Differential Alterations in Topology Property of Resting State Networks Associated With Mental Health and Childhood Trauma.

Context: Childhood trauma can lead to greater vulnerability to psychopathology and can affect person's mental health throughout his or her life cycle. Research on the associations between childhood trauma and developmental outcomes is critical to creating effective interventions. Objective: The study intended to identify brain networks that are susceptible to childhood trauma by comparing differences in the networks of individuals with and without trauma, to investigate how changes in networks can mediate the effects childhood adversity on mental health. Design: The research team performed a prospective cross-sectional survey. Setting: The study took place at the Second Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 80 individuals aged 18-30 years, with and without childhood trauma. Outcome Measures: Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The research team: (1) assessed participants' depressive symptoms using the Beck Depression Inventory (BDI); anxiety levels using the State-Trait Anxiety Inventory (STAI); personality traits using the Three-Dimensional Personality Questionnaire (TPQ), and childhood traumatic experiences using the Childhood Trauma Questionnaire (CTQ); (2) analyzed the data using independent component analysis (ICA) and graph theory based on resting-state functional networks to assess the functional connectivity (FC) and global efficiency of participants' brains; (3) performed a correlation analysis between changes in the topological properties of participants' brains and neglect and abuse, (4) explored the mediating effects between childhood trauma and mental health, and (5) explored gender as a moderator of the relationship between neglect and changes in the global efficiency of within-network connectivity. Results: Childhood trauma was associated with altered global efficiency of the salience network (SAN) and the default mode network (DMN). Compared with the healthy control group, the childhood trauma group's global efficiency of the SAN for the left (P = .022) and right (P = .013) bilateral anterior insula were significantly higher and the global efficiency of the DMN for the right lateral precuneus was significantly lower (P = .022). Compared with males, neglect was significantly more likely to affect the global efficiency of the SAN for females (R2 = 0.473, t = -2.33, F(3,76) = 24.66, B = -0.005, and P = .022). The childhood trauma group's mean score for novelty seeking on the TPQ was significantly higher than that of the healthy control group (P = .029), showing that the global efficiency of the SAN and DMN had a significant role as a mediator between neglect and novelty seeking. Conclusions: These findings indicate that childhood trauma can alter resting-state functional networks in healthy youth. This abnormality in brain circuitry is especially relevant to the DMN and SAN networks.

Plasma metabolic profiling reveals that chromium yeast alleviates the negative effects of heat stress in mid-lactation dairy cows.

Chromium yeast (CY) supplementation has the potential to alleviate the negative effects of heat stress in dairy cows, but the mechanism remains elusive. We aimed to identify the metabolic mechanisms whereby CY supplementation alleviates the negative effects of heat stress in mid-lactation dairy cows. Twelve Holstein dairy cows with similar milk yield (24.6 ± 1.5 kg/d), parity (2 or 3) and days in milk (125 ± 8 d) were fed the same basal diet containing 0.09 mg of Cr/kg DM. They were allocated randomly to 2 groups: a control group (CON, without CY supplementation) and a CY group (CY, administered 0.36 mg Cr/kg DM). The experiment was performed over 8 weeks during a hot summer, in which the mean temperature-humidity index was 79.0 ± 3.13 (>72), indicating that the dairy cows were exposed to heat stress. Chromium yeast supplementation reduced rectal temperature (P = 0.032), and increased the lactation performance by increasing the yield of milk (+2.6 kg/d), protein, lactose and total solid, and protein and lactose percentages in the milk of the heat-stressed dairy cows (P < 0.05). Supplementation with CY increased the serum glucose and thyroxine concentrations, but reduced the urea nitrogen, insulin, and triiodothyronine concentrations on d 56 (P < 0.05). Furthermore, plasma metabolomic analysis was performed using liquid chromatography tandem-mass spectrometry, which identified 385 metabolites in the two groups. Subsequently, 16 significantly different metabolites in the plasma, were significantly higher in the CY group (variable importance for the projection >1.0, P < 0.05), and found to be involved in 6 Kyoto Encyclopedia of Genes and Genomes pathways, including those involved in nicotinate and nicotinamide metabolism. Specifically, plasma concentration of nicotinamide was higher after CY supplementation, which might also contribute to the reduction of rectal temperature, the regulation of glucose homeostasis, and an improvement in the lactation performance of heat-stressed dairy cows. In conclusion, CY supplementation reduces rectal temperature, influences metabolism by reducing serum insulin concentration and increasing serum glucose and plasma nicotinamide concentrations, and finally increases lactation performance of heat-stressed dairy cows.

Supplementation With Zinc Proteinate Increases the Growth Performance by Reducing the Incidence of Diarrhea and Improving the Immune Function of Dairy Calves During the First Month of Life.

Two experiments were conducted to identify the optimal dose of zinc proteinate (ZP) in the diet for dairy calves and then to compare early supplementation with the ZP or zinc methionine (ZM) on the growth performance, incidence of diarrhea, antioxidant status, and immune function of dairy calves during their first month of life. In Experiment 1, forty newborn female Holstein dairy calves were randomly divided into four groups (n = 10): a control group (without ZP supplementation, ZP0) or groups that received ZP supplementation at 40, 80, and 120 mg zinc/day, respectively (ZP40, ZP80, and ZP120). The experiment lasted 14 days, and the growth performance, incidence of diarrhea, and serum zinc concentration were analyzed. In Experiment 2, thirty-six newborn female Holstein dairy calves were randomly allocated to three groups (n = 12): a negative control group (without zinc supplementation, CON), a positive control group (supplemented with 80 mg zinc/day in the form of zinc methionine, ZM), and a ZP group (supplemented with 80 mg zinc/day in the form of ZP). The experiment lasted 28 days, and the growth performance, incidence of diarrhea, serum zinc concentration, serum antioxidant indicators, and concentrations of plasma immunoglobulins and cytokines were determined on days 7, 14, 21, and 28. Results showed that in Experiment 1, supplementation with ZP to yield 80 mg zinc/day increased the ADG (P < 0.01) and serum zinc concentration (P < 0.01), and decreased the F/G (P < 0.01) and the incidence of diarrhea (P < 0.05) during days 1-14. In Experiment 2, compared with the CON group, ZP increased the ADG (P < 0.01), serum zinc concentration (P < 0.01), and plasma immunoglobulin G (IgG; P < 0.01) and IgM (P < 0.01) concentrations, but reduced the incidence of diarrhea (P < 0.01), serum malondialdehyde (P < 0.01), and plasma interleukin-1ß (P < 0.01) concentrations during days 1-28. Overall, ZP supplementation to yield 80 mg zinc/day improves the growth performance and immune function, and decrease the incidence of diarrhea of dairy calves, which was comparable to the same dose of zinc in the form of ZM.

Melatonin Modulates Lactation by Regulating Prolactin Secretion Via Tuberoinfundibular Dopaminergic Neurons in the Hypothalamus- Pituitary System.

In-depth studies have identified many hormones important for controlling mammary growth and maintaining lactation. One of these is melatonin, which is synthesized and secreted by the pineal gland to regulate circadian rhythms, improve antioxidant capacity, and enhance immunity. Prolactin is secreted by the pituitary gland and is associated with the growth and development of mammary glands as well as initiation and maintenance of lactation. The hypothalamus-pituitary system, the most important endocrine system in the body, regulates prolactin secretion mainly through dopamine released from tuberoinfundibular dopaminergic neurons. This review provides a reference for further study and describes the regulation of lactation and prolactin secretion by melatonin, primarily via the protection and stimulation of tuberoinfundibular dopaminergic neurons.

Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor-associated macrophage in a sorafenib-resistant tumor model.

Tumor-associated macrophages (TAMs) play essential roles in tumor invasion and metastasis, and contribute to drug resistance. Clinical evidence suggests that TAM levels are correlated with local tumor relapse, distant metastasis, and poor prognosis in patients. In this study, we synthesized a TAM-targeted probe (IRD-αCD206) by conjugating a monoclonal anti-CD206 antibody with a near-infrared phthalocyanine dye. We then investigated the potential application of the IRD-αCD206 probe to near-infrared fluorescence (NIRF) imaging and photoimmunotherapy (PIT) of tumors resistant to treatment with the kinase inhibitor sorafenib. Sorafenib treatment had no effect on tumor growth in a 4T1 mouse model of breast cancer, but induced M2 macrophage polarization in tumors. M2 macrophage recruitment by sorafenib-treated 4T1 tumors was noninvasively visualized by in vivo NIRF imaging of IRD-αCD206. Small-animal single-photon emission computed tomography (SPECT)/CT and intratumoral microdistribution analysis indicated TAM-specific localization of the IRD-αCD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD-αCD206 suppressed the growth of sorafenib-resistant tumors. In vivo CT imaging and ex vivo histological analysis confirmed the inhibition of lung metastasis in mice by IRD-αCD206 PIT. These results demonstrate the utility of the IRD-αCD206 probe for TAM-targeted diagnostic imaging and treatment of tumors that are resistant to conventional therapeutics.

A near-infrared phthalocyanine dye-labeled agent for integrin αvß6-targeted theranostics of pancreatic cancer.

Integrin αvß6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin αvß6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin αvß6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. (18)F-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin αvß6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin αvß6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer.