We report single-mode and multimode lasing from isolated spherical liquid microcavities containing CdSe/ZnS nanocrystal quantum dots. Lasing is observed at densities more than 2 orders of magnitude lower than previously demonstrated or theoretically predicted, assuming a uniform nanocrystal quantum dot distribution. Charged droplets, between 10 and 40 microm in size, are electrodynamically levitated and optically pumped. Substantial laser signals at low thresholds are measured from the directional emission normal to the pump beam, owing to the high Q cavity modes.

Rationale: Increased microglial activation and neuroinflammation within autonomic brain regions have been implicated in sustained hypertension (HTN) and their inhibition by minocycline, an anti-inflammatory antibiotic, produces beneficial effects. These observations led us to propose a dysfunctional brain-gut communication hypothesis for HTN. However, it has been difficult to reconcile whether an anti-inflammatory or antimicrobial action is the primary beneficial effect of minocycline in HTN. Accordingly, we utilized chemically modified tetracycline-3 (CMT-3), a derivative of tetracycline that has potent anti-inflammatory activity, to address this question. Objective: Test the hypothesis that central administration of CMT-3 would inhibit microglial activation, attenuate neuroinflammation, alter selective gut microbial communities, protect the gut wall from developing HTN-associated pathology, and attenuate HTN. Methods and Results: Rats were implanted with radio-telemetry devices for recording mean arterial pressure (MAP). Angiotensin II (AngII) was infused subcutaneously using osmotic minipumps to induce HTN. Another osmotic mini-pump was surgically implanted to infuse CMT-3 intracerebroventricularly (ICV). ICV CMT-3 infusion was also investigated in spontaneously hypertensive rats (SHR). Physiological, pathological, immuno-histological parameters, and fecal microbiota were analyzed. ICV CMT-3 significantly inhibited AngII-induced increases in number of microglia, their activation and proinflammatory cytokines in the paraventricular nucleus of hypothalamus. Further, ICV CMT-3 attenuated increased MAP, normalized sympathetic activity and left ventricular hypertrophy in AngII-rats as well as in the SHR. Finally, CMT-3 beneficially restored certain gut microbial communities altered by AngII and attenuated pathological alterations in gut wall. Conclusions: These observations demonstrate that inhibition of microglial activation alone was sufficient to induce significant antihypertensive effects. This was associated with unique changes

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B 0 AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.

Pulmonary hypertension (PH) is a devastating disease and its successful treatment remains to be accomplished despite recent advances in pharmacotherapy. It has been proposed that PH be considered as a systemic disease, rather than primarily a disease of the pulmonary vasculature. Consequently, an investigation of the intricate interplay between multiple organs such as brain, vasculature, and lung in PH could lead to the identification of new targets for its therapy. However, little is known about this interplay. This study was undertaken to examine the concept that altered autonomic-pulmonary communication is important in PH pathophysiology. Therefore, we hypothesize that activation of microglial cells in the paraventricular nucleus of hypothalamus and neuroinflammation is associated with increased sympathetic drive and pulmonary pathophysiology contributing to PH. We utilized the monocrotaline rat model for PH and intracerebroventricular administration of minocycline for inhibition of microglial cells activation to investigate this hypothesis. Hemodynamic, echocardiographic, histological, immunohistochemical, and confocal microscopic techniques assessed cardiac and pulmonary function and microglial cells. Monocrotaline treatment caused cardiac and pulmonary pathophysiology associated with PH. There were also increased activated microglial cells and mRNA for proinflammatory cytokines (IL [interleukin]-1β, IL-6, and TNF [tumor necrosis factor]-α) in the paraventricular nucleus. Furthermore, increased sympathetic drive and plasma norepinephrine were observed in rats with PH. Intracerebroventricular infusion of minocycline inhibited all these parameters and significantly attenuated PH. These observations implicate a dysfunctional autonomic-lung communication in the development and progression of PH providing new therapeutic targets, such as neuroinflammation, for PH therapy.