Biofilm formation is closely related to the pathogenetic processes of Klebsiella pneumoniae, which frequently causes infections in immunocompromised individuals. The immune system of astronauts is compromised in spaceflight. Accordingly, K. pneumoniae, which used to be isolated from orbiting spacecraft and astronauts, poses potential threats to the health of astronauts and mission security. Microgravity is a key environmental cue during spaceflight. Therefore, determining its effects on bacterial biofilm formation is necessary. In this study, K. pneumoniae ATCC BAA‐1705 was exposed to a simulated microgravity (SMG) environment. K. pneumoniae grown under SMG formed thicker biofilms compared with those under normal gravity (NG) control after 2 weeks of subculture. Two indicative dyes (i.e., Congo red and calcofluor) specifically binding to cellulose fibers and/or fimbriae were utilized to reconfirm the enhanced biofilm formation ability of K. pneumoniae grown under SMG. Further analysis showed that the biofilms formed by SMG‐treated K. pneumoniae were susceptible to cellulase digestion. Yeast cells mannose‐resistant agglutination by K. pneumoniae type 3 fimbriae was more obvious in the SMG group, which suggests that cellulose production and type 3 fimbriae expression in K. pneumoniae were both enhanced under the SMG condition. Transcriptomic analysis showed that 171 genes belonging to 15 functional categories were dysregulated in this organism exposed to the SMG conditions compared with those in the NG group, where the genes responsible for the type 3 fimbriae (mrkABCDF) and its regulator (mrkH) were upregulated.

Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia, and reduced uterine perfusion pressure (RUPP). RUPP causes imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT 1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, smooth muscle and various components of the extracellular matrix. Generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels causes decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. Enhanced mechanisms of vascular smooth muscle contraction, such as intracellular Ca 2+ , protein kinase C, and Rho-kinase cause further increases in vasoconstriction. Changes in matrix metalloproteinases and extracellular matrix cause inadequate vascular remodeling and increased arterial stiffening, leading to further increases in vascular resistance and hypertension.Therapeutic options are currently limited, but understanding the molecular determinants of microvascular dysfunction could help in the design of new approaches for the prediction and management of preeclampsia. K E Y W O R D S endothelium, extracellular matrix, microvessels, placental ischemia, vascular smooth muscle | 3 of 25 YU et al. to microvascular dysfunction, decreased vascular relaxation, increased vasoconstriction, aberrant vascular remodeling, and HTN.Throughout the review we will briefly define the factor involved, and describe the levels during normal pregnancy followed by the changes in human PE and experimental HTN-Preg. We will then discuss how identifying the molecular determinant of microvascular dysfunction could help design new approaches in the prediction and management of PE. | DEFEC TIVE PL ACENTATI ON AND UTEROPL ACENTAL ISCHEMIA IN PEDuring early pregnancy, the placenta is developed as a maternalfetal interface through several biological processes including vasculogenesis, angiogenesis, and trophoblast invasion and remodeling of spiral arteries. Vasculogenesis is the development of de novo blood vessels from endothelial progenitor cells and occurs ~18-35 days after conception in humans. Angiogenesis is the sprouting of new blood vessels from preexisting vessels and is regulated by the coordinated actions of proangiogenic factors and the invasive capability of trophoblast cells. 12 Healthy pregnancy requires adequate placental vascularization. During the first trimester, the placental extravillous trophoblasts invade deep into the maternal de...

Introduction Hyperhomocysteineamia (HHcy) has long been suggested as a risk factor for atherosclerosis. However the association between HHcy and peripheral arterial disease (PAD) is still controversial. There is a lack of research on this topic in the Chinese population. This study aims to provide further results. Methods 240 PAD patients and 240 control subjects were evaluated for both serum total homocysteine levels and ankle brachial indexes (ABIs). Multivariable logistic regression models were used to estimate the association between HHcy and the risk of developing PAD. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and histories of chronic disease. Results The multivariate logistic analyses revealed that the risk of PAD was significantly associated with serum homocysteine levels. The interaction analysis showed no interactive role in the association between HHcy and PAD, indicating that homocysteine was associated with PAD independent of classical vascular risk factors. Conclusion In conclusion, HHcy is an independent risk factor for PAD in the Chinese Han population. A prospective and randomized clinical trial of homocysteine lowering therapy in the Chinese population is needed to assess the causal nature of the relationship.

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