Association between white matter hyperintensity and anxiety/depression.

Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: ß = 0.152, deep white matter hyperintensity: ß = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: ß = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.

Research progress on Brassicaceae plants: a bibliometrics analysis.

The Brassicaceae is a worldwide family that produces ornamental flowers, edible vegetables, and oilseed plants, with high economic value in agriculture, horticulture, and landscaping. This study used the Web of Science core dataset and the CiteSpace bibliometric tool to quantitatively visualize the number of publications, authors, institutions, and countries of 3139 papers related to Brassicaceae plants from 2002 to 2022. The keywords and references were divided into two phases: Phase 1 (2002-2011) and Phase 2 (2012-2022) for quantitative and qualitative analysis. The results showed: An average annual publication volume of 149 articles, with an overall fluctuating upward trend; the research force was mainly led by Professor Ihsan A. Al-shehbaz from Missouri Botanical Garden; and the United States had the highest number of publications. In the first phase, research focused on the phylogeny of Brassicaceae plants, while the second phase delved into diverse research based on previous studies, research in areas such as polyploidy, molecular technique, physiology, and hyperaccumulator has been extended. Based on this research, we propounded some ideas for future studies on Brassicaceae plants and summarized the research gaps.

Causal relationship between gut microbiota and rheumatoid arthritis: a two-sample Mendelian randomisation study.

OBJECTIVES: To assess whether there is a bidirectional causal relationship between the composition of gut microbiota and rheumatoid arthritis (RA), and to identify specific pathogenic bacterial taxa via the Mendelian randomisation (MR) analysis. METHODS: We acquired single nucleotide polymorphisms (SNPs) associated with the composition of gut microbiota (n=18,340) and with RA (n=331,313) from publicly available genome-wide association studies (GWAS). The genome-wide threshold was 1 × 10-5 in the forward MR analysis and was 5 × 10-8 in the reverse MR analysis. Inverse variance weighted (IVW) was the main method to analyse causality, and MR results were verified by several sensitivity analyses including weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO). RESULTS: The IVW method suggested that eight taxa were positively correlated with RA, including: MollicutesRF9 (pIVW <0.01), Alphaproteobacteria (pIVW <0.01), Betaproteobacteria (p IVW =0.04), Bacteroidaceae (pIVW <0.01), Adlercreutzia (pIVW <0.01), Bacteroides (pIVW <0.01), Butyricimonas (p IVW =0.03) and Holdemanella (pIVW =0.03). Six bacterial taxa were negatively correlated with RA, including Desulfovibrionales (pIVW = 0.01), Methanobacteriales (pIVW <0.01), Methanobacteria (PIVW <0.01), Desulfovibrionaceae (pIVW <0.01), Methanobacteriaceae (pIVW <0.01) and Butyrivibrio (pIVW =0.02). Heterogeneity (p>0.05) and pleiotropy (p>0.05) analysis confirmed the robustness of the MR results. CONCLUSIONS: We identified some specific bacterial taxa that were causally associated with the risk of RA, providing new insights into prevention and diagnosis of RA.

Insight into the Causal Relationship between Gut Microbiota and Back Pain: A Two Sample Bidirectional Mendelian Randomization Study.

Observational studies have shown that alterations in gut microbiota composition are associated with low back pain. However, it remains unclear whether the association is causal. To reveal the causal association between gut microbiota and low back pain, a two-sample bidirectional Mendelian randomization (MR) analysis is performed. The inverse variance weighted regression (IVW) is performed as the principal MR analysis. MR-Egger and Weighted Median is further conducted as complementary analysis to validate the robustness of the results. Finally, a reverse MR analysis is performed to evaluate the possibility of reverse causation. The inverse variance weighted (IVW) method suggests that Peptostreptococcaceae (odds ratio [OR] 1.056, 95% confidence interval [CI] [1.015-1.098], P IVW = 0.010), and Lactobacillaceae (OR 1.070, 95% CI [1.026-1.115], P IVW = 0.003) are positively associated with back pain. The Ruminococcaceae (OR 0.923, 95% CI [0.849-0.997], P IVW = 0.033), Butyricicoccus (OR 0.920, 95% CI [0.868 - 0.972], P IVW = 0.002), and Lachnospiraceae (OR 0.948, 95% CI [0.903-0.994], P IVW = 0.022) are negatively associated with back pain. In this study, underlying causal relationships are identified among gut microbiota and low back pain. Notably, further research is needed on the biological mechanisms by which gut microbiota influences low back pain.

Pathogen-Targeting Bimetallic Nanozymes as Ultrasonic-Augmented ROS Generator against Multidrug Resistant Bacterial Infection.

Clinical treatment of multidrug resistant (MDR) pathogens-induced infection is emerging as a growing challenge in global public health due to the limited selection of clinically available antibiotics. Nanozymes as artificial enzymes that mimicked natural enzyme-like activities, are received great attention for combating MDR pathogens. However, the relatively deficient catalytic activity in the infectious microenvironment and inability to precisely targeting pathogen restrains their clinical anti-MDR applications. Here, pathogen-targeting bimetallic BiPt nanozymes for nanocatalytic therapy against MDR pathogen are reported. Benefiting from electronic coordination effect, BiPt nanozymes exhibit dual-enzymatic activities, including peroxidase-mimic and oxidase-mimic activities. Moreover, the catalytic efficiency can be efficiently increased 300-fold by ultrasound under inflammatory microenvironment. Notably, BiPt nanozyme is further cloaked with a platelet-bacteria hybrid membrane (BiPt@HMVs), thus presenting excellent homing effect to infectious sites and precise homologous targeting to pathogen. By integrating accurate targeting with highly efficient catalytic, BiPt@HMVs can eliminate carbapenem-resistant Enterobacterales and methicillin-resistant Staphylococcus aureus in osteomyelitis rats model, muscle-infected mice model, and pneumonia mice model. The work provides an alternative strategy based on nanozymes for clinically addressing MDR bacteria-induced infections.

Hybrid Cycloalkyl-Alkyl Chain-Based Symmetric/Asymmetric Acceptors with Optimized Crystal Packing and Interfacial Exciton Properties for Efficient Organic Solar Cells.

Hybrid cycloalkyl-alkyl side chains are considered a unique composite side-chain system for the construction of novel organic semiconductor materials. However, there is a lack of fundamental understanding of the variations in the single-crystal structures as well as the optoelectronic and energetic properties generated by the introduction of hybrid side chains in electron acceptors. Herein, symmetric/asymmetric acceptors (Y-C10ch and A-C10ch) bearing bilateral and unilateral 10-cyclohexyldecyl are designed, synthesized, and compared with the symmetric acceptor 2,2'-((2Z,2'Z)-((12,13-bis(2-butyloctyl)-3,9 bis(ethylhexyl)-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2″,3″':4',5']thieno[2',3':4,5] pyrrolo[3,2-g]thieno[2',3':4,5]thieno[3,2-b]indole-2,10- diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (L8-BO). The stepwise introduction of 10-cyclohexyldecyl side chains decreases the optical bandgap, deepens the energy level, and enables the acceptor molecules to pack closely in a regular manner. Crystallographic analysis demonstrates that the 10-cyclohexyldecyl chain endows the acceptor with a more planar skeleton and enforces more compact 3D network packing, resulting in an active layer with higher domain purity. Moreover, the 10-cyclohexyldecyl chain affects the donor/acceptor interfacial energetics and accelerates exciton dissociation, enabling a power conversion efficiency (PCE) of >18% in the 2,2'-((2Z,2'Z)-((12,13-bis(2-ethylhexyl)-3,9-diundecyl12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2″,3″':4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (Y6) (PM6):A-C10ch-based organic solar cells (OSCs). Importantly, the incorporation of Y-C10ch as the third component of the PM6:L8-BO blend results in a higher PCE of 19.1%. The superior molecular packing behavior of the 10-cyclohexyldecyl side chain is highlighted here for the fabrication of high-performance OSCs.

Estrogen receptors mediate the antidepressant effects of aerobic exercise: A possible new mechanism.

Purpose: This study aimed to examine whether aerobic exercise exerts mood-modulating effects through an estrogen signaling mechanism. Method: The experiment was divided into two parts. The first part is to compare the three modeling methods to obtain the most obvious method of depression-like phenotype for further study in the second part. The first part of ovariectomized rats (age, 13 weeks) was tested when rats were 14 or 22 weeks old or in the sixth week after 3 weeks of chronic restraint stress. The second part was to treat the animals with the most obvious depression-like phenotype in different ways, placebo treatment or estradiol (E2) replacement therapy was administered, aerobic training, or estrogen receptor antagonist treatment. The cognitive (Barnes maze and 3-chamber social tests), anxiety-like (open-field and elevated plus maze tests) and depression-like (sucrose preference and forced swim tests) behaviors of rats in both parts were analyzed to study the effects of estrogen depletion and aerobic exercise. Results: Rats did not develop depressive symptoms immediately after ovariectomy, however, the symptoms became more pronounced with a gradual decrease in ovarian hormone levels. Compared with the placebo or control groups, the exercise and E2 groups showed improved performance in all behavioral test tasks, and the antidepressant effects of aerobic exercise were comparable to those of estrogen. Moreover, the estrogen receptor antagonist has markedly inhibited the antidepressant effects of aerobic exercise. Conclusion: Estrogen receptors may mediate the antidepressant effects of aerobic exercise. In addition, an increasingly fragile ovarian hormonal environment may underlies chronic restraint stress-induced depression.

Direct visualization of living bacterial genotypes using CRISPR/Cas12a-circular reporter nanoprobes.

Bacterial genotyping is important for understanding the complex microbiota. Although fluorescence in situ hybridization (FISH) has enabled bacterial community identification with high spatial resolution, its unavoidable cell fixation steps and signal generation by multi-probe stacking greatly limit its application in living bacterial genotyping. Here, we designed polyethyleneimine-encapsulated CRISPR/Cas12a-circular reporter nanoprobes (CasCLR) for rapid and sensitive visualization of gene information in living bacteria. We found that, nanoprobe-based sequential delivery of Cas12a/crRNA and circular reporter into bacteria allowed single genomic loci to initiate trans-cleavage activity of Cas12a, thereby cleaving CLR to generate amplified fluorescent signals for imaging of target gene. Using CasCLR, we can sensitively analyze the percentage of target bacteria in co-culture experiments and directly detect pathogenic bacteria in uncultured mouse gut microbe. In addition, CasCLR has the ability to sensitively analyze specific genotype of microbial communities in vivo. This nanobiotechnology-based bacterial gene analysis is expected to advance understanding of in vivo bacterial cytogenetic information.

Nanomaterial-Based Zinc Ion Interference Therapy to Combat Bacterial Infections.

Pathogenic bacterial infections are the second highest cause of death worldwide and bring severe challenges to public healthcare. Antibiotic resistance makes it urgent to explore new antibacterial therapy. As an essential metal element in both humans and bacteria, zinc ions have various physiological and biochemical functions. They can stabilize the folded conformation of metalloproteins and participate in critical biochemical reactions, including DNA replication, transcription, translation, and signal transduction. Therefore, zinc deficiency would impair bacterial activity and inhibit the growth of bacteria. Interestingly, excess zinc ions also could cause oxidative stress to damage DNA, proteins, and lipids by inhibiting the function of respiratory enzymes to promote the formation of free radicals. Such dual characteristics endow zinc ions with unparalleled advantages in the direction of antibacterial therapy. Based on the fascinating features of zinc ions, nanomaterial-based zinc ion interference therapy emerges relying on the outstanding benefits of nanomaterials. Zinc ion interference therapy is divided into two classes: zinc overloading and zinc deprivation. In this review, we summarized the recent innovative zinc ion interference strategy for the treatment of bacterial infections and focused on analyzing the antibacterial mechanism of zinc overloading and zinc deprivation. Finally, we discuss the current limitations of zinc ion interference antibacterial therapy and put forward problems of clinical translation for zinc ion interference antibacterial therapy.

Quantitative Proteomics Reveals Metabolic Reprogramming in Host Cells Induced by Trophozoites and Intermediate Subunit of Gal/GalNAc Lectins from Entamoeba histolytica.

Entamoeba histolytica is an intestinal protozoan parasite with remarkable ability to kill and phagocytose host cells, causing amoebic colitis and extraintestinal abscesses. The intermediate subunit (Igl) of galactose (Gal)- and N-acetyl-d-galactosamine (GalNAc)-specific lectins is considered an important surface antigen involved in the pathogenesis of E. histolytica. Here, we applied mass spectrometry-based quantitative proteomics technology to analyze the protein expression profile changes occurring in host Caco2 cells incubated with E. histolytica trophozoites or stimulated by purified native Igl protein. The expression levels of 1,490 and 489 proteins were significantly altered in the E. histolytica-treated and Igl-treated groups, respectively, among 6,875 proteins totally identified. Intriguingly, central carbon metabolism of host cells was suppressed in both E. histolytica-treated and Igl-treated groups, with evidence of decreased expression levels of several key enzymes, including pyruvate kinase muscle type 2, presenting a Warburg-like effect in host cells. Besides, Igl had potential physical interactions with central carbon metabolism enzymes and the proteolytic degradation family members proteasome subunit alpha and beta, which may be responsible for the degradation of key enzymes in carbon metabolism. These results provided a novel perspective on the pathogenic mechanism of E. histolytica and compelling evidence supporting the important role of Igl in the virulence of E. histolytica. IMPORTANCE Metabolic reprogramming is considered a hallmark of some infectious diseases. However, in amoebiasis, a neglected tropical disease caused by protozoan parasite E. histolytica, metabolic changes in host cells have yet to be proven. In this study, advanced data-independent acquisition mass spectrometry-based quantitative proteomics was applied to investigate the overall host cellular metabolic changes as high-throughput proteomics could measure molecular changes in a cell or tissue with high efficiency. Enrichment analysis of differentially expressed proteins showed biological processes and cellular pathways related to amoeba infection and Igl cytotoxicity. Specifically, central carbon metabolism of host cells was dramatically suppressed in both E. histolytica-treated and Igl-treated groups, indicating the occurrence of a Warburg-like effect induced by trophozoites or Igl from E. histolytica. Distinct differences in ubiquitin-mediated proteolysis, rapamycin (mTOR) signaling pathway, autophagy, endocytosis, and tight junctions provided novel perspectives on the pathogenic mechanism of E. histolytica.

A Novel TLR4-Binding Domain of Peroxiredoxin From Entamoeba histolytica Triggers NLRP3 Inflammasome Activation in Macrophages.

Macrophages promote early host responses to infection by releasing pro-inflammatory cytokines, and they are crucial to combat amoebiasis, a disease affecting millions of people worldwide. Macrophages elicit pro-inflammatory responses following direct cell/cell interaction of Entamoeba histolytica, inducing NLRP3 inflammasome activation with high-output IL-1ß/IL-18 secretion. Here, we found that trophozoites could upregulate peroxiredoxins (Prx) expression and abundantly secrete Prxs when encountering host cells. The C-terminal of Prx was identified as the key functional domain in promoting NLRP3 inflammasome activation, and a recombinant C-terminal domain could act directly on macrophage. The Prxs derived from E. histolytica triggered toll-like receptor 4-dependent activation of NLRP3 inflammasome in a cell/cell contact-independent manner. Through genetic, immunoblotting or pharmacological inhibition methods, NLRP3 inflammasome activation was induced through caspase-1-dependent canonical pathway. Our data suggest that E. histolytica Prxs had stable and durable cell/cell contact-independent effects on macrophages following abundantly secretion during invasion, and the C-terminal of Prx was responsible for activating NLRP3 inflammasome in macrophages. This new alternative pathway may represent a potential novel therapeutic approach for amoebiasis, a global threat to millions.

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity.

The accumulated evidence from animal and human studies supports that exercise is beneficial to physical health. Exercise can upregulate various neurotrophic factors, activate neuroplasticity, and play a positive role in improving and enhancing cerebrovascular function. Due to its economy, convenience, and ability to prevent or ameliorate various aging-related diseases, exercise, a healthy lifestyle, is increasingly popularized by people. However, the mechanism by which exercise performs this function and how it is transmitted from muscles to the brain remains incompletely understood. Here, we review the beneficial effects of exercise with different intensities on the brain with a focus on the positive effects of lactate on neuroplasticity and cerebrovascular plasticity. Based on these recent studies, we propose that lactate, a waste previously misunderstood as a by-product of glycolysis in the past, may be a key signal molecule that regulates the beneficial adaptation of the brain caused by exercise. Importantly, we speculate that a central protective mechanism may underlie the cognitive benefits induced by exercise.

Vortices-interaction-induced microstreaming for the pump-free separation of particles.

Microfluidic techniques have emerged as promising strategies for a wide variety of synthetic or biological sorting. Unfortunately, there is still a lack of sorting with automatic and handy operation. In contrast to passively generated vortices, the thermocapillary vortices produced by temperature gradient have the advantages of flexible manipulation, stable strength, and simple integration. In this Letter, we present a device used for the pump-free separation of particles through vortices interaction without external fluidic control systems required for the majority of existing devices. Specifically, the device induces a different flow type upon the actuation of optical power, and the flow functions, such as simultaneous pumping and sorting, agree with stimulation results very well. More importantly, our developed sorting device can achieve separations by means of tunable cutoff diameter size. Therefore, this versatile device can be utilized to sort complex samples with the advantages of portability, user-friendly control, and automation.

Nuclear Factor-Y in Mouse Pancreatic ß-Cells Plays a Crucial Role in Glucose Homeostasis by Regulating ß-Cell Mass and Insulin Secretion.

Pancreatic ß-cell mass and insulin secretion are determined by the dynamic change of transcription factor expression levels in response to altered metabolic demand. Nuclear factor-Y (NF-Y) is an evolutionarily conserved transcription factor playing critical roles in multiple cellular processes. However, the physiological role of NF-Y in pancreatic ß-cells is poorly understood. The current study was undertaken in a conditional knockout of Nf-ya specifically in pancreatic ß-cells (Nf-ya ßKO) to define the essential physiological role of NF-Y in ß-cells. Nf-ya ßKO mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced ß-cell proliferation resulting in decreased ß-cell mass was observed in these mice, which was associated with disturbed actin cytoskeleton. NF-Y-deficient ß-cells also exhibited impaired insulin secretion with a reduced Ca2+ influx in response to glucose, which was associated with an inefficient glucose uptake into ß-cells due to a decreased expression of GLUT2 and a reduction in ATP production resulting from the disruption of mitochondrial integrity. This study is the first to show that NF-Y is critical for pancreatic islet homeostasis and function through regulation in ß-cell proliferation, glucose uptake into ß-cells, and mitochondrial energy metabolism. Modulating NF-Y expression in ß-cells may therefore offer an attractive approach for therapeutic intervention.

Mitochondria-Associated Endoplasmic Reticulum Membranes in the Pathogenesis of Type 2 Diabetes Mellitus.

The endoplasmic reticulum (ER) and mitochondria are essential intracellular organelles that actively communicate via temporally and spatially formed contacts called mitochondria-associated membranes (MAMs). These mitochondria-ER contacts are not only necessary for the physiological function of the organelles and their coordination with each other, but they also control the intracellular lipid exchange, calcium signaling, cell survival, and homeostasis in cellular metabolism. Growing evidence strongly supports the role of the mitochondria-ER connection in the insulin resistance of peripheral tissues, pancreatic ß cell dysfunction, and the consequent development of type 2 diabetes mellitus (T2DM). In this review, we summarize current advances in the understanding of the mitochondria-ER connection and specifically focus on addressing a new perspective of the alterations in mitochondria-ER communication in insulin signaling and ß cell maintenance.

SHP-1 suppresses the antiviral innate immune response by targeting TRAF3.

Type I interferons play a pivotal role in innate immune response to virus infection. The protein tyrosine phosphatase SHP-1 was reported to function as a negative regulator of inflammatory cytokine production by inhibiting activation of NF-κB and MAPKs during bacterial infection, however, the role of SHP-1 in regulating type I interferons remains unknown. Here, we demonstrated that knockout or knockdown of SHP-1 in macrophages promoted both HSV-1- and VSV-induced antiviral immune response. Conversely, overexpression of SHP-1 in L929 cells suppressed the HSV-1- and VSV-induced immune response; suppression was directly dependent on phosphatase activity. We identified a direct interaction between SHP-1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63-linked ubiquitination; SHP-1 inhibited K63-linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446. Taken together, our results identify SHP-1 as a negative regulator of antiviral immunity and suggest that SHP-1 may be a target for intervention in acute virus infection.

Revealing Crystallization-Induced Blue-Shift Emission of a Di-Boron Complex by Enhanced Photoluminescence and Electrochemiluminescence.

Elucidating the effects of crystallization-induced blue-shift emission of a newly synthesized di-boron complex (DBC) by enhanced photoluminescence (PL) and electrochemiluminescence (ECL) in the annihilation pathway was realized for the first time. The 57 nm blue-shift and great enhancement in the crystalline lattice relative to the DBC solution were attributed to the restriction of intramolecular rotation (RIR) and confirmed by PL imaging, X-ray diffraction, as well as DFT calculations. It was discovered that ECL at crystalline film/solution interfaces can be further enhanced by means of both co-reactant route and RIR. The RIR contributions with co-reactant increased ECL up to 5 times more. Very interestingly, the co-reactant system was found to give off a red-shifted light emission. Mechanistic studies reveal that a difference between location of the ECL in the co-reactant route and that in the annihilation pathway leads to an alternative emission wavelength.

Effects of genetic variations in Acads gene on the risk of chronic obstructive pulmonary disease.

Short-chain acyl-CoA dehydrogenase (SCAD), encoded by the Acads gene, functions in the mitochondrial ß-oxidation of saturated short-chain fatty acids. SCAD deficiency results in mitochondrial dysfunction, which is one underlying biological mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis. In this case-control study, we aimed to examine the effects of Acads gene polymorphisms on the susceptibility to COPD. A total of 16 tagging single-nucleotide polymorphisms (SNPs) in Acads gene region was identified and genotyped in 646 unrelated ethnic Chinese Han individuals including 279 patients with COPD and 367 healthy controls, their allelic and genotypic associations with COPD were determined by different genetic models. Furthermore, we estimated the linkage disequilibrium and haplotypes from these tested variants and determined the effects of haplotypes on the risk of COPD. The allelic and genotypic frequencies of SNPs rs2239686 and rs487915 in Acads gene were significantly different between COPD patients and controls, no statistically significant results were observed for other SNPs. Minor alleles A of rs2239686 and T of rs487915 were associated with a decreased pulmonary function and an increased COPD risk in a dominant manner. Functional analysis indicated that the risk allele A of rs2239686 could increase Acads expressions and the intracellular reactive oxygen species content. Haplotype analysis revealed that the haplotypes CTCCT in block 2 (rs3794216-rs3794215-rs34491494-rs558314-rs7312316) as well as GC in block 3 (rs2239686-rs487915) were protective against COPD, while haplotypes CTCGC in block 2 and AT in block 3 exhibited significant associations with the increased susceptibility to COPD. Our results suggest that Acads gene could potentially be a risk factor of COPD and thus its genetic variants might be as genetic biomarkers to predict the COPD susceptibility.

ß-arrestin 2 quenches TLR signaling to facilitate the immune evasion of EPEC.

The protein translocated intimin receptor (Tir) from enteropathogenic Escherichia coli shares sequence similarity with the host cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs). The ITIMs of Tir are required for Tir-mediated immune inhibition and evasion of host immune responses. However, the underlying molecular mechanism by which Tir regulates immune inhibition remains unclear. Here we demonstrated that ß-arrestin 2, which is involved in the G-protein-coupled receptor (GPCR) signal pathway, interacted with Tir in an ITIM-dependent manner. For the molecular mechanism, we found that ß-arrestin 2 enhanced the recruitment of SHP-1 to Tir. The recruited SHP-1 inhibited K63-linked ubiquitination of TRAF6 by dephosphorylating TRAF6 at Tyr288, and inhibited K63-linked ubiquitination and phosphorylation of TAK1 by dephosphorylating TAK1 at Tyr206, which cut off the downstream signal transduction and subsequent cytokine production. Moreover, the inhibitory effect of Tir on immune responses was diminished in ß-arrestin 2-deficient mice and macrophages. These findings suggest that ß-arrestin 2 is a key regulator in Tir-mediated immune evasion, which could serve as a new therapeutic target for bacterial infectious diseases.

Generation and manipulation of oil-in-water micro-droplets by confined thermocapillary microvortices.

Optofluidic manipulation of droplets is critical in droplet-based microfluidic systems for chemistry, biology, and medicine. Here, we reported a thermocapillary microvortices-based manipulation platform for controlling oil-in-water droplets through integrating a photothermal waveguide into a microfluidic chip. The sizes and shapes of the droplets can be controlled by adjusting optical power or positions of the water-oil interface. Here, teardrop-shaped droplets, which can encapsulate and accumulate mesoscopic matters easily, were generated when the water-oil interface and the channel boundaries approached the photothermal waveguide center simultaneously. The results showed that the thermocapillary microvortices have good controllability of droplet positions, droplet volumes, and encapsulated-particle distribution and thus it will be a powerful droplet manipulation strategy for microreactors and microcapsules.