Therapeutic potential of Cordyceps sinensis targeting oxidative stress and inflammatory response in the treatment of COPD rats: insights from metabolomics analysis.

This study aimed to investigate the effects of wild Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) rats through metabolomics approach, combined with biochemical parameters evaluations. Consequently, C. sinensis exhibited regulatory effects on the lung's metabolic profiles in COPD rats. Treatment with C. sinensis potentially modulated glycerophospholipid metabolism, glutathione metabolism, and tryptophan metabolism, thereby alleviating oxidative stress (by decreasing MDA and GSSG, while increasing SOD and GSH) and inflammatory response (by inhibiting TNF-α, IL-8, and MMP-9) in COPD rats while improving lung tissue damage.

Construction of homologous branched oligomer megamolecules based on linker-directed protein assembly.

Utilizing the building blocks of recombinant proteins and synthetic linkers, we have obtained two distinct octameric megamolecules with diverse branched structures. This approach combines principles from both click chemistry and protein engineering technology, enabling the integration of functional domains within highly ordered protein assemblies for biomedical applications.

Pharmacometabolomics and mass spectrometry imaging approach to reveal the neurochemical mechanisms of Polygala tenuifolia.

Polygala tenuifolia, commonly known as Yuanzhi (YZ) in Chinese, has been shown to possess anti-insomnia properties. However, the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear. Herein, we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging (MSI)-based spatial resolved metabolomics. According to the results, 17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain, which might be the major components contributing to the sedative-hypnotic effects. Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction, serotonergic synapse, dopaminergic synapse, and dopaminergic synapse, among other pathways. LC-MS/MS-based targeted metabolomics and Western blot (WB) revealed that tryptophan-serotonin-melatonin (Trp-5-HT-Mel) and tyrosine-norepinephrine-adrenaline (Tyr-Ne-Ad) are the key regulated pathways. Dopa decarboxylase (DDC) upregulation and phenylethanolamine N-methyltransferase (PNMT) downregulation further confirmed these pathways. Furthermore, MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland (PG), and Ad in the brainstem, including the middle brain (MB), pons (PN), and hypothalamus (HY). In summary, this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine, YZ.

A review on solid-state recycling of aluminum machining chips and their morphology effect on recycled part quality.

The increasing demand for sustainable manufacturing has revived the interest in solid-state recycling (SSR) as a promising alternative method for aluminum waste. In this context, chips generated during machining processes constitute a substantial portion of aluminum waste, offering significant potential for recycling and mitigating waste. However, the machining chip morphology significantly impacts the properties of chip-based recycled parts. This review paper examines the current state-of-the-art solid-state recycling methods, focusing on hot forging, extrusion, equal channel angular pressing, friction stir extrusion and field-assisted sintering. It investigates the impact of aluminum chip morphology on the properties of the directly recycled material, emphasizing the chip machining consequence on the final quality of the product. Several studies reported that the strain and operating temperature are the most influential factors in SSR processes, followed by chip size with an average length of less than 4 mm. Yet, the heating time up to 3 h also had a major impact on chip weld strength. The findings highlighted the significance of aluminum chip morphology in improving the quality of recycled material. The properties of direct recycled samples primarily depend on chip weld strength and microstructure. Overall, this study presented a comprehensive overview of the current state of solid-state recycling and emphasized the significance of chip morphology in advancing the recycling process. Consequently, it equips researchers with a valuable resource for developing effective strategies for sustainable recycling of aluminum chips with high quality.

Effect of excessive internet gaming on inhibitory control based on resting EEG and ERP.

Previous research indicates that individuals with Internet gaming disorder (IGD) show impaired inhibitory control and abnormal EEG/ERP patterns. However, it is unclear how those individuals with excessive Internet game use (EUG) but without addiction differ. This study examined inhibitory control, resting EEG, and ERP in EUG gamers compared to non-gamers. Fifteen participants in each group underwent 4-min eyes-closed EEG recordings and a color-word Stroop task. Results showed no significant differences in reaction time, accuracy, or P3 amplitude between EUG gamers and non-gamers. However, EUG gamers exhibited shortened P3 latency, which may suggest enhanced inhibitory control. Additionally, EUG gamers showed reduced theta and alpha band power during the resting state compared to non-gamers. These findings suggest that excessive gaming without addiction may enhance inhibitory control and influence brain activity differently from IGD.

Response surface methodology and machine learning optimisations comparisons of recycled AA6061-B4C-ZrO2 hybrid metal matrix composites via hot forging forming process.

The optimal conditions of applied factors to reuse Aluminium AA6061 scraps are (450, 500, and 550) °C preheating temperature, (1-15) % Boron Carbide (B4C), and Zirconium (ZrO2) hybrid reinforced particles at 120 min forging time via Hot Forging (HF) process. The response surface methodology (RSM) and machine learning (ML) were established for the optimisations and comparisons towards materials strength structure. The Ultimate Tensile Strength (UTS) strength and Microhardness (MH) were significantly increased by increasing the processed temperature and reinforced particles because of the material dispersion strengthening. The high melting point of particles caused impedance movements of aluminium ceramics dislocations which need higher plastic deformation force and hence increased the material's mechanical and physical properties. But, beyond Al/10 % B4C + 10 % ZrO2 the strength and hardness were decreased due to more particle agglomeration distribution. The optimisation tools of both RSM and ML show high agreement between the reported results of applied parameters towards the materials' strength characterisation. The microstructure analysis of Field Emission Scanning Electron Microscopy (FE-SEM) and Atomic Force Microscope (AFM) provides insights mapping behavioural characterisation supports related to strength and hardness properties. The distribution of different volumes of ceramic particle proportion was highlighted. The environmental impacts were also analysed by employing a life cycle assessment (LCA) to identify energy savings because of its fewer processing steps and produce excellent hybrid materials properties.

Selection of Stable Reference Genes for QRT-PCR in Tree Peony 'Doulv' and Functional Analysis of PsCUC3.

(1) Background: Tree peonies display extensive cultivar diversity due to widespread hybridization, resulting in a complex genetic architecture. This complexity complicates the selection of universal reference genes across different cultivars for qRT-PCR analyses. Paeonia suffruticosa 'Doulv', notable for its unique green blooms in China, exhibits chlorosis post-flowering and features petaloid stamens and pistils. (2) Methods: Based on published literature and RNA-seq data from 'Doulv', nine candidate reference genes-ACT (Actin), TUB (ß-Tubulin), UBC (Ubiquitin Conjugating Enzyme), UBQ (Ubiquitin), UPL (Ubiquitin Protein Ligase), PP2A (Protein Phosphatase 2A), PP2C (Protein Phosphatase 2C), MBF1A (Multiprotein Bridging Factor 1A), and GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)-were selected. Their expression stability was assessed across various tissues and developmental stages of 'Doulv' flowers using qRT-PCR, with evaluations conducted via GeNorm_v3.5, NormFinder_v20, and BestKeeper_v1.0. Gene cloning and expression analyses of PsCUC3, including its subcellular localization, were performed. (3) Results: GAPDH and ACT were identified as the most stable reference genes in petaloid stamens across various developmental stages of 'Doulv', whereas UBC and MBF1A were optimal across different tissues. Notably, specific conserved amino acids in PsCUC3 from 'Doulv' diverged from those in NAM/CUC3 proteins of other species, impacting its protein structure. PsCUC3 expression analysis revealed no correlation with chlorophyll content in petaloid stamens but an association with petaloid organ development. Furthermore, PsCUC3 was predominantly localized in the nucleus. (4) Conclusions: This study comprehensively evaluated suitable reference genes using GeNorm_v3.5, NormFinder_v20, and BestKeeper_v1.0 software, establishing a robust qRT-PCR detection system for 'Doulv' peony. These results provide a solid experimental foundation for further research on 'Doulv' peony. Building on this experimental foundation, the functional analysis of the PsCUC3 gene was conducted. The findings suggest a potential association between the PsCUC3 gene and floral morphology alterations in 'Doulv', identifying PsCUC3 as crucial for understanding the molecular mechanisms influencing floral structure in tree peonies.

Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity.

Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.

Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

The important role of EPS in mediated biosynthesis of CdS QDs: Comparative study of EPS-intact and EPS-free.

In this study, we investigated the adsorption of Cd(II) and the biosynthesis of CdS quantum dots (QDs) mediated by cells of sulfate-reducing bacteria before and after the removal of EPS to determine whether EPS or the cell wall plays a major role. Potentiometric titration revealed that the concentration of proton-active binding sites on cells with EPS (EPS-intact) was notably higher than that on cells without EPS (EPS-free) and that the sites were predominantly carboxyl, phosphoryl, hydroxyl, and amine groups. The protein content in EPS-intact cells was higher, and thus the Cd(II) adsorption capacity was stronger. The CdS QDs biosynthesized using EPS-intact possessed better properties, including uniform size distribution, good crystallinity, small particle size, high fluorescence, and strong antimicrobial activity, and the yields were significantly higher than those of EPS-free by a factor of about 1.5-3.7. Further studies revealed that alkaline amino acids in EPS play a major role and serve as templates in the biosynthesis of QDs, whereas they were rarely detected in the cell wall. This study emphasizes the important role of EPS in the bacterial binding of metals and efficient recycling of hazardous waste in water.

Integrating spatial and single-cell transcriptomics reveals tumor heterogeneity and intercellular networks in colorectal cancer.

Single cell RNA sequencing (scRNA-seq), a powerful tool for studying the tumor microenvironment (TME), does not preserve/provide spatial information on tissue morphology and cellular interactions. To understand the crosstalk between diverse cellular components in proximity in the TME, we performed scRNA-seq coupled with spatial transcriptomic (ST) assay to profile 41,700 cells from three colorectal cancer (CRC) tumor-normal-blood pairs. Standalone scRNA-seq analyses revealed eight major cell populations, including B cells, T cells, Monocytes, NK cells, Epithelial cells, Fibroblasts, Mast cells, Endothelial cells. After the identification of malignant cells from epithelial cells, we observed seven subtypes of malignant cells that reflect heterogeneous status in tumor, including tumor_CAV1, tumor_ATF3_JUN | FOS, tumor_ZEB2, tumor_VIM, tumor_WSB1, tumor_LXN, and tumor_PGM1. By transferring the cellular annotations obtained by scRNA-seq to ST spots, we annotated four regions in a cryosection from CRC patients, including tumor, stroma, immune infiltration, and colon epithelium regions. Furthermore, we observed intensive intercellular interactions between stroma and tumor regions which were extremely proximal in the cryosection. In particular, one pair of ligands and receptors (C5AR1 and RPS19) was inferred to play key roles in the crosstalk of stroma and tumor regions. For the tumor region, a typical feature of TMSB4X-high expression was identified, which could be a potential marker of CRC. The stroma region was found to be characterized by VIM-high expression, suggesting it fostered a stromal niche in the TME. Collectively, single cell and spatial analysis in our study reveal the tumor heterogeneity and molecular interactions in CRC TME, which provides insights into the mechanisms underlying CRC progression and may contribute to the development of anticancer therapies targeting on non-tumor components, such as the extracellular matrix (ECM) in CRC. The typical genes we identified may facilitate to new molecular subtypes of CRC.

Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy.

Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8+ T cells (TCM) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8+ T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8+ T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44hiCD62L+CD8+ TCM cells. Enhancement of CD8+ TCM cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8+ T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8+ T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8+ TCM cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.

The effect of friction stir processing on mechanical, wear and corrosion characteristics of Cu-AlN-BN surface composite.

This research investigates the impact of hybrid particles dispersed onto the surface of a copper matrix using Friction Stir Processing (FSP) on its microstructural, mechanical, and corrosion behavior. The hybrid particles under study consist of equal fractions of Aluminium Nitride (AlN) and Boron Nitride (BN). Microstructural characterization confirms breakdown of grain size due to dynamic recrystallization and presence of particles, along with their effective bonding to copper matrix. Attained results indicated a significant enhancement in hardness, with an increase of up to 3.9 % upon the introduction of particles onto the surface. Moreover, the tensile properties exhibit noticeable improvements in terms of ultimate tensile strength (6.39 %) and yield strength (6.12 %), albeit at the expense of reduced ductility in the copper matrix. Furthermore, the wear rate (decreases up to 22 %) and corrosion rate of the developed composites demonstrate a decreasing trend with the introduction of particles. This improvement can be attributed to the reduction in grain size during the FSP process and the formation of a nitride passive layer facilitated by the reinforced hybrid particles, thereby effectively inhibiting the corrosion rate.

B Cells and IL-21-Producing Follicular Helper T Cells Cooperate to Determine the Dynamic Alterations of Premetastatic Tumor Draining Lymph Nodes of Breast Cancer.

Metastasis is the major cause of cancer-related death, and lymph node is the most common site of metastasis in breast cancer. However, the alterations that happen in tumor-draining lymph nodes (TDLNs) to form a premetastatic microenvironment are largely unknown. Here, we first report the dynamic changes in size and immune status of TDLNs before metastasis in breast cancer. With the progression of tumor, the TDLN is first enlarged and immune-activated at early stage that contains specific antitumor immunity against metastasis. The TDLN is then contracted and immunosuppressed at late stage before finally getting metastasized. Mechanistically, B and follicular helper T (Tfh) cells parallelly expand and contract to determine the size of TDLN. The activation status and specific antitumor immunity of CD8+ T cells in the TDLN are determined by interleukin-21 (IL-21) produced by Tfh cells, thus showing parallel changes. The turn from activated enlargement to suppressed contraction is due to the spontaneous contraction of germinal centers mediated by follicular regulatory T cells. On the basis of the B-Tfh-IL-21-CD8+ T cell axis, we prove that targeting the axis could activate TDLNs to resist metastasis. Together, our findings identify the dynamic alterations and regulatory mechanisms of premetastatic TDLNs of breast cancer and provide new strategies to inhibit lymph node metastasis.

Photosynthetic capacity and assimilate transport of the lower canopy influence maize yield under high planting density.

Photosynthesis is a major trait of interest for the development of high-yield crop plants. However, little is known about the effects of high-density planting on photosynthetic responses at the whole-canopy level. Using the high-yielding maize (Zea mays L.) cultivars "LY66," "MC670," and "JK968," we conducted a 2-yr field experiment to assess ear development in addition to leaf characteristics and photosynthetic parameters in each canopy layer at 4 planting densities. Increased planting density promoted high grain yield and population-scale biomass accumulation despite reduced per-plant productivity. MC670 had the strongest adaptability to high-density planting conditions. A physiological analysis showed that increased planting density primarily led to decreases in the single-leaf area above the ear for LY66 and MC670 and below the ear for JK968. Furthermore, high planting density decreased chlorophyll content and the photosynthetic rate due to decreased canopy transmission, leading to severe decreases in single-plant biomass accumulation in the lower canopy. Moreover, increased planting density improved presilking biomass transfer, especially in the lower canopy. The yield showed significant positive relationships with photosynthesis and biomass in the lower canopy, demonstrating the important contributions of these leaves to grain yield under dense planting conditions. Increased planting density led to retarded ear development as a consequence of reduced glucose and fructose contents in the ears, indicating reductions in sugar transport that were associated with limited sink organ development, reduced kernel number, and yield loss. Overall, these findings highlighted the photosynthetic capacities of the lower canopy as promising targets for improving maize yield under dense planting conditions.

The chloroplast singlet oxygen-triggered biosynthesis of salicylic acid and jasmonic acid is mediated by EX1 and GUN1 in Arabidopsis.

Reactive oxygen species (ROS) and defence hormones like salicylic acid (SA) and jasmonic acid (JA) play pivotal roles in triggering cell death. However, the precise mechanism governing the interaction between ROS and SA/JA remains elusive. Recently, our research revealed that RNAi mutants with suppressed expression of PROGRAMMED CELL DEATH8 (PCD8) exhibit an overabundance of tetrapyrrole intermediates, particularly uroporphyrinogen III (Uro III), leading to the accumulation of singlet oxygen (1O2) during the transition from darkness to light, thereby instigating leaf necrosis. In this investigation, we uncovered that 1O2 stimulates biosynthesis of SA and JA, activating SA/JA signalling and the expression of responsive genes in PCD8 RNAi (pcd8) mutants. Introducing NahG or knocking out PAD4 or NPR1 significantly alleviates the cell death phenotype of pcd8 mutants, while coi1 partially mitigates the pcd8 phenotype. Further exploration revealed that EX1 and GUN1 can partially rescue the pcd8 phenotype by reducing the levels of Uro III and 1O2. Notably, mutations in EX1 mutations but not GUN1, substantially diminish SA content in pcd8 mutants compared to the wild type, implying that EX1 acts as the primary mediator of 1O2 signalling-mediated SA biosynthesis. Moreover, the triple ex1 gun1 pcd8 displays a phenotype similar to ex1. Overall, our findings underscore that the 1O2-induced cell death phenotype requires EX1/GUN1-mediated retrograde signalling in pcd8 mutants, providing novel insights into the interplay between ROS and SA/JA.

Solvent-tuned perovskite heterostructures enable visual linoleic acid assay and edible oil species discrimination via wavelength shift.

Linoleic acid (LA) detection and edible oils discrimination are essential for food safety. Recently, CsPbBr3@SiO2 heterostructures have been widely applied in edible oil assays, while deep insights into solvent effects on their structure and performance are often overlooked. Based on the suitable polarity and viscosity of cyclohexane, we prepared CsPbBr3@SiO2 Janus nanoparticles (JNPs) with high stability in edible oil and fast halogen-exchange (FHE) efficiency with oleylammonium iodide (OLAI). LA is selectively oxidized by lipoxidase to yield hydroxylated derivative (oxLA) capable of reacting with OLAI, thereby bridging LA content to naked-eye fluorescence color changes through the anti-FHE reaction. The established method for LA in edible oils exhibited consistent results with GC-MS analysis (p > 0.05). Since the LA content difference between edible oils, we further utilized chemometrics to accurately distinguish (100%) the species of edible oils. Overall, such elaborated CsPbBr3@SiO2 JNPs enable a refreshing strategy for edible oil discrimination.

Recent Advances in Broadband Photodetectors from Infrared to Terahertz.

The growing need for the multiband photodetection of a single scene has promoted the development of both multispectral coupling and broadband detection technologies. Photodetectors operating across the infrared (IR) to terahertz (THz) regions have many applications such as in optical communications, sensing imaging, material identification, and biomedical detection. In this review, we present a comprehensive overview of the latest advances in broadband photodetectors operating in the infrared to terahertz range, highlighting their classification, operating principles, and performance characteristics. We discuss the challenges faced in achieving broadband detection and summarize various strategies employed to extend the spectral response of photodetectors. Lastly, we conclude by outlining future research directions in the field of broadband photodetection, including the utilization of novel materials, artificial microstructure, and integration schemes to overcome current limitations. These innovative methodologies have the potential to achieve high-performance, ultra-broadband photodetectors.

Alpha neurofeedback training improves visual working memory in healthy individuals.

Neurofeedback (NF) training is a closed-loop brain training in which participants learn to regulate their neural activation. NF training of alpha (8-12 Hz) activity has been reported to enhance working memory capacity, but whether it affects the precision in working memory has not yet been explored. Moreover, whether NF training distinctively influences performance in different types of working memory tasks remains unclear. Therefore, the present study conducted a randomized, single-blind, sham-controlled experiment to investigate how alpha NF training affected the capacity and precision of working memory, as well as the related neural change. Forty participants were randomly and equally assigned to the NF group and the sham control group. Both groups received NF training (about 30 min daily) for five consecutive days. The NF group received alpha (8-12 Hz) training, while the sham control group received sham NF training. We found a significant alpha increase within sessions but no significant difference across sessions. However, the behavioral performance and neural activity in the modified Sternberg task did not show significant change after alpha NF training. On the contrary, the alpha NF training group significantly increased visual working memory capacity measured by the Corsi-block tapping task and improved visual working memory precision in the interference condition in a color-recall task. These results suggest that alpha NF training influences performance in working memory tasks involved in the visuospatial sketchpad. Notably, we demonstrated that alpha NF training improves the quantity and quality of visual working memory.