Design and development of multilayer cotton masks via machine learning.

With the ongoing COVID-19 pandemic, reusable high-performance cloth masks are recommended for the public to minimize virus spread and alleviate the demand for disposable surgical masks. However, the approach to design a high-performance cotton mask is still unclear. In this study, we aimed to find out the relationship between fabric properties and mask performance via experimental design and machine learning. Our work is the first reported work of employing machine learning to develop protective face masks. Here, we analyzed the characteristics of Egyptian cotton (EC) fabrics with different thread counts and measured the efficacy of triple-layered masks with different layer combinations and stacking orders. The filtration efficiencies of the triple-layered masks were related to the cotton properties and the layer combination. Stacking EC fabrics in the order of thread count 100-300-100 provides the best particle filtration efficiency (45.4%) and bacterial filtration efficiency (98.1%). Furthermore, these key performance metrics were correctly predicted using machine-learning models based on the physical characteristics of the constituent EC layers using Lasso and XGBoost machine-learning models. Our work showed that the machine learning-based prediction approach can be generalized to other material design problems to improve the efficiency of product development.

Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.

BACKGROUND: Rodents with deficiency of or resistance to the proopiomelanocortin-derived peptide gamma-melanocyte stimulating hormone (gamma-MSH) develop marked salt-sensitive hypertension. We asked whether this hypertension was accompanied by abnormal glucose metabolism. METHODS: gamma-MSH-deficient Pc2(-/-) mice, and resistant Mc3r(-/-) mice were studied acutely for measurement of blood pressure and glucose and insulin concentrations after > or =1 week of a high-sodium diet (HSD; 8% NaCl) compared to a normal-sodium diet (NSD; 0.4% NaCl). Mc3r(-/-) also underwent glucose tolerance test (GTT) and insulin tolerance test. RESULTS: Both knockout strains were hypertensive and also exhibited fasting hyperglycemia and hyperinsulinemia on the HSD. Mc3r(-/-) mice on the HSD had impaired glucose tolerance and insulin-mediated glucose disposal compared to wild-type mice on either the HSD or the NSD, or to Mc3r(-/-) mice on the NSD. CONCLUSIONS: These results indicate an interaction of interrupted gamma-MSH signaling with the HSD to cause hypertension on the one hand and abnormal glucose metabolism, with the characteristics of insulin resistance, on the other. Further study of the nature of this interaction should provide new insight into the mechanisms by which salt-sensitive hypertension and insulin resistance are linked.

Increased cGMP phosphodiesterase activity mediates renal resistance to ANP in rats with bile duct ligation.

BACKGROUND: Liver disease resulting from common bile duct ligation (CBDL) causes abnormal sodium metabolism that is manifested by resistance to the natriuretic action of atrial natriuretic peptide (ANP). This resistance is corrected both in vitro and in vivo by zaprinast, a selective inhibitor of a guanosine cyclic-3'-5'-monophosphate (cGMP)-specific phosphodiesterase (PDE5). Several other PDEs with affinity for cGMP are expressed in kidney and could also be involved in this response. METHODS: We measured cGMP hydrolysis in inner medullary collecting duct (IMCD) cell homogenates from kidneys of sham-operated and CBDL rats and quantitated the amount of PDE5 protein by Western blotting and immunoprecipitation studies. We also characterized ANP responsiveness in vivo of kidneys of anesthetized sham and CBDL rats by measuring sodium excretion before and after volume expansion (VE). RESULTS: Kinetic analysis of PDE5 activity in homogenates of IMCD cells isolated from kidneys of sham-operated rats indicated a Vmax of 85.3 +/- 1.7 versus 157 +/- 2.9 pmol/mg/min from CBDL rats (P < 0.01), without a difference in Km. Enzyme activity was inhibited competitively by 1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)pyrazol[3,4d]-pyrimidin-4-(5H)-one (DMPPO), a potent and specific inhibitor of PDE5, with an apparent Ki of 4.5 +/- 0.7 and 4.9 +/- 0.7 nmol/L and an IC50 of 6.1 +/- 0.8 and 8.7 +/- 0.7 nmol/L in sham and CBDL rats, respectively (P = NS). DMPPO exhibited very poor inhibitory activity against the calcium-calmodulin-dependent PDE1 in IMCD homogenates from sham rats (Ki 1.3 +/- 0.1 micromol/L and IC50 1.9 +/- 0.2 micromol/L). Western analysis using an antiserum made against bovine lung PDE5 revealed a twofold increase in PDE5 protein in cytosolic extracts from IMCD of CBDL rat kidneys compared with sham-operated controls, and immunoprecipitation studies indicated that the increase in PDE5 protein accounted for the observed increase in cGMP hydrolysis. DMPPO (10 nmol/L) normalized the blunted ANP-dependent cGMP accumulation by IMCD cells from CBDL rats in vitro. Intrarenal infusion of DMPPO (0.5 nmol/min) in CBDL rats corrected both the impaired natriuretic response to VE and the blunted VE-related increase in urinary cGMP excretion from the infused, but not the contralateral kidney. CONCLUSION: These results demonstrate that renal resistance to ANP in CBDL rats is accompanied by heightened activity of PDE5, which is due largely to an increase in PDE5 protein. Other PDEs could contribute only a minor part to the enhanced cGMP hydrolysis observed in kidneys of CBDL rats. This PDE5-dependent ANP resistance may represent an important contributor to the sodium retention of liver disease.

Dietary sodium modulates mRNA abundance of enzymes involved in pituitary processing of proopiomelanocortin.

The messenger RNA abundance of proopiome-lanocortin (POMC) is increased in neurointermediate lobe (NIL) of rat pituitary when ingesting a high sodium diet (8%; HSD), as is the plasma concentration of the natriuretic peptide gamma-melanocyte stimulating hormone (gammay-MSH) derived from it. We examined whether the HSD also increases the mRNA abundance in rat NIL of proconvertases 1 and 2 (PC1, PC2), enzymes involved in the processing of POMC into gamma-MSH. PC1 mRNA increased by 40% after two weeks of the HSD and by 84% after three weeks. PC2 mRNA increased by 40% after two weeks and by more than 3 fold after three weeks. These results for PC2 were confined to NIL as shown by in situ hybridization at one and two weeks, and were accompanied by a significant increase in NIL PC2 protein after three weeks of the HSD as measured by immunoblotting. The increases in PC1 and PC2 mRNA abundance were paralleled by an increase in POMC mRNA level in NIL. Plasma gamma-MSH immunoreactivity averaged 35.1 +/- 3.3 fmol/ml in rats on the LSD, but increased to 70.9 +/- 4.8 fmol/ml after 3 weeks of the HSD (p < 0.002 vs LSD). These results confirm that the HSD increases the plasma concentration of gamma-MSH, consistent with a role for it as a circulating natriuretic peptide. The increased NIL expression of PC1 and PC2 in parallel with POMC in response to the HSD suggests that these changes are part of the coordinated response to states of sodium surfeit.

Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.

The objective of this study was to investigate the relationships among various humoral factors thought to be involved in the regulation of blood pressure during high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin resistance was assessed by the steady-state plasma glucose concentration at the end of a 3-hour insulin suppression test. Insulin resistance correlated inversely with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The increase in mean arterial pressure associated with the high-sodium diet correlated directly with the gain in weight (P<0.05) and inversely with the increase in urinary nitrate excretion (P<0.0001). In a multiple regression model, more than 2/3 of the variance in mean arterial pressure was accounted for by the gain in weight and change in urinary nitrate excretion. The steady-state plasma glucose concentrations obtained with the 2 diets were similar, indicating that insulin resistance was unaffected by sodium intake. During high sodium intake, plasma renin activity and aldosterone decreased and plasma atrial natriuretic peptide increased; these changes did not correlate with the change in mean arterial pressure, insulin resistance, or change in urinary nitrate excretion. To the extent that urinary nitrate excretion reflects activity of the endogenous nitric oxide system, these results suggest that the salt sensitivity of mean arterial pressure may be related to blunted generation of endogenous nitric oxide. The results also demonstrate that insulin-resistant individuals have an impaired natriuretic response to high sodium intake.

Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists.

gamma-Melanocyte-stimulating hormone (gamma-MSH), atrial natriuretic peptide (ANP), and oxytocin have been identified as candidate hormonal mediators of the reflex natriuresis that follows acute unilateral nephrectomy (AUN). Pharmacological characterization of the third melanocortin receptor (MC3-R) indicates that it uniquely responds to physiological concentrations of gamma-MSH. We tested the roles of gamma-MSH, ANP, and oxytocin in the postnephrectomy natriuresis by carrying out AUN during continuous intrarenal infusion of specific antagonists for their cognate receptors. In anesthetized Sprague-Dawley rats, urinary sodium excretion (UNaV) increased from 0.34 +/- 0.04 to 1.12 +/- 0.11 mu eq/min 90 min after AUN (P < 0.001). No change in UNaV occurred in rats undergoing a sham AUN procedure. Plasma immunoreactive gamma-MSH concentration was 53 +/- 8 fmol/ml after sham AUN but 112 +/- 17 fmol/ml after AUN (P < 0.01). SHU-9119 and SHU-9005 are substituted derivatives of alpha-MSH with potent antagonism at the MC3-R in vitro. Infusion of these compounds at 5 pmol/min completely blocked the natriuretic response to AUN despite a similar elevation in plasma gamma-MSH (111 +/- 12 vs. 49 +/- 8 fmol/ml in sham rats, P < 0.01). Intrarenal infusion of the ANP receptor antagonist A-71915 (5 pmol/min) or the oxytocin receptor antagonist [d(CH2)(5)1, Tyr(Me)2,Orn8] vasotocin (10 pmol/min) effectively inhibited the natriuresis induced by intravenous infusion of ANP or oxytocin (each at 1 pmol/min), respectively, but did not block the natriuresis after AUN. Plasma immunoreactivity of these peptides was not increased after AUN. These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma gamma-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R. The data indicate that gamma-MSH or a closely related peptide mediates postnephrectomy natriuresis and provide further support for the possibility that gamma-MSH may play a wider role in sodium homeostasis.