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The discovery of the Schøyen–Virginia manuscript of the Uttaragrantha provides significant insights into the Mūlasarvāstivāda Vinaya. This newly identified Sanskrit manuscript offers a fresh perspective on monastic law codes, contributing original Sanskrit terms previously known only through Tibetan and Chinese translations, thereby enhancing our knowledge of Sanskrit–Tibetan–Chinese Vinaya terminologies. Also, by adding itself as a new textual witness to the Mūlasarvāstivāda Vinaya, it demonstrates the complex textual history and underscores the potential multiplicity in the Mūlasarvāstivāda Vinaya traditions or even the “Greater Sarvāstivāda” Vinaya traditions. Variations in chapter sequencing across extant versions of the Uttaragrantha suggest the possibility of the chapters originally existing as independent texts rather than as a collective, the Uttaragrantha. This article presents the latest findings on the Sanskrit manuscript fragments of the Uttaragrantha in the Schøyen Collection and the private collection, Virginia. Furthermore, it attempts to show the role of the S-V manuscript of the Uttaragrantha in improving our textual understanding of the Uttaragrantha and examining the potential multiplicity in the Mūlasarvāstivāda Vinaya traditions.

Santa Barbara Amorphous-15 (SBA) is a stable and mesoporous silica material. Quaternized SBA-15 with alkyl chains (Q SBA ) exhibits electrostatic attraction for anionic molecules via the N + moiety of the ammonium group, whereas its alkyl chain length determines its hydrophobic interactions. In this study, Q SBA with different alkyl chain lengths were synthesized using the trimethyl, dimethyloctyl, and dimethyoctadecyl groups (C1Q SBA , C8Q SBA , and C18Q SBA , respectively). Carbamazepine (CBZ) is a widely prescribed pharmaceutical compound, but is difficult to remove using conventional water treatments. The CBZ adsorption characteristics of Q SBA were examined to determine its adsorption mechanism by changing the alkyl chain length and solution conditions (pH and ionic strength). A longer alkyl chain resulted in slower adsorption (up to 120 min), while the amount of CBZ adsorbed was higher for longer alkyl chains per unit mass of Q SBA at equilibrium. The maximum adsorption capacities of C1Q SBA , C8Q SBA , and C18Q SBA , were 3.14, 6.56, and 24.5 mg/g, respectively, as obtained using the Langmuir model. For the tested initial CBZ concentrations (2–100 mg/L), the adsorption capacity increased with increasing alkyl chain length. Because CBZ does not dissociate readily (pK a  = 13.9), stable hydrophobic adsorption was observed despite the changes in pH (0.41–0.92, 1.70–2.24, and 7.56–9.10 mg/g for C1Q SBA , C8Q SBA , and C18Q SBA , respectively); the exception was pH 2. Increasing the ionic strength from 0.1 to 100 mM enhanced the adsorption capacity of C18Q SBA from 9.27 ± 0.42 to 14.94 ± 0.17 mg/g because the hydrophobic interactions were increased while the electrostatic attraction of the N + was reduced. Thus, the ionic strength was a stronger control factor determining hydrophobic adsorption of CBZ than the solution pH. Based on the changes in hydrophobicity, which depends on the alkyl chain length, it was possible to enhance CBZ adsorption and investigate the adsorption mechanism in detail. Thus, this study aids the development of adsorbents suitable for pharmaceuticals with controlling molecular structure of QSBA and solution conditions.

Classification of headache disorders is dependent on a subjective self-report from patients and its interpretation by physicians. We aimed to apply objective data-driven machine learning approaches to analyze patient-reported symptoms and test the feasibility of the automated classification of headache disorders. The self-report data of 2162 patients were analyzed. Headache disorders were merged into five major entities. The patients were divided into training (n = 1286) and test (n = 876) cohorts. We trained a stacked classifier model with four layers of XGBoost classifiers. The first layer classified between migraine and others, the second layer classified between tension-type headache (TTH) and others, and the third layer classified between trigeminal autonomic cephalalgia (TAC) and others, and the fourth layer classified between epicranial and thunderclap headaches. Each layer selected different features from the self-reports by using least absolute shrinkage and selection operator. In the test cohort, our stacked classifier obtained accuracy of 81%, sensitivity of 88%, 69%, 65%, 53%, and 51%, and specificity of 95%, 55%, 46%, 48%, and 51% for migraine, TTH, TAC, epicranial headache, and thunderclap headaches, respectively. We showed that a machine-learning based approach is applicable in analyzing patient-reported questionnaires. Our result could serve as a baseline for future studies in headache research.

Wind-wave hybrid power generation systems have the potential to become a significant source of affordable renewable energy. However, their strong interactions with both wind- and wave-induced forces raise a number of technical challenges for modelling. The present study undertakes a numerical investigation on multi-body hydrodynamic interaction between a wind-wave hybrid floating platform and multiple wave energy converters (WECs) in a frequency domain. In addition to the exact responses of the platform and the WECs, the power take-off (PTO) mechanism was taken into account for analysis. The coupled hydrodynamic coefficients and wave exciting forces were obtained from WAMIT, the 3D diffraction/radiation solver based on the boundary element method. The overall performance of the multiple WECs is presented and compared with the performance of a single isolated WEC. The analysis showed significant differences in the dynamic responses of the WECs when the multi-body interaction was considered. In addition, the PTO damping effect made a considerable difference to the responses of the WECs. However, the platform response was only minimally affected by PTO damping. With regard to energy capture, the interaction effect of the designed multiple WEC array layout is evaluated. The WEC array configuration showed both constructive and destructive effects in accordance with the incident wave frequency and direction.

Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water‐soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM‐induced metabolic regulation and the therapeutic efficacy of NAM in triple‐negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid β‐oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next‐generation anti‐metabolic agent for TNBC treatment. Nicotinamide is a niacin (vitamin B3) supplement. Using multiomics systems biology, we showed that nicotinamide increased the activities of reverse electron transport (RET) and lipid metabolic pathways in triple‐negative breast cancer (TNBC), collectively leading to an increase in reactive oxygen species (ROS) levels. The increased ROS level suppressed tumor growth and metastasis in human organoids and xenograft mouse models.

Background Resistance to chemotherapy remains a major clinical challenge in triple-negative breast cancer (TNBC), an intrinsic subtype with limited available therapeutic options. The expression of moesin (MSN) is upregulated in TNBC patients, but little is known about the role of MSN in breast carcinogenesis. Methods We investigated the MSN-dependent autocrine loop between extracellular interleukin 6 (IL-6) and NF-κB, along with a signaling cascade involving GTPase-mediated STAT3 phosphorylation. Various in vitro and in vivo assays were used to evaluate tumor initiation, growth, and stemness properties in TNBC models. Results High MSN expression was correlated with shorter overall and disease-free survival in TNBC patients. In vivo, MSN promotes tumor initiation and growth. Mechanistically, MSN-mediated IL-6/NF-κB autoregulatory feedback enhances IL-6 transcription. IL-6 binding to LPAR1 activated MSN phosphorylation, which then sequentially phosphorylated the CDC42-PAK4 complex, triggering nuclear translocation of the pSTAT3-MSN complex. This led to pSTAT3-mediated activation of cancer stemness genes (IGFN1, EML1, and SRGN), contributing to Adriamycin resistance. Notably, combination treatment with the FDA-approved STAT3 inhibitor Atovaquone and Adriamycin restored drug sensitivity. Conclusions Our findings uncover the critical role of MSN in regulating STAT3-mediated cancer stemness via the IL-6/NF-κB signaling axis. These results provide a strong rationale for repositioning STAT3 inhibitors such as Atovaquone as a therapeutic strategy in Adriamycin-resistant TNBC patients exhibiting pSTAT3-MSN complex upregulation.

Staphylococcus aureus (S. aureus) is a major Gram-positive pathogen, and treatment of S. aureus infections is often challenging due to widespread antibiotic resistance. In Gram-positive bacteria such as S. aureus, D-alanylation of teichoic acids (TA) reduces the net negative charge of the cell envelope and contributes to resistance to diverse antibiotics, particularly cationic antimicrobial peptides. D-alanylation is mediated by the dltABCD operon, which encodes four proteins (DltA, DltB, DltC, and DltD), all of which is essential for the multistep transfer of D-alanine to teichoic acids. Here, we present the first crystal structure of the S. aureus D-alanyl carrier protein DltC and analyze its interaction with DltA using AlphaFold3 and all-atom molecular dynamics simulations. We further show that single substitutions of SaDltA-SaDltC interface residues abolish SaDltC mediated enhancement of SaDltA catalysis. Together, these findings define a catalytically critical S. aureus DltA-DltC interface and provide a structural insight for targeting the D-alanylation pathway as a potential anti-Staphylococcus strategy.

The human auditory cortex around Heschl’s gyrus (HG) exhibits diverging patterns across individuals owing to the heterogeneity of its substructures. In this study, we investigated the subregions of the human auditory cortex using data-driven machine-learning techniques at the individual level and assessed their structural and functional profiles. We studied an openly accessible large dataset of the Human Connectome Project and identified the subregions of the HG in humans using data-driven clustering techniques with individually calculated imaging features of cortical folding and structural connectivity information obtained via diffusion magnetic resonance imaging tractography. We characterized the structural and functional profiles of each HG subregion according to the cortical morphology, microstructure, and functional connectivity at rest. We found three subregions. The first subregion (HG 1 ) occupied the central portion of HG, the second subregion (HG 2 ) occupied the medial-posterior-superior part of HG, and the third subregion (HG 3 ) occupied the lateral-anterior-inferior part of HG. The HG 3 exhibited strong structural and functional connectivity to the association and paralimbic areas, and the HG 1 exhibited a higher myelin density and larger cortical thickness than other subregions. A functional gradient analysis revealed a gradual axis expanding from the HG 2 to the HG 3 . Our findings clarify the individually varying structural and functional organization of human HG subregions and provide insights into the substructures of the human auditory cortex.

Eating disorder is highly associated with obesity and it is related to brain dysfunction as well. Still, the functional substrates of the brain associated with behavioral traits of eating disorder are underexplored. Existing neuroimaging studies have explored the association between eating disorder and brain function without using all the information provided by the eating disorder related questionnaire but by adopting summary factors. Here, we aimed to investigate the multivariate association between brain function and eating disorder at fine-grained question-level information. Our study is a retrospective secondary analysis that re-analyzed resting-state functional magnetic resonance imaging of 284 participants from the enhanced Nathan Kline Institute-Rockland Sample database. Leveraging sparse canonical correlation analysis, we associated the functional connectivity of all brain regions and all questions in the eating disorder questionnaires. We found that executive- and inhibitory control-related frontoparietal networks showed positive associations with questions of restraint eating, while brain regions involved in the reward system showed negative associations. Notably, inhibitory control-related brain regions showed a positive association with the degree of obesity. Findings were well replicated in the independent validation dataset (n = 34). The results of this study might contribute to a better understanding of brain function with respect to eating disorder.

Zhi Qian (支謙, fl. ca. 220–257 CE), a prolific Yuezhi-Chinese translator of Indian Buddhist scriptures into Chinese, is widely known for his broad range of styles and terminology. For several decades, his translation activities and his legacy in the history of Chinese Buddhist literature have been a rich field of research, particularly within the context of the transmission of Buddhism from India to China. In the present article, as a follow-up study to “Buddhism for Chinese readers: Zhi Qian’s Literary Refinements in the Foshuo pusa benye jing,” recently published by the authors in this journal, we offer additional reflections on distinctive features of Zhi Qian’s language. We focus on four unusual and interesting renderings in the Foshuo pusa benye jing (佛說菩薩本業經, T. 281), namely (1) santu 三塗; (2) shezui 捨罪; (3) kong 空, wu xiang 無想 and bu yuan 不願; and (4) sishi buhu 四時不護. Through an analysis of these words and phrases, we discuss Zhi Qian’s translation techniques and lexical idiosyncrasies, highlighting their significance in our understanding of the dynamics of language contact and change in the early period of the Chinese Buddhist tradition. Thus, the paper investigates some key Buddhist terms as coined by the early translators on the basis of the classical Chinese and illustrates the semantic changes of the Chinese language taking place in the period as well as influence of Buddhist regimes of knowledge.