Identification of O-arylated huperzinines as novel cholinergic anti-inflammatory pathway agonists against gout arthritis.

Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O-arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1ß production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation. Compared with the clinical drugs hydrocortisone and indomethacin, as well as commercially available CAP agonists GTS-21 and pnu282987, 3k and 3q possessed greater potency against MSU-induced IL-1ß production. Meanwhile, these molecules possessed less cytotoxicity against promonocytic THP-1 macrophages when compared with colchicine. This work reports a concise strategy for direct modification of 2-pyridone moiety from natural Lycodine alkaloids, and provides novel frameworks for discovering CAP activators and drugs for gout arthritis.

Innate Lymphoid Cells: A Link between the Nervous System and Microbiota in Intestinal Networks.

Innate lymphoid cells (ILCs) are a novel family of innate immune cells that act as key coordinators of intestinal mucosal surface immune defense and are essential for maintaining intestinal homeostasis and barrier integrity by responding to locally produced effector cytokines or direct recognition of exogenous or endogenous danger patterns. ILCs are also involved in the pathogenesis of inflammatory bowel disease (IBD). Many studies have demonstrated the occurrence of crosstalk between ILCs and intestinal microbiota, and ILCs have recently been shown to be connected to the enteric nervous system (ENS). Thus, ILCs may act as a key link between the nervous system and microbiota in intestinal networks. In this review, we briefly summarize the role of the ILCs in the intestinal tract (particularly in the context of IBD) and discuss the relationship between ILCs and the microbiota/ENS.

Involvement of VKORC1 in the inhibition of calcium oxalate crystal formation in HK-2 cells.

The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of urolithiasis patients. This study searched for direct evidence to define the inhibitory activity of VKORC1 against calcium oxalate (CaOx) crystal formation. In the experiment of VKORC1 overexpression, HK-2 cells were transfected with the pFLAG-CMV-7.1-VKORC1 plasmid as a pFLAG-CMV-7.1-VKORC1 transfection group or the pFLAG-CMV-7.1 plasmid as a pFLAG-CMV-7.1 control group. In the experiment of VKORC1 knockdown, HK-2 cells were transfected with the PGPU6/GFP/Neo-VKORC1shRNA-2 as a PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group or the PGPU6/GFP/Neo-shRNA-NC plasmid as a PGPU6/GFP/Neo-shRNA-NC control group. The expression of VKORC1 in HK-2 cells was detected by real-time quantitative PCR and Western blotting. The CaOx crystal formation was observed under the laser-scanning confocal microscope. It was found that the expression levels of VKORC1 mRNA and protein were significantly higher in the pFLAG-CMV-7.1-VKORC1 transfection group than in the pFLAG-CMV-7.1 control group (P<0.01). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled CaOx monohydrate (COM) crystal medium for 48 h was 14±4 per field (100×) in the pFLAG-CMV-7.1-VKORC1 transfection group and 26±5 per field (100×) in the pFLAG-CMV-7.1 control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the pFLAG-CMV-7.1-VKORC1 transfection group was significantly reduced as compared with the pFLAG-CMV-7.1 control group (P<0.05). The expression levels of VKORC1 mRNA and protein were significantly lower in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group than in the PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled COM crystal medium was 65±11 per field (100×) in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group and 24±6 per field (100×) in the PGPU6/GFP/Neo-shRNA-NC control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group was significantly increased as compared with the PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). These findings suggested that the VKORC1 protein could inhibit CaOx salt crystallization, adhesion and aggregation. This research would help us to understand the mechanisms involving the interaction between crystallization and epithelial cells and the formation of CaOx.

Recent Progress on Durable Metal-N-C Catalysts for Proton Exchange Membrane Fuel Cells.

It is essential for the widespread application of proton exchange membrane fuel cells (PEMFCs) to investigate low-cost, extremely active, and long-lasting oxygen reduction catalysts. Initial performance of PGM-free metal-nitrogen-carbon (M-N-C) catalysts for oxygen reduction reaction (ORR) has advanced significantly, particularly for Fe-N-C-based catalysts. However, the insufficient stability of M-N-C catalysts still impedes their use in practical fuel cells. In this review, we focus on the understanding of the structure-stability relationship of M-N-C ORR catalysts and summarize valuable guidance for the rational design of durable M-N-C catalysts. In the first section of this review, we discuss the inherent degrading mechanisms of M-N-C catalysts, such as carbon corrosion, demetallation, H2 O2 attack, etc. As we gain a thorough comprehension of these deterioration mechanisms, we shift our attention to the investigation of strategies that can mitigate catalyst deterioration and increase its stability. These strategies include enhancing the anti-oxidation of carbon, fortifying M-N bonds, and maximizing the effectiveness of free radical scavengers. This review offers a prospective view on the enhancement of the stability of non-noble metal catalysts.

Phosphorus-Doping Enables the Superior Durability of a Palladium Electrocatalyst towards Alkaline Oxygen Reduction Reactions.

The sluggish kinetics of oxygen reduction reactions (ORRs) require considerable Pd in the cathode, hindering the widespread of alkaline fuel cells (AFCs). By alloying Pd with transition metals, the oxygen reduction reaction's catalytic properties can be substantially enhanced. Nevertheless, the utilization of Pd-transition metal alloys in fuel cells is significantly constrained by their inadequate long-term durability due to the propensity of transition metals to leach. In this study, a nonmetallic doping strategy was devised and implemented to produce a Pd catalyst doped with P that exhibited exceptional durability towards ORRs. Pd3P0.95 with an average size of 6.41 nm was synthesized by the heat-treatment phosphorization of Pd nanoparticles followed by acid etching. After P-doping, the size of the Pd nanoparticles increased from 5.37 nm to 6.41 nm, and the initial mass activity (MA) of Pd3P0.95/NC reached 0.175 A mgPd-1 at 0.9 V, slightly lower than that of Pd/C. However, after 40,000 cycles of accelerated durability testing, instead of decreasing, the MA of Pd3P0.95/NC increased by 6.3% while the MA loss of Pd/C was 38.3%. The durability was primarily ascribed to the electronic structure effect and the aggregation resistance of the Pd nanoparticles. This research also establishes a foundation for the development of Pd-based ORR catalysts and offers a direction for the future advancement of catalysts designed for practical applications in AFCs.

Strong Electronic Metal-Support Interactions Enable the Increased Spin State of Co-N4 Active Sites and Performance for Acidic Oxygen Reduction Reaction.

Nonprecious metal catalysts, particularly M-N-C catalysts, are widely recognized as promising contenders for the oxygen reduction reaction (ORR). However, a notable performance gap persists between M-N-C catalysts and Pt-based catalysts under acidic conditions. In this study, hybrid catalysts comprising single Co atoms and ultralow concentrations of Pt3Co intermetallic nanoparticles (NPs) are introduced to enhance ORR performance. Under acidic conditions, these hybrid catalysts demonstrate ORR efficiency with a half-wave potential of 0.895 V, negligible decay even after 80 000 cycles, and a high maximum power density of 1.34 W cm-2 in fuel cells. This performance surpasses those of Co-N-C and Pt/Co-N-C catalysts. Both experimental findings and theoretical computations suggest that the heightened ORR activity stems from an increase in the spin density of Co sites induced by noble metal NPs, facilitating the activation of O-O bonds via side-on overlapping and enabling a transition in the reaction pathway from associative to dissociative processes. This research offers a promising avenue for the systematic design of M-N-C cathodes with an enhanced performance for acidic fuel cells.

Highly Stable Pt-Based Oxygen Reduction Electrocatalysts toward Practical Fuel Cells: Progress and Perspectives.

The high cost and poor reliability of cathodic electrocatalysts for the oxygen reduction reaction (ORR), which requires significant amounts of expensive and scarce platinum, obstructs the broad applications of proton exchange membrane fuel cells (PEMFCs). The principles of ORR and the reasons for the poor stability of Pt-based catalysts are reviewed. Moreover, this paper discusses and categorizes the strategies for enhancing the stability of Pt-based catalysts in fuel cells. More importantly, it highlights the recent progress of Pt-based stability toward ORR, including surface-doping, intermetallic structures, 1D/2D structures, rational design of support, etc. Finally, for atomic-level in-depth information on ORR catalysts in fuel cells, potential perspectives are suggested, such as large-scale preparation, advanced interpretation techniques, and advanced simulation. This review aims to provide valuable insights into the fundamental science and technical engineering for practical Pt-based ORR electrocatalysts in fuel cells.

Rethinking the complexity and uncertainty of spatial networks applied to forest ecology.

Characterizing tree spatial patterns and interactions are helpful to reveal underlying processes assembling forest communities. Spatial networks, despite their complexity, are powerful to examine spatial interactions at an individual level using well-defined patterns. However, complex forestation networks introduce uncertainties. Validation methods are needed to assess whether network-based metrics can identify different processes. Here, we constructed three types of networks, which reflect various aspects of tree competition. Based on five spatial null models and 199 Monte-Carlo simulations, we were able to select network-based metrics that exhibited well performance in distinguishing different processes. This technique was then applied to a tropical forest dataset in Costa Rica. We found that the average node degree and the clustering coefficient are good metrics like the paired correlation function. In addition, the network approach can identify fine-scale spatial variations of tree competition and its underlying causes. Our analyzes also indicate that a bit of caution is needed when defining the network structure as well as designing network-based metrics. We suggested that validation techniques using corresponding spatial null models are critically important to reduce the negative effects caused by uncertainties of the network.

Percutaneous Endoscopic Posterior Lumbar Interbody Fusion with Unilateral Laminotomy for Bilateral Decompression Vs. Open Posterior Lumbar Interbody Fusion for the Treatment of Lumbar Spondylolisthesis.

Background: Endoscopic lumbar interbody fusion is a new technology that is mostly used for single-segment and unilateral lumbar spine surgery. The purpose of this study is to introduce percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) with unilateral laminotomy for bilateral decompression (ULBD) for lumbar spondylolisthesis and evaluate the efficacy by comparing it with open posterior lumbar interbody fusion (PLIF). Methods: Twenty-eight patients were enrolled in PE-PLIF with the ULBD group and the open PLIF group. The perioperative data of the two groups were compared to evaluate the safety of PE-PLIF with ULBD. The visual analog scale (VAS) back pain, VAS leg pain, and Oswestry Disability Index (ODI) scores of the two groups preoperatively and postoperatively were compared to evaluate clinical efficacy. Preoperative and postoperative imaging data were collected to evaluate the effectiveness of the operation. Results: No differences in baseline data were found between the two groups (p > 0.05). The operation time in PE-PLIF with the ULBD group (221.2 ± 32.9 min) was significantly longer than that in the PLIF group (138.4 ± 25.7 min) (p < 0.05), and the estimated blood loss and postoperative hospitalization were lower than those of the PLIF group (p < 0.05). The postoperative VAS and ODI scores were significantly improved in both groups (p < 0.05), but the postoperative VAS back pain score in the PE-PLIF group was significantly lower than that in the PLIF group (p < 0.05). The excellent and good rates in both groups were 96.4% according to MacNab's criteria. The disc height and cross-sectional area of the spinal canal were significantly improved in the two groups after surgery (p < 0.05), with no difference between the groups (p > 0.05). The fusion rates in PE-PLIF with the ULBD group and the PLIF group were 89.3% and 92.9% (p > 0.05), respectively, the cage subsidence rates were 14.3% and 17.9% (p > 0.05), respectively, and the lumbar spondylolisthesis reduction rates were 92.72 ± 6.39% and 93.54 ± 5.21%, respectively (p > 0.05). Conclusion: The results from this study indicate that ULBD can be successfully performed during PE-PLIF, and the combined procedure is a safe and reliable treatment method for lumbar spondylolisthesis.

Catalpol ameliorates depressive-like behaviors in CUMS mice via oxidative stress-mediated NLRP3 inflammasome and neuroinflammation.

The purpose of the present study was to investigate whether catalpol exhibited neuroprotective effects in chronic unpredictable mild stress (CUMS) mice through oxidative stress-mediated nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin-domain-containing 3 (NLRP3) inflammasome and neuroinflammation. Deficits in behavioral tests, including open field test (OFT), forced swim test (FST), and elevated plus-maze test (EPM), were ameliorated following catalpol administration. To study the potential mechanism, western blots, quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence imaging were performed on the hippocampus samples. We found that the defects of behavioral tests induced by CUMS could be reversed by the absence of NLRP3 and NLRP3 inflammasome might be involved in the antidepressant effects of catalpol on CUMS mice. Similar to the NLRP3 inflammasome, the expression of interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and inducible nitride oxide synthase (iNOS) were increased after CUMS. The current study demonstrated that catalpol possessed anti-inflammatory effect on CUMS mice and inhibited microglial polarization to the M1 phenotype. In addition, the activity of mitochondrial oxidative stress might be involved in the NLRP3 activation, which was proved by the downregulation of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved IL-1ß, after the administration of mitochondrion-targeted antioxidant peptide SS31. Taken together, we provided evidence that catalpol exhibited antidepressive effects on CUMS mice possibly via the oxidative stress-mediated regulation of NLRP3 and neuroinflammation.

Engineering of Long-Term Stable Transparent Nanoemulsion Using High-Gravity Rotating Packed Bed for Oral Drug Delivery.

BACKGROUND: Oil-in-water drug nanoemulsion forms drug delivery systems with high oral bioavailability. The conventional fabrication methods of nanoemulsion are low energy emulsification methods and high energy emulsification methods. However, both two methods are not ideal for industrial production. The problem of low energy emulsification methods is the high dosage of surfactant and co-surfactant which has potential biosecurity issues. What is more, high energy emulsification methods have some disadvantages, like the destruction of drug components, the price of equipment and the difficulties of industrial production. Hence, there have been a few commercial drug nanoemulsions so far. METHODS: In this work, we reported a novel method for the fabrication of stable and transparent drug nanoemulsion which contains hydrophilic drug rosuvastatin (ROS) calcium or hydrophobic drug silybinin (SYN) by using high-gravity rotating packed bed (RPB). The drug nanoemulsion was systematically characterized by droplet size, size distribution, stability and in vitro drug release as well as Caco-2 cells permeability. RESULTS: Compared with the self-emulsification method (SE), high-gravity technology could reduce 75% amount of mixed surfactants. The as-prepared nanoemulsion exhibited a very narrow droplet size distribution with a size of 13.53 ± 0.53 nm and a polydispersity index of 0.073 ± 0.018. Meanwhile, the drug nanoemulsion was physicochemically stable at 25°C and 4°C for one-year storage. Furthermore, both ROS and SYN nanoemulsion displayed higher cell permeability and in vitro dissolution than that of commercial formulations. CONCLUSION: These results demonstrate that RPB can be a potential device to facilitate the industrial production of drug nanoemulsion.

A Novel Antidiabetic Monomers Combination Alleviates Insulin Resistance Through Bacteria-Cometabolism-Inflammation Responses.

The present study sought to examine the therapeutic effect of a novel antidiabetic monomer combination (AMC) in treating type 2 diabetes mellitus (T2DM); while also elucidating the potential functional mechanism. Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to establish T2DM. The AMC group showed significant reduction in weight, fasting blood glucose (FBG), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and experienced reduced insulin resistance based on oral glucose tolerance testing (OGTT) and hyperinsulinemic-euglycemic clamp testing ("gold standard" for determining in vivo insulin sensitivity). Further, AMC restored the altered intestinal flora by increasing the abundance of the beneficial bacteria Akkermansia, and decreasing the number of harmful bacteria, including Bacteroides, Odoribacter, Prevotella 9, Alistipes, and Parabacteroides. Components of the host-microbial metabolome were also significantly changed in the AMC group compared to the HFD group, including hydroxyphenyllactic acid, palmitoleic acid, dodecanoic acid, linoleic acid, and erucic acid. Furthermore, AMC was found to inhibit inflammation and suppress signaling pathways related to insulin resistance. Lastly, spearman correlation analysis revealed relationships between altered microbial community and co-metabolite levels, co-metabolites and inflammatory cytokines. Hence, the potential mechanism responsible for AMC-mediated alleviation of insulin resistance was suggested to be involved in modulation of bacteria-cometabolism-inflammation responses.

Tunable nonlinear optical responses and carrier dynamics of two-dimensional antimonene nanosheets.

Sb nanosheets, also known as antimonene, have received ever-growing consideration as a promising new type of two-dimensional (2D) material due to their many attractive properties. However, how their nonlinear optical (NLO) properties are affected by their nanosheet structure and measurement conditions remains unclear. Herein, we report a successful size-selective production method for Sb nanosheets, which is based on a combination of lithium ion intercalation, solvent exfoliation and size selection centrifugation. This high-yield and size-selective preparation method enables fundamental investigation on the relation of the intrinsic optical properties of Sb nanosheets. Nanosecond Z-scan measurements revealed a unique size-dependent broadband NLO response. When the average size is reduced from 3 micrometers to 50 nanometers, the Sb nanosheets exhibit a clear transition from saturable absorption to reversed saturable absorption. Ultrafast transient absorption spectroscopic investigation indicated that exciton cooling is significantly faster in a small nanosheet than in large ones, revealing that the different exciton relaxation dynamic plays key roles in the distinct size-tunable nonlinear optical response. This work paves new ways towards the mass production and practical application of antimonene.

Cognitive Enhancing Effect of High-Frequency Neuronavigated rTMS in Chronic Schizophrenia Patients With Predominant Negative Symptoms: A Double-Blind Controlled 32-Week Follow-up Study.

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier-NCT03774927.

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia.

Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.

Effects of the long wavelength-filtered continuous spectrum on natural refractive development in juvenile guinea pigs.

AIM: To investigate the effects of spectral composition and light intensity on natural refractive development in guinea pigs. METHODS: A total of 124 pigmented guinea pigs (2-week-old) were randomly assigned to three groups at high (Hi; 4000 lx), medium (Me; 400 lx) and low (Lo; 50 lx) light intensities under a 12:12 light/dark cycle for 6wk. Each group was subdivided into subgroups with the following spectra: broad spectrum Solux halogen light (BS), 600 nm above-filtered continuous spectrum (600F), 530 nm above-filtered continuous spectrum (530F), and 480 nm above-filtered continuous spectrum (480F; HiBS: n=10, Hi600F: n=10, Hi530F: n=10, Hi480F: n=10, MeBS: n=10, Me600F: n=10, Me530F: n=10, Me480F: n=10, LoBS: n=11, Lo600F: n=12, Lo530F: n=10, Lo480F: n=11). Refractive error, corneal curvature radius, and axial dimensions were determined by cycloplegic retinoscopy, photokeratometry, and A-scan ultrasonography before and after 2, 4, and 6wk of treatment. Average changes from both eyes in the ocular parameters and refractive error were compared among different subgroups. RESULTS: After 6wk of exposure, high-intensity lighting enhanced hyperopic shift; medium- and low-intensity lighting enhanced myopic shift (P<0.05). Under the same spectrum, axial increase was larger in the low light intensity group than in the medium and high light intensity groups (HiBS: 0.65±0.02 mm, MeBS: 0.67±0.01 mm, LoBS: 0.82±0.02 mm; Hi600F: 0.64±0.02 mm, Me600F: 0.67±0.01 mm, Lo600F: 0.81±0.01 mm; Hi530F: 0.64±0.02 mm, Me530F: 0.67±0.01 mm, Lo530F: 0.73±0.02 mm; Hi480F: 0.64±0.01 mm, Me480F: 0.66±0.01 mm, Lo480F: 0.72±0.02 mm; P<0.05). Under 400 lx, there was a faster axial increase in the MeBS group than in the Me480F group (P<0.05). Under 50 lx, axial length changes were significantly larger in LoBS and Lo600F than in Lo530F and Lo480F (P<0.01). CONCLUSION: Under high-intensity lighting, high light intensity rather than spectrum distributions that inhibits axial increase. Under medium- and low-intensity lighting, filtering out the long wavelength inhibits axial growth in juvenile guinea pigs.

Preliminary study on visual recognition under low visibility conditions caused by artificial dynamic smog.

AIM: To quantitatively evaluate the effect of a simulated smog environment on human visual function by psychophysical methods. METHODS: The smog environment was simulated in a 40×40×60 cm3 glass chamber filled with a PM2.5 aerosol, and 14 subjects with normal visual function were examined by psychophysical methods with the foggy smog box placed in front of their eyes. The transmission of light through the smog box, an indication of the percentage concentration of smog, was determined with a luminance meter. Visual function under different smog concentrations was evaluated by the E-visual acuity, crowded E-visual acuity and contrast sensitivity. RESULTS: E-visual acuity, crowded E-visual acuity and contrast sensitivity were all impaired with a decrease in the transmission rate (TR) according to power functions, with invariable exponents of -1.41, -1.62 and -0.7, respectively, and R2 values of 0.99 for E and crowded E-visual acuity, 0.96 for contrast sensitivity. Crowded E-visual acuity decreased faster than E-visual acuity. There was a good correlation between the TR, extinction coefficient and visibility under heavy-smog conditions. CONCLUSION: Increases in smog concentration have a strong effect on visual function.

Brain-derived neurotrophic factor levels and its Val66Met gene polymorphism predict tardive dyskinesia treatment response to Ginkgo biloba.

BACKGROUND: Tardive dyskinesia (TD) has no well-accepted treatments or known pathophysiology, but low brain-derived neurotrophic factor (BDNF) may play an important role in its pathophysiology. Ginkgo biloba (EGb-761) is a potent antioxidant that has neuroprotective effects mediated through enhancing BDNF levels. We hypothesized that treatment with EGb-761 would increase serum BDNF levels and reduce TD, particularly among schizophrenia patients who have the BDNF valine 66 to methionine (Val66Met) genotype (Val/Val). METHODS: Serum BDNF levels and genotyping for the BDNF gene Val66Met polymorphism were assessed in Chinese schizophrenic patients with (n = 368) and without (n = 563) TD as well as healthy control subjects (n = 546). About half of the TD patients (n = 157) then participated in a double-blind, randomized, placebo-control 12-week treatment with 240 mg per day of EGb-761. Serum BDNF levels were measured again at posttreatment. Clinical efficacy was determined using the Abnormal Involuntary Movement Scale (AIMS). RESULTS: TD patients had lower BDNF levels than the non-TD patients and healthy controls. EGb-761 treatment improved symptoms of TD and increased BDNF levels compared with placebo treatment. Moreover, the improvement of AIMS total score correlated with the increase in BDNF levels. Furthermore, improvement in the AIMS score was greatest in those with the Val/Val allele and lowest with the Met/Met allele. CONCLUSIONS: The BDNF system may be implicated in the pathophysiology of TD and its improvement with antioxidant treatment. Furthermore, patients with the genetic potential for greater BDNF release (Val/Val at 66) may obtain a greater reduction in TD from EGb-761 treatment.

Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). Extract of Ginkgo biloba (EGb) is a potent antioxidant possessing free radical-scavenging activities. The aim of the study was to evaluate the efficacy of EGb-761, a standardized extract given in capsule form, in treating TD in schizophrenia patients. METHOD: Inpatients with DSM-IV-diagnosed schizophrenia and TD (n = 157) in a mainland China Veterans Affairs psychiatric hospital were randomly assigned to 12 weeks of treatment with either EGb-761, 240 mg/d (n = 78) or a placebo (n = 79) in a double-blind manner. Primary outcome measures were (1) change from baseline in the Abnormal Involuntary Movement Scale (AIMS) score and (2) proportion of patients with a ≥ 30% reduction in their AIMS total score at week 12. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS) and cognitive performance as measured by the Continuous Performance Test-37 Version and the 3-card Stroop task. Patients were recruited for the study between December 2006 and May 2007. RESULTS: Of the 157 patients who were randomly assigned, 152 (96.8%) completed the study. EGb-761 treatment significantly decreased the AIMS total score in patients with TD compared to those who were given a placebo (2.13 ± 1.75 vs -0.10 ± 1.69; P < .0001), with 40 (51.3%) and 4 (5.1%) patients achieving response in the EGb-761 and placebo treatment groups, respectively. There were no between-group differences in the PANSS total score or cognitive measures from baseline to week 12. CONCLUSIONS: EGb-761 appears to be an effective treatment for reducing the symptoms of TD in schizophrenia patients, and improvement may be mediated through the well-known antioxidant activity of this extract. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00672373.

[Pattern on the spread of novel influenza A (H1N1) and quantitative assessment of containment in mainland China].

OBJECTIVE: To study the epidemic tendency of emerging influenza A (H1N1) in mainland China, and to explore the different patterns of spread on the disease under the following contexts: (1) To stop the temperature screening program at the border areas of the country; (2) To stop measures of prevention and control on those identified cases and their close contacts; (3) To strengthen programs for the foreign immigrants on 'home quarantine'. METHODS: Under relevant parameters and information on the transmission link from different reference data, the patterns of influenza spread were simulated by Monte Carlo method. RESULTS: The temperature screening on border could inhibit the transmission of influenza A (H1N1) to some extent, so that after 3 months the cumulative number of cases will be reduced by 21.5% (1718 cases) and transmission speed of influenza A (H1N1) in mainland China will be delayed by about 4 days. Furthermore, taking positive measures of prevention and control could efficiently slow down the epidemic, so that after 3 months the cumulative number of cases will be reduced by 93.4% (about 90 thousand cases) and it would be delayed by about 15 days if influenza A (H1N1) spreads to the whole country. In addition, if the immigrants were able to practise quarantine measures consciously by themselves at home the effect of prevention and control against influenza A (H1N1) would be more significant. If 30%, 60% and 90% of immigrants would take quarantine measures home consciously, after 3 months the cumulative number of cases will be reduced by about 15% (about 940 cases), 34% (about 2230 cases) and 64% (about 4180 cases), respectively. Also, influenza A (H1N1) spreads to the whole country will be delayed by about 4 days, 10 days and 25 days, respectively. It is difficult to curb fully the development of the epidemic by taking existing control measures, and influenza A (H1N1) may spread to almost all provinces after about 3 months. CONCLUSION: The effects of existing prevention and control measures were objectively assessed and the results showed the necessity and effectiveness of these measures against the transmission of influenza A (H1N1), in the mainland of China.