Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy.

The induction of cuproptosis, a recently identified form of copper-dependent immunogenic cell death, is a promising approach for antitumor therapy. However, sufficient accumulation of intracellular copper ions (Cu2+) in tumor cells is essential for inducing cuproptosis. Herein, an intelligent cuproptosis-inducing nanosystem is constructed by encapsulating copper oxide (CuO) nanoparticles with the copper ionophore elesclomol (ES). After uptake by tumor cells, ES@CuO is degraded to release Cu2+ and ES to synergistically trigger cuproptosis, thereby significantly inhibiting the tumor growth of murine B16 melanoma cells. Moreover, ES@CuO further promoted cuproptosis-mediated immune responses and reprogrammed the immunosuppressive tumor microenvironment by increasing the number of tumor-infiltrating lymphocytes and secreted inflammatory cytokines. Additionally, combining ES@CuO with programmed cell death-1 (PD-1) immunotherapy substantially increased the antitumor efficacy in murine melanoma. Overall, the findings of this study can lead to the use of a novel strategy for cuproptosis-mediated antitumor therapy, which may enhance the efficacy of immune checkpoint inhibitor therapy.

Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance.

Gestational diabetes mellitus (GDM) is a common obstetric disease among pregnant women. This study aimed to explore the effect of dietary pattern management to reduce the incidence of GDM. Here, we, retrospectively, analyzed the influence of dietary patterns on the occurrence of GDM and the correlation between dietary patterns and intestinal microbiome distribution and inflammation in pregnant women. Moreover, patients were assigned to the dietary pattern management group and the nondietary pattern management group, and the effects of dietary patterns on the intestinal microbiome distribution and inflammatory factors were investigated. We found that the intestinal microbiome was changed in GDM patients compared with the healthy controls. The relative abundance of probiotics Lactobacillus and Bifidobacterium significantly decreased in patients with GDM. Moreover, compared with the control group, the expression levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Furthermore, dietary pattern management led to intestinal microbiome changes in patients with GDM. In conclusion, dietary pattern management could alleviate GDM via affecting the intestinal microbiome as well as inflammatory conditions in patients.

Add-on atypical anti-psychotic treatment alleviates auditory verbal hallucinations in patients with chronic post-traumatic stress disorder.

Auditory verbal hallucinations are common symptoms of post traumatic distress disorder. Previous studies have demonstrated alterations in the salience network (SN) in patients with post traumatic distress disorder and that hyperactivity of the SN is associated with AVHs in patients with psychosis. Patients with post traumatic distress disorder may benefit from aripiprazole; however, studies investigating the effect of aripiprazole on AVHs and activity in the SN in patients with post traumatic distress disorder are scarce. Therefore, we conducted an outcomes analysis using functional magnetic resonance imaging to explore the effects of add-on aripiprazole treatment on AVHs and brain functional connectivity in patients with post traumatic distress disorder. AVHs were alleviated by add-on aripiprazole treatment (Auditory Hallucination Rating Scale [AHRS] score reduced by ≥ 50%) in 22.7% of patients. Functional activity in the SN was obviously decreased in patients in whom AHRS scores were reduced ≥ 50% following add-on aripiprazole treatment compared to patients in whom AHRS scores were reduced by <50%. The decrease in functional connectivity within the SN was significantly correlated with the reduction in total AHRS scores. Although this study was associated with several limitations, the findings suggest that add-on aripiprazole treatment can alleviate AVHs in patients with post traumatic distress disorder by reducing activity in the SN.

Understanding auditory verbal hallucinations in healthy individuals and individuals with psychiatric disorders.

Auditory verbal hallucinations(AVHs) are psychiatric manifestations that are common in patients with psychiatric disorders and can occur in healthy individuals. This review summarizes the existing literature on the phenomenological features of auditory verbal hallucinations, imaging findings, and interventions, focusing on patients with schizophrenia who experience auditory verbal hallucinations, in addition to patients with borderline personality disorder, bipolar disorder, major depressive disorder, and posttraumatic stress disorder, as well as healthy individuals. The phenomenological features of AVHs vary in different psychiatric disorders, and the symptoms are associated with changes in specific brain structures and disturbances in brain function, blood flow, and metabolism. Interventions for auditory verbal hallucinations include antipsychotic drugs, neurostimulation, and cognitive behavioral therapy.

Effects of Repetitive Transcranial Magnetic Stimulation Treatment on Event-Related Potentials in Schizophrenia.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ. METHODS: One hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group. RESULTS: Compared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05). CONCLUSIONS: Based on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.

Effects of maternal exposure to di-n-butyl phthalate during pregnancy and breastfeeding on ovarian development and function of F1 female rats.

This study aimed to investigate the effects of maternal exposure to di-n-butyl phthalate (DBP) during pregnancy and breastfeeding on F1 ovarian development and function. A rat model of maternal exposure to DBP during pregnancy and breastfeeding was established by gavage feeding female Sprague Dawley rats with 0, 10, 100, or 600mg/kg/day DBP from gestational day (GD) 12 to postnatal day (PND) 21. F1 offspring were weaned on PND21 and were not exposed to DBP afterward. The age of vaginal opening and estrus onset, estrous cyclicity, c-Kit-ligand expression on ovarian granulosa cells, and the weight of ovaries and uterus of F1 female offspring were not affected, whereas serum levels of estradiol and progesterone were increased significantly by maternal exposure to 10mg/kg/day DBP from GD12 to PND21. Although F1 ovarian function may not be adversely affected by maternal exposure to DBP, the increased reproductive hormone levels may interfere in F1 rat fertility.