Aqueous Synthesis, Doping, and Processing of n-Type Ag2Se for High Thermoelectric Performance at Near-Room-Temperature.

Herein, we have successfully synthesized binary Ag2Se, composite Ag0:Ag2Se, and ternary Cu+:Ag2Se through an ambient aqueous-solution-based approach in a one-pot reaction at room temperature and atmospheric pressure without involving high-temperature heating, multiple-processes treatment, and organic solvents/surfactants. Effective controllability over phases and compositions/components are demonstrated with feasibility for large-scale production through an exquisite alteration in reaction parameters especially pH for enhancing and understanding thermoelectric properties. Thermoelectric ZT reaches 0.8-1.1 at near-room-temperature for n-type Ag2Se and Cu+ doping further improves to 0.9-1.2 over a temperature range of 300-393 K, which is the largest compared to that reported by wet chemistry methods. This improvement is related to the enhanced electrical conductivity and the suppressed thermal conductivity due to the incorporation of Cu+ into the lattice of Ag2Se at very low concentrations (x%Cu+:Ag2Se, x = 1.0, 1.5, and 2.0).

Polylactic acid face masks: Are these the sustainable solutions in times of COVID-19 pandemic?

The global massive consumption of disposable face masks driven by the ongoing COVID-19 pandemic has emerged as a blooming disaster to both the land and marine environment that might last for generations. Growing public concerns have been raised over the management and control of this new form of plastic pollution, and one of the proposed sustainable solution is to use renewable and/or biodegradable resources to develop mask materials in order to minimize their environmental impacts. As a representative biodegradable polymer, polylactic acid (PLA) has been proposed as a promising candidate to produce non-woven face masks instead of those fossil-based polymers. To further explore the feasibility of this alternative mask material, the present work aims to study both the hydrolytic and bio-degradation behaviors of pure PLA-derived 3-ply disposable face masks at ambient temperature. Hydrolytic degradability was investigated at different pH conditions of 2, 7 and 13 with the whole piece of face mask soaked for regular timed intervals up to 8 weeks. Weight loss study showed neutral and acidic conditions had minimal effect on PLA masks, but rapid degradation occurred under basic conditions in the first week with a sharp 25% decrease in weight that slowly tapered off, coupled with solution pH dropping from 13 to 9.6. This trend was supported by mechanical property, bacterial filtration efficiency (BFE) and particulate filtration efficiency (PFE) studies. Masks soaked in basic conditions had their modulus and tensile strength dropped by more than 50% after 8 weeks where the middle layer reached 68% and 90% respectively just after 48 h, and BFE and PFE decreased by 14% and 43% respectively after 4 weeks, which was much more significant than those in neutral and acidic conditions. Base degradation was also supported by nuclear magnetic resonance (NMR) and fourier transform infrared (FTIR), which disclosed that only the middle layer undergo major degradation with random chain scission and cleavage of enol or enolate chain ends, while outer and inner layers were much less affected. Scanning electron microscopy (SEM) attributed this observation to thinner PLA fibers for the middle layer of 3-7 µm diameter, which on average is 3 times smaller. This degradation was further supported by gel permeation chromatography (GPC) which saw an increase in lower molecular weight fragment Mw ~ 800 Da with soaking duration. The biodegradation behavior was studied under OECD 301F specification in sewage sludge environment. Similarly, degradation to the middle meltblown layer was more extensive, where the average weight loss and carbon loss was 25.8% and 25.7% respectively, double that of outer/inner spunbond layer. The results showed that the face masks did not completely disintegrate after 8 weeks, but small solubilized fragments of PLA formed in the biodegradation process can be completely mineralized into carbon dioxide without generation of secondary microplastic pollution in the environment. PLA masks are therefore a slightly greener option to consider in times of a pandemic that the world was caught unprepared; however future research on masks could be geared towards a higher degradability material that fully breaks down into non-harmful components while maintaining durability, filtration and protection properties for users.

Cardiovascular effects of melanocortins.

Melanocortins (MSH's) are three structurally related peptides derived from proopiomelanocortin. They regulate several physiologic functions including energy metabolism, appetite, and inflammation. Recent work in rodents has also identified important effects of MSH's, particularly γ-MSH, on sodium metabolism and blood pressure regulation. Normal rats and mice respond to a high sodium diet with an increase in the plasma concentration of γ-MSH, and remain normotensive, while those with genetic or pharmacologic γ-MSH deficiency become hypertensive on a high sodium diet. This hypertension is corrected by exogenous administration of the peptide. Mice lacking the γ-MSH receptor (the melanocortin 3 receptor, Mc3r) also become hypertensive on a high sodium diet but remain so when administered γ-MSH, and infusions of physiologic levels of the peptide stimulate urinary sodium excretion in normal rats and mice, but not in mice with deletion of Mc3r. The salt-sensitive hypertension in rodents with impaired γ-MSH signaling appears due to stimulation of noradrenergic activity, since plasma noradrenaline is increased and the hypertension is rapidly corrected with infusion of the α-adrenoceptor antagonist phentolamine. In contrast to the antihypertensive property of physiologic levels of γ-MSH, intravenous or intracerebroventricular injections of high levels of the peptide raise blood pressure. This occurs in mice lacking Mc3r, indicating an interaction with some other central receptor. Finally, the salt-sensitive hypertension in rodents with disruption of γ-MSH signaling is accompanied by insulin resistance, an observation which offers a new window into the study of the association of salt-sensitive hypertension with insulin resistance and type II diabetes.

Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat.

Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0.5 µg/min), or a combination. The right (noninfused) kidney served as a control. Intrarenal NONOate had no effect on mean arterial pressure (MAP); however, SILD reduced MAP in virgin rats, and the combination of NONOate+SILD reduced MAP in both virgin and pregnant rats. Neither NONOate nor SILD altered glomerular filtration rate. NONOate and SILD each stimulated sodium excretion (U(Na)V) and fractional excretion of sodium (FE(Na)) in virgin rats, but the combination did not result in an additional natriuretic response. However, NONOate infusion did not increase U(Na)V or FE(Na) in pregnant rats, but the natriuretic response to NONOate was restored with SILD, and SILD alone produced a natriuresis during pregnancy. Sodium nitroprusside (10(-4) mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10(-7) mol/l). Therefore, increased intrarenal PDE5 mediates the blunted natriuretic response to NO, and loss of responsiveness to the cGMP-dependent, natriuretic agents may contribute to volume expansion during pregnancy.

Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone.

A close association between salt-sensitive hypertension and insulin resistance has been recognized for more than two decades, although the mechanism(s) underlying this relationship have not been elucidated. Recent data in mice with genetic disruption of the gamma-melanocyte-stimulating hormone (gamma-MSH) system suggest that this system plays a role in the pathophysiological relationship between hypertension and altered glucose metabolism during ingestion of a high-sodium diet (8% NaCl, HSD). We tested the hypothesis that these two consequences of interrupted gamma-MSH signalling were the result of sympathetic activation by studying rats treated with the dopaminergic agonist bromocriptine (5 mg kg(-1) i.p., daily for 1 week; Bromo) to cause relative gamma-MSH deficiency. Bromo-treated rats fed the HSD developed hypertension and also exhibited fasting hyperglycaemia (P < 0.005) and hyperinsulinaemia (P < 0.025). Furthermore, Bromo-treated rats on the HSD had impaired glucose tolerance and blunted insulin-mediated glucose disposal. Intravenous infusion of gamma(2)-MSH, or of the alpha-adrenergic receptor antagonist phentolamine, to Bromo-HSD rats lowered both mean arterial pressure (MAP) and blood glucose to normal after 15 min (P < 0.001 versus control), but had no effect in rats receiving vehicle and fed the HSD; gamma(2)-MSH infusion also reduced the elevated plasma noradrenaline to control levels in parallel with the reductions in MAP and blood glucose concentration. Infusion of hydralazine to Bromo-HSD rats lowered MAP but had only a trivial effect on blood glucose. We conclude that rats with relative gamma-MSH deficiency develop abnormal glucose metabolism, with features of insulin resistance, in association with hypertension when ingesting the HSD. Elevated plasma noradrenaline concentration in Bromo-HSD rats is normalized by gamma(2)-MSH infusion, suggesting that an adrenergic mechanism may link the salt-sensitive hypertension and the impaired glucose metabolism of relative gamma-MSH deficiency.

Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat.

BACKGROUND: Rats with suppression of pituitary intermediate lobe (IL) function by treatment with the dopaminergic agonist bromocriptine develop salt-sensitive hypertension accompanied by a deficiency of gamma-melanocyte-stimulating hormone (gamma-MSH). METHODS: To study the time course, and establish the causal role, of gamma-MSH deficiency in the development of salt-sensitive hypertension, we instrumented 12 male Sprague-Dawley rats with radiotelemetry transmitters to record intraaortic mean arterial pressure (MAP). One week later, they were placed on a high-sodium diet (8% NaCl, HSD) and received daily intraperitoneal injections of bromocriptine (5 mg/kg). The rats were also implanted with micro-osmotic pumps to deliver either a stable analog of gamma-MSH ([Nle3, D-Phe6]-gamma-MSH, NDP-gamma-MSH) at 12 pmol/h or normal saline vehicle. RESULTS: In vehicle-treated rats on the HSD and receiving bromocriptine injections, MAP rose so that it was significantly greater than that in NDP-gamma-MSH-treated animals by Day 4, and reached a stable plateau of approximately 135 mm Hg between Days 7 and 14. After Day 14, bromocriptine injections were stopped, and MAP in vehicle-infused rats fell progressively despite continued ingestion of the HSD, so that by Day 18, MAP was no longer different from NDP-gamma-MSH-infused animals. The MAP in the latter group did not vary significantly from the control level of 101+/-4 mm Hg throughout the 21 days of the experiment. CONCLUSIONS: These results indicate that gamma-MSH deficiency is a consequence of the bromocriptine treatment responsible for the salt-sensitive hypertension, and these results also identify the time course during which this hypertension develops.

Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones.

OBJECTIVE: Alpha and gamma-melanocyte stimulating hormones (MSH) are peptides that possess potent hypertensinogenic actions when injected intravenously or intracerebroventricularly. We sought to define the central receptor(s) mediating these cardiovascular actions. METHODS: We gave bolus injections of synthetic alpha or gamma-MSH intravenously or intracerebroventricularly to anesthetized wild-type (Mc3r+/+, Mc4r+/+) mice and mice with targeted disruption of the gamma-MSH receptor (Mc3r-/-) or the melanocortin 4 receptor (Mc4r-/-). RESULTS: Gamma-MSH injected intravenously increased mean arterial pressure (MAP) and heart rate (HR) dose-dependently, with the effect being evident at 10 mol/kg; the maximum increase, at 10 mol/kg, was 38 mmHg in both strains from similar control MAP. Parallel increases in HR also occurred. Injection of the sodium channel blocker, benzamil, 4 microg/kg intracerebroventricularly, before intravenous gamma-MSH completely prevented the increases in MAP and HR in both strains. Injection of 2 x 10 mol/g body weight alpha-MSH intravenously had no effect on MAP or HR in Mc4r wild-type or -/- mice. However, the same dose given intracerebroventricularly to wild-type mice increased MAP from 76 +/- 4 to 95 +/- 5 mmHg at 10 min (P < 0.01) and HR from 416 +/- 15 to 480 +/- 15 beats/min (P < 0.01). In Mc4r-/- mice, the intracerebroventricular administration of the peptide did not alter these variables, in contrast to the results in wild-type mice. CONCLUSION: Both MSH peptides exert their hypertensinogenic effects through central sites of action, which probably reflect the activation of sympathetic outflow. The actions of intracerebroventricular alpha-MSH appear to be mediated via Mc4r, whereas those of gamma-MSH are independent of its receptor Mc3r, but reflect the activation of a sodium channel in the central nervous system. These results help to reconcile the hypertensive action of gamma-MSH injections with the hypertension observed in states of gamma-MSH deficiency.

Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney.

Gamma-melanocyte stimulating hormone (gamma-MSH) is a circulating natriuretic peptide hormone derived from proopiomelanocortin (POMC); its concentration in plasma and pituitary POMC mRNA abundance, increase in rats ingesting a high-sodium diet (HSD, 8% NaCl) compared with a low-sodium diet (LSD, 0.07% NaCl). RT-PCR of rat kidney RNA demonstrated reaction products of the expected size in both cortex and medulla for MC3-R, MC4-R, and MC5-R mRNA; no signal for MC1-R or MC2-R was detected. Relative to beta-actin or cyclophilin, abundance of the three receptor transcripts after 1 wk of the LSD was approximately equal in both cortex and medulla. After 1 wk of the HSD, mRNA abundance of MC4-R and MC5-R was unchanged, whereas that of MC3-R in medulla more than doubled, the ratio of MC3-R/beta-actin signal increasing from 0.38 +/- 0.04 on LSD to 0.84 +/- 0.04 on HSD (P < 0.001). No significant increase occurred in the cortex. The increase in MC3-R expression induced by dietary sodium was observed in inner medullary collecting duct (IMCD) cells isolated from the kidneys of HSD rats, suggesting that these cells were the major site of receptor expression in the medulla. Immunoblots of whole medullary and IMCD cell homogenates detected MC3-R immunoreactive protein; its expression was twice as great in samples from HSD vs. LSD rat kidneys, paralleling the increase in MC3-R mRNA abundance on the HSD. No changes in MC4-R or MC5-R protein expression were observed. Incubation of IMCD cell suspensions with increasing concentrations of gamma2-MSH led to increased cAMP accumulation, with values from rats on the HSD being roughly double the values from LSD rats. Intrarenal infusion of gamma2-MSH (500 fmol/min) increased sodium and cAMP excretion from the infused but not contralateral kidney of HSD rats, while having no effect in LSD rats. These data show that MC3-R is expressed in rat IMCD cells in a manner modulated by dietary sodium intake. Because MC3-R is the receptor with which gamma-MSH interacts, our findings suggest the existence of a sodium-regulating system, activated in response to a HSD, which increases urinary sodium excretion to balance the high-sodium intake.

1,25 dihydroxyvitamin d amplifies type a natriuretic peptide receptor expression and activity in target cells.

1,25 dihydroxyvitamin D (VD) has been shown to exert a number of beneficial effects on cardiovascular function, including reduction in BP and inhibition of cardiac hypertrophy. In an effort to identify a possible mechanistic link between VD and these salutary effects, the role of VD in controlling the activity and expression of the type A natriuretic peptide receptor (NPR-A), a receptor that signals reductions in BP and suppression of cellular growth in the myocardium and vascular wall, was investigated. VD, as well as the nonhypercalcemic analogue RO-25-6760, increased NPR-A-dependent cyclic guanosine monophosphate production and NPR-A gene expression in cultured rat aortic smooth muscle cells. The increase in NPR-A expression was associated with an increase in NPR-A gene promoter activity that was critically dependent on the presence of a functional VD receptor response element located approximately 495 bp upstream from the transcription start site of the gene. This element was associated with the VD receptor/retinoid X receptor complex in vitro. Mutation of this element resulted in complete elimination of the VD-dependent induction of the NPR-A gene promoter but did not affect osmotic stimulation of the promoter. Treatment of rats with RO-25-6760 for 7 d increased the atrial natriuretic peptide-dependent excretion of sodium and cyclic guanosine monophosphate without affecting mean arterial BP or plasma calcium levels. This was associated with a twofold increase in NPR-A mRNA levels in the inner medulla. Amplification of NPR-A activity represents a plausible mechanism to account for at least some of the beneficial effects that VD exerts on cardiovascular function.

Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat.

Increased cGMP-specific phosphodiesterase (PDE5) activity in renal inner medullary collecting duct (IMCD) cells contributes to resistance to atrial natriuretic peptide (ANP) and the excessive sodium retention seen in experimental nephrotic syndrome and liver cirrhosis. Normal pregnancy is also accompanied by sodium retention and plasma volume expansion, and pregnant rats are resistant to the natriuretic action of ANP. The authors investigated a possible role of increased renal PDE5 activity in the physiologic sodium retention of normal rat pregnancy. The natriuresis and increased urinary cGMP excretion (U(cGMP)V) evoked by acute volume expansion (a measure of renal responsiveness to endogeneous ANP) was blunted in 16-d pregnant versus virgin rats, despite equivalent increases in circulating ANP in pregnants and virgins. The ANP-dependent cGMP accumulation in isolated IMCD cells from pregnants was blunted versus virgins and restored by the PDE5-selective antagonist DMPPO (10(-7) mol/L). PDE5 activity in vitro and PDE5 protein abundance in IMCD were greater in pregnants. Four days postpartum, volume expansion natriuresis, U(cGMP)V, and PDE5 protein levels in IMCD cell homogenates had returned to virgin values. These results demonstrate that normal rat pregnancy leads to in vivo and in vitro renal resistance to ANP, in association with heightened activity of the cGMP-specific PDE5 in IMCD. This may contribute to the physiologic sodium retention of normal pregnancy.

Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat.

Gamma-melanocyte-stimulating hormone (gamma-MSH) is a natriuretic peptide derived from proopiomelanocortin (POMC) in the pituitary neurointermediate lobe (NIL); its plasma concentration in rats doubles after ingestion of a high (HSD; 8% NaCl) compared with a low sodium diet (LSD; 0.07%). Because NIL function is regulated through dopaminergic pathways, we asked whether dopaminergic stimulation with bromocriptine (5 mg/kg IP daily for 1 week) or inhibition with haloperidol (5 mg/kg IP for 1 week) alters the gamma-MSH response to a HSD. In vehicle-treated rats, plasma gamma-MSH and NIL gamma-MSH content on the HSD were both markedly elevated over values in rats on the LSD (P<0.001); no difference in mean arterial pressure (MAP) occurred. In haloperidol-treated rats on the LSD, both plasma gamma-MSH and NIL gamma-MSH content were greater than in vehicle-treated rats (P<0.05) and did not increase further on the HSD; MAP was also no different. In bromocriptine-treated rats, neither plasma gamma-MSH nor NIL gamma-MSH content increased on the HSD versus LSD, and MAP was markedly elevated on the HSD (132+/-3 versus 106+/-3 mm Hg, P<0.001). Intravenous infusion of gamma-MSH (0.4 pmol/min) to bromocriptine-treated rats on the HSD restored plasma gamma-MSH concentration to a level appropriate for the HSD and lowered MAP from 131+/-6 to 108+/-5 mm Hg (P<0.01). These results demonstrate that the increases in NIL content and plasma concentration of gamma-MSH normally occurring during ingestion of the HSD are prevented by dopaminergic suppression of NIL function. This results in deficiency of gamma-MSH on the HSD and is accompanied by elevated blood pressure, which is corrected by infusion of the peptide. gamma-MSH may be an important component in the normal response to a HSD; interruption of this response leads to salt-sensitive hypertension.

Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse.

The gamma-melanocyte-stimulating hormone (gamma-MSH) is a natriuretic peptide derived from the N-terminal region of proopiomelanocortin (POMC). Evidence suggests that it may be part of the coordinated response to a low-sodium diet (LSD). We tested the effect of the HSD (8% NaCl) compared with LSD (0.07%) on mean arterial pressure (MAP) in mice with targeted disruption of the PC2 gene (PC2(-/-)), necessary for processing of POMC into gamma-MSH, or the melanocortin receptor 3 gene (Mc3r(-/-); the receptor for MSH). In wild-type mice, HSD for 1 week did not alter MAP versus LSD mice, but plasma gamma-MSH immunoreactivity was more than double the LSD value. In contrast, in PC2(-/-) mice, MAP on the LSD was not greater than in wild-type mice, but plasma gamma-MSH was reduced to one-seventh the wild-type value. On the HSD, MAP rose to a markedly hypertensive level while plasma gamma-MSH concentration remained severely depressed. Intravenous infusion of gamma-MSH (0.2 pmol/min) for 30 min to PC2(-/-) mice after 1 week of HSD lowered MAP from hypertensive levels to normal; infusion of alpha-MSH at the same rate had no effect. Injection of 60 fmol of gamma-MSH into the lateral cerebral ventricle of hypertensive mice also lowered MAP to normal. Administration of a stable analogue of gamma-MSH intra-abdominally by microosmotic pump to PC2(-/-) mice prevented the development of hypertension when ingesting the HSD. In mice with targeted disruption of the Mc3r gene, the HSD also led to marked hypertension accompanied by elevated plasma levels of gamma-MSH; infusion of exogenous gamma-MSH to these mice had no effect on MAP. These results strongly suggest that PC2-dependent processing of POMC into gamma-MSH is necessary for the normal response to the HSD. gamma-MSH deficiency results in marked salt-sensitive hypertension that is rapidly improved with exogenous gamma-MSH through a central site of action. alpha-MSH infused at the same rate had no effect on MAP, indicating that the hypertension is a specific consequence of impaired POMC processing into gamma-MSH. Absence of Mc3r produces gamma-MSH resistance and hypertension on the HSD. These findings demonstrate a novel pathway mediating salt-sensitivity of blood pressure.