Repeated Social Defeat Stress Induces an Inflammatory Gut Milieu by Altering the Mucosal Barrier Integrity and Gut Microbiota Homeostasis

Background Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation. Methods We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the microbiome, gut permeability assay (on mouse colon, using an Ussing chamber), immunoblotting, and immunohistochemical analyses were performed. Polarized intestinal epithelial cells and 3-dimensional crypt cultures were used for mechanistic analysis. Results The RSDS mice harbor a heightened proinflammatory gut environment and microbiota dysbiosis. The RSDS mice further showed significant dysregulation of gut barrier functions, including transepithelial electrical resistance, mucin homeostasis, and antimicrobial responses. RSDS mice also showed a specific increase in intestinal expression of claudin-2, a tight junction protein, and epinephrine, a stress-induced neurotransmitter. Treating intestinal epithelial cells or 3-dimensional cultured crypts with norepinephrine or intestinal luminal contents (fecal contents) upregulated claudin-2 expression and inhibited transepithelial electrical resistance. Conclusions Traumatic stress induces dysregulation of gut barrier functions, which may underlie the observed gut microbiota changes and proinflammatory gut milieu, all of which may have an interdependent effect on the health and increased risk of comorbidities in patients with PTSD

Supramolecular photochemistry of encapsulated caged ortho-nitrobenzyl triggers

ortho-Nitrobenzyl (oNB) triggers have been extensively used to release various molecules of interest. However, the toxicity and reactivity of the spent chromophore, o-nitrosobenzaldehyde, remains an unaddressed difficulty. In this study we have applied the well-established supramolecular photochemical concepts to retain the spent trigger o-nitrosobenzaldehyde within the organic capsule after release of water-soluble acids and alcohols. The sequestering power of organic capsules for spent chromophores during photorelease from ortho-nitrobenzyl esters, ethers and alcohols is demonstrated with several examples.National Science FoundationNational Science Foundation (NSF) [CHE-1807729]Kansas University Endowment AssociationFCT - Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [UID/Multi/04326/2019, EMBRC.PT ALG-01-0145-FEDER-022121

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis.

BACKGROUND: Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited. METHODS: We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs. RESULTS: Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4-24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings. CONCLUSIONS: Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings

Fac and mer isomers of Ru(II) tris(pyrazolyl-pyridine) complexes as models for the vertices of coordination cages: structural characterisation and hydrogen-bonding characteristics

We have prepared a series of mononuclear fac and mer isomers of Ru(II) complexes containing chelating pyrazolyl-pyridine ligands, to examine their differing ability to act as hydrogen-bond donors in MeCN. This was prompted by our earlier observation that octanuclear cube-like coordination cages that contain these types of metal vertex can bind guests such as isoquinoline-N-oxide (K = 2100 M−1 in MeCN), with a significant contribution to binding being a hydrogen-bonding interaction between the electron-rich atom of the guest and a hydrogen-bond donor site on the internal surface of the cage formed by a convergent set of CH2 protons close to a 2+ metal centre. Starting with [Ru(LH)3]2+ [LH = 3-(2-pyridyl)-1H-pyrazole] the geometric isomers were separated by virtue of the fact that the fac isomer forms a Cu(I) adduct which the mer isomer does not. Alkylation of the pyrazolyl NH group with methyl iodide or benzyl bromide afforded [Ru(LMe)3]2+ and [Ru(Lbz)3]2+ respectively, each as their fac and mer isomers; all were structurally characterised. In the fac isomers the convergent group of pendant –CH2R or –CH3 protons defines a hydrogen-bond donor pocket; in the mer isomer these protons do not converge and any hydrogen-bonding involving these protons is expected to be weaker. For both [Ru(LMe)3]2+ and [Ru(Lbz)3]2+, NMR titrations with isoquinoline-N-oxide in MeCN revealed weak 1 : 1 binding (K ≈ 1 M−1) between the guest and the fac isomer of the complex that was absent with the mer isomer, confirming a difference in the hydrogen-bond donor capabilities of these complexes associated with their differing geometries. The weak binding compared to the cage however occurs because of competition from the anions, which are free to form ion-pairs with the mononuclear complex cations in a way that does not happen in the cage complexes. We conclude that (i) the presence of fac tris-chelate sites in the cage to act as hydrogen-bond donors, and (ii) exclusion of counter-ions from the central cavity leaving these hydrogen-bonding sites free to interact with guests, are both important design criteria for future coordination cage hosts

Light-emitting conjugated microporous polymers based on an excited-state intramolecular proton transfer strategy and selective switch-off sensing of anions

Conjugated microporous polymers (CMPs) are a novel class of porous materials that possess pi-conjugated porous architectures, and are very popular to construct light-emitting materials. However, most CMPs emit weak luminescence. Here, highly emissive CMP-A and CMP-B were designed on the basis of an excited-state intramolecular proton transfer (ESIPT) strategyviaintramolecular hydrogen bonds between hydroxyl groups and imine bonds, which endow the CMPs with strong orange-red luminescence with high absolute fluorescence quantum yield of 10% in the solid state. Interestingly, the ESIPT strategy restriction caused the fluorescence quenching pathway through the hydrogen-bond interaction between the hydroxyl groups and anions. The process could only be triggered by fluoride anions while other halogen anions (chloride and bromide) and acid anions (hex-phosphate, hydrogen sulfate, and nitrate) kept inactive, which offered the selective fluorescence switch-off sensing of the fluoride anions. Remarkably, the CMPs also exhibited high sensitivity and selectivity to fluoride anions. The detection limit was below two hundred nanomolar, which is ranked the best among fluoride sensor systems. This research opened a new structure design for chemical-sensors in porous materials