A Distinct Metabolically Defined Central Nucleus Circuit Bidirectionally Controls Anxiety-Related Behaviors.

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeA neurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeA neurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeA neurons directly projected to the bed nucleus of the stria terminalis (BNST; sEHCeA-BNST). Optogenetic activation and inhibition of the sEHCeA-BNST pathway produced anxiolytic and anxiogenic effects, respectively. In summary, our studies reveal a set of molecular and circuit mechanisms of sEHCeA neurons underlying anxiety.SIGNIFICANCE STATEMENT Soluble epoxide hydrolase (sEH), a key enzyme that catalyzes the degradation of EETs, is shown to play a key role in mood disorders. It is well known that sEH is mostly localized in astrocytes in the prefrontal cortex and regulates depressive-like behaviors. Notably, sEH is also expressed in central nucleus of the amygdala (CeA) neurons. While the CeA has been studied for its role in the regulation of anxiety, the molecular and circuit mechanism is quite complex. In the present study, we explored a previously unknown cellular and circuitry mechanism that guides sEHCeA neurons response to anxiety. Our findings reveal a critical role of sEH in the CeA, sEHCeA neurons and CeA-bed nucleus of the stria terminalis (BNST) pathway in regulation of anxiety-related behaviors.

Treatment outcomes and prognostic factors for non- malignancy associated secondary hemophagocytic lymphohistiocytosis in children.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that requires prompt diagnosis and appropriate treatment. A risk-stratification model that could be used to identify high-risk pediatric patients with HLH who should be considered for second-line therapies, including salvage regimens and allogeneic hematopoietic cell transplantation (HCT), was developed. METHODS: The medical records of 88 pediatric patients (median age 1.4 years, range 0.2-15 years) with non-malignancy associated secondary HLH were retrospectively reviewed. Treatment strategies included dexamethasone, etoposide, and cyclosporine. RESULTS: Survival analysis showed HLH patients with infections other than Epstein-Barr virus (EBV) and unknown causes experienced better 5-year overall survival (OS) than patients with HLH due to autoimmune disease, EBV or immunodeficiency (76% vs. 65, 33.3, 11%, p < 0.001). On multivariate analysis, among all patients, non-response at 8 weeks was the most powerful predictor of poor OS. When treatment response was excluded, hemoglobin < 60 g/L and albumin < 25 g/L at diagnosis were associated with poor OS. In patients with EBV-HLH, hemoglobin < 60 g/L at diagnosis was associated with poor OS. A prognostic risk score was established and weighted based on hazard ratios calculated for three parameters measured at diagnosis: hemoglobin < 60 g/L (2 points), platelets < 30 × 109/L (1 point), albumin < 25 g/L (2 points). Five-year OS of low-risk (score 0-1), intermediate-risk (score 2), and poor-risk (score ≥ 3) patients were 88, 38, and 22%, respectively (p < 0.001). CONCLUSIONS: These findings indicate that clinicians should be aware of predictive factors at diagnosis and consider 8-week treatment response to identify patients with high-risk of disease progression and the need for second-line therapy and allogeneic HCT.

[Effect of ultraviolet irradiation on the proliferation of acute promyelocytic leukemia cells under hypoxic conditions and related mechanisms].

OBJECTIVE: To study the effect of 280 nm-LED ultraviolet irradiation on the proliferation of acute promyelocytic leukemia (APL) HL-60 cells under hypoxic conditions and related mechanism. METHODS: HL-60 cells in the logarithmic growth phase were selected and divided into control, hypoxia, ultraviolet and hypoxia+ultraviolet groups. The cells in the hypoxia group were treated with cobalt chloride (with a final concentration of 150 µmol/L), those in the ultraviolet group were irradiated by 280 nm-LED ultraviolet with an energy intensity of 30 J/m2, and those in the hypoxia+ultraviolet group were treated with cobalt chloride and then irradiated by 280 nm-LED ultraviolet. After 48 hours of treatment, the cells were placed under an invert microscope to observe cell morphology. CCK-8 assay was used to measure the inhibition rate of cell proliferation. Annexin V-FITC/PI double staining flow cytometry was used to evaluate cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression of Bcl-2. Each experiment above was repeated three times independently. RESULTS: Compared with the control group, the experimental groups showed shrinkage, decreased brightness, and disordered arrangement of cells, and the number of cells decreased over the time of culture. There were significant differences in the inhibition rate of cell proliferation and cell apoptosis rate among the groups (P<0.01), and the hypoxia+ultraviolet group showed the strongest inhibition of cell proliferation and induction of cell apoptosis, followed by the ultraviolet group and the hypoxia group. Compared with the control group, the other three groups had a gradual reduction in the mRNA expression of Bcl-2, and the hypoxia+ultraviolet group had a significantly greater reduction than the hypoxia and ultraviolet groups (P<0.01). CONCLUSIONS: Both hypoxia and ultraviolet irradiation can inhibit the proliferation of HL-60 cells and induce cell apoptosis, and ultraviolet irradiation has a better effect on proliferation inhibition and cell apoptosis under hypoxic conditions than under normoxic conditions, possibly by downregulating the mRNA expression of Bcl-2.

A genetic method for sex determination in Ovis spp. by interruption of the zinc finger protein, Y-linked (ZFY) gene on the Y chromosome.

The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene on the Y chromosome have not been completely elucidated, due, in part, to difficulties in gene targeting analysis of the Y chromosome. The zinc finger protein, Y-linked (ZFY) gene was first proposed to be a sex determination factor, although its function in spermatogenesis has recently been elucidated. Nevertheless, ZFY gene targeting analysis has not been performed to date. In the present study, RNA interference (RNAi) was used to generate ZFY-interrupted Hu sheep by injecting short hairpin RNA (shRNA) into round spermatids. The resulting spermatozoa exhibited abnormal sperm morphology, including spermatozoa without tails and others with head and tail abnormalities. Quantitative real-time polymerase chain reaction analysis showed that ZFY mRNA expression was decreased significantly in Hu sheep with interrupted ZFY compared with wild-type Hu sheep. The sex ratio of lambs also exhibited a bias towards females. Together, the experimental strategy and findings of the present study reveal that ZFY also functions in spermatogenesis in Hu sheep and facilitate the use of RNAi in the control of sex in Hu sheep.

Acute myeloid leukemia following etoposide therapy for EBV-associated hemophagocytic lymphohistiocytosis: a case report and a brief review of the literature.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by prolonged fever, cytopenia, hepatosplenomegaly, rash, icterus, and other neurological symptoms. Successful treatment of HLH by etoposide has improved outcomes for children with HLH. However, the development of treatment-related acute myeloid leukemia (t-AML) after the usage of this drug is a concern. CASE PRESENTATION: We report a case of acquired EBV-triggered HLH with progression to t-AML following etoposide therapy with cytogenetic abnormality for t (11; 19) (q23; p13) resulting in MLL gene fusion. The development of t-AML was detected 23 months after HLH diagnosis. CONCLUSIONS: Although the successful treatment of HLH by etoposide has improved outcomes for children with HLH, t-AML is a serious complication of topoisomerase II inhibitor therapy and is characterized by the presence of gene rearrangement. This study suggests that HLH patients undergoing therapy with HLH-2004 protocol need monitoring for future malignancy, especially in the initial 2 to 3 years.

Treatment outcome of young children with acute lymphoblastic leukaemia: achievements and directions implied from Shanghai Children's Medical Centre based SCMC-ALL-2005 protocol.

This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (<2 years old) with acute lymphoblastic leukaemia (ALL), which was designed to improve treatment outcome in Chinese paediatric patients. These aims were pursued through risk-directed stratification based on presenting clinical and genetic features, minimal residual disease (MRD) levels and treatment response. All the patients achieved completed remission with 5-year event-free survivals of 82·6 ± 9·7% (low risk), 52·6 ± 8·4% (intermediate risk), 28·6 ± 17·1% (high risk). Disease recurrence was detected in bone marrow, bone marrow plus testis, testis alone and central nervous system in 16 (24·2%), 1 (1·5%), 1 (1·5%) and 1 (1·5%) patients respectively. No deaths were reported during induction. The SCMC-ALL-2005 trial for ALL patients <2 years old indicated high remission induction and low infection and treatment-related mortality rates.

Astrocytic adenosine 5'-triphosphate release regulates the proliferation of neural stem cells in the adult hippocampus.

Astrocytes are key components of the niche for neural stem cells (NSCs) in the adult hippocampus and play a vital role in regulating NSC proliferation and differentiation. However, the exact molecular mechanisms by which astrocytes modulate NSC proliferation have not been identified. Here, we identified adenosine 5'-triphosphate (ATP) as a proliferative factor required for astrocyte-mediated proliferation of NSCs in the adult hippocampus. Our results indicate that ATP is necessary and sufficient for astrocytes to promote NSC proliferation in vitro. The lack of inositol 1,4,5-trisphosphate receptor type 2 and transgenic blockage of vesicular gliotransmission induced deficient ATP release from astrocytes. This deficiency led to a dysfunction in NSC proliferation that could be rescued via the administration of exogenous ATP. Moreover, P2Y1-mediated purinergic signaling is involved in the astrocyte promotion of NSC proliferation. As adult hippocampal neurogenesis is potentially involved in major mood disorder, our results might offer mechanistic insights into this disease.

Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

[Effect of bacillus Callmette-Guérin on cytotxicity of cytotoxic T lymphocyte from children with acute lymphoblastic leukemia for killing HL-60 cells in vitro].

OBJECTIVE: To study the effect of bacillus Callmette-Guérin (BCG) on cytotxicity of cytotoxic T lymphocyte (CTL) from human peripheral blood of children with acute lymphoblastic leukemia (ALL) for killing HL-60 cells in vitro. METHODS: The mononuclear cells were isolated from peripheral blood of ALL children and healthy children, and were cultured with RPMI1640, interleukin-2 (IL-2), phytohemagglutinin (PHA) and BCG.The growth of CTLs was observed by light microscopy. The proportions of CD3, CD3+CD4+ and CD3+CD8+ were determined by flow cytometry 10 days after culture. MTT method was performed to detect the cytotoxicity of CTLs for killing HL-60 cells. RESULTS: Neither the cell number nor the volume of CTLs changed significantly within 2 days of culture, but both began increasing on the 3rd day of culture and reached a peak on the 6-10th days. On the 10th day of culture, the cell number of CTLs in the BCG treatment group was much higher than in the group without BCG treatment. The CD3+CD8+ proportion in the leukemia group was much higher than in the control group. With the effect of BCG, the CD3+CD8+ proportion of the two groups became much higher. The cytotoxicity of CTLs for killing HL-60 cells in the leukemia group was weaker than in the control group. CONCLUSIONS: BCG along with IL-2 and PHA promotes the proliferation of CTLs and enhances the ability of CTLs in killing HL-60 cells.

Tyrosine Kinase Inhibitors for Pediatric Leukemia: History and Current Status.

Tyrosine kinase inhibitors (TKIs) block the activity of tyrosine kinases by competitive inhibition of ATP at the catalytic tyrosine kinase binding site and inhibit oncogenic signaling. One important target of TKIs is BCR-ABL1, which is constitutively activated in leukemia cells. In this review, we briefly describe the development of TKIs from the first generation to the third generation, and summarize their use in the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia in children. We highlight several future directions in the development of TKIs for pediatric leukemia therapy. In conclusion, we focus on chronic myeloid leukemia and acute lymphoblastic leukemia as the examples of pediatric blood cancer that significantly benefit from TKIs-based target therapy. Further development of TKIs will allow us to better manage pediatric leukemia.

[Establishment of An Animal Model of Acute B Lymphoblastic Leukemia with Minimal Residual Disease].

OBJECTIVE: To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease. METHODS: The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis. RESULTS: There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections. CONCLUSION: The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.

Muramyl Dipeptide modulates differentiation, maturity of dendritic cells and anti-tumor effect of DC-mediated T cell in acute leukemia children.

BACKGROUND: Targeted therapy is a potentially useful approach for antileukemic therapy, in particular eliminating minimal residual disease(MRD) to prevent tumor relapse. This study was aimed to find out an effective, nontoxic dendritic cell (DC) maturating agent for the immunotherapy of acute leukemia. RESULTS: MDP-matured DCs(M-DCs) expressed higher level of phenotypic markers and secreted higher cytokine level, while lower than TNF-α-matured DCs (T-DCs) and co-administration of MDP and TNF-α-matured DCs (MT-DCs). MT-DCs promoted significantly allogeneic T-cells reaction. As a result, allogeneic T-cell proliferated significantly and secreted higher amount of IFN-γ. HL60-derived antigens were presented more effectively by MT-DCs to cytotoxic T lymphocytes (CTLs) to induce more beneficial anti-tumor effects in a dose-dependent manner. METHODS: Purified mononuclear cells (MNCs) from bone marrow of acute leukemia children were differentiated by granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant human interleukin-4 (rhIL-4) and further matured by either Muramyl Dipeptide (MDP), tumor necrosis factor-alpha (TNF-α) or co-administration of MDP and TNF-α. CONCLUSIONS: These results demonstrate MDP can be used as a candidate clinical agent for antigen specific cancer immunotherapy.

Two new triterpene glycosides with monomethyl malonate groups from the rhizome of Cimifuga foetida L.

Two new 9,19-cycloartane triterpene glycosides 1-2, together with four known compounds--26-deoxyactein (3), actein (4), 7,8-didehydro-26-deoxyactein (5) and cimiaceroside B (6)--were isolated from the rhizome of Cimicifuga foetida. The new triterpene glycosides were identified as 23-O-methyl-24-deoxy-2'-O-(3''-methylmalonyl)-cimiaceroside B (1) and 2'-O-(3''-methylmalonyl)actein (2) based on analysis of their spectral data and chemical reactions.

Ultraviolet light-emitting diode irradiation induces reactive oxygen species production and mitochondrial membrane potential reduction in HL-60 cells.

OBJECTIVE: Ultraviolet light-emitting diode (UV LED) irradiation at 280 nm has been confirmed to induce apoptosis in cultured HL-60 cells, but the underlying mechanisms remain unclear. This study aimed to investigate the effects of 280 nm UV LED irradiation on reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) in HL-60 cells. METHODS: HL-60 cells were irradiated with 0, 8, 15, or 30 J/m2 of 280 nm UV LED and incubated for 2 hours. The intracellular ROS levels were assessed using the fluorescent probe 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and a fluorescence plate reader. MMP was determined by flow cytometry using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazol-carbocyanine iodide (JC-1) staining. The apoptosis-related proteins Bax and Bcl-2 were evaluated by western blot. RESULTS: UV LED irradiation at 280 nm induced a dose-dependent increase in ROS production and loss of MMP, and it activated apoptosis at irradiation doses of 8 to 30 J/m2. These results were consistent with a previous apoptosis study from the authors' group. CONCLUSION: Enhanced ROS production and mitochondrial depolarization are two distinct but interacting events, and both are involved in UV LED-induced apoptosis in HL-60 cells.

Shape Prediction of the Sheet in Continuous Roll Forming Based on the Analysis of Exit Velocity.

Continuous roll forming (CRF) is a new technology that combines continuous forming and multi-point forming to produce three-dimensional (3D) curved surfaces. Compared with other methods, the equipment of CRF is very simple, including only a pair of bendable work rolls and the corresponding shape adjustment and support assembly. By controlling the bending shapes of the upper and lower rolls and the size of the roll gap during forming, double curvature surfaces with different shapes can be produced. In this paper, a simplified expression of the exit velocity of the sheet is provided, and the formulas for the calculation of the longitudinal curvature radius are further derived. The reason for the discrepancy between the actual and predicted values of the longitudinal radius is deeply discussed from the perspective of the distribution of the exit velocity. By using the response surface methodology, the effects of the maximum compression ratio, the sheet width, the sheet thickness, and the transverse curvature radius on the longitudinal curvature radius are analyzed. Meanwhile, the correction coefficients of the predicted formulas for the positive and negative Gaussian curvature surfaces are obtained as 1.138 and 0.905, respectively. The validity and practicability of the modified formulas are verified by numerical simulations and forming experiments.

Effects of intermittently scanned continuous glucose monitoring on blood glucose control and the production of urinary ketone bodies in pregestational diabetes mellitus.

OBJECTIVE: To investigate the effects of intermittently scanned continuous glucose monitoring (isCGM) on blood glucose control, clinical value of blood glucose monitoring and production of urinary ketone bodies in pregestational diabetes mellitus. METHOD: A total of 124 patients with pregestational diabetes mellitus at 12-14 weeks of gestation admitted to the gestational diabetes clinic of our hospital from December 2016 to December 2018 were selected and randomly divided into two groups. Sixty patients adopted self-monitoring of blood glucose (SMBG) were taken as the control group, and the other 64 patients adopted isCGM system by wearing the device for 14 days. Blood sugar control, glycosylated albumin level, ketone production in urine, the maximum and minimum of blood sugar value measured by different monitoring methods and their occurrence time were observed in the two groups. RESULT: (1) No statistically significant differences were found between the groups in terms of maternal age, gestational age at first visit, family history, duration of diabetes, education level, total insulin dose, chronic hypertension, abortion history, nulliparity, assisted reproductive technology, history of macrosomia childbirth, pre-pregnancy BMI, and overweight (%) at the first visit and hypoglycemia, (2) the value of Glycated Albumin was lower in the CGM group compared to the control group at 2ed weeks (14.6 ± 2.2 vs. 16.8 ± 2.7, p < 0.001). The women in the CGM group spent increased time in the recommended glucose control target range of 3.5-7.8 mmol/L (69 ± 10% vs. 62 ± 11%, p < 0.001) and reduced time above target compared with those in the control group at 2 weeks (25 ± 7% vs. 31 ± 8%, p < 0.001). In the second week of the study, the positive rate of urinary ketone body in isCGM group was lower than that in the control group (42 ± 5 vs. 54 ± 5, p < 0.001), and (3) the minimum blood glucose of 31.2% (20/64) cases in isCGM group appeared during 0:00-2:59 at night, and 26.6% (17/64) cases appeared during 3:00-5:59 at night. The minimum values of 40.0% (24/60) cases in the control group appeared within the 30 min before lunch, 23.3% (14/60) within the 30 min before breakfast, and 11.7% (7/60) within the 30 min before dinner. The cases of minimum of blood sugar before meals accounted for 75% of all the minimum values, and the cases of minimum at night only accounted for 8.3%. CONCLUSION: Intermittently scanned continuous glucose monitoring can reduce hyperglycemia exposure and ketone body formation in pregestational diabetes mellitus. In addition, isCGM is better than SMBG in detecting nocturnal hypoglycemia.

Fuzi polysaccharide-1 produces antidepressant-like effects in mice.

Current antidepressants are clinically effective only after several weeks of administration. We show that Fuzi polysaccharide-1 (FPS), a new water-soluble polysaccharide isolated from Fuzi, which has been used to treat mood disorders in traditional Chinese medicine for centuries, increases the number of newborn cells in the dentate gyrus in adult mice, and most of these cells subsequently differentiate into new neurons. We also found that FPS administration reduces immobility in the forced swim test, and latency in the novelty suppressed-feeding test. Moreover, a 14-d regimen with FPS reverses avoidance behaviour and inhibition of hippocampal neurogenesis induced by chronic defeat stress. In contrast, imipramine, a well known antidepressant, reverses this avoidance behaviour only after 4 wk of continuous administration. Finally, acute treatment with FPS had no effect on brain monoamine levels in frontal cortex but significantly increases BDNF in the hippocampus, while the antidepressant effect and enhancement of cell proliferation induced by FPS administration were totally blocked by K252a, an inhibitor of trkB in a chronic social defeat depression model, suggesting that the neurogenic and antidepressant effects of FPS may involve BDNF signalling. In conclusion, our findings suggest that FPS could be developed as a putative antidepressant with a rapid onset of action.

Roles and mechanisms of Ca2+ in regulating primary root growth of plants.

Calcium (Ca2+) as a universal signal molecule plays pivotal roles in plant growth and development. It regulates root morphogenesis mainly through mediating phytohormone and stress signalings or affecting these signalings. In recent years, much progress has been made in understanding the roles of Ca2+ in primary root development. Here, we summarize recent advances in the functions and mechanisms of Ca2+ in modulating primary root growth in plants under normal and stressful conditions.

Update on roles of nitric oxide in regulating stomatal closure.

Nitric oxide (NO) as an important secondary messager plays crucial roles in modulating stomatal movement, especially abscisic acid (ABA)-induced stomatal closure. Accumulating evidence indicates that NO positively and negatively regulates guard cell ABA signaling. NO is also implicated in stomatal closure mediated by hydrogen sulfide, small peptides, polyamines, and methyl jasmonate. In this review, we summarize recent advances on the roles and the underlying mechanisms of NO in regulating stomatal closure in plants.