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Using silicon/reduced graphene oxide (Si/rGO) composites as lithium-ion battery (LIB) anodes can effectively buffer the volumetric expansion and shrinkage of Si. Herein, we designed and prepared Si/rGO-b with a sandwiched structure, formed by a duple combination of ammonia-modified silicon (m-Si) nanoparticles (NP) with graphene oxide (GO). In the first composite process of m-Si and GO, a core-shell structure of primal Si/rGO-b (p-Si/rGO-b) was formed. The amino groups on the m-Si surface can not only hybridize with the GO surface to fix the Si particles, but also form covalent chemical bonds with the remaining carboxyl groups of rGO to enhance the stability of the composite. During the electrochemical reaction, the oxygen on the m-Si surface reacts with lithium ions (Li + ) to form Li 2 O, which is a component of the solid-electrolyte interphase (SEI) and is beneficial to buffering the volume expansion of Si. Then, the p-Si/rGO-b recombines with GO again to finally form a sandwiched structure of Si/rGO-b. Covalent chemical bonds are formed between the rGO layers to tightly fix the p-Si/rGO-b, and the conductive network formed by the reintroduced rGO improves the conductivity of the Si/rGO-b composite. When used as an electrode, the Si/rGO-b composite exhibits excellent cycling performance (operated stably for more than 800 cycles at a high-capacity retention rate of 82.4%) and a superior rate capability (300 mA h/g at 5 A/g). After cycling, tiny cracks formed in some areas of the electrode surface, with an expansion rate of only 27.4%. The duple combination of rGO and the unique sandwiched structure presented here demonstrate great effectiveness in improving the electrochemical performance of alloy-type anodes.

Esophageal squamous cell carcinoma (ESCC) is a deadly consequence of radiation exposure to the esophagus. ESCC arises from esophageal epithelial cells that undergo malignant transformation and features a perturbed squamous cell differentiation program. Understanding the dose- and radiation quality-dependence of the esophageal epithelium response to radiation may provide insights into the ability of radiation to promote ESCC. We have explored factors that may play a role in esophageal epithelial radiosensitivity and their potential relationship to ESCC risk. We have utilized a murine three-dimensional (3D) organoid model that recapitulates the morphology and functions of the stratified squamous epithelium of the esophagus to study persistent dose- and radiation quality-dependent changes. Interestingly, although high-linear energy transfer (LET) Fe ion exposure induced a more intense and persistent alteration of squamous differentiation and 53BP1 DNA damage foci levels as compared to Cs, the MAPK/SAPK stress pathway signaling showed similar altered levels for most phospho-proteins with both radiation qualities. In addition, the lower dose of high-LET exposure also revealed nearly the same degree of morphological changes, even though only ~36% of the cells were predicted to be hit at the lower 0.1 Gy dose, suggesting that a bystander effect may be induced. Although p38 and ERK/MAPK revealed the highest levels following high-LET exposure, the findings reveal that even a low dose (0.1 Gy) of both radiation qualities can elicit a persistent stress signaling response that may critically impact the differentiation gradient of the esophageal epithelium, providing novel insights into the pathogenesis of radiation-induced esophageal injury and early stage esophageal carcinogenesis., Competing Interests: Deepa M. Sridharan is from Soley Theraperutics, Inc. The authors declare no conflicts of interest.

Background: Children with asthma may have a reduced ventilatory capacity, which could lead to symptoms and early termination of a cardiopulmonary exercise test (CPET). The purpose of this study was to examine the effects of short-acting beta agonist (albuterol) administration on estimated ventilatory capacity in children with asthma., Methods: Fifteen children (eleven boys, 10.6 ± 0.9 years) completed spirometry at baseline, after 180 µg of albuterol, and after the CPET in this cross-sectional study. Ventilatory capacity was calculated from forced vital capacity (FVC) and isovolume forced expiratory time from 25 to 75% of FVC (isoFET 25-75 ) as follows: FVC/2 × [60/(2 × isoFET 25-75 )]. Differences in outcome variables between baseline, after albuterol administration, and after the CPET were detected with repeated measures mixed models with Bonferroni post hoc corrections., Results: Estimated ventilatory capacity was higher after albuterol (68.7 ± 21.2 L/min) and after the CPET (75.8 ± 25.6 L/min) when compared with baseline (60.9 ± 22.0 L/min; P = 0.003). Because forced vital capacity did not change, the increased ventilatory capacity was primarily due to a decrease in isoFET 25-75 (i.e., an increase in mid-flows or isoFEF 25-75 )., Conclusion: Albuterol administration could be considered prior to CPET for children with asthma with relatively well-preserved FEV 1 values to increase ventilatory capacity pre-exercise and potentially avoid symptom-limited early termination of testing.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 ( SCN1A ) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

During tumorigenesis, urokinase (uPA) and uPA receptor (uPAR) play essential roles in mediating pathological progression in many cancers. To understand the crosstalk between the uPA/uPAR signaling and cancer, as well as to decipher their cellular pathways, we proposed to use cancer driver genes to map out the uPAR signaling. In the study, an integrated pharmaceutical bioinformatics approach that combined modulator identification, driver gene ontology networking, protein targets prediction and networking, pathway analysis and uPAR modulator screening platform construction was employed to uncover druggable targets in uPAR signaling for developing a novel anti-cancer modality. Through these works, we found that uPAR signaling interacted with 10 of 21 KEGG cancer pathways, indicating the important role of uPAR in mediating intracellular cancerous signaling. Furthermore, we verified that receptor tyrosine kinases (RTKs) and ribosomal S6 kinases (RSKs) could serve as signal hubs to relay uPAR-mediated cellular functions on cancer hallmarks such as angiogenesis, proliferation, migration and metastasis. Moreover, we established an in silico virtual screening platform and a uPAR-driver gene pair rule for identifying potential uPAR modulators to combat cancer. Altogether, our results not only elucidated the complex networking between uPAR modulation and cancer but also provided a paved way for developing new chemical entities and/or re-positioning clinically used drugs against cancer.

It is well known that the development of lightweight alloys with improved comprehensive performance and application value are the future development directions for the ultra-high-strength 7xxx series Al-Zn-Mg-Cu alloys used in the aircraft field. As the lightest metal element in nature, lithium (Li) has outstanding advantages in reducing the density and increasing the elastic modulus in aluminum alloys, so Al-Zn-Mg-Cu alloys containing Li have gained widespread attention. Furthermore, since the Al-Zn-Mg-Cu alloy is usually strengthened by aging treatment, it is crucial to understand how Li addition affects its aging precipitation process. As such, in this article, the effects and mechanism of Li on the aging precipitation behavior and the impact of Li content on the aging precipitation phase of Al-Zn-Mg-Cu alloys are briefly reviewed, and the influence of Li on the service properties, including mechanical properties, wear resistance, and fatigue resistance, of Al-Zn-Mg-Cu alloys are explained. In addition, the corresponding development prospects and challenges of the Al-Zn-Mg-Cu-Li alloy are also proposed. This review is helpful to further understand the role of Li in Al-Zn-Mg-Cu alloys and provides a reference for the development of high-strength aluminum alloys containing Li with good comprehensive properties.

Urothelial carcinoma (UC) is characterized by a high incidence of TP53 mutation, and overcoming resistance to cisplatin-based chemotherapy in UC is a major concern. Wee1 is a G2/M phase regulator that controls the DNA damage response to chemotherapy in TP53 -mutant cancers. The combination of Wee1 blockade with cisplatin has shown synergistic efficacy in several types of cancers, but little is known regarding UC. The antitumor efficacy of the Wee1 inhibitor (AZD-1775) alone or in combination with cisplatin was evaluated in UC cell lines and a xenograft mouse model. AZD-1775 enhanced the anticancer activity of cisplatin by increasing cellular apoptosis. AZD-1775 inhibited the G2/M checkpoint, improving the sensitivity of mutant TP53 UC cells to cisplatin by enhancing the DNA damage process. We confirmed that AZD-1775 combined with cisplatin reduced tumor volume and proliferation activity and increased the markers of cell apoptosis and DNA damage in the mouse xenograft model. In summary, the Wee1 inhibitor AZD-1775 combined with cisplatin elicited a promising anticancer efficacy in UC, and constitutes an innovative and promising therapeutic strategy.

During space travel, astronauts will experience a unique environment that includes continuous exposure to microgravity and stressful living conditions. Physiological adaptation to this is a challenge and the effect of microgravity on organ development, architecture, and function is not well understood. How microgravity may impact the growth and development of an organ is an important issue, especially as space flight becomes more commonplace. In this work, we sought to address fundamental questions regarding microgravity using mouse mammary epithelial cells in 2D and 3D tissue cultures exposed to simulated microgravity. Mouse mammary HC11 cells contain a higher proportion of stem cells and were also used to investigate how simulated microgravity may impact mammary stem cell populations. In these studies, we exposed mouse mammary epithelial cells to simulated microgravity in 2D and then assayed for changes in cellular characteristics and damage levels. The microgravity treated cells were also cultured in 3D to form acini structures to define if simulated microgravity affects the cells' ability to organize correctly, a quality that is of key importance for mammary organ development. These studies identify changes occurring during exposure to microgravity that impact cellular characteristics such as cell size, cell cycle profiles, and levels of DNA damage. In addition, changes in the percentage of cells revealing various stem cell profiles were observed following simulated microgravity exposure. In summary, this work suggests microgravity may cause aberrant changes in mammary epithelial cells that lead to an increase in cancer risk.

Alterations in the gut microbiota composition and their associated metabolic dysfunction exist in psoriasis. However, the impact of biologics on shaping gut microbiota is not well known. This study aimed to determine the association of gut microorganisms and microbiome-encoded metabolic pathways with the treatment in patients with psoriasis. A total of 48 patients with psoriasis, including 30 cases who received an IL-23 inhibitor (guselkumab) and 18 cases who received an IL-17 inhibitor (secukinumab or ixekizumab) were recruited. Longitudinal profiles of the gut microbiome were conducted by using 16S rRNA gene sequencing. The gut microbial compositions dynamically changed in psoriatic patients during a 24-week treatment. The relative abundance of individual taxa altered differently between patients receiving the IL-23 inhibitor and those receiving the IL-17 inhibitor. Functional prediction of the gut microbiome revealed microbial genes related to metabolism involving the biosynthesis of antibiotics and amino acids were differentially enriched between responders and non-responders receiving IL-17 inhibitors, as the abundance of the taurine and hypotaurine pathway was found to be augmented in responders treated with the IL-23 inhibitor. Our analyses showed a longitudinal shift in the gut microbiota in psoriatic patients after treatment. These taxonomic signatures and functional alterations of the gut microbiome could serve as potential biomarkers for the response to biologics treatment in psoriasis.

Since the discovery of fluorescent proteins (FPs), their rich fluorescence spectra and photochemical properties have promoted widespread biological research applications. FPs can be classified into green fluorescent protein (GFP) and its derivates, red fluorescent protein (RFP) and its derivates, and near-infrared FPs. With the continuous development of FPs, antibodies targeting FPs have emerged. The antibody, a class of immunoglobulin, is the main component of humoral immunity that explicitly recognizes and binds antigens. Monoclonal antibody, originating from a single B cell, has been widely applied in immunoassay, in vitro diagnostics, and drug development. The nanobody is a new type of antibody entirely composed of the variable domain of a heavy-chain antibody. Compared with conventional antibodies, these small and stable nanobodies can be expressed and functional in living cells. In addition, they can easily access grooves, seams, or hidden antigenic epitopes on the surface of the target. This review provides an overview of various FPs, the research progress of their antibodies, particularly nanobodies, and advanced applications of nanobodies targeting FPs. This review will be helpful for further research on nanobodies targeting FPs, making FPs more valuable in biological research.

This study explored the structural characteristics, mechanical properties, and oxidation behavior of W-enriched TaWSiN films prepared through co-sputtering. The atomic ratios [W/(W + Ta)] of the as-deposited films maintained a range of 0.77-0.81. The TaWSiN films with a Si content of 0-13 at.% were crystalline, whereas the film with 20 at.% Si was amorphous. The hardness and Young's modulus of crystalline TaWSiN films maintained high levels of 26.5-29.9 GPa and 286-381 GPa, respectively, whereas the hardness and Young's modulus of the amorphous Ta 7 W 33 Si 20 N 40 films exhibited low levels of 18.2 and 229 GPa, respectively. The oxidation behavior of TaWSiN films was investigated after annealing at 600 °C in a 1%O 2 -Ar atmosphere, and cone-like Ta 0.3 W 0.7 O 2.85 oxides formed and extruded from the TaWSiN films.

Background: Structural stigma in the form of discriminatory laws and policies impacts the mental health of sexual and gender minorities, especially with regard to suicidality. However, this relationship could be moderated by resilience. The past two years has brought anti-SGM legislation, particularly transgender sports bans, at the state level in the United States into focus. This study aims to understand if the relationship between familiarity with transgender sports bans (proposed or enacted) and suicidality was moderated by individual or community resilience., Methods: This was a cross-sectional study of survey data collected from a national sample of 1033 SGM adults in the United States between 28 January and 7 February 2022. Univariate and multivariate moderation analyses were used., Results: In the univariate analyses and the final model, community resilience moderated the relationship between structural stigma and suicidality ( p = 0.0002); however, individual resilience did not ( p = 0.0664)., Conclusion: Interventions to bolster community resilience may attenuate the negative mental health impacts of structural stigma and are warranted, along with concerted efforts to minimize structural stigma in the form of discriminatory laws and policies targeting people who are SGM.

The tumor-suppressor gene, WW domain-containing oxidoreductase (WWOX), has been found to be lost in various types of cancers. ROS result as a tightly regulated signaling process for the induction of cell senescence. The aim of this study was to investigate the role of WWOX in the regulation of ROS and cell senescence, which is intriguing in terms of the possible mechanism of WWOX contributing to bladder cancer. In this study, we used the AY-27 rat bladder tumor cell line and F344 orthotopic bladder tumor models to reveal the pro-senescence effects of WWOX and the corresponding underlying mechanism in bladder cancer. WWOX-overexpressing lentivirus (LV-WWOX) remarkably stimulated cellular senescence, including increased senescence-associated secretory phenotype (SASP) formation, enlarged cellular morphology, and induced SA-β-Gal-positive staining. A further mechanism study revealed that the pro-senescence effect of LV-WWOX was dependent on increased intercellular reactive oxygen species (ROS) generation, which subsequently triggered p21/p27. Moreover, LV-WWOX significantly inhibited the tumor size by 30.49% in the F344/AY-27 rat orthotopic model (p < 0.05) by activating cellular senescence. The expression of p21 was significantly enhanced in the orthotopic bladder tumors under WWOX treatment. The orthotopic bladder tumors in the groups of rats verified the effect in vivo. Our study suggests that WWOX, an ROS-dependent senescence-induced gene, could be further studied for its therapeutic implications in bladder cancer.

Long noncoding (lnc)RNAs are reported to be key regulators of tumor progression, including hepatocellular carcinoma (HCC). The lncRNA long intergenic noncoding RNA 00673 (LINC00673) was indicated to play an important role in HCC progression, but the impacts of genetic variants (single-nucleotide polymorphisms, SNPs) of LINC00673 on HCC remain unclear. A TaqMan allelic discrimination assay was performed to analyze the genotypes of three tagging SNPs, viz., rs9914618 G > A, rs6501551 A > G, and rs11655237 C > T, of LINC00673 in 783 HCC patients and 1197 healthy subjects. Associations of functional SNPs of LINC00673 with HCC susceptibility and clinicopathologic variables were analyzed by logistic regression models. After stratification by confounding factor, we observed that elderly patients (≥60 years) with the LINC00673 rs9914618 A allele had an increased risk of developing HCC under a codominant model (p = 0.025) and dominant model (p = 0.047). Moreover, elderly patients carrying the GA + AA genotype of rs9914618 exhibited a higher risk of having lymph node metastasis compared to those who were homozygous for the major allele (p = 0.013). Genotype screening of rs9914618 in HCC cell lines showed that cells carrying the AA genotype expressed higher LINC00673 levels compared to the cells carrying the GG genotype. Further analyses of clinical datasets from the Cancer Genome Atlas (TCGA) showed that LINC00673 expressions were upregulated in HCC tissues compared to normal tissues, and were correlated with advanced clinical stages and poorer prognoses. In conclusions, our results suggested that the LINC00673 rs9914618 polymorphism may be a promising HCC biomarker, especially in elderly populations.

In this paper, we present a wound-dressing-based antenna fabricated via screen-printed and inkjet-printed technologies. To inkjet print a conductive film on wound dressing, it must be screen-printed, UV-curable-pasted, and hard-baked to provide appropriate surface wettability. Two passes were UV-curable-pasted and hard-baked at 100 °C for 2 h on the wound dressing to obtain 65° WCA for silver printing. The silver film was printed onto the wound dressing at room-tempature with 23 μm droplet spacing for three passes, then sintered at 120 °C for 1 h. By optimizing the inkjet printing conditions by modifying the surface morphologies and electrical properties, three-pass printed silver films with 3.15 μm thickness and 1.05 × 10 7 S/m conductivity were obtained. The insertion losses at the resonant frequency (17 and 8.85 GHz) were -2.9 and -2.1 dB for the 5000 and 10,000 μm microstrip transmission lines, respectively. The material properties of wound dressing with the relative permittivity and loss-tangent of 3.15-3.25 and 0.04-0.05, respectively, were determined by two transmission line methods and used for antenna design. A quasi-Yagi antenna was designed and implemented on the wound-dressing with an antenna bandwidth of 3.2-4.6 GHz, maximal gain of 0.67 dBi, and 42% radiation efficiency. The bending effects parallel and perpendicular to the dipole direction of three fixtures were also examined. The gain decreased from 0.67 to -1.22 dBi and -0.44 dBi for a flat to curvature radius of 5 cm fixture after parallel and perpendicular bending, respectively. Although the maximal gain was reduced with the bending radius, the directivity of the radiation pattern remained unchanged. The feasibility of a wound-dressing antenna demonstrates that inkjet-printed technology enables fast fabrication with low cost and environmental friendliness. Additionally, inkjet-printed technology can be combined with sensing technology to realize remote medical monitoring, such as with smart bandages, for assessment of chronic wound status or basic physical conditions.

Background: Discriminatory laws and policies are a form of structural stigma that is associated with increased suicidality among sexual and gender minority (SGM) people. Unfortunately, in the United States, there has been an increase in state-level discriminatory laws and policies targeting SGM people in 2021 and 2022, particularly, transgender sports bans. The purpose of this study was to (1) determine if familiarity with transgender sports bans was associated with suicidality among SGM adults; and (2) determine if interpersonal stigma and/or individual stigma mediated this association., Methods: This was a cross-sectional study of data collected from a national sample of 1033 SGM adults in the United States between 28 January and 7 February 2022. Univariate and serial mediator models were used in this analysis., Results: The increased suicidality was associated with familiarity with state-level transgender sports bans among SGM adults ( p -value = 0.0150). Even after interpersonal and individual stigma mediated this relationship, the association between suicidality and familiarity with state-level transgender sports bans remained ( p -value = 0.0106)., Conclusion: State-level transgender sports bans appear to exacerbate existing disparities in mental health, especially for individuals who are familiar with the bans. They directly discriminate against people who are transgender and indirectly stigmatize the broader SGM community.

Seven new coumarinolignans, walthindicins A-F ( 1a , 1b , 2 - 5 , 7 ), along with five known analogs ( 6 , 8 - 11 ), were isolated from the roots of Waltheria indica . The structures of the new compounds are determined by detailed nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. Compounds were tested for their antioxidant activity in Human Cervical Cancer cells (HeLa cells). Compounds 1a and 6 showed higher reactive oxygen species (ROS) inhibitory activity at 20 μg/mL when compared with other natural compound-based antioxidants such as ascorbic acid. Considering the role of ROS in nuclear-factor kappa B (NF-κB) activation, compounds 1a and 6 were evaluated for NF-κB inhibitory activity and showed a concentration-dependent inhibition in Human Embryonic Kidney 293 cells (Luc-HEK-293).

Chronic kidney disease (CKD) is a chronic and often irreversible disease that requires active self-care to mitigate adverse outcomes. This study aimed to analyze the associations of demographic and disease data, frailty, health literacy (HL), and CKD self-care (CKDSC) in patients with CKD. We conducted a cross-sectional study at two hospitals in Taiwan. A total of 144 CKD patients with a mean age of 66.8 ± 9.1 years were included in the study. Among them, 79.2% were in CKD G3, and the mean time since diagnosis of CKD was 86 ± 48 months. Approximately 62.5% were identified as non-frail. The mean of HL and CKDSC were 11.76 ± 4.10 and 62.12 ± 9.31. In multivariate linear regression analysis, age ≥ 65 years (odds ratio (OR) = 5.67, 95% confidence interval (CI) 1.59-9.75), non-frailty (OR = 2.19, 95% CI 0.02-5.40), and high critical HL (OR = 1.43, 95% CI 0.13-2.90) showed significant positive correlation with CKDSC. Therefore, management of patients with CKD should focus on the young population, reinforcing health education strategies that improve critical HL and preventing frailty that may interfere with self-care. In addition, the patient's social support resources should be expanded to achieve the goal of CKDSC.

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5−7% of school-age children. ADHD is usually marked by an ongoing pattern of inattention or hyperactivity−impulsivity, leading to functioning or developmental problems. A common ADHD assessment tool is the Swanson, Nolan, and Pelham (SNAP) questionnaire. However, such scales provide only a subjective perspective, and most of them are used to evaluate therapeutic effects at least 3−12 months after medication initiation. Therefore, we employed an objective assessment method to provide more accurate evaluations of therapeutic effects in 25 children with ADHD (23 boys and 2 girls). To evaluate the participants’ improvement and treatment’s effectiveness, the pixel subtraction technique was used in video analysis. We compared the efficacy of 1-month Ritalin or Concerta treatment by evaluating the movement in each video within 3 h of medication administration. The movement value was defined as the result of a calculation when using the pixel subtraction technique. Based on behavior observation and SNAP scores, both parent- and teacher-reported scores decreased after 1 month of medication (reduction rates: 19.61% and 16.38%, respectively). Specifically, the parent-reported hyperactivity subscale and teacher-reported oppositional subscale decreased more significantly. By contrast, the reduction rate was 39.27%, as evaluated using the average movement value (AMV). Considering symptomatic improvement as a >25% reduction in scores, the result revealed that the AMV decreased in 18 patients (72%) compared with only 44% and 56% of patients based on parent- and teacher-reported hyperactivity subscale scores. In conclusion, the pixel subtraction method can serve as an objective and reliable evaluation of the therapeutic effects of ADHD medication in the early stage.

Oxytropis falcata Bunge is a plant used in traditional Tibetan medicine, with reported anti-inflammatory and antioxidants effects and alleviation of myocardial ischemia reperfusion injury (MIRI). However, the underlying mechanism against MIRI and the phytochemical composition of O. falcata are vague. One fraction named OFF1 with anti-MIRI activity was obtained from O. falcata , and the chemical constituents were identified by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS). The potential targets and signaling pathways involved in the action of O. falcata against MIRI were predicted by network pharmacology analysis, and its molecular mechanism on MIRI was determined by in vitro assays. The results revealed that flavonoids are the dominant constituents of OFF1. A total of 92 flavonoids reported in O. falcata targeted 213 potential MIRI-associated factors, including tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2), and the NF-κB signaling pathway. The in vitro assay on H9c2 cardiomyocytes subjected to hypoxia/reoxygenation injury confirmed that the flavonoids in OFF1 reduced myocardial marker levels, apoptotic rate, and the inflammatory response triggered by oxidative stress. Moreover, OFF1 attenuated MIRI by downregulating the ROS-mediated JNK/p38MAPK/NF-κB pathway. Collectively, these findings provide novel insights into the molecular mechanism of O. falcata in alleviating MIRI, being a potential therapeutic candidate.

Colorectal cancer (CRC) is one of the most common cancers worldwide and a longstanding critical challenge for public health. Screening has been suggested to effectively reduce both the incidence and mortality of CRC. However, the drawback of the current screening modalities, both stool-based tests and colonoscopies, is limited screening adherence, which reduces the effectiveness of CRC screening. Blood tests are more acceptable than stool tests or colonoscopy as a first-line screening approach. Therefore, identifying blood biomarkers for detecting CRC and its precancerous neoplasms is urgently needed to fulfill the unmet clinical need. Currently, many kinds of blood contents, such as circulating tumor cells, circulating tumor nucleic acids, and extracellular vesicles, have been investigated as biomarkers for CRC detection. Among these, small extracellular vesicles (sEVs) have been demonstrated to detect CRC effectively in recent reports. sEVs enable intercellular shuttling-for instance, trafficking between recipient cancer cells and stromal cells-which can affect tumor initiation, proliferation, angiogenesis, immune regulation; metastasis, the cancer-specific molecules, such as proteins, microRNAs, long noncoding RNAs, and circular RNAs, loaded into cancer-derived sEVs may serve as biomarkers for the detection of cancers, including CRC. Indeed, accumulating evidence has shown that nucleic acids and proteins contained in CRC-derived sEVs are effective as blood biomarkers for CRC detection. However, investigations of the performance of sEVs for diagnosing CRC in clinical trials remains limited. Thus, the effectiveness of sEV biomarkers for diagnosing CRC needs further validation in clinical trials.

Background: In long-term care facilities, there are frequent conflicts related to elderly residents' sexual expression. Nurse aides usually handle such conflicts with negative or negligent attitudes; therefore, elderly sexuality is considered "problem behavior" and is stigmatized., Objectives: This study aimed to improve elderly residents' quality of sexual life by enhancing nurse aides' knowledge and attitudes toward elderly sexuality through sexuality workshops., Methods: A quasi-experimental study was conducted with 64 nurse aides and 58 residents, who were divided into two groups, i.e., an experimental group and a control group, according to the floor where the residents resided. The nurse aides in the experimental group participated in sexuality workshops and were compared with those in the control group with respect to their knowledge of and attitudes toward sexuality; the residents' quality of sexual life was also compared between groups., Results: Compared with the control group, in the experimental group, the nurse aides' knowledge of and attitudes toward elderly sexuality as well as the residents' quality of sexual life significantly and continually improved after the sexuality workshops., Conclusion: The four-week sexuality workshop is effective and may be used as an example in developing occupational education programs regarding elderly sexuality in long-term care facilities.

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX; notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy; in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.

(1) Background: This study investigated the changes in step frequency, walking ability, and standing posture of students with intellectual disabilities by integrating step training into the students' physical education curriculum; (2) Methods: The centroid formula was used to estimate the geometric center of the students' bodies in video footage of each participant. Each participant's stepping frequency per minute was recorded. After training, the teachers involved were interviewed regarding the participants' everyday activities in school. Each step training session was recorded by two video cameras. Each step training session was observed and photographed by a senior physical education teacher with special education qualifications; (3) Results: The step training increased the stability of the participants' body axes. The participants' average steps per minute of the participants significantly improved from 24.200 ± 7.554 to 28.700 ± 8.629. Additionally, despite the students exhibiting anxious behavior (e.g., squeezing their hands and grasping at their clothes) at baseline, the frequency of these behaviors decreased significantly from week 4. Overall, the students' daily activities, motivation, interpersonal interaction, self-confidence, and anxiety behaviors improved; (4) Conclusions: After the 8-week step program, the participants with intellectual disabilities improved their step frequency, movement stability, ability to perform daily activities, walking speed, motivation, interpersonal interaction, and self-confidence, and they exhibited a lower level of anxiety-related behaviors.

Psoriasis is a chronic inflammatory disease which is caused by the interaction between genetic and environmental factors. Evidence shows an association of psoriasis with co-morbidities including cardiovascular diseases, metabolic syndrome and hyperuricemia. Genome-wide association studies have revealed that the ABCG2 gene encoding ATP-binding cassette G2 protein was associated with inflammation and higher serum urate concentrations. In this study, we aimed to evaluate the role of ABCG2 gene polymorphisms on the susceptibility to psoriasis. The genotype distribution of two ABCG2 single nucleotide polymorphisms (SNPs), rs2231142 and rs2231137, was examined in 410 psoriasis patients and 1,089 gender-matched non-psoriasis controls. We found that heterozygotes (GT) for rs2231142 was associated with a decreased risk of psoriasis ( p = 0.001; adjusted OR = 0.532; 95% CI, 0.370-0.765) after adjusting for age, as compared with homozygotes for the major allele (GG). Subjects who carried at least one polymorphic allele (homozygote or heterozygote for the minor allele) were less susceptible to psoriasis ( p = 0.002; adjusted OR = 0.594; 95% CI, 0.249-0.823) and bearing higher serum urate levels ( p = 0.026) than those homozygous for the major allele. Our results indicated that the ABCG2 gene polymorphism was associated with the risk of psoriasis.

Orthokeratology (OK) lens wear is an effective modality to inhibit axial elongation in myopic children. Willingness for commitment from both parents and children contributes to the success of OK treatment. We aimed to develop and assess the usability of a mobile application on OK lens wear by quantitatively and qualitatively evaluating parents with myopic children and eye care professionals (ECPs). Moreover, the preliminary outcome was also evaluated in this study. The app was developed and tested using a co-design approach involving key stakeholders. Two prototype tests were conducted during the feasibility and utility assessment. The app features include self-reported compliance documentation, analytics, and personalized and generalized messages for compliance behaviors of OK lenses. After the trial period, the full usage of app functions ranged from 40% to 60% among the enrolled parents. After app implementation, the compliance with follow-up visits substantially improved. Qualitative data show that the high-satisfaction app functions reported by parents were the app's reminder and axial length recording, although it was recommended that the number of compliance questions should be reduced to minimize the survey completion time. Additionally, who should complete the recording of the axial length data as well as the management and reminder for the follow-up visit remained controversial. This is the first app developed to improve parents of myopic children's compliance with OK lens wear and to assist ECPs and parents in collaboratively monitoring and managing the use and care of OK lenses among myopic children. This study highlights the importance of interdisciplinary collaboration in the design, development, and validation of such an app.

We conducted a cross-sectional study to clarify the relationship between oral health and physical frailty (PF). A sample of 903 community-dwelling individuals aged ≥ 65 years were enrolled from random communities in Chiayi County. The self-perceived oral health (SPOH) and oral health assessment tool (OHAT), which consists of eight items, was used for the evaluation of their oral health status. PF was assessed based on the Study of Osteoporotic Fracture index. Overall, 14.6% of the participants had PF. In an adjusted model, restricted food types (odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.2-2.09, p = 0.001), self-reported dental status (OR = 1.61, 95% CI: 1.2-2.15, p = 0.001), number of teeth (OR = 0.98, 95% CI: 0.96-0.99, p = 0.006), frequency of tooth cleaning (OR = 0.83, 95% CI: 0.68-1.0, p = 0.049), OHAT score (OR = 1.09, 95% CI: 1.02-1.17, p < 0.017), and saliva items of OHAT (OR = 1.52, 95% CI: 1.11-2.1, p = 0.010) were significantly associated with PF. SPOH is a crucial indicator of PF; longitudinal analyses are necessary to understand the underlying pathway of risk factors for frailty onset.

Heme oxygenases (HOs) act on heme degradation to produce carbon monoxide (CO), free iron, ferritin, and biliverdin. Upregulation of cellular HO-1 levels is signature of oxidative stress for its downstream effects particularly under pro-oxidative status. Subcellular traffics of HO-1 to different organelles constitute a network of interactions compromising a variety of effectors such as pro-oxidants, ROS, mitochondrial enzymes, and nucleic transcription factors. Some of the compartmentalized HO-1 have been demonstrated as functioning in the progression of cancer. Emerging data show the multiple roles of HO-1 in tumorigenesis from pathogenesis to the progression to malignancy, metastasis, and even resistance to therapy. However, the role of HO-1 in tumorigenesis has not been systematically addressed. This review describes the crosstalk between HO-1 and oxidative stress, and following redox regulation in the tumorigenesis. HO-1-regulated signaling pathways are also summarized. This review aims to integrate basic information and current progress of HO-1 in cancer research in order to enhance the understandings and facilitate following studies.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children. Several scales are available to evaluate ADHD therapeutic effects, including the Swanson, Nolan, and Pelham (SNAP) questionnaire, the Vanderbilt ADHD Diagnostic Rating Scale, and the visual analog scale. However, these scales are subjective. In the present study, we proposed an objective and automatic approach for evaluating the therapeutic effects of medication in patients with (ADHD). The approach involved using movement quantification of patients' skeletons detected automatically with OpenPose in outpatient videos. Eleven skeleton parameter series were calculated from the detected skeleton sequence, and the corresponding 33 features were extracted using autocorrelation and variance analysis. This study enrolled 25 patients with ADHD. The outpatient videos were recorded before and after medication treatment. Statistical analysis indicated that four features corresponding to the first autocorrelation coefficients of the original series of four skeleton parameters and 11 features each corresponding to the first autocorrelation coefficients of the differenced series and the averaged variances of the original series of 11 skeleton parameters significantly decreased after the use of methylphenidate, an ADHD medication. The results revealed that the proposed approach can support physicians as an objective and automatic tool for evaluating the therapeutic effects of medication on patients with ADHD.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA ( p DNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF p DNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured -34.8 ± 1.8 mV with 0.01% ( w / v ) high molecular weight chitosan (HMWC); the p DNA loading efficiency reached 90% at a nanoparticle to p DNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF p DNA polyplex was non-toxic to mouse iPSCs for up to 80 μg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF p DNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

Background: The aim of this study was to make a comparison of clinicopathological characteristics of oral leukoplakia between male and female patients following carbon dioxide laser excision for oral leukoplakia and analyze the factors associated with the treatment outcomes in female patients., Methods: Medical records of patients with oral leukoplakia receiving laser surgery from 2002 to 2020 were retrospectively reviewed and analyzed statistically., Results: A total of 485 patients were enrolled, including 412 male (84.95%) and 73 female (15.05%). Regarding the locations, the predilection site of oral leukoplakia in male patients was buccal mucosa ( p = 0.0001) and that for women patients was tongue ( p = 0.033). The differences of recurrence and malignant transformation between both sexes were not significant ( p > 0.05). Among female patients, area of oral leukoplakia was the risk factor related to recurrence ( p < 0.05). Clinical morphology and postoperative recurrence were the risk factors related to malignant transformation ( p < 0.05)., Conclusions: In comparison with male patients, there was no significant difference of the postoperative recurrence and malignant transformation of oral leukoplakia in female patients. Among the female patients, clinicians should pay more attention to large-sized and non-homogeneous leukoplakia, and postoperative recurrent lesions.

Few studies have examined associations between neighborhood built environments (BE) and longitudinally measured cognition. We examined whether four BE characteristics were associated with six-year change in global cognition and processing speed. We obtained data on 1816 participants without dementia from the Multi-Ethnic Study of Atherosclerosis. BE measures included social destination density, walking destination density, proportion of land dedicated to retail, and network ratio (street connectivity). Global cognition was measured with the Cognitive Abilities Screening Instrument (CASI) and processing speed with the Digit Symbol Coding test (DSC). Multivariable random intercept logistic models tested associations between neighborhood BE at 2010-2012 and maintained/improved cognition (versus decline) from 2010-2018, and mediation by minutes of physical activity (PA)/week. The sample was an average of 67 years old (standard deviation = 8.2) (first cognitive measurement) and racially/ethnically diverse (29% African American, 11% Chinese, 17% Hispanic, 44% White). Compared to individuals with no walking destinations in the 1-mile surrounding their residence, those with 716 walking destinations (maximum observed) were 1.24 times more likely to have maintain/improved DSC score (Odds ratio: 1.24; 95% confidence interval: 1.03-1.45). No other associations were observed between BE and cognition, and PA minutes/week did not mediate the association between walking destination density and DSC change. This study provides limited evidence for an association between greater neighborhood walking destinations and maintained/improved processing speed in older age and no evidence for associations between the other BE characteristics and cognition. Future studies with finer grained BE and cognitive measures and longer-term follow up may be required.

Background: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed., Methodology: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts., Results: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone., Conclusion: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.

In recent decades, the obesity epidemic has resulted in morbidity and mortality rates increasing globally. In this study, using obese mouse models, we investigated the relationship among urokinase plasminogen activator (uPA), metabolic disorders, glomerular filtration rate, and adipose tissues. Two groups, each comprised of C57BL/6J and BALB/c male mice, were fed a chow diet (CD) and a high fat diet (HFD), respectively. Within the two HFD groups, half of each group were euthanized at 8 weeks (W8) or 16 weeks (W16). Blood, urine and adipose tissues were collected and harvested for evaluation of the effects of obesity. In both mouse models, triglyceride with insulin resistance and body weight increased with duration when fed a HFD in comparison to those in the groups on a CD. In both C57BL/6J and BALB/c HFD mice, levels of serum uPA initially increased significantly in the W8 group, and then the increment decreased in the W16 group. The glomerular filtration rate declined in both HFD groups. The expression of uPA significantly decreased in brown adipose tissue (BAT), but not in white adipose tissue, when compared with that in the CD group. The results suggest a decline in the expression of uPA in BAT in obese m models as the serum uPA increases. There is possibly an association with BAT fibrosis and dysfunction, which may need further study.

Back pain resulted from spine disorders reaches 60-80% prevalence in humans, which seriously influences life quality and retards economic production. Conventional electrical pain relief therapy uses radiofrequency to generate a high temperature of 70-85 °C on the electrode tip to destroy the neural transmission and stop the pain. However, due to the larger area of stimulation, eliciting significant side effects, such as paralysis, contraction, and a slightly uncomfortable feeling, our study aimed to design a tiny and stretchable neural stimulatory electrode that could be precisely anchored adjacent to the dorsal root ganglion which needs therapy and properly interfere with the sensory neural transmission. We also designed a subcutaneously implantable wireless power transmission (WPT) device to drive the neural stimulatory electrode. Through the study, we elaborated the design concept and clinical problems, and achieved: (1) the architecture design and simulation of the transdermal wireless power transferred device, (2) a wrap-able pulsed radiofrequency (PRF) stimulatory electrode, (3) an insulation packaging design of the titanium protection box. The feasibility study and hands-on prototype were also carried out.

Non-small cell lung cancer (NSCLC) is a typical inflammation-associated cancer, and lung adenocarcinoma (LUAD) is the most common histopathological subtype. Epidermal growth factor receptor (EGFR) mutations are the most common driver mutations of LUAD, and they have been identified as important therapeutic targets by EGFR tyrosine kinase inhibitors. Interleukin (IL)-17A secreted by T-helper 17 lymphocytes is a proinflammatory cytokine that plays an important role in cancer pathogenesis. The present study was designed to investigate the possible associations among IL-17A genetic polymorphisms, EGFR mutation status, and the clinicopathologic development of LUAD in a Taiwanese population. Our study population consisted of 277 LUAD patients harboring the wild-type (WT) EGFR or a mutant (MT) EGFR. Four single-nucleotide polymorphisms (SNPs) of IL-17A in the peripheral blood, including rs8193036(C > T), rs8193037(G > A), rs2275913(G > A), and rs3748067(C > T) loci, were genotyped using a TaqMan allelic discrimination assay. Our results showed that none of these IL-17A SNPs were correlated with the risk of developing mutant EGFR. However, patients with a smoking habit who carried the GA genotype of IL-17A rs8193037 had a significantly lower susceptibility to EGFR mutations (adjusted odds ratio (AOR): 0.225; 95% confidence interval (CI): 0.056~0.900, p = 0.035). Moreover, compared to individuals carrying the CC genotype of rs8193036 at IL-17A, T-allele carriers (CT + TT) were at higher risk of developing more-advanced stages (stage III or IV; p = 0.020). In the WT EGFR subgroup analysis, IL-17A rs8193036 T-allele carriers had higher risks of developing an advanced tumor stage ( p = 0.016) and lymphatic invasion ( p = 0.049). Further analyses of clinical datasets revealed correlations of IL-17 receptor A (IL-17RA) and IL-17RC expressions with a poor prognosis of LUAD patients with a smoking history or with higher levels of tumor-infiltrating lymphocytes. In conclusion, our results suggested that two functional promoter polymorphisms of IL-17A, i.e., rs8193036 and rs8193037, were associated with the EGFR mutation status and progression in LUAD patients, indicating that these two genetic variants might act as possible markers for predicting patients' clinical prognoses.

Background: Low cardiorespiratory fitness is associated with increased risk of hypertension and atherosclerosis in adults with prehypertension. The purpose of this study was to quantify cardiorespiratory fitness and to examine the utility of supramaximal constant-load verification testing for validating maximal oxygen uptake (VO 2max ) attainment in adults with prehypertension., Methods: Eleven adults (four women) with prehypertension (22.5 ± 2.9 y; body mass index (BMI): 24.6 ± 3.2 kg·m 2 ) underwent an incremental exercise test followed 15 min later by a verification test at 105% of maximal work rate on a cycle ergometer., Results: There was no statistical difference in VO 2 between the incremental (2.23 ± 0.54 L·min -1 ) and verification tests (2.28 ± 0.54 L·min -1 ; p = 0.180). Only three out of eleven participants had a higher VO 2 during the verification when compared with the incremental test. If the verification test had not been conducted, one participant would have been incorrectly classified as having low cardiorespiratory fitness based on incremental test results alone., Conclusions: Verification testing validates the attainment of VO 2max and can potentially reduce the over-diagnosis of functional impairment (i.e., deconditioning) in adults with prehypertension.

Intravesical administration of chemotherapeutic agents can enhance drug accumulation in tumors and reduce systemic side effects. Nanocarriers were developed for intravesical administration and exploit the permeation enhancement effect. In vitro permeation evaluation, the drug transdermal amount and accumulation amounts in the tissue of gemcitabine-loaded nanocarriers through biological membrane significantly increased about 14.8~33.0-fold and 1.5~14.1-fold respectively, when compared to a control group of 1% gemcitabine saline solution. In in vivo intravesical administration, the drug accumulation amount in bladder tissue of nanocarrier of 75.2 ± 5.4 μg was revealed as being comparably higher than that of the control group of 44.8 ± 6.4 μg. In confocal laser scanning microscopy imagery, the penetration depth of fluorescent dyes-rhodamine was increased from 80 μm up to 120 μm when a nanocarrier was used. This result implies that the nanocarrier is a promising drug delivery agent for intravesical administration.

Combined chemotherapy is an effective and safe treatment for cancers. Co-administration of cisplatin and gemcitabine produces a synergistic effect for bladder cancer treatment, so viscous microemulsions were developed for co-delivery of cisplatin and gemcitabine to extend the retention time and improve the permeability of chemotherapeutic drugs into the urothelium by intravesical administration. Results showed that the deposition amounts of cisplatin and gemcitabine significantly increased in in vitro and in vivo study. The penetration depth in bladder tissue samples increased from 60 to 120 μm. The dual-loaded formulation also showed thermodynamic and chemical stability, demonstrating that these gel-based microemulsions are promising drug delivery carriers for chemotherapy agents by intravesical administration.

Nano-silicate platelets (NSP), an exfoliated product from natural clays, have been validated for biosafety and as an effective supplement to alleviate mycotoxicosis. Since NSP induced noticeable cell death, we therefore investigated further the mechanism of cytotoxicity caused by NSP. Exposure to NSP impaired membrane integrity and caused cell death in a dose-dependent manner. Reactive oxygen species (ROS) generation other than of NADH oxidase origin, and subcellular interactions by internalized NSP also contributed to NSP-induced cell death. NSP persistently provoked receptor-interacting protein 1 Ser/Thr (RIP1) kinase and caspase 6 and 3/7 activation without altering caspase 8 activity and induced evident chromatolysis of necrosis in the later stage. These events proceeded along with increased ER stress and mitochondrial permeability, to final Cyt-C (Cytochrome C) release and AIF (apoptosis inducing factor) translocation, a hallmark of cell necroptosis. Fluorescent probing further manifested NSP traffic, mostly adherence on the cell surfaces, or via internalization, being compartmentalized in the nuclei, cytosols, and mitochondria. Pharmacological approaches with specific inhibitors suggested that endocytosis and particularly RIP1 kinase provocation mediate NSP-induced cell death independent of caspase activation. In conclusion, the necroptotic process contributes to most of the cell death induced by NSP due to membrane interactions/impaired integrity, ROS generation, and subcellular interactions by internalized NSP.

The as spun amorphous (Fe 78 Si 9 B 13 ) 99.5 Zr 0.5 (Zr0.5) and (Fe 78 Si 9 B 13 ) 99 Zr 1 (Zr1) ribbons having a Fenton-like reaction are proved to bear a good degradation performance in organic dye wastewater treatment for the first time by evaluating their degradation efficiency in methylene blue (MB) solution. Compared to the widely studied (Fe 78 Si 9 B 13 ) 100 Zr 0 (Zr0) amorphous ribbon for degradation, with increasing c Zr (Zr atomic content), the as-spun Zr0, Zr0.5 and Zr1 amorphous ribbons have gradually increased degradation rate of MB solution. According to δc (characteristic distance) of as-spun Zr0, Zr0.5 and Zr1 ribbons, the free volume in Zr1 ribbon is higher Zr0 and Zr0.5 ribbons. In the reaction process, the Zr1 ribbon surface formed the 3D nano-porous structure with specific surface area higher than the cotton floc structure formed by Zr0 ribbon and coarse porous structure formed by Zr0.5 ribbon. The Zr1 ribbon's high free volume and high specific surface area make its degradation rate of MB solution higher than that of Zr0 and Zr0.5 ribbons. This work not only provides a new method to remedying the organic dyes wastewater with high efficiency and low-cost, but also improves an application prospect of Fe-based glassy alloys.

Depressed colorectal neoplasm exhibits high malignant potential and shows rapid invasiveness. We investigated the genomic profile of depressed neoplasms and clarified the survival outcome and treatment response of the cancers arising from them. We examined 20 depressed and 13 polypoid neoplasms by genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations (CNAs) in an independent cohort of 37 depressed and 42 polypoid neoplasms. Finally, the CNAs were tested as biomarkers in 530 colorectal cancers (CRCs) to clarify the clinical outcome of depressed neoplasms. CNAs in MYC , CCNA1 , and BIRC7 were significantly enriched in depressed neoplasms and designated as the D-marker panel. CRCs with a D-marker panel have significantly shorter progression-free survival compared with those without ( p = 0.012), especially in stage I ( p = 0.049), stages T 1+2 ( p = 0.027), and proximal cancers ( p = 0.002). The positivity of the D-marker panel was an independent risk factor of cancer progression (hazard ratio (95% confidence interval) = 1.52 (1.09-2.11)). Furthermore, the proximal CRCs with D-marker panels had worse overall and progression-free survival when taking oxaliplatin as chemotherapy than those that did not. The D-marker panel may help to optimize treatment and surveillance in proximal CRC and develop a molecular test. However, the current result remains preliminary, and further validation in prospective trials is warranted in the future.

: Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM., Methods: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and β cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed., Results: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/- mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, β cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels., Conclusion: uPA may play a substantial role in insulin secretion, β cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future., Competing Interests: The authors declare no conflicts of interest

Dedicator of cytokinesis 1 (DOCK1) is a critical regulator of cancer metastasis. Claudins are transmembrane proteins that play a role in epithelial barrier integrity. Due to a loss or low expression of claudins (CLDN), the claudin-low type of triple-negative breast cancer (TNBC) is characterized by a mesenchymal-like phenotype with strong metastatic potential. In order to elucidate the mechanism of DOCK1 in cancer metastasis, we first analyzed the transcriptomic changes using a clinical database of human TNBC and found that the increase in DOCK1 expression was highly correlated with the poor survival rate of TNBC patients. Interference with DOCK1 expression by shRNA resulted in re-expression of claudin-1 in conjunction with significant inhibition of cell viability and motility of claudin-low breast cancer cells. Accordingly, overexpression of claudin-1 suppressed cell viability and migration. Genetic knockdown and pharmacological blockade of Rac1/Rac2 up-regulated claudin-1. DOCK1 knockdown also caused a decrease in DNA methyltransferase (DNMT) expression and an increase in claudin-1 transcript and promoter activity. Furthermore, RRP1B mediated DOCK1 depletion, which up-regulated claudin-1 expression, cell viability, and motility in claudin-low breast cancer cells. This study demonstrated that DOCK1 mediates growth and motility through down-regulated claudin-1 expression via the RRP1BDNMTclaudin-1 pathway and that claudin-1 serves as an important effector in DOCK1-mediated cancer progression and metastasis in claudin-low breast cancer cells., Competing Interests: The authors declare no conflict of interest.

Zr-Si-N films with atomic ratios of N/(Zr + Si) of 0.54-0.82 were fabricated through high-power impulse magnetron sputtering (HiPIMS)-radio-frequency magnetron sputtering (RFMS) cosputtering by applying an average HiPIMS power of 300 W on the Zr target, various RF power levels on the Si target, and negative bias voltage levels of 0-150 V connected to the substrate holder. Applying a negative bias voltage on substrates enhanced the ion bombardment effect, which affected the chemical compositions, mechanical properties, and residual stress of the Zr-Si-N films. The results indicated that Zr-Si-N films with Si content ranging from 1.4 to 6.3 atom % exhibited a high hardness level of 33.2-34.6 GPa accompanied with a compressive stress of 4.3-6.4 GPa, an H/E* level of 0.080-0.107, an H 3 /E* 2 level of 0.21-0.39 GPa, and an elastic recovery of 62-72%.

In this study, we explored the considerations and the influencing factors for the technological integration of educational curricula based on the technological pedagogical content knowledge (TPCK) framework for health profession educators (HPEs). A mixed methodology was used that included semi-structured interviews with 15 HPEs and an online TPCK survey with a randomly selected sample of 319 HPEs from 217 Taiwanese universities. Five themes emerged, namely, supplementing traditional teaching methods, improving immediate educator-student interactions, tracking the learning process and improving the record-keeping, keeping up with technological trends, and advancing professional learning objectives for different student needs. The presence of pre-existing platforms and inspiration from colleagues and students were facilitators, whereas the risk of technological problems and the need to invest extra time into the preparation process were impediments to technology integration in the curriculum. Of the online respondents (n = 210), 64.2% have integrated at least one technological method into their curriculum. The logistic regression model revealed that gender, prior knowledge regarding how to incorporate technology with teaching, high mean TPCK scores, and relevant school policies were significant predictors of technology integration in the curriculum. Based on these results, recommendations for development in the health profession included efforts to equip HPEs with TPCK, in order to integrate technology into the curriculum effectively.

In this study, a long carbon chain dimer acid is introduced into a nylon 6 structure and is copolymerized with different structural amines to produce amorphous nylon 6 by 4,4'-methylenebis(2-methylcyclohexylamine) (MMCA) in different copolymerization ratios. The effect of different structures and copolymerization ratios on the properties of nylon 6 is determined, along with the thermal properties, crystallinity, water absorption, dynamic mechanical properties, and optical properties. It is found that the melting point and the thermal cracking temperature Td10 of nylon 6 are respectively between 176 °C and 213 °C and 378 °C to 405 °C. The effect of introducing a bicyclohexane group containing a methyl side chain is greater than that of a meta-benzene ring, so COMM (synthesized by Caprolactam (C), dimer oleic acid (OA), and 4,4'-Methylenebis(2-methylcyclohexylamine) (MMCA)) has the lowest melting point, enthalpy, and crystallinity. As the copolymerization ratio increases, its thermal properties decrease. 10% is the lowest crystallinity. The amine structure containing a bicycloalkyl group has lower water absorption and a 10% copolymerization ratio gives the lowest water absorption. It contains the bicycloalkyl group, COM (synthesized by Caprolactam (C), dimer oleic acid (OA) and 4,4'-Methylenebis(cyclohexylamine) (MCA)), which has the highest loss modulus. The lowest loss modulus is noted for a copolymerization ratio of 7% and the value of tan δ increases as the copolymerization ratio increases. The introduction of nylon 6 with the bicycloalkyl groups, COMM and COM, significantly increases transparency. As the copolymerization ratio increases, the transparency increases and the haze decreases. The best optical properties are achieved for 10% copolymerization.

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases. Ferroptosis is a newly identified iron- and lipid peroxidation-dependent cell death. The critical role of HO-1 in heme metabolism makes it an important candidate to mediate protective or detrimental effects via ferroptosis induction. This review summarizes the current understanding on the regulatory mechanisms of HO-1 in ferroptosis. The amount of cellular iron and reactive oxygen species (ROS) is the determinative momentum for the role of HO-1, in which excessive cellular iron and ROS tend to enforce HO-1 from a protective role to a perpetrator. Despite the dark side that is related to cell death, there is a prospective application of HO-1 to mediate ferroptosis for cancer therapy as a chemotherapeutic strategy against tumors.

The implementation of evidence-based practice (EBP) in health care has been focused mainly on hospital settings and there is little research on EBP adoption and implementation among school nurses in Taiwan. This study aimed to determine primary school nurses' perceptions regarding EBP and to explore the factors that influence EBP in Taiwan. A cross-sectional design was used and the School Nurse Evidence-Based Practice Questionnaire was developed to collect data. A total of 2679 elementary school nurses in Taiwan were invited to participate in this study, and 1200 completed questionnaires were returned, with a 45% response rate. Participants' mean age was 37.5 (range: 31⁻62) years and the mean duration of employment as a school nurse was 8.4 (range: 1⁻20) years. The majority of participants had a Bachelor's degree (56%). The results revealed that participants had insufficient EBP knowledge and skills. However, they had a positive attitude toward and moderate self-efficacy in EBP. The demographic data positively correlated with knowledge, attitudes, skills, self-efficacy, and influencing factors. Certain influencing factors were highlighted. As school nurses play a crucial role in promoting children's health, they ought to embrace EBP so as to provide more effective services. School organization should play a supportive role with regard to EBP implementation.

Recent studies have revealed the influence of fine particulate matter (PM 2.5 ) on increased medication use, hospital admission, and emergency room visits for asthma attack in children, but the lagged influence of PM 2.5 on children&rsquo;s asthma and geographic disparities of children&rsquo;s asthma have rarely been discussed simultaneously. This study investigated the documented diagnosis of children&rsquo;s asthma in clinic visits for children aged less than 15 years old that were associated with PM 2.5 in two counties located in west-central Taiwan during 2005⁻2010. The result shows that PM 2.5 had a significant lagged effect on children&rsquo;s asthma for up to 6 days. A significantly higher relative risk for children&rsquo;s asthma was more likely to happen at 2-day lag compared to the present day when PM 2.5 increased from 36.17 &mu;g/m³ to 81.26 &mu;g/m³. Considering all lagged effects, the highest relative risk for children&rsquo;s asthma was 1.08 (95% CI = 1.05, 1.11) as PM 2.5 increased as high as 64.66 &mu;g/m³. In addition, geographic disparities of children&rsquo;s asthma were significant, and 47.83% of areas were identified to have children vulnerable to asthma. To sum up, our findings can serve as a valuable reference for the implementation of an early warning to governmental agencies about a susceptible population of children.