Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.

NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.

Anesthesia for cesarean delivery and subsequent depression: A nationwide retrospective cohort study.

BACKGROUND: Postpartum depression is a major psychiatric disorder associated with maternal suicide and child developmental disturbances. In this study, we aimed to investigate whether general anesthesia for cesarean delivery is associated with a higher rate of new-onset depression after delivery than neuraxial anesthesia. METHODS: This is a nationwide retrospective cohort study using data retrieved from the National Health Insurance Research Database between 2014 and 2018. Women who had cesarean delivery under general or neuraxial anesthesia were enrolled. After 1:4 propensity score matching, there were 4544 and 18,176 women under the general and neuraxial anesthesia groups, respectively. The primary outcome was new-onset depression diagnosed after delivery in a time-to-event analysis setting. RESULTS: After propensity-score matching, the rate of new-onset depression diagnosed within 1 year was 1.10 % (50/4488) and 0.86 % (157/18176) after cesarean delivery under general and neuraxial anesthesia, respectively. For depression diagnosed within 90 days of delivery, significant difference between the two groups was noted (0.51 % vs. 0.30 %, P = 0.031). In the time-to-event analysis with Cox regression model, women who delivered under general anesthesia were associated with significantly higher risk of postpartum depression within 90 days (Hazard ratio [HR], 1.71; 95 % CI, 1.05-2.79) compared with those under neuraxial anesthesia. LIMITATIONS: The observational design only allows asserting association, rather than establishing causality between exposure and outcomes. CONCLUSIONS: Women who underwent cesarean delivery under general anesthesia had a higher risk of subsequent depression within 90 days than those under neuraxial anesthesia. Early screening for depressive disorders might facilitate timely management.

Direct Excitation Transfer in Plasmonic Metal-Chalcopyrite-Hybrids: Insights from Single Particle Line Shape Analysis.

Hybrid nanomaterials containing both noble metal and semiconductor building blocks provide an engineerable platform for realizing direct or indirect charge and energy transfer for enhanced plasmonic photoconversion and photocatalysis. In this work, silver nanoparticles (AgNPs) and chalcopyrite (CuFeS2) nanocrystals (NCs) are combined into a AgNP@CuFeS2 hybrid structure comprising NCs embedded in a self-assembled lipid coating around the AgNP core. In AgNP@CuFeS2 hybrid structures, both metallic and semiconductor NCs support quasistatic resonances. To characterize the interactions between these resonances and their effect on potential charge and energy transfer, direct interfacial excitation transfer between the AgNP core and surrounding CuFeS2 NCs is probed through single particle line shape analysis and supporting electromagnetic simulations. These studies reveal that CuFeS2 NCs localized in the evanescent field of the central AgNP induce a broadening of the metal NP line shape that peaks when an energetic match between the AgNP and CuFeS2 NC resonances maximizes direct energy transfer. Dimers of AgNPs whose resonances exhibit poor energetic overlap with the CuFeS2 NC quasistatic resonance yield much weaker line shape broadening in a control experiment, corroborating the existence of resonant energy transfer in the AgNP@CuFeS2 hybrid. Resonant coupling between the metallic and semiconductor building blocks in the investigated hybrid architecture provides a mechanism for utilizing the large optical cross-section of the central AgNP to enhance the generation of reactive charge carriers in the surrounding semiconductor NCs for potential applications in photocatalysis.

Evaluation of the Stereochemistry of Staphyloferrin A for Developing Staphylococcus-Specific Targeting Conjugates.

Bacteria in the genus Staphylococcus are pathogenic and harmful to humans. Alarmingly, some Staphylococcus, such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) have spread worldwide and become notoriously resistant to antibiotics, threatening and concerning public health. Hence, the development of new Staphylococcus-targeting diagnostic and therapeutic agents is urgent. Here, we chose the S. aureus-secreted siderophore staphyloferrin A (SA) as a guiding unit. We developed a series of Staphyloferrin A conjugates (SA conjugates) and showed the specific targeting ability to Staphylococcus bacteria. Furthermore, among the structural factors we evaluated, the stereo-chemistry of the amino acid backbone of SA conjugates is essential to efficiently target Staphylococci. Finally, we demonstrated that fluorescent Staphyloferrin A probes (SA-FL probes) could specifically target Staphylococci in complex bacterial mixtures.

Valorization of broiler edible byproducts: a chicken-liver hydrolysate with hepatoprotection against binge drinking.

Over 10,000 metric-ton broiler livers are produced annually in Taiwan. Concerning unpleasant odor and healthy issue, broiler livers are not attractive to consumers. Although the patented chicken-liver hydrolysates (CLHs) through pepsin digestion possess several biofunctionalities, there is no study on hepatoprotection of CLH-based formula capsule (GBHP01) against binge drinking (Whiskey, 50% Alc./Vol.). GBHP01 led to an accelerated blood-alcohol clearance in rats, as evidenced by lowering blood-alcohol increment within 0 to 4 h, increasing blood-alcohol decrement within 4 to 8 h, and smaller blood alcohol concentration areas under the curve (BAC AUC) in the 8-h period (p < 0.05). The ameliorative effects of GBHP01 against binge drinking in rats over 6 wk were attributed to accelerated alcohol metabolism by further increasing alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities while downregulating cytochrome P450 2E1 (CYP2E1) protein expression, elevating antioxidant capacity, decreasing zonula occludens-1 (ZO-1) protein decrement and serum endotoxin, and reducing inflammation related protein levels, that is, toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK), and proinflammatory cytokines. The development of CLH supplements could not only enhance the added value of broiler livers through nutraceutical development but also offer a strategy to maximize the utilization of poultry processing residues, as shown in this study.

Correlations of factors associated with job values, job stress and job satisfaction among hospital nursing assistants.

AIM: To investigate the correlation between job values, job stress, and job satisfaction among nursing assistants in a hospital setting. DESIGN: A cross-sectional study. METHODS: Data were collected from nursing assistants working in a regional hospital and a medical center in Northern Taiwan. A self-rated structured questionnaire was used to collect data on participants' demographic characteristics, job values, job stress, and job satisfaction. Descriptive statistics, t test, one-way analysis of variance, Pearson's correlation coefficient, and stepwise regression were used for data analysis. RESULTS: A total of 135 questionnaires were distributed; of them, 132 were returned, resulting in a response rate of 97.8%. The average age of the participants was 57.08 ± 5.86 years, with the majority being female, high school educated, and married. Most participants (70%) had >5 years of experience in working as nursing assistants. The average job satisfaction score of was 63.63, indicating a moderate level of job satisfaction. Job satisfaction exhibited a significantly positive correlation with job values but a significantly negative correlation with job stress. Job value was negatively correlated with job stress. Stepwise regression revealed that job values significantly explained the variance in job satisfaction among hospital nursing assistants. CONCLUSIONS: Nursing assistants are integral to clinical practice. To enhance their job satisfaction and professional development, health-care institutions and policymakers should implement strategies such as providing continual training, offering recognition and rewards to enhance sense of accomplishment. PATIENT OR PUBLIC CONTRIBUTION: This study involves no patient or public contribution.

Fabrication of Stable Liquid-like Wetting Buckled Surfaces as Bioinspired Antibiofouling Coatings by Using Silicon-Containing Block Copolymers.

Inspired by animals with a slippery epidermis, durable slippery antibiofouling coatings with liquid-like wetting buckled surfaces are successfully constructed in this study by combining dynamic-interfacial-release-induced buckling with self-assembled silicon-containing diblock copolymer (diBCP). The core diBCP material is polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS). Because silicon-containing polymers with intrinsic characters of low surface energy, they easily flow over and cover a surface after it has undergone controlled thermal treatment, generating a slippery wetting layer on which can eliminate polar interactions with biomolecules. Additionally, microbuckled patterns result in curved surfaces, which offer fewer points at which organisms can attach to the surface. Different from traditional slippery liquid-infused porous surfaces, the proposed liquid-like PDMS wetting layer, chemically bonded with PS, is stable and slippery but does not flow away. PS-b-PDMS diBCPs with various PDMS volume fractions are studied to compare the influence of PDMS segment length on antibiofouling performance. The surface characteristics of the diBCPs─ease of processing, transparency, and antibiofouling, anti-icing, and self-cleaning abilities─are examined under various conditions. Being able to fabricate ecofriendly silicon-based lubricant layers without needing to use fluorinated compounds and costly material precursors is an advantage in industrial practice.

Hypothyroidism following carbon monoxide poisoning: An epidemiological study supported by animal experiments.

Previous studies have suggested a possible association between carbon monoxide poisoning (COP) and hypothyroidism, but the evidence is limited. Therefore, the aim of this study was to further investigate this relationship. Using data from the Taiwan National Health Research Database, we identified 32,162 COP patients and matched with 96,486 non-COP patients by age and index date for an epidemiological study. The risk of hypothyroidism was compared between the two cohorts until 2018. Independent predictors of hypothyroidism were analyzed using competing risk analysis. An animal study was also conducted to support the findings. COP patients had an increased risk of hypothyroidism compared to non-COP patients in the overall analysis (adjusted hazard ratio [AHR]= 3.88; 95 % confidence interval [CI]: 3.27-4.60) and in stratified analyses by age, sex, and comorbidities. The increase in the overall risk persisted even after more than six years of follow-up (AHR= 4.19; 95 % CI: 3.18-5.53). Independent predictors of hypothyroidism, in addition to COP, included age ≥65 years, female sex, hyperlipidemia, and mental disorder. The animal study showed damages in the hypothalamus, pituitary gland, and thyroid, as well as altered hormone levels 28 days after COP exposure. The epidemiological results showed an increased risk of hypothyroidism in COP patients, which was further supported by the animal study. These findings suggest the need for close monitoring of thyroid function in COP patients, especially in those who are age ≥65 years, female, and have hyperlipidemia or mental disorder.

Unplanned emergency department visits within 90 days of hip hemiarthroplasty for osteoporotic femoral neck fractures: Reasons, risks, and mortalities.

Objectives: Bipolar hemiarthroplasty is commonly performed to treat displaced femoral neck fractures in osteoporotic patients. This study aimed to assess the occurrence and outcomes of unplanned return visits to the emergency department (ED) within 90 days following bipolar hemiarthroplasty for displaced femoral neck fractures. Methods: The clinical data of 1322 consecutive patients who underwent bipolar hemiarthroplasty for osteoporotic femoral neck fractures at a tertiary medical center were analyzed. Data from the patients' electronic medical records, including demographic information, comorbidities, and operative details, were collected. The risk factors and mortality rates were analyzed. Results: Within 90 days after surgery, 19.9% of patients returned to the ED. Surgery-related reasons accounted for 20.2% of the patient's returns. Older age, a high Charlson comorbidity index score, chronic kidney disease, and a history of cancer were identified as significant risk factors for unplanned ED visits. Patients with uncemented implants had a significantly greater risk of returning to the ED due to periprosthetic fractures than did those with cemented implants (P = 0.04). Patients who returned to the ED within 90 days had an almost fivefold greater 1-year mortality rate (15.2% vs 3.1%, P < 0.001) and a greater overall mortality rate (26.2% vs 10.5%, P < 0.001). Conclusions: This study highlights the importance of identifying risk factors for unplanned ED visits after bipolar hemiarthroplasty, which may contribute to a better prognosis. Consideration should be given to the use of cemented implants for hemiarthroplasty, as uncemented implants are associated with a greater risk of periprosthetic fractures.

Peripheral blood cells RNA-seq identifies differentially expressed gene network linked to lymphocyte subsets alterations and active lupus nephritis associated with declines in renal function.

Background: The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN). Methods: We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined. We stratified 55 of 95 patients as high or low subset group according to the median percentage of each lymphocyte subset and the association with changes in the eGFR (ΔeGFR) were analyzed. Peripheral blood bulk RNA-seq to identify differentially expressed genes (DEGs) in 9 active LN vs. 9 inactive LN patients and the DEG-derived network was constructed by Ingenuity Pathway Analysis (IPA). Results: The mean ΔeGFR of low NK-low memory CD4+ T-high naive CD4+ T group (31.01 mL/min/1.73 m2) was significantly greater than that of high NK-high memory CD4+ T-low naive CD4+ T group (11.83 mL/min/1.73 m2; P = 0.0175). Kaplan-Meier analysis showed that the median time for ΔeGFR decline to mean ΔeGFR is approximately 10 years for high NK-high memory CD4+ T-low naive CD4+ T group and approximately 5 years for low NK-low memory CD4+ T-high naive CD4+ T group (log-rank test P = 0.0294). Conclusions: Our study highlighted important connections between DEG-derived network, lymphocyte subset composition, and disease status of LN and GN. A novel scoring system based on lymphocyte subset proportions effectively stratified patients into groups with differential risks for declining renal function.

Tissue distribution and retention drives efficacy of rapidly clearing VHL-based PROTACs.

BACKGROUND: Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics are not known. METHODS: A typical von Hippel-Lindau tumor suppressor (VHL)-PROTAC 14C-A947 (BRM degrader)-was synthesized and its tissue distribution kinetics was studied by quantitative whole-body autoradiography (QWBA) and tissue excision in rats following IV dosing. Bile duct-cannulated (BDC) rats allowed the elucidation of in vivo clearance pathways. Distribution kinetics was evaluated in the tissues and tumors of mice to support PK-PD correlation. In vitro studies enabled the evaluation of cell uptake mechanisms and cell retention properties. RESULTS: Here, we show that A947 quickly distributes into rat tissues after IV dosing, where it accumulates and is retained in tissues such as the lung and liver although it undergoes fast clearance from circulation. Similar uptake/retention kinetics enable tumor growth inhibition over 2-3 weeks in a lung cancer model. A947 quickly excretes in the bile of rats. Solute carrier (SLC) transporters are involved in hepatocyte uptake of PROTACs. Sustained BRM protein degradation is seen after extensive washout that supports prolonged cell retention of A947 in NCI-H1944 cells. A947 tissue exposure and pharmacodynamics are inversely correlated in tumors. CONCLUSIONS: Plasma sampling for VHL-PROTAC does not represent the tissue concentrations necessary for efficacy. Understanding of tissue uptake and retention could enable less frequent IV administration to be used for therapeutic dosing.

Proteolysis-targeting chimeras (PROTACs) are a type of potential cancer medicine designed to target proteins primarily present in tumours. There is limited data on how it is absorbed, distributed, metabolised and excreted from tissues. Here, we studied the tissue distribution of synthetic PROTAC molecules labelled with radioactivity following intravenous injection in rodent models. We find that PROTAC can rapidly distribute to target tumour tissues and its prolonged retention within the tumour cells can contribute to prevention of further tumour growth, as demonstrated in the lung cancer model. These findings suggest the evaluation of PROTAC therapeutic effectiveness directly from tumour tissues provides more relevant assessment than sampling from blood circulation, which may have implications for a reduction in intravenous dosing.

Assessment of the feasibility of human amniotic membrane stem cell-derived cardiomyocytes in vitro.

Myocardial infarction (MI) is a leading cause of death worldwide, resulting in extensive loss of cardiomyocytes and subsequent heart failure. Inducing cardiac differentiation of stem cells is a potential approach for myocardial regeneration therapy to improve post-MI prognosis. Mesenchymal stem cells (MSCs) have several advantages, including immune privilege and multipotent differentiation potential. This study aimed to explore the feasibility of chemically inducing human amniotic membrane MSCs (hAMSCs) to differentiate into cardiomyocytes in vitro. Human amniotic membrane (AM) samples were obtained from routine cesarean sections at Far Eastern Memorial Hospital. The isolated cells exhibited spindle-shaped morphology and expressed surface antigens CD73, CD90, CD105, and CD44, while lacking expression of CD19, CD11b, CD19, CD45, and HLA-DR. The SSEA-1, SSEA-3, and SSEA-4 markers were also positive, and the cells displayed the ability for tri-lineage differentiation into adipocytes, chondrocytes, and osteoblasts. The expression levels of MLC2v, Nkx2.5, and MyoD were analyzed using qPCR after applying various protocols for chemical induction, including BMP4, ActivinA, 5-azacytidine, CHIR99021, and IWP2 on hAMSCs. The group treated with 5 ng/ml BMP4, 10 ng/ml Activin A, 10 µM 5-azacytidine, 7.5 µM CHIR99021, and 5 µM IWP 2 expressed the highest levels of these genes. Furthermore, immunofluorescence staining demonstrated the expression of α-actinin and Troponin T in this group. In conclusion, this study demonstrated that hAMSCs can be chemically induced to differentiate into cardiomyocyte-like cells in vitro. However, to improve the functionality of the differentiated cells, further investigation of inductive protocols and regimens is needed.

The Xanthine Derivative KMUP-1 Inhibits Hypoxia-Induced TRPC1 Expression and Store-Operated Ca2+ Entry in Pulmonary Arterial Smooth Muscle Cells.

Exposure to hypoxia results in the development of pulmonary arterial hypertension (PAH). An increase in the intracellular Ca2+ concentration ([Ca2+]i) in pulmonary artery smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation. This study investigated the mechanism by which KMUP-1, a xanthine derivative with phosphodiesterase inhibitory activity, inhibits hypoxia-induced canonical transient receptor potential channel 1 (TRPC1) protein overexpression and regulates [Ca2+]i through store-operated calcium channels (SOCs). Ex vivo PASMCs were cultured from Sprague-Dawley rats in a modular incubator chamber under 1% O2/5% CO2 for 24 h to elucidate TRPC1 overexpression and observe the Ca2+ release and entry. KMUP-1 (1 µM) inhibited hypoxia-induced TRPC family protein encoded for SOC overexpression, particularly TRPC1. KMUP-1 inhibition of TRPC1 protein was restored by the protein kinase G (PKG) inhibitor KT5823 (1 µM) and the protein kinase A (PKA) inhibitor KT5720 (1 µM). KMUP-1 attenuated protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 1 µM)-upregulated TRPC1. We suggest that the effects of KMUP-1 on TRPC1 might involve activating the cyclic guanosine monophosphate (cGMP)/PKG and cyclic adenosine monophosphate (cAMP)/PKA pathways and inhibiting the PKC pathway. We also used Fura 2-acetoxymethyl ester (Fura 2-AM, 5 µM) to measure the stored calcium release from the sarcoplasmic reticulum (SR) and calcium entry through SOCs in hypoxic PASMCs under treatment with thapsigargin (1 µM) and nifedipine (5 µM). In hypoxic conditions, store-operated calcium entry (SOCE) activity was enhanced in PASMCs, and KMUP-1 diminished this activity. In conclusion, KMUP-1 inhibited the expression of TRPC1 protein and the activity of SOC-mediated Ca2+ entry upon SR Ca2+ depletion in hypoxic PASMCs.

Global prevalence and risk factors of emergence delirium in pediatric patients undergoing general anesthesia: A systemic review and meta-analysis.

PROBLEM: Emergence delirium (ED) in children post-general anesthesia has been persistently underestimated, impacting the well-being of children, nurses, and even parents. This study employs integrated analysis to establish a comprehensive understanding of ED, including its occurrence and related risk factors, emphasizing the imperative for enhanced awareness and comprehension among pediatric nursing care providers. ELIGIBILITY CRITERIA: A systematic review and meta-analysis were conducted using four electronic databases, namely PubMed, CINAHL via EBSCOhost, Embase via Elsevier, and ProQuest Dissertations and Theses. RESULTS: This meta-analysis included 16 studies involving 9598 children who underwent general anesthesia. The pooled prevalence of ED was 19.2% (95% confidence interval [CI] = 0.12 to 0.29), with younger patients exhibiting a higher prevalence of ED. ED research is scant in Africa and is mostly limited to the Asia Pacific region and Northern Europe. Neck and head surgery (odds ratio [OR] = 2.34, 95% CI = 1.29 to 4.27) were significantly associated with ED risk. CONCLUSIONS: ED should be monitored in children who receive general anesthesia. In this study, ED had a prevalence rate of 19.2%, and head and neck surgery were significantly associated with ED risk. Therefore, healthcare professionals should carefully manage and prevent ED in children undergoing general anesthesia. IMPLICATIONS: A comprehensive understanding of ED's prevalence and risk factors is crucial for enhancing nursing care. Adopting a family-centered care approach can empower parents with information to collaboratively care for their children, promoting a holistic approach to pediatric healthcare.

Retinoblastoma Incidence in Taiwan Over a Recent 20-Year Period: A Comprehensive Nationwide Study.

Purpose: Continuous advancements in medical diagnostic technology and the growing availability of resources suggest a potential for fluctuations in the incidence rate of retinoblastoma (Rb). This study aimed to analyze incidence data of Rb patients in Taiwan from 1999 to 2018, utilizing the nationwide Taiwan Cancer Registry (TCR) database. Additionally, we investigated the treatment modalities used for these Rb patients and compared them with those observed in other countries. Patients and Methods: We conducted a retrospective cohort study utilizing data from the TCR database. The study cohort comprised individuals who were newly diagnosed with Rb between 1999 and 2018. The incidence of Rb was calculated as the number of patients with Rb per million live births, both for the entire population and for different gender groups and time periods. The trends in Rb incidence from 1999 to 2018 across various age groups and sexes were presented with the linear trend test. Results: From 1999 to 2018, a total of 248 cases of Rb were identified. The overall incidence rate over this 20-year period was 60.20 cases per million live births, corresponding to 1 case per 16,611 live births. Incidence rates for each 5-year period between 1999 and 2018 exhibited no significant differences. The study cohort was predominantly male, with 134 cases (54.03%) being males and 114 cases (45.97%) being females, resulting in an overall male-to-female sex ratio of 1.18. Females had lower relative risk than males (RR: 0.92, 95% CI: 0.72-1.19). Primary surgical intervention was the preferred treatment modality for over 75% of the cases. Conclusion: This retrospective epidemiology study, using TCR from 1999 to 2018, indicated that no discernible trend of retinoblastoma incidence in Taiwan. Nevertheless, continuous monitoring of incidence rates and exploration of treatment strategies for retinoblastoma within the Taiwanese population are important to address potential changes in developing medical practices.

Age-related difference in oral adaptation to masticatory perturbation.

OBJECTIVES: Mastication can be influenced by intraoral perturbation (e.g., hard food). We developed the masticatory perturbation task (MPT) to assess the perturbation effect during mastication and quantify the degree of adaptation to masticatory perturbation in younger and older adults. DESIGN: Thirty-eight younger and 38 older participants completed the MPT, which consisted of three trials assessing masticatory performance (MP) without perturbation (i.e., the baseline condition) and three trials assessing MP with perturbation (i.e., the perturbation condition). Perturbation was implemented by concurrently chewing test food on the preferred side and a drinking straw on the nonpreferred side. We estimated the perturbation effect as the ΔMP between the baseline and perturbation conditions and the adaptation effect as the ΔMP between the third and the first trials for both age groups. RESULTS: We found a significant perturbation effect, i.e., a lower MP in the perturbation condition than in the baseline condition, and an adaptation effect, i.e., a higher MP in the third trial than the first trial, in both groups. Moreover, the older group showed a lower degree of adaptation than the younger group. CONCLUSION: The masticatory perturbation task revealed the perturbation effect during mastication and the adaptation to masticatory perturbation. The results revealed an association between age and masticatory adaptation.

Comparative survival analysis of bladder preservation therapy versus radical cystectomy in muscle-invasive bladder cancer.

BACKGROUND: Bladder preservation therapy is an alternative to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). The purpose of this study is to compare survival outcomes between bladder preservation therapy and radical cystectomy in MIBC patients using an Asian nationwide cancer registry database. METHODS: From the Taiwan Cancer Registry database and the Taiwan National Health Insurance Research Database, we identified bladder cancer patients from 2008 to 2018. The patients with urothelial carcinoma and clinical stage T2-T4aN0-1 M0 were included. Propensity score matching by age, gender, clinical stage, cT classification, and Charlson Comorbidity Index score was used between those receiving bladder preservation therapy or radical cystectomy. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared using the Kaplan-Meier method. Multivariate Cox regression models were used to determine the predictive factors of OS, CSS, and DFS. RESULTS: Following the propensity score matching, 393 MIBC patients were analyzed, 131 (33.3%) receiving bladder preservation therapy and 262 (66.7%) receiving radical cystectomy. After 5 years of the follow-up period the overall duration was with a median of 15.6 months. The treatment groups did not differ significantly in OS, CSS, and DFS (p = 0.2681, 0.7208, and 0.3616, respectively). In multivariable Cox regression models, bladder preservation therapy remained non-inferior to radical cystectomy in OS (adjusted hazard ratio [aHR] 1.08; 95% confidence interval [CI], 0.77-1.50; p = 0.6689), CSS (aHR, 1.06; 95% CI, 0.72-1.57; p = 0.7728), and DFS (aHR, 0.76; 95% CI, 0.46-1.27; p = 0.2929). Additionally, among patients ≥80 years, the use of bladder preservation therapy compared with radical cystectomy resulted in an equivalent OS, CSS and DSS. CONCLUSION: In Asian populations, bladder preservation therapy yielded similar survival outcomes as radical cystectomy in MIBC patients. Based on the results, it is evident that a multidisciplinary approach and shared decision-making are recommended for bladder cancer treatment.

An alleviative effect of Lonicerae japonicae flos water extract against liver fibrogenesis in vitro and in vivo.

Lonicerae japonicae (L. japonicae) flos is a medical and food homology herb. This study investigated the phenolic acid and flavonoid contents in L. japonicae flos water extract solution (LJWES) and the preventive effects of LJWES against liver fibrogenesis via FL83B cells and rats. LJWES contains many polyphenols, such as chlorogenic acid, morin, and epicatechin. LJWES increased cell viability and decreased cytotoxicity in thioacetamide (TAA)-treated FL83B cells (75 mM) (p < .05). LJWES decreased (p < .05) gene expressions of Tnf-α, Tnfr1, Bax, and cytochrome c but upregulated Bcl-2 and Bcl-xl in TAA-treated cells; meanwhile, increased protein levels of P53, cleaved caspase 3, and cleaved caspase 9 in TAA treated cells were downregulated (p < .05) by LJWES supplementation. In vivo, results indicated that TAA treatment increased serum liver damage indices (alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) and cytokines (interleukin-6 and transforming growth factor-ß1) levels and impaired liver antioxidant capacities (increased thiobarbituric acid reactive substance value but decreased catalase/glutathione peroxidase activities) in rats (p < .05) while LJWES supplementation amended (p < .05) them. Liver fibrosis scores, collagen deposition, and alpha-smooth muscle actin deposition in TAA-treated rats were also decreased by LJWES supplementation (p < .05). To sum up, LJWES could be a potential hepatoprotective agent against liver fibrogenesis by enhancing antioxidant ability, downregulating inflammation in livers, and reducing apoptosis in hepatocytes.

Fabrication of Self-Wrinkling Polymer Films with Tunable Patterns through an Interfacial-Fuming-Induced Surface Instability Process.

Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering.