Compatible multilayer magnetic field system for quantum sensing with atoms.

Magnetic fields provide a valuable method to manipulate atomic energy levels and interactions in quantum precision measurements, but achieving precise measurements requires collaboration between the magnetic field system and the optical detection system. We propose a magnetic field system that incorporates a fast-switching magnetic field and an alternating magnetic field. Specifically, we enhance the switching speed by making structural improvements during the switching operation. An independent control approach is employed to reduce the switching time caused by electromagnetic induction across the coil using multilayer coils. The results demonstrate an inverse correlation between the rise and fall times of the magnetic field switch and the number of independently stacked coil layers, indicating the possibility of achieving further improvements in switching speed through structural enhancements. The system developed here has considerable potential for application to diverse quantum systems.

Near-Infrared Light-Triggered NO Nanogenerator for Gas-Enhanced Photodynamic Therapy and Low-Temperature Photothermal Therapy to Eliminate Biofilms.

Purpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.

Anticancer activity of 8-hydroxyquinoline-triphenylphosphine rhodium(III) complexes targeting mitophagy pathways.

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1-H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a-YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 µM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a-YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.

Construction of Cs2AgBiCl6/COF Heterojunction for Boosted Photocatalytic Thioester Oxidation.

Lead-free halide perovskites as a new kind of potential candidate for photocatalytic organic synthesis have attracted much attention recently. The rational heterojunction construction is regarded as an efficient strategy to delicately regulate their catalytic performances. Herein, a semi-conductive covalent organic framework (COF) nanosheet, C4N, is employed as the functional component to construct Cs2AgBiCl6/C4N (CABC/C4N) heterojunction. It is found that the C4N nanosheets with rich surface functional groups can serve as heterogeneous nucleation sites to manipulate the growth of CABC nanocrystals and afford close contact between each other, therefore facilitate the transfer and spatial separation of photogenerated charge carriers, as verified by in situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy. Moreover, the oxygen affinity of C4N endows the heterojunctions with outstanding aerobic reactivity, thus improving the photocatalytic performance largely. The optimal CABC/C4N heterojunction delivers a thioanisole conversion efficiency of 100% after 6 h, which is 2.2 and 7.7-fold of that of CABC and C4N. This work provides a new ideal for the design and application of lead-free perovskite heterojunction photocatalysts for organic reactions.

Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid.

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench.

BACKGROUND: The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. RESULTS: In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50-9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. CONCLUSIONS: Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract.

Robust cooperative of cadmium sulfide with highly ordered hollow microstructure coordination polymers for regulating the photocatalytic performance.

Accurately controlling and achieving selective reactivity at difficult-to-access reaction sites in organic molecules is challenging owing to the similar local and electronic environments of multiple reaction sites. In this work, we regulated multiple reaction sites in a highly selective and active manner using cobalt coordination polymers (Co-CP) 1 and 1a with various particle sizes and morphologies ranging from large granular to ordered hollow hemispheres by introducing sodium dodecyl sulfate (SDS) as a surfactant. The size and morphology of the catalysts could be tuned by controlling the amount of SDS. An SDS concentration of 0.03 mmol generated 1a having a highly ordered hollow hemispherical microstructure with a well-defined platform as a pre-made building unit. Cadmium sulfide (CdS), as a typical photocatalyst, was subsequently uniformly anchored in-situ on the premade building unit 1a to produce CdS@1a composites, that inherited the originally ordered hollow hemispherical microstructure while integrating CdS as well-dispersed catalytic active sites. Furthermore, the well-established CdS@1a composites were used as photocatalysts in selective oxidation reactions under air atmosphere with blue irradiation. The CdS0.109@1a composite with unique structural characteristics, including uniformly distributed and easily accessible catalytic sites and excellent photoelectrochemical performance, served as a highly efficient heterogeneous photocatalyst for promoting the selective oxidation of sulfides to sulfoxides as the sole products. This work presents an approach for fabricating CPs as premade building units that function as well-defined platforms for integration with photocatalysts, enabling tuning of the structure-selectivity-activity relationships.

Drug-Loaded Tumor-Derived Microparticles Elicit CD8+ T Cell-Mediated Anti-Tumor Response in Hepatocellular Carcinoma.

Background: Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment. Methods: Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities. Results: Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine. Conclusion: Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine.

Prediction of positive pulmonary nodules based on machine learning algorithm combined with central carbon metabolism data.

BACKGROUND: Lung cancer causes a huge disease burden, and early detection of positive pulmonary nodules (PPNs) as an early sign of lung cancer is extremely important for effective intervention. It is necessary to develop PPNs risk recognizer based on machine learning algorithm combined with central carbon metabolomics. METHODS: The study included 2248 participants at high risk for lung cancer from the Ma'anshan Community Lung Cancer Screening cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to screen 18 central carbon-related metabolites in plasma, recursive feature elimination (RFE) was used to select all 42 features, followed by five machine learning algorithms for model development. The performance of the model was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, precision, recall, and F1 scores. In addition, SHapley Additive exPlanations (SHAP) was performed to assess the interpretability of the final selected model and to gain insight into the impact of features on the predicted results. RESULTS: Finally, the two prediction models based on the random forest (RF) algorithm performed best, with AUC values of 0.87 and 0.83, respectively, better than other models. We found that homogentisic acid, fumaric acid, maleic acid, hippuric acid, gluconic acid, and succinic acid played a significant role in both PPNs prediction model and NPNs vs PPNs model, while 2-oxadipic acid only played a role in the former model and phosphopyruvate only played a role in the NPNs vs PPNs model. This model demonstrates the potential of central carbon metabolism for PPNs risk prediction and identification. CONCLUSION: We developed a series of predictive models for PPNs, which can help in the early detection of PPNs and thus reduce the risk of lung cancer.

Circ_0023990 Promotes the Proliferation, Invasion, and Glycolysis of Esophageal Squamous Cell Carcinoma Cells Via Targeting miR-6884-5p/PAK1 Axis.

Circular RNAs are emerging players in human cancers, including esophageal squamous cell carcinoma (ESCC). Herein, we assessed the expression level of circ_0023990 and explored the molecular mechanisms of circ_0023990 in ESCC. circ_0023990, miR-6884-5p, and PAK1 expressions in ESCC tissues and cells were detected by quantitative real-time polymerase chain reaction and western blot. ESCC cells were transfected with different constructs to alter the expression of circ_0023990, miR-6884-5p, and PAK1. The effect of circ_0023990 on the proliferation, invasion, and glycolysis of ESCC cells was observed. The interaction between circ_0023990 and miR-6884-5p and between miR-6884-5p and PAK1 were explored. A mouse model of ESCC was established to study the in vivo effect of circ_0023990 knockdown on tumor formation.The expression levels of circ_0023990 was upregulated in ESCC tissues and cells. Inhibiting circ_0023990 suppressed the proliferation, invasion, and glycolysis of ESCC cells. circ_0023990 might target miR-6884-5p and consequently modulate the expression and activity of PAK1. Knockdown of circ_0023990 led to significantly reduced tumor volume and weight in mice with ESCC.These findings overall suggest an oncogenic role of circ_0023990 in ESCC. Future research is warranted to confirm the expression pattern and clinical significance of circ_0023990 in ESCC.

Synthesis and anticancer mechanisms of four novel platinum(II) 4'-substituted-2,2':6',2''-terpyridine complexes.

Mitophagy, a selective autophagic process, has emerged as a pathway involved in degrading dysfunctional mitochondria. Herein, new platinum(II)-based chemotherapeutics with mitophagy-targeting properties are proposed. Four novel binuclear anticancer Pt(II) complexes with 4'-substituted-2,2':6',2''-terpyridine derivatives (tpy1-tpy4), i.e., [Pt2(tpy1)(DMSO)2Cl4]·CH3OH (tpy1Pt), [Pt(tpy2)Cl][Pt(DMSO)Cl3]·CH3COCH3 (tpy2Pt), [Pt(tpy3)Cl][Pt(DMSO)Cl3] (tpy3Pt), and [Pt(tpy4)Cl]Cl·CH3OH (tpy4Pt), were designed and prepared. Moreover, their potential antitumor mechanism was studied. Tpy1Pt-tpy4Pt exhibited more selective cytotoxicity against cisplatin-resistant SK-OV-3/DDP (SKO3cisR) cancer cells compared with those against ovarian SK-OV-3 (SKO3) cancer cells and normal HL-7702 liver (H702) cells. This selective cytotoxicity of Tpy1Pt-tpy4Pt was better than that of its ligands (i.e., tpy1-tpy4), the clinical drug cisplatin, and cis-Pt(DMSO)2Cl2. The results of various experiments indicated that tpy1Pt and tpy2Pt kill SKO3cisR cancer cells via a mitophagy pathway, which involves the disruption of the mitophagy-related protein expression, dissipation of the mitochondrial membrane potential, elevation of the [Ca2+] and reactive oxygen species levels, promotion of mitochondrial DNA damage, and reduction in the adenosine triphosphate and mitochondrial respiratory chain levels. Furthermore, in vivo experiments indicated that the dinuclear anticancer Pt(II) coordination compound (tpy1Pt) has remarkable therapeutic efficiency (ca. 52.4%) and almost no toxicity. Therefore, the new 4'-substituted-2,2':6',2''-terpyridine Pt(II) coordination compound (tpy1Pt) is a potential candidate for next-generation mitophagy-targeting dinuclear Pt(II)-based anticancer drugs.

The catabolic specialization of the marine bacterium Polaribacter sp. Q13 to red algal ß1,3/1,4-mixed-linkage xylan.

Catabolism of algal polysaccharides by marine bacteria is a significant process of marine carbon cycling. ß1,3/1,4-Mixed-linkage xylan (MLX) is a class of xylan in the ocean, widely present in the cell walls of red algae. However, the catabolic mechanism of MLX by marine bacteria remains elusive. Recently, we found that a marine Bacteroidetes strain, Polaribacter sp. Q13, is a specialist in degrading MLX, which secretes a novel MLX-specific xylanase. Here, the catabolic specialization of strain Q13 to MLX was studied by multiomics and biochemical analyses. Strain Q13 catabolizes MLX with a canonical starch utilization system (Sus), which is encoded by a single xylan utilization locus, XUL-Q13. In this system, the cell surface glycan-binding protein SGBP-B captures MLX specifically, contributing to the catabolic specificity. The xylanolytic enzyme system of strain Q13 is unique, and the enzymatic cascade dedicates the stepwise hydrolysis of the ß1,3- and ß1,4-linkages in MLX in the extracellular, periplasmic, and cytoplasmic spaces. Bioinformatics analysis and growth observation suggest that other marine Bacteroidetes strains harboring homologous MLX utilization loci also preferentially utilize MLX. These results reveal the catabolic specialization of MLX degradation by marine Bacteroidetes, leading to a better understanding of the degradation and recycling of MLX driven by marine bacteria.IMPORTANCERed algae contribute substantially to the primary production in marine ecosystems. The catabolism of red algal polysaccharides by marine bacteria is important for marine carbon cycling. Mixed-linkage ß1,3/1,4-xylan (MLX, distinct from hetero-ß1,4-xylans from terrestrial plants) is an abundant red algal polysaccharide, whose mechanism of catabolism by marine bacteria, however, remains largely unknown. This study reveals the catabolism of MLX by marine Bacteroidetes, promoting our understanding of the degradation and utilization of algal polysaccharides by marine bacteria. This study also sets a foundation for the biomass conversion of MLX.

Metagenomic insights into the dynamic degradation of brown algal polysaccharides by kelp-associated microbiota.

Marine bacteria play important roles in the degradation and cycling of algal polysaccharides. However, the dynamics of epiphytic bacterial communities and their roles in algal polysaccharide degradation during kelp decay are still unclear. Here, we performed metagenomic analyses to investigate the identities and predicted metabolic abilities of epiphytic bacterial communities during the early and late decay stages of the kelp Saccharina japonica. During kelp decay, the dominant epiphytic bacterial communities shifted from Gammaproteobacteria to Verrucomicrobia and Bacteroidetes. In the early decay stage of S. japonica, epiphytic bacteria primarily targeted kelp-derived labile alginate for degradation, among which the gammaproteobacterial Vibrionaceae (particularly Vibrio) and Psychromonadaceae (particularly Psychromonas), abundant in alginate lyases belonging to the polysaccharide lyase (PL) families PL6, PL7, and PL17, were key alginate degraders. More complex fucoidan was preferred to be degraded in the late decay stage of S. japonica by epiphytic bacteria, predominantly from Verrucomicrobia (particularly Lentimonas), Pirellulaceae of Planctomycetes (particularly Rhodopirellula), Pontiellaceae of Kiritimatiellota, and Flavobacteriaceae of Bacteroidetes, which depended on using glycoside hydrolases (GHs) from the GH29, GH95, and GH141 families and sulfatases from the S1_15, S1_16, S1_17, and S1_25 families to depolymerize fucoidan. The pathways for algal polysaccharide degradation in dominant epiphytic bacterial groups were reconstructed based on analyses of metagenome-assembled genomes. This study sheds light on the roles of different epiphytic bacteria in the degradation of brown algal polysaccharides.IMPORTANCEKelps are important primary producers in coastal marine ecosystems. Polysaccharides, as major components of brown algal biomass, constitute a large fraction of organic carbon in the ocean. However, knowledge of the identities and pathways of epiphytic bacteria involved in the degradation process of brown algal polysaccharides during kelp decay is still elusive. Here, based on metagenomic analyses, the succession of epiphytic bacterial communities and their metabolic potential were investigated during the early and late decay stages of Saccharina japonica. Our study revealed a transition in algal polysaccharide-degrading bacteria during kelp decay, shifting from alginate-degrading Gammaproteobacteria to fucoidan-degrading Verrucomicrobia, Planctomycetes, Kiritimatiellota, and Bacteroidetes. A model for the dynamic degradation of algal cell wall polysaccharides, a complex organic carbon, by epiphytic microbiota during kelp decay was proposed. This study deepens our understanding of the role of epiphytic bacteria in marine algal carbon cycling as well as pathogen control in algal culture.

Lipid metabolism and oxidative stress in patients with Alzheimer's disease and amnestic mild cognitive impairment.

Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non-targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC-MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)-CH3, and PE (20:0_20:4)-H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high-performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (p = 0.003), whereas plasma SOD levels were lower in the AD (p < 0.001) and aMCI (p = 0.045) groups than in NC, and GSH-Px activity were higher in the AD group than in the aMCI group (p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.

Dual-specificity phosphatase 1 inhibits Singapore grouper iridovirus replication via regulating apoptosis in Epinephelus coioides.

The dual-specificity phosphatase (DUSP) family plays key roles in the maintenance of cellular homeostasis and apoptosis etc. In this study, the DUSP member DUSP1 of Epinephelus coioides was characterized: the length was 2371 bp including 281 bp 5' UTR, 911 bp 3' UTR, and a 1125 bp open reading frame encoding 374 amino acids. E. coioides DUSP1 has two conserved domains, a ROHD and DSPc along with a p38 MAPK phosphorylation site, localized at Ser308. E. coioides DUSP1 mRNA can be detected in all of the tissues examined, and the subcellular localization showed that DUSP1 was mainly distributed in the nucleus. Singapore grouper iridovirus (SGIV) infection could induce the differential expression of E. coioides DUSP1. Overexpression of DUSP1 could inhibit SGIV-induced cytopathic effect (CPE), the expressions of SGIV key genes, and the viral titers. Overexpression of DUSP1 could also regulate SGIV-induced apoptosis, and the expression of apoptosis-related factor caspase 3. The results would be helpful to further study the role of DUSP1 in viral infection.

8-hydroxyquinoline-N-oxide copper(II)- and zinc(II)-phenanthroline and bipyridine coordination compounds: Design, synthesis, structures, and antitumor evaluation.

Fourteen novel tumor-targeting copper(II) and zinc(II) complexes, [Cu(ONQ)(QD1)(NO3)]·CH3OH (NQ3), [Cu(ONQ)(QD2)(NO3)] (NQ2), [Cu(NQ)(QD2)Cl] (NQ3), [Cu(ONQ)(QD1)Cl] (NQ4), [Cu(ONQ)(QD3)](NO3) (NQ5), [Cu(ONQ)(QD3)Cl] (NQ6), [Zn(ONQ)(QD4)Cl] (NQ7), [Zn(ONQ)(QD1)Cl] (NQ8), [Zn(ONQ)(QD5)Cl] (NQ9), [Zn(ONQ)(QD2)Cl] (NQ10), [Zn(ONQ)(QD6)Cl] (NQ11), [Zn(ONQ)(QD7)Cl] (NQ12), and [Zn(ONQ)(QD3)Cl] (NQ13) supported on 8-hydroxyquinoline-N-oxide (H-ONQ), 2,2'-dipyridyl (QD1), 5,5'-dimethyl-2,2'-bipyridyl (QD2), 1,10-phenanthroline (QD3), 4,4'-dimethoxy-2,2'-bipyridyl (QD4), 4,4'-dimethyl-2,2'-bipyridyl (QD5), 5-chloro-1,10-phenanthroline (QD6), and bathophenanthroline (QD7), were first synthesized and characterized using various spectroscopic techniques. Furthermore, NQ1-NQ13 exhibited higher antiproliferative activity and selectivity for cisplatin-resistant SK-OV-3/DDP tumor cells (CiSK3) compared to normal HL-7702 cells based on results obtained from the cell counting Kit-8 (CCK-8) assay. The complexation of copper(II) ion with QD2 and ONQ ligands resulted in an evident increase in the antiproliferation of NQ1-NQ6, with NQ6 exhibiting the highest antitumor potency against CiSK3 cells compared to NQ1-NQ5, H-ONQ, QD1-QD7, and NQ7-NQ13 as well as the reference cisplatin drug with an IC50 value of 0.17 ± 0.05 µM. Mechanistic studies revealed that NQ4 and NQ6 induced apoptosis of CiSK3 cells via mitophagy pathway regulation and adenosine triphosphate (ATP) depletion. Further, the differential induction of mitophagy decreased in the order of NQ6 > NQ4, which can be attributed to the major impact of the QD3 ligand with a large planar geometry and the Cl leaving group within the NQ6 complex. In summary, these results confirmed that the newly synthesized H-ONQ copper(II) and zinc(II) coordination metal compounds NQ1-NQ13 exhibit potential as anticancer drugs for cisplatin-resistant ovarian CiSK3 cancer treatment.

Which biomarkers predict hard-to-heal diabetic foot ulcers? A scoping review.

Diabetic foot ulcers (DFUs) often develop into hard-to-heal wounds due to complex factors. Several biomarkers capable of identifying those at risk of delayed wound healing have been reported. Controlling or targeting these biomarkers could prevent the progression of DFUs into hard-to-heal wounds. This scoping review aimed to identify the key biomarkers that can predict hard-to-heal DFUs. Studies that reported biomarkers related to hard-to-heal DFUs, from 1980 to 2023, were mapped. Studies were collected from the following databases: MEDLINE, CINAHL, EMBASE, and ICHUSHI (Japana Centra Revuo Medicina), search terms included "diabetic," "ulcer," "non-healing," and "biomarker." A total of 808 articles were mapped, and 14 (10 human and 4 animal studies) were included in this review. The ulcer characteristics in the clinical studies varied. Most studies focused on either infected wounds or neuropathic wounds, and patients with ischemia were usually excluded. Among the reported biomarkers for the prediction of hard-to-heal DFUs, the pro-inflammatory cytokine CXCL-6 in wound fluid from non-infected and non-ischemic wounds had the highest prediction accuracy (area under the curve: 0.965; sensitivity: 87.27%; specificity: 95.56%). CXCL-6 levels could be a useful predictive biomarker for hard-to-heal DFUs. However, CXCL6, a chemoattractant for neutrophilic granulocytes, elicits its chemotactic effects by combining with the chemokine receptors CXCR1 and CXCR2, and is involved in several diseases. Therefore, it's difficult to use CXCL6 as a prevention or treatment target. Targetable specific biomarkers for hard-to-heal DFUs need to be determined.

Targeted metabolomics reveals the association between central carbon metabolism and pulmonary nodules.

With the widespread application of low-dose computed tomography (LDCT) technology, pulmonary nodules have aroused more attention. Significant alteration in plasma metabolite levels, mainly amino acid and lipid, have been observed in patients of PNs. However, evidence on the association between central carbon metabolism and PNs are largely unknown. The aim of this study was to investigate the underlying association of PNs and plasma central carbon metabolites. We measured the levels of 16 plasma central carbon metabolites in 1954 participants who gained LDCT screening in MALSC cohort. The inverse probability weighting (IPW) technique was used to control for bias due to self-selection for LDCT in the assessed high-risk population. The least absolute shrinkage and selection operator (LASSO) penalized regression was used to deal with the problem of multicollinearity among metabolites and the combined association of central carbon metabolites with PNs was estimated by using quantile g-computation (QgC) models. A quartile increase in 3-hydroxybutyric acid, gluconic acid, succinic acid and hippuric acid was positively associated with the PNs risk, whereas a quartile increase in 2-oxadipic acid and fumaric acid was negatively associated with the risk of PNs in multiple-metabolite models. A positive but insignificant joint associations of the mixture of 16 metabolites with PNs was observed by using QgC models analyses. Further studies are warranted to clarify the association between circulating metabolites and PNs and the biological mechanisms.

Dynamic prefrontal inhibition code mediates reward devaluation.

Repeated reward intake decreases its subjective pleasantness, which is a common phenomenon called reward devaluation. In this issue of Neuron, Yuan et al.1 unravel that blunted inhibitory response of anterior cingulate cortex (ACC) encodes this process, whose hypersensitization leads to anhedonia.

Integrative Metabolomics and Whole Transcriptome Sequencing Reveal Role for TREM2 in Metabolism Homeostasis in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide. Dysregulation of various metabolism pathways may mediate the development of AD pathology and cognitive dysfunction. Variants of triggering receptor expressed on myeloid cells-2 (TREM2) are known to increase the risk of developing AD. TREM2 plays a role in AD development by maintaining cellular energy and biosynthesis, but the precise mechanism through which it accomplishes this is unknown. Metabolomic analysis of hippocampal tissue from APP/PS1 and APP/PS1-TREM2 knockout (KO) mice found that TREM2 KO was associated with abnormalities in several metabolism pathways, and the effect was particularly pronounced in lipid metabolism and glucose metabolism pathways. Consistently, transcriptomic analysis of these mice determined that most differentially expressed genes were involved in energy metabolism pathways. We screened seven differentially expressed genes in APP/PS1-TREM2 KO mice that may influence AD development by altering energy metabolism. Integrative analysis of the metabolomic and transcriptomic profiles showed that TREM2 may regulate lipid metabolism and sphingolipid metabolism by affecting lipoprotein lipase (LPL) expression, thereby influencing AD progression. Our results prompt further studies of the interactions among TREM2, LPL, glucolipid metabolism, and sphingolipid metabolism in AD to identify new diagnostic and treatment strategies.