Probiotic Potential and Safety Assessment of Lactiplantibacillus plantarum cqf-43 and Whole-Genome Sequence Analysis.

This study reports the whole-genome sequence of Lactiplantibacillus plantarum cqf-43 isolated from healthy sow feces. Based on genomic analysis, we performed a comprehensive safety assessment of strain cqf-43, using both in vitro and in vivo experiments, and explored its probiotic potential. The total genome length measures 3,169,201 bp, boasting a GC content of 44.59%. Through phylogenetic analyses, leveraging both 16S rRNA gene and whole-genome sequences, we confidently categorize strain cqf-43 as a member of Lactiplantibacillus. Genome annotation using Prokka unveiled a total of 3141 genes, encompassing 2990 protein-coding sequences, 71 tRNAs, 16 rRNAs, and 1 tmRNA. Functional annotations derived from COG and KEGG databases highlighted a significant abundance of genes related to metabolism, with a notable emphasis on carbohydrate utilization. The genome also revealed the presence of prophage regions and CRISPR-Cas regions while lacking virulence and toxin genes. Screening for antibiotic resistance genes via the CARD database yielded no detectable transferable resistance genes, effectively eliminating the potential for harmful gene transfer. It is worth highlighting that the virulence factors identified via the VFDB database primarily contribute to bolstering pathogen resilience in hostile environments. This characteristic is particularly advantageous for probiotics. Furthermore, the genome is devoid of menacing genes such as hemolysin, gelatinase, and biogenic amine-producing genes. Our investigation also unveiled the presence of three unannotated secondary metabolite biosynthetic gene clusters, as detected by the online tool antiSMASH, suggesting a great deal of unknown potential for this strain. Rigorous in vitro experiments confirmed tolerance of strain cqf-43 in the intestinal environment, its antimicrobial efficacy, sensitivity to antibiotics, absence of hemolysis and gelatinase activity, and its inability to produce biogenic amines. In addition, a 28-day oral toxicity test showed that the strain cqf-43 did not pose a health hazard in mice, further establishing it as a safe strain.

Effects of dietary supplementation with bioactive peptides derived from rapeseed protein on the growth performance, serum biochemistry and faecal micro-organism composition of weaned piglets.

The present study investigated the effects of supplementing bioactive peptides derived from rapeseed protein (rapeseed peptide, Rsp) on the growth performance, serum biochemistry and faecal micro-organism composition of weaned piglets. Sixty Duroc × Landrace × Yorkshire weaned piglets of similar weights were randomly divided into three groups. The control group (NC) was fed a basal diet, and the two treatment groups, Rsp-1 and Rsp-2, were fed a basal diet supplemented with 1% or 2% Rsp, respectively, for 28 days. Each treatment consisted of five replicates with four piglets per replicate. The results showed that Rsp treatment significantly improved the average daily gain and had a better feed-to-gain ratio (p < 0.05). The diarrhoea incidence and indices of Rsp-1 and Rsp-2 groups were significantly lower than the NC group (p < 0.05), and the effect of Rsp-2 on reducing the incidence of diarrhoea was significantly higher than that of Rsp-1 (p < 0.05). The serum albumin, serum immunoglobulin A and catalase levels of the Rsp-1 and Rsp-2 groups were significantly better than the NC group (p < 0.05). Additionally, Rsp treatment significantly gained the relative abundance of faecal Lactobacillaceae and decreased the relative abundance of faecal Eubacterium_coprostanoligenes_group, Treponema and Coprococcus (p < 0.05). In summary, Rsp supplementation improved the growth performance, ameliorated the diarrhoea, enhanced the immune and antioxidant functions and changed the composition of faecal micro-organisms in piglets. These findings indicate that Rsp positively affected the health of weaned piglets.

Role of ROS-Induced NLRP3 Inflammasome Activation in the Formation of Calcium Oxalate Nephrolithiasis.

Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.

Effects of enriched environment on depression and anxiety-like behavior induced by early life stress: A comparison between different periods.

BACKGROUND: Brain development is a prolonged process and it is sensitive to the environment during critical periods. Stress in early life is believed to increase vulnerability to depression, while enriched environment (EE) has beneficial effects on neural plasticity and depression. In this study, we compared the therapeutic effect of EE during different periods on early life stress-induced depression, and investigated the role of brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT) on the effect of EE. Plasma corticosterone level was also detected to evaluate the reactivity of hypothalamic-pituitary-adrenal axis. METHODS: C57BL/6 mice were subjected to a 4-h maternal separation (MS) procedure during postnatal days 2-21. After this separation, the mice were assigned to standard environment groups (SE), EE in the early period groups (3-8 weeks, EEE) and EE in the adult groups (8-13 weeks, EEA). Depression and anxiety behavior were evaluated at 14-weeks of age. The plasma corticosterone was quantified utilizing enzyme-linked immunosorbent assay. Hippocampus BDNF and AKT/p-AKT were detected using Western blotting. RESULTS: The results showed that MS increased depression and anxiety level, while EE in both intervention periods alleviated the symptoms of depression and anxiety. The EEE group showed better effects in terms of anhedonia and anxiety than the EEA group. The difference in despair behavior between the EEE and EEA groups was not significant. MS increased plasma corticosterone level, while EE decreased corticosterone level in both intervention periods. EE increased BDNF and p-AKT expression in the hippocampus, with stronger effects in the EEE group. CONCLUSION: EE during the early development period was more effective in alleviating depression and anxiety induced by early life stress. BDNF and AKT may play a significant role in the effect of EE, and further research is needed to explore the detailed neurobiological mechanisms.

Screening of the college students at clinical high risk for psychosis in China: a multicenter epidemiological study.

BACKGROUND: To investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students. METHODS: An epidemiological survey of the prevalence of the CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done following a 3-stage procedure. Participants were initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome. RESULTS: Twenty-three thousand sixty-three college students completed the survey during September 2017 to October 2018. Seventy-two students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. Thirteen and forty-six were set as the cutoff points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects. CONCLUSIONS: The 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in the general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.

Regulation of endoplasmic reticulum stress on the damage and apoptosis of renal tubular epithelial cells induced by calcium oxalate crystals.

This study aimed to observe whether calcium oxalate (CaOx) crystals can induce the activation of endoplasmic reticulum (ER) stress in human renal cortex proximal tubule epithelial (HK-2) cells and to explore the regulatory of ER stress on the damage and apoptosis of HK-2 cells induced by CaOx crystals. We detected the optimal CaOx crystal concentration and intervention time by Western blot. ER stress modifiers tunicamycin (TM) and 4-phenylbutyric acid (4-PBA) were used to regulate the ER stress of HK-2 cells. The activities of ER stress marker proteins GRP78 and CHOP were evaluated by Western blot and immunohistochemistry. Western blot and TUNEL staining were used to detect cell apoptosis. We observed cell-crystal adhesion with an optical microscope. Lactate dehydrogenase (LDH) test kit and IL-1ß enzyme-linked immunosorbent assay kit were used to detect and evaluate HK-2 cell damage. We found that the expression of ER stress marker proteins GRP78 and CHOP gradually increased with the increase in CaOx crystal concentration and intervention time and reached the maximum at 2.0 mmol/L and 24 h. The use of ER stress modifiers TM and 4-PBA can effectively regulate the ER stress level induced by CaOx crystals, and the level of apoptosis is positively correlated with the level of ER stress. 4-PBA pretreatment remarkably reduced cell-crystal adhesion and the secretions of IL-1ß and LDH, whereas the results of TM pretreatment were the opposite. In summary, the damage and apoptosis of HK-2 cells induced by CaOx crystals are closely related to the level of ER stress. Inhibiting the ER stress of HK-2 cells can substantially reduce the cell damage and apoptosis induced by CaOx crystals.

Effect of aromatherapy on preoperative anxiety in adult patients: A meta-analysis of randomized controlled trials.

BACKGROUND: and purpose: Preoperative anxiety is an important factor for postoperative complications, and many patients are using aromatherapy to relieve preoperative anxiety. This study aimed to evaluate the effect of aromatherapy on preoperative anxiety in adult patients. METHODS: An electronic search of six databases (Cochrane Library, PubMed, Embase, CINAHL, CNKI, and WanFang Data) was conducted for full-text publications of trials published from the inception of the databases to February 20, 2020. All randomized controlled trials (RCTs) where aromatherapy was used for treatment of preoperative anxiety were included. Interventions included all types of aromatherapy compared to standard care or placebo. The primary outcome was self-rated anxiety and the secondary outcome was adverse effect. Two researchers independently screened and extracted relevant data. A random-effects model was utilized to calculate the effect size as mean difference (MD). RESULTS: Our search retrieved 347 records. Thirteen trials were included for qualitative analysis, of which ten RCTs with 750 patients were included for meta-analysis. Most studies had a high or unclear selection and performance bias. Overall, aromatherapy was found to decrease preoperative anxiety significantly compared to the control group (MD = -3.95, 95%CI [-6.36, -1.53], P = 0.001). According to subgroup analysis, most subgroups showed a significant effect of aromatherapy on preoperative anxiety, except for the no treatment subgroup (MD: 5.40, 95%CI: 7.76 to 0.71) and female subgroup (MD: 3.96, 95%CI: 9.19 to 1.27). CONCLUSION: Aromatherapy may be an effective complementary treatment for preoperative anxiety. Nevertheless, due to methodological limitations of the included trials, further studies with strict control of the research design are required for firm recommendations.

Bacillus velezensis DP-2 isolated from Douchi and its application in soybean meal fermentation.

BACKGROUND: Soybean meal (SBM) is the most common protein source used in the poultry and livestock industries. It has high-quality protein, an excellent amino acid (AA) profile, and positive isoflavone properties. However, the antigen proteins in SBM are unsuitable for young animals. The objective of this study was to identify a Bacillus strain that can degrade soybean antigen proteins, and to evaluate the feasibility of its application in SBM fermentation. RESULTS: Bacillus velezensis DP-2 was isolated from Douchi, a fermented Chinese food. It degraded 96.14% and 66.51% of glycinin and ß-conglycinin, and increased the trichloroacetic acid-soluble protein (TCAN) content by 5.46 times in the SBM medium. DP-2 could secrete alkaline protease and neutral protease, with productivities of 5.85 and 5.99 U mL-1 . It had broad-spectrum, antibacterial activities against Rhizopus nigricans HR, Fusarium oxysporum ACCC37404, Penicillium digitatum SQ2, Aspergillus flavus C1, Aspergillus niger ACCC30005, Trichoderma viride YZ1, Candida tropicalis CICC1630, and Salmonella sp. ZY. For SBM fermentation, the optimal inoculum rate, temperature, and fermentation time of DP-2 were 2.21 × 107 CFU g-1 , 37 °C, and 48 h, respectively. The fermented soybean meal (FSBM) was cream-colored and glutinous. Its crude protein (CP), soluble protein, and TCA-N content were improved by 13.45%, 12.53%, and 6.37 times, respectively. The glycinin and ß-conglycinin content were reduced by 78.00% and 43.07%, respectively, compared with raw SBM. CONCLUSIONS: Bacillus velezensis DP-2 has potential as a starter culture for SBM fermentation. © 2020 Society of Chemical Industry.

Possible Involvement of the IL-6/JAK2/STAT3 Pathway in the Hypothalamus in Depressive-Like Behavior of Rats Exposed to Chronic Mild Stress.

INTRODUCTION: The interleukin-6/janus kinase 2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) pathway plays an important role in immune function, but little research has focused on this pathway in depression. We sought to examine the relationship between the IL-6/JAK2/STAT3 pathway and depressive-like behavior. METHODS: Using a chronic mild stress (CMS) paradigm, a total of 36 adult male Sprague-Dawley rats were divided into four matched groups: (1) control + vehicle, (2) CMS + vehicle, (3) control + paroxetine, and (4) CMS + paroxetine. We investigated the effects of CMS on depressive-like behavior by using the forced swimming test (FST). Subsequently, the mRNA levels of members of the IL-6/JAK2/STAT3 pathway were assessed by qRT-PCR. RESULTS: We found that rats exposed to CMS displayed a significant increase in immobility time and a decrease in climbing time in the FST. Moreover, mRNA levels of IL-6, JAK2, and STAT3 in the hypothalamus were increased following CMS. We also found that mRNA levels of IL-6, JAK2, and STAT3 were normalized by paroxetine administration, which coincided with normalization of the depressive-like behavior. CONCLUSIONS: The IL-6/JAK2/STAT3 pathway may be activated in depression, and targeting this pathway may provide a novel effective therapeutic approach for the treatment of depression.

Atorvastatin inhibits renal inflammatory response induced by calcium oxalate crystals via inhibiting the activation of TLR4/NF-κB and NLRP3 inflammasome.

This study aimed to investigate the renal protective effect of atorvastatin (ATV) on the kidney inflammation induced by calcium oxalate (CaOx) crystals. A cell model of cell-crystal interactions and a rat model of CaOx kidney stone were established. The expressions of TLR4, NF-κB, NLRP3, and cleaved caspase-1 in cells and rat kidney tissues were detected using Western blot, immunohistochemical, and/or immunofluorescence. The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) in cells, and lactic acid dehydrogenase (LDH) in the culture medium were measured. The secreted levels of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor-α (TNF-α) were examined by ELISA. The serum levels of creatinine (CRE) and blood urea nitrogen (BUN) were measured. von Kossa staining was used for the evaluation of renal lens deposition. The CaOx model group showed significantly decreased SOD level; increased concentrations of MDA; ROS and LDH; elevated expressions of TLR4, NF-κB, NLRP3, and cleaved caspase-1; and the elevated release of IL-1ß, IL-18, IL-6, and TNF- α as compared to the control group. The treatment with ATV significantly inhibited the formation of CaOx kidney stone by increasing the level of SOD; downregulating MDA, ROS, and LDH; inhibiting the expressions of TLR4, NF-κB, NLRP3 and cleaved caspase-1; and blocking the secretion of inflammatory cytokines. In addition, the serum levels of CRE and BUN, and the intrarenal crystal deposition were also significantly decreased in ATV-treated rats. In summary, oxidative stress, TLR4/NF-κB, and NLRP3 inflammasome pathways are involved in renal inflammatory responses induced by CaOx crystals. ATV treatment significantly suppressed oxidative stress, inhibited the activation of TLR4/NF-κB and NLRP3 inflammasome pathways, and decreased the release of inflammatory mediators, thereby ameliorating CaOx crystal-induced damage and crystal deposition in HK-2 cells and rat kidney tissues.

Effect of endoplasmic reticulum stress-mediated excessive autophagy on apoptosis and formation of kidney stones.

AIMS: This study was designed to reveal the role and underlying mechanism of excessive autophagy mediated by ERS via the PERK-eIF2α pathway in the apoptosis and formation of CaOx kidney stones. MAIN METHODS: Ethylene glycol (EG) was used to establish a rat model of CaOx kidney stones, and 100 mg/kg of ERS inhibitor 4-phenylbutyric acid (4-PBA) or 60 mg/kg of autophagy inhibitor chloroquine (CQ) was administered daily to the rats. Four weeks after administration, we collected blood and kidney tissues to analyze the occurrence of ERS and autophagy, apoptosis, renal function, renal tubular crystal deposition, and kidney damage, respectively. KEY FINDINGS: We observed that both 4-PBA and CQ treatment significantly inhibited the excessive autophagy and reduced apoptosis as well as decreasing p-PERK and p-eIF2α expressions. Meanwhile, the proportion of kidney weight, contents of creatinine and blood urea nitrogen, excretion of neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, and renal tubular deposition were markedly down-regulated. SIGNIFICANCE: The findings in this study suggested that ERS induced excessive autophagy via the PERK-eIF2α pathway, regulating cell damage and apoptosis. ERS-mediated inhibition of excessive autophagy effectively protected kidney function and prevented the apoptosis and formation of kidney stones.

Autophagy-endoplasmic reticulum stress inhibition mechanism of superoxide dismutase in the formation of calcium oxalate kidney stones.

BACKGROUND: Nephrolithiasis is a common disease in urology, and its pathogenesis is associated with various factors. Recent studies have shown that reactive oxygen species (ROS) can promote autophagy in the formation of kidney stones and exacerbate kidney injury. Endoplasmic reticulum stress (ERS), a key factor in regulating intracellular environmental homeostasis, is also directly related to ROS production. Therefore, this study aimed to investigate the regulatory effect of superoxide dismutase (SOD) on autophagy-ERS response during the formation of calcium oxalate (CaOx) kidney stones in rats. METHODS: Thirty-two rats were randomly divided into four groups (n = 8): normal control group, stone model group, stone model with atorvastatin group, and stone model with diethyldithiocarbamic acid (DETC) group. Rat models of CaOx kidney stones were established by intragastric administration of 0.75 % ethylene glycol for 4 weeks. Kidney/body weight was used to assess renal enlargement. Renal function was assessed by measuring serum SOD, creatinine (CRE), and blood urea nitrogen (BUN) levels. The expression of autophagy-related proteins LC3B and BECN1 was detected through immunohistochemical staining. Meanwhile, the expression of autophagy-ERS response-related proteins LC3B, BECN1, p62, GRP78, and CHOP was detected using Western blot and RT-PCR. Renal tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (Kim-1) were determined through enzyme-linked immunosorbent assay. The apoptosis of renal tubular cells and the expression of their signature proteins cleaved Caspase-3, Bax and Bcl-2 were detected using Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Western blot assays, respectively. Crystal deposition and histological tissue injury were assessed through Von Kossa staining. RESULTS: Compared with the control group, the stone model group showed higher kidney/body weight ratio; evidently higher expression of autophagy-ERS response- and apoptosis-related proteins LC3B, BECN1, GRP78, CHOP, Bax and cleaved Caspase-3; and lower levels of p62, bcl-2 protein, and SOD. The stone model group also showed higher levels of apoptosis, serum CRE, BUN, NGAL, and Kim-1, as well as considerably greater crystal deposition and renal injury, than the control group. Atorvastatin reduced the levels of autophagy-ERS response, kidney injury, and crystal deposition, but they were increased by DETC. CONCLUSION: Enhanced SOD activity can protect the kidneys by reducing autophagy-ERS response and CaOx kidney stone formation. Atorvastatin may be a new option for the prevention and treatment of nephrolithiasis.

Effect of M2 Macrophages on Injury and Apoptosis of Renal Tubular Epithelial Cells Induced by Calcium Oxalate Crystals.

BACKGROUND: M2 macrophages have important roles in diseases such as tumours, cardiovascular diseases and renal diseases. This study aimed to determine the effects and protective mechanism of M2 macrophages against oxidative stress injury and apoptosis induced by calcium oxalate crystals (CaOx) in renal tubular epithelial cells (HK-2) under coculture conditions. METHODS: THP-1 cells were induced to differentiate into M2 macrophages by using phorbol-12-myristate-13-acetate, IL-4 and IL-13. Morphological features were observed by microscopy. Phenotypic markers were identified by reverse transcription-polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay (ELISA). HK-2 cells were treated with 0.5 mg/mL CaOx crystals and co-cultured with M2 macrophages or apocynin. The viability of HK-2 cells was detected by CCK-8 assay. The lactate dehydrogenase (LDH) activity of HK-2 cells was analysed using a microplate reader. The apoptosis of HK-2 cells was examined by flow cytometry and Hoechst 33258 staining. Reactive oxygen species (ROS) expression and mitochondrial membrane potential in HK-2 cells were detected by a fluorescence microplate reader. Western blot analysis was conducted to detect the expression of p47phox, Bcl-2, cleaved caspase-3, cytochrome c, p38 MAPK, phospho-p38 MAPK, Akt and phospho-Akt. RESULTS: The results of morphology, reverse transcription-polymerase chain reaction, Western blot and ELISA showed that THP-1 cells were successfully polarised to M2 macrophages. The results of co-culture suggested that M2 macrophages or apocynin significantly increased the cell viability and decreased the LDH activity and apoptosis rate after HK-2 cells were challenged with CaOx crystals. The expression of the p47phox protein and the concentration of ROS were reduced, the release of mitochondrial membrane potential and the expression of the Bcl-2 protein were upregulated and the protein expression of cleaved caspase-3 and cytochrome c was downregulated. The expression of the phosphorylated form of p38 MAPK increased. Under coculture conditions with M2 macrophages, the Akt protein of HK-2 cells treated with CaOx crystals was dephosphorylated, but the phosphorylated form of Akt was not reduced by apocynin. CONCLUSIONS: M2 macrophages reduced the oxidative stress injury and apoptosis of HK-2 cells by downregulating the activation of NADPH oxidase, reducing the production of ROS, inhibiting the phosphorylation of p38 MAPK and enhancing the phosphorylation of Akt. We have revealed one of the possible mechanisms by which M2 macrophages reduce the formation of kidney stones.

Calcifying nanoparticles induce cytotoxicity mediated by ROS-JNK signaling pathways.

Calcifying nanoparticles (CNPs) play an important role in kidney stone formation, but the mechanism(s) are unclear. CNPs were isolated and cultured from midstream urine of patients with kidney stones. CNP morphology and characteristics were examined by electron microscopy and electrophoresis analysis. Chemical composition was analyzed using energy-dispersive X-ray microanalysis and Western blotting. Human renal proximal convoluted tubule cell (HK-2) cultures were exposed to CNPs for 0, 12 and 72 h, and production of reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis levels were evaluated. CNPs isolated from patients showed classical morphology, the size range of CNPs were 15-500 nm and negative charge; they were found to contain fetuin-A. Exposure of HK-2 cells to CNPs induced ROS production, decreased mitochondrial membrane potential and decreased cell viability. Transmission electron microscopy showed that CNPs can enter the cell by phagocytosis, and micrographs revealed signs of apoptosis and autophagy. CNPs increased the proportion of apoptotic cells, down-regulated Bcl-2 expression and up-regulated Bax expression. CNPs also up-regulated expression of LC3-B, Beclin-1and p-JNK.CNPs are phagocytosed by HK-2 cells, leading to autophagy, apoptosis and ROS production, in part through activation of JNK signaling pathways. ROS and JNK pathways may contribute to CNP-induced cell injury and kidney stone formation.

Different levels of facial expression recognition in patients with first-episode schizophrenia: A functional MRI study.

BACKGROUND: The impairment of facial expression recognition has become a biomarker for early identification of first-episode schizophrenia, and this kind of research is increasing. AIMS: To explore the differences in brain area activation using different degrees of disgusted facial expression recognition in antipsychotic-naïve patients with first-episode schizophrenia and healthy controls. METHODS: In this study, facial expression recognition tests were performed on 30 first-episode, antipsychotic-naïve patients with schizophrenia (treatment group) and 30 healthy subjects (control group) with matched age, educational attainment and gender. Functional MRI was used for comparing the differences of the brain areas of activation between the two groups. RESULTS: The average response time difference between the patient group and the control group in the 'high degree of disgust' facial expression recognition task was statistically significant (1.359 (0.408)/2.193 (0.625), F=26.65, p<0.001), and the correct recognition rate of the treatment group was lower than that of the control group (41.05 (22.25)/59.84 (13.91, F=19.81, p<0.001). Compared with the control group, the left thalamus, right lingual gyrus and right middle temporal gyrus were negatively activated in the patients with first-episode schizophrenia in the 'high degree of disgust' emotion recognition, and there was a significant activation in the left and right middle temporal gyrus and the right caudate nucleus. However, there was no significant activation difference in the 'low degree of disgust' recognition. CONCLUSIONS: In patients with first-episode schizophrenia, the areas of facial recognition impairment are significantly different in different degrees of disgust facial expression recognition.

Brain regional homogeneity and function connectivity in attenuated psychosis syndrome -based on a resting state fMRI study.

BACKGROUND: By combining regional homogeneity (ReHo) and functional connectivity (FC) analyses, this study aimed to explore brain functional alterations in Attenuated Psychosis Syndrome (APS), which could provide complementary information for the neurophysiological indicators for schizophrenia (SZ) associated brain dysfunction. METHODS: Twenty-one APS subjects and twenty healthy controls were enrolled in the data acquisition of demographics and clinical characteristics as well as structural and resting-state functional magnetic resonance imaging (rs-fMRI). ReHo analysis was conducted to determine the peak coordinate of the abnormal regional brain activity. Then, identified brain regions were considered as seed regions and were used to calculate FC between reginal brain voxels and whole brain voxels. Finally, potential correlations between imaging indices and clinical data were also explored. RESULTS: Four APS and two HC subjects were excluded because the largest dynamic translation or rotation had exceeded 2 mm / 2°. Compared with healthy controls (HCs), APS subjects exhibited higher ReHo values in the right middle temporal gyrus (MTG) and lower ReHo values in the left middle frontal gyrus (MFG), left superior frontal gyrus (SFG), left postcentral gyrus (PoCG), and left superior frontal gyrus, medial (SFGmed). Considered these areas as seed regions, the APS subjects showed abnormal enhancement in functional brain connections, predominantly in the frontal and temporal lobes. CONCLUSIONS: We concluded that the APS subjects had spatially regional dysfunction and remoted synchronous dysfunction in the frontal and temporal lobes of the brain, and changes in ReHo and FC patterns may reveal the mechanism of brain dysfunctions and may serve as an imaging biomarker for the diagnosis and evaluation of SZ.

JSH-23 prevents depressive-like behaviors in mice subjected to chronic mild stress: Effects on inflammation and antioxidant defense in the hippocampus.

Nuclear factor-kappa B (NF-κB), which is reported to play an important role in the pathogenesis of depression, also has a central role in the genesis and progression of inflammation. Here, we have targeted the nuclear translocation of NF-κB using 4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23) to elucidate its role in depression. We investigated the antidepressant-like effects of JSH-23 in the chronic mild stress (CMS) mouse model, which is a valid, reasonably reliable, and useful model of depression. The antidepressant-like effects of JSH-23 were evaluated using the sucrose preference test (SPT) and the forced swimming test (FST). We also assessed inflammatory markers [interleukin (IL)-6 and tumor necrosis factor-α (TNF-α)] and components of antioxidant defense [superoxide dismutase (SOD) and nuclear factor erythroid-2-related factor 2 (Nrf 2)] in the hippocampus. Fluoxetine, a classical antidepressant, was used in this study as a positive control. Administration of JSH-23 significantly prevented the decreased sucrose preference in the SPT and prevented the increased immobility time in the FST caused by CMS, but had no effect on locomotor activity. Expression of NF-κB p65 protein in the hippocampus was decreased, and elevated levels of IL-6 and TNF-α were reduced, after JSH-23 administration. In addition to its anti-inflammatory effect, JSH-23 treatment increased the expression of SOD and Nrf 2 in the hippocampus, suggesting that it strengthens antioxidant defense. The current study demonstrated that inhibiting the NF-κB signaling cascade using JSH-23 prevented depressive-like behaviors by decreasing inflammation and improving antioxidant defense in the hippocampus. We concluded that NF-κB activation plays an important role in the pathophysiology of depression and that targeting NF-κB signaling may provide a novel and effective therapy for depression. Additional preclinical studies and clinical trials are, however, needed to further elucidate the effects of this therapeutic strategy.

Efficient continuous-wave and short-pulse Ho3+-doped fluorozirconate glass all-fiber lasers operating in the visible spectral range.

In this work, efficient visible Ho3+-doped fluorozirconate glass (Ho:ZBLAN) all-fiber lasers operating in continuous-wave (CW) and Q-switching regimes are experimentally demonstrated. The combination of a direct blue pump, a highly-doped Ho:ZBLAN fiber and the fiber end-facet mirrors contributes to a simple all-fiber configuration. A tunable laser emission in the green spectral range of 543-550 nm is achieved with >150 mW output power and a tunable deep-red laser around 754-758 nm is also obtained with about 16 mW output power. Interestingly, stable visible self-Q-switched operation was successfully observed. For the green Q-switched all-fiber laser, a maximum single pulse energy of 196 nJ is realized with a repetition rate of 97.66 kHz and a pulse duration of 605 ns. As the pump power is increased, the deep-red Q-switched all-fiber laser has the pulse repetition rate from 59.88 to 100.5 kHz and the pulse duration from 4.85 to 2.02 µs, corresponding to the maximum pulse energy of 58 nJ. To the best of our knowledge, this work is the first demonstration of Ho:ZBLAN all-fiber lasers emitting in the visible spectral range (i.e., both green and deep-red wavelengths).

Inhibition of Autophagy Attenuated Ethylene Glycol Induced Crystals Deposition and Renal Injury in a Rat Model of Nephrolithiasis.

BACKGROUND/AIMS: Nephrolithiasis is a common and frequently occurring disease, its exact pathogenesis is remains unclear. Emerging data suggest that autophagy plays a vital role in the pathophysiological processes of kidney diseases. Therefore, this study was designed to investigate the potential role of autophagy in the formation of calcium oxalate (CaOx) kidney stones in rat model. METHODS: Thirty-two rats were randomly divided into four groups (eight rats/group): untreated control group, stone model group, rapamycin-treated group, chloroquine-treated group. Rat models of CaOx nephrolithiasis was administration of 0.75% ethylene glycol (EG) in their drinking water for 4 weeks. Western blot and transmission electron microscope (TEM) were used to detect the expression of autophagy related protein LC3-II, BECN1 and p62 and autophagic vacuoles respectively. Renal function was evaluated by measuring the levels of serum CRE and BUN. Renal tubular injury markers NGAL and Kim-1 was determined by ELISA kits. Von Kossa staining was used to assess crystal deposits and histological tissue injury. TUNEL staining was employed to assess apoptosis of the renal tubular cell. RESULTS: Compare with the controls, the expression of autophagy related protein LC3-II, BECN1 and number of autophagic vacuoles were increased significantly, whereas the p62 protein level was decreased in the stone model group. The levels of apoptosis, serum CRE and BUN, NGAL and Kim-1 in the stone model group were increased compared with the control group and crystals deposition and renal injury were increased significantly. However, the levels of autophagy, kidney injury and crystal deposition were decreased by chloroquine but increased by rapamycin. CONCLUSION: These findings suggested that rats were administration of ethylene glycol could lead to the formation of CaOx nephrolithiasis and autophagy activation. Inhibiting autophagy could be an effective therapeutic approach for decreasing the formation of nephrolithiasis.