Overexpression of MTHFD2 represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer.

Introduction: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), whose aberrant expression is common in cancers, has recently been identified as a potential regulator of immune response. However, its immune-related role in bladder cancer (BLCA) and its association with immunotherapy efficacy remain unclear. Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) was applied to analyze the immunological roles and prognostic value of MTHFD2 in pan-cancers. The association of MTHFD2 with several immunological features of tumor microenvironment (TME), including cancer-immunity cycle, immune cells infiltration, immune checkpoints expression, and T cell inflamed score was analyzed in TCGA-BLCA cohort. The predictors of cancer treatments effectiveness, including the expression and mutation of certain genes, molecular subtypes, and several signatures were evaluated as well. These results were validated by another independent cohort (GSE48075). Finally, the predictive value of MTHFD2 for TME and immunotherapy efficacy were validated using immunohistochemistry assay and RNA sequencing data from IMvigor210 cohort, respectively. Results: MTHFD2 was found to be positively associated with several immunological features of an inflamed tumor microenvironment (TME) in various cancers and could predict BLCA patients' prognosis. In BLCA, high expression of MTHFD2 was observed to be positively related with the cancer-immunity cycle, the infiltration of several immune cells, and the expression of immunoregulators and T-cell inflamed scores, indicating a positive correlation with the inflamed TME. Moreover, patients with high MTHFD2 expression were more likely to be basal-like subtypes and respond to BLCA treatments, including immunotherapy, chemotherapy, and target therapy. The clinical data of the IMvigor210 cohort confirmed the higher response rates and better survival benefits of immunotherapy in high-MTHFD2-expression patients. Conclusion: Collectively, high MTHFD2 predicts an inflamed TME, a basal-like subtype, and a better response to various therapeutic strategies, especially the ICB therapy, in bladder cancer.

Gold Nanostars Combined with the Searched Antibody for Targeted Oral Squamous Cell Carcinoma Therapy.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral and maxillofacial region. Due to the special physiological and anatomical position of the oral cavity, the disease often has a significant impact on the chewing, swallowing, language, and breathing functions of patients. In recent years, with the development of medical molecular biology, molecular targeted therapy has received increasing clinical attention and has gradually become a new method for the treatment of malignant tumors. In this research, gold nanostars with a high photothermal effect combined with the searched targeted antibody were used for OSCC therapy. We use the data set in the public database and construct a gene co-expression module by weighted gene co-expression network analysis (WGCNA). It was found that the turquoise module and the midnight blue module had the greatest connection to tumorigenesis. Cytoscape software was used to analyze the important modules, and the top 10 genes of each module were selected; the survival analysis of the top 10 genes was carried out by gene expression profiling interactive analysis (GEPIA), which indicated that these genes (SERPINH1, MMP11, ADAM12, FADS3, SLC36A2, C1QTNF7, SCRG1, and APOBEC2) have statistical significance as key genes that are related to the tumorigenesis of OSCC. Then, the anti-SERPINH1 antibody targeted to SERPINH1 was chosen as the inhibitor and combined with gold nanostars for photothermal assisted targeted therapy. Thus, the searched key genes can be regarded as biomarkers and therapeutic targets for further precise diagnosis.

Evaluation of the hyperbaric oxygen therapy on the flash visual evoked potential P2 in patients with severe traumatic brain injury.

BACKGROUND: Studies have shown that hyperbaric oxygen therapy (HBOT) can improve the extraction rate and latency of cortical evoked potential N20 in patients with severe traumatic brain injury, but there are only a few studies on the effect of flash visual evoked potential. OBJECTIVE: This study investigated the effect of hyperbaric oxygen therapy on the P2 wave of flash visual evoked potentials in patients with severe traumatic brain injury. METHODS: In total, we examined 40 TBI patients who received HBOT, in combination with medication, and 38 TBI patients who received medication alone. The FVEPs apparatus was used to detect the P2 wave extraction rate and the latency of the elicited waveform before and after treatment in both the medicated-only controls and HBOT-treated cohorts. RESULTS: Compared with the control group, the HBOT treatment group showed a higher P2 wave elicitation rate, and the P2 wave latency of the HBOT treatment group was significantly shortened (p < 0.05, all). CONCLUSIONS: HBOT, in combination with drug therapy, can significantly increase the P2 wave extraction rate and shorten P2 latency in patients with TBI.

MET-targeted NIR II luminescence diagnosis and up-conversion guided photodynamic therapy for triple-negative breast cancer based on a lanthanide nanoprobe.

In this research, degradable peptide-modified upconversion nanoparticles (ZUPEA) were designed for the NIR II imaging and upconversion luminescence (UCL) guided photodynamic therapy (PDT) of triple-negative breast cancer (TNBC). Ultra-small rare-earth nanoparticles (RENPs) and the polymer mPEG-PLGA are polymerized into nano-microspheres via a double emulsion synthesis method, and a photosensitizer molecule (ZnPc) is added during the polymerization process to generate ZUPEA. Under 980 nm excitation, this strategy enhanced the red emission at 650 nm, showing an energy transfer efficiency of 38.3%, and the designed RENPs have better NIR II imaging abilities with a core@shell structure. These ZUPEA nanoparticles have good photodynamic therapeutic effects in vitro, and they can be degraded into small nanoparticles with a size of less than 6 nm. The cMBP-peptide-modified luminescent probe can recognize MDA-MB-231 TNBC cells in vivo when intravenously injected due to the positive targeted imaging effects of the cMBP peptide toward MET and negative targeted imaging effects relating to enhanced permeability and retention (EPR ). This specially designed ZUPEA probe with integrated diagnosis and treatment functionality provides new ideas and prospects for the use of rare-earth nanoparticles in the clinical treatment of tumors.

NIR II Luminescence Imaging for Sentinel Lymph Node and Enhanced Chemo-/Photothermal Therapy for Breast Cancer.

In this research, a NIR II luminescence imaging and enhanced chemo-/photothermal therapy system of CuS-DOX-Nd/FA NPs for breast cancer and lymph node tracing under single 808 nm irradiation is proposed. Nd-DTPA molecular cluster with the NIR II imaging effect as the carrier was designed to load the ultrasmall CuS nanoparticles and chemotherapeutic drug doxorubicin hydrochloride (DOX). The composite probe is used for tumor lesion imaging and tracking the breast cancer sentinel lymph nodes with simultaneous chemo-/photothermal therapy (PTT) for breast cancer under the single 808 nm laser. This designed probe not only has high permeability and retention (EPR) targeting effect but also can respond to the tumor microenvironment (TME), realizing more precise and efficient release of DOX at the cancer focus. At the same time, CuS as a drug carrier has a good photothermal therapy effect (photothermal conversion efficiency: 27.9%). The serialized released chemotherapy DOX and synergistic PTT effect can be used to the treat the in situ breast cancer land and simultaneously kill the metastasis cancer. The system made the combined molecular clusters Nd-DTPA achieve NIR II imaging of tumor lesions of breast cancer and lymph node to obtain the integration of diagnosis of the transferred disease for better prognosis. The feasibility of the system had obvious tumor growth inhibition effect with NIR II imaging guided is verified by a series of in vitro and in vivo experiments.

Targeted Luminescent Probes for Precise Upconversion/NIR II Luminescence Diagnosis of Lung Adenocarcinoma.

In this research, the antibody of the searched hub genes has been proposed to combine with a rare-earth composite for an upconversion luminescence (UCL) and downconversion (DCL) NIR-II imaging strategy for the diagnosis of lung adenocarcinoma (LUAD). Weighted gene co-expression network analysis is used to search the most relevant hub genes, and the required top genes that contribute to tumorigenesis (negative: CLEC3B, MFAP4, PECAM1, and FHL1; positive: CCNB2, CDCA5, HMMR, and TOP2A) are identified and validated by survival analysis and transcriptional and translational results. Meanwhile, fluorescence imaging probes (NaYF4:Yb,Er,Eu@NaYF4:Nd, denoted as NYF:Eu NPs) with multimodal optical imaging properties of downconversion and upconversion luminescence in the visible region and luminescence in the near infrared II region are designed with various uniform sizes and enhanced penetration and sensitivity. Finally, when the NYF:Eu NP probe is combined with antibodies of these chosen positive hub genes (such as, TOP2A and CCNB2), the in vitro and in vivo animal experiments (flow cytometry, cell counting kit-8 assay using A549 cells, and in vivo immunohistochemistry IHC microscopy images of LUAD from patient cases) indicate that the designed nanoprobes can be excellently used as a targeted optical probe for future accurate diagnosis and surgery navigation of LUAD in contrast with other cancer cells and normal cells. This strategy of antibodies combined with optical probes provides a dual-modal luminescence imaging method for precise medicine.

Degradable pH-responsive NIR-II imaging probes based on a polymer-lanthanide composite for chemotherapy.

In this research, a pH-sensitive degradable nanoprobe was designed by combining hydrophobic rare earth nanoparticles with biocompatible mPEG-PLGA nanomicelles for near infrared II (NIR-II) imaging-guided anti-tumor chemotherapy. The as-synthesized nanoprobes (about 300 nm) with a highly enhanced permeability and retention (EPR) effect show great potential in the diagnosis of solid tumors, providing new prospects for clinical tumor diagnosis. Then, the degradable composite probes increase the imaging sensitivity of the probe and allow for the slow release of the internal anti-tumor drugs, reducing the loss of the drug during delivery. Finally, ultra-small rare earth nanoparticles (about 6 nm) can be excreted after hydrolysis of the composite probe to reduce the enrichment of the inorganic nanoparticles in vivo. Thus, this degradable NIR-II imaging probe based on a polymer-lanthanide composite could be a promising candidate for preclinical cancer chemotherapy and surgery navigation under a single 808 nm laser.

Surface Plasmonic Enhanced Imaging-Guided Photothermal/Photodynamic Therapy Based on Lanthanide-Metal Nanocomposites under Single 808 nm Laser.

In this research, we design the integration of Au/Ag nanocages with upconversion nanoparticles (UCNPs) as the theranostic agent under single 808 nm with enhanced imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) properties. Different with the conventional theranostic agent, Au/Ag@UCNPs can emit higher blue emission under 808 nm laser and generate higher reactive oxygen species than that of Au@UCNPs due to higher crossed absorbance between the nanocages and UCNPs. Furthermore, the temperature change of Au/Ag@UCNPs (9.7 °C) is much higher than that of phosphate-buffered saline solution (0.6 °C) under 808 nm laser, indicating there is a low side effect to normal cells when Au/Ag@UCNPs are utilized as the photoactive agent. Finally, the in vitro and in vivo experiments show that the tumor is almost ablated totally due to high synergistic PDT and PTT effects of Au/Ag@UCNPs, revealing it could be potentially applied in the clinical theranostic field.