Kirigami-based metastructures with programmable multistability.

SignificanceDifferent from most existing multistable structures whose multiple stable states are achieved through the combinational effect of bistable units, we invent a generic tristable kirigami cuboid. The three stable states have fundamentally distinct geometric configurations and chirality, and the transformation among them can be realized by tension/compression or clockwise/counterclockwise twist. Tessellating the units in series, a family of multistable metamaterials can be constructed, the mechanical behaviors of which are programmable by the unit geometry, the material of the elastic joints, the number of units, and the loading conditions. As a demonstration of the potential applications, a frequency reconfigurable antenna for 5G triple-band communication is developed based on a tristable unit, and the frequency tunability is verified by experiments.

Catheter-Assisted Bioinspired Adhesive Magnetic Soft Millirobot for Drug Delivery.

Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.

Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

Influence of key component interactions in flour on the quality of fried flour products.

In the field of food, the interaction between various components in food is commonly used to regulate food quality. Starches, proteins, and lipids are ubiquitous in the food system and play a critical role in the food system. The interaction between proteins, starches, and lipids components in flour is the molecular basis for the formation of the classical texture of dough, and has a profound impact on the processing properties of dough and the quality of flour products. In this article, the composition of the key components of flour (starch, protein and lipid) and their functions in dough processing were reviewed, and the interaction mechanism of the three components in the dynamic processing of dough from mixing to rising to frying was emphatically discussed, and the effects of the components on the network structure of dough and then on the quality of fried flour products were introduced. The analysis of the relationship between dough component interaction, network structure and quality of fried flour products is helpful to reveal the common mechanism of quality change of fried flour products, and provide a reference for exploring the interaction of ingredients in starch food processing.

Thiazolidine-2,4-dione derivatives as potential α-glucosidase inhibitors: Synthesis, inhibitory activity, binding interaction and hypoglycemic activity.

In order to find effective α-glucosidase inhibitors, a series of thiazolidine-2,4-dione derivatives (C1 âˆ¼ 36) were synthesized and evaluated for α-glucosidase inhibitory activity. Compared to positive control acarbose (IC50 = 654.35 ± 65.81 µM), all compounds (C1 âˆ¼ 36) showed stronger α-glucosidase inhibitory activity with IC50 values of 0.52 ± 0.06 âˆ¼ 9.31 ± 0.96 µM. Among them, C23 with the best anti-α-glucosidase activity was a reversible mixed-type inhibitor. Fluorescence quenching suggested the binding process of C23 with α-glucosidase in a static process. Fluorescence quenching, CD spectra, and 3D fluorescence spectra results also implied that the binding of C23 with α-glucosidase caused the conformational change of α-glucosidase to inhibit the activity. Molecular docking displayed the binding interaction of C23 with α-glucosidase. Compound C23 (8 âˆ¼ 64 µM) showed no cytotoxicity against LO2 and 293 cells. Moreover, oral administration of C23 (50 mg/kg) could reduce blood glucose and improve glucose tolerance in mice.

New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation.

A series of chromone derivatives bearing thiazolidine-2,4-dione moiety (5 âˆ¼ 37) were synthesized and evaluated for their PTP1B inhibitory activity, interaction analysis and effects on insulin pathway in palmitic acid (PA)-induced HepG2 cells. The results showed that all derivatives presented potential PTP1B inhibitory activity with IC50 values of 1.40 ± 0.04 âˆ¼ 16.83 ± 0.54 µM comparing to that of positive control lithocholic acid (IC50: 9.62 ± 0.14 µM). Among them, compound 9 had the strongest PTP1B inhibitory activity with the IC50 value of 1.40 ± 0.04 µM. Inhibition kinetic study revealed that compound 9 was a reversible mixed-type inhibitor against PTP1B. CD spectra results confirmed that compound 9 changed the secondary structure of PTP1B by their interaction. Molecular docking explained the detailed binding between compound 9 and PTP1B. Compound 9 also showed 19-fold of selectivity for PTP1B over TCPTP. Moreover compound 9 could recovery PA-induced insulin resistance by increasing the phosphorylation of IRSI and AKT. CETSA results showed that compound 9 significantly increased the thermal stability of PTP1B.

Cognitive benefits of folic acid, docosahexaenoic acid and a combination of both nutrients in mild cognitive impairment; possible alterations though mitochondrial function and DNA damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA+DHA (FA 800µg/d + DHA 800mg/d), FA (800µg/d), DHA (800mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow, scores of full intelligence quotient (FIQ) (ßDHA: 1.302, 95%CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95%CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95%CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA+DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000034351. Registered 3 July 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=53345.

Anisotropic structure building unit involving diverse chemical bonds: a new opportunity for high-performance second-order NLO materials.

We define the anisotropic structure building unit that encompasses diverse chemical bonds (ABUCB). The ABUCB is highly likely to cause anisotropy in both crystallographic structure and spatial electron distribution, ultimately resulting in enhanced macroscopic optical anisotropy. Accordingly, the (PO3F)2- or (SO3F)- tetrahedron involving the unique P-F or S-F bond serves as such an ABUCB. The distinct chemical bond effectively alters the microscopic nature of the structure building unit, such as polarizability anisotropy, hyperpolarizability, and geometry distortion; this consequently changes the macroscopic second-order nonlinear optical (2nd-NLO) properties of the materials. In this review, we summarize both typical and newly emerged compounds containing ABUCBs. These compounds encompass approximately 90 examples representing six distinct categories, including phosphates, borates, sulfates, silicates, chalcogenides and oxyhalides. Furthermore, we demonstrate that the presence of ABUCBs in DUV/UV NLO compounds contributes to an increase in birefringence and retention of a large band gap, facilitating phase matching in high-energy short-wavelength spectral ranges. On the other hand, the inclusion of ABUCBs in IR NLO compounds offers a feasible method for increasing the band gap and consequently enhancing the larger laser-induced damage threshold. This review consolidates various trial-and-error explorations and presents a novel strategy for designing 2nd-NLO compounds, potentially offering an opportunity for the development of high-performance 2nd-NLO materials.

Single-center phase 2 study of PD-1 inhibitor combined with DNA hypomethylation agent + CAG regimen in patients with relapsed/refractory acute myeloid leukemia.

Anti-PD-1 monotherapy had limited clinical efficacy in relapsed/refractory (r/r) AML patients with higher PD-1 and PD-L1 expression. Hence, we investigated the efficacy and safety of PD-1 inhibitor with DNA hypomethylating agent (HMA) + CAG regimen in patients who had failed prior AML therapy. In this phase 2, single-arm study, r/r AML patients received azacitidine or decitabine plus CAG regimen with tislelizumab. Primary endpoints were efficacy (objective response rate [ORR]) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). Statistical analyses were performed using Stata 14.0 and SPSS 20.0 software where P < 0.05 denoted significance. Twenty-seven patients were enrolled patients and completed 1 cycle, and 14 (51.9%) and 4 (14.8%) patients completed 2 and 3 cycles, respectively. ORR was 63% (14: complete remission [CR]/CR with incomplete hematologic recovery [CRi], 3: partial remission (PR), 10: no response [NR]). Median OS (mOS) and EFS were 9.7 and 9.2 months, respectively. With a median follow-up of 8.2 months (1.1-26.9), the mOS was not reached in responders (CR/CRi/PR) while it was 2.4 months (0.0-5.4) in nonresponders (P = 0.002). Grade 2-3 immune-related adverse events (irAEs) were observed in 4 (14.8%) patients and 3 nonresponders died of lung infection after treatment. Tislelizumab + HMA + CAG regimen showed improved outcomes in r/r AML patients with lower pretherapy leukemia burden. irAEs were mild and low-grade and higher pretherapy bone marrow CD4+ CD127+ PD-1+ T cells might serve as a predictor of treatment response.ClinicalTrials.gov identifier NCT04541277.

CiTSA: a comprehensive platform provides experimentally supported signatures of cancer immunotherapy and analysis tools based on bulk and scRNA-seq data.

Immunotherapy has greatly changed the status of cancer treatment, and many patients do not respond or develop acquired resistance. The related research is blocked by lacking of comprehensive resources for researchers to discovery and analysis signatures, then further exploring the mechanisms. Here, we first offered a benchmarking dataset of experimentally supported signatures of cancer immunotherapy by manually curated from published literature works and provided an overview. We then developed CiTSA ( http://bio-bigdata.hrbmu.edu.cn/CiTSA/ ) which stores 878 entries of experimentally supported associations between 412 signatures such as genes, cells, and immunotherapy across 30 cancer types. CiTSA also provides flexible online tools to identify and visualize molecular/cell feature and interaction, to perform function, correlation, and survival analysis, and to execute cell clustering, cluster activity, and cell-cell communication analysis based on single cell and bulk datasets of cancer immunotherapy. In summary, we provided an overview of experimentally supported cancer immunotherapy signatures and developed CiTSA which is a comprehensive and high-quality resource and is helpful for understanding the mechanism of cancer immunity and immunotherapy, developing novel therapeutic targets and promoting precision immunotherapy for cancer.

Self-Supported Pd Nanorod Arrays for High-Efficient Nitrate Electroreduction to Ammonia.

Electrochemical nitrate (NO3 - ) reduction to ammonia (NH3 ) offers a promising pathway to recover NO3 - pollutants from industrial wastewater that can balance the nitrogen cycle and sustainable green NH3 production. However, the efficiency of electrocatalytic NO3 - reduction to NH3 synthesis remains low for most of electrocatalysts due to complex reaction processes and severe hydrogen precipitation reaction. Herein, high performance of nitrate reduction reaction (NO3 - RR) is demonstrated on self-supported Pd nanorod arrays in porous nickel framework foam (Pd/NF). It provides a lot of active sites for H* adsorption and NO3 - activation leading to a remarkable NH3 yield rate of 1.52 mmol cm-2  h-1 and a Faradaic efficiency of 78% at -1.4 V versus RHE. Notably, it maintains a high NH3 yield rate over 50 cycles in 25 h showing good stability. Remarkably, large-area Pd/NF electrode (25 cm2 ) shows a NH3 yield of 174.25 mg h-1 , be promising candidate for large-area device for industrial application. In situ FTIR spectroscopy and density functional theory calculations analysis confirm that the enrichment effect of Pd nanorods encourages the adsorption of H species for ammonia synthesis following a hydrogenation mechanism. This work brings a useful strategy for designing NO3 - RR catalysts of nanorod arrays with customizable compositions.

Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

Integrative analysis of γδT cells and dietary factors reveals predictive values for autism spectrum disorder in children.

BACKGROUND: Autism spectrum disorder (ASD) includes a range of multifactorial neurodevelopmental disabilities characterized by a variable set of neuropsychiatric symptoms. Immunological abnormalities have been considered to play important roles in the pathogenesis of ASD, but it is still unknown which abnormalities are more prominent. METHODS: A total of 105 children with ASD and 105 age and gender-matched typically developing (TD) children were recruited. An eating and mealtime behavior questionnaire, dietary habits, and the Bristol Stool Scale were investigated. The immune cell profiles in peripheral blood were analyzed by flow cytometry, and cytokines (IFN-γ, IL-8, IL-10, IL-17A, and TNF-α) in plasma were examined by Luminex assay. The obtained results were further validated using an external validation cohort including 82 children with ASD and 51 TD children. RESULTS: Compared to TD children, children with ASD had significant eating and mealtime behavioral changes and gastrointestinal symptoms characterized by increased food fussiness and emotional eating, decreased fruit and vegetable consumption, and increased stool astriction. The proportion of γδT cells was significantly higher in children with ASD than TD children (ß: 0.156; 95% CI: 0.888 âˆ¼ 2.135, p < 0.001) even after adjusting for gender, eating and mealtime behaviors, and dietary habits. In addition, the increased γδT cells were evident in all age groups (age < 48 months: ß: 0.288; 95% CI: 0.420 âˆ¼ 4.899, p = 0.020; age ≥ 48 months: ß: 0.458; 95% CI: 0.694 âˆ¼ 9.352, p = 0.024), as well as in boys (ß: 0.174; 95% CI: 0.834 âˆ¼ 2.625, p < 0.001) but not in girls. These findings were also confirmed by an external validation cohort. Furthermore, IL-17, but not IFN-γ, secretion by the circulating γδT cells was increased in ASD children. Machine learning revealed that the area under the curve in nomogram plots for increased γδT cells combined with eating behavior/dietary factors was 0.905, which held true in both boys and girls and in all the age groups of ASD children. The decision curves showed that children can receive significantly higher diagnostic benefit within the threshold probability range from 0 to 1.0 in the nomogram model. CONCLUSIONS: Children with ASD present with divergent eating and mealtime behaviors and dietary habits as well as gastrointestinal symptoms. In peripheral blood, γδT cells but not αßT cells are associated with ASD. The increased γδT cells combined with eating and mealtime behavior/dietary factors have a high value for assisting in the diagnosis of ASD.

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy.

Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier's endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

Advances on Hormones in Cosmetics: Illegal Addition Status, Sample Preparation, and Detection Technology.

Owing to the rapid development of the cosmetic industry, cosmetic safety has become the focus of consumers' attention. However, in order to achieve the desired effects in the short term, the illegal addition of hormones in cosmetics has emerged frequently, which could induce skin problems and even skin cancer after long-term use. Therefore, it is of great significance to master the illegal addition in cosmetics and effectively detect the hormones that may exist in cosmetics. In this review, we analyze the illegally added hormone types, detection values, and cosmetic types, as well as discuss the hormone risks in cosmetics for human beings, according to the data in unqualified cosmetics in China from 2017 to 2022. Results showed that although the frequency of adding hormones in cosmetics has declined, hormones are still the main prohibited substances in illegal cosmetics, especially facial masks. Because of the complex composition and the low concentration of hormones in cosmetics, it is necessary to combine efficient sample preparation technology with instrumental analysis. In order to give the readers a comprehensive overview of hormone analytical technologies in cosmetics, we summarize the advanced sample preparation techniques and commonly used detection techniques of hormones in cosmetics in the last decade (2012-2022). We found that ultrasound-assisted extraction, solid phase extraction, and microextraction coupled with chromatographic analysis are still the most widely used analytical technologies for hormones in cosmetics. Through the investigation of market status, the summary of sample pretreatment and detection technologies, as well as the discussion of their development trends in the future, our purpose is to provide a reference for the supervision of illegal hormone residues in cosmetics.

Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives.

To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1-20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 µM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 µM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.

miR-142a-5p promoted osteoblast differentiation via targeting nuclear factor IA.

miR-142a-5p plays critical roles in multiple biological processes and diseases, such as inflammation and tumorigenesis. However, it remains to be explored if and how miR-142a-5p contributes to osteoblast differentiation. In this study, our results showed that miR-142a-5p was highly expressed in bone tissue of mice and increased during osteogenesis in preosteoblast MC3T3-E1 cells. Supplementing miR-142a-5p activity using miR-142a-5p agomir promoted osteogenic differentiation in stromal cell line ST2 and preosteoblastic line MC3T3-E1. Conversely, miR-142a-5p antagomir, an inhibitor of endogenous miR-142a-5p, could reduce osteoblast differentiation in ST2 and MC3T3-E1 cells. Nuclear factor IA (NFIA), a site-specific transcriptional factor, was demonstrated to be directly targeted by miR-142a-5p. Overexpression of NFIA inhibited miR-142a-5p-mediated osteoblast differentiation in ST2 cells. Furthermore, mechanism explorations revealed that Wnt/ß-catenin signaling transcriptionally regulated the expression of miR-142a-5p during osteogenic differentiation. ß-catenin binds to the T-cell factor/lymphoid enhancer factor binding motif within the promoter of miR-142 and positively regulates its transcriptional activity. Our findings suggested that miR-142a-5p promoted osteoblast differentiation via targeting NFIA.

Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial.

PURPOSE: This study aimed to assess the effects of folic acid (FA) combined with a docosahexaenoic acid (DHA) intervention on the cognitive function and inflammatory cytokines in elderly subjects with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited 240 individuals with MCI in Tianjin, China, and randomly allocated into 4 groups: FA + DHA (FA 800 µg/d + DHA 800 mg/d), FA (FA 800 µg/d), DHA (DHA 800 mg/d), and placebo. Cognitive function, serum folate and homocysteine (Hcy), plasma DHA and inflammatory cytokines levels were measured at baseline and 6 months. RESULTS: Daily oral FA, DHA and their combined use for 6 months significantly improved the full-scale intelligence quotient (FSIQ) and some subtests of Wechsler Adult Intelligence Scale compared to the placebo. The increases of FSIQ, arithmetic, picture completion scores in the FA group and picture completion, block design scores in the DHA group were significantly less than that in the FA combined DHA group (P < 0.05). Meanwhile, daily oral FA, DHA and their combined use for 6 months significantly decreased plasma inflammatory cytokines compared to the placebo. The changes of interleukin-1ß levels in the FA group and interleukin-6 levels in the DHA group were significantly less than that in the FA + DHA group (P < 0.05). CONCLUSIONS: Daily oral FA, DHA and their combined use for 6 months can significantly improve cognitive function and decrease plasma inflammatory cytokines in MCI individuals. The combination of FA and DHA was more beneficial than each individual nutrient on their own.

Genetic diversity and molecular epidemiology of outbreaks of Klebsiella pneumoniae mastitis on two large Chinese dairy farms.

Klebsiella pneumoniae is an opportunistic and environmental mastitis-causing pathogen, with potential for contagious transmission. Repetitive element sequence-based PCR was used to determine genetic diversity and explore potential transmission and reservoirs for mastitis caused by K. pneumoniae on 2 large Chinese dairy farms. A total of 1,354 samples was collected from the 2 dairy farms, including milk samples from cows with subclinical and clinical mastitis, bedding, feces, feed, teat skin, and milking liners. Environmental samples were collected from all barns and milking parlors and extramammary samples from randomly selected dairy cows on both farms. In total, 272 and 93 K. pneumoniae isolates were obtained from Farms A and B, respectively (with ~8K and 2K lactating cows, respectively). Isolation rates from clinical mastitis (CM), subclinical mastitis (SCM), and environmental or extramammary samples were 34, 23 and 37%, respectively for Farm A and 42, 3, and 34% for Farm B. The K. pneumoniae isolated from CM milk and extramammary or environmental sources had high genetic diversity (index of diversity >90%) on the 2 farms and from SCM on Farm A. However, on Farm B, 9 SCM isolates were classified as 2 genotypes, resulting in a relatively low index of diversity (Simpson's index of diversity = 0.39; 95% CI = 0.08-0.70). Genotypes of K. pneumoniae causing mastitis were commonly detected in feces, bedding, and milking liners (Farm A), or from teat skin, sawdust bedding, and feed (Farm B). Based on its high level of genetic diversity, we inferred K. pneumoniae was an opportunistic and environmental pathogen causing outbreaks of CM on these 2 large Chinese dairy farms. Nevertheless, that only a few genotypes caused SCM implied some strains had increased udder adaptability and a contagious nature or a common extramammary source. Finally, control of intramammary infections caused by K. pneumoniae on large Chinese dairy farms must consider farm-level predictors, as the 2 outbreaks had distinct potential environmental sources of infection.

Clinical Efficacy and Possible Mechanism of Endoscopic Vidian Neurectomy for House Dust Mite-Sensitive Allergic Rhinitis.

BACKGROUND/AIMS: Endoscopic vidian neurectomy (EVN) for allergic rhinitis (AR) has good clinical effects. However, the pathophysiological basis of the effect of EVN on AR is still poorly understood. This study aimed to investigate the efficacy of EVN on house dust mite (HDM)-sensitive AR and the dynamic changes of serum immunoglobulin E and some immune regulatory factors. METHODS: Twenty HDM-sensitive AR patients were treated with bilateral EVN (EVN group), 15 HDM-sensitive AR patients were treated with subcutaneous immunotherapy (SCIT group), and 15 healthy subjects served as healthy controls. Quality of daily life was assessed by the scores of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQs). The visual analog scale was used to assess clinical efficacy. Serum molecules were measured by ELISA and the UNICAP system. RESULTS: Compared with the SCIT group, the RQLQs in the EVN group were lower 12 months after treatment (both p < 0.05). There was no significant difference in improving nasal itching and sneezing (both p > 0.05), but the clinical efficacy of bilateral EVN was greater than SCIT in improving nasal obstruction, rhinorrhea, eye itching, and lachrymation 12 months after treatment (all p < 0.05). Compared with before treatment, the serum levels of total immunoglobulin E (tIgE), Dermatophagoides pteronyssinus- and Dermatophagoides farinae-specific immunoglobulin E (sIgE), and tumor necrosis factor (TNF)-α in the EVN group and the serum levels of TNF-α and interleukin-4 in the SCIT group were lower 12 months after treatment (all p < 0.05). CONCLUSION: The short-term efficacy of bilateral EVN is more effective than SCIT in treating HDM-sensitive AR. This may be because the surgery reduced the tIgE and sIgE levels. TNF-α may be involved in the therapeutic mechanism.