Skin preparation-free, stretchable microneedle adhesive patches for reliable electrophysiological sensing and exoskeleton robot control.

High-fidelity and comfortable recording of electrophysiological (EP) signals with on-the-fly setup is essential for health care and human-machine interfaces (HMIs). Microneedle electrodes allow direct access to the epidermis and eliminate time-consuming skin preparation. However, existing microneedle electrodes lack elasticity and reliability required for robust skin interfacing, thereby making long-term, high-quality EP sensing challenging during body movement. Here, we introduce a stretchable microneedle adhesive patch (SNAP) providing excellent skin penetrability and a robust electromechanical skin interface for prolonged and reliable EP monitoring under varying skin conditions. Results demonstrate that the SNAP can substantially reduce skin contact impedance under skin contamination and enhance wearing comfort during motion, outperforming gel and flexible microneedle electrodes. Our wireless SNAP demonstration for exoskeleton robot control shows its potential for highly reliable HMIs, even under time-dynamic skin conditions. We envision that the SNAP will open new opportunities for wearable EP sensing and its real-world applications in HMIs.

Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle.

Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2-8 °C or 22-28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.

Co-expression of human calreticulin significantly improves the production of HIV gp140 and other viral glycoproteins in plants.

Plant molecular farming (PMF) is rapidly gaining traction as a viable alternative to the currently accepted paradigm of producing biologics. While the platform is potentially cheaper and more scalable than conventional manufacturing systems, expression yields and appropriate post-translational modifications along the plant secretory pathway remain a challenge for certain proteins. Viral fusion glycoproteins in particular are often expressed at low yields in plants and, in some cases, may not be appropriately processed. Recently, however, transiently or stably engineering the host plant has shown promise as a strategy for producing heterologous proteins with more complex maturation requirements. In this study we investigated the co-expression of a suite of human chaperones to improve the production of a human immunodeficiency virus (HIV) type 1 soluble gp140 vaccine candidate in Nicotiana benthamiana plants. The co-expression of calreticulin (CRT) resulted in a dramatic increase in Env expression and ameliorated the endoplasmic reticulum (ER) stress response - as evidenced by lower transcript abundance of representative stress-responsive genes. The co-expression of CRT similarly improved accumulation of glycoproteins from Epstein-Barr virus (EBV), Rift Valley fever virus (RVFV) and chikungunya virus (CHIKV), suggesting that the endogenous chaperone machinery may impose a bottleneck for their production. We subsequently successfully combined the co-expression of human CRT with the transient expression of human furin, to enable the production of an appropriately cleaved HIV gp140 antigen. These transient plant host engineering strategies are a promising approach for the production of high yields of appropriately processed and cleaved viral glycoproteins.

Could a first-trimester blood phosphatidylethanol concentration ⩾4 nM be useful to identify women with moderate-to-heavy prenatal alcohol exposure who are at high risk of adverse pregnancy outcomes?

It is accepted that blood phosphatidylethanol (PEth) concentrations are reliable biomarkers of ethanol (alcohol) exposure. We therefore conducted a preliminary study to test the hypothesis that elevated blood PEth concentrations can help to identifying women with prenatal alcohol exposure who are at higher risk of adverse pregnancy outcomes. The study included 35 first-trimester pregnant women who self-reported alcohol ingestion and had PEth blood concentration ⩾4 nM at recruitment. As a control group, 233 first-trimester pregnant women who self-reported as being either abstainers or light alcohol drinkers and had blood PEth concentrations <4 nM, were also included. All participants were followed up until completion of their pregnancies. Women with prenatal alcohol exposure and PEth concentrations ⩾4 nM had a risk ratio of spontaneous abortions of 3.21 (95%CI 0.93-11.06; P=0.074). Because of the potential implications in the prenatal care of women reporting risky alcohol exposure, the preliminary results from the present study indicate the need for testing the hypothesis in a more definitive approach.

Simple high-throughput analytical method using ultra-performance liquid chromatography coupled with tandem mass spectrometry to quantify total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine.

BACKGROUND: Since the urinary concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a reliable biomarker of exposure to tobacco smoke, we developed a relatively simple high-throughput chromatographic method to quantify total urinary NNAL concentrations in the general population. METHODS: The high-throughput analytical method was developed using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) to identify and quantify total urinary NNAL concentrations in 10 non-smokers and 15 otherwise healthy smokers. RESULTS: Loss of nitric oxide at m/z 30 was found to be the predominant mass transitioned, and therefore was used as the SIM transition to quantify both NNAL and NNAL-methyl-d3 in urine. The analytical method did not require sample derivatization. Standard curves for total NNAL concentrations were linear between 20 and 1500 pg/mL, with coefficients of determination >0.95. Precision and accuracy ranged from 2.2% to 8.6% (CV) and from -5.6% to 10.9% (percent error), respectively. The lowest limit of quantification was 6.7 pg/mL, and 2.0 pg/mL the lowest limit of detection (LLOD). Total urinary NNAL concentrations in non-smoker subjects were

A Study about the Cause and Clinicopathologic Findings of Injection-Induced Dermatitis.

BACKGROUND: Cases of dermatitis induced by the injection of certain drugs have been reported. OBJECTIVE: The aim of this study was to assess the cause and clinicopathologic findings of injection-induced dermatitis, and to reveal whether the reaction has any relation to the patient's age, injection site, drug concentration, and time interval from the injection to the occurrence of the skin lesion. METHODS: In this study, we enrolled 10 patients who developed erythematous skin lesions after the injection of causative drugs. The lesions were compared to each other according to the injection site, time interval from the injection to the occurrence of the skin lesion, and clinical characteristics. We performed intradermal and patch tests in each patient with different concentrations of causative drugs. RESULTS: The most common causative drugs were diclofenac and vitamin K1. The eczematous type was the most frequent clinical type. The intradermal test showed more positive results than the patch test. The patch tests with diclofenac (as is, 2.5%, 5%, and 10%) and vitamin K1 (10%) were all negative in 10 patients. Furthermore, intradermal tests with diclofenac (as is) and vitamin K1 (0.1%, 1%, and 10%) were performed in 8 patients. Six patients had a positive reaction, consisting of erythema, induration, and vesiculation, after 1 and 2 days. CONCLUSION: Our results showed that the most common causative agents were diclofenac and vitamin K1. Moreover, it seems that that intradermal test is more useful than the patch test in the diagnosis of injection-induced dermatitis.

Iron nanoparticle-induced activation of plasma membrane H(+)-ATPase promotes stomatal opening in Arabidopsis thaliana.

Engineered nanomaterials (ENMs) enable the control and exploration of intermolecular interactions inside microscopic systems, but the potential environmental impacts of their inevitable release remain largely unknown. Plants exposed to ENMs display effects, such as increase in biomass and chlorophyll, distinct from those induced by exposure to their bulk counterparts, but few studies have addressed the mechanisms underlying such physiological results. The current investigation found that exposure of Arabidopsis thaliana to nano zerovalent iron (nZVI) triggered high plasma membrane H(+)-ATPase activity. The increase in activity caused a decrease in apoplastic pH, an increase in leaf area, and also wider stomatal aperture. Analysis of gene expression indicated that the levels of the H(+)-ATPase isoform responsible for stomatal opening, AHA2, were 5-fold higher in plants exposed to nZVI than in unexposed control plants. This is the first study to show that nZVI enhances stomatal opening by inducing the activation of plasma membrane H(+)-ATPase, leading to the possibility of increased CO2 uptake.

Effect of intracoronary shunt on right ventricular function during off-pump grafting of dominant right coronary artery with poor collateral.

Although numerous studies have validated the efficacy of intracoronary shunt on reducing left ventricular dysfunction during off-pump coronary artery bypass surgery (OPCAB), there is lack of evidence supporting its role on right ventricular (RV) function during right coronary artery (RCA) revascularization. Therefore, we studied the effect of intracoronary shunt during grafting of dominant RCA without visible collateral supply on global RV function using thermodilution method. Forty patients scheduled for multivessel OPCAB with right dominant coronary circulation without collateral supply confirmed by angiography were randomized to RCA revascularization either with a shunt (n=20) or soft snare occlusion (n=20). RV ejection fraction (RVEF) was recorded at baseline, during RCA grafting, and 15 min after reperfusion. Corresponding RV stroke work index (RVSWI) was calculated. RVEF and RVSWI decreased significantly during RCA grafting and returned to baseline values after reperfusion in both groups without any significant differences between the groups. Intracoronary shunt did not exert any beneficial effect on global RV function during RCA grafting, even in the absence of visible collateral supply. Regarding the possibility of graft failure by intracoronary shunt-induced endothelial damage, routine use of intracoronary shunt during RCA grafting is not recommended in patients with preserved biventricular function.

Protective effect of the ethanol extract of the roots of Brassica rapa on cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats.

A study was conducted to determine whether the ethanol extract of the roots of Brassica rapa (EBR) ameliorates cisplatin-induced nephrotoxicity in terms of oxidative stress, as characterized by lipid peroxidation, reactive oxygen species (ROS) production, and glutathione (GSH) depletion in LLC-PK1 cells. Pretreatment of cells with EBR prevented cisplatin-induced decreases in cell viability and cellular GSH content. The effect of EBR was then investigated in rats given EBR for 14 d before cisplatin administration. A single dose of cisplatin (7 mg/kg, i.p.) caused kidney damage manifested by an elevation in blood urea nitrogen (BUN), serum creatinine, and urine lactate dehydrogenase (LDH) levels. Also, renal tissue from cisplatin-treated rats showed a significant increase in malondialdehyde (MDA) production, and in the activities of aldehyde oxidase (AO) and xanthine oxidase (XO). Moreover, a significant decrease in the activities of antioxidant enzymes, such as, glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) was observed in cisplatin-treated rats versus saline-treated normal group. In contrast, rats given EBR showed lower blood levels of BUN and creatinine, and of urinary LDH. Moreover, EBR prevented the rise of MDA production and the induction of AO and XO activities. This extract also recovered the reduced activities of GPx, SOD and CAT. Taken together, our data indicate that the ethanol extract of the roots of Brassica rapa (EBR) has a protective effect against cisplatin-induced nephrotoxicity because it attenuates oxidative stress.

Iridoid glycosides isolated from Oldenlandia diffusa inhibit LDL-oxidation.

An iridoid glycoside, oldenlandoside III (5) was isolated from the n-butanol fraction of methanol extracts of the aerial parts of Oldenlandia diffusa Roxb. along with six others previously characterized iridoid glycosides; geniposidic acid (1), scandoside (2), feretoside (3), 10-omicron-benzoylscandoside methyl ester (4), asperulosidic acid (6) and deacetylasperulosidic acid (7). Compounds 1, 2, and 7 inhibited LDL-oxidation, and showed 63.3+/-2.0, 62.2+/-1.6, and 63.8+/-1.5% inhibition, respectively, at a concentration of 20 microg/mL.