Lactylation: The emerging frontier in post-translational modification.

Lactate, a metabolic byproduct, has gained recognition as a highly influential signaling molecule. Lactylation, an emerging form of post-translational modification derived from lactate, plays a crucial role in numerous cellular processes such as inflammation, embryonic development, tumor proliferation, and metabolism. However, the precise molecular mechanisms through which lactylation governs these biological functions in both physiological and pathological contexts remain elusive. Hence, it is imperative to provide a comprehensive overview of lactylation in order to elucidate its significance in biological processes and establish a foundation for forthcoming investigations. This review aims to succinctly outline the process of lactylation modification and the characterization of protein lactylation across diverse organisms. Additionally, A summary of the regulatory mechanisms of lactylation in cellular processes and specific diseases is presented. Finally, this review concludes by delineating existing research gaps in lactylation and proposing primary directions for future investigations.

Selectivity Mechanism of Pyrrolopyridone Analogues Targeting Bromodomain 2 of Bromodomain-Containing Protein 4 from Molecular Dynamics Simulations.

Bromodomain and extra-terminal domain (BET) proteins play an important role in epigenetic regulation and are linked to several diseases; therefore, they are interesting targets. BET has two bromodomains: bromodomain 1 (BD1) and BD2. Selective targeting of BD1 or BD2 may produce different activities and greater effects than pan-BD inhibitors. However, the selective mechanism of the specific core must be studied at the atomic level. This study determined the effectiveness of pyrrolopyridone analogues to selectively inhibit BD2 using a pan-BD inhibitor (ABBV-075) and a selective-BD2 inhibitor (ABBV-744). Molecular dynamics simulations and calculations of binding free energies were used to systematically study the selectivity of BD2 inhibition by the pyrrolopyridone analogues. Overall, the pyrrolopyridone analogue inhibitors targeting BD2 interacted mainly with the following amino acid pairs between bromodomain-containing protein 4 (BRD4)-BD1 and BRD4-BD2 complexes: I146/V439, N140/N433, D144/H437, P82/P375, V87/V380, D88/D381, and Y139/Y432. The pyrrolopyridone analogues targeting BRD4-BD2 were divided into five regions based on selectivity mechanism. These results suggest that the R3 and R5 regions of pyrrolopyridone analogues can be modified to improve the selectivity between BRD4-BD1 and BRD4-BD2. The selectivity of BD2 inhibition by pyrrolopyridone analogues can be used to design novel BD2 inhibitors based on a pyrrolopyridone core.

Deciphering the Biological Effects of Radiotherapy in Cancer Cells.

Radiotherapy remains an effective conventional method of treatment for patients with cancer. However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment. Consequently, there is need for a comprehensive understanding of the regulatory mechanisms of tumor cells in response to radiation to improve radiotherapy efficacy. The current study aims to highlight new developments that illustrate various forms of cancer cell death after exposure to radiation. A summary of the cellular pathways and important target proteins that are responsible for tumor radioresistance and metastasis is also provided. Further, the study outlines several mechanistic descriptions of the interaction between ionizing radiation and the host immune system. Therefore, the current review provides a reference for future research studies on the biological effects of new radiotherapy technologies, such as ultra-high-dose-rate (FLASH) radiotherapy, proton therapy, and heavy-ion therapy.

Split-type electrochemiluminescent gene assay platform based on gold nanocluster probe for human papillomavirus diagnosis.

Persistent high-risk human papillomavirus (HPV) infection is the leading cause of cervical cancer. Efficient detection of HPV16 E7 is necessary for early diagnosis and cure of the disease. Here, a novel and high-performance Au nanocluster (AuNC) probe-based split-type electrochemiluminescent (ECL) assay platform has been established to detect these oncogenes, in which the nucleic acid hybridization assay and the ECL measurements are performed independently. The proposed approach combines superior magnetic nanobead enrichment and separation technology, specific nucleic acid hybridization technology, and high-efficiency AuNC probe ECL strategy, and shows excellent advantages. First, the split-type ECL sensing platform can effectively avoid interference from biological samples and adequately uses the ECL efficiency of the AuNC probe. Furthermore, the ultrahigh sensitivity assay of HPV DNA can be achieved without any complex nucleic acid amplification technique. Taking advantage of the above merits of split-type detection, the ECL DNA sensor achieved ideal low detection of 6.8 aM and a wide dynamic range bridging 10 orders of magnitude HPV16 E7. Furthermore, together with its favorable and powerful specificity, high sensitivity, and good selectivity, this strategy could detect HPV16 E7 DNA in human samples, which showed great consistency with the FDA-approved approach (Hybrid capture 2, HC2). Therefore, this work proposes a facile and reliable split-type ECL platform for HPV diagnosis and shows great potential for the early diagnosis of other diseases.

Gold nanoclusters/graphene quantum dots complex-based dual-emitting ratiometric fluorescence probe for the determination of glucose.

Herein, we report the design of a single-excitation/double-emission ratiometric fluorescence nanosensor for the determination of glucose. The sensing system combines glucose oxidation catalyzed by glucose oxidase, Fenton chemistry, Fe3+-sensitive fluorescent gold nanoclusters (AuNCs), and Fe3+-inert fluorescent graphene quantum dots (GQDs). We used orange-fluorescent AuNCs co-modified with bovine serum albumin and 3-mercaptopropionic acid as the indicator probe, and GQDs with the same excitation wavelength as the BSA/MPA-AuNCs, but with different emission wavelength, as the reference probe. The fluorescence intensity-ratio between 420 nm and 575 nm (F420/F575) was used to quantitatively determine glucose with a low detection limit of 0.18 µM, and the nanosensor was successfully used to detect glucose in human serum. This ratiometric fluorescence sensing system, based on AuNCs and GQDs, ensures sensitive and convenient determination of glucose, and has broad application prospects for biomedical-analysis applications.

Sensitive and selective nitrite assay based on fluorescent gold nanoclusters and Fe2+/Fe3+ redox reaction.

In recent years, gold nanoclusters (AuNCs) have received considerable attention as optical transducers in chemo/biosensors. Herein, a facile and efficient assay for NO2- has been successfully developed based on the fluorescence quenching of AuNCs co-modified by bovine serum albumin and 3-mercaptopropionic acid (BSA/MPA-AuNCs). In the presence of NO2- under acidic conditions, Fe2+ can be readily oxidized and transformed to Fe3+, which can significantly suppress the fluorescence of BSA/MPA-AuNCs via non-radiative electron-transfer mechanism. The linear range and detection limit for this system were found to be 5-30 µM (r = 0.9975) and 0.7 µM, respectively. Other common anions and cations showed only very minor interference with the NO2- detection. Furthermore, the effectiveness of the proposed sensing strategy was validated by the demonstration of good performance in the determination of the amount of NO2- in ham samples, rendering it a powerful tool for the assessment of food security and water quality.

Magnetic EDTA functionalized CoFe2O4 nanoparticles (EDTA-CoFe2O4) as a novel catalyst for peroxymonosulfate activation and degradation of Orange G.

EDTA functionalized CoFe2O4 nanoparticles (EDTA-CoFe2O4) synthesized using a facile one-pot solvothermal method were employed as catalysts to activate peroxymonosulfate (PMS) with Orange G (OG) as the target pollutant. Effects of operating parameters including initial solution pH, catalyst dosage, PMS dosage, and water matrix components such as Cl-, NO3-, CO32-, and humic acid were evaluated. A degradation efficiency of 93% was achieved in 15 min with 1 mM PMS and 0.2 g/L EDTA-CoFe2O4 catalyst, while only 57% of OG was degraded within 15 min in CoFe2O4/PMS system. The degradation of OG followed pseudo-first-order kinetics, and the apparent first-order date constant (k obs) for OG in EDTA-CoFe2O4/PMS and CoFe2O4/PMS system was determined to be 0.152 and 0.077 min-1, respectively. OG degradation by EDTA-CoFe2O4/PMS was enhanced with the increase of catalyst and PMS doses at respective range of 0.1-2.0 g/L and 0.5-10.0 mM. Higher efficiency of OG oxidation was observed within a wide pH range (3.0-9.0), implying the possibility of applying EDTA-CoFe2O4/PMS process under environmental realistic conditions. Humic acid (HA) at low concentration accelerated the removal of OG; however, a less apparent inhibitive effect was observed at HA addition of 10 mg/L. The k obs value was found to decrease slightly from 0.1601 to 0.1274, 0.1248, and 0.1152 min-1 with the addition of NO3-, CO32-, and Cl-, respectively, but near-complete removal of OG could still be obtained after 15 min. Both of the sulfate radicals and hydroxyl radicals were produced in the reaction, and sulfate radicals were the dominant according to the scavenging tests and electron paramagnetic resonance (EPR) tests. Finally, a degradation mechanism was proposed, and the stability and reusability of the EDTA-CoFe2O4 were evaluated.