Integrated Optimization of Crystal Facets and Nanoscale Spatial Confinement toward the Boosted Catalytic Performance of Pd Nanocrystals.

Tuning the surface chemical property and the local environment of nanocrystals is crucial for realizing a high catalytic performance in various reactions. Herein, we aim to elucidate the structure sensitivity of Pd facets on the surface catalytic hydrogenation reaction and to identify what role the nanoconfinement effect plays in the catalytic properties of Pd nanocrystal catalysts. By controlling the coating structures of mesoporous silica (mSiO2) on Pd nanocrystals with different exposed facets that include {100}, {111}, and {hk0}, we present a series of Pd@mSiO2 nanoreactors in core-shell and yolk-shell structures and the discovery of a partial-coated structure, which can provide different types of nanoconfinement, and we propose a seed size-dominated growth mechanism. We demonstrate that a superior activity was exhibited in Pd nanocrystals enclosed by the {hk0} facet as compared to the Pd{100} and Pd{111} facets, and substantially enhanced efficiency and stability were achieved in Pd@mSiO2 particles with yolk-shell structures, indicating a crucial superiority of optimizing the configuration of crystal facets and nanoconfinement. Our study provides an efficient strategy to rationally design and optimize nanocatalysts for promoting catalytic performance.

Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study.

BACKGROUND: In observational studies, there exists an association between obesity and epigenetic age as well as telomere length. However, varying and partially conflicting outcomes have notably arisen from distinct studies on this topic. In the present study, two-way Mendelian randomization was used to identify potential causal associations between obesity and epigenetic age and telomeres. METHODS: A genome-wide association study was conducted using data from individuals of European ancestry to investigate bidirectional Mendelian randomization (MR) regarding the causal relationships between obesity, as indicated by three obesity indicators (body mass index or BMI, waist circumference adjusted for BMI or WCadjBMI, and waist-to-hip ratio adjusted for BMI or WHRadjBMI), and four epigenetic age measures (HannumAge, HorvathAge, GrimAge, PhenoAge), as well as telomere length. To assess these causal associations, various statistical methods were employed, including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode. To address the issue of multiple testing, we applied the Bonferroni correction. These methods were used to determine whether there is a causal link between obesity and epigenetic age, as well as telomere length, and to explore potential bidirectional relationships. Forest plots and scatter plots were generated to show causal associations between exposures and outcomes. For a comprehensive visualization of the results, leave-one-out sensitivity analysis plots, individual SNP-based forest plots for MR analysis, and funnel plots were included in the presentation of the results. RESULTS: A strong causal association was identified between obesity and accelerated HannumAge, GrimAge, PhenoAge and telomere length shrinkage. The causal relationship between WCadjBMI and PhenoAge acceleration (OR: 2.099, 95%CI: 1.248-3.531, p = 0.005) was the strongest among them. However, only the p-values for the causal associations of obesity with GrimAge, PhenoAge, and telomere length met the criteria after correction using the Bonferroni multiple test. In the reverse MR analysis, there were statistically significant causal associations between HorvathAge, PhenoAge and GrimAge and BMI, but these associations exhibited lower effect sizes, as indicated by their Odds Ratios (ORs). Notably, sensitivity analysis revealed the robustness of the study results. CONCLUSIONS: The present findings reveal a causal relationship between obesity and the acceleration of epigenetic aging as well as the reduction of telomere length, offering valuable insights for further scientific investigations aimed at developing strategies to mitigate the aging process in humans.

Cytokinin oxidase/dehydrogenase OsCKX11 coordinates source and sink relationship in rice by simultaneous regulation of leaf senescence and grain number.

The flag leaf and grain belong to the source and sink, respectively, of cereals, and both have a bearing on final yield. Premature leaf senescence significantly reduces the photosynthetic rate and severely lowers crop yield. Cytokinins play important roles in leaf senescence and determine grain number. Here, we characterized the roles of the rice (Oryza sativa L.) cytokinin oxidase/dehydrogenase OsCKX11 in delaying leaf senescence, increasing grain number, and coordinately regulating source and sink. OsCKX11 was predominantly expressed in the roots, leaves, and panicles and was strongly induced by abscisic acid and leaf senescence. Recombinant OsCKX11 protein catalysed the degradation of various types of cytokinins but showed preference for trans-zeatin and cis-zeatin. Cytokinin levels were significantly increased in the flag leaves of osckx11 mutant compared to those of the wild type (WT). In the osckx11 mutant, the ABA-biosynthesizing genes were down-regulated and the ABA-degrading genes were up-regulated, thereby reducing the ABA levels relative to the WT. Thus, OsCKX11 functions antagonistically between cytokinins and ABA in leaf senescence. Moreover, osckx11 presented with significantly increased branch, tiller, and grain number compared with the WT. Collectively, our findings reveal that OsCKX11 simultaneously regulates photosynthesis and grain number, which may provide new insights into leaf senescence and crop molecular breeding.

Enantioselective N-heterocyclic carbene-catalyzed synthesis of saccharine-derived dihydropyridinones with cis-selectivity.

The enantioselective N-heterocyclic carbene-catalyzed [2 + 4] cyclocondensation of α-chloroaldehydes and saccharine-derived 1-azadienes was developed, giving the corresponding saccharine-derived dihydropyridinones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

Enantioselective N-heterocyclic carbene-catalyzed synthesis of trifluoromethyldihydropyridinones.

The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of α-chloroaldehydes and trifluoromethyl N-Boc azadienes was developed, giving the corresponding 3,4-disubstituted-6-trifluoromethyldihydropyridin-2(1H)-ones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

N-Heterocyclic carbene-catalyzed [3 + 3] cyclocondensation of bromoenals with hydrazones: highly enantioselective synthesis of dihydropyridazones.

The N-heterocyclic carbene-catalyzed [3 + 3] cyclocondensation of bromoenals and hydrazones is developed to give the corresponding chiral 4,5-dihydropyridazones in good yields with excellent enantioselectivities.

Enantioselective N-heterocyclic carbene-catalyzed synthesis of indenopyrones.

The chiral N-heterocyclic carbene-catalyzed [4 + 2] cyclization of α-chloroaldehydes and arylidene indanediones was developed, giving the corresponding indenopyrones in good yields with high diastereoselectivities and enantioselectivities.

Expression of NF45 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth.

Nuclear factor of activated T cells 45 kDa (NF45), is a transcription factor that interacts with NF90 to regulate gene expression. It has been proved to be associated with tumor proliferation in various human malignancies. However, the role of NF45 in glioma is poorly understood. The aim of our study was to examine the relationship between NF45 expression and pathological grade in glioma and the impact of NF45 on the proliferation of glioma cells. Expression levels of NF45 are significantly elevated in high-grade human tissue samples compared with low-grade human glioma tissues samples (P < 0.0001) in Western blot analysis. The result of immunohistochemical also revealed that the expression of NF45 was overexpressed in 121 resected gliomas of different pathologic grades and associated with Ki-67. To investigate the role of NF45 in glioma carcinogenesis, we reduced the expression of NF45 by small interfering RNAs, and results showed suppression of cell proliferation, arrest of the cell cycle, and reduction in clone in vitro. Importantly, we show that SiNF45 can induce the expression of p21 and reduce the expression of proliferating cell nuclear antigen (PCNA) and cyclin E. These findings indicate that NF45 plays an important role in the growth regulation of glioma cells, suggesting that NF45 maybe a molecular marker for pathology and a novel therapeutic target for malignant glioma.

Exercise promotes brain health: a systematic review of fNIRS studies.

Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner.

Integrated bioinformatics and multiomics reveal Liupao tea extract alleviating NAFLD via regulating hepatic lipid metabolism and gut microbiota.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear. PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy. METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT). RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways. CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.

A Burkholderia pseudomallei protein microarray reveals serodiagnostic and cross-reactive antigens.

Understanding the way in which the immune system responds to infection is central to the development of vaccines and many diagnostics. To provide insight into this area, we fabricated a protein microarray containing 1,205 Burkholderia pseudomallei proteins, probed it with 88 melioidosis patient sera, and identified 170 reactive antigens. This subset of antigens was printed on a smaller array and probed with a collection of 747 individual sera derived from 10 patient groups including melioidosis patients from Northeast Thailand and Singapore, patients with different infections, healthy individuals from the USA, and from endemic and nonendemic regions of Thailand. We identified 49 antigens that are significantly more reactive in melioidosis patients than healthy people and patients with other types of bacterial infections. We also identified 59 cross-reactive antigens that are equally reactive among all groups, including healthy controls from the USA. Using these results we were able to devise a test that can classify melioidosis positive and negative individuals with sensitivity and specificity of 95% and 83%, respectively, a significant improvement over currently available diagnostic assays. Half of the reactive antigens contained a predicted signal peptide sequence and were classified as outer membrane, surface structures or secreted molecules, and an additional 20% were associated with pathogenicity, adaptation or chaperones. These results show that microarrays allow a more comprehensive analysis of the immune response on an antigen-specific, patient-specific, and population-specific basis, can identify serodiagnostic antigens, and contribute to a more detailed understanding of immunogenicity to this pathogen.

Impact of Environmental Regulation on Regional Innovative Ability: From the Perspective of Local Government Competition.

We empirically investigate the relationship between environmental regulation and regional innovative ability from the perspective of government competition with a dynamic spatial model, using the 2011-2020 Chinese interprovincial panel dataset as the sample. Empirical underpinnings reveal the interconnection between environmental regulation and regional innovative ability. Further, it has been substantiated as follows: (1) environmental regulation affects regional innovative ability significantly. From the national level perspective, environmental regulation is negatively correlated with regional innovative ability. Further, vigorous environmental regulation deters regional innovative ability and produces a crowding out effect; (2) Environmental regulation has a significant spatial spillover effect on regional technological innovative ability. Meanwhile, the promulgation of environmental policy in the region will affect the innovative ability of neighboring regions; (3) It has also been concluded that there is a strategic competition among local governments in promulgation of environmental regulation, specifically in eastern and central regions which has been signified through regional regressions result. Comprehensively, the current study provides recommendations to governments for allocation of environmental policy under the aegis of regional innovation for improving regional innovative ability.

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1ß Induced Inflammatory Response in Intervertebral Disc Degeneration.

Objective: The determination of miRNA-mRNA pairs for intervertebral disc degeneration (IVDD) regulated by pro-inflammatory cytokines were investigated. Methods: Two dataset (accession number GSE27494 and GSE41883 from platform GPL1352) of expression profiling was downloaded from Gene Expression Omnibus (GEO). The annulus cells were isolated from annulus fibrosus in patients with degenerative disc disease. The cells were then cultured in a three-dimensional (3D) collagen containing with/without proinflammatory cytokines (tumor necrosis factor alpha (TNF-α) or interleukin beta (IL-1ß)). After being cultured for 14 days, the isolated total RNA was analyzed via microarray, and the expression array data were obtained using BRB-Array Tools followed by analyzing the differentially expressed genes (DEGs) and the prediction of potential miRNA targets of hub genes through online database. Results: Firstly, 52 and 296 DEGs were found in IL-1ß- and TNF-α-induced annulus cells, respectively, of these there had 42 common DEGs (co-DEGs) with 34 increased transcripts and 8 reduced ones. Based on the GO and KEGG software, these co-DEGs were mainly enriched in the response to lipopolysaccharide (LPS) and molecule of bacterial origin, the regulation of receptor ligand activity and signaling receptor activator activity, as well as the following signaling pathways, including TNF signaling pathway, IL-17 signaling pathway, and NF-κB signaling pathway. Top hub genes (CXCL1, CXCL2, CXCL8, IL1Β and PTGS2) regulated by several potential microRNAs were involved in TNF-α/IL-1ß treated annulus cells. Conclusions: Several candidate genes regulated by miRNAs caused by TNF-α/IL-1ß in the annulus cells were found, which will guide diagnosis and treatment for degenerative disc disease.

The complete chloroplast genome sequence of Nymphoides peltata (S.G.Gmel.) Kuntze.

Nymphoides peltata is an aquatic floating weed widely distributed in the northern hemisphere of Eurasia. To better determine its phylogenetic relationships with other Nymphoides species and other aquatic plant species, the chloroplast genome of N. peltata was sequenced. The chloroplast genome size is 152,198 bp, consisting of a large single-copy region (84,223 bp) and a small single-copy region (17,817 bp) separated by a pair of inverted repeats with a length of 25,079 bp. The chloroplast genome contains 127 genes, including 85 protein-coding genes, 34 tRNA genes, and eight rRNAs. The maximum-likelihood phylogenetic tree showed that N. peltata is more closely related to other Nymphoides species, providing new insight into the evolution and genetic diversity of aquatic weeds.

Effect of Cognitive Reappraisal on Archery Performance of Elite Athletes: The Mediating Effects of Sport-Confidence and Attention.

Through empirical studies or laboratory tests, previous studies have shown that sport-confidence, attention, and emotion regulation are key factors in archery performance. The present study aims to further identify the effects and pathways of sport-confidence, attention, and cognitive reappraisal (a specific emotion regulation strategy) on real-world archery performance by constructing a hypothesized model to provide a basis for scientific training of athletes to improve sport performance. A survey design was utilized on a sample of 61 athletes (12 international-level athletes, 30 national-level athletes, and 19 first-class athletes) from the Chinese National Archery Team to test the model. The measurement and hypothesized models were tested using partial least squares structural equation modeling (PLS-SEM). The results indicate that the model fit well and explained 33.6% of the variance in archery performance. Sport-confidence (total effects = 0.574, p < 0.001) and attention (total effects = 0.344, p = 0.009) were important predictive indicators of archery performance, while the relationship between cognitive reappraisal and archery performance showed considerable complexity (direct effects = -0.268, p = 0.020; total effects = -0.007, p = 0.964). We conclude that the development of sport-confidence and attention of archery athletes should be strengthened, but athletes who use cognitive reappraisal in archery competition should be mindful of its potential appropriation of cognitive resources and should be directed to improve sport-confidence or develop a positive orientation to arouse excitement.

Physical activity intervention promotes working memory and motor competence in preschool children.

Objective: This study investigated the effects of 12 weeks of specifically designed physical activity intervention on working memory and motor competence in preschool children and explored the correlation between working memory changes and motor competence changes by the intervention. Methods: Four classes of preschool children were grouped into an intervention group and a control group. Children in the intervention group received a 12-week physical activity intervention, while children in the control group followed their daily routine as usual. Before and after the intervention period, children were assessed with the 1-back task and Movement Assessment Battery for Children, second edition (MABC-2) to measure their working memory and motor competence, respectively. Results: Regarding working memory, the accuracy on the 1-back task increased significantly in the intervention group relative to the control group. The intervention group demonstrated a greater decrease in response time from pre- to posttest than the control group, but the difference was not statistically significant. Regarding motor competence, children's manual dexterity, aiming and catching and total score increased significantly in the intervention group relative to the control group, while no significant difference in static and dynamic balance was observed between the two groups. Furthermore, the correlation results showed that changes in the efficacy and efficiency of working memory were positively related to changes in static and dynamic balance and the total score on the MABC-2. Conclusion: These findings demonstrated that 12 weeks of specifically designed physical activity intervention could improve preschool children's efficacy of working memory as well as manual dexterity, aiming and catching and global motor competence. The improvement in the efficacy and efficiency of working memory was positively related to the improvement in static and dynamic balance and global motor competence.

The Potential Advantages of Tai Chi Chuan in Promoting Inhibitory Control and Spontaneous Neural Activity in Young Adults.

Tai Chi Chuan (TCC) is assumed to exert beneficial effects on functional brain activity and cognitive function in elders. Until now, empirical evidence of TCC induced intra-regional spontaneous neural activity and inhibitory control remains inconclusive. Whether the effect of TCC is better than that of other aerobic exercises is still unknown, and the role of TCC in younger adults is not yet fully understood. Here we used resting-state functional MRI (fMRI) to investigate the effects of 8-week TCC (n = 12) and brisk walking (BW, n = 12) on inhibitory control and fractional amplitude of low-frequency fluctuations (fALFF). The results found that TCC had significant effects on inhibitory control performance and spontaneous neural activity that were associated with significantly increased fALFF in the left medial superior frontal gyrus (Cohen's d = 1.533) and the right fusiform gyrus (Cohen's d = 1.436) and decreased fALFF in the right dorsolateral superior frontal gyrus (Cohen's d = 1.405) and the right paracentral lobule (Cohen's d = 1.132).TCC exhibited stronger effects on spontaneous neural activity than the BW condition, as reflected in significantly increased fALFF in the left medial superior frontal gyrus (Cohen's d = 0.862). There was a significant positive correlation between the increase in fALFF in the left medial superior frontal gyrus and the enhancement in inhibitory control performance. The change in fALFF in the left medial superior frontal gyrus was able to explain the change in inhibitory control performance induced by TCC. In conclusion, our results indicated that 8 weeks of TCC intervention could improve processing efficiency related to inhibitory control and alter spontaneous neural activity in young adults, and TCC had potential advantages over BW intervention for optimizing spontaneous neural activity.

The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody.

Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development of SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from a convalescent patient. Antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the SARS-CoV-2 Spike protein. SC31 exhibited potent anti-SARS-CoV-2 activities in multiple animal models. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, treatment with SC31 greatly reduced viral loads and attenuated pro-inflammatory responses linked to the severity of COVID-19. Importantly, a comparison of the efficacies of SC31 and its Fc-null LALA variant revealed that the optimal therapeutic efficacy of SC31 requires Fc-mediated effector functions that promote IFNγ-driven anti-viral immune responses, in addition to its neutralization ability. A dose-dependent efficacy of SC31 was observed down to 5mg/kg when administered before viral-induced lung inflammatory responses. In addition, antibody-dependent enhancement was not observed even when infected mice were treated with SC31 at sub-therapeutic doses. In SARS-CoV-2-infected hamsters, SC31 treatment significantly prevented weight loss, reduced viral loads, and attenuated the histopathology of the lungs. In rhesus macaques, the therapeutic potential of SC31 was evidenced through the reduction of viral loads in both upper and lower respiratory tracts to undetectable levels. Together, the results of our preclinical studies demonstrated the therapeutic efficacy of SC31 in three different models and its potential as a COVID-19 therapeutic candidate.

Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole.

OBJECTIVES: Melioidosis, a potentially fatal disease of humans and animals, is caused by the gram-negative bacterium, Burkholderia pseudomallei. There is no approved vaccine or effective prophylaxis. Given its potential as a bioterrorism agent and a cause of serious laboratory-acquired infection, we studied the efficacy of pre- and post-exposure oral antibiotic prophylaxis in BALB/c mice infected with aerosolized B. pseudomallei through the inhalational route. METHODS: Amoxicillin/clavulanic acid, doxycycline or co-trimoxazole was administered 48 h before infection as pre-exposure prophylaxis, orally, twice daily and continued up to 10 days post-challenge. In the post-exposure prophylaxis regimen, the oral antibiotics were administered twice daily, at 0, 10, 24 and 48 h and continued for 10 days. Survival of all animals was observed until 21 days. RESULTS: All infected control animals developed infection between 24 and 48 h, and died within 5 days. Animals receiving amoxicillin/clavulanic acid as pre-exposure prophylaxis succumbed to the disease at day 7, whereas those in the co-trimoxazole and doxycycline groups had survival rate of 100% and 80%, respectively, at day 21. As post-exposure prophylaxis, all antibiotics were not effective when treatment was initiated 48 h post-challenge. However, animals receiving co-trimoxazole had a 100% survival rate when the antibiotic was started 0, 10 and 24 h post-infection, and amoxicillin/clavulanic acid was the least effective. CONCLUSIONS: Co-trimoxazole appears to be an effective oral antibiotic both as pre- and post-exposure prophylaxis to B. pseudomallei. Data derived from this study have important implications on the management of laboratory accidents or following an intentional release of B. pseudomallei, a potential bioterrorism agent.

Burkholderia pseudomallei aerosol infection results in differential inflammatory responses in BALB/c and C57Bl/6 mice.

Melioidosis is caused by the Gram-negative bacterium Burkholderia pseudomallei, whose portals of entry into the body include subcutaneous, ingestion and inhalation routes. Animal models play an important role in furthering our understanding of this disease, which is associated with high morbidity and mortality in susceptible subjects. Previous studies using intranasal inoculation showed a differential susceptibility to inhalational melioidosis in BALB/c and C57Bl/6 mice and attributed the difference to genetic factors and host response. However, a recent study found no difference in susceptibility when the two species of mice were exposed to nebulized bacteria. We sought to address this discrepancy by using a nasal route only, instead of whole-body aerosol exposure system. Employing three different clinical strains of B. pseudomallei and following the progression of disease development in both BALB/c and C57Bl/6 mice, we found that BALB/c mice were at least 10- to 100-fold more susceptible to infection than C57Bl/6 mice. Comparison of bacterial burdens in aerosol-challenged mice, at both the pulmonary and distant sites of infection, suggests that C57Bl/6 mice were more efficient in clearing the bacteria than BALB/c mice. In addition, a comprehensive study of a wide panel of chemokines and cytokines at the protein level demonstrated that hyperproduction of proinflammatory cytokines in aerosol-challenged BALB/c mice did not translate into better protection and survival of these mice, whereas a moderate increase in these proteins in aerosol-challenged C57Bl/6 mice was more beneficial in clearing the infection. This suggests that high levels of proinflammatory cytokines are detrimental and contribute to the immunopathogenesis of the infection.