Serum Metabolomics Analysis Revealed Metabolic Pathways Related to AECOPD Complicated with Anxiety and Depression.

Background: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis. Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways. Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long-term depression, retrograde endocannabinoid signaling, and so on. Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression.

Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.

BACKGROUND: The dynamics of mitochondrial respiratory cristae (MRC) and its impact on oxidative phosphorylation (OXPHOS) play a crucial role in driving the progression of high-grade glioma (HGG). However, the underlying mechanism remains unclear. METHODS: In the present study, we employed machine learning-based transmission electron microscopy analysis of 7141 mitochondria from 54 resected glioma patients. Additionally, we conducted bioinformatics analysis and multiplex immunohistochemical (mIHC) staining of clinical glioma microarrays to identify key molecules involved in glioma. Subsequently, we modulated the expression levels of mitochondrial dynamic-1-like protein (DNM1L/DRP1), and its two receptors, mitochondrial fission protein 1 (FIS1) and mitochondrial fission factor (MFF), via lentiviral transfection to further investigate the central role of these molecules in the dynamics of glioblastoma (GBM) cells and glioma stem cells (GSCs). We then evaluated the potential impact of DNM1L/DRP1, FIS1, and MFF on the proliferation and progression of GBM cells and GSCs using a combination of CCK-8 assay, Transwell assay, Wound Healing assay, tumor spheroid formation assay and cell derived xenograft assay employing NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mouse model. Subsequently, we validated the ability of the DNM1L/DRP1-FIS1 axis to remodel MRC structure through mitophagy by utilizing Seahorse XF analysis technology, mitochondrial function detection, MRC abundance detection and monitoring dynamic changes in mitophagy. RESULTS: Our findings revealed that compared to low-grade glioma (LGG), HGG exhibited more integrated MRC structures. Further research revealed that DNM1L/DRP1, FIS1, and MFF played pivotal roles in governing mitochondrial fission and remodeling MRC in HGG. The subsequent validation demonstrated that DNM1L/DRP1 exerts a positive regulatory effect on FIS1, whereas the interaction between MFF and FIS1 demonstrates a competitive inhibition relationship. The down-regulation of the DNM1L/DRP1-FIS1 axis significantly impaired mitophagy, thereby hindering the remodeling of MRC and inhibiting OXPHOS function in glioma, ultimately leading to the inhibition of its aggressive progression. In contrast, MFF exerts a contrasting effect on MRC integrity, OXPHOS activity, and glioma progression. CONCLUSIONS: This study highlights that the DNM1L/DRP1-FIS1 axis stabilizes MRC structures through mitophagy in HGG cells while driving their OXPHOS activity ultimately leading to robust disease progression. The inhibition of the DNM1L/DRP1-FIS1 axis hinders MRC remodeling and suppresses GBM progression. We propose that down-regulation of the DNM1L/DRP1-FIS1 axis could be a potential therapeutic strategy for treating HGG.

Mechanism of carbonized humic acid and magnesium aluminum-layered double hydroxide promoting biohydrogen generation.

Dark fermentation (DF) is prone to low hydrogen (H2) yield. In this work, magnesium aluminum-layered double hydroxide and carbonized humic acid (MgAl-LDH/CHA) was synthesized by co-precipitation to reveal the mechanism in rising bioH2 generation. The results indicated that MgAl-LDH released Mg and Al ions slowly in DF system, improving the activity of H2-producing microbes (HPM) for more H2. The H2 yield increased from 169.3 mL/g glucose to 244.9 mL/g glucose, which was 44.7 % higher than that for the control yield. MgAl-LDH/CHA increased Proteobacteria content from 30.9 % to 43.7 %, making it form a complex microbial community and participate in DF metabolism with Firmicutes and other microbes together. Besides, MgAl-LDH/CHA could serve as an electron shuttle that likely effectively promotes electron transfer in DF, significantly reduced the energy requirements of HPM, thus raising metabolic activity. It provides direction for the multi-element composite applied in DF system.

Super enhanced purification of denatured-refolded ubiquitinated proteins by ThUBD revealed ubiquitinome dysfunction in liver fibrosis.

Ubiquitination is crucial for maintaining protein homeostasis and plays a vital role in diverse biological processes. Ubiquitinome profiling and quantification are of great scientific significance. Artificial ubiquitin-binding domains (UBDs) have been widely employed to capture ubiquitinated proteins. The success of this enrichment relies on recognizing native spatial structures of ubiquitin and ubiquitin chains by UBDs under native conditions. However, the use of native lysis conditions presents significant challenges, including insufficient protein extraction, heightened activity of deubiquitinating enzymes (DUBs) and proteasomes in removing the ubiquitin signal, and purification of a substantial number of contaminant proteins, all of which undermine the robustness and reproducibility of ubiquitinomics. In this study, we introduced a novel approach that combines denatured-refolded ubiquitinated sample preparation (DRUSP) with a tandem hybrid UBD (ThUBD) for ubiquitinomic analysis. The samples were effectively extracted using strongly denatured buffers and subsequently refolded using filters. DRUSP yielded a significantly stronger ubiquitin signal, nearly 3 times greater than that of the Control method. Then, 8 types of ubiquitin chains were quickly and accurately restored; therefore, they were recognized and enriched by ThUBD with high efficiency and no biases. Compared with the Control method, DRUSP showed extremely high efficiency in enriching ubiquitinated proteins, improving overall ubiquitin signal enrichment by approximately 10-fold. Moreover, when combined with ubiquitin chain-specific UBDs, DRUSP had also been proven to be a versatile approach. This new method significantly enhanced the stability and reproducibility of ubiquitinomics research. Finally, DRUSP was successfully applied to deep ubiquitinome profiling of early mouse liver fibrosis with increased accuracy, revealing novel insights for liver fibrosis research.

Evolutionary game analysis of multi-agent cooperation strategy analysis in agricultural water conservancy PPP project under digitization background.

This study constructed a system dynamics (SD) evolutionary game model, from which we analyzed the conditions that need to be met by multi-agents to achieve cooperation in agricultural water conservancy (AWC) Public-Private Partnership (PPP) projects. Simultaneously, this study used numerical simulation to depict the impact of initial participation willingness, reward, punishment, income, and other parameters of local governments, project enterprises, and farmers on the evolution strategy. The results firstly showed that the basic conditions for tripartite cooperation are to strengthen the rewards and punishments for project enterprises and improve the participation benefits of farmers. Secondly, it showed that increasing the rewards for farmers and improving the project dividend benefits can effectively motivate farmers to participate. Thirdly, it showed that enhancing the incentive subsidies and reputation benefits for project enterprise's participation, as well as strengthening the supervision of local government, boosts the motivation of project enterprises significantly. However, it is vital to ensure that the reward amounts are not too high to allow local government to play its guiding role efficiently. Lastly, the results indicated that digital technology can help reduce the participation cost of local government, project enterprises and farmers, and improve the external reputation benefits of each participant, thus forming a win-win situation for all three participants. Analyzing the cooperation strategies of the three parties in AWC PPP projects provides theoretical support and a decision-making basis for the efficient operation of AWC PPP projects under the digital background, and also provides practical policy recommendations for the high-quality development of AWC.

Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection.

IL-1ß represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1ß in the process of ferroptosis. However, the relationship between IL-1ß and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1ß induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1ß is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1ß playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

UFMylation is involved in serum inflammatory cytokines generation and splenic T cell activation induced by lipopolysaccharide.

UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4+ and total CD8+ T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4+CD69+ and CD8+CD69+T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo.

Advances and Challenges in Large-Area Perovskite Light-Emitting Diodes.

Metal halide perovskite light-emitting diodes (PeLEDs) have shown promise for high-definition displays and flat-panel lighting because of their wide color gamut, narrow emission band, and high brightness. The external quantum efficiency of PeLEDs increased rapidly from ≈1% to more than 25% in the past few years. However, most of these high-performance devices are fabricated using a spin coating method with a small device area of <0.1 cm2, limiting their commercial applications. Recently, large-area PeLEDs have attracted growing attention and significant breakthroughs have been reported. This perspective first introduces the pros and cons of each technique in making large-area PeLEDs. The advances in the fabrication of large-area PeLEDs are then summarized using spin coating and mass-production methods such as inkjet printing, blade coating, and thermal evaporation. Moreover, the challenging issues will be discussed that are urgent to be solved for large-area PeLEDs.

Effect of moxibustion on ATP-sensitive potassium channel (KATP) of bladder in detrusor overactivity rats. / 隔姜隔盐灸"神阙"å¯¹é€¼å°¿è‚Œè¿‡åº¦æ´»åŠ¨å¤§é¼ è†€èƒ±ATP敏感性钾离子通道的影响.

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001)；the voiding threshold pressure was significantly decreased (P<0.001)；the bladder perfusion volume was increased (P<0.001)；the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.

Primary cutaneous cribriform tumor: A case report and literature review.

In the updated 5th edition of the WHO Classification of Skin Tumors, primary cutaneous cribriform carcinoma has been renamed cribriform tumor. This entity is a rare sweat gland neoplasm with undetermined malignant potential, with only 46 cases reported to date. Herein, we present a case of a 30-year-old female with a solitary nodule in the left thigh subcutaneous tissue. Histopathological examination revealed a well-defined dermal nodule composed of monomorphic, deeply staining cells arranged in solid nests, tubular, and cribriform patterns, with no recurrence or distant metastasis observed during a 1-year follow-up. Summarizing all 47 cases, they exhibited consistent, reproducible histological morphology and similar immunohistochemistry. Although the tumor nests lacked myoepithelial cells peripherally, all cleanly excised cases showed no recurrence or distant metastasis, suggesting a benign biological behavior. We argue against overtreatment.