HPV integration: a precise biomarker for detection of residual/recurrent disease after treatment of CIN2-3.

BACKGROUND: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. METHODS: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. RESULTS: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. CONCLUSIONS: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

Atomically dispersed nanozyme-based synergistic mild photothermal/nanocatalytic therapy for eradicating multidrug-resistant bacteria and accelerating infected wound healing.

Constructing a synergistic multiple-modal antibacterial platform for multi-drug-resistant (MDR) bacterial eradication and effective treatment of infected wounds remains an important and challenging goal. Herein, we developed a multifunctional Cu/Mn dual single-atom nanozyme (Cu/Mn-DSAzymes)-based synergistic mild photothermal/nanocatalytic-therapy for a MDR bacterium-infected wound. Cu/Mn-DSAzymes with collaborative effects exhibit remarkable dual CAT-like and OXD-like enzyme activities and could efficiently catalyze cascade enzymatic reactions with a low level of H2O2 as an initial reactant to produce reparative O2 and lethal ˙O2-. Moreover, a black N-doped carbon nanosheet supports of Cu/Mn-DSAzymes show superior NIR-II-triggered photothermal performance, endowing them with photothermal-enhanced dual enzyme catalysis. In addition, such enhanced dual enzyme catalysis likely improves the susceptibility and lethality of photothermal effects on MDR bacteria. In vitro and in vivo studies demonstrate that Cu/Mn-DSAzyme-mediated synergistic nanocatalytic and photothermal effects possess dramatic antibacterial outcomes against MDR bacteria and evidently reduced inflammation at wound sites. Moreover, the combined photothermal effect and O2 release mediated by Cu/Mn-DSAzymes promotes macrophage polarization to reparative M2 phenotype, collagen deposition, and angiogenesis, considerably accelerating wound healing. Therefore, Cu/Mn-DSAzyme-based synergetic dual-modal antibacterial therapy is a promising strategy for MDR bacterium-infected wound treatment, owing to their excellent antibacterial ability and significant tissue remodeling effects.

Analysis of odor compounds in Lee Kum Kee brand oyster sauce and oyster enzymatic hydrolysate: Comparison and relationship.

Oyster sauce (OS) is a highly processed oyster product. However, the significant price difference between OS and fresh oysters raises a question: Does authentic OS truly contain components from oysters or oyster enzymatic hydrolysates (OEH)? Therefore, the odor compounds of Lee Kum Kee oyster sauce (LKK), 4 OEHs, and 6 other seafood enzymatic hydrolysates (SEHs) were analyzed by using solid-phase microextraction and gas chromatography-olfactometry-mass spectrometry technology (SPME-GC-O-MS). The results of multivariate statistical analysis demonstrated the effective discrimination between LKK and OEHs from other SEHs. According to the VIP value and the differences in the composition of odor compounds among different samples, 15 essential odor compounds were screened out, which could distinguish whether the samples contained OEHs. Among them, acetic acid, 2-pentylfuran, 2-ethyl furan, 2-methylbutanal, and nonanal were only detected in LKK and OEHs, which further indicated the existence of OEH in LKK.

Developing Single-Atomic Manganese Nanozymes for Synergistic Mild Photothermal/Multienzymatic Therapy.

Synergistic mild photothermal/nanozyme therapy with outstanding hyperthermia performance and excellent multienzyme properties is highly needed for osteosarcoma treatment. Herein, we have developed efficient single-atom nanozymes (SANs) consisting of Mn sites atomically dispersed on nitrogen-doped carbon nanosheets (denoted as Mn-SANs) for synergistic mild photothermal/multienzymatic therapy against osteosarcoma. Benefiting from their black N-doped carbon nanosheet matrices, Mn-SANs showed an excellent NIR-II-triggered photothermal effect. On the other hand, Mn-SANs with atomically dispersed Mn sites have outstanding multienzyme activities. Mn-SANs can catalyze endogenous H2O2 in osteosarcoma into O2 by catalase (CAT)-like activity, which can effectively ease osteosarcoma hypoxia and trigger the oxidase (OXD)-like catalysis that converts O2 to the cytotoxic superoxide anion radical (•O2-). At the same time, Mn-SANs can also mimic glutathione oxidase (GSHOx) to effectively consume the antioxidant glutathione (GSH) in osteosarcoma and inhibit intracellular glutathione peroxidase 4 (GPX4) expression. Such intratumoral •O2- production, GSH depletion, and GPX4 inactivation mediated by Mn-SANs can create a large accumulation of lipid peroxides (LPO) and •O2-, leading to oxidative stress and disrupting the redox homeostasis in osteosarcoma cells, which can ultimately induce osteosarcoma cell death. More importantly, heat shock proteins (HSPs) can be significantly destroyed via Mn-SAN-mediated plentiful LPO and •O2- generation, thus effectively impairing osteosarcoma cells resistant to mild photothermal therapy. Overall, through the cooperative effect of chemical processes (boosting •O2-, consuming GSH, and enhancing LPO) and biological processes (inactivating GPX4 and hindering HSPs), collaborative mild photothermal/multienzymatic therapy mediated by Mn-SANs is a promising strategy for efficient osteosarcoma treatment.