Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting cellular senescence in senile osteoporosis: therapeutic potential of traditional Chinese medicine

Senile osteoporosis (SOP) is a prevalent manifestation of age-related bone disorders, resulting from the dysregulation between osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption, coupled with the escalating burden of cellular senescence. Traditional Chinese medicine (TCM) herbs, renowned for their remarkable attributes encompassing excellent tolerability, low toxicity, heightened efficacy, and minimal adverse reactions, have gained considerable traction in OP treatment. Emerging evidence substantiates the therapeutic benefits of various TCM formulations and their active constituents, including Zuogui wan, Fructus Ligustri Lucidi, and Resveratrol, in targeting cellular senescence to address SOP. However, a comprehensive review focusing on the therapeutic efficacy of TCM against SOP, with a particular emphasis on senescence, is currently lacking. In this review, we illuminate the pivotal involvement of cellular senescence in SOP and present a comprehensive exploration of TCM formulations and their active ingredients derived from TCM, delineating their potential in SOP treatment through their anti-senescence properties. Notably, we highlight their profound effects on distinct aging models that simulate SOP and various senescence characteristics. Finally, we provide a forward-looking discussion on utilizing TCM as a strategy for targeting cellular senescence and advancing SOP treatment. Our objective is to contribute to the unveiling of safer and more efficacious therapeutic agents for managing SOP.
TiO2-Based Photocatalytic Building Material for Air Purification in Sustainable and Low-Carbon Cities: A Review

TiO2-based building materials possess air purification, self-cleaning, and sterilization functionalities, making them innovative green building materials with significant potential for future energy-saving and emission-reduction applications. However, the transition from laboratory-scale to practical applications poses substantial challenges in improving the photocatalytic efficiency and stability of TiO2-based building materials. In recent years, researchers have made considerable efforts to enhance their efficiency and stability. This paper provides a concise overview of the photocatalytic principles employed in buildings for air purification, discusses preparation techniques for TiO2-based building materials, explores strategies to improve their efficiency, outlines key factors influencing their performance in practical applications, analyzes limitations, and discusses future development trends. Finally, we propose recommendations for further research on photocatalytic buildings and their real-world implementation as a valuable reference for developing highly efficient and stable photocatalytic building materials. The aim of this paper is to guide the application of TiO2-based photocatalysts in green buildings towards creating more efficient and stable low-carbon buildings that support sustainable urban growth.
REPURCHASE INTENTION PADA BITCOIN DI INDONESIA

Investasi pada Bitcoin di Indonesia meningkat setiap tahunnya, hal ini dikarekan para investor yang melihat peluang keuntungan yang baik dan mengerti pentingnya untuk melakukan investasi. Hal ini juga didasari, bahwa bitcoin sebagai wadah investasi yang dianggap mudah untuk digunakan menjadi pilihan para investor. Penelitian ini dilakukan guna mengetahui faktor apakah yang menjadi pendorong dalam melakukan repurchase intention terhadap bitcoin. Metodologi penelitian ini adalah dengan penyebaran kuesioner melalui form online terhadap 172 investor bitcoin yang melakukan pembelian bitcoin secara berkelajutan. Pada penelitian ini menemukan bahwa perceived of enjoyment, expectation dan perceived ease of use dalam penggunaan berpengaruh signifikan terhadap repurchase intention bitcoin, sedangkan satisfaction dalam penggunaan tidak memiliki pengaruh terhadap repurchase intention bitcoin.
Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model

Introduction Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody. Methods The efficacy of the vector was confirmed in vitro in three mesothelioma cell lines – H226, Mero-82, and MSTO-211H, and subsequently the antineoplastic properties in combination with anti-PD-1 was evaluated in xenograft H226 mesothelioma BALB/c and humanized NSG mouse models. Results and discussion Anticancer efficacy was attributed to reduced tumour volume and increased infiltration of tumour infiltrating lymphocytes, including activated cytotoxic T-cells (GrB+CD8+). Additionally, a correlation between tumour volume and activated CD8+ tumour infiltrating lymphocytes was observed. These findings were confirmed by transcriptomic analysis carried out on resected human tumour tissue, which also revealed upregulation of CD83 and CRTAM, as well as several chemokines (CXCL3, CXCL9, CXCL11) in the tumour microenvironment. Furthermore, according to observations, the combinatorial therapy had the strongest effect on reducing mesothelin and MUC16 levels. Gene set enrichment analysis suggested that the combinatorial therapy induced changes to the expression of genes belonging to the “adaptive immune response” gene ontology category. Combinatorial therapy with oncolytic adenovirus with checkpoint inhibitors may improve anticancer efficacy and survival by targeted cancer cell destruction and triggering of immunogenic cell death. Obtained results support further assessment of the AdV5/3-D24-ICOSL-CD40L in combination with checkpoint inhibitors as a novel therapeutic perspective for mesothelioma treatment.
Health-related quality of life and recovery capital among recovery residents taking medication for opioid use disorder in Texas

Background Recovery from opioid use disorder (OUD) includes improvements in health-related quality of life (HRQOL) and is supported by recovery capital (RC). Little is known about RC and HRQOL among recovery residents taking medication for OUD. We described HRQOL and RC and identified predictors of HRQOL. Methods Project HOMES is an ongoing longitudinal study implemented in 14 recovery homes in Texas. This is a cross-sectional analysis of data from 358 participants’ on HRQOL (five EQ-5D-5L dimensions—mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and RC (Assessment of Recovery Capital scores) collected from April 2021 to June 2023. Statistical analyses were conducted using T-, Chi-squared, and Fisher’s exact tests. Results Most participants were 35 years/older (50.7%), male (58.9%), non-Hispanic White (68.4%), heterosexual (82.8%), and reported HRQOL problems, mainly anxiety/depression (78.4%) and pain/discomfort (55.7%). Participants who were 35 years/older [mean (SD) = 42.6 (7.3)] were more likely to report mobility and pain/discomfort problems than younger participants. Female participants were more likely to report pain/discomfort problems than male participants. Sexual minorities were more likely to report anxiety/depression problems than heterosexual participants. Married participants and those in committed relationships were more likely to report problems conducting self-care than single/never-married participants. Comorbid conditions were associated with mobility, pain/discomfort, and usual activities problems. Most participants reported high social (65.4%), personal (69.0%), and total (65.6%) RC. Low personal RC was associated with mobility (aOR = 0.43, CI = 0.24–0.76), self-care (aOR = 0.13, CI = 0.04–0.41), usual activities (aOR = 0.25, CI = 0.11–0.57), pain/discomfort (aOR = 0.37, CI = 0.20–0.68), and anxiety/depression (aOR = 0.33, CI = 0.15–0.73) problems. Low total RC was associated with problems conducting self-care (aOR = 0.20, CI = 0.07–0.60), usual activities (aOR = 0.43, CI = 0.22–0.83), pain/discomfort problems (aOR = 0.55, CI = 0.34–0.90), and anxiety/depression (aOR = 0.20, CI = 0.10–0.41) problems. Social RC was not associated with HRQOL. Conclusion Personal and total RC and comorbid conditions predict HRQOL. Although the opioid crisis and the increasing prevalence of comorbidities have been described as epidemics, they are currently being addressed as separate public health issues. Our findings underscore the importance of ensuring residents are provided with interprofessional care to reduce the burden of comorbidities, which can negatively impact their OUD recovery. Their RC should be routinely assessed and enhanced to support their recovery and improve HRQOL.
Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer

Background TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). Methods In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat. Results At 12 years median follow-up, overall and disease-free survivals between randomized arms were comparable, while survival time free from alteration significantly improved with H-IGRT which showed a gain of restricted mean survival time of 1.46 years over CRT, P=0.041. Discussion The finding establishes TomoBreast as a proof-of-concept that hypofractionated image-guided radiation-therapy can improve the sparing of lung-heart function in breast cancer adjuvant therapy without loss in disease-free survival. Hypofractionation is advantageous, conditional on using an advanced radiation technique. Multicenter validation may be warranted. Trial registration https://clinicaltrials.gov/ct2/show/NCT00459628. Registered 12 April 2007.
Vegetable and Fruit Intake Variety and Cardiovascular Health and Mortality: A Systematic Review and Meta-Analysis of Observational Studies

Introduction: A multitude of evidence supports the consumption of a higher quantity of vegetables and fruits for their cardiovascular benefits. Nonetheless, the extent to which variety is associated with cardiovascular health remains unclear. Objective: To conduct a systematic review and meta-analysis of observational studies (prospective cohort and cross-sectional studies) assessing the role of a variety of vegetable and fruit consumption in cardiovascular morbidity and mortality in adults. Data Sources: MEDLINE-PubMed, Cochrane databases, and reference lists were searched through March 2023. Data Extraction: Two independent reviewers extracted data and assessed the risk of bias (National Heart, Lung, and Blood Institute Tool and Newcastle–Ottawa Scale). Data Analysis: Data were pooled (fixed and random [DerSimonian and Laird] effects for <5 and ≥5 study comparisons, respectively), and heterogeneity was assessed using the Cochran Q statistic and quantified (I2 statistic). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the overall certainty of the evidence. Five cross-sectional (n = 45,761) and seven prospective studies (n = 253,422) met the eligibility criteria. Greater variety of vegetable and fruit consumption was prospectively related to decreased all-cause mortality (risk ratio, 0.89 [95% CI, 0.82–0.97], seven study comparisons, n = 196,925), while no significant associations were observed with assessed cardiovascular-related mortality or morbidity. For all outcomes, the certainty of the evidence was graded as “low” or “very low” owing to inconsistency and/or imprecision. Conclusions: Overall, this study shows that greater variety in vegetable and fruit consumption may reduce all-cause mortality and highlights the need for additional studies with a higher degree of evidence to better understand its role in cardiovascular health.
Antifungal Effect of Bacillus velezensis ZN-S10 against Plant Pathogen Colletotrichum changpingense and Its Inhibition Mechanism

In order to optimize crop production and mitigate the adverse impacts associated with the utilization of chemical agents, it is necessary to explore new biocontrol agents. Bacillus velezensis has been widely studied as a biocontrol agent because of its efficient and ecofriendly plant disease control mechanisms. This study shows that the strain ZN-S10 effectively reduces the area of leaf spots caused by the pathogen Colletotrichum changpingense ZAFU0163-1, which affects conidia production and germination, inhibits mycelium growth, and induces mycelium deformation. In antifungal experiments with crude extracts, we observed a delay in the cell cycle of conidia, which may be responsible for the inhibition of conidial germination. Among the bioactive metabolites detected through integrated LC-MS- and GC-MS-based untargeted metabolomics, 7-O-Succinyl macrolactin A, telocinobufagin, and surfactin A may be the main antifungal metabolites of strain ZN-S10. The presence of 7-O-Succinyl macrolactin A could explain the cell damage in germ tubes. This is the first report of telocinobufagin detected in B. velezensis. These results are significant for understanding the inhibitory mechanisms employed by B. velezensis and should serve as a reference in the production of biocontrol agents.
Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review)

Genomic instability is an essential hallmark of cancer, and cellular DNA damage response (DDR) defects drive tumorigenesis by disrupting genomic stability. Several studies have identified abnormalities in DDR-associated genes, and a dysfunctional ubiquitin-proteasome system (UPS) is the most common molecular event in metastatic castration-resistant prostate cancer (PCa). For example, mutations in Speckle-type BTB/POZ protein-Ser119 result in DDR downstream target activation deficiency. Skp2 excessive upregulation inhibits homologous recombination repair and promotes cell growth and migration. Abnormally high expression of a deubiquitination enzyme, ubiquitin-specific protease 12, stabilizes E3 ligase MDM2, which further leads to p53 degradation, causing DDR interruption and genomic instability. In the present review, the basic pathways of DDR, UPS dysfunction, and its induced DDR alterations mediated by genomic instability, and especially the potential application of UPS and DDR alterations as biomarkers and therapeutic targets in PCa treatment, were described.
Efficacy and safety of definitive chemoradiotherapy with or without induction immune checkpoint inhibitors in patients with stage III non-small cell lung cancer

Background In the era of immunotherapy, the optimal combination of immune checkpoint inhibitors (ICIs) and chemoradiotherapy (CRT) for stage III non-small cell lung cancer (NSCLC) is not defined. The current study investigated the efficacy and safety of definitive CRT(dCRT) plus consolidation ICIs with or without induction ICIs in stage III NSCLC. Methods 123 consecutive patients treated with dCRT followed by consolidation ICIs at our institution from 2018 to 2022 were retrospectively reviewed. Failure patterns, survival outcomes, and toxicity profiles were analyzed. Results The 1- and 2- year PFS rates were 75.3% and 56.9%, respectively, and median PFS was 30.83 months from the start of treatment. In-field failure (18.7%) was the most common failure pattern. The most common adverse event (AE) was pneumonitis caused by ICIs or RT. The incidence of Grade 3-4 and Grade 5 pneumonitis was 5.7% and 1.6%, respectively. Further analysis showed that the induction plus consolidation ICIs group has significantly lower cumulative incidence of distant metastasis rates (HR: 0.30, 95%CI: 0.09-1.00, p=0.043) and higher incidence of pneumonitis (p=0.039) compared with patients in the consolidation ICIs group. Conclusions Combined CRT and consolidation ICIs achieved encouraging efficacy and manageable toxicity in patients with stage III NSCLC in China. Induction plus consolidation ICIs might reduce distant metastasis and deserve further investigation.
Effects of the Long-Term Administration of Uridine on the Functioning of Rat Liver Mitochondria in Hyperthyroidism

The effect of uridine (30 mg/kg for 7 days; intraperitoneally) on the functions of liver mitochondria in rats with experimentally induced hyperthyroidism (HT) (200 µg/100 g for 7 days, intraperitoneally) is studied in this paper. An excess of thyroid hormones (THs) led to an intensification of energy metabolism, the development of oxidative stress, a significant increase in the biogenesis, and changes in the content of proteins responsible for the fusion and fission of mitochondria. The injection of uridine did not change the concentration of THs in the blood of hyperthyroid rats (HRs) but normalized their body weight. The exposure to uridine improved the parameters of oxidative phosphorylation and corrected the activity of some complexes of the electron transport chain (ETC) in the liver mitochondria of HRs. The analysis of ETC complexes showed that the level of CI–CV did not change by the action of uridine in rats with the condition of HT. The application of uridine caused a significant increase in the activity of superoxide dismutase and lowered the rate of hydrogen peroxide production. It was found that uridine affected mitochondrial biogenesis by increasing the expression of the genes Ppargc1a and NRF1 and diminishing the expression of the Parkin gene responsible for mitophagy compared with the control animals. In addition, the mRNA level of the OPA1 gene was restored, which may indicate an improvement in the ETC activity and oxidative phosphorylation in the mitochondria of HR. As a whole, the results obtained demonstrate that uridine has a protective effect against HT-mediated functional disorders in the metabolism of rat liver mitochondria.
Adaptations of the Pleistocene island canid Cynot he rium sardous (Sardinia, Italy) for hunting small prey

Summary Cynot he rium sardous is a small canid that lived on the island of Sardinia-Corsica during the Pleistocene. Once on the island, the species gradually adapted, and became specialized in hunting small prey like the lagomorph Prolagus. Moreover, in order to fulfil mass-related ener getic requi rements, the species had to reduce body size compared to its ancestor Xenocyon, which was larger than the grey wolf. Cynotherium carried its head much in the way foxes do, and was able to hold its body low to the ground when stalking. In addition, it could move its head laterally better than any living canid. Samen vat ting Cynot he rium sardous is een kleine hond achtige, die leefde op het eiland Sardinie-Corsica gedu rende het Pleis toceen. Eenmaal op het eiland paste de soort zich aan en specialiseerde zich in het jagen op kleine prooi zoals de haasachtige Prolagus. Om aan de energiebehoeften, gere lateerd aan lichaamsgewicht, te voldoen, moest de soort kleiner worden, vergeleken met zijn voor ouder, Xeno cyon, die groter was dan de huidige grijze wolf. Cynot he rium hield zijn hoofd ongeveer zoals vossen doen, en hield het lichaam laag bij de grond bij het besluipen van de prooi. Daarbij kon hij zijn kop verder zijwaarts bewegen dan alle nu levende hond achtigen.
WDSRL: Multi-Domain Neural Machine Translation With Word-Level Domain-Sensitive Representation Learning

Due to the strong reliance on domain-specific knowledge, the joint learning manner of domain discrimination and translation has been widely considered in the Multi-Domain Neural Machine Translation (MDNMT) task. However, the word ambiguity problem still inevitably exists in MDNMT, especially when mixed multi-domain data is brought into the model training phase. Although word-level MDNMT can mitigate this problem to some extent, poor domain discrimination yet remains and severely hinders performance. Based on the above limitation, we observed that coarser granularity strings may provide more specific semantics, which is more conducive to domain discrimination. Thus, we propose a Word-level Domain-Sensitive Representation Learning (WDSRL) method. Specifically, we focus on two aspects of our approach: domain representation and domain discrimination. To extend the scope of domain representation, we adopt Convolution Neural Networks (CNN) to encode Local Domain Representation at different granularities, and then integrate Topic Knowledge Representation into each word. By doing so, context features related to the domain could be comprehensively enriched. Regarding domain discrimination, we design a Domain-Sensitive Discriminator, which could not only generate domain features for each word but also enhance domain representation learning. Experimental results demonstrate our substantial improvements over several representative baselines on multiple language pairs. Furthermore, the extensive analysis also indicates the superiority of our proposed domain-sensitive feature encoding strategy and domain-sensitive discriminator for word-level representation learning.
Harnessing mechanobiology for kidney organoid research

Recently, organoids have emerged as revolutionizing tools with the unprecedented potential to recreate organ-specific microanatomy in vitro. Upon their derivation from human pluripotent stem cells (hPSCs), organoids reveal the blueprints of human organogenesis, further allowing the faithful recapitulation of their physiology. Nevertheless, along with the evolution of this field, advanced research exposed the organoids’ shortcomings, particularly regarding poor reproducibility rates and overall immatureness. To resolve these challenges, many studies have started to underscore the relevance of mechanical cues as a relevant source to induce and externally control hPSCs differentiation. Indeed, established organoid generation protocols from hPSCs have mainly relyed on the biochemical induction of fundamental signalling pathways present during kidney formation in mammals, whereas mechanical cues have largely been unexplored. This review aims to discuss the pertinence of (bio) physical cues within hPSCs-derived organoid cultures, while deciphering their effect on morphogenesis. Moreover, we will explore state-of-the-art mechanobiology techniques as revolutionizing means for understanding the underlying role of mechanical forces in biological processes in organoid model systems.