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Epigenetic-targeted therapy has been applied in the treatment of several types of cancer. Herein, based on the synergistic antitumor effects of co-targeting HDACs and EZH2 in some hematological malignancies, a novel series of tazemetostat-based HDACs/EZH2 dual inhibitors were rationally designed, synthesized, and biologically evaluated. Satisfyingly, compounds 22a and 22b were identified as potent HDACs/EZH2 dual inhibitors with robust antiproliferative activities against one diffuse large-cell B cell lymphomas (DLBCL) cell line harboring EZH2 mutation and multiple acute myeloid leukemia (AML) cell lines. Notably, after a short-term treatment in the EZH2 mutant DLBCL cell line (SU-DHL-6), 22a and 22b displayed much stronger antiproliferative activities than the approved EZH2 inhibitor tazemetostat, while after a long-term treatment in SU-DHL-6 cells, 22a and 22b displayed comparable or even superior antiproliferative activities to the approved HDACs inhibitor SAHA. In AML cells, compounds 22a and 22b displayed much more potent antiproliferative activities than tazemetostat, as well as distinctive differentiation-inducing abilities and superior apoptosis-inducing abilities relative to tazemetostat and SAHA. Moreover, the synergistic anti-AML effects of HDACs/EZH2 dual inhibitors combined with various anti-AML drugs were demonstrated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to discuss the clinical value of health education using an animated video for postoperative patients with digital subtraction angiography (DSA)-guided implantable venous access ports. Retrospective study. Based on expert consensus and clinical experience, we created an animated video presenting postoperative health education for patients to watch after infusion port implantation and uploaded it to a multimedia room. A total of 93 patients who underwent DSA-guided implantable venous access port placement at our hospital from March to June 2022 and from July to October 2022 were selected. Forty-six patients who received traditional oral and written education from March to June 2022 were selected as the control group. Forty-seven patients who received animated video-assisted health education from July to October 2022 were selected as the experimental group. The time spent on health education and patients' awareness of the educational content were compared between the 2 groups. The time spent on health education in the experimental group was 3.51 ± 0.62 minutes, which was less than that of the control group, 6.76 ± 1.14 minutes (t = 17.07, P < .001). Patients' awareness of educational content in the experimental group was 8.62 ± 1.26 points, which was significantly better than the control group's 7.26 ± 1.63 points (t = -4.490, P < .001). Animated video-assisted health education can enable patients to gain a better understanding of educational content in a shorter time. Moreover, it can improve nurses' interventional efficiency. Therefore, this health education method is worthy of clinical promotion., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aqueous zinc-ion batteries (AZIBs) are competitive alternatives for large-scale energy-storage devices owing to the abundance of zinc and low cost, high theoretical specific capacity, and high safety of these batteries. High-performance and stable cathode materials in AZIBs are the key to storing Zn 2+ . Manganese-based cathode materials have attracted considerable attention because of their abundance, low toxicity, low cost, and abundant valence states (Mn 2+ , Mn 3+ , Mn 4+ , and Mn 7+ ). However, as a typical cathode material, birnessite-MnO 2 (δ-MnO 2 ) has low conductivity and structural instability. The crystal structure may undergo severe distortion, disorder, and structural damage, leading to severe cyclic instability. In addition, its energy-storage mechanism is still unclear, and most of the reported manganese oxide-based materials do not have excellent electrochemical performance. Herein, we propose a copper-doped Cu 0.05 K 0.11 Mn 0.84 O 2 ·0.54H 2 O (Cu 2 -KMO) cathode, which exhibits a large interlayer spacing, a stable structure, and accelerated reaction kinetics. This cathode was prepared using a simple hydrothermal method. The AZIB assembled using Cu 2 -KMO showed high specific capacity (600 mA h g -1 at 0.1 A g -1 after 75 cycles). The dissolution-deposition energy storage mechanism of Cu-KMO in AZIBs with double electron transfer was revealed using ex situ tests. The good electrochemical performance of the Cu 2 -KMO cathode fabricated by the doping strategy in this study provides ideas for the subsequent preparation of manganese dioxide using other strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gastric cancer remains a significant global health concern with poor prognosis. This study investigates the role of neutrophils in gastric cancer progression and their potential as prognostic indicators. Using multi-omics approaches, including Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and single-cell analysis, we identified neutrophil-associated gene signatures and developed a robust prognostic model. Our findings reveal distinct gastric cancer subtypes based on neutrophil-associated genes, with one subtype showing increased neutrophil infiltration and poorer prognosis. Single-cell analysis uncovered neutrophil-associated alterations in cell composition, gene expression profiles, and intercellular communication within the tumor microenvironment. Additionally, we explored the relationship between neutrophil-associated genes, microbiota composition, and alternative splicing events in gastric cancer. Furthermore, we identified QKI as a key regulator of alternative splicing and demonstrated its role in promoting malignant phenotypes and enhancing TGF-beta signaling and epithelial-mesenchymal transition in gastric cancer cells by wet experiment. Lastly, the role of QKI in the association with drug resistance and the identification of specific agents for treating QKI-associated drug resistance were also explored. This comprehensive study provides novel insights into the complex interplay between neutrophils, the tumor microenvironment, microbiota, alternative splicing and gastric cancer progression, offering potential new targets for therapeutic intervention., Competing Interests: Declarations Conflict of Interests The authors declare that they have no competing interests. Ethics approval Not applicable. Consent to participate Not applicable. Consent to publish Not applicable., (© 2024. The Author(s).)

Background: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is a sham-controlled trial investigating the safety and efficacy of RDN in China., Methods: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; Shanghai Angiocare Medical Technology, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months., Results: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P <0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P <0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P =0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P =0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up., Conclusions: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02901704., Competing Interests: X. Jiang is supported by Iberis-HTN trial fund from Shanghai Angiocare Medical Technology, CAMS Innovation Fund for Medical Sciences (grant Nos. 2021-I2M-C&T-B-026 and 2021-I2M-C&T-B-027). He has received speaker honoraria fees from Medtronic and Terumo. Felix Mahfoud is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219, Project ID 322900939), and Deutsche Herzstiftung. He has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical, and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. L. Lauder received speaker honoraria/consulting fees from AstraZeneca, Medtronic, Pfizer, and ReCor. Brad Hubbard is an employee of EastPoint Innovation Center. X. Hu is an employee of Shanghai Angiocare Medical Technology. R. Gao received institutional research grants from Shanghai Angiocare Medical Technology (Shanghai, China) and Biotyx Medical (Shenzhen, China). The remaining authors report no conflicts of interest related to this article.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway plays a crucial role in initiating anti-tumor immunity. Despite the development of various STING agonists, their effectiveness is often limited by suboptimal activation efficiency and poor sustainability. To address this, a Mn/MoO 3- x nanoagonist featuring Mn single-atom sites is presented, designed for cascade cGAS/STING activation in tumor-specific catalytic metalloimmunotherapy. The single-atom nanoagonist (SANA) is meticulously crafted by doping Mn atoms into defective molybdenum oxide (MoO 3- x ), enabling robust peroxidase-mimicking catalysis and inducing severe double-stranded DNA (dsDNA) damage in tumors. Of note, Mn 2+ and MoO 4 2- can be responsively released from Mn/MoO 3- x SANA and enhance the sensitivity of cGAS to dsDNA. Importantly, MoO 4 2- with a relatively slow-release profile and facile cellular accumulation compensates for Mn 2+ that has poor cellular accumulation due to continuous efflux, thus continuatively triggering the secretion of type I interferon for beyond 72 h. Remarkably, Mn/MoO 3- x SANA significantly inhibits tumor growth and metastasis without supplementary STING agonists or external stimulation. This study offers a promising cascade cGAS/STING activation approach to enhance the efficacy and sustainability of catalytic metalloimmunotherapy., (© 2024 Wiley‐VCH GmbH.)

We have synthesized two sialic acid derivatives substituted with an ortho -nitrobenzyl alcohol (o-NBA) group that can undergo light-mediated conjugation with primary amines at their 5- or 9-carbon position. The o-NBA derivatives were shown to react with multiple lysine residues of human serum albumin (HSA) when exposed to 365 nm light irradiation within 10 min. The resulting sugar conjugates were characterized by mass spectroscopy and used for fluorescence-based cell imaging.

Midkine (MDK) is a neurotrophic growth factor highly expressed during embryogenesis, currently recognized as a multifaceted factor in cancer progression and drug resistance. MDK has demonstrated greater accuracy than existing biomarkers. Serum MDK is a valuable indicator for the non-invasive early detection of tumors. It dynamically changes following surgical tumor excision and prior to recurrence, facilitating prognosis and treatment response evaluation. However, existing methods struggle to achieve the sensitivity required for clinical applications. Herein, we developed a triple-mode biosensor with oriented self-construction and built-in error-checking for rapid, sensitive, and convenient MDK detection. The sensor construction adhered to the principle of achieving oriented and strong covalent connections to ensure high sensitivity. Biosynthesized quantum dots (BQDs) were introduced to orient antibodies, enhancing the exploration of active binding sites and significantly increasing antibody-capturing ability. To further enhance sensitivity and signal amplification, Au@Pt nanorods-Ab 2 (MF-Probe) were used as multifunctional probes, incorporating an error-checking mechanism to minimize false results. Detection was feasible using an electrochemical workstation, a microplate reader, and even a mobile phone. The sensor exhibited a wide linear range from 5 fg/mL to 100 ng/mL and a low limit of detection (LOD) of 1.620 fg/mL. It accurately distinguished MDK levels in the serum of healthy donors and cancer patients. Compared to existing ELISA kits, it exhibited a lower LOD and a more sensitive response to trace MDK, suggesting it is a promising tool for cancer diagnosis and prognostic evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Depression and anxiety are common psychological issues among international medical students in universities, which have serious negative impacts on their learning and life. The present study aimed to evaluate the efficacy of positive emotional writing in alleviating symptoms of anxiety and depression, as well as enhancing subjective well-being among this population., Method: This study was conducted at an international college of a comprehensive university in central China. A total of ninety-two participants who met the inclusion criteria were recruited to participate in a single-blind randomized controlled trial, in which participants were not aware that there was an experimental group and a control group. Participants in control received daily psychological care weekly for 8 weeks (n = 46). Correspondingly, participants in experimental group received the positive emotional writing intervention on the basis of daily psychological care. Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS) and General Well-being Scale (GWB) were used to evaluate the effect of the intervention. Data from 89 students who completed the entire study (experimental group, n = 44; control group, n = 45) were analyzed., Results: After the intervention, the scores of SDS and SAS in the experimental group significantly decreased, while the subjective well-being score significantly increased. Although the SAS score of the control group after intervention was significantly lower than before, the decrease in SDS and SAS scores, as well as the increase in GWB score, were significantly greater in the experimental group than in the control group., Conclusion: The findings suggest that positive emotional writing can effectively reduce the depression and anxiety of international medical students, and significantly enhance their subjective well-being, providing ideas for management to solve the psychological problems of international medical students., Trial Registration Number: ChiCTR2400087815. Registered at Chinese Clinical Trial Registry., (© 2024. The Author(s).)

Competing Interests: Declarations. Conflicts of interest: None.

Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO 4 nanocatalyst, dubbed 'artificial metabzyme'. It showcases dual active centres, namely, Fe 2+ and tetrahedral Mo 4+ , that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO 4 metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Regulated cell death (RCD) is a genetically controlled form of cell death that plays an important role in organogenesis, tissue remodeling, and pathogenesis of cancers. Transforming growth factor-beta-activation kinase 1 (TAK1) is a member of the serine/threonine protein kinase family, which can respond to internal and external stimuli and participate in inflammatory responses through multiple signaling pathways and cellular processes. In the last two decades, the regulatory roles of TAK1 at the crossroads of multiple RCD pathways, including apoptosis, necroptosis, pyroptosis, and PANoptosis were revealed by 801 articles retrieved from the Web of Science Core Collection database. To analyze global research trends and hotspots concerning the role of TAK1 in RCD, the bibliometric and visualized analysis were applied in the current study., Methods: The data for this bibliometrics study were retrieved from the Web of Science Core Collection database. The search formula was (TS=(Apoptosis) OR TS=(pyroptosis) OR TS=(Necroptosis) OR TS=(PANoptosis) OR TS=(Autophagy) OR TS=(Ferroptosis) OR TS=(cuproptosis)) AND ((TS=(TAK1)) OR TS=(MAP3K7)). The co-occurrence and co-cited analysis on basic bibliometric parameters were conducted by VOSviewer. The dual-map overlay of journals, citation bursts, keyword timelines, and keyword bursts were analyzed by CiteSpace., Results: A total of 801 articles from 46 countries have been included in the analysis. The number of publications demonstrates a consistent increase from 1999 to 2024. The primary research institutions driving this field are Osaka University Notably, the Journal of Biological Chemistry stands out as the most popular journal in this domain. These publications collectively involve contributions from 4663 authors, with Jun Tsuji emerging as a prolific author. Jun Tsuji also gains the highest co-citation frequency. Emerging research hotspots are encapsulated by keywords, including apoptosis, NF-κB, inflammation, autophagy, and TNFα., Conclusion: This is the first bibliometric and visualized study to analyze the global trends and hotspots of TAK1 in RCD. Based on the analysis of 801 articles, the results provide a retrospective and comprehensive visualized view of the research hotspots and frontiers of TAK1 at the crossroads of multiple RCD signaling pathways and propose ideas for guiding their future investigations in molecular mechanisms and therapeutic strategies in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GY declared a shared affiliation, with no collaboration, with one of the authors, RL, to the handling editor at the time of the review., (Copyright © 2024 Huang, He, Wan, Ban, Chen, Hu, Wan, Lu, Zhang and Xiong.)

Exploring the spatial-temporal changes, driving forces, and future development tendency of the carbon sequestration service function of the Three-River-Source National Park ecosystem has great significance for regional ecological protection and sustainable development. Historical land-use data of Three-River-Source National Park from 1990 to 2020 were selected at five-year intervals, and based on the PLUS-InVEST-Geodector model, the spatial-temporal changes of historical carbon storage were analyzed, and the driving forces of spatial-temporal variation were explored combined with multiple factors. The carbon storage of Three-River-Source National Park in 2030 was predicted under the scenarios of natural development and ecological protection. The results showed that： ① The carbon storage of Three-River-Source National Park showed a fluctuating characteristic of increase-decrease-increase-decrease from 1990 to 2020, the carbon storage was increased by 41.85×10 6 t overall, and the grassland took the largest contribution. ② The spatial distribution characteristics of carbon storage in Three-River-Source National Park had little change between 1990 to 2020, and the evolution of the spatial distribution was relatively stable. The contribution ratio of the Yangtze River source park, Lancang River source park, and Yellow River source park was 7∶1∶2, which was roughly equivalent to the park area. ③ The major driving factors of the spatial-temporal variation of carbon storage in Three-River-Source National Park from 1990 to 2020 were： FVC, soil type, and annual precipitation. The interactive detection of each driving factor showed dual-factor enhancement and nonlinear enhancement. ④ The carbon storage of Three-River-Source National Park was predicted to decrease by 4.87% and 3.98% from 2020 to 2030 under the scenarios of natural development and ecological protection, respectively, and the carbon storage reduction under the ecological protection scenario had a significant inhibitory effect. The findings can provide data support for national spatial planning of Three-River-Source National Park and the enhancement of terrestrial ecosystem carbon storage.

Competing Interests: The authors have no conflicts of interest to declare.

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Resveratrol, a naturally occurring polyphenolic compound, has captivated the scientific community with its promising therapeutic potential across a spectrum of diseases. This review explores the complex role of resveratrol in modulating ferroptosis, a newly identified form of programmed cell death, and its potential implications for managing cardiovascular and cerebrovascular disorders, cancer, and other conditions. Ferroptosis is intricately linked to the pathogenesis of diverse diseases, with resveratrol exerting multifaceted effects on this process. It mitigates ferroptosis by modulating lipid peroxidation, iron accumulation, and engaging with specific cellular receptors, thereby manifesting profound therapeutic benefits in cardiovascular and cerebrovascular conditions, as well as oncological settings. Moreover, resveratrol's capacity to either suppress or induce ferroptosis through the modulation of signaling pathways, including Sirt1 and Nrf2, unveils novel therapeutic avenues. Despite resveratrol's limited bioavailability, advancements in molecular modification and drug delivery optimization have amplified its clinical utility. Future investigations are poised to unravel the comprehensive mechanisms underpinning resveratrol's action and expand its therapeutic repertoire. We hope this review could furnish a detailed and novel insight into the exploration of resveratrol in the regulation of ferroptosis and its therapeutic prospects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peng, Hu, Liu, Liu, Huang and Wen.)

Tumor metastasis is a continuous and dynamic process and is a major cause of tumor-related death in triple-negative breast cancer. However, this biological process remains largely unknown in triple-negative breast cancer. The emergence of single-cell sequencing enables a deeper understanding of the tumor microenvironment and provides a new strategy for discovering the potential mechanism of tumor metastasis. Herein, we integrated the single-cell expression profiling of primary and metastatic triple-negative breast cancer by Seurat package. Nine tumor cell subgroups were identified. Enrichment analysis suggested tumor subgroups (C0, C4) were associated with tumor metastasis with poor prognosis in TNBC. Weighted gene co-expression network was constructed and identified NENF was a metastasis-related gene. Subsequently, RT-qPCR, Immunohistochemistry, and western blot confirmed NENF is highly expressed in TNBC tissues. And cell function assays indicated NENF promote cell invasion and migration through regulating EMT in TNBC. Finally, TIDE and Connectivity Map database suggest the candidate drugs for targeting NENF. In conclusion, our findings provide a new insight into the progression and metastasis of TNBC and uncover NENF may be a prognostic biomarker and potential therapy targets., (© 2024. The Author(s).)

Background: Primary hepatic lymphoma (PHL) is a rare primary liver tumor. The purpose of this study was to investigate the crucial imaging characteristics of PHL., Methods: CT/MR data and clinical features of 16 patients with pathologically proven PHL were retrospectively reviewed. The assessed imaging characteristics included lesion distribution, growth appearance, density or signal characteristics, and typical signs during the dynamic enhancement., Results: A total of sixteen patients were included in this study, ranging in age from 27 to 86 years (nine men and seven women; mean age, 62 years). Right upper abdominal pain, malaise, or first detection during physical examination were the chief complaint. Dynamic contrast-enhanced CT and MRI demonstrated focal masses in thirteen patients (13/16, 81%), and multiple nodules in three patients (3/16, 19%). The lesions showed vascular floating sign in 10 patients (10/16, 63%) and biliary pass-through sign in 6 patients (6/16, 37%). Necrosis in PHLs were observed in 10 patients (10/16, 63%) and presented target sign on T2WI in 5 out of 11 patients (5/11, 45%) undergoing MRI. After enhancement, PHLs had multinodular sign in the arterial phase in 10 patients (10/16, 63%), and presented washout of contrast medium in the portal-venous or delayed phase in 12 patients (12/16, 75%), pseudocapsule in the delayed phase in 15 patients (15/16, 94%), and double-ring sign in the delayed phase in 8 patients (8/16, 50%)., Conclusion: PHL is generally seen in elderly patients with elevated beta-2-microglobulin levels. Its distinctive imaging features including obviously low ADC value, biliary/vascular floating sign, multinodular sign and double-ring sign in the delayed phase, may help to diagnose and differentiate PHL., (© 2024. The Author(s).)

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time., Competing Interests: Competing interests statement:The authors declare no competing interest.

Since 2010, the Chinese economy has transitioned from a high-speed growth model to a high-quality development model. During this period, the logistics industry has witnessed rapid growth, leading to significant carbon emissions and posing severe threats to the ecological environment. To investigate the spatiotemporal variations in carbon emissions in China's logistics industry, we conducted a correlation analysis using Moran's I index and a bivariate spatial autocorrelation model from 2010 to 2021. Additionally, we employed a geographically and temporally weighted regression model （GTWR） to examine the spatial heterogeneity of factors influencing provincial-level logistics-related carbon emissions. The results indicated that over the study period, there was a shift from insignificant spatial relationships to significant positive spatial correlations among provincial-level logistics carbon emissions in China. Furthermore, varying degrees of spatial clustering were observed. The findings regarding factor heterogeneity revealed that freight turnover volume, per capita GDP of the logistics industry, and infrastructure level exhibited positive spatial correlations with logistics-related carbon emissions, whereas energy intensity showed negative spatial correlations with such emissions. Comparing the results from the geographically weighted regression （GWR） and ordinary least squares regression （OLS）, it was evident that the adjusted R-squared values for the OLS, GWR, and GTWR models were 0.541, 0.567, and 0.838, respectively. This suggests that our adopted GTWR model provided a superior fit and offered better explanations for spatiotemporal heterogeneity between various influencing factors and logistics-related carbon emissions. These research findings can serve as valuable references for formulating province-specific strategies to reduce carbon emissions within China's economy under its high-quality development context.

Information technology has created new ways for people to participate in environmental protection. Ant Forest, a pro-environmental game that actively encourages users to take part in offline environmental activities through online gaming content, has gained great popularity. However, research in this area is still limited, and the effect of playing such games on users' pro-environmental intentions in real life and the underlying mechanisms are unknown. Therefore, this research draws from Persuasive Systems Design model and value theory and examines the relationships between design features of Ant Forest, users' values and their pro-environmental behavioural intentions. The research model is empirically tested by survey data from 428 Ant Forest users. Results indicate that users' self-enhancement values, including utilitarian, hedonic and social values, and self-transcendence values, including altruistic and biospheric values, all positively affect their continued gameplay intentions and therefore affect their pro-environmental behavioural intentions. Additionally, the primary task support, social support, dialogue support, and system credibility of Ant Forest have varying positive effects on users' perceived values., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study is to segment creeping fat and intestinal wall on computed tomography enterography (CTE) and develop a radiomic model to predict 1-year surgery risk in patients with Crohn's disease., Methods: This retrospective study included 135 Crohn's disease patients who underwent CTE between January and December 2021 (training cohort) and 69 patients between January and June 2022 (test cohort). A total of 1874 radiomic features were extracted from the intestinal wall and creeping fat respectively on the venous phase CTE images, and radiomic models were constructed based on the selected features using the Boruta and extreme gradient boosting algorithms. The combined models were established by integrating clinical predictors and radiomic models. The receiver operating characteristic curve, calibration curve, and decision curve analyses were used to compare the predictive performance of models., Results: In the training and test cohorts, the area under the curve (AUC) values of the creeping fat radiomic model for surgery risk stratification were 0.916 and 0.822, respectively, similar to the intestinal model with AUC values of 0.889 and 0.822. Moreover, the combined radiomic model was superior to the single models, showing good discrimination with the highest AUC values (training cohort: 0.963; test cohort: 0.882). Addition of clinical predictors to the radiomic models failed to significantly improve the diagnostic ability., Conclusion: The CTE-based creeping fat radiomic model provided additional information to the intestinal radiomic model, and their combined radiomic model enables accurate surgery risk prediction of Crohn's disease patients within 1 year of CTE., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC)., Methods: Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC., Results: Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus., Conclusion: Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Hu, Han, Tan and Song.)

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.

Background and Objectives : Frailty in older adults is associated with adverse health outcomes. This study aimed to analyze the frailty status of community-dwelling older adults in Taiwan using the Kihon Checklist (KCL) and explore associations with demographic, physiological, and functional factors. Materials and Methods : In this cross-sectional study, 278 community-dwelling older adults were classified as robust, prefrail, or frail based on their KCL scores. Participants underwent physical fitness assessments including muscle strength and endurance tests, walking speed tests, and flexibility tests. One-way ANOVA and logistic regression analyses were used to examine differences and associations between frailty status and physical fitness indicators. Results : 36% of participants were robust, 47.1% prefrail, and 16.9% frail. The robust group significantly outperformed the prefrail and frail groups in the 30 s sit-to-stand test, 2.44 m sit-to-walk test, and walking speed ( p < 0.001). The 2.44 m sit-to-walk test was a significant predictor of prefrailty (OR = 1.18, 95% CI = 1.02-1.36) after adjusting for other physical fitness indicators. Conclusions : Lower limb functional capacity, particularly in the 2.44 m sit-to-walk test, was significantly associated with pre-frailty among community-dwelling older adults in Taiwan. Early screening, the classification of frailty by the Kihon Checklist, and targeted interventions focusing on lower limb strength, endurance, and mobility are crucial for preventing and delaying frailty progression in older populations.

Physical exercise (PE) may be the single most important and accessible lifestyle habit throughout life, it inhibits the neuroinflammatory response and protects the brain against damage. As the innate cells in brain, microglia undergo morphological and functional changes to communicate with neurons protecting the neurons from injury. Herein, aiming at exploring the effects of PE on the communication between microglia-neuron during acute ischemic cerebral infarction, we carried out running wheel training before the conduction of transient middle cerebral artery occlusion (tMCAO) in C57BL/6 J and Cx3cr1-GFP mice. We found that microglial P2Y12 expression in the peri-infarct area was decreased, microglial dynamics and microglia-neuron communications were impaired, using in vivo two-photon imaging. PE up-regulated the microglial P2Y12 expression, increased the microglial dynamics, and promoted the contacts of microglia with neurons. As a result, PE inhibited neuronal Ca 2+ overloads and protected against damage of the neuronal mitochondria in acute tMCAO. Mechanistically, PE increased the cannabinoid receptor 2 (CB 2 R) in microglia, promoted the phosphorylation of Nrf2 (NF-E2-related factor 2) at ser-344, increased the transcription factor level of Mafk, and up-regulated the level of P2Y12, whereby PE increased the levels of CB 2 R to promote microglia-neuron contacts to monitor and protect neuronal function., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cyanobacteria have great potential in CO 2 -based bio-manufacturing and synthetic biological studies. The filamentous cyanobacterium, Leptolyngbya sp. strain BL0902, is comparable to Arthrospira ( Spirulina ) platensis in commercial-scale cultivation while proving to be more genetically tractable. Here, we report the analyses of the whole genome sequence, gene inactivation/overexpression in the chromosome and deletion of non-essential chromosomal regions in this strain. The genetic manipulations were performed via homologous double recombination using either an antibiotic resistance marker or the CRISPR/Cpf1 editing system for positive selection. A desD -overexpressing strain produced γ-linolenic acid in an open raceway photobioreactor with the productivity of 0.36 g·m -2 ·d -1 . Deletion mutants of predicted patX and hetR , two genes with opposite effects on cell differentiation in heterocyst-forming species, were used to demonstrate an analysis of the relationship between regulatory genes in the non-heterocystous species. Furthermore, a 50.8-kb chromosomal region was successfully deleted in BL0902 with the Cpf1 system. These results supported that BL0902 can be developed into a stable photosynthetic cell factory for synthesizing high value-added products, or used as a model strain for investigating the functions of genes that are unique to filamentous cyanobacteria, and could be systematically modified into a genome-streamlined chassis for synthetic biological purposes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Wang, Huang, Yu, Hu, Ning and Xu.)

Objective: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms., Methods: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments., Results: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues., Conclusions: CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the safety and efficacy of the granisetron transdermal delivery system (GTDS) combined with Dexamethasone for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving Capecitabine plus Oxaliplatin (CapeOX) therapy., Design: Open-label, prospective, multi-center phase II trial., Setting: Three institutions., Participants: Fifty-four patients scheduled to receive CapeOX chemotherapy., Interventions: Participants received GTDS (3.1 mg applied to the upper arm 48 h before chemotherapy, replaced on day 5, and discarded on day 12) and Dexamethasone., Main Outcome Measures: The primary endpoint was the complete control rate of CINV. Secondary endpoints included the duration of delayed complete control, complete control rate in the acute phase, safety, and quality of life., Results: The complete control rate for delayed CINV over the entire period (25-480 h) was 72.7% (95% CI 0.57-0.88). The duration of delayed complete control was 17.2 ± 4.5 days, with 51.5% of patients experiencing no nausea during the delayed phase. The complete control rate in the acute phase was 81.8% (95% CI 0.69-0.95). No serious adverse events related to the antiemetic regimen were reported., Conclusion: Prolonged administration of GTDS is safe and effective for preventing CINV in patients with gastrointestinal malignancies treated with CapeOX., Trial Registration: ClinicalTrials.gov registry (NCT05325190); registered on October 10, 2021., (© 2024. The Author(s).)

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt 2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Acute myeloid leukemia (AML) is a hematopoietic malignancy with a high relapse rate and progressive drug resistance. Alternative polyadenylation (APA) contributes to post-transcriptional dysregulation, but little is known about the association between APA and AML. The APA quantitative trait locus (apaQTL) is a powerful method to investigate the relationship between APA and single nucleotide polymorphisms (SNPs). We quantified APA usage in 195 Chinese AML patients and identified 4922 cis-apaQTLs related to 1875 genes, most of which were newly reported. Cis-apaQTLs may modulate the APA selection of 115 genes through poly(A) signals. Colocalization analysis revealed that cis-apaQTLs colocalized with cis-eQTLs may regulate gene expression by affecting miRNA binding sites or RNA secondary structures. We discovered 207 cis-apaQTLs related to AML risk by comparing genotype frequency with the East Asian healthy controls from the 1000 Genomes Project. Genes with cis-apaQTLs were associated with hematological phenotypes and tumor incidence according to the PHARMGKB and MGI databases. Collectively, we profiled an atlas of cis-apaQTLs in Asian AML patients and found their association with APA selection, gene expression, AML risk, and complex traits. Cis-apaQTLs may provide insights into the regulatory mechanisms related to APA in AML occurrence, progression, and prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The study aims to investigate the causal relationship between cheese intake and caries occurrence by a two-sample Mendelian randomization method (TSMR)., Methods: Data from a genome-wide association study (GWAS) on cheese intake as an exposure factor were collected, and dental caries was the outcome variable, appropriate SNPs were selected as instrumental variables (IVs). The TSMR was analyzed by the inverse variance weighting (IVW) method, weighted median method, MR-Egger regression method, simple model and weighted model., Results: We identified forty-four single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (cheese) that were associated with cheese intake, and IVW was adopted. The IVW method supported a relationship between cheese intake and the risk of dental caries occurrence[OR,1.00(95 %CI,0.99-1.00), P = 0.039 < 0.05]. There was no horizontal pleiotropy between the IVs(b = -0.0037, P = 0.39), and the sensitivity analysis using the "leave-one-out" method was robust to causal effects., Conclusion: The results of the TSMR analysis supported that an appropriate intake of cheese could reduce the occurrence of dental caries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The rapid development of society and economy has resulted in a substantial increase in energy consumption, consequently exacerbating pollution issues. Current research predominantly focuses on energy-saving and emission reduction in road transportation within individual cities or the three major economic regions of China:the Yangtze River Delta, the Pearl River Delta, and the Beijing-Tianjin-Hebei Region. However, there is a dearth of studies addressing the southeastern coastal economic region. Located at the heart of China's southeastern coastal economic development, the provinces of Guangdong, Fujian, and Zhejiang unavoidably face challenges associated with energy consumption and emissions while pursuing economic growth. To address these challenges, this study employed a LEAP model to construct various scenarios for road transportation in the key coastal cities of Guangdong, Fujian, and Zhejiang from 2015 to 2035. These scenarios included a baseline scenario (BAU), an existing policy scenario (EPS), and an improved policy scenario (MPS). The MPS and EPS encompassed vehicle structure optimization (VSO), improved fuel economy (IFE), and reduced annual average mileage (RDM). By simulating and evaluating these scenarios, the energy-saving and emission reduction potentials of road transportation in the key coastal cities were assessed. The results indicated that, in the primary scenario, the MPS exhibited the most significant improvements in energy-saving, carbon reduction, and pollutant reduction effects. By 2035, the MPS achieved a remarkable 75% energy-saving rate compared to that in the baseline scenario, accompanied by reductions of 68%, 59%, 66%, 70%, and 64% in CO 2 , CO, NO x , PM 2.5 , and SO 2 emissions, respectively. In the secondary scenario, the improved scenario of enhancing fuel economy achieved a notable 30% reduction in energy consumption. Additionally, the scenarios involving vehicle structure adjustment (yielding reductions of 36%, 30%, 36%, 26%, and 40%) and annual average mileage reduction (resulting in reductions of 37%, 37%, 36%, 37%, and 36%) demonstrated significant reductions in CO 2 , CO, NO x , PM 2.5 , and SO 2 emissions.

Purpose: The optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC., Materials and Methods: We conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding., Results: A total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025)., Conclusion: Following neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC., (© 2024. The Author(s).)

Sodium-ion hybrid capacitors (SIHCs) have attracted much attention due to integrating the high energy density of battery and high out power of supercapacitors. However, rapid Na + diffusion kinetics in cathode is counterbalanced with sluggish anode, hindering the further advancement and commercialization of SIHCs. Here, aiming at conversion-type metal sulfide anode, taking typical VS 2 as an example, a comprehensive regulation of nanostructure and electronic properties through NH 4 + pre-intercalation and Mo-doping VS 2 (Mo-NVS 2 ) is reported. It is demonstrated that NH 4 + pre-intercalation can enlarge the interplanar spacing and Mo-doping can induce interlayer defects and sulfur vacancies that are favorable to construct new ion transport channels, thus resulting in significantly enhanced Na + diffusion kinetics and pseudocapacitance. Density functional theory calculations further reveal that the introduction of NH 4 + and Mo-doping enhances the electronic conductivity, lowers the diffusion energy barrier of Na + , and produces stronger d-p hybridization to promote conversion kinetics of Na + intercalation intermediates. Consequently, Mo-NVS 2 delivers a record-high reversible capacity of 453 mAh g -1 at 3 A g -1 and an ultra-stable cycle life of over 20 000 cycles. The assembled SIHCs achieve impressive energy density/power density of 98 Wh kg -1 /11.84 kW kg -1 , ultralong cycling life of over 15000 cycles, and very low self-discharge rate (0.84 mV h -1 )., (© 2023 Wiley‐VCH GmbH.)

Cancer cells rely on aerobic glycolysis and DNA repair signals to drive tumor growth and develop drug resistance. Yet, fine-tuning aerobic glycolysis with the assist of nanotechnology, for example, dampening lactate dehydrogenase (LDH) for cancer cell metabolic reprograming remains to be investigated. Here we focus on anaplastic thyroid cancer (ATC) as an extremely malignant cancer with the high expression of LDH, and develop a pH-responsive and nucleus-targeting platinum nanocluster (Pt@TAT/sPEG) to simultaneously targets LDH and exacerbates DNA damage. Pt@TAT/sPEG effectively disrupts LDH activity, reducing lactate production and ATP levels, and meanwhile induces ROS production, DNA damage, and apoptosis in ATC tumor cells. We found Pt@TAT/sPEG also blocks nucleotide excision repair pathway and achieves effective tumor cell killing. In an orthotopic ATC xenograft model, Pt@TAT/sPEG demonstrates superior tumor growth suppression compared to Pt@sPEG and cisplatin. This nanostrategy offers a feasible approach to simultaneously inhibit glycolysis and DNA repair for metabolic reprogramming and enhanced tumor chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as 'warm blobs', have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America., (© 2024. The Author(s).)

Background: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial., Objective: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia., Methods: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β 2 -agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV 1 ) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56., Results: Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV 1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV 1 , and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population., Conclusions: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nanshan Zhong reports financial support was provided by AstraZeneca. Kefang Lai reports financial support was provided by AstraZeneca. Dejun Sun reports financial support was provided by AstraZeneca. Ranran Dai reports financial support was provided by AstraZeneca. Ronnie Samoro reports financial support was provided by AstraZeneca. Hae-Sim Park reports financial support was provided by AstraZeneca. Annika Astrand reports a relationship with AstraZeneca that includes: employment and equity or stocks. David Cohen reports a relationship with AstraZeneca that includes: employment and equity or stocks. Maria Jison reports a relationship with AstraZeneca that includes: employment and equity or stocks. Vivian H Shih reports a relationship with AstraZeneca that includes: employment and equity or stocks. Viktoria Werkstrom reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yuhui Yao reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yajuan Zhang reports a relationship with AstraZeneca that includes: employment and equity or stocks. Wenying Zheng reports a relationship with AstraZeneca that includes: employment and equity or stocks. Tanya Jandu and Helen Brereton of inScience Communications, Springer Healthcare Ltd, UK, provided medical writing support, which was funded by AstraZeneca. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer., Methods: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology., Results: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64)., Conclusions: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging., Clinical Relevance Statement: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT., Key Points: • Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. • The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. • Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Layered sodium vanadium materials have aroused increasing interest owing to their open layered structures and high theoretical capacity. Nevertheless, the strong electrostatic interactions between vanadium oxide layers and intercalated Zn 2+ and the weak electronic conductivity severely limit their further development. Here, we design a series of cobalt ion-doped sodium vanadium electrode materials with nanoflower-like morphologies. Due to the open interlayer space and improved electron transfer enabled by cobalt ion preintercalation and sufficient contact area between the electrode and electrolyte provided by the three-dimensional (3D) flower-like morphology, the cobalt ion-doped sodium vanadate (CNVO-2) cathode exhibits excellent electrochemical performance, including an exceptional specific capacity (411 mA h g -1 at 0.5 A g -1 ) and ultrahigh structural stability (90.4 % capacity retention after 3000 cycles at 10 A g -1 ), outperforming many advanced ZIBs cathode materials. In addition, through various ex situ characterization techniques, an ionic exchange and multiple ion cointercalation mechanism is first revealed in sodium vanadate cathode material., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.

Purpose: This study was designed to examine the hypothesis that discourse task types influence language performance in Mandarin Chinese-speaking people and to reveal the discourse task-specific linguistic properties of persons with anomic aphasia compared to neurotypical controls., Method: Language samples from persons with aphasia ( n = 31) and age- and education-matched controls ( n = 31) across four discourse tasks (sequential-picture description, single-picture description, story narrative, and procedural discourse) were collected from Mandarin AphasiaBank. Task-specific distributions of parts of speech were analyzed using mosaic plots. The main effects of tasks in each group and the between-group differences within each task for several typical linguistic variables were evaluated, including the mean length of utterance, tokens, moving-average type-token ratio, words per minute, propositional density, noun-verb ratio, noun percentage, and verb percentage., Results: The results revealed an impact of discourse tasks on most language variables in both groups. In the healthy controls, story narratives yielded the highest total words and lowest verb percentage. In the aphasia group, procedural discourse elicited the fewest total words and densest expressions, whereas their single-picture descriptions had the highest noun-verb ratio. For all tasks, the aphasia group performed worse than the control group in the mean length of utterance, tokens, moving-average type-token ratio, and words per minute. For noun-verb ratio, noun percentage, and verb percentage, only one task (i.e., single-picture description) showed significant between-group differences., Conclusion: The selection of discourse tasks should be addressed in assessments and interventions for Mandarin Chinese-speaking individuals with aphasia to obtain more accurate and feasible outcomes.

Purpose: This study aimed to explore how well persons with anomic aphasia communicate information during discourse regarding quantity, quality, and efficiency compared to neurotypical controls, to investigate the influence of discourse tasks on informativeness and efficiency and to examine impact factors like aphasia severity and cognitive ability., Method: Language samples of four discourse tasks from 31 persons with anomic aphasia and 31 neurotypical controls were collected from Mandarin AphasiaBank. Correct information unit (CIU) analysis measures including the total number of CIUs, percentage of CIUs, CIUs per minute, and words per minute were calculated. Group differences and the effects of discourse tasks on informativeness and efficiency were investigated. Correlations of CIU analysis measures with aphasia severity and cognitive ability were examined., Results: Persons with anomic aphasia showed lower efficiency in conveying information than controls. They underperformed controls on all CIU analysis measures when executing story narrative tasks. Discourse tasks influenced the informativeness and efficiency of both groups. Neurotypical controls delivered the greatest quantity of information most efficiently when narrating stories. Persons with anomic aphasia exhibited reduced quantity of information during procedural discourse and displayed superior information quality in sequential-picture descriptions. Discourse information may be impacted by aphasia severity and cognitive ability, with varying effects depending on the task., Conclusions: Persons with anomic aphasia are inefficient in communicating discourse messages and perform poorly on all measures in story narratives. When measuring discourse information, the effects of discourse tasks and factors like aphasia severity and cognitive ability should be considered.

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients., (© 2024. The Author(s).)