Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

The influence of childhood emotional neglect experience on brain dynamic functional connectivity in young adults.

Background: Childhood emotional neglect (CEN) confers a great risk for developing multiple psychiatric disorders; however, the neural basis for this association remains unknown. Using a dynamic functional connectivity approach, this study aimed to examine the effects of CEN experience on functional brain networks in young adults.Method: In total, 21 healthy young adults with CEN experience and 26 without childhood trauma experience were recruited. The childhood trauma experience was assessed using the childhood trauma questionnaire (CTQ), and eligible participants underwent resting-state functional MRI. Sliding windows and k-means clustering were used to identify temporal features of large-scale functional connectivity states (frequency, mean dwell time, and transition numbers).Result: Dynamic analysis revealed two separate connection states: state 1 was more frequent and characterized by extensive weak connections between the brain regions. State 2 was relatively infrequent and characterized by extensive strong connections between the brain regions. Compared to the control group, the CEN group had a longer mean dwell time in state 1 and significantly decreased transition numbers between states 1 and 2.Conclusion: The CEN experience affects the temporal properties of young adults' functional brain connectivity. Young adults with CEN experience tend to be stable in state 1 (extensive weak connections between the brain regions), reducing transitions between states, and reflecting impaired metastability or functional network flexibility.

We focus solely on the childhood emotional neglect experience and its long-term effects on brain function.Eligible participants with and without childhood emotional neglect were identified through a large-scale screen among young adults.The results found childhood emotional neglect experiences have a long-term impact on brain flexibility.

ROS-responsive ADPH nanoparticles for image-guided surgery.

In recent years, organic fluorescent probes with tumor microenvironment (TME)-responsive fluorescence turn-on properties have been increasingly used in imaging-guided tumor resection due to their higher signal-to-noise ratio for tumor imaging compared to non-responsive fluorescent probes. However, although researchers have developed many organic fluorescent nanoprobes responsive to pH, GSH, and other TME, few probes that respond to high levels of reactive oxygen species (ROS) in the TME have been reported in imaging-guided surgery applications. In this work, we prepared Amplex® Red (ADHP) with excellent ROS response performance as an ROS-responsive nanoprobe and studied its application in image-guided tumor resection for the first time. To confirm whether the nanoprobe can be used as an effective biological indicator to distinguish tumor sites, we first detected 4T1 cells with the ADHP nanoprobe, demonstrating that the probe can utilize ROS in tumor cells for responsive real-time imaging. Furthermore, we conducted fluorescence imaging in vivo in 4T1 tumor-bearing mice, and the ADHP probe can rapidly oxidize to form resorufin in response to ROS, which can effectively reduce the background fluorescence signal compared with the single resorufin probe. Finally, we successfully carried out image-guided surgery of 4T1 abdominal tumors under the guidance of fluorescence signals. This work provides a new idea for developing more TME-responsive fluorescent probes and exploring their application in image-guided surgery.

The influence of childhood emotional neglect on emotional face processing in young adults.

Childhood emotional neglect (CEN) refers to a failure to meet the basic emotional needs of a child, which can seriously impact interpersonal communication and psychological health in young adults. Emotional face processing is critical in interpersonal communication; however, whether CEN affects this processing in young adults has not been investigated. Therefore, the current study aimed to explore the effects of CEN on emotional face processing in young adults. Using the Child Trauma Questionnaire, an online survey was conducted with 5010 students from four universities in Tianjin, China. After online interviews and diagnosis by professional doctors, we obtained 20 participants with CEN (CEN group) and 20 without CEN (control group). None of the participants had any mental diseases. A 2 × 4 mixed design was used to investigate the differences in accuracy and response time when identifying the valence of the emotional faces. Compared to the control group, the CEN group identified the valence of all emotional faces more slowly, but there was no significant difference between the two groups in terms of accuracy. CEN caused delayed emotional face processing in young adults, which may be related to unresponsive, unavailable, and limited emotional interaction patterns between parents and their children.

Diagnosis and treatment of a small intestinal neuroendocrine neoplasm by double balloon enteroscopy combined with laparoscopy: a case report

We report the case of a jejunum neuroendocrine neoplasm with liver metastases, the lesion showed somatostatin receptor expression in the junction of duodenum and jejunum without enlarged lymph nodes in 68Ga-DOTA-NOC PET/CT scan, definitive diagnosis and treatment depend on double-balloon enteroscopy and laparoscopy. This is a meaningful and thought-provoking process. (AU)

Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes.

Owing to the complementary high spatial resolution and signal-to-noise ratio, the dual-modality imaging technique of photoacoustic imaging (PAI)/the second near-infrared window fluorescence imaging (NIR-II FI) holds great promise for the detection of tumor tissues and sentinel lymph nodes (SLNs). Herein, by developing two aggregation-induced emission luminogens (AIEgens) (C-NTBD and O-NTBD) with benzodithiadiazole as the electron acceptor, PAI/NIR-II FI was applied to the diagnosis and treatment of neuroendocrine neoplasms (NENs) and their SLNs for the first time. Both AIEgens exhibited good PAI properties as well as intense NIR-II fluorescence emission. Among them, C-NTBD nanoparticles (NPs) have better PAI and NIR-II FI performance with maximum absorption at 732 nm and emission peak at 1042 nm. In NENs-bearing nude mice model, after successful preoperative localization of NENs by PAI, NIR-II FI was then used to detect SLNs. Under the NIR-II FI guidance of C-NTBD NPs, an SLN with a diameter of 1 mm located in the chest wall and far away from the primary tumor site was even detected and precisely removed. This dual-modality imaging technology could improve the detection of NENs and the accuracy of intraoperative SLNs dissection, improve patient prognosis, and provide a new strategy for the precise treatment of NENs.

Fabrication of Zn-Cu-Ni Ternary Oxides in Nanoarrays for Photo-Enhanced Pseudocapacitive Charge Storage.

To meet the increasing demands of energy consumption, sustainable energy sources such as solar energy should be better employed to promote electrochemical energy storage. Herein, we fabricated a bifunctional photoelectrode composed of copper foam (CF)-supported zinc-nickel-copper ternary oxides in nanoarrays (CF@ZnCuNiOx NAs) to promote photo-enhanced pseudocapacitive charge storage. The as-fabricated CF@ZnCuNiOx NAs have shown both photosensitive and pseudocapacitive characteristics, demonstrating a synergistic effect on efficient solar energy harvest and conversion. As a result, a high areal specific capacitance of 2741 mF cm-2 (namely 418 µAh cm-2) under light illumination can be calculated at 5 mA cm-2, which delivered photo-enhancement of 38.3% compared to that obtained without light. In addition, the photoelectric and photothermal effects of the light energy on pseudocapacitive charge storage have been preliminarily studied and compared. This work may provide some evidence on the different mechanisms of photoelectric/thermal conversion for developing solar-driven energy storage devices.

Curcumol enhances cisplatin sensitivity of gastric cancer: involvement of microRNA-7 and the nuclear factor-kappa B/snail family transcriptional repressor 1 axis.

Cisplatin is a primary chemotherapeutic drug for gastric cancer (GC) patients, but the drug resistance remains the leading cause of treatment failure and high mortality. Curcumol is a bioactive sesquiterpenoid that has reportedly been linked to cisplatin sensitivity in GC. This study focuses on the exact functions of curcumol in the cisplatin sensitivity of GC cells and the molecules of action. The curcumol treatment reduced the viability and migration and enhanced cisplatin sensitivity of GC cells in a dose-dependent manner. Microarray analysis suggested that microRNA-7 (miR-7) was the most upregulated miRNA in GC cells after curcumol treatment. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the curcumol-affected genes, including the target genes of miR-7, were enriched in the nuclear factor-kappa B (NF-κB) pathway, whose activity was suppressed after curcumol treatment. miR-7 was found to target and suppress RELA proto-oncogene (RELA, also known as p65), a NF-κB subunit. Downregulation of miR-7 blocked the sensitizing effects of curcumol on cells to cisplatin and led to increased expression of NF-κB p65 and snail family transcriptional repressor 1 (SNAIL). Further downregulation of RELA enhanced, whereas upregulation of SNAIL suppressed the sensitivity again. In summary, this study suggests that curcumol sensitizes GC cells to cisplatin via miR-7 and the suppression of the NF-κB/SNAIL axis. The findings may offer new thoughts that curcumol in combination with cisplatin might be a useful strategy for GC management.

Diagnosis and treatment of a small intestinal neuroendocrine neoplasm by double balloon enteroscopy combined with laparoscopy: a case report.

We report the case of a jejunum neuroendocrine neoplasm with liver metastases, the lesion showed somatostatin receptor expression in the junction of duodenum and jejunum without enlarged lymph nodes in 68Ga-DOTA-NOC PET/CT scan, definitive diagnosis and treatment depend on double-balloon enteroscopy and laparoscopy. This is a meaningful and thought-provoking process.

Development and validation of prognostic nomograms for patients with colon neuroendocrine neoplasms.

BACKGROUND: Colon neuroendocrine neoplasms (NENs) have one of the poorest median overall survival (OS) rates among all NENs. The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system-currently the most commonly used prediction model-has limited prediction accuracy because it does not include parameters such as age, sex, and treatment. The aim of this study was to construct nomograms containing various clinically important parameters to predict the prognosis of patients with colon NENs more accurately. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a retrospective analysis of colon NENs diagnosed from 1975 to 2016. Data were collected from 1196 patients; almost half were female (617/1196, 51.6%), and the average age was 61.94 ± 13.05 years. Based on the age triple cut-off values, there were 396 (33.1%), 408 (34.1%), and 392 (32.8%) patients in age groups 0-55 years, 55-67 years, and ≥ 68 years, respectively. Patients were randomized into training and validation cohorts (3:1). Independent prognostic factors were used for construction of nomograms to precisely predict OS and cancer-specific survival (CSS) in patients with colon NENs. RESULTS: Multivariate analysis showed that age ≥ 68 years, sex, tumor size, grade, chemotherapy, N stage, and M stage were independent predictors of OS. In the validation cohort, the Concordance index (C-index) values of the OS and CSS nomograms were 0.8345 (95% confidence interval [CI], 0.8044-0.8646) and 0.8209 (95% CI, 0.7808-0.861), respectively. C-index also indicated superior performance of both nomograms (C-index 0.8347 for OS and 0.8668 for CSS) compared with the AJCC TNM classification (C-index 0.7159 for OS and 0.7366 for CSS). CONCLUSIONS: We established and validated new nomograms for more precise prediction of OS and CSS in patients with colon NENs to facilitate individualized clinical decisions.

A simple reduction-sensitive micelles co-delivery of paclitaxel and dasatinib to overcome tumor multidrug resistance.

Multidrug resistance (MDR) is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C18 as a co-delivery system to load the paclitaxel (PTX) and dasatinib (DAS) for treatment of MCF-7/ADR cells. The co-loaded micelles had a good dispersity and a spherical shape with a uniform size distribution, and they could quickly disassemble and rapidly release drugs under the reduction environment. Compared with MCF-7 cells, the DAS and PTX co-loaded redox-sensitive micelle (SS-PDNPs) showed stronger cytotoxicity and a more improving intracellular drug concentration than other drug formulations in MCF-7/ADR cells. In summary, the results suggested that the simple co-delivery micelles of PTX and DAS possessed significant potential to overcome drug resistance in cancer therapy.

Fulvestrant increases gefitinib sensitivity in non-small cell lung cancer cells by upregulating let-7c expression.

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), namely, gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. About 50% of this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as the one corresponding to T790M. In our previous study, we found that combined treatment with fulvestrant and gefitinib decreases the proliferation of H1975 NSCLC cells, compared to treatment with either fulvestrant or gefitinib alone; however, the molecular mechanism for the improved effects of the combination treatment are still unknown. In this study, we confirmed that fulvestrant increases the gefitinib sensitivity of H1975 cells and found that let-7c was most upregulated in the fulvestrant-treated cells. Our data revealed that let-7c increases gefitinib sensitivity by repressing RAS and inactivating the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our findings suggest that let-7c plays an important role in fulvestrant-induced upregulation of gefitinib sensitivity in H1975 cells.

Combine therapy of gefitinib and fulvestrant enhances antitumor effects on NSCLC cell lines with acquired resistance to gefitinib.

Gefitinib, an EGFR receptor tyrosine kinase inhibitor, is approved for clinical use in the treatment of non-small cell lung cancer (NSCLC), but the emergence of mutations resistant to these inhibitors, such as T790M, has become a clinical problem. According to statistics, female patients, the presence of adenocarcinoma or non-smokers experienced a higher response rate. This may be involved in interaction between the estrogen receptor (ER) and the epidermal growth factor receptor (EGFR). To test whether inhibition of the ER signaling pathway affects the antitumor effect of gefitinib, gefitinib and an ER antagonist, fulvestrant, were administered to NSCLC cell lines with acquired resistance to gefitinib. Compared with treatment of either fulvestrant or gefitinib alone, drug combination obviously decreased proliferation of H1976, H1650 and PC-9 cells coming from adenocarcinoma. Rapid activations of EGFR pathway by E2ß were observed in H1975 cells with T790M mutation. Additionally, EGFR and ERs expression were down-regulated respectively in response to estrogen and EGF but up-regulated in response to fulvestrant and gefitinib in vitro. These results suggest that there is a functional cross-signaling between the EGFR/ER pathways in NSCLC with acquired resistance to gefitinib, possibly providing rationale for combining gefitinib with anti-estrogen therapy for advanced NSCLC treatment.