Characterization of DmToll and DmToll7 homologue in Litopenaeus vannamei based on structure analysis.

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that recognize invading pathogens and activate downstream signaling pathways. The number of 10 Tolls is found in Litopenaeus vannamei but have not yet been identified as the corresponding Toll homologue of model animal. In this study, we predicted the three-dimensional (3D) structures of 10 LvTolls (LvToll1-10) with AlphaFold2 program. The per-residue local distance difference test (pLDDT) scores of LvTolls showed the predicted structure of LvTolls had high accuracy (pLDDT>70). By structural analysis, 3D structures of LvToll2 and LvToll3 had high similarity with Drosophila melanogaster Toll and Toll7, respectively. 3D structure of LvToll7 and LvToll10 were not similar to that of other LvTolls. Moreover, we also predicted that LvSpätzle4 had high structural similarity to DmSpätzle. There were 9 potential hydrogen bonds in LvToll2-LvSpätzle4 complex. Importantly, co-immunoprecipitation assay showed that LvToll2 could bind with LvSpätzle4. Collectively, this study provides new insight for researching invertebrate immunity by identifying the protein of model animal homologue.

Identification and characterization of a TLR4 homologue in Eriocheir sinensis based on structure analysis.

Toll-like receptor 4 (TLR4) plays an essential role in the activation of innate immunity by recognizing diverse pathogenic components of bacteria. Six Tolls were found in Eriocheir sinensis but have not yet been identified as mammalian TLR4 homolog. For this purpose, we predicted three-dimensional (3D) structures of EsTolls (EsToll1-6) with AlphaFold2. 3D structure of LRRs and TIR most had high accuracy (pLDDT >70). By structure analysis, 3D structures of EsToll6 had a high overlap with HsTLR4. Moreover, we also predicted potential 11 hydrogen bonds and 3 salt bridges in the 3D structure of EsToll6-EsML1 complex. 18 hydrogen bonds and 7 salt bridges were predicted in EsToll6-EsML2 complex. Co-immunoprecipitation assay showed that EsToll6 could interact with EsML1 and EsML2, respectively. Importantly, TAK242 (a mammalian TLR4-specific inhibitor) could inhibit the generation of ROS stimulated by lipopolysaccharides (LPS) in EsToll6-EsML2-overexpression Hela cells. Collectively, these results implied that EsToll6 was a mammalian TLR4 homolog and provided a new insight for researching mammalian homologs in invertebrates.

Light Induced Proton Coupled Charge Transfer Triggers Counterion Directional Translocation.

We demonstrate directed translocation of ClO4 - anions from cationic to neutral binding site along the synthetized BPym-OH dye molecule that exhibits coupled excited-state intramolecular proton-transfer (ESIPT) and charge-transfer (CT) reaction (PCCT). The results of steady-state and time-resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited-state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red-shifted fluorescence band (at 750 nm, extending to near-IR region) appears at the time ~83 ps as a result of electrochromic modulation of PCCT reaction. It occurs at substantial delay to PCCT that displayed fluorescence band at 640 nm and risetime of <200 fs. Thus, it becomes possible to visualize the manifestations of light-triggered ion translocation and of its driving force by fluorescence techniques and to separate them in time and energy domains.

Celecoxib attenuates interleukin 33-induced expression of vascular cell adhesion molecule-1 in human ovarian endometriotic stromal cells.

OBJECTIVE: Endometriosis is an estrogen-dependent chronic inflammatory disease in women of reproductive age. A review of the literature revealed that cytokines and inflammatory factors are associated with endometriosis-associated infertility. Interleukin 33 (IL-33) is a strong inducer of other pro-inflammatory cytokines. Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in recruiting inflammatory cells, whose expression facilitates leukocyte adhesion and is rapidly induced by pro-inflammatory cytokines. Many studies have indicated that VCAM-1 expression is high in endometriosis; however, whether the expression of VCAM-1 is related to IL-33 is unclear. MATERIALS AND METHODS: Human ovarian endometriotic stromal cells (hOVEN-SCs) were treated with IL-33 to enable investigation of cell characterization, gene and protein expression, and signal pathways. Proliferation potential was measured using an MTT assay. Gene expression was analyzed using reverse transcription-polymerase chain reaction. Protein expression assay was performed using western blot analysis. RESULTS: This study investigated the effects of IL-33 on VCAM-1 and COX-2 expression in hOVEN-SCs. First, the results revealed that the IL-33/ST2/mitogen-activated protein kinase (MAPK) signaling pathway could increase the expression of VCAM-1 and COX-2 in hOVEN-SCs. Second, we discovered that COX-2 expression was essential for IL-33-induced VCAM-1 expression because the effects could be negated through NS398, a selective COX-2 inhibitor. Finally, treatment of IL-33-treated hOVEN-SCs with celecoxib significantly and dose-responsively decreased VCAM-1 expression. CONCLUSION: Taken together, these results indicate that IL-33 can upregulate VCAM-1 expression in hOVEN-SCs through the IL-33/ST2/MAPK/COX-2 signaling pathway and thereby contribute to endometriosis.

Using silver nanoparticle-decorated whey protein isolate amyloid fibrils to modify the electrode surface used for electrochemical detection of para-nitrophenol.

Due to their organized structures, remarkable stiffness, and nice biocompatibility and biodegradability, amyloid fibrils serve as building blocks for versatile sustainable materials. Silver nanoparticles (AgNPs) are commonly used as the nano-catalysts for various electrochemical reactions. Given their large specific surface area and high surface energy, AgNPs exhibit high aggregation propensity, which hampers their electrocatalytic performance. Food protein wastes have been identified to be associated with climate change and environmental impacts, and a surplus of whey proteins in dairy industries causes high biological and chemical demands, and greenhouse gas emissions. This study is aimed at constructing sustainable electrode surface modifiers using AgNP-deposited whey protein amyloid fibrils (AgNP/WPI-AFs). AgNP/WPI-AFs were synthesized and characterized via spectroscopic techniques, electron microscopy, and X-ray diffraction. Next, the electrocatalytic performance of AgNP/WPI-AF modified electrode was assessed via para-nitrophenol (p-NP) reduction combined with various electrochemical analyses. Moreover, the reaction mechanism of p-NP electrocatalysis on the surface of AgNP/WPI-AF modified electrode was investigated. The detection range, limit of detection, sensitivity, and selectivity of the AgNP/WPI-AF modified electrode were evaluated accordingly. This work not only demonstrates an alternative for whey valorization but also highlights the feasibility of using amyloid-based hybrid materials as the electrode surface modifier for electrochemical sensing purposes.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Hyperbaric Oxygen Therapy Attenuated the Motor Coordination and Cognitive Impairment of Polyglutamine Spinocerebellar Ataxia SCA17 Mice.

Spinocerebellar ataxias (SCAs) are a large and diverse group of autosomal-dominant neurodegenerative diseases. No drugs have been approved for these relentlessly progressive and fatal SCAs. Our previous studies indicate that oxidative stress, neuroinflammation, and neuronal apoptosis are elevated in the SCA17 mice, which are the main therapeutic targets of hyperbaric oxygen treatment (HBOT). HBOT is considered to be an alternative and less invasive therapy for SCAs. In this study, we evaluated the HBOT (2.2 ATA for 14 days) effect and the persistence for the management of SCA17 mice and their wild-type littermates. We found HBOT attenuated the motor coordination and cognitive impairment of SCA17 mice and which persisted for about 1 month after the treatment. The results of several biochemistry and liver/kidney hematoxylin and eosin staining show the HBOT condition has no obvious toxicity in the mice. Immunostaining analyses show that the neuroprotective effect of HBOT could be through the promotion of BDNF production and the amelioration of neuroinflammation. Surprisingly, HBOT executes different effects on the male and female SCA17 mice, including the reduction of neuroinflammation and activation of CaMKII and ERK. This study suggests HBOT is a potential alternative therapeutic treatment for SCA17. Accumulated findings have revealed the similarity in disease pathomechanisms and possible therapeutic strategies in polyQ diseases; therefore, HBOT could be an optional treatment as well as the other polyQ diseases.

The impact of external resources on the development of an indigenous school in rural areas: Taking a junior high school in Taiwan as an example.

The UN SDGs presented a vision for sustainability and the reduction of inequality within a country. The Taiwanese government uses many external resources to develop rural education. This study was conducted in a small public junior high school in a remote indigenous community in central Taiwan. Due to the economic downturn, the population in the indigenous community is outflowing, and the number of students is decreasing. With external resources, such as the Project of Female Science and Technology Talent Development from the Ministry of Science and Technology in Taiwan and other plans, this study introduces a full-time researcher as a teacher to promote science education in the research school. Implementing the projects improves students' academic performance and encourages students to participate in science competitions and achieve success. This study explores first the impact of the school's implementation of the Ministry of Science and Technology program on the development of the school; second, the results of the development of the school-based curriculum; and finally, it quantifies the statistics of the students' changes in the National High School Entrance Examination results. The impact of external resources on school development is determined by analyzing the performance of the participating students. This study finds that the Ministry of Science and Technology program plays an essential role in the development of the school, providing a key platform for teachers' growth, enriching school funding, developing featured courses, and encouraging students' performance. External resources have significantly improved students' results on the National Examination and facilitated students' motivation to learn science.

Schizophrenia patients discharged on antipsychotic polypharmacy from a public psychiatric hospital in Taiwan, 2006-2021.

The aim of this study was to identify the factors associated with antipsychotic polypharmacy (APP), investigate whether APP could affect the risk of rehospitalization, and explore temporal trends in APP use. Schizophrenia patients discharged from the study hospital between 2006 and 2021 (n = 16,722) were included in the analysis. The logistic regression model was employed to determine the predictors significantly associated with APP use. Survival analysis was used to compare time to rehospitalization between APP and antipsychotic monotherapy (AMT). The temporal trend of APP use was analyzed using the Cochran-Armitage Trend test. In comparison with the patients (n = 10,909) who were discharged on AMT, those (n = 5,813) on APP were significantly more likely to be male gender, to receive LAIs, to take clozapine, to take anticholinergic agents, to have a greater number of previous hospitalizations, and to have a higher CPZ equivalent dose of antipsychotic prescription. The prescription rate of APP significantly increased from 18.4 % in 2006 to 44.9 % in 2021. Compared with AMT, APP was associated with more clozapine use, more LAI use, higher doses of antipsychotics, and an increased risk of rehospitalization. In addition, the prescription of APP continued to increase during the study period.

Impact of cerebral collateral flow on stroke outcomes after carotid stenting.

OBJECTIVE: Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries. METHODS: This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses. RESULTS: A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001). INTERPRETATION: Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.

Schizophrenia Patients Discharged on Clozapine Plus Long-Acting Injectable Antipsychotics From a Public Psychiatric Hospital in Taiwan, 2006-2021.

BACKGROUND: Some schizophrenia patients treated with clozapine experience an inadequate response and adherence problems. The purpose of this study was to compare time to rehospitalization within 6 months in schizophrenia patients discharged on 3 clozapine regimens. Additionally, the temporal trend of prescription rate in each group was also explored. METHODS: Schizophrenia patients discharged from the study hospital from January 1, 2006, to December 31, 2021, (n = 3271) were included in the analysis. The type of clozapine prescribed at discharge was divided into 3 groups: clozapine plus long-acting injectable antipsychotics (clozapine + LAIs), clozapine plus other oral antipsychotics (clozapine + OAPs), and clozapine monotherapy. Survival analysis was used to compare time to rehospitalization within 6 months after discharge among the 3 groups. The temporal trend in the prescription rate of each group was analyzed using the Cochran-Armitage Trend test. RESULTS: Patients discharged on clozapine + LAIs had a significantly longer time to rehospitalization than those on clozapine + OAPs or clozapine monotherapy. The prescription rates of clozapine + LAIs and clozapine + OAPs significantly increased over time, whereas the prescription rates of clozapine monotherapy significantly decreased. CONCLUSIONS: Compared with the clozapine + OAPs group, the clozapine + LAIs group had a lower risk of rehospitalization and a lower dose of clozapine prescribed. Therefore, if a second antipsychotic is required for patients who are taking clozapine alone, LAIs should be considered earlier.

Developing targeted drug delivery carriers for breast cancer using glutathione-sensitive doxorubicin-coupled glycated bovine serum albumin nanoparticles.

Incorporation of the nano-based carriers into drug delivery provides a promising alternative to overcome the limitations of the conventional chemotherapy. Doxorubicin (DOXO) is an effective chemotherapeutic drug widely used in chemotherapy for breast cancer treatment. A globular protein bovine serum albumin (BSA) holds great potential as carriers in pharmaceutical applications. This work is aimed at developing the DOXO-coupled glycated BSA nanoparticles via desolvation method for improving the capability of targeting the GLUT5 transporters over-expressed on breast cancer cells. Fructosamine assay and Fourier transform infrared spectroscopy were employed to determine the content of fructosamine structure and structural changes on the surfaces of nanoparticles, respectively. Additionally, the synthesized BSA nanoparticles were further characterized by electron microscopy and dynamic light scattering. Results revealed that the DOXO-coupled glycated BSA nanoparticles were spherically shaped with a hydrodynamic diameter of ~60.74 nm and a ζ-potential of ~ - 42.20 mV. Moreover, the DOXO release behavior of as-synthesized DOXO-coupled glycated BSA nanoparticles was examined under different conditions. Finally, the DOXO-coupled glycated BSA nanoparticles were found to exhibit cytotoxicity toward both MCF-7 and MDA-MB-231 cells. Our findings evidently suggested that the drug-coupled glycated BSA nanoparticles serve as the potential candidates for targeted drug delivery platform used in breast cancer therapy.

Shimia ponticola sp. nov., an aerobic anoxygenic photoheterotrophic bacterium, isolated from surface seawater in the South China Sea.

A Gram-stain-negative marine bacterium, designated as WX04T, was isolated from the South China Sea. The genome of strain WX04T contained a complete photosynthetic gene cluster and is the first identified photoheterotroph of the genus Shimia with high photochemical efficiency (Fv/Fm=0.705±0.010), indicating its diverse metabolic and growth strategies, and unique evolution in the genus Shimia. The genome size of strain WX04T is 3.78 Mbp, and the G+C content is 58.8 %. Its isolate formed pink colonies and the cells were non-flagellated and rod-shaped. Growth was observed at 15-35 °C (optimum, 30 °C), at pH 5.0-11.0 (optimum, pH 7.0) and in the presence of 3-5 % (w/v) NaCl (optimum, 3 %). Both catalase activity and oxidase activity were found to be negative. The 16S rRNA gene sequence analyses revealed that this isolate represents a novel species within the genus Shimia, sharing 96.8 and 95.6% sequence identities with Shimia aestuarii DSM 15283T and Shimia marina DSM 26895T, respectively. The respiratory quinone was ubiquinone-10 (100 %). The primary cellular fatty acids (>5 %) were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C18 : 0,C18 : 1 ω7c 11-methyl and C10 : 0 3-OH. The dominant polar lipids of strain WX04T comprised phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol. The combined polyphasic data shows that strain WX04T is a novel species within the genus Shimia, which is proposed as Shimia ponticola sp. nov., and the type strain is WX04T (=KCTC 62628T=MCCC 1K02295T).

Numerical Analysis of Hydrogen Peroxide Addition and Oxygen-Enriched Methane Combustion.

Methane (CH4)/air lean combustion can be enhanced by increasing the concentration of the oxidizer, like oxygen (O2) enrichment, or adding a strong oxidant to the reactant. Hydrogen peroxide (H2O2) is a strong oxidizer that yields O2, steam, and appreciable heat after decomposition. This study numerically investigated and compared the effects of H2O2 and O2-enriched conditions on the adiabatic flame temperature, laminar burning velocity, flame thickness, and heat release rates of CH4/air combustion using the San Diego mechanism. The result showed that in fuel-lean conditions, the adiabatic flame temperature changed from H2O2 addition > O2-enriched scenario to O2-enriched scenario > H2O2 addition with increasing α. This transition temperature was not affected by the equivalence ratio. Adding H2O2 enhanced the laminar burning velocity of the CH4/air lean combustion more than the O2-enriched scenario. The thermal and chemical effects are quantified in various H2O2 additions, and it is found that the chemical effect has a noticeable contribution to the laminar burning velocity compared with the thermal effect, especially in higher H2O2 addition. Further, the laminar burning velocity had a quasi-linear correlation with (OH)max in the flame. The maximum heat release rate was observed at lower temperatures for H2O2 addition and higher temperatures for the O2-enriched scenario. The flame thickness was significantly reduced upon adding H2O2. Finally, the dominant reaction to the heat release rate changed from the reaction of CH3 + O ↔ CH2O + H in the CH4/air or O2-enriched scenario to the reaction of H2O2 + OH ↔ H2O + HO2 in the H2O2 addition scenario.

Application of Amyloid-Based Hybrid Membranes in Drug Delivery.

The properties of amyloid fibrils, e.g., unique structural characteristics and superior biocompatibility, make them a promising vehicle for drug delivery. Here, carboxymethyl cellulose (CMC) and whey protein isolate amyloid fibril (WPI-AF) were used to synthesize amyloid-based hybrid membranes as vehicles for the delivery of cationic and hydrophobic drugs (e.g., methylene blue (MB) and riboflavin (RF)). The CMC/WPI-AF membranes were synthesized via chemical crosslinking coupled with phase inversion. The zeta potential and scanning electron microscopy results revealed a negative charge and a pleated surface microstructure with a high content of WPI-AF. FTIR analysis showed that the CMC and WPI-AF were cross-linked via glutaraldehyde and the interacting forces between membrane and MB or RF was found to be electrostatic interaction and hydrogen bonding, respectively. Next, the in vitro drug release from membranes was monitored using UV-vis spectrophotometry. Additionally, two empirical models were used to analyze the drug release data and relevant rate constant and parameters were determined accordingly. Moreover, our results indicated that in vitro drug release rates depended on the drug-matrix interactions and transport mechanism, which could be controlled by altering the WPI-AF content in membrane. This research provides an excellent example of utilizing two-dimensional amyloid-based materials for drug delivery.

Risk factors for relapse among methamphetamine users receiving a joint legal-medical treatment program as a diversion intervention: A one-year follow-up study.

BACKGROUND: Methamphetamine (METH) is a Schedule II illicit drug in Taiwan. A 12-month legal-medical joint intervention program has been developed for first-time METH offenders during deferred prosecution. Risk factors associated with METH relapse use among these individuals were unknown. METHODS: We enrolled a total of 449 METH offenders referred by the Taipei District Prosecutor's Office to Taipei City Psychiatric Center. The study defines relapse as having any positive urine toxicology result or self-report of METH use during 12-month treatment. We compared demographic and clinical variables between a relapse group and nonrelapse group and used a Cox proportional hazards model to determine variables associated with time to relapse. RESULTS: Of all participants, 37.8 % relapsed to use METH and 23.2 % were noncompleters in the one-year follow-up. Compared to the nonrelapse group, the relapse group had lower educational attainment, more severe psychological symptoms, longer duration of METH use, higher odds of polysubstance use, higher craving severity, and higher odds of positive baseline urine. The Cox analysis revealed individuals with positive urine results and higher craving severity at baseline were at higher risks of METH relapse (hazard ratio [95 % CI]: 3.85 [2.61-5.68] and 1.71 [1.19-2.46], respectively, p < 0.001). Baseline positive urine results and high craving could also predict a shorter length of time to relapse than their respective counterparts. CONCLUSIONS: Positive urine screening for METH at baseline and high craving severity are two indicators of an increased risk of drug relapse. Tailored treatment plans incorporating these findings to prevent relapse are warranted in our joint intervention program.

Ophthalmic artery flow direction change predicts recurrence of ischemic stroke after carotid stenting: a longitudinal observational study.

BACKGROUND AND PURPOSE: The implantation of carotid artery stents prevents recurrent ischemic stroke in patients with carotid stenosis. This study aimed to investigate associations between change of ophthalmic artery flow (COAF) post carotid stenting and recurrent ischemic stroke, as well as the link toward the anterior and posterior circulations and patients' prognosis after carotid stenting. METHODS: This retrospective, longitudinal cohort study recruited 87 left side carotid stenosed ischemic stroke patients undergoing left side carotid stenting between year of 2009 and 2013, and patients were followed up to 9 years after carotid procedures. Clinical data were derived from medical records. The primary outcome was stroke recurrence. Predictive factors were stenosis > 50% in one intracranial artery and ROAF. Kaplan-Meier and Cox regression analyses were used to identify risk factors associated with stroke recurrence. RESULTS: Among 87 included patients undergone left side carotid stent treatment, 44 had stroke recurrence within 3 years after carotid stenting. The recurrence group had significantly greater proportions of COAF after stenting (p = 0.001), and middle cerebral artery (MCA) and basilar artery or vertebral artery (BA/VA) stenosis > 50% (all p < 0.001) than the no-recurrence group. Survival was significantly shorter in patients with COAF than in those without (p < 0.01). Regression analysis showed that COAF was associated with stroke recurrence (HR: 3.638, 95% CI 1.54-8.62, p = 0.003). The recurrence rate was highest in patients with bilateral MCA stenosis > 50% (100%), followed by left MCA stenosis > 50% plus BA/VA stenosis > 50% (83.33%) or COAF (82.14%). Patients with bilateral MCA stenosis < 50% had no recurrence within 3-year follow-up. CONCLUSIONS: Prognosis after carotid stenting is poorer for patients with MCA stenosis > 50%, BA/VA stenosis > 50% and/or COAF. Carotid duplex and magnetic resonance angiography provide definitive information for prognosis prediction.

Oct-4 induces cisplatin resistance and tumor stem cell-like properties in endometrial carcinoma cells.

OBJECTIVE: Research has suggested that tumor-initiating tumor stem cells are derived from normal stem cells and that tumor cells undergo progressive de-differentiation to achieve a stem cell-like state. Tumor stem cells are characterized by high proliferation ability, high plasticity, expression of multi-drug resistance proteins, and the ability to seed new tumors. Octamer-binding transcription factor 4 (Oct-4) and its activation targets are overexpressed in the tumor stem cells of various types of tumors, and this expression is associated with the pathogenesis, development, and poor prognosis of tumors. The primary objective of this study was to test if a stably transfected with Oct-4 gene cell line, RL95-2/Oct-4, has the characteristics of tumor stem cells. MATERIALS AND METHODS: Human endometrial carcinoma cells (RL95-2) were transfected with a plasmid carrying genes for Oct-4 and green fluorescent protein (GFP). The stably transfected cells, RL95-2/Oct-4, were selected using G418 and observed to express the GFP reporter gene under the control of the Oct-4 promoter. GFP expression levels of RL95-2/Oct-4 cells were measured using flow cytometry. The proliferation potential of cells was determined according to cumulative population doubling and colony-formation efficiency. Gene expression was analyzed using reverse transcription-polymerase chain reaction. RESULTS: RL95-2/Oct-4 cells not only exhibited increased expression of the three most important stem cell genes, Oct-4, Nanog, and Sox2, but also had increased expression of the endometrial tumor stem cell genes CD133 and ALDH1. Furthermore, enhanced expression of these genes in the RL95-2/Oct-4 cells was associated with higher colony-forming ability and growth rate than in parental RL95-2 cells. We also observed that cisplatin induced less cell death in RL95-2/Oct-4 cells than in RL95-2 cells, indicating that RL95-2/Oct-4 cells were more resistant to chemotherapeutic agents. CONCLUSION: The study findings contribute to investigate the effects of Oct-4 on tumor stem cell origins.

Association of leukocyte mitochondrial DNA copy number with longitudinal C-reactive protein levels and survival in older adults: a cohort study.

BACKGROUND: Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk. METHODS: This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis. RESULTS: Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up. CONCLUSIONS: A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.