Automatic wild bird repellent system that is based on deep-learning-based wild bird detection and integrated with a laser rotation mechanism.

Wild bird repulsion is critical in agriculture because it helps avoid agricultural food losses and mitigates the risk of avian influenza. Wild birds transmit avian influenza in poultry farms and thus cause large economic losses. In this study, we developed an automatic wild bird repellent system that is based on deep-learning-based wild bird detection and integrated with a laser rotation mechanism. When a wild bird appears at a farm, the proposed system detects the bird's position in an image captured by its detection unit and then uses a laser beam to repel the bird. The wild bird detection model of the proposed system was optimized for detecting small pixel targets, and trained through a deep learning method by using wild bird images captured at different farms. Various wild bird repulsion experiments were conducted using the proposed system at an outdoor duck farm in Yunlin, Taiwan. The statistical test results of our experimental data indicated that the proposed automatic wild bird repellent system effectively reduced the number of wild birds in the farm. The experimental results indicated that the developed system effectively repelled wild birds, with a high repulsion rate of 40.3% each day.

The lncRNA TPT1-AS1 promotes the survival of neuroendocrine prostate cancer cells by facilitating autophagy.

The lncRNA tumor protein translationally controlled 1-antisense RNA 1 (TPT1-AS1) is known for its oncogenic role in various cancers, but its impact on the pathological progression of prostate cancer remains unclear. Our previous study demonstrated that the RE1-silencing transcription factor (REST) regulates neuroendocrine differentiation (NED) in prostate cancer (PCA) by derepressing specific long non-coding RNAs (lncRNAs), including TPT1-AS1. In this study, we revealed that TPT1-AS1 is overexpressed in LNCaP and C4-2B cells after IL-6 and enzalutamide treatment. By analyzing The Cancer Genome Atlas (TCGA) prostate adenocarcinoma dataset, we detected upregulated TPT1-AS1 expression in neuroendocrine-associated PCA but not in prostate adenocarcinoma. Single-cell RNA sequencing data further confirmed the increased TPT1-AS1 levels in neuroendocrine prostate cancer (NEPC) cells. Surprisingly, functional experiments indicated that TPT1-AS1 overexpression had no stimulatory effect on NED in LNCaP cells and that TPT1-AS1 knockdown did not inhibit IL-6-induced NED. Transcriptomic analysis revealed the essential role of TPT1-AS1 in synaptogenesis and autophagy activation in neuroendocrine differentiated PCA cells induced by IL-6 and enzalutamide treatment. TPT1-AS1 was found to regulate the expression of autophagy-related genes that maintain neuroendocrine cell survival through autophagy activation. In conclusion, our data expand the current knowledge of REST-repressed lncRNAs in NED in PCA and highlight the contribution of TPT1-AS1 to protect neuroendocrine cells from cell death rather than inducing NED. Our study suggested that TPT1-AS1 plays a cytoprotective role in NEPC cells; thus, targeting TPT1-AS1 is a potential therapeutic strategy.

Synthesis and Characterization of Sol-Gelled Barium Zirconate as Novel MTA Radiopacifiers.

Barium zirconate (BaZrO3, BZO), which exhibits superior mechanical, thermal, and chemical stability, has been widely used in many applications. In dentistry, BZO is used as a radiopacifier in mineral trioxide aggregates (MTAs) for endodontic filling applications. In the present study, BZO was prepared using the sol-gel process, followed by calcination at 700-1000 °C. The calcined BZO powders were investigated using X-ray diffraction and scanning electron microscopy. Thereafter, MTA-like cements with the addition of calcined BZO powder were evaluated to determine the optimal composition based on radiopacity, diametral tensile strength (DTS), and setting times. The experimental results showed that calcined BZO exhibited a majority BZO phase with minor zirconia crystals. The crystallinity, the percentage, and the average crystalline size of BZO increased with the increasing calcination temperature. The optimal MTA-like cement was obtained by adding 20% of the 700 °C-calcined BZO powder. The initial and final setting times were 25 and 32 min, respectively. They were significantly shorter than those (70 and 56 min, respectively) prepared with commercial BZO powder. It exhibited a radiopacity of 3.60 ± 0.22 mmAl and a DTS of 3.02 ± 0.18 MPa. After 28 days of simulated oral environment storage, the radiopacity and DTS decreased to 3.36 ± 0.53 mmAl and 2.84 ± 0.27 MPa, respectively. This suggests that 700 °C-calcined BZO powder has potential as a novel radiopacifier for MTAs.

Effects of Calcination Temperature on the Synthesis of One-Pot Sol-Gelled Barium Titanate Powder and Its Performance as an Endodontic Radiopacifier.

Barium titanate (BaTiO3, BTO), conventionally used for dielectric and ferroelectric applications, has been assessed for biomedical applications, such as its utilization as a radiopacifier in mineral trioxide aggregates (MTA) for endodontic treatment. In the present study, BTO powders were prepared using the sol-gel process, followed by calcination at 400-1100 °C. The X-ray diffraction technique was then used to examine the as-prepared powders to elucidate the effect of calcination on the phase composition and crystalline size of BTO. Calcined BTO powders were then used as radiopacifiers for MTA. MTA-like cements were investigated to determine the optimal calcination temperature based on the radiopacity and diametral tensile strength (DTS). The experimental results showed that the formation of BTO phase was observed after calcination at temperatures of 600 °C and above. The calcined powders were a mixture of BaTiO3 phase with residual BaCO3 and/or Ba2TiO4 phases. The performance of MTA-like cements with BTO addition increased with increasing calcination temperature up to 1000 °C. The radiopacity, however, decreased after 7 days of simulated oral environmental storage, whereas an increase in DTS was observed. Optimal MTA-like cement was obtained by adding 40 wt.% 1000 °C-calcined BTO powder, with its resulting radiopacity and DTS at 4.83 ± 0.61 mmAl and 2.86 ± 0.33 MPa, respectively. After 7 days, the radiopacity decreased slightly to 4.69 ± 0.51 mmAl, accompanied by an increase in DTS to 3.13 ± 0.70 MPa. The optimal cement was biocompatible and verified using MG 63 and L929 cell lines, which exhibited cell viability higher than 95%.

A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion.

Cargo translocation across membranes is a crucial aspect of secretion. In conventional secretion signal peptide-equipped proteins enter the endoplasmic reticulum (ER), whereas a subset of cargo lacking signal peptides translocate into the ER-Golgi intermediate compartment (ERGIC) in a process called unconventional protein secretion (UcPS). The regulatory events at the ERGIC in UcPS are unclear. Here we reveal the involvement of ERGIC-localized small GTPases, Rab1 (Rab1A and Rab1B) and Rab2A, in regulating UcPS cargo transport via TMED10 on the ERGIC. Rab1 enhances TMED10 translocator activity, promoting cargo translocation into the ERGIC, whereas Rab2A, in collaboration with KIF5B, regulates ERGIC compartmentalization, establishing a UcPS-specific compartment. This study highlights the pivotal role of ERGIC-localized Rabs in governing cargo translocation and specifying the ERGIC's function in UcPS.

The gamification and development of a chatbot to promote oral self-care by adopting behavior change wheel for Taiwanese children.

Background: Oral health is closely related to general health and quality of life. School-aged children are at a critical stage for developing their self-care ability in oral health. Digital interventions can encourage and facilitate oral self-care in children. Objective: This study aims to present the development of an educational chatbot for school-aged children to address their oral self-care and evaluate its usability. Methods: The development and evaluation of the chatbot for oral self-care consisted of four stages: target behavior analysis, intervention design, system development, and the chatbot evaluation. The target behavior analysis identified barriers to children's engagement in oral self-care based on dentists' clinical observations; hence, the requirements for achieving the desired behavior were categorized according to the capability-opportunity-motivation behavior model. Interventional functions were created following the behavior change wheel. A menu-driven chatbot was created and evaluated for usability as well as likeability. Results: The barriers and requirements for achieving good behavior in school-aged children's oral self-care were identified by the dental professionals. Intervention strategy incorporated specific functions enriched with gamification features to support school-aged children in developing their abilities for engaging in oral self-care. The intervention functions consist of capability establishment, motivation enhancement, and opportunity creation, which were designed to support children in their oral self-care practices. The designed chatbot was piloted with a convenient sample of 30 school-aged children and their accompanying parents at the pediatric dental clinic. The results indicated good usability, with a mean usability score of 79.91, and high likeability with a mean score of 4.32 out of 5 for the designed chatbot. Conclusions: The educational chatbot incorporated a combination of clinical dentistry practice and guidelines, aiming to promote oral self-care behavior in school-aged children. The designed chatbot achieved high scores for its usability and user likability.

Exploring Bile-Acid Changes and Microflora Profiles in Chicken Fatty Liver Disease Model.

Excessive liver fat causes non-alcoholic fatty liver disease (NAFLD) in laying hens, reducing egg production. Addressing NAFLD via bile-acid metabolism is gaining attention. We induced NAFLD in 7-week-old ISA female chickens with a high-cholesterol, low-choline diet (CLC) for 6 weeks. LC/MS was used to analyze serum and cecal bile acids, while cecal digesta DNA underwent 16S rRNA sequencing. The distribution of bile acid varied in healthy (CON) and CLC-fed chickens. CLC increased secondary bile acids (TLCA, TUDCA, THDCA, TDCA) in serum and primary bile acids (CDCA, TCDCA, isoDCA) in serum, as well as glycochenodeoxycholic acid (GCDCA) in cecal contents. CLC upregulated bile-acid synthesis enzymes (CYP7A1, CYP8B1) in the liver. Bile-acid receptor gene expression (HNF4A, FXR, LXR) was similar between groups. Microbiota abundance was richer in CON (alpha-diversity), with distinct separation (beta-diversity) between CON and CLC. The Firmicutes/Bacteroidetes ratio slightly decreased in CLC. Taxonomic analysis revealed higher Bacteroides, Alistipes, Megamonas in CLC but lower Barnesiella. CLC had more Mucispirillum, Eubacterium_coprostanoligenes_group, Shuttleworthia, and Olsenella, while CON had more Enterococcus, Ruminococcaceae_UCG_014, and Faecalibacterium. This study unveils bile-acid and microflora changes in a chicken NAFLD model, enhancing our understanding of fatty liver disease metabolism and aiding targeted interventions.

Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Serum Cytokines Correlate with Pretreatment Body Mass Index-adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery.

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1ß), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1ß, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1ß, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.

Taping alone for persistent ventral curvature after urethral plate transection in hypospadias.

INTRODUCTION: Ventral penile curvature is a key factor in determining the surgical approach to proximal hypospadias repair. However, there is limited evidence regarding the efficacy and long-term effects of the procedures used to address curvature. This study aimed to evaluate the effects of urethral plate transection alone with tissue traction therapy on penile curvature in two-stage repair of proximal hypospadias. MATERIAL AND METHODS: This was a prospective study of primary hypospadias patients who underwent a two-stage repair with urethral plate transection as the sole straightening procedure. After stage 1, taping was applied as tissue traction therapy and continued until stage 2. Penile curvature was measured using a goniometer under artificial erection before and immediately after urethral plate transection and during the second stage of repair. The primary focus of this investigation is the angle of curvature after 6-month taping. RESULTS: The study included 46 patients with a median age of 13 months at the start of treatment. The median angle of penile ventral curvature was 70° after degloving, 60° after urethral plate transection, and 0° during the second stage of repair. Full correction of ventral curvature was achieved in 42 patients (91 %). DISCUSSION: This publication is the first of its kind to propose taping as a method for penile traction therapy in hypospadias. The study reveals that penile ventral lengthening can be achieved through tissue traction therapy following UP transection alone. These findings challenge the current consensus that complete straightening of the penis in the first stage is necessary to prevent recurrent curvature and that ventral lengthening is required to correct corporal disproportion. However, further validation and long-term data are needed to definitively confirm the effectiveness of tissue traction therapy after urethral plate transection. CONCLUSIONS: This study demonstrated significant resolution rate of penile ventral curvature in proximal hypospadias following urethral plate transection alone with taping. Long-term follow-up studies are needed to confirm the sustainability of the results through puberty.

Clinical effects and mechanisms of a Chinese patent medicine, Tongxinluo capsule, as an adjuvant treatment in coronary heart disease.

Coronary heart disease (CHD) is the leading cause of death globally, posing a serious threat to human health. However, the current treatment approaches available for CHD fall short of the ideal results. Tongxinluo (TXL) is a traditional Chinese medicine (TCM) that has been employed in the clinical treatment of cardiovascular and cerebrovascular diseases (such as angina pectoris, stroke, etc.) in China for many years and holds great potential as a prospective treatment. TXL either as a standalone treatment or in combination with interventions recommended in CHD guidelines has been shown to be effective and well tolerated in clinical trials for CHD. Drawing on the evidence from clinical trials and experimental studies, this review will focus on the cardiovascular protective properties and related mechanisms of TXL. By searching 8 Chinese and English databases, more than 4000 articles were retrieved. These articles were categorized, then read, and finally written into this review. In this review, the pharmacological properties of TXL include regulation of blood lipids, improvement of endothelial function, anti-inflammatory, antioxidant, inhibition of apoptosis and regulation of autophagy, anti-fibrosis, promotion of angiogenesis, and modulation of exosome communication. The information provided in this review will help the reader to comprehend better the insights that TCM has developed over time in practice and provide new perspectives for the treatment of CHD.

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy.

This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.

Gender difference in emotional distress among nursing and health science college students: An online survey.

This cross-sectional study investigates the self-reported emotional distress of medical, nursing, dental, pharmacy, and public health students and identifies gender-related differences through an online survey. The data of 364 students were analyzed using Pearson correlation coefficients and multiple logistic regression. Emotional distress was more prevalent among female respondents (11.7 %) than male (3.8 %) respondents. The stigma, isolation, and depression experienced by female respondents influenced their emotional distress, whereas only the depression of male respondents influenced their emotional distress. Our findings suggest that mental health professionals should consider gender-specific factors when developing interventions for the study population to minimize emotional distress.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Inhibition of tumor migration and invasion by fenofibrate via suppressing epithelial-mesenchymal transition in breast cancers.

The recurrence and metastasis in breast cancer within 3 years after the chemotherapies or surgery leads to poor prognosis with approximately 1-year overall survival. Large-scale scanning research studies have shown that taking lipid-lowering drugs may assist to reduce the risk of death from many cancers, since cholesterol in lipid rafts are essential for maintain integral membrane structure and functional signaling regulation. In this study, we examined five lipid-lowering drugs: swertiamarin, gemfibrozil, clofibrate, bezafibrate, and fenofibrate in triple-negative breast cancer, which is the most migration-prone subtype. Using human and murine triple-negative breast cancer cell lines (Hs 578 t and 4 T1), we found that fenofibrate displays the highest potential in inhibiting the colony formation, wound healing, and transwell migration. We further discovered that fenofibrate reduces the activity of pro-metastatic enzymes, matrix metalloproteinases (MMP)-9 and MMP-2. In addition, epithelial markers including E-cadherin and Zonula occludens-1 are increased, whereas mesenchymal markers including Snail, Twist and α-smooth muscle actin are attenuated. Furthermore, we found that fenofibrate downregulates ubiquitin-dependent GDF-15 degradation, which leads to enhanced GDF-15 expression that inhibits cell migration. Besides, nuclear translocation of FOXO1 is also upregulated by fenofibrate, which may responsible for GDF-15 expression. In summary, fenofibrate with anti-cancer ability hinders TNBC from migration and invasion, and may be beneficial to repurposing use of fenofibrate.

A Content Analysis of African Americans' Experience of Engaging in Qigong Exercise Intervention in a Community Setting.

Introduction: Although an increasing number of African Americans 50 years of age and older practice qigong, a mind-body exercise, to manage their health conditions, little is known about their perceptions and experiences of engaging in and learning qigong exercise. This study aimed to explore the subjective perceptions of the health benefits, engagement, adherence, and learning of qigong exercise in African Americans 45-85 years of age as a foundation for promoting this approach for African Americans' physical and psychological health. Methods: Fifteen African Americans were enrolled in a 1-h qigong exercise program twice a week for 8 weeks (a total of 16 sessions) in the activity center of a local church. Participants were interviewed after the intervention to explore their perceptions of learning and practicing qigong exercise. Interviews were conducted in person, audio recorded, transcribed verbatim, and analyzed using content analysis. Results: Five themes emerged: (1) Perceived benefits of practicing qigong, (2) helpful strategies for qigong learning, (3) facilitators for home qigong practice, (4) motivators for qigong exercise adherence, and (5) recommending qigong to others. qigong exercise was perceived to be effective for balance, flexibility, muscle strength, sleep quality, emotion regulation, and stress management. Nearly 75% of participants reported home qigong practice at least twice a week. Conclusions: Middle-age and older African Americans' responses provide insights on health benefits associated with practicing qigong exercise, adherence, home practice, and learning, which may serve as the first step to promoting the use of qigong exercise in this population and may be adopted to similar exercise interventions with minority older adults in the future.

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma.

Purpose: Uterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma. Materials and methods: This is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen. Results: Fifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events. Conclusion: Use of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma.

Endodontic Radiopacifying Application of Barium Titanate Prepared through a Combination of Mechanical Milling and Heat Treatment.

Mineral trioxide aggregates (MTA) are commonly used as endodontic filling materials but suffer from a long setting time and tooth discoloration. In the present study, the feasibility of using barium titanate (BTO) for discoloration and a calcium chloride (CaCl2) solution to shorten the setting time was investigated. BTO powder was prepared using high-energy ball milling for 3 h, followed by sintering at 700-1300 °C for 2 h. X-ray diffraction was used to examine the crystallinity and crystalline size of the as-milled and heat-treated powders. MTA-like cements were then prepared using 20-40 wt.% BTO as a radiopacifier and solidified using a 0-30% CaCl2 solution. The corresponding radiopacity, diametral tensile strength (DTS), initial and final setting times, and discoloration performance were examined. The experimental results showed that for the BTO powder prepared using a combination of mechanical milling and heat treatment, the crystallinity and crystalline size increased with the increasing sintering temperature. The BTO sintered at 1300 °C (i.e., BTO-13) exhibited the best radiopacity and DTS. The MTA-like cement supplemented with 30% BTO-13 and solidified with a 10% CaCl2 solution exhibited a radiopacity of 3.68 ± 0.24 mmAl and a DTS of 2.54 ± 0.28 MPa, respectively. In the accelerated discoloration examination using UV irradiation, the color difference was less than 1.6 and significantly lower than the clinically perceptible level (3.7). This novel MTA exhibiting a superior color stability, shortened setting time, and excellent biocompatibility has potential for use in endodontic applications.

Imperatorin ameliorates pulmonary fibrosis via GDF15 expression.

Background: Pulmonary fibrosis features in damaged pulmonary structure or over-produced extracellular matrix and impaired lung function, leading to respiratory failure and eventually death. Fibrotic lungs are characterized by the secretion of pro-fibrotic factors, transformation of fibroblasts to myofibroblasts, and accumulation of matrix proteins. Hypothesis/purpose: Imperatorin shows anti-inflammatory effects on alveolar macrophages against acute lung injury. We attempt to evaluate the properties of imperatorin on the basis of fibroblasts. Methods: In in vitro, zymosan was introduced to provoke pro-fibrotic responses in NIH/3T3 or MRC-5 pulmonary fibroblasts. Imperatorin was given for examining its effects against fibrosis. The mice were stimulated by bleomycin, and imperatorin was administered to evaluate the prophylactic potential in vivo. Results: The upregulated expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen protein due to zymosan introduction was decreased by imperatorin in fibroblasts. Zymosan induced the activity of transglutaminase 2 (TGase2) and lysyl oxidase (LOX), which was also inhibited by the administration of imperatorin. Imperatorin alone enhanced sirtuin 1 (SIRT1) activity and growth differentiation factor 15 (GDF15) secretion in fibroblasts via LKB1/AMPK/CREB pathways. In addition, GDF15 exerted a beneficial effect by reducing the protein expression of CTGF, α-SMA, and collagen and the activities of TGase and LOX. Moreover, orally administered imperatorin showed prophylactic effects on bleomycin-induced pulmonary fibrosis in mice. Conclusion: Imperatorin reduces fibrotic marker expression in fibroblasts and also increases GDF15 secretion via the LKB1/AMPK/CREB pathway, attenuating pro-fibrotic responses in vitro. Imperatorin also alleviates pulmonary fibrosis induced by bleomycin in vivo.

Single-cell analysis of castration-resistant prostate cancers to identify potential biomarkers for diagnosis and prognosis of neuroendocrine prostate cancer.

The high heterogeneity and low percentage of neuroendocrine cells in prostate cancer limit the utility of traditional bulk RNA sequencing and even single-cell RNA sequencing to find better biomarkers for early diagnosis and stratification. Re-clustering of specific cell-type holds great promise for identification of intra-cell-type heterogeneity. However, this has not yet been used in studying neuroendocrine prostate cancer heterogeneity. Neuroendocrine cluster(s) were individually identified in each castration-resistant prostate cancer specimen and combined for trajectory analysis. Three neuroendocrine states were identified. Neuroendocrine state 2 with the highest AR score was considered the initial starting state of neuroendocrine transdifferentiation. State 1 and state 3 with distinct high neuroendocrine scores and marker genes enriched in N-Myc and REST target genes, respectively, were considered as two different types of neuroendocrine differentiated cancer cells. These two states contained distinct groups of prostate cancer biomarkers and a strong distinguishing ability of normal versus cancerous prostate across different pathological grading was found in the N-Myc-associated state. Our data highlight the central role of N-Myc and REST in mediating lineage plasticity and classifying neuroendocrine phenotypes.