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Fei-Ran Yang,1,* Si-Yi Li,1,* Xi-Wen Hu,1 Xiu-Rong Li,2 Hui-Jie Li2 1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui-Jie Li; Xiu-Rong Li, Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road, Jinan, Shandong, 250014, People’s Republic of China, Email 2008lihuijie@163.com; szylxr2012@126.comBackground: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin.Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein–protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells.Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes.Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.Graphical Abstract: Keywords: lung adenocarcinoma, curcumin, antitumor effect, bioinformatics analysis, TCGA

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.

Background Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. Methods The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. Results Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. Conclusions These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.

Thermochemical and electronic trapping/detrapping mechanism-based resistance switching in TiO2 is one of the most extensively researched topics in the field of resistance-switching random access memory (ReRAM). In this study, the subtle correlation between the formation and rupture of the Magneli-based conducting filament (CF), which is the mechanism of non-polar thermochemical-reaction-based switching, and the electron trapping/detrapping at the defect centers, which is the mechanism of bipolar electronic switching, is examined in detail. The chemical interaction between the TiN top electrode and the TiO2 layer generates a stable and immobile electron trapping layer, which is called a “switching layer”, whereas the thin region between the just-mentioned switching layer and the remaining Magneli CF after the thermochemical reset comprises a non-switching layer. The seemingly very complicated switching behavior with respect to the bias polarity, compliance current, and detailed biasing sequence could be reasonably explained by the phenomenological model based on the combined motions of the CF, switching layer, and non-switching layer. Light-induced detrapping experiments further supplement the suggested switching model.