Pharmacological treatments for vascular dementia: a systematic review and Bayesian network meta-analysis.

Background: Vascular dementia (VaD) is one of the most prevalent, burdensome, and costly forms of dementia. Pharmacological treatment is often the first-line choice for clinicians; however, there is a paucity of comparative information regarding the multiple available drug options. Methods and Analysis: A systematic review and network meta-analysis were conducted on randomized trials involving adult patients with VaD, sourced from PubMed, the Cochrane Library, EMBASE, Web of Science, OPENGREY, ClinicalTrials.gov, Wanfang Data, and CNKI. The primary outcomes included changes in Mini-Mental State Examination (MMSE) scores, activities of daily living (ADL) scores, and the incidence of adverse reactions. Efficacy and safety of intervention strategies were comprehensively analyzed using forest plots, cumulative ranking probability curves (SUCRA), and funnel plots, all generated with R software. Results: A total of 194 RCTs comparing 21 different anti-VaD drugs with placebos or no treatment were analysed. Regarding MMSE scores, the five most effective drugs were Butylphthalide, Huperzine A, Edaravone, Rivastigmine, and Memantine. For ADL scores, the top five drugs in efficacy were Huperzine A, Butylphthalide, Tianzhi granule, Nicergoline, and Idebenone. In terms of the incidence of adverse drug reactions, Co-dergocrine Mesylate, Tongxinluo capsule, Butylphthalide, Piracetam, and Oxiracetam demonstrated favourable safety profiles. Conclusion: This study enhances the understanding of the relative benefits and risks associated with various VaD treatments, providing a valuable reference for clinical decision-making. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier registration number.

Kondoa tianchiensis f.a., sp. nov., an anamorphic yeast species isolated from plant leaves.

Two yeast strains, NYNU 236122 and NYNU 236180, were isolated from plant leaves collected in Tianchi Mountain, Henan Province, central China. Molecular phylogenetic analyses revealed the closest relatives of the strains are three described Kondoa species, Kondoa chamaenerii, Kondoa miscanthi, and Kondoa subrosea. Genetically, the isolated strains differed from the type strains of their three related species by 2-11(0.2-1.8%) base substitutions in the D1/D2 domain, 16-40 (2.6-5.6%) base mismatches in the internal transcribed spacer region, and more than 10.1% base substitutions in the partial RPB2 gene. Furthermore, the two strains differ physiologically from their closest related species, K. chamaenerii, in their ability to assimilate dl-lactate, nitrite, and l-lysine and their inability to assimilate nitrate. Additionally, they differ from K. miscanthi and K. subrosea in their ability to assimilate inulin, d-gluconate, and l-lysine. The species name of Kondoa tianchiensis f.a., sp. nov. is proposed with holotype CICC 33616T (Mycobank MB 853544).

Precise tracking of nanoparticles in plant roots.

One of the foremost challenges in nanobiotechnology is obtaining direct evidence of nanoparticles' absorption and internalization in plants. Although confocal laser scanning microscopy (CLSM) or transmission electron microscopy (TEM) are currently the most commonly used tools to characterize nanoparticles in plants, subjectivity of researchers, incorrect sample handling, inevitable fluorescence leakage and limitations of imaging instruments lead to false positives and non-reproducibility of experimental results. This protocol provides an easy-to-operate dual-step method, combining CLSM for macroscopic tissue examination and TEM for cellular-level analysis, to effectively trace single particles in plant roots with accuracy and precision. In addition, we also provide detailed methods for processing plant materials before imaging, including cleaning, and staining, to maximize the accuracy and reliability of imaging. This protocol involves currently commonly used nanomaterial types, such as metal-based and doped carbon-based materials, and enables accurate localization of nanoparticles with different sizes at the cell level in Arabidopsis thaliana root samples either through contrast or element mapping analysis. It serves as a valuable reference and benchmark for scholars in plant science, chemistry and environmental studies to understand the interaction between plant roots and nanomaterials and to detect the distribution of nanomaterials in plants. Excluding plant culture time, the protocol can be completed in 4-5 d.

Design and application of a high-precision counterweighted self-calibrating surface thermometer.

In this study, a high-precision counterweight self-calibrating surface thermometer is designed to reduce human and environmental influences on a thermocouple surface thermometer during measuring. A self-weighted spring structure based on a copper substrate is designed to ensure perfect contact between the surface thermometer and the temperature source. In conjunction, a wind guard is coupled with insulating materials to optimize the thermal exchange of the surface thermometer. Subsequently, the maximum error is reduced to ±1.5 °C by system hardware optimization. However, hardware calibration alone is insufficient. Furthermore, a back propagation neural network is employed to calibrate the surface thermometer. Temperature sensor data are collected under various surface source temperatures and airflow velocities to train the neural network. Hence, the effectiveness of the proposed Gaussian function in enhancing the measurement accuracy of the surface temperature sensor is demonstrated. The results show higher stability and repeatability in temperature measurement than thermocouple-based surface thermometers. The proposed thermometer exhibits robustness against environmental and operational variability with a maximum indication error of -0.2 °C. In contrast, the maximum error of the surface thermometer is between -2.8 and -6.8 °C. Regarding repeatability, the standard deviation with the proposed device is 0.2%, highlighting its accuracy and consistency of performance. These results can mostly be attributed to the synergistic effect of clever mechanical design and software optimization, resulting in a surface thermometer with outstanding accuracy and repeatability.

Construction and verification of a risk prediction model for cognitive frailty in older patients with chronic obstructive pulmonary disease and diabetes mellitus.

OBJECTIVE: We explored risk factors for cognitive frailty in older patients with chronic obstructive pulmonary disease (COPD) and diabetes mellitus to develop and verify a risk prediction model for cognitive frailty. METHODS: This was a cross-sectional study. Convenience sampling was used to randomly select 378 patients hospitalized between February 2022 and December 2023. We allocated 265 patients who visited between February 2022 and February 2023 to a modeling group to analyze risk factors for cognitive frailty and create a logistic regression model for risk prediction. Another 113 patients who visited between March 2023 and December 2023 were included in a validation group for model verification. RESULTS: The cognitive frailty incidence in the 265 patients was 35.09% (93/265). Regression analysis showed that age >80 years (odds ratio [OR] = 4.576), regular exercise (OR = 0.390, polypharmacy (OR = 3.074), depression (OR = 2.395) duration of COPD combined with diabetes (OR = 1.902), Family APGAR index score (OR = 0.428), and chronic pain (OR = 2.156) were factors influencing the occurrence of cognitive frailty in older patients with COPD accompanied by diabetes. CONCLUSIONS: The constructed risk prediction model for cognitive frailty in older patients with COPD and diabetes showed good predictive value, aiding in the clinical identification of high-risk patients and facilitating timely intervention and guidance.

A telomere-to-telomere cotton genome assembly reveals centromere evolution and a Mutator transposon-linked module regulating embryo development.

Assembly of complete genomes can reveal functional genetic elements missing from draft sequences. Here we present the near-complete telomere-to-telomere and contiguous genome of the cotton species Gossypium raimondii. Our assembly identified gaps and misoriented or misassembled regions in previous assemblies and produced 13 centromeres, with 25 chromosomal ends having telomeres. In contrast to satellite-rich Arabidopsis and rice centromeres, cotton centromeres lack phased CENH3 nucleosome positioning patterns and probably evolved by invasion from long terminal repeat retrotransposons. In-depth expression profiling of transposable elements revealed a previously unannotated DNA transposon (MuTC01) that interacts with miR2947 to produce trans-acting small interfering RNAs (siRNAs), one of which targets the newly evolved LEC2 (LEC2b) to produce phased siRNAs. Systematic genome editing experiments revealed that this tripartite module, miR2947-MuTC01-LEC2b, controls the morphogenesis of complex folded embryos characteristic of Gossypium and its close relatives in the cotton tribe. Our study reveals a trans-acting siRNA-based tripartite regulatory pathway for embryo development in higher plants.

Mycenabrunnescens (Basidiomycota, Mycenaceae), a new species of Mycena sect. Pterigenae from China.

Background: Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycenagalericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described. New information: Mycenabrunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M.albiceps and M.flosoides.

Elevation of IL-8 secretion induced by PEDV infection via NF-κB signaling pathway.

Porcine epidemic diarrhea virus (PEDV) is associated with severe enteritis, which contributes to high mortality in piglets. The aim of this study was to describe molecular mechanisms associated with proinflammatory cytokine(s) production during PEDV infection. We showed that infection of porcine intestine epithelial cell clone J2 (IPEC-J2) with PEDV induces a gradual increase in interleukin 8 (IL-8) production at different time points, as well as infection of Vero E6 with PEDV. The secretion of IL-8 in these two cell lines infected with PEDV is related to the activation of NF-κB. Furthermore, the cells expressing PEDV M or E protein can induce the upregulation of IL-8. These findings suggest that the IL-8 production can be the initiator of inflammatory response by the host cells upon PEDV infection.

Identification of Novel Target DCTPP1 for Colorectal Cancer Therapy with the Natural Small-molecule Inhibitors Regulating Metabolic Reprogramming.

Colorectal cancer (CRC) is one of the most common malignant tumours. Identification of new effective drug targets for CRC and exploration of bioactive small-molecules are clinically urgent. The human dCTP pyrophosphatase 1 (DCTPP1) is a newly identified pyrophosphatase regulating the cellular nucleotide pool but remains unexplored as potential target for CRC treatment. Here, twelve unprecedented chemical architectures terpene-nonadride heterodimers (1-12) and their monomers (13-20) were isolated from endophyte Bipolaris victoriae S27. Compounds 1-12 represented the first example of terpene-nonadride heterodimers, in which nonadride monomers of 1 and 2 were also first example of 5/6 bicyclic nonadrides. A series of assays showed that 2 could repress proliferation and induce cell cycle arrest, apoptotic and autophagic CRC cell death in vitro and in vivo. Clinical cancer samples data revealed that DCTPP1 was a novel target associated with poor survival in CRC. DCTPP1 was also identified as a new target protein of 2. Mechanistically, compound 2 bound to DCTPP1, inhibited its enzymatic activity, intervened with amino acid metabolic reprogramming, and exerted anti-CRC activity. Our study demonstrates that DCTPP1 was a novel potential biomarker and therapeutic target in CRC, and 2 was the first natural anti-CRC drug candidate targeting DCTPP1.

Development and validation of the head and neck cancer psychosocial distress scale (HNCPDS) to identify patients at high risk for psychological problems : a multicenter study.

To develop the Head and Neck Cancer Psychosocial Distress Scale (HNCPDS) with the aim of identifying high-risk individuals for psychosocial distress among patients, and to assess its reliability, validity and applicability. Using the classical test theory, a total of 435 head and neck cancer patients from six tertiary hospitals in China were recruited for developing the HNCPDS. Delphi expert consultation and item analysis were used to improve the content validity of the preliminary HNCPDS. Factor analysis (FA) and Structural equation modeling (SEM) were used to test the structural validity of HNCPDS. Cronbach's alpha coefficient, Spearman-Brown coefficient and Intra-class correlation coefficient (ICC) were used to test the internal consistency and retest reliability of HNCPDS. Multiple stepped-linear regression was used to analyze the risk factors of psychological disorder, and Pearson correlation coefficient was used to analyze the correlation between psychosocial distress and quality of life (QOL). The HNCPDS consisted of 14 items, which were divided into 3 subscales: 3 items for cancer discrimination, 5 items for anxiety and depression, and 6 items for social phobia. The HNCPDS had good validity [KMO coefficient was 0.947, Bartlett's test was 5027.496 (P < 0.001), Cumulative variance contribution rate was 75.416%, and all factor loadings were greater than 0.55], reliability (Cronbach's alpha coefficient was 0.954, Spearman-Brown coefficient was 0.955, test-retest reliability was 0.845) and acceptability [average completion time (14.31 ± 2.354 min) and effective completion rate of 90.63%]. Financial burden, sex, age and personality were found to be independent risk factors for HNCPDS (P < 0.05), and patients with higher HNCPDS scores reported a lower QOL (P < 0.01). The HNCPDS is effective and reliable in early identification and assessment of the level of psychosocial distress in patients with head and neck cancer, which can provide an effective basis for health education, psychological counseling, and social support in the future.

Emergence of a novel pathogenic porcine G1P[7] rotavirus in China.

Among group A rotaviruses (RVAs), the G1 genotype is the main genotype causing diarrhea in children, but it has rarely been reported in pigs. During our epidemiological investigation, we detected G1P[7] rotavirus infection in piglets across several provinces in China and then isolated a porcine G1P[7] rotavirus strain (CN1P7). Sequencing revealed that the virus constellation was G1-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analyses revealed that CN1P7 most likely emerged due to genetic reassortment among porcine, human, giant panda and dog rotavirus strains. In vivo experiments were conducted on two-day-old piglets, which revealed that the CN1P7 strain was pathogenic to piglets. The virus was shed through the digestive tract and respiratory tract. In addition to the intestine, the CN1P7 strain displayed extraintestinal tropisms in piglets. Histopathological analysis revealed that the lung and small intestine were the targets of CN1P7. This study is the first to explore the molecular and pathogenic characterization of a pig-origin G1P[7] rotavirus.

Contrasting association pattern of plasma low-density lipoprotein with white matter integrity in APOE4 carriers versus non-carriers.

Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer's disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown. In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1917 older adults (aged 65.0-81.0 years; 52.4 % female). Although no main association was observed between either APOE4 or metabolites with WM integrity (adjusted P > 0.05), significant interactions between APOE4 and metabolites with WM integrity were identified. Among the examined metabolites, higher concentrations of low-density lipoprotein and very low-density lipoprotein were associated with a lower level of WM integrity (b=-0.12, CI=-0.14,-0.10) among APOE4 carriers. Conversely, among non-carriers, they were associated with a higher level of WM integrity (b=0.05, CI=0.04,0.07), demonstrating a significant moderation role of APOE4 (b =-0.18, CI=-0.20,-0.15, P<0.00001).

Macrophage-based cancer immunotherapy: Challenges and opportunities.

Macrophages play crucial roles in the tumor microenvironment (TME), exerting diverse functions ranging from promoting tumor growth and metastasis to orchestrating anti-tumor immune responses. Their plasticity allows them to adopt distinct activation states, often called M1-like (pro-inflammatory) and M2-like (anti-inflammatory or pro-tumoral), significantly influencing tumor progression and response to therapy. Harnessing the potential of macrophages in cancer immunotherapy has emerged as a promising strategy, with increasing interest in targeting these cells directly or modulating their functions within the TME. This review explores the intricate interplay between macrophages, the TME, and immunotherapeutic approaches. We discuss the dynamic phenotypic and functional heterogeneity of tumor-associated macrophages (TAMs), their impact on disease progression, and the mechanisms underlying their response to immunotherapy. Furthermore, we highlight recent advancements in macrophage-based immunotherapeutic strategies, including macrophage-targeting agents, adoptive cell transfer, and engineering approaches. Understanding the complex crosstalk between macrophages and the TME is essential for developing effective immunotherapeutic interventions that exploit the immunomodulatory functions of macrophages to enhance anti-tumor immunity and improve clinical outcomes for cancer patients.

Free-breathing time-resolved 4D MRI with improved T1-weighting contrast.

This work proposes MP-Grasp4D (magnetization-prepared golden-angle radial sparse parallel 4D) MRI, a free-breathing, inversion recovery (IR)-prepared, time-resolved 4D MRI technique with improved T1-weighted contrast. MP-Grasp4D MRI acquisition incorporates IR preparation into a radial gradient echo sequence. MP-Grasp4D employs a golden-angle navi-stack-of-stars sampling scheme, where imaging data of rotating radial stacks and navigator stacks (acquired at a consistent rotation angle) are alternately acquired. The navigator stacks are used to estimate a temporal basis for low-rank subspace-constrained reconstruction. This allows for the simultaneous capture of both IR-induced contrast changes and respiratory motion. One temporal frame of the imaging volume in MP-Grasp4D MRI is reconstructed from a single stack and an adjacent navigator stack on average, resulting in a nominal temporal resolution of 0.16 seconds per volume. Images corresponding to the optimal inversion time (TI) can be retrospectively selected for providing the best image contrast. Reader studies were conducted to assess the performance of MP-Grasp4D MRI in liver imaging across 30 subjects in comparison with standard Grasp4D MRI without IR preparation. MP-Grasp4D MRI received significantly higher scores (P < 0.05) than Grasp4D in all assessment categories. There was a moderate to almost perfect agreement (kappa coefficient from 0.42 to 0.9) between the two readers for image quality assessment. When the scan time is reduced, MP-Grasp4D MRI preserves image contrast and quality, demonstrating additional acceleration capability. MP-Grasp4D MRI improves T1-weighted contrast for free-breathing time-resolved 4D MRI and eliminates the need for explicit motion compensation. This method is expected to be valuable in different MRI applications such as MR-guided radiotherapy.

DeepEMC-T2 mapping: Deep learning-enabled T2 mapping based on echo modulation curve modeling.

PURPOSE: Echo modulation curve (EMC) modeling enables accurate quantification of T2 relaxation times in multi-echo spin-echo (MESE) imaging. The standard EMC-T2 mapping framework, however, requires sufficient echoes and cumbersome pixel-wise dictionary-matching steps. This work proposes a deep learning version of EMC-T2 mapping, called DeepEMC-T2 mapping, to efficiently estimate accurate T2 maps from fewer echoes. METHODS: DeepEMC-T2 mapping was developed using a modified U-Net to estimate both T2 and proton density (PD) maps directly from MESE images. The network implements several new features to improve the accuracy of T2/PD estimation. A total of 67 MESE datasets acquired in axial orientation were used for network training and evaluation. An additional 57 datasets acquired in coronal orientation with different scan parameters were used to evaluate the generalizability of the framework. The performance of DeepEMC-T2 mapping was evaluated in seven experiments. RESULTS: Compared to the reference, DeepEMC-T2 mapping achieved T2 estimation errors from 1% to 11% and PD estimation errors from 0.4% to 1.5% with ten/seven/five/three echoes, which are more accurate than standard EMC-T2 mapping. By incorporating datasets acquired with different scan parameters and orientations for joint training, DeepEMC-T2 exhibits robust generalizability across varying imaging protocols. Increasing the echo spacing and including longer echoes improve the accuracy of parameter estimation. The new features proposed in DeepEMC-T2 mapping all enabled more accurate T2 estimation. CONCLUSIONS: DeepEMC-T2 mapping enables simplified, efficient, and accurate T2 quantification directly from MESE images without dictionary matching. Accurate T2 estimation from fewer echoes allows for increased volumetric coverage and/or higher slice resolution without prolonging total scan times.

Th1/Th2 Imbalance in Peripheral Blood Echoes Microglia State Dynamics in CNS During TLE Progression.

Central and systemic inflammation play pivotal roles in epileptogenesis and proepileptogenesis in temporal lobe epilepsy (TLE). The interplay between peripheral CD4+ T cells and central microglia orchestrates the "systemic-central" immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed an imbalance in Th1/Th2 subsets in the periphery，accompanied by related cytokines release in TLE patients. they proposed that this peripheral Th1/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li-pilocarpine-induced TLE rats, a peripheral Th1/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4+ T cells infiltrated through the compromised blood-brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4+ T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1/Th2 imbalance in modulating the "systemic-central" response in TLE, highlighting Notch1 as a potential therapeutic target.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

The ratio of PKM1/PKM2 is the key factor affecting the glucose metabolism and biological function of colorectal cancer cells.

Background: Despite evidence suggesting a significant role of pyruvate kinase muscle isozyme (PKM) in cancer development, its particular function in colorectal cancer (CRC) remains unclear. This study aimed to elucidate the specific role and mechanism of PKM and its isoforms, PKM1 and PKM2, in the progression of CRC. Methods: We analyzed PKM, PKM1, and PKM2 expression in CRC tissues and their correlation with clinicopathological features. Plasmids were constructed to modulate these isoforms' expression in CRC cells. Cellular behavior changes, including glucose metabolism alterations, were assessed using the Seahorse Energy Meter, and the Cell Counting Kit-8 (CCK8) assay to determine the inhibitory concentration of 5-fluorouracil (5-FU) on different CRC cell groups. Results: Our results showed significant PKM overexpression in CRC tissues, which was correlated with negative prognostic factors such as advanced T stages and lymph node metastasis. A lower PKM1/PKM2 ratio was associated with these adverse outcomes. Functionally, PKM1 overexpression decreased cell migration and invasion, increasing 5-FU sensitivity. Conversely, PKM2 overexpression promoted malignant traits and reduced 5-FU sensitivity. Intriguingly, the introduction of glycolysis inhibitors attenuated the impact of PKM on the biological functions of CRC cells, suggesting a glycolysis-dependent mechanism. Conclusions: This study establishes the PKM1/PKM2 ratio as crucial in CRC progression and 5-FU response. PKM1 overexpression reduces CRC malignancy and increases 5-FU sensitivity, while PKM2 does the opposite. Notably, glycolysis inhibitors lessen PKM's impact on CRC cells, highlighting a glycolysis-dependent mechanism. These insights suggest targeting PKM isoforms and glycolysis pathways as a promising CRC therapeutic strategy, potentially enhancing treatment efficacy.

Prolonged Microcystis restraint through allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM): Optimal formulation, characterization, effects and synergistic inhibition mechanisms.

The Microcystis blooms have caused serious damage to aquatic ecosystems. Microspheres containing allelochemicals with sustained-release properties have the potential to function as a cost-effective and environmentally friendly algaecide against M. aeruginosa. In the current investigation, we successfully optimized the synthesis of allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM), which demonstrated a high embedding rate (90.17 %) and loading rate (0.65 %), with an accumulative release rate of 53.27 % on day 30. To investigate the sustained-release mechanism of CM-AC@SM, the sustained-release process of allelochemicals was determined using the Folin-Phenol method and the immersion behavior of the CM-AC@SM was characterized through SEM and XPS. Results showed that allelochemicals were released in the delayed-dissolution mode. In addition, to elucidate the synergistic mechanism of CM-AC@SM towards the inhibition of M. aeruginosa, this study comprehensively assessed the effects of allelochemicals, carbon material and CM-AC@SM on the morphology, antioxidant system activity and photosynthetic activity of M. aeruginosa. The findings indicated that allelochemicals and carbon material induced intracellular protein and nucleic acid leakage by increasing cell membrane permeability, disrupted the extracellular and intracellular morphology of algae, triggered peroxidative damage and restrained antioxidant system activity by stimulating the generation of reactive oxygen species. Simultaneously, the activity of photosystem II was inhibited by allelochemicals and carbon material, substantiated by the reduction in Fv/Fo and Fv/Fm ratios. Hence, CM-AC@SM shows promise in inhibiting M. aeruginosa, offering an efficient approach for the future large-scale control of harmful algal blooms (HABs).

Nature of the Active Center for the Oxygen Reduction on Ag-Based Single-Atom Alloy Clusters.

The development of alternative alloy catalysts with high activity, surpassing platinum group metals, for the oxygen reduction reaction (ORR) is urgently needed in the field of electrocatalysis. The Ag-based single-atom alloy (AgSAA) cluster has been proposed as a promising catalyst for the ORR; however, enhancing its activity under operational conditions remains challenging due to limited insights into its actual active site. Here, we demonstrate that the operando formation of the MO x (OH) y complex serves as the key active site for catalyzing the ORR over AgSAA cluster catalysts, as revealed through comprehensive neural network potential molecular dynamics simulations combined with first-principles calculations. The volcano plot of the ORR over the MO x (OH) y complex addresses the gaps inherent in traditional metallic alloy models for pure AgSAA cluster catalysts in ORR catalysis. The appropriate orbital hybridization between OH and the dopant metal in the MO x (OH) y complexes indicated that the Ag54Co1, Ag54Pd1, and Ag54Au1 clusters are optimal AgSAA catalysts for the ORR. Our work underscores the significance of theoretical modeling considering the reaction atmosphere in uncovering the true active site for the ORR, which can be extended to other reaction systems for rational catalyst design.