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Over the past decade, the number and diversity of identified protein post-translational modifications (PTMs) have grown significantly. However, most PTMs occur at relatively low abundance, making selective enrichment of modified peptides essential. To address this, we developed a thermodynamic model describing the free beads enrichment in suspension enrichment process and derived a theoretical relationship between material dosage and analyte recovery. The model predicts a non-linear trend, with enrichment efficiency increasing up to an optimal dosage and declining thereafter—a pattern confirmed by experimental data. We validated the model using centrifugation-based enrichment for glycosylated peptides and magnetic-based enrichment for phosphorylated peptides. In both cases, the results aligned with theoretical predictions. Additionally, the optimal dosage varied among peptides with the same modification type, highlighting the importance of tailoring enrichment strategies. This study provides a solid theoretical and experimental basis for optimizing PTMs enrichment and advancing more sensitive, accurate, and efficient mass spectrometry-based proteomic workflows.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed unprecedented challenges to public health and economic stability. Central to SARS-CoV-2 pathogenesis is its ability to evade the host immune response by hijacking host pathways via the interaction between viral and host proteins. We identified Ras-GTPase-activating protein SH3 domain-binding protein 1/2 (G3BP1/G3BP2) as a critical host factor that interacts with the viral nucleocapsid (N) protein, emerging from a comparative analysis of proteomic data from multiple studies. We revisited the underlying molecular mechanisms by confirming the residues required for the interaction between G3BP1/G3BP2 and SARS-CoV-2 N protein and showed that this interaction disrupts stress granule formation. Intriguingly, we observed that the ablation of both G3BP1 and G3BP2 enhanced SARS-CoV-2 replication. Our data collectively supports the notion that G3BP1 and G3BP2 play a critical role in modulating the host–virus interface during SARS-CoV-2 infection, and that their multifaceted function in cellular defense extends beyond the stress granule pathway.

Methylerythritol cyclodiphosphate (MEcPP) is an intermediate in the biosynthesis of isoprenoids in plant plastids and in bacteria, and acts as a stress signal in plants. Here, we show that MEcPP regulates biofilm formation in Escherichia coli K-12 MG1655. Increased MEcPP levels, triggered by genetic manipulation or oxidative stress, inhibit biofilm development and production of fimbriae. Deletion of fimE , encoding a protein known to downregulate production of adhesive fimbriae, restores biofilm formation in cells with elevated MEcPP levels. Limited proteolysis-coupled mass spectrometry (LiP-MS) reveals that MEcPP interacts with the global regulatory protein H-NS, which is known to repress transcription of fimE . MEcPP prevents the binding of H-NS to the fimE promoter. Therefore, our results indicate that MEcPP can regulate biofilm formation by modulating H-NS activity and thus reducing fimbriae production. Further research is needed to test whether MEcPP plays similar regulatory roles in other bacteria. Methylerythritol cyclodiphosphate is an intermediate in the biosynthesis of isoprenoids in plants and bacteria, and acts as a stress signal in plants. Here, Guo et al. show that, in addition, the metabolite can inhibit biofilm formation in Escherichia coli by modulating the activity of the DNA-binding protein H-NS, thus downregulating the production of adhesive fimbriae.

Although the metabolism of yolk lipids such as docosahexaenoic acid (DHA) is pivotal for embryonic development, the underlying mechanism remains elusive. Here we find that the zebrafish hydroxysteroid (17-β) dehydrogenase 12a ( hsd17b12a ), which encodes an intestinal epithelial-specific enzyme, is essential for the biosynthesis of long-chain polyunsaturated fatty acids in primitive intestine of larval fish. The deficiency of hsd17b12a leads to severe developmental defects in the primitive intestine and exocrine pancreas. Mechanistically, hsd17b12a deficiency interrupts DHA synthesis from essential fatty acids derived from yolk-deposited triglycerides, and consequently disrupts the intestinal DHA-phosphatidic acid (PA)-phosphatidylglycerol (PG) axis. This ultimately results in developmental defects of digestive organs, primarily driven by ferroptosis. Our findings indicate that the DHA-PA-PG axis in the primitive intestine facilitates the uptake of yolk lipids and promotes the expansion of digestive organs, thereby uncovering a mechanism through which DHA regulates embryonic development. Lipid utilization from the yolk sac plays a crucial role in embryonic development. Here, Chen et al. generate hsd17b12a mutant zebrafish and discover that a docosahexaenoic acid (DHA)-phosphatidic acid (PA)-phosphatidylglycerol (PG) (DHA-PA-PG) axis facilitates the uptake of yolk lipids and promotes the expansion of digestive organs.

Mental fatigue is a key cause of chronic diseases and traffic accidents, which is difficult to be quantitatively evaluated. In order to non-intrusively detect fatigue state, an optical fiber sensing system is proposed, which is non-invasive and does not require direct contact with skin. The fiber sensor was fabricated through phase mask exposure method and packaged by sensitivity-enhanced structure, which can suppress transverse force and increase signal amplitude by 5%. A fatigue-inducing experiment was carried out, and the heartbeat signals of 20 subjects under different fatigue states were collected by the proposed sensing system. A series of heart rate variability indicators were calculated from the sensing signals, and their statistical significance for fatigue was analyzed. The experiment results showed that the values of SDNN and LF/HF increased significantly with subjects’ fatigue level. This study shows that the proposed fiber optic sensing system has practical value in fatigue state monitoring.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and poor survival outcomes. This study evaluated the anticancer potential of seco-duocarmycin SA (seco-DSA), a potent DNA-alkylating agent, alone and in combination with proton radiation in human GBM cell lines. Human glioblastoma cell lines T98G and LN18 were treated with varying concentrations of seco-DSA, proton radiation doses (2, 4, or 8 Gy), or both. Proton irradiation was delivered with a 250-MeV beam. Clonogenic survival, cell proliferation, and cell cycle distribution were analyzed using colony formation and flow cytometry assays. Proteomic analysis of LN18 cells was performed by LC-MS/MS followed by bioinformatic pathway analysis. Statistical significance was determined using a two-tailed unpaired t-test (p ≤ 0.05), and Bliss synergy scores were calculated to assess treatment interactions. Combination therapy produced additive and synergistic inhibition of colony formation and enhanced G2/M phase arrest compared with either treatment alone. Apoptosis and necrosis increased modestly but did not fully account for observed cytotoxicity. Proteomic profiling revealed differential expression of proteins involved in DNA repair, apoptosis, and senescence, indicating that seco-DSA broadened radiation-induced stress responses. Seco-DSA potentiates the cytotoxic effects of proton radiation in GBM cells through enhanced clonogenic inhibition and modulation of cell cycle and DNA repair pathways. These findings support seco-DSA as a promising radiosensitizer for further preclinical evaluation.

Viruses, such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infect hosts and take advantage of host cellular machinery for genome replication and new virion production. Identifying and elucidating host pathways for viral infection is critical for understanding the development of the viral life cycle and novel therapeutics. The SARS-CoV-2 N protein is critical for viral RNA (vRNA) genome packaging in new virion formation. Using our quantitative Förster energy transfer/Mass spectrometry (qFRET/MS) coupled method and immunofluorescence imaging, we identified three SUMOylation sites of the SARS-CoV-2 N protein. We found that (1) Small Ubiquitin-like modifier (SUMO) modification in Nucleocapsid (N) protein interaction affinity increased, leading to enhanced oligomerization of the N protein; (2) one of the identified SUMOylation sites, K65, is critical for its nuclear translocation. These results suggest that the host human SUMOylation pathway may be critical for N protein functions in viral replication and pathology in vivo. Thus, blocking essential host pathways could provide a novel strategy for future anti-viral therapeutics development, such as for SARS-CoV-2 and other viruses.

The Journal retracts the article “Adsorption capability and mechanism of MgO nanomaterials synthesized by ultrasonic electrodeposition for Pb(II)” [...]

This work describes the process of synthesizing magnesia (MgO) nanomaterials through ultrasonic electrodeposition, followed by an examination of their ability and mechanism to remove Pb(II) from industrial soil at 100, 150, and 200 W ultrasonic powers. Nanomaterials were examined for their surface shape and phase composition using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffractometry (XRD). The capability of magnesia nanomaterials to adsorb Pb(II) improved greatly when operated at 150 W, attaining a maximal 68.94 mg/g value. Adsorption of Pb(II) onto magnesia nanomaterial surfaces was examined by utilizing the pseudo-second-order kinetic and Langmuir models. The nanomaterials exhibited significant features of both chemical and monolayer adsorptions for Pb(II) as a result of the intense chemical interactions between the atoms of the magnesia nanomaterials’ surface and Pb(II), as shown by Fourier transform infrared (FTIR) analysis. At 30 °C, the magnesia nanomaterial exhibited the highest adsorption capacity for Pb(II), suggesting that temperature played a significant role in this capacity. Furthermore, the Langmuir model produced a correlation coefficient greater than 0.99, indicating an excellent fit for the adsorption behavior of magnesia towards Pb(II). The findings suggest that ultrasonic power significantly impacts the adsorption characteristics of magnesia nanoparticles synthesized via ultrasonic electrodeposition. Specifically, ultrasonic power of 150 W yields the most efficient adsorption characteristics. Moreover, the 150 W-fabricated magnesia materials demonstrated exceptional pH compatibility.

The jumonji domain-containing protein 6 (JMJD6) gene catalyzes the arginine demethylation and lysine hydroxylation of histone and a growing list of its known substrate molecules, including p53 and U2AF65, suggesting a possible role in mRNA splicing and transcription in cancer progression. Mass spectrometry-based technology offers the opportunity to detect SNP variants accurately and effectively. In our study, we conducted a combined computational and filtration workflow to predict the nonsynonymous single nucleotide polymorphisms (nsSNPs) present in JMJD6, followed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and validation. The computational approaches SIFT, PolyPhen-2, SNAP, I-Mutant 2.0, PhD-SNP, PANTHER, and SNPS&GO were integrated to screen out the predicted damaging/deleterious nsSNPs. Through the three-dimensional structure of JMJD6, H187R (rs1159480887) was selected as a candidate for validation. The validation experiments showed that the mutation of this nsSNP in JMJD6 obviously affected mRNA splicing or the transcription of downstream genes through the reduced lysyl-hydroxylase activity of its substrates, U2AF65 and p53, further indicating the accuracy of this prediction method. This research provides an effective computational workflow for researchers with an opportunity to select prominent deleterious nsSNPs and, thus, remains promising for examining the dysfunction of proteins.