammasome By Reducing Mitochondrial Dysfunction in Macrophages and Alleviates Dextran Sulfate Sodium-induced Colitis in a Mouse Model.

The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1ß and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate. LCZ696 also reduces caspase-11 and GSDMD activation, lactate dehydrogenase release, propidium iodide uptake, and the extracellular release of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in ATP-activated macrophages, suggesting a potential mitigation of pyroptosis. Mechanistically, LCZ696 lowers mitochondrial reactive oxygen species and preserves mitochondrial integrity. Importantly, it does not significantly impact NLRP3, proIL-1ß, inducible nitric oxide synthase, cyclooxygenase-2 expression, or NF-κB activation in lipopolysaccharide-activated macrophages. LCZ696 partially inhibits the NLRP3 inflammasome through the induction of autophagy. In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1ß and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment.

Sense of Coherence as a Mediator Between Functional Status and Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Poor functional status relating to heart failure (HF) negatively affects health-related quality of life (HRQOL). Patients with HF, especially those with New York Heart Association (NYHA) Class III or IV HF, often exhibit poor HRQOL because of physical limitations and HF-related symptoms. Although sense of coherence (SOC) has been reported to be a determinant of HRQOL, its role as a mediator between functional status and HRQOL remains unclear, and few studies have explored the prevalence of HF in patients in NYHA Classes I and II. PURPOSE: This study was designed to investigate SOC as a mediator between different functional status classes and HRQOL in patients with HF. METHODS: A cross-sectional study was conducted on patients with HF recruited from a hospital in northern Taiwan from April 2020 to September 2020. The Minnesota Living with Heart Failure Questionnaire and a questionnaire on sociodemographic characteristics; functional classification in terms of NYHA Classes I, II, and III; and SOC were administered. The PROCESS v3.5 (by Andrew F. Hayes) macro was applied to analyze the effects, and Model 4 was used to examine the mediating role of SOC on the relationship between NYHA functional class and HRQOL. RESULTS: Of the 295 participants, SOC was found to mediate the effects of functional status on HRQOL more significantly in patients in Class II than those in Class III but not more significantly in patients in Class I than those in Class III. A weaker mediating effect of SOC was noted on the relationship between functional status and HRQOL in patients with HF in NYHA Class II than those in Class III. CONCLUSIONS: In patients with HF, poor functional status often reduces HRQOL significantly. SOC mediates the relationship between functional status and HRQOL more significantly in those in NYHA Class II than those in Class III. Nursing staff should work to increase patients' SOC by strengthening their coping capacity and improving their functional status to improve their HRQOL.

Circ_0002395 promotes aerobic glycolysis and proliferation in pancreatic adenocarcinoma cells via miR-548c-3p/PDK1 axis.

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.

Discovery of N-(phenylsulfonyl)thiazole-2-carboxamides as potent α-glucosidase inhibitors.

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC50 value of 53.0 ± 7.7 µM, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 ± 9.2 µM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.

Novel Coumarin Derivatives Inhibit the Quorum Sensing System and Iron Homeostasis as Antibacterial Synergists against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound 4t was identified as the most effective biofilm inhibitor (IC50 = 3.6 µM). Further mechanistic studies have confirmed that 4t not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in P. aeruginosa. Additionally, 4t significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that 4t is a potentially novel antibacterial synergist candidate to treat bacterial infections.

Unravelling the impact of dental workforce training and education programmes on policy evolution: a mixed-method study protocol.

BACKGROUND: The dental workforce plays a crucial role in delivering quality oral healthcare services, requiring continuous training and education to meet evolving professional demands. Understanding the impact of dental workforce training and education programmes on policy evolution is essential for refining existing policies, implementing evidence-based reforms and ensuring the growth of the dental profession. Therefore, this study protocol aims to assess the influence of dental workforce training and education programmes on policy evolution in Malaysia. METHODS: A mixed-method research design will be employed, combining quantitative surveys and qualitative interviews. Stakeholder theory and policy change models will form the theoretical framework of the study. Participants from various stakeholder groups will be recruited using purposive sampling. Data collection will involve surveys and one-on-one semi-structured interviews. Descriptive statistics, inferential analysis and thematic analysis will be used to analyse the data. Integration of quantitative and qualitative data will be used to provide a comprehensive understanding of the data. DISCUSSION: This study will shed light on factors influencing policy decisions related to dental education and workforce development in Malaysia. The findings will inform evidence-based decision-making, guide the enhancement of dental education programmes and improve the quality of oral healthcare services. Challenges related to participant recruitment and data collection should be considered, and the study's unique contribution to the existing body of knowledge in the Malaysian context will be discussed.

AGEs promote atherosclerosis by increasing LDL transcytosis across endothelial cells via RAGE/NF-κB/Caveolin-1 pathway.

OBJECTIVE: To elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease. METHODS AND RESULTS: The effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression. Our molecular assessment revealed that AGEs activate the RAGE-NF-κB signaling, which then recruits the NF-κB subunit p65 to the RAGE promoter and consequently enhances RAGE transcription, thereby forming a positive feedback loop between the NF-κB signaling and RAGE expression. Increased NF-κB signaling ultimately upregulated Caveolin-1, promoting LDL transcytosis, and inhibition of RAGE suppressed AGE-induced LDL transcytosis. In ApoE-/- mice on a high-fat diet, atherosclerotic plaque formation was accelerated by AGEs but suppressed by EC-specific knockdown of RAGE. CONCLUSION: AGEs accelerate the development of diabetes-related AS by increasing the LDL transcytosis in ECs through the activation of the RAGE/NF-κB/Caveolin-1 axis, which may be targeted to prevent or treat diabetic macrovascular complications.

Efficiencies of Various in situ Polymerizations of Liquid Electrolytes and the Practical Implications for Quasi Solid-state Batteries.

In situ polymerization of liquid electrolytes is currently the most feasible way for constructing solid-state batteries, which, however, is affected by various interfering factors of reactions and so the electrochemical performance of cells. To disclose the effects from polymerization conditions, two types of generally used in situ polymerizing reactions of ring-opening polymerization (ROP) and double bond radical polymerization (DBRP) were investigated on the aspects of monomer conversion and electrochemical properties (Li+ -conductivity and interfacial stability). The ROP generated poly-ester and poly-carbonate show a high monomer conversion of ≈90 %, but suffer a poor Li+ -conductivity of lower than 2×10-5  S cm-1 at room temperature (RT). Additionally, the terminal alkoxy anion derived from the ROP is not resistant to high-voltage cathodes. While, the DBRP produced poly-VEC(vinyl ethylene carbonate) and poly-VC(vinylene carbonate) show lower monomer conversions of 50-80 %, delivering relatively higher Li+ -conductivities of 2×10-4  S cm-1 at RT. Compared two polymerizing reactions and four monomers, the VEC-based F-containing copolymer possesses advantages in Li+ -conductivity and antioxidant capacity, which also shows simultaneous stability towards Li-metal with the help of LiF-based passivating layer, allowing a long-term stable cycling of high-voltage quasi solid-state cells.

Stable Hexaazatrinaphthalene-Based Planar Polymer Cathode Material for Organic Lithium-Ion Batteries.

Organic materials have garnered intensive focus as a new group of electrodes for lithium-ion batteries (LIBs). However, many reported organic electrodes so far still exhibit unsatisfying cycling stability because of the dissolution in the electrolytes. Herein, a novel azo-linked hexaazatrianphthalene (HATN)-based polymer (AZO-HATN-AQ) is designed and fabricated by the polymerization of trinitrodiquinoxalino[2,3-a:2',3'-c]phenazine (HATNTN) and 2,6-diaminoanthraquinone (DAAQ). The abundant redox-active sites, extended π-conjugated planar conformation, and low energy gap endow the AZO-HATN-AQ electrode with high theoretical capacity, excellent solubility resistance, and fast Li-ion transport. In particular, the fully lithiated AZO-HATN-AQ still keeps the planar structure, contributing to the excellent cycling stability. As a result, AZO-HATN-AQ cathodes show high specific capacity (240 mAh g-1 at 0.05 A g-1), prominent rate capability (98 mAh g-1 at 8 A g-1), and outstanding cycling stability (120 mAh g-1 after 2000 cycles at 4 A g-1 with 85.7% capacity retention) simultaneously. This study demonstrates that rational structure design of the polymer electrodes is an effective approach to achieving excellent comprehensive electrochemical performance.