P. aeruginosa tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in cystic fibrosis.

Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of Pseudomonas aeruginosa (P. aeruginosa) in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5' tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates of P. aeruginosa. The 5' tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion. In mouse lungs, increased expression of the 5' tRNA-fMet halves in OMVs attenuated KC (murine homolog of IL-8) secretion and neutrophil recruitment. Furthermore, there was less IL-8 and neutrophils in bronchoalveolar lavage fluid isolated from pwCF during the period of exposure to tobramycin versus the period off tobramycin. In conclusion, we have shown in mice and in vitro studies on CF-HBEC that tobramycin reduces inflammation by increasing 5' tRNA-fMet halves in OMVs that are delivered to CF-HBEC and reduce IL-8 and neutrophilic airway inflammation. This effect is predicted to improve lung function in pwCF receiving tobramycin for P. aeruginosa infection.NEW & NOTEWORTHY The experiments in this report identify a novel mechanism, whereby tobramycin reduces inflammation in two models of CF. Tobramycin increased the secretion of tRNA-fMet halves in OMVs secreted by P. aeruginosa, which reduced the OMV-LPS-induced inflammatory response in primary cultures of CF-HBEC and in mouse lung, an effect predicted to reduce lung damage in pwCF.

P. aeruginosa tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis.

Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of Pseudomonas aeruginosa (P. aeruginosa) in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5' tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates of P. aeruginosa . The 5' tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion. In mouse lung, increased expression of the 5' tRNA-fMet halves in OMVs attenuated KC secretion and neutrophil recruitment. Furthermore, there was less IL-8 and neutrophils in bronchoalveolar lavage fluid isolated from pwCF during the period of exposure to tobramycin versus the period off tobramycin. In conclusion, we have shown in mice and in vitro studies on CF-HBEC that tobramycin reduces inflammation by increasing 5' tRNA-fMet halves in OMVs that are delivered to CF-HBEC and reduce IL-8 and neutrophilic airway inflammation. This effect is predicted to improve lung function in pwCF receiving tobramycin for P. aeruginosa infection. New and noteworthy: The experiments in this report identify a novel mechanim whereby tobramycin reduces inflammation in two models of CF. Tobramycin increased the secretion of tRNA-fMet haves in OMVs secreted by P. aeruginiosa , which reduced the OMV-LPS induced inflammatory response in primary cultures of CF-HBEC and in mouse lung, an effect predicted to reduce lung damage in pwCF. Graphical abstract: The anti-inflammatory effect of tobramycin mediated by 5' tRNA-fMet halves secreted in P. aeruginosa OMVs. (A) P. aeruginosa colonizes the CF lungs and secrets OMVs. OMVs diffuse through the mucus layer overlying bronchial epithelial cells and induce IL-8 secretion, which recruits neutrophils that causes lung damage. ( B ) Tobramycin increases 5' tRNA-fMet halves in OMVs secreted by P. aeruginosa . 5' tRNA-fMet halves are delivered into host cells after OMVs fuse with lipid rafts in CF-HBEC and down-regulate protein expression of MAPK10, IKBKG, and EP300, which suppresses IL-8 secretion and neutrophils in the lungs. A reduction in neutrophils in CF BALF is predicted to improve lung function and decrease lung damage.

A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway. Here, we present a system of reporters for comparative studies of EJC-independent and EJC-enhanced NMD. This system also enables the study of NMD-associated outcomes such as premature termination codon (PTC) readthrough and truncated protein degradation. These reporters are compatible with fluorescence or luminescence-based readouts via transient transfection or stable integration. Using this reporter system, we show that EJC-enhanced NMD RNA levels are reduced by 2- or 9-fold and protein levels are reduced by 7- or 12-fold compared to EJC-independent NMD, depending on the reporter gene used. Additionally, the extent of readthrough induced by G418 and an NMD inhibitor (SMG1i), alone and in combination, varies across NMD substrates. When combined, G418 and SMG1i increase readthrough product levels in an additive manner for EJC-independent reporters, while EJC-enhanced reporters show a synergistic effect. We present these reporters as a valuable toolkit to deepen our understanding of NMD and its associated mechanisms.

Contamination and health risks brought by arsenic, lead and cadmium in a water-soil-plant system nearby a non-ferrous metal mining area.

Heavy metal(loid)s contamination prevails in the water-soil-plant system around non-ferrous metal mining areas. The present study aimed to evaluate the heavy metal(loid)s contamination in Nandan Pb-Zn mining area (Guangxi, China). A total of 36 river water samples, 75 paired paddy soil and rice samples, and 128 paired upland soil and plant samples were collected from this area. The concentrations of arsenic (As), lead (Pb), and cadmium (Cd) in these samples were measured. Results showed that the average water quality indexes (WQIs) at the 12 sampling sites along the main river ranged from 41 to 5008, indicating the water qualities decreasing from "Excellent" to "Undrinkable". The WQIs nearby tailings or industrial park were significantly higher than those at the other sites. 34.0% and 64.5% of soil samples exceeded the risk screening values for As and Cd. The Pb and Cd concentrations in all rice samples exceeded the Chinese food safety limits by 18.7% and 82.7%, respectively. Leafy vegetables had a higher concentration of As, Pb, and Cd than other vegetables, exceeding the maximum permissible limits by 14.1%, 61.2%, and 40.0%, respectively. The biological accumulation coefficient (BAC) of Cd was the highest in rice and lettuce leaves. The hazard quotients (HQs) of As and Cd, indicating non-carcinogenic risks, were 4.15 and 1.76 in adult males, and 3.40 and 1.45 in adult females, all higher than the permitted level (1.0). The carcinogenic probabilities of As and Cd from rice and leafy vegetables consumption were all higher than 1 × 10-4. We conclude that metal(loid)s contamination of the water-soil-plant system has posed great non-carcinogenic and carcinogenic risks to the local population.

A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway. Here, we present a system of reporters for comparative studies of EJC-independent and EJC-enhanced NMD. This system also enables the study of NMD-associated outcomes such as premature termination codon (PTC) readthrough and truncated protein degradation. These reporters are compatible with fluorescence or luminescence-based readouts via transient transfection or stable integration. Using this reporter system, we show that EJC-enhanced NMD RNA levels are reduced by 2- or 9-fold and protein levels are reduced by 7- or 12-fold compared to EJC-independent NMD, depending on the reporter gene used. Additionally, the extent of readthrough induced by G418 and SMG1i, alone and in combination, varies across NMD substrates. When combined, G418 and SMG1i increase readthrough product levels in an additive manner for EJC-independent reporters, while EJC-enhanced reporters show a synergistic effect. We present these reporters as a valuable toolkit to deepen our understanding of NMD and its associated mechanisms.

Remodeling of the cardiovascular hemodynamic environment by lower limb heat exposure: A computational fluid dynamic study.

BACKGROUND: Lower limb heat exposure (LLHE) is a promising strategy for the daily management of cardiovascular health because of its non-pharmaceutical advantages. To support the application of this strategy in cardiovascular protection, we examined its impact on the global hemodynamic environment. METHODS: Skin blood flow (SBF) of eight locations on the lower limbs was measured before and after LLHE (40 °C and 44 °C) in ten healthy subjects by using a laser Doppler flowmeter. A closed-loop model of circulation uses changes in SBF to quantify the influence of LLHE on the blood flow of the arterial trunk (from ascending aorta to the femoral artery) and visceral branches (coronary, celiac, renal, and mesenteric arteries). RESULTS: The SBF in all locations tested on the lower limbs increased significantly (p<0.001) with LLHE and a 3.39-fold and 7.40-fold increase in mean SBF were observed under 40 °C and 44 °C conditions, respectively. In the model, the peak (3.9-25.1%), end-diastolic (13.7-107.3%), and mean blood flow (8.5-86.5%) in the arterial trunk increased with the increase in temperature, but the retrograde flow in the thoracic aorta and abdominal aorta Ⅰ increased at least twice in the diastolic period. Furthermore, LLHE also increased the blood flow of the visceral branches (2.5-20.7%). CONCLUSION: These findings suggest that LLHE is expected to be a daily strategy for enhancing the functions of both the arterial trunk and visceral arteries, but the increased blood flow reversal in the thoracic and abdominal aortas warrants further investigation.

[Animal experimental study on the effects of different levels of amputation on cardiovascular system].

Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations. The results showed that amputation caused pathological changes in the cardiovascular system of animals, including endothelial injury, inflammation, and angiosclerosis. The degree of cardiovascular injury was higher in the AKA group than in the BKA group. This study sheds light on the internal mechanisms of amputation's impact on the cardiovascular system. Based on the amputation level of patients, the findings recommend more comprehensive and targeted monitoring after surgery and necessary interventions to prevent cardiovascular diseases.

Shear Adhesion of Ice on Large-Sized Grooved Aluminum Surfaces.

Ice adhesion is important when designing aircraft anti-icing/de-icing systems. Major and minor grooves are common in the skin of aircraft. However, the effects of millimeter-scale grooves on ice adhesive strength have not been given due attention. Specimens with varying depths, widths, and numbers of grooves were fabricated by machining to investigate the ice adhesive characteristics of large-sized grooved aluminum surfaces. After the ice cube was frozen on the surface using a silicon mold, the adhesive force was measured using a self-assembled shear adhesive force setup. A correlation between groove size and apparent adhesive strength in the perpendicular loading direction was established based on the experimental results. Every 1% increase in the groove width ratio was associated with an 18.7 kPa increase in apparent adhesive strength. The increasing speed of the adhesion rapidly decayed as the groove depth increased. The increase in adhesion reached 99% of the maximum increase when the groove depth reached 0.8 times the width. The number of grooves had little effect on the adhesion when the total width of the grooves was kept constant. Stress distribution analysis was conducted using the finite element method, and the results were in accordance with the cracking phenomena in the experiments. The adhesive strength in the parallel loading direction was 30% lower than that in the perpendicular loading direction for all six chosen surfaces. This study is the first to propose a quantitative relationship between the surface textures of millimeter-sized grooves and ice adhesive strength. The loading orientation also had a substantial influence on adhesion. The results will serve as a valuable reference for future studies on ice adhesion on textured surfaces and for improving the performance of anti-icing/de-icing systems.

Effect of lower extremity amputation on cardiovascular hemodynamic environment: An in vitro study.

Lower extremity amputation (LEA) was associated with a greater risk of cardiovascular disease, but its hemodynamic mechanisms have not been fully studied. Therefore, to clarify the interrelationship between them, and figure out the potential pathogenesis, the exploration of the hemodynamic environment change of patients after LEA was premeditatedly executed. A near-physiological mock circulatory system (MCS) was employed in the present work to replicate the cardiovascular circulation after LEA in a short time and the unsteady-state numerical simulation was utilized as an auxiliary method to observe the changes of the hemodynamic environment inside the blood vessel. Higher severity of LEA leads to higher peripheral vascular impedance, higher blood pressure, and more obvious redistribution of blood perfusion volume. In addition, higher severity of LEA leads to lower wall shear stress (WSS), higher oscillatory shear index (OSI), and higher relative residence time (RRT) appeared in the infrarenal abdominal aorta and the iliac artery, while these changes are closely related to the higher probability of cardiovascular diseases. Results showed that different degrees of LEA (varying heights, unilateral/bilateral) have diverse effects on the patient's hemodynamic environment. This study explained the potential pathogenesis of cardiovascular diseases after LEA from a hemodynamic perspective and provided a certain reference value for the improvement of the cardiovascular hemodynamic environment and the prevention of cardiovascular diseases in lower extremity amputees.

[Establishment of an animal model to study the effects of amputation on the cardiovascular system].

Lower limb amputation is a significant change in body structure. Loss of muscle, blood vessels, and blood leads to a redistribution of blood flow and changes in resistance at the end of blood vessels. In view of the significant increase in the prevalence of cardiovascular disease after lower limb amputation, the mechanism of which is still unclear, this study aims to establish an animal research model that can verify and explore the effects of amputation on cardiovascular system, and provide the experimental basis for subsequent animal experiments when exploring the effect of different amputation levels on the cardiovascular system. SPF New Zealand rabbits were divided into normal group ( n = 6) and amputation group ( n = 6). The amputation group was treated with above-knee amputation. The changes of low-density liptein cholesterol (LDL-C) and total cholesterol (TC) in serum of all the rabbits were monitored regularly after the surgery. The arterial pathological examination was conducted after the experimental rabbits were executed. The results showed that compared with the normal group, serum LDL-C content and TC content in the amputation group were significantly increased ( P<0.05); The blood vessels of the amputated rabbits had pathological changes such as degeneration and necrosis of smooth muscle cells in the middle membrane layer and rupture of elastic fibers. At the abdominal aorta and aortic arch, the elastic fiber area expression percentage (EFEP) of the experimental group was significantly lower than that of the normal group. The results suggest that the cardiovascular system of rabbits has the tendency of decreased arterial elasticity and lipid deposition in blood after amputation, indicating that the animal research model on the effect of amputation on the cardiovascular system has been successfully established, and can provide an experimental platform for further study on the mechanism of the effect of amputation on the cardiovascular system.

The hemodynamic effect of eccentricity in visceral branched aneurysms with multilayer stents.

It is preliminarily acknowledged that multilayer stent (MS) is a promising alternative technology in the treatment of visceral branched aneurysms, but hemodynamic consequences of eccentricity in such aneurysms with MS are less examined. In this work, we performed a time-dependent simulation of branched aneurysms of various eccentricities with different stent layers, and thrombosis-related parameters, such as time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and relative residence time (RRT), were also analyzed. Our results revealed that MS can generally restore laminar flow inside the stent, and allow proper perfusion to vital organs while also fostering a relatively secluded hemodynamic environment for thrombosis formation. Particularly, a flow in the aneurysm sac communicating between the main artery and side branch forms at early systole. However, MS fails to completely eliminate detrimental flow impingement after peak systole, which may hinder aneurysm recovery, especially in the cases of eccentric aneurysms. Therefore, saccular aneurysms should be treated with more caution than fusiform aneurysms. And further therapeutic attempts to keep both perfusion in the proximal region of the aneurysm and isolation in the distal region of the aneurysm should be considered.

Reallocation of cutaneous and global blood circulation during sauna bathing through a closed-loop model.

OBJECTIVE: Sauna bathing (SB) is an important strategy in cardiovascular protection, but there is no mathematical explanation for the reallocation of blood circulation during heat-induced superficial vasodilation. We sought to reveal such reallocation via a simulated hemodynamic model. METHODS: A closed-loop cardiovascular model with a series of electrical parameters was constructed. The body surface was divided into seven blocks and each block was modeled by a lumped resistance. These resistances were adjusted to increase skin blood flow (SBF), with the aim of reflecting heat-induced vasodilation during SB. Finally, the blood pressure was compared before and after SB, and the blood flow inside the aorta and visceral arteries were also analyzed. RESULTS: With increasing SBF in this model, the systolic, diastolic, and mean blood pressure in the arterial trunk decreased by 13-29, 18-36, and 19-37 mmHg, respectively. Despite the increase in the peak and mean blood flow in the arterial trunk, the diastolic blood flow reversal in the thoracic and abdominal aortas increased significantly. Nevertheless, the blood supply to the heart, liver, stomach, spleen, kidney, and intestine decreased by at least 25%. Moreover, the pulmonary blood flow increased significantly. CONCLUSION: Simulated heat-induced cutaneous vasodilation in this model lowers blood pressure, induces visceral ischemia, and promotes pulmonary circulation, suggesting that the present closed-loop model may be able to describe the effect of sauna bathing on blood circulation. However, the increase of retrograde flow in the aortas found in this model deserves further examination.

[Effect of lower limb amputation level on aortic hemodynamics: a numerical study].

It has been found that the incidence of cardiovascular disease in patients with lower limb amputation is significantly higher than that in normal individuals, but the relationship between lower limb amputation and the episodes of cardiovascular disease has not been studied from the perspective of hemodynamics. In this paper, numerical simulation was used to study the effects of amputation on aortic hemodynamics by changing peripheral impedance and capacitance. The final results showed that after amputation, the aortic blood pressure increased, the time averaged wall shear stress of the infrarenal abdominal aorta decreased and the oscillatory shear index of the left and right sides was asymmetrically distributed, while the time averaged wall shear stress of the iliac artery decreased and the oscillatory shear index increased. The changes above were more significant with the increase of amputation level, which will result in a higher incidence of atherosclerosis and abdominal aortic aneurysm. These findings preliminarily revealed the influence of lower limb amputation on the occurrence of cardiovascular diseases, and provided theoretical guidance for the design of rehabilitation training and the optimization of cardiovascular diseases treatment.

Clinical and hemodynamic insights into the use of internal iliac artery balloon occlusion as a prophylactic technique for treating postpartum hemorrhage.

Recently, the effectiveness of internal iliac artery balloon occlusion (IIABO) for treating postpartum hemorrhage caused by pernicious placenta previa (PPP) has been questioned. We conducted a retrospective analysis and hemodynamic simulation to assess the IIABO's effectiveness. The retrospective analysis involved 480 patients with PPP, among which 288 underwent IIABO treatment and the remaining 192 were used as controls. Blood loss and preoperative indicators were recorded, and multiple regression analysis was applied to test the effect of preoperative indicators on blood loss. Hemorrhage mechanisms were simulated using a numerical model. Results suggested that no significant difference in blood loss (1836 ± 1440 ml vs. 1784 ± 1647 ml, p = 0.22) was observed between the two groups. In addition, preoperative indicators, including age, weight, gestational age, gravidity, parity, blood type, anemia, or diabetes, were not associated with blood loss. In the simulation, after the intra-iliac artery was blocked, blood loss was caused by a reversed flow in the intrapelvic arteries, uterine veins, and uterine venules. The ratio of the time-averaged hemorrhage velocity (TAHV) in the balloon group to that in the control group was lower than that obtained in a clinical study (13.0% vs. 88.9%); in the presence of collateral circulation, blood loss occurred from collateral circulation and uterine venules after IIABO intervention, and the TAHV was 60%-90% that of the control group, which was closer to the clinical results (88.9%). These results suggest that IIABO cannot effectively treat postpartum hemorrhage because of the collateral circulation and reversed flow in the uterine venules.

Numerical insights into the determinants of stent performance for the management of aneurysm with a visceral vessel attached.

PURPOSE: As the factors affecting the efficacy of the bare-metal stent in the treatment of aneurysm with a visceral vessel attached were not fully understood, we aimed to discuss the effects of different characteristics of the stent on the hemodynamics and flexibility in the treatment of the aneurysm. METHODS: Single-layer (with different strut widths) and multi-layer (with a different number of struts) stent models divided into three porosity groups, with porosities of 72.3, 60.5, and 52.4%, were modeled for a comparison of their hemodynamic isolation and flexibility performance via computational fluid dynamics and finite element methods. RESULTS: The velocity and timeaveraged wall shear stress decreased more noticeably with multi-layer stent interventions. A higher oscillatory shear index and relative residence time occurred at the aneurysmal sac wall after multi-layer stents were employed. Time-averaged wall shear stress on the aneurysmal wall decreased with an increase in the number of struts or a decrease in pore size, but oscillatory shear index and relative residence time increased as the number of struts increased or the pore size decreased. Besides, all stents affect the branch patency slightly. In the bending test, when the porosity exceeded 60.5%, multi-layer stents were more flexible. CONCLUSION: The number of struts or pore size of stent dominated the isolation in the management of the aneurysm and affected the flexibility significantly when the porosity was below 60.5%. These findings may contribute to the special design of the stent in the treatment of such types of aneurysms.

Association of lead and cadmium exposure with kidney stone incidence: A study on the non-occupational population in Nandan of China.

BACKGROUND: Environmental lead (Pb) and cadmium (Cd) pollution has been considered a risk factor in the etiology of kidney stones. However, the association between Pb and Cd exposure and kidney stone incidence has yet to be determined. OBJECTIVES: This study aimed to determine a possible the association between kidney stones with Pb and Cd exposure (alone or combined) in a non-occupational population. METHODS: Pb and Cd contaminations in soil-plant system were determined by flame atomic absorption spectrophotometry. Health risk assessment of dietary Pb or Cd intake from rice and vegetables were calculated. Kidney stones were diagnosed with urinary tract ultrasonography. Urinary cadmium (UCd) and blood lead (BPb) levels were determined by graphite-furnace atomic absorption spectrometry. Multivariate logistic regression models were constructed. RESULTS: The hazard indexes (HI) of Pb and Cd were 7.91 and 7.31. The odds ratio (OR) was 2.83 (95 %CI:1.38-5.77) in males with high BPb (BPb ≥ 100 µg/L), compared with those with low BPb (BPb＜100 µg/L). Compared to those with low BPb and low UCd (BPb＜100 µg/L and UCd＜2 µg/g creatinine), the ORs were 2.58 (95 % CI:1.17-5.70) and 3.43 (95 % CI:1.21-9.16) in females and males with high BPb and high UCd (BPb ≥100 µg/L and UCd ≥2 µg/g creatinine), respectively. The OR was 3.16 (95 % CI:1.26-7.88) in males with high BPb and low UCd (BPb ≥ 100 µg/L and UCd ＜2 µg/g creatinine), compared to those with low BPb and low UCd. CONCLUSIONS: Kidney stones incidence was increased by high Pb exposure in males, and by Pb and Cd co-exposure in males and females.

Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen that forms antibiotic-resistant biofilms, which facilitate chronic infections in immunocompromised hosts. We have previously shown that P. aeruginosa secretes outer-membrane vesicles that deliver a small RNA to human airway epithelial cells (AECs), in which it suppresses the innate immune response. Here, we demonstrate that interdomain communication through small RNA-containing membrane vesicles is bidirectional and that microRNAs (miRNAs) in extracellular vesicles (EVs) secreted by human AECs regulate protein expression, antibiotic sensitivity, and biofilm formation by P. aeruginosa Specifically, human EVs deliver miRNA let-7b-5p to P. aeruginosa, which systematically decreases the abundance of proteins essential for biofilm formation, including PpkA and ClpV1-3, and increases the ability of beta-lactam antibiotics to reduce biofilm formation by targeting the beta-lactamase AmpC. Let-7b-5p is bioinformatically predicted to target not only PpkA, ClpV1, and AmpC in P. aeruginosa but also the corresponding orthologs in Burkholderia cenocepacia, another notorious opportunistic lung pathogen, suggesting that the ability of let-7b-5p to reduce biofilm formation and increase beta-lactam sensitivity is not limited to P. aeruginosa Here, we provide direct evidence for transfer of miRNAs in EVs secreted by eukaryotic cells to a prokaryote, resulting in subsequent phenotypic alterations in the prokaryote as a result of this interdomain communication. Since let-7-family miRNAs are in clinical trials to reduce inflammation and because chronic P. aeruginosa lung infections are associated with a hyperinflammatory state, treatment with let-7b-5p and a beta-lactam antibiotic in nanoparticles or EVs may benefit patients with antibiotic-resistant P. aeruginosa infections.

Transfer RNA-Derived Fragments, the Underappreciated Regulatory Small RNAs in Microbial Pathogenesis.

In eukaryotic organisms, transfer RNA (tRNA)-derived fragments have diverse biological functions. Considering the conserved sequences of tRNAs, it is not surprising that endogenous tRNA fragments in bacteria also play important regulatory roles. Recent studies have shown that microbes secrete extracellular vesicles (EVs) containing tRNA fragments and that the EVs deliver tRNA fragments to eukaryotic hosts where they regulate gene expression. Here, we review the literature describing microbial tRNA fragment biogenesis and how the fragments secreted in microbial EVs suppress the host immune response, thereby facilitating chronic infection. Also, we discuss knowledge gaps and research challenges for understanding the pathogenic roles of microbial tRNA fragments in regulating the host response to infection.

Acute Hemodynamic Improvement by Thermal Vasodilation inside the Abdominal and Iliac Arterial Segments of Young Sedentary Individuals.

OBJECTIVE: To study the hemodynamic response to lower leg heating intervention (LLHI) inside the abdominal and iliac arterial segments (AIAS) of young sedentary individuals. METHODS: A Doppler measurement of blood flow was conducted for 5 young sedentary adults with LLHI. Heating durations of 0, 20, and 40 min were considered. A lumped parameter model (LPM) was used to ascertain the hemodynamic mechanism. The hemodynamics were determined via numerical approaches. RESULTS: Ultrasonography revealed that the blood flow waveform shifted upwards under LLHI; in particular, the mean flow increased significantly (p < 0.05) with increasing heating duration. The LPM showed that its mechanism depends on the reduction in afterload resistance, not on the inertia of blood flow and arterial compliance. The time-averaged wall shear stress, time-averaged production rate of nitric oxide, and helicity in the external iliac arteries increased more significantly than in other segments as the heating duration increased, while the oscillation shear index (OSI) and relative residence time (RRT) in the AIAS declined with increasing heating duration. There was a more obvious helicity response in the bilateral external iliac arteries than the OSI and RRT responses. CONCLUSION: LLHI can effectively induce a positive hemodynamic environment in the AIAS of young sedentary individuals.