The combination therapy of oncolytic virotherapy.

Introduction: Compared to other cancer immunotherapies, oncolytic viruses possess several advantages, including high killing efficiency, excellent targeting capabilities, minimal adverse reactions, and multiple pathways for tumor destruction. However, the efficacy of oncolytic viruses as a monotherapy often falls short of expectations. Consequently, combining oncolytic viruses with traditional treatments to achieve synergistic effects has emerged as a promising direction for the development of oncolytic virus therapies. Methods: This article provides a comprehensive review of the current progress in preclinical and clinical trials exploring the combination therapies involving oncolytic viruses. Results: Specifically, we discuss the combination of oncolytic viruses with immune checkpoint inhibitors, chemotherapy, targeted therapy, and cellular therapy. Discussion: The aim of this review is to offer valuable insights and references for the further advancement of these combination strategies in clinical applications. Further research is necessary to refine the design of combination therapies and explore novel strategies to maximize the therapeutic benefits offered by oncolytic viruses.

Construction and Validation of Novel Ferroptosis-related Risk Score Signature and Prognostic Prediction Nomogram for Patients with Colorectal Cancer.

Background: Colorectal cancer (CRC) has a high morbidity and mortality. Ferroptosis is a phenomenon in which metabolism and cell death are closely related. The role of ferroptosis-related genes in the progression of CRC is still not clear. Therefore, we screened and validated the ferroptosis-related genes which could determine the prevalence, risk and prognosis of patients with CRC. Methods: We firstly screened differentially expressed ferroptosis-related genes by The Cancer Genome Atlas (TCGA) database. Then, these genes were used to construct a risk-score model using the least absolute shrinkage and selection operator (LASSO) regression algorithm. The function and prognosis of the ferroptosis-related genes were confirmed using multi-omics analysis. The gene expression results were validated using publicly available databases and qPCR. We also used publicly available data and ferroptosis-related genes to construct a prognostic prediction nomogram. Results: A total of 24 differential expressed genes associated with ferroptosis were screened in this study. A three-gene risk score model was then established based on these 24 genes and GPX3, CDKN2A and SLC7A11 were selected. The significant prognostic value of this novel three-gene signature was also assessed. Furthermore, we conducted RT-qPCR analysis on cell lines and tissues, and validated the high expression of CDKN2A, GPX3 and low expression of SLC7A11 in CRC cells. The observed mRNA expression of GPX3, CDKN2A and SLC7A11 was consistent with the predicted outcomes. Besides, eight variables including selected ferroptosis related genes were included to establish the prognostic prediction nomogram for patients with CRC. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations. Also, the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. Conclusions: The present study constructed and validated a novel ferroptosis-related three-gene risk score signature and a prognostic prediction nomogram for patients with CRC. Also, we screened and validated the ferroptosis-related genes GPX3, CDKN2A, and SLC7A11 which could serve as novel biomarkers for patients with CRC.

Tumor regression and safe distance of distal margin after neoadjuvant therapy for rectal cancer.

Neoadjuvant therapy has been widely employed in the treatment of rectal cancer, demonstrating its utility in reducing tumor volume, downstaging tumors, and improving patient prognosis. It has become the standard preoperative treatment modality for locally advanced rectal cancer. However, the efficacy of neoadjuvant therapy varies significantly among patients, with notable differences in tumor regression outcomes. In some cases, patients exhibit substantial tumor regression, even achieving pathological complete response. The assessment of tumor regression outcomes holds crucial significance for determining surgical approaches and establishing safe margins. Nonetheless, current research on tumor regression patterns remains limited, and there is considerable controversy surrounding the determination of a safe margin after neoadjuvant therapy. In light of these factors, this study aims to summarize the primary patterns of tumor regression observed following neoadjuvant therapy for rectal cancer, categorizing them into three types: tumor shrinkage, tumor fragmentation, and mucinous lake formation. Furthermore, a comparison will be made between gross and microscopic tumor regression, highlighting the asynchronous nature of regression in the two contexts. Additionally, this study will analyze the safety of non-surgical treatment in patients who achieve complete clinical response, elucidating the necessity of surgical intervention. Lastly, the study will investigate the optimal range for safe surgical resection margins and explore the concept of a safe margin distance post-neoadjuvant therapy.

Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus.

It is challenging to characterize single or a few biomolecules in physiological milieus without excluding the influences of surrounding environment. Here we utilize optical plasmonic trapping to construct a dynamic nanocavity, which reduces the diffraction-limited detection volume and provides reproducible electromagnetic field enhancements to achieve high-throughput single-molecule surface-enhanced Raman spectroscopy (SERS) characterizations in aqueous environments. Specifically, we study human Islet Amyloid Polypeptide (amylin, hIAPP) under different physiological pH conditions by combining spectroscopic experiments and molecular dynamics (MD) simulations. Based on a statistically significant amount of time-dependent SERS spectra, two types of low-populated transient species of hIAPP containing either turn or ß-sheet structure among its predominant helix-coil monomers are characterized during the early-stage incubation at neutral condition, which play a crucial role in driving irreversible amyloid fibril developments even after a subsequent adjustment of pH to continue the prolonged incubation at acidic condition. Our results might provide profound mechanistic insight into the pH-regulated amyloidogenesis and introduce an alternative approach for investigating complex biological processes at the single-molecule level.

Tunable lipid-coated nanoporous silver sheet for characterization of protein-membrane interactions by surface-enhanced Raman scattering (SERS).

Membrane environments affect protein structures and functions through protein-membrane interactions in a wide range of important biological processes. To better study the effects from the lipid's hydrophilic and hydrophobic interaction with protein on different membrane regions, we developed the lipid-coated nanoporous silver sheets to provide tunable supported lipid monolayer/bilayer environments for in situ surface-enhanced Raman vibrational spectroscopy (SERS) characterizations. Under the controllable surface pressure, lipid monolayer/bilayer was coated along the microscopic curved surface of nanoporous silver sheets to serve as a cell membrane mimic as well as a barrier to avoid protein denaturation while empowering the high SERS enhancements from the underlying metallic bases allowing detection sensitivity at low physiological concentrations. Moreover, we fine-tuned the lipid packing density and controlled the orientation of the deposited lipid bilayers and monolayers to directly monitor the protein structures upon interactions with various membrane parts/positions. Our results indicate that lysozyme adopted the α-helical structure in both hydrophilic and hydrophobic interaction with lipid membrane. Interestingly, alpha-synuclein folded into the α-helical structure on the negatively charged lipid heads, whereas the hydrophobic lipid tails induced the ß-sheet structural conversion of alpha-synuclein originated from its unstructured monomers. These direct observations on protein hydrophilic and hydrophobic interaction with lipid membrane might provide profound insights into the formation of the ß-sheet-containing alpha-synuclein oligomers for further membrane disruptions and amyloid genesis associated with Parkinson's disease. Hence, with the controllability and tunability of lipid environments, our platform holds great promise for more general applications in investigating the influences from membranes and the correlative structures of proteins under both hydrophilic and hydrophobic effects.

Correction: Highly reusable nanoporous silver sheet for sensitive SERS detection of pesticides.

Correction for 'Highly reusable nanoporous silver sheet for sensitive SERS detection of pesticides' by Huanyu Chi et al., Analyst, 2020, 145, 5158-5165, https://doi.org/10.1039/D0AN00999G.

Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structures.

Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful tool to detect biomolecules in aqueous environments. However, it is challenging to identify protein structures at low concentrations, especially for the proteins existing in an equilibrium mixture of various conformations. Here, we develop an in situ optical tweezers-coupled Raman spectroscopy to visualize and control the hotspot between two Ag nanoparticle-coated silica beads, generating tunable and reproducible SERS enhancements with single-molecule level sensitivity. This dynamic SERS detection window is placed in a microfluidic flow chamber to detect the passing-by proteins, which precisely characterizes the structures of three globular proteins without perturbation to their native states. Moreover, it directly identifies the structural features of the transient species of alpha-synuclein among its predominant monomers at physiological concentration of 1 µM by reducing the ensemble averaging. Hence, this SERS platform holds the promise to resolve the structural details of dynamic, heterogeneous, and complex biological systems.

Highly reusable nanoporous silver sheet for sensitive SERS detection of pesticides.

Surface-enhanced Raman spectroscopy (SERS) enables pesticide detection at the point-of-need, but its practical application is limited by expensive and disposable SERS substrates. Here, we report a reusable nanoporous silver (NPAg) sheet for the SERS detection of organochlorine pesticides, aiming to maximize the cost-efficiency of substrate regeneration. The NPAg sheet is prepared by a reduction-induced decomposition method without chemical induced random aggregations. This SERS substrate is sensitive to various analytes regardless of their affinity to a metal surface such as rhodamine B, dichlorodiphenyl-trichloroethane (DDT), and lindane due to its large surface area and the coral rock-like morphology. The SERS signal of lindane, a typical organochlorine pesticide, is identified and quantified with a minimum detectable concentration of 3 × 10-7 M (87 ppb), which is below the maximum residue limits in various foods set by the regulators across the world. More importantly, after a few minutes of ultrasonic cleaning in water, the NPAg sheet can be reused at least 20 times with a reproducible SERS activity. Furthermore, the NPAg sheet remains stable in terms of its sensitivity and reusability after several months of bare strorage. Therefore, the NPAg sheet as a SERS substrate holds great promise for mass production and convenient applications in low-cost pesticide analysis.