Microbial infection promotes amyloid pathology in a mouse model of Alzheimer's disease via modulating γ-secretase.

Microbial infection as a type of environmental risk factors is considered to be associated with long-term increased risk of dementia, including Alzheimer's disease (AD). AD is characterized by two neuropathologically molecular hallmarks of hyperphosphorylated tau and amyloid-ß (Aß), the latter generated by several biochemically reactive enzymes, including γ-secretase. However, how infectious risk factors contribute to pathological development of the AD core molecules remains to be addressed. In this work, we utilized a modified herpes simplex virus type 1 (mHSV-1) and found that its hippocampal infection locally promotes Aß pathology in 5 × FAD mice, the commonly used amyloid model. Mechanistically, we identified HSV-1 membrane glycoprotein US7 (Envelope gI) that interacts with and modulates γ-secretase and consequently facilitates Aß production. Furthermore, we presented evidence that adenovirus-associated virus-mediated locally hippocampal overexpression of the US7 aggravates Aß pathology in 5 × FAD mice. Collectively, these findings identify a herpesviral factor regulating γ-secretase in the development and progression of AD and represent a causal molecular link between infectious pathogens and neurodegeneration.

Study of miRNA interactome in active rheumatoid arthritis patients reveals key pathogenic roles of dysbiosis in the infection-immune network.

OBJECTIVES: To characterize serum microRNA (miR) and the miR interactome of active RA patients in RA aetiology and pathogenesis. METHODS: The differentially expressed miRs (DEmiRs) in serum of naïve active RA patients (NARAPs, n = 9, into three pools) vs healthy controls (HCs, n = 15, into five pools) were identified with Agilent human miR microarray analysis. Candidate driver genes in epigenetic and pathogenic signalling pathway modules for RA were analysed using miRTarBase and a molecular complex detection algorithm. The interactome of these DEmiRs in RA pathogenesis were further characterized with gene ontology and Kyoto Encyclopaedia of Genes and Genomes. RESULTS: Three upregulated DEmiRs (hsa-miR-187-5p, -4532, -4516) and eight downregulated DEmiRs (hsa-miR-125a-3p, -575, -191-3p, -6865-3p, -197-3p, -6886-3p, -1237-3p, -4436b-5p) were identified in NARAPs. Interactomic analysis from heterogeneous experimentally validated sources yielded 1719 miR-target interactions containing 5.67% strong and 94.33% less strong experimental evidence. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses allocated the upregulated DEmiRs in the infection modules and the downregulated DEmiRs in the immune signalling pathways. Specifically, these DEmiRs revealed the significant contributions of the intestinal microbiome dysbiosis in the infection-inflammation-immune network for activation of T cells, immune pathways of IL-17, Toll-like receptor, TNF, Janus kinase-signal transducer and activator of transcription, osteoclast cell differentiation pathway and IgA production to the active RA pathogenesis. CONCLUSIONS: Our experiment-based interactomic study of DEmiRs in serum of NARAPs revealed novel clinically relevant miRs interactomes in the infection-inflammation-immune network of RA. These results provide valuable resources for understanding the integrated function of the miR network in RA pathogenesis and the application of circulating miRs as biomarkers for early aetiologic RA diagnosis.

Enhancement of nitrite reduction and enrichment of Methylomonas via conductive materials in a nitrite-dependent anaerobic methane oxidation system.

Nitrite-dependent anaerobic methane-oxidizing (n-damo) process has a promising prospect in anaerobic wastewater treatment, utilizing methane as the sole electron source to remove nitrite. However, the metabolic activity of n-damo bacteria is too low for practical application. This study aimed to stimulate n-damo process by introducing conductive nano-magnetite and/or electron shuttle anthraquinone-2,6-disulfonate (AQDS), and also set a comparative treatment of adding insulated ferrihydrite. The results showed that the nitrite reduction rate was enhanced the most significantly in treatment with nano-magnetite, approximately 1.6 times higher than that of the control without any supplement. While ferrihydrite application showed an adverse effect on n-damo process. The well-known aerobic methane oxidizer Methylomonas spp. was found to be enriched under n-damo condition with the supplementation of nano-magnetite and/or AQDS, but abundance of n-damo bacteria did not exhibit significant increase. It was hypothesized that Methylomonas spp. could be survived under anaerobic n-damo condition using oxygen produced by n-damo bacteria for the self-growth, and the nitrite reduction could be promoted through the enhancement of microbial interspecies electron transfer triggered by the introduction of conductive materials. It opens a new direction for the stimulation of n-damo activity, which needs more evidences to verify the hypothetic mechanism.

Optimization of membrane unit location in a full-scale membrane bioreactor using computational fluid dynamics.

The location of membrane units in the membrane tank is a key factor in the construction of a full-scale membrane bioreactor (MBR), as it would greatly affect the hydrodynamics in the tank, which could in turn affect the membrane fouling rate while running. Yet, in most cases, these units were empirically installed in tanks, no theory guides were currently available for the design of a proper location. In this study, the hydrodynamics in the membrane tank of a full-scale MBR was simulated using computational fluid dynamics (CFD). Five indexes (iLu, iLa, iLb, iLint, iLw) were used to indicate the unit location, and each of them was discussed for their individual impact on the risk water velocity (v0.05) in the membrane unit region. An optimal design with all the indexes equaling 0.6 was proposed, and was found to have a promotion of 146.9% for v0.05.

Analysis of the mixing performance of a full-scale membrane bioreactor for municipal wastewater treatment.

High energy consumption remains to be a key problem for application of membrane bioreactor (MBR). Optimization of MBR to save energy requires a compressive understanding of the performance of the reactor, among which the mixing performance is a significant parameter, however received little attention. In this study, a tracer experiment was carried out in a full-scale MBR for municipal wastewater treatment in China. The mixing performance of both the entire plant and the membrane tanks were evaluated. The entire plant was found to be a cascade of 2.15 continuous stirred tank reactors (CSTRs) with 8.02% of dead zones. The membrane tanks were also found to deviate from CSTR. The mixing energy was analyzed and compared with literature data from three aspects: the specific power used per unit of tank volume (Ps,v), per unit of permeate volume (Ps,p), and per unit of membrane area (Ps,m).

Crystallographically Aligned Perovskite Structures for High-Performance Polarization-Sensitive Photodetectors.

Polarization-sensitive perovskite photodetectors are realized by crystallographically aligning 1D perovskite arrays. High-quality inorganic perovskite single crystals with crystallographic order are fabricated by strictly manipulating the dewetting process of organic solution, yielding photodetectors with high photoresponsivity and fast response speed.

"Capillary-Bridge Lithography" for Patterning Organic Crystals toward Mode-Tunable Microlaser Arrays.

A versatile "capillary-bridge lithography" technique is developed for patterning 1D organic single crystals and microring structures through controlling the generation and dewetting of capillary bridges on an interface with asymmetric wettability. High-performance Fabry-Pérot and whispering-gallery mode lasing emission with tunable modes are achieved on these 1D and microring structures.

"Liquid Knife" to Fabricate Patterning Single-Crystalline Perovskite Microplates toward High-Performance Laser Arrays.

A facile and effective "liquid knife" is created by controlling the dewetting process of the liquid precursor, yielding patterning single-crystalline perovskite microplates with uniform size, precise positioning, high quality, and low lasing thresholds. The sizes and location of single-crystalline perovskite are controllable, leading to mode-tunable lasing emission and patterned lasers.

Reducing aeration energy consumption in a large-scale membrane bioreactor: Process simulation and engineering application.

Reducing the energy consumption of membrane bioreactors (MBRs) is highly important for their wider application in wastewater treatment engineering. Of particular significance is reducing aeration in aerobic tanks to reduce the overall energy consumption. This study proposed an in situ ammonia-N-based feedback control strategy for aeration in aerobic tanks; this was tested via model simulation and through a large-scale (50,000 m(3)/d) engineering application. A full-scale MBR model was developed based on the activated sludge model (ASM) and was calibrated to the actual MBR. The aeration control strategy took the form of a two-step cascaded proportion-integration (PI) feedback algorithm. Algorithmic parameters were optimized via model simulation. The strategy achieved real-time adjustment of aeration amounts based on feedback from effluent quality (i.e., ammonia-N). The effectiveness of the strategy was evaluated through both the model platform and the full-scale engineering application. In the former, the aeration flow rate was reduced by 15-20%. In the engineering application, the aeration flow rate was reduced by 20%, and overall specific energy consumption correspondingly reduced by 4% to 0.45 kWh/m(3)-effluent, using the present practice of regulating the angle of guide vanes of fixed-frequency blowers. Potential energy savings are expected to be higher for MBRs with variable-frequency blowers. This study indicated that the ammonia-N-based aeration control strategy holds promise for application in full-scale MBRs.

Hydrodynamic optimization of membrane bioreactor by horizontal geometry modification using computational fluid dynamics.

Geometry property would affect the hydrodynamics of membrane bioreactor (MBR), which was directly related to membrane fouling rate. The simulation of a bench-scale MBR by computational fluid dynamics (CFD) showed that the shear stress on membrane surface could be elevated by 74% if the membrane was sandwiched between two baffles (baffled MBR), compared with that without baffles (unbaffled MBR). The effects of horizontal geometry characteristics of a bench-scale membrane tank were discussed (riser length index Lr, downcomer length index Ld, tank width index Wt). Simulation results indicated that the average cross flow of the riser was negatively correlated to the ratio of riser and downcomer cross-sectional area. A relatively small tank width would also be preferable in promoting shear stress on membrane surface. The optimized MBR had a shear elevation of 21.3-91.4% compared with unbaffled MBR under same aeration intensity.

[Studies on chemical constituents of Zhuang medicine Excoecaria venenata and their cytotoxic activity].

Fourteen compounds were isolated from 95% ethanol extract by silica gel, MCI, and ODS column chromatography. These compounds were respectively identified as quercetin (1), kaempferol (2), (+)-catechin (3), fraxin (4), protocatechuic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), apocynol A (9), baccatin (10), cerevisterol (11), ellagic acid (12), 3, 3',4'-tri-0-methylellagic acid(13) and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(14) by analyzing their spectral data and comparing with the previously reported literatures. Except for gallic acid (6), all other compounds were isolated from this plant for the first time. Compounds 1, 2 and 6 showed moderate anti-proliferation activities on tumor cells.

Hydraulic optimization of membrane bioreactor via baffle modification using computational fluid dynamics.

Baffles are a key component of an airlift membrane bioreactor (MBR), which could enhance membrane surface shear for fouling control. In order to obtain an optimal hydraulic condition of the reactor, the effects of baffle location and size were systematically explored in this study. Computational fluid dynamics (CFD) was used to investigate the hydrodynamics in a bench-scale airlift flat sheet MBR with various baffle locations and sizes. Validated simulation results showed that side baffles were more effective in elevating membrane surface shear than front baffles. The maximum average shear stress was achieved by adjusting baffle size when both front and side baffles were installed. With the optimized baffle configuration, the shear stress was 10-30% higher than that without baffles at a same aeration intensity (specific air demand per membrane area in the range of 0-0.45m(3)m(-2)h(-1)). The effectiveness of baffles was particularly prominent at lower aeration intensities.

Simultaneous treatment of renal cysts and stones with single-session retroperitoneoscopic renal cyst decortication and retroperitoneoscopy-assisted percutaneous nephrolithotomy.

INTRODUCTION: To determine the safety and efficacy of single-session retroperitoneoscopic renal cyst decortication in conjunction with retroperitoneoscopy-assisted percutaneous nephrolithotomy (PCNL) for simultaneous treatment of renal cysts and stones. PATIENTS AND METHODS: We enrolled 15 patients (10 men and 5 women, mean age 41 years), who underwent one-stage retroperitoneoscopic renal cyst decortication and retroperitoneoscopy-assisted PCNL between January 2008 and May 2009 for symptomatic renal cysts and concomitant large kidney stones (mean stone area 6.6 cm(2)). Intraoperative blood loss, duration of operation, and postoperative complications were evaluated. Median follow-up time was 22 months (range 12-26). RESULTS: Average total operative time was 83 ± 12 min and mean duration of PCNL was 45 ± 5 min. Mean estimated blood loss was 80 ± 21 ml. A plain abdominal radiograph revealed an absence of residual stones in all cases. No cyst recurrence occurred within the follow-up period. The mean pre- and postoperative pain score was 7.3 ± 0.8 and 2.8 ± 0.6, respectively. All patients resumed ambulatory activities on the first postoperative day. No severe complications related to the procedure were encountered. CONCLUSION: The combined laparoscopic approach for simultaneous treatment of renal cysts and stones is safe and feasible. These results encourage further studies to determine long-term outcomes of this combined surgery.