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The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

A 78-year-old woman with a history of colon cancer with metastasis to the liver was presented to our emergency department because of bilateral groin pain and difficulty in walking, which had gradually increased during the previous 5 days. The pain was of sudden onset, radiating to the back, without aggravating or relieving factors. It was associated with constipation, dysuria and vaginal discharge. She reported passing fecal matter from the vagina one month ago. On physical examination, she appeared malnourished. Her blood pressure was 98/65 mmHg, with a 108 beats/min heart rate and 28 breaths/min respiratory rate. She was afebrile. Physical examinations were unremarkable, except for pale conjunctiva, abdominal distention, and diffuse tenderness especially over the umbilicus with guarding tenderness. Bowel sounds were decreased. Pelvic examination showed a yellowish odorous vaginal discharge from the external orifice of uterus. A complete blood cell count showed the following: leukocyte count, 34,200/mm3; segmented neutrophils, 87.5%; hemoglobin level of 7.4 mg/dl; hematocrit, 18.8%; and platelet, 180000/uL. Other laboratory studies included: glucose, 86 mg/dL; serum urea nitrogen, 28 mg/dL; serum creatinine, 0.87 mg/dL; sodium, 142 mEq/L; potassium, 4.8 mEq/L; albumin, 2.5g/dL; a carbohydrate antigen 19-9 level of 3,244 U/ml, and a carcinoembryonic antigen (CEA) level of 64.6 ng/ml. Coronal and axial cuts of patient’s abdominopelvic computed Tomography (CT) are shown in figures 1 and 2.

Informed by ecological approaches to second language development (SLD), the current study looked into three adult English-as-a-foreign-language (EFL) learners' quests of engaging in lifelong, informal language learning in the digital age. Data from in-depth interviews revealed that popular culture presented in different media forms offered learners with an entry point into English learning as well as continuous sources of information and entertainment in the digital age. In their informal language learning, the participants all stressed the important role of mastering the fundamental language elements (e.g. vocabulary and diction) and being able to apply their knowledge to real-life settings. Their depictions of their ideal self also revealed their learning goals and future aspirations. These research outcomes contribute to our understanding of the complex ecology of lifelong informal language learning in the digital age. As lifelong learning becomes ever more important in the modern knowledge-based society, these research results provide insights into ways of supporting learners inside and outside the formal classroom boundaries.

The objective of this study was to explore the effect of the character of chitosans used, and the regeneration conditions employed on, the yield and physicochemical characteristics of regenerated products. Different concentrations of acetic acid were used to dissolve chitosans of 61.7% and 94.9% degree of deacetylation (DD), and weight-average molecular weight (Mw) of 176 and 97 kDa, respectively; they were then precipitated with an 8 N NaOH solution, followed by washing and neutral and freeze drying to get the regenerated products. Yields of regenerated products and their physicochemical properties, such as ash content, bulk density, Mw, polydispersity index (PDI), DD, and crystallinity were measured. A higher concentration of acetic acid used resulted in a higher yield. The purity of the regenerated product increased significantly, whereas the bulk density and crystallinity decreased significantly after regeneration. The regeneration process showed its merits of narrowing down the PDI of regenerated products. The DD and structure of chitosan was changed insignificantly after the regeneration process.

Sacrococcygeal teratoma (SCT) is a neoplasm derived from more than one primitive germ cell layer. SCTs have rarely been reported in adults. We present a case of a 17-year-old youth who complained of a painful mass over his left buttock. The mass had been growing gradually since his childhood. Magnetic resonance imaging showed a well-defined soft-tissue mass which contained mainly fat tissue and large intestine. The patient had complete excision of the tumor and coccyx. The gross impression and histology revealed a mature teratoma.

A 78-year-old woman with a history of colon cancer with metastasis to the liver was presented to our emergency department because of bilateral groin pain and difficulty in walking, which had gradually increased during the previous 5 days. The pain was of sudden onset, radiating to the back, without aggravating or relieving factors. It was associated with constipation, dysuria and vaginal discharge. She reported passing fecal matter from the vagina one month ago. On physical examination, she appeared malnourished. Her blood pressure was 98/65 mmHg, with a 108 beats/min heart rate and 28 breaths/min respiratory rate. She was afebrile. Physical examinations were unremarkable, except for pale conjunctiva, abdominal distention, and diffuse tenderness especially over the umbilicus with guarding tenderness. Bowel sounds were decreased. Pelvic examination showed a yellowish odorous vaginal discharge from the external orifice of uterus. A complete blood cell count showed the following: leukocyte count, 34,200/mm3; segmented neutrophils, 87.5%; hemoglobin level of 7.4 mg/dl; hematocrit, 18.8%; and platelet, 180000/uL. Other laboratory studies included: glucose, 86 mg/dL; serum urea nitrogen, 28 mg/dL; serum creatinine, 0.87 mg/dL; sodium, 142 mEq/L; potassium, 4.8 mEq/L; albumin, 2.5g/dL; a carbohydrate antigen 19-9 level of 3,244 U/ml, and a carcinoembryonic antigen (CEA) level of 64.6 ng/ml. Coronal and axial cuts of patient’s abdominopelvic computed Tomography (CT) are shown in figures 1 and 2.

Abstract Background Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory cytokine; however, its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research, we investigated the role and mechanism of IL-1Ra in malignant progression of PDA. Results Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples, we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors, we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene, encoding IL-1Ra, and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice, highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently, we found an increase in CD8+ T cells and a decrease in CD11b+Ly6G− immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells, we utilized a luciferase-based reporter CD4+ T cell line and splenocytes, which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8+ T cells, and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes. Conclusions Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra, and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of PDA.

Abstract Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Abstract Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer. Here, we demonstrated the tumor-suppressive role of the AR and found that activated AR could directly bind to the regulatory sequence of muscarinic acetylcholine receptor 4 (CHRM4) and downregulate its expression. CHRM4 was highly expressed in prostate cancer cells after androgen-deprivation therapy (ADT). CHRM4 overexpression may drive neuroendocrine differentiation of prostate cancer cells and is associated with immunosuppressive cytokine responses in the tumor microenvironment (TME) of prostate cancer. Mechanistically, CHRM4-driven AKT/MYCN signaling upregulated the interferon alpha 17 (IFNA17) cytokine in the prostate cancer TME after ADT. IFNA17 mediates a feedback mechanism in the TME by activating the CHRM4/AKT/MYCN signaling-driven immune checkpoint pathway and neuroendocrine differentiation of prostate cancer cells. We explored the therapeutic efficacy of targeting CHRM4 as a potential treatment for NEPC and evaluated IFNA17 secretion in the TME as a possible predictive prognostic biomarker for NEPC.

Suhor ("Journal of Curriculum Studies" 16, 247-257, 1984) defines "transmediation" as the "translation of content from one sign system to another" (p. 250). Research has shown that encouraging learners to transmediate meanings across modes provides them with opportunities to represent meanings in multiple ways. In fact, Fueyo ("Counterpoints" 176, 21-34, 2002) stated that thinking and expressing oneself through a range of sign systems is a basic educational right in a democratic society. The current study continues the research on transmediation by investigating how a class of Taiwanese English-as-a-foreign-language (EFL) adolescent students translated the textual content of Roald Dahl's (1988) classic novel "Matilda" into non-textual modes (e.g., drawings and drama skits). The participants engaged in a two-stage transmediational process by first drawing an individual illustration to accompany a passage taken from the novel and then working in groups to represent their favorite chapters in a multimodal manner. Results indicated various degrees of transferring and transforming the original textual content. It was also found that allowing students to choose the content to focus on for their final transmediational projects did not motivate students to transform their knowledge of the novel to a greater degree, as most of them were more concerned with accurately presenting the textual content. This article concludes with teaching suggestions and research directions to encourage practitioners and researchers to look further into the uses of transmediational practices in literacy instruction and research.

Purpose: In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia–Pacific region. Method: Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. Result: A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. Conclusion: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia–Pacific region.

Background: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. Methods: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0–18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. Results: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017–2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. Conclusions: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

LaFexNi1−xO3 perovskite oxides were prepared by the sol–gel method under various conditions, including different pH values (pH 0 and pH 7) and different calcination temperatures (500–800 °C) as well as different Fe/Ni ratios (1/9, 3/7, 5/5, 7/3, 9/1). The samples were examined by XRD, DRS, BET, and SEM to reveal their crystallinity, light-absorption ability, specific surface area, and surface features, respectively. The photocatalytic Fenton reaction was conducted using various LaFexNi1−xO3 perovskite oxides to decompose the methylene blue molecules. Accordingly, the synthesis condition of pH 0, calcination temperature at 700 °C, and Fe/Ni ratio = 7/3 could form LaFe0.7Ni0.3O3 perovskite oxides as highly efficient photocatalysts. Moreover, various conditions during the photocatalytic degradation were verified, such as pH value, catalyst dosage, and the additional amount of H2O2. LaFe0.7Ni0.3O3 perovskite oxides could operate efficiently under pH 3.5, catalyst dosage of 50 mg/150 mL, and H2O2 concentration of 133 ppm to decompose the MB dye in the 1st order kinetic rate constant of 0.0506 s−1.

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However, the metabolic pathways that regulate NE differentiation (NED) in PCa remain unclear. Herein, we show a regulatory mechanism in NED-associated metabolism dysfunction induced by ADT, whereby overexpression of pyruvate kinase L/R (PKLR) mediates oxidative stress through upregulation of reactive oxygen species modulator 1 (ROMO1), thereby promoting NED and aggressiveness. ADT mediates the nuclear translocation of PKLR, which binds to the MYCN/MAX complex to upregulate ROMO1 and NE-related genes, leading to altered mitochondrial function and NED of PCa. Targeting nuclear PKLR/MYCN using bromodomain and extra-terminal motif (BET) inhibitors has the potential to reduce PKLR/MYCN-driven NED. Abundant ROMO1 in serum samples may provide prognostic information in patients with ADT. Our results suggest that ADT resistance leads to upregulation of PKLR/MYCN/ROMO1 signaling, which may drive metabolic reprogramming and NED in PCa. We further show that increased abundance of serum ROMO1 may be associated with the development of NE-like PCa.