Lactobacillus plantarum CQPC02 intervenes in mouse lupus nephritis by regulating the NF-κB signaling pathway.

A strain of Lactobacillus plantarum CQPC02 (LP-CQPC02) isolated from naturally fermented kimchi was utilized in this investigation. In order to construct an animal model of lupus nephritis, pristane was used. We then used a kit to identify markers in mouse blood and tissues and a quantitative polymerase chain reaction (qPCR) to measure the expression of genes associated to nuclear factor kappa-B (NF-κB) in mouse kidney tissue. According to the results of the experiments, oral administration of LP-CQPC02 LP-CQPC02 may lessen the lupus nephritis-related rise in urine protein as well as the cytokine levels that were rising in the serum and renal tissues, including IL-6, IL-12, tumor necrosis factor alpha, and interferon. Additionally, in mice with nephritis, LP-CQPC02 can lower serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raise total protein (TP) and albumin (ALB) levels. In mice with nephritis, LP-CQPC02 can also reduce the positive rate of double-stranded deoxyribonucleic acid (dsDNA). Pathological sections were examined, and it was shown that LP-CQPC02 can lessen tissue damage such incomplete glomerular morphology and inflammatory infiltration brought on by nephritis. In the kidneys of mice with lupus nephritis, LP-CQPC02 can upregulate the expression of inhibitor of NF-κB (IκB-α), downregulate the expression of NF-κB, transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Lactobacillus plantarum CQPC02 has been confirmed to have an intervention effect on nephritis in mice and has the potential as a probiotic.

A novel micron europium cluster coordination polymer as a strong electrochemiluminescent emitter for accurate and sensitive detection of tetracycline.

In this work, a self-luminescent micron europium cluster coordination polymer (Eu-CCP) cathode electrochemiluminescence (ECL) emitter is first reported. The mass percentage of Eu in Eu-CCP is 50.1%, indicating that Eu-CCP has a high-nucleation luminescence center. In addition, our Eu-CCP possesses a stable and efficient ECL red emission performance, and the intensity is approximately 6.5-fold higher than that of the traditional tris(2,2'-bipyridyl)ruthenium(II) dichloride. The enhancement of Eu-CCP luminescence in our system is due to the following reasons: (1) the mixed ligand and high nuclear europium luminescent center can cooperate to improve the quenching effect induced by water or hydroxyl groups; and (2) external coreaction accelerator and coreactant enhancement. We also investigate the application of Eu-CCP in ECL sensors by sensitive detection of tetracycline (TC). The low detection limit (73.5 fmol·L-1), high selectivity, good stability and satisfactory recoveries indicate that our ECL strategy can be used to detect TC accurately and sensitively.

Lanthanide Ce(III)/Tb(III) bimetallic coordination polymer as an advanced electrochemiluminescence emitter for epinephrine sensing application.

By rationally introducing Ce(III) and Tb(III) into a coordination polymer (CP), a series of lanthanide bimetallic coordination polymers (Tb:Ce-BCPs) has been prepared in this work. Compared with pure Tb-CP and Ce-CP, bimetallic Tb:Ce-BCPs show stronger and more stable ECL intensity, which is mainly attributed to the "dual sensitization effect" combined with the energy transfer from Ce(III) to Tb(III) and the antenna effect from the ligand to the center atoms of Ce(III) and Tb(III). In the meantime, after explore the ECL intensity and morphologies of all these Tb:Ce-BCPs, the results show that the morphologies and ECL intensities of Tb:Ce-BCPs can be adjusted by doping different molar ratios of Ce(III) in Tb:Ce-BCP. Excitingly, Ce(III) can also act as a co-reaction accelerator, effectively promoting S2O82- to generate more SO4•-, thereby enhancing the ECL intensity of Tb:Ce-BCP. That is to say, Ce(III) plays a triple role in Tb:Ce-BCP. Furthermore, the ECL strength of Tb:Ce-BCP decreased by only 1.8% and 3.5%, respectively after the modified electrode was scanned for 800 s and stored for one month. Enlightened by the excellent ECL properties of Tb:Ce-BCP, we modified Tb:Ce-BCP directly on the surface of electrode, and explored its application in electroanalytical chemistry through the detection of epinephrine (EP) and the detection limit is 33 fmol L-1. Significantly, our ECL sensing strategy promotes the application of lanthanides in ECL sensor and opens vast possibilities for the synthesis of a new generation of ECL emitter in electroanalytical fields.

Presenilin enhancer 2 is crucial for the transition of apical progenitors into neurons but into not basal progenitors in the developing hippocampus.

Recent evidence has shown that presenilin enhancer 2 (Pen2; Psenen) plays an essential role in corticogenesis by regulating the switch of apical progenitors (APs) to basal progenitors (BPs). The hippocampus is a brain structure required for advanced functions, including spatial navigation, learning and memory. However, it remains unknown whether Pen2 is important for hippocampal morphogenesis. To address this question, we generated Pen2 conditional knockout (cKO) mice, in which Pen2 is inactivated in neural progenitor cells (NPCs) in the hippocampal primordium. We showed that Pen2 cKO mice exhibited hippocampal malformation and decreased population of NPCs in the neuroepithelium of the hippocampus. We found that deletion of Pen2 neither affected the proliferative capability of APs nor the switch of APs to BPs in the hippocampus, and that it caused enhanced transition of APs to neurons. We demonstrated that expression of the Notch1 intracellular domain (N1ICD) significantly increased the population of NPCs in the Pen2 cKO hippocampus. Collectively, this study uncovers a crucial role for Pen2 in the maintenance of NPCs during hippocampal development.

Novel Enhanced Lanthanide Electrochemiluminescence Luminophores: Ce3+-Doped TbPO4 Facile Synthesis and Detection for Mucin1.

Despite the upsurging interest in electrochemiluminescence (ECL) of lanthanides, the research in this field is still in its infancy due to the low intensity. In this work, a series of Ce3+-doped terbium orthophosphates (TbPO4:Ce) in different proportions have been synthesized through the co-precipitation method at room temperature. Meanwhile, through the investigation of morphologies and ECL properties of these TbPO4:Ce, it is concluded that the ECL intensity reaches the maximum when the molar ratio of Tb/Ce is 9:1 and the material is nanorod-shaped. The ECL intensity of TbPO4:Ce is significantly improved by doping with Ce3+ due to the dual sensitization strategy of the antenna effect from PO43- to Tb3+ and the energy transfer from Ce3+ to Tb3+. Interestingly, doping with Ce3+ can not only adjust morphology of TbPO4:Ce but also improve the ECL intensity. In addition, to verify the application of TbPO4:Ce, two single mucin1 (MUC1) aptamers are linked together to form a dual MUC1 aptamer chain. Then, a simple and sensitive ECL biosensor is constructed for the detection of MUC1, which can recognize the double amount of MUC1 and quench the ECL signal. As expected, the proposed biosensor shows good stability and acceptable selectivity and achieves sensitive detection of MUC1 with a dynamic range from 1 fg·mL-1 to 10 ng·mL-1 and a limit of detection of 0.5 fg·mL-1. This work may pave a new avenue for the study of direct ECL emission of lanthanides and prove to be ideal for the research of new ECL luminophores in electrochemical analysis.

Pen-2 Negatively Regulates the Differentiation of Oligodendrocyte Precursor Cells into Astrocytes in the Central Nervous System.

Mutations on γ-secretase subunits are associated with neurologic diseases. Whereas the role of γ-secretase in neurogenesis has been intensively studied, little is known about its role in astrogliogenesis. Recent evidence has demonstrated that astrocytes can be generated from oligodendrocyte precursor cells (OPCs). However, it is not well understood what mechanism may control OPCs to differentiate into astrocytes. To address the above questions, we generated two independent lines of oligodendrocyte lineage-specific presenilin enhancer 2 (Pen-2) conditional KO mice. Both male and female mice were used. Here we demonstrate that conditional inactivation of Pen-2 mediated by Olig1-Cre or NG2-CreERT2 causes enhanced generation of astrocytes. Lineage-tracing experiments indicate that abnormally generated astrocytes are derived from Cre-expressing OPCs in the CNS in Pen-2 conditional KO mice. Mechanistic analysis reveals that deletion of Pen-2 inhibits the Notch signaling to upregulate signal transducer and activator of transcription 3, which triggers activation of GFAP to promote astrocyte differentiation. Together, these novel findings indicate that Pen-2 regulates the specification of astrocytes from OPCs through the signal transducer and activator of transcription 3 signaling.SIGNIFICANCE STATEMENT Astrocytes and oligodendrocyte (OLs) play critical roles in the brain. Recent evidence has demonstrated that astrocytes can be generated from OL precursor cells (OPCs). However, it remains poorly understood what mechanism governs the differentiation of OPCs into astrocytes. In this study, we took advantage of OL lineage cells specific presenilin enhancer 2 (Pen-2) conditional KO mice. We show that deletion of Pen-2 leads to dramatically enhanced astrocyte differentiation from OPCs in the CNS. Mechanistic analysis reveals that deletion of Pen-2 inhibits Hes1 and activates signal transducer and activator of transcription 3 to trigger GFAP activation which promotes astrocyte differentiation. Overall, this study identifies a novel function of Pen-2 in astrogliogenesis from OPCs.

A Superstable Luminescent Lanthanide Metal Organic Gel Utilized in an Electrochemiluminescence Sensor for Epinephrine Detection with a Narrow Potential Sweep Range.

Metal organic gels (MOGs) as a new type of porous soft-hybrid supramolecular material have attracted widespread interest in various aspects due to their unique optical properties. In this work, we report a novel electrochemiluminescence (ECL) emission (679 nm) lanthanide MOG, which has been synthesized by a simple and rapid method at room temperature. This MOG (Tb-Ru-MOG) consists of a central metal ion, terbium (III), and two different ligands, tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium (II) dichloride (Ru(dcbpy)32+) and 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine (Hcptpy). Compared with the classic system of tris(2,2'-bipyridyl) ruthenium (II) dichloride (Ru(bpy)32+)/S2O82-, Tb-Ru-MOG/S2O82- owns a narrower potential sweep range (0.00 to -0.85 V) and a more stable and stronger ECL signal. Interestingly, the ECL intensity only decreased 2.0 and 0.1% after continuous scanning for 8000 s and storing at room temperature for 3 months. The possible ECL mechanism has been discussed in detail, which is mainly attributed to the internal synergies (antenna effect and energy transfer) and external co-reactant. Inspired by the unique luminescence characteristics of Tb-Ru-MOG, the application in electroanalytical chemistry was identified by the ECL on-off response for epinephrine with a linear range from 1.0 × 10-10 to 1.0 × 10-3 mol·L-1 and a detection limit of 5.2 × 10-11 mol·L-1. The results suggest that the as-proposed Tb-Ru-MOG will provide a robust pathway for new ECL luminophores in analysis.

Deletion of PDK1 in oligodendrocyte lineage cells causes white matter abnormality and myelination defect in the central nervous system.

PDK1 (3-Phosphoinositide dependent protein kinase-1) is a member in the PI3K (phosphatidylinositol 3 kinase) pathway and is implicated in neurodevelopmental disease with microcephaly. Although the role of PDK1 in neurogenesis has been broadly studied, it remains unknown how PDK1 may regulate oligogenesis in the central nervous system (CNS). To address this question, we generated oligodendrocyte (OL) lineage cells specific PDK1 conditional knockout (cKO) mice. We find that PDK1 cKOs display abnormal white matter (WM), massive loss of mature OLs and severe defect in myelination in the CNS. In contrast, these mutants exhibit normal neuronal development and unchanged apoptosis in the CNS. We demonstrate that deletion of PDK1 severely impairs OL differentiation. We show that genetic or pharmacological inhibition of PDK1 causes deficit in the mammalian target of rapamycin (mTor) signaling and down-regulation of Sox10. Together, these results highlight a critical role of PDK1 in OL differentiation during postnatal CNS development.

Chiral MnIII (Salen) Immobilized on Organic Polymer/Inorganic Zirconium Hydrogen Phosphate Functionalized with 3-Aminopropyltrimethoxysilane as an Efficient and Recyclable Catalyst for Enantioselective Epoxidation of Styrene.

Organic polymers/inorganic zirconium hydrogen phosphate (ZSPP, ZPS-IPPA, and ZPS-PVPA) functionalized with 3-aminopropyltrimethoxysilane were prepared and used to support chiral MnIII (salen) complexes (Jacobsen's catalyst). Different characterization methods demonstrated that the chiral MnIII (salen) complexes was successfully supported on the surface of the carrier (ZSPP, ZPS-IPPA, or ZPS-PVPA) through a 3-aminopropyltrimethoxysilane group spacer. The supported catalysts effectively catalyzed epoxidation of styrene with m-chloroperbenzoic acid (m-CPBA) as an oxidant in the presence of N-methylmorpholine N-oxide (NMO) as an axial base. These results (ee%, 53.3⁻63.9) were significantly better than those achieved under a homogeneous counterpart (ee%, 46.2). Moreover, it is obvious that there was no significant decrease in catalytic activity after the catalyst 3 was recycled four times (cons%: from 95.0 to 92.6; ee%: from 64.7 to 60.1). Further recycles of catalyst 3 resulted in poor conversions, although the enantioselectivity obtained was still higher than that of corresponding homogeneous catalyst even after eight times. After the end of the eighth reaction, the solid catalyst was allowed to stand in 2 mol/L of dilute hydrochloric acid overnight, prompting an unexpected discovery that the catalytic activity of the catalyst was recovered again at the 9th and 10th cycles of the catalyst.

Conditional Inactivation of Pen-2 in the Developing Neocortex Leads to Rapid Switch of Apical Progenitors to Basal Progenitors.

The transition of apical progenitors (APs) to basal progenitors (BPs) is an important neurogenic process during cortical expansion. Presenilin enhancer 2 (Pen-2, also named as Psenen) is a key subunit of γ-secretase and has been implicated in neurodevelopmental disease. However, it remains unknown how Pen-2 may regulate the maintenance of APs. To address this question, we generated a conditional KO (cKO) mouse in which Pen-2 is specifically inactivated in neural progenitor cells in the telencephalon. Both male and female embryos were used. We show that Pen-2 cKO cortices display remarkable depletion of Aps, but transient increase on BPs, compared with controls. We demonstrate that the proliferation rate of APs or BPs is not changed, but the switch of APs to BPs is dramatically accelerated in Pen-2 cKO cortices. Molecular analyses reveal decreased levels of Hes1 and Hes5 but increased levels of Ngn2 and NeuroD1 in Pen-2 KO cells. We report that expression of Notch1 intracellular domain in Pen-2 cKO cortices restores the population of APs and BPs. In summary, these findings highlight a central role of the Notch signaling in Pen-2-dependent maintenance of neural stem cells in the developing neocortex.SIGNIFICANCE STATEMENT Presenilin enhancer 2 (Pen-2) has been implicated in neurodevelopmental disease. However, mechanisms by which Pen-2 regulates cortical development are not understood. In this study, we generated neural progenitor cell-specific Pen-2 conditional KO mice. We observe depletion of apical progenitors and transiently increased the number of basal progenitors in the developing neocortex of Pen-2 mutant mice. Mechanistic analyses reveal decreased levels of Hes1 and Hes5, but increased levels of neurogenic transcription factors in Pen-2 mutant cortices, compared with controls. We demonstrate that reintroduction of Notch intracellular domain into mutant mice restores the population of apical progenitors to basal progenitors. The above findings strongly suggest that the Pen-2-Notch pathway plays an essential role in the maintenance of neural stem cells during cortical development.

Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development.

Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO) mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.

Increased adult neurogenesis associated with reactive astrocytosis occurs prior to neuron loss in a mouse model of neurodegenerative disease.

AIMS: This study was to investigate whether cell proliferation and adult neurogenesis are affected at early neurodegenerative stage when neuron loss has not begun to display. METHODS AND RESULTS: Forebrain-specific nicastrin (NCT) conditional knockout (cKO) mice were generated by crossing NCTf/f with CaMKIIα-Cre Tg mice. BrdU was used as a lineage tracer to label proliferating neural progenitor cells (NPCs). Immunohistochemistry (IHC) on BrdU indicated that the total number of BrdU positive (+) cells was increased in NCT cKO mice. IHC on doublecortin (DCX) showed that the total number of DCX+ cells was also increased in NCT cKO mice. NCT cKO mice displayed significant astrogliosis as well. However, NCT cKO mice at 3 months did not show significant neuronal death or synaptic loss. CONCLUSIONS: NCT-dependent γ-secretase activity plays an important role in cell proliferation and immature neuron generation. Enhanced neurogenesis and astrogliosis may be early cellular events prior to the occurrence of neuronal death in neurodegenerative disease.

Preventative effects of fermented Chimonobambusa quadrangularis shoot on activated carbon-induced constipation.

The present study aimed to determine the preventative effects of fermented Chimonobambusa quadrangularis shoot (FCQS) on activated carbon constipation in Kun Ming mice. FCQS has a more loose fiber tissue structure than unfermented fresh C. quadrangularis shoot (CQS), which is preferable for relieving constipation. In mice fed with FCQS for 9 days the time from consumption to their first black stool defecation (117 min) was shorter than the control group (192 min) and the CQS group (148 min); however, it was longer than the normal (85 min) and bisacodyl treatment (99 min) groups. The gastrointestinal transit of the FCQS group (73.8%) was increased, as compared with the control (37.9%) and CQS (61.7%) groups; however, it was decreased as compared with the normal (100%) and bisacodyl (88.3%) groups. By observing the hemotoxylin and eosin-stained section of mice intestine, it was demonstrated that FCQS reduced injury to the intestinal tract resulting from constipation and alleviated the damage caused to the intestinal villi over the effects observed in the CQS group. Furthermore, FCQS was also able to increase the serum levels of motilin, endothelin-1, vasoactive intestinal peptide and acetylcholinesterase compared with the control group. c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF) mRNA and protein expression levels in the small intestinal cells of FCQS-fed mice were increased, as compared with CQS-fed mice. Transient receptor potential cation channel subfamily V member 1 (TRPV1) and nitric oxide synthase (NOS) expression levels of small intestinal cells of FCQS-fed mice were reduced, as compared with CQS-fed mice. These findings demonstrated that FCQS may induce improved preventative effects on constipation, compared with CQS.

Chiral MnIII (Salen) Covalently Bonded on Modified ZPS-PVPA and ZPS-IPPA as Efficient Catalysts for Enantioselective Epoxidation of Unfunctionalized Olefins.

Chiral MnIII (salen) complex supported on modified ZPS-PVPA (zirconium poly(styrene-phenylvinylphosphonate)) and ZPS-IPPA (zirconium poly(styrene-isopropenyl phosphonate)) were prepared using ⁻CH2Cl as a reactive surface modifier by a covalent grafting method. The supported catalysts showed higher chiral induction (ee: 72%⁻83%) compared with the corresponding homogeneous catalyst (ee: 54%) for asymmetric epoxidation of α-methylstrene in the presence of 4-phenylpyridine N-oxide (PPNO) as axial base using NaClO as an oxidant. ZPS-PVPA-based catalyst 1, with a larger pore diameter and surface area, was found to be more active than ZPS-IPPA-based catalyst 2. In addition, bulkier alkene-like indene, was efficiently epoxidized with these supported catalysts (ee: 96%⁻99%), the results were much higher than those for the homogeneous system (ee: 65%). Moreover, the prepared catalysts were relatively stable and can be recycled at least eight times without significant loss of activity and enantioselectivity.

Insect tea extract attenuates CCl4-induced hepatic damage through its antioxidant capacities in ICR mice.

The Insect tea extract (ITE) contained many polyphenols, the aim of the present study was to determine the preventive effects of ITE on CCl4-induced hepatic damage in mice. ITE treated mice could reduce hepatic injury compared to the control mice. The 200 mg/kg ITE increased TC, ALB, SOD, CAT, GSH-Px serum levels, and decreased ALT, AST, ALP, TG, BUN, NO, MDA levels compared to the control group. By histological observation, ITE reduced injury to hepatic cells, and these effects were close to that seen with the drug silymarin. The antioxidant related mRNA and protein expressions of Mn SOD, Gu/Zn SOD, CAT, and GSH-Px increased with ITE treatment in hepatic damage mice. ITE treated mice also showed higher IκB-α mRNA and protein expression, and lower NF-κB-p65, iNOS, COX-2 expressions than those of control mice. These results proved ITE has a prophylactic effect in protecting against hepatic injury through the antioxidant capacities.