Biomimetic Electronic Skin Based on a Stretchable Ionogel Mechanoreceptor Composed of Crumpled Conductive Rubber Electrodes for Synchronous Strain, Pressure, and Temperature Detection.

Electronic skin (e-skin) is showing a huge potential in human-computer interaction, intelligent robots, human health, motion monitoring, etc. However, it is still challenging for e-skin to realize distinguishable detection of stretching strain, vertical pressure, and temperature through a simple noncoupling structure design. Here, a stretchable multimodal biomimetic e-skin was fabricated by integrating layer-by-layer self-assembled crumpled reduced graphene oxide/multiwalled carbon nanotubes film on natural rubber (RGO/MWCNTs@NR) as stretchable conductive electrodes and polyacrylamide/NaCl ionogel as a dielectric layer into an ionotropic capacitive mechanoreceptor. Unlike natural skin receptors, the sandwich-like stretchable ionogel mechanoreceptor possessed a distinct ionotropic capacitive behavior for strain and pressure detection. The results showed that the biomimetic e-skin displayed a negative capacitance change with superior stretchability (0-300%) and a high gauge factor of 0.27 in 180-300% strain, while exhibiting a normal positive piezo-capacitance behavior in vertical pressure range of 0-15 kPa with a maximal sensitivity of 1.759 kPa-1. Based on this feature, the biomimetic e-skin showed an excellent synchronous detection capability of planar strain and vertical pressure in practical wearable applications such as gesture recognition and grasping movement detection without a complicated mathematical or signal decoupling process. In addition, the biomimetic e-skin exhibited a quantifiable linear responsiveness to temperature from 20-90 °C with a temperature coefficient of 0.55%/°C. These intriguing properties gave the biomimetic e-skin the ability to perform a complete function similar to natural skin but beyond its performance for future wearable devices and artificial intelligence devices.

Recent advances in lignin-based carbon materials and their applications: A review.

As the most abundant natural aromatic polymer, tens of million of tons of lignin produced in paper-making or biorefinery industry are used as fuel annually, which is a low-value utilization. Moreover, burning lignin results in large amounts of carbon dioxide and pollutants in the air. The potential of lignin is far from being fully exploited and the search for high value-added application of lignin is highly pursued. Because of the high carbon content of lignin, converting lignin into advanced carbon-based structural or functional materials is regarded as one of the most promising solutions for both environmental protection and utilization of renewable resources. Significant progresses in lignin-based carbon materials (LCMs) including porous carbon, activated carbon, carbon fiber, carbon aerogel, nanostructured carbon, etc., for various valued applications have been witnessed in recent years. Here, this review summarized the recent advances in LCMs from the perspectives of preparation, structure, and applications. In particular, this review attempts to figure out the intrinsic relationship between the structure and functionalities of LCMs from their recent applications. Hopefully, some thoughts and discussions on the structure-property relationship of LCMs can inspire researchers to stride over the present barriers in the preparation and applications of LCMs.

Moxibustion for anorexia in COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. The purpose of this study was to evaluate the efficacy and safety of moxibustion in the treatment of anorexia in patients with COVID-19. METHODS: According to the retrieval strategies, randomized controlled trials on moxibustion therapies for C19-A will be obtained from the China National Knowledge Infrastructure, WanFang Data, Chinese Scientific Journals Database, PubMed, Embase, and Cochrane Library, regardless of publication date or language. Studies will be screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed with the Markov chain Monte Carlo method and carried out with Stata 14.2 and WinBUGS 1.4.3 software. Ultimately, the quality of the evidence obtained from the results will be evaluated. RESULTS: This study will evaluate whether moxibustion therapy can effectively treat anorexia in patients with COVID-19. CONCLUSION: This study will provide evidence for whether moxibustion therapy is beneficial to the treatment of anorexia in patients with COVID-19. TRIAL REGISTRATION NUMBER: CRD42022302499.

[Professor YANG Ji-guo's experience in treatment of functional gastrointestinal diseases with acupuncture combined with umbilicus moxibustion].

Professor YANG Ji-guo's clinical experience in treatment of functional gastrointestinal diseases was summerized. Professor YANG Ji-guo believes that this disease is caused by the deficiency of six fu organs. Dysfunction of six fu organs in descending transportation is the basic pathogenesis. The principle of acupoint selection includes benefiting gastrointestinal functions, unblocking and purging six fu, soothing liver qi and calming down the mind. In treatment, acupuncture is combined with umbilicus moxibustion. In acupuncture, the deqi promoting technique by rotating and trembling needle is adopted. Focusing on the deficiency of six fu organs, umbilicus moxibustion is adopted to benefit the spleen and stomach and harmonize the functions of six fu organs for both biao (symptoms) and ben (root cause).

The enhancing antifungal effect of AD1 aptamer-functionalized amphotericin B-loaded PLGA-PEG nanoparticles with a low-frequency and low-intensity ultrasound exposure on C.albicans biofilm through targeted effect.

The prevalence and fatality rates with fungal biofilm-associated infections urgently need to develop targeted therapeutic approaches to augment the action of antifungal drugs. This study developed amphotericin B-loaded PLGA-PEG nanoparticles (AmB-NPs) with AD1 aptamer conjugation on its surface via an EDC/NHS technique. Their high nuclease resistance of the conjugation was confirmed by PAGE gel electrophoresis. The targeting and toxicity of AD1-AmB-NPs in the subcutaneous C. albicans infection model were evaluated. AD1-AmB-NPs can bind to different morphological forms(including yeast cells, germ tubes, hyphae) of C. albicans biofilms and extracellular matrix material. Low-frequency and low-intensity ultrasound (LFU, with a fixed frequency of 42 kHz, at the intensity of 0.30 W/cm2 for 15 min) significantly promoted permeability of the biofilm and allowed AD1-AmB-NPs into the deepest layers of the biofilm. After 7 days of treatment, the combination treatment of AD1-AmB-NPs and LFU, kills at least 99% of the biofilm fungal population in vivo comparison with ultrasound alone or AD1-AmB-NPs alone, and returned to normal subcutaneously. Our data suggest that the combined strategy of AD1-AmB-NPs and ultrasound treatment selective delivered of therapeutic drugs to the infection site and exhibited significant synergistic antifungal effects.

Development of risk prediction models for lung cancer based on tumor markers and radiological signs.

BACKGROUND: Accurate prediction of malignancy risk for pulmonary lesions with pleural effusion improves early diagnosis of lung cancer. This study aimed to develop and validate a model to predict lung cancer. METHODS: Clinical data of 536 patients with pulmonary diseases were collected. The risk factors were identified by regression analysis. Three prediction models were developed. The predictive performances of the models were measured by the area under the curves (AUCs) and calibrated with 1000 bootstrap samples to minimize the over-fitting bias. The net benefits of the models were evaluated by decision curve analysis. Finally, a separate cohort of 134 patients was used to validate the models externally. RESULTS: Seven independent risk factors were identified from 18 clinical variables, which included the pleural fluid carcinoembryonic antigen (CEA), serum cytokeratin-19 fragment (CYFRA 21-1), the ratio of CEA in the pleural fluid to serum, extrathoracic cancer history (>5 years), tumor size, vessel convergence, and lobulation. The AUCs of the three models were 0.976, 0.927, and 0.944 in the training set and 0.930, 0.845, and 0.944 in the external set, respectively. The accuracies of the three models were 89.6%, 81.4%, and 88.8%. Model 1 showed the best iteration fit (R2  = 0.84, 0.68, and 0.73) and a higher net benefit on decision curve analysis when compared to the other two models. CONCLUSION: The advantageous model could assess the risk of lung cancer in patients with pleural effusion and act as a useful tool for early identification of lung cancer.

[Exploration of the Suitable Culture Conditions for Extracellular Microvesicles Derived from Human Mesenchymal Stem Cells].

OBJECTIVE: To explore the appropriate procedures for preparing extracellular microvesicles (MV) derived from human mesenchymal stem cells (MSC). METHODS: Human MSCs from umbilical cords were cultured in a serum-free medium and maintained in a basal medium for 72 hours after the cell confluence reached to 80%. The supernatants of cultured cells were collected and MVs were enriched. MVs were identified by flow cytometry and electron microscopy. The total protein amount in MVs was used as a parameter for the content of MVs. The supernatants were adjusted to different pH values, and the output of MVs was detected. The supernatants were also collected for enriching the MV and detecting the protein content of MV after the cells were maintained in the basic medium for different time. RESULTS: Flow cytometric analysis showed that the MVs expressed CD9, CD63 and CD81, morphologically presented round under an electron microscope and the diameter of MV was around 100 nm. After enrichment of MV, the protein content of MVs in the supernatants was 416.8±128.1, 255.4±77.9 and 142.8±46.4 µg per 107 MSC，respectively at pH of supernatant 3, 7 and 9 (P＜0.05). The protein content of the supernatants per 107 MSC was 173.6±44.5, 262.4±49.6 and 364.2±37.8 µg respectively after starvation culture for 48, 72 and 96 hrs (P＜0.05). CONCLUSION: MVs can be readily collected after MSCs were starved for 96 hours, and the pH of the supernatants is adjusted at 3.0.

Clinical and Pathologic Features of a Suspected Selenium Deficiency in Captive Plains Zebras.

Previous studies have shown that selenium (Se) deficiency is associated with nutritional myopathy, known as white muscle disease (WMD), in horses. However, correlations between Se deficiency and clinical findings, such as hematologic biochemical values and pathological features, have not been evaluated in captive plains zebras. The purpose of the present study was to investigate the clinical and pathologic features that may be caused by a Se deficiency in the captive plains zebra. Clinical findings, feed analyses, hematologic biochemical analyses, response to treatment, and pathologic examination were assessed in six affected plains zebras. The dietary concentration of Se in feed was also tested. Sudden death occurred in two cases during the first day of the onset of symptoms. Two zebras died at 4 days and two zebras survived after treatment. The clinical signs in affected animals were characterized by general weakness, astasia, and abnormal postural positions. The Se concentration in hay from the breeding stable was low, based on the reference value. Glutathione peroxidase (GSH-Px) activity was lower compared with the equine reference value. Multiple areas of subcutaneous steatitis and pale skeletal muscle and myocardium were revealed at gross necropsy. Degeneration and necrosis of myocardial and skeletal muscles, as well as congestion of the liver, lung, and kidney were found via histopathological examination. No suspected bacterial infections were found. Feed analyses, response to treatment, serum GSH-Px activity, and pathological features suggest that Se deficiency may have caused the disease in the six affected captive plains zebra.

Association Between Serum Cortisol and Chronic Kidney Disease in Patients with Essential Hypertension.

BACKGROUND/AIMS: Serum cortisol level is elevated in patients with essential hypertension. We aimed at investigating the association of serum cortisol levels with parameters of renal function in essential hypertension. METHODS: One hundred and seventy-eight patients with essential hypertension participated in the study. Fasting serum samples were collected at 8:00 am. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine- cystatin C equation (eGFRcr-cys). Correlation analysis and stepwise regression analysis were used to detect the relationship between cortisol and eGFRcr-cys. The distributions of serum cortisol were split by the tertiles and subjects were stratified into those with low, median and high levels accordingly. RESULTS: Serum cortisol levels were significantly higher in subjects whose eGFRcr-cys<90 ml/min/1.73 m2 than subjects whose eGFRcr-cys>90 ml/min/1.73 m2 (394.0±93.4 vs. 343.2±98.4 nmol/L, P=0.001). Age, systolic blood pressure, and serum total cholesterol, uric acid, cortisol levels were significantly associated with eGFRcr-cys, serum levels of creatinine and cystatin C. After adjusting for clinical factors, serum cortisol level had a statistically significant negative association with the eGFRcr-cys (ß=-0.19, P=0.027), and positive associations with cystatin C (ß=0.31, P=0.001) and creatinine (ß=0.14, P=0.044). With the increment of cortisol tertile, the eGFRcr-cys significantly decreased (93.18±14.36 vs. 84.61±14.67 vs. 81.29±12.36 ml/min/1.73 m2 for low, median and high tertile, respecively, P=0.001). CONCLUSION: Serum cortisol level was negatively correlated with eGFRcr-cys in subjects with essential hypertension. Further studies are needed to investigate whether cortisol plays a role in hypertensive nephropathy development.

[Progesterone Promotes Human Bone Marrow Mesenchymal Stem Cells to Synthesize Fibronectin via ERK Pathway].

OBJECTIVE: To investigate whether the progesterone can promote fibronection (FN) synthesis by human bone marrow mesenchymal stem cells (MSCs) and to explore the potential underlying mechanism. METHODS: The human bone marrow MSCs were cultured in a serum-free medium with progesterone for 72 hours, the MTT test was performed to observe the proliferation status and adhension ability of the treated cells. Western blot was used to detect the content of FN in MSDs with GAPDH as the internal reference, the phosphorylation of ERK1/2, as well as the FN content in MSC treated by PD98059, a specific inhibitor of ERK1/2. RESULTS: The progesterone at a range of certain doses not effect on the proliferation of human bone marrow MSCs. Progesterone (25 µg/L) treatment enhanced the FN expression and adherent ability of marrow MSCs. Progesterone could induce prompt phosphorylation of ERK 1/2 and its promoting effects on FN synthesis was reversed by PD98059. CONCLUSION: The progesterone can promote FN synthesis by human bone marrow MSCs via ERK 1/2 pathway, and it might be used to culture MSCs in serum-free medium.

[Putrescine Promotes Human Marrow Mesenchymal Stem Cells to Differentiate along Osteogenic Pathway].

OBJECTIVE: To investigate the effects of putrescine on the growth and differentiation of human bone marrow mesenchymal stem cells (MSC) to develop a new inductive medium mixture for their osteogenic differentiation. METHODS: Human bone marrow MSC were collected from three healthy donors and were used to observe the growth-promoting activity of putrescine with MTT test. Experiments were divided into 3 groups: (1) putrescine group, (2) positive control group (presence of dexamethasone, ascorbate, and glycerol phosphate) and negative group (d-alpha with 5% FCS). The cellular expression level of Runx-2 was detected by PCR assay after the culture was maintained for 1 week. After 2 weeks, the intracellular activity of alkaline phosphatase was revealed by histochemistry staining, the phosphatase activity, and the protein concentration in the cell lysates were also detected. Furthermore, MSC were cultured in the presence of putrescine for 2 weeks and Oil-red O staining was performed to reveal the differentiated adipocytes; the cells induced by the standard agent cocktail were used as the positive control. RESULTS: Putrescine promoted the proliferation of human marrow MSC in a dose-dependent manner. MSC exposed to putrescine at a concentration of 100 µmol/L for 1 week expressed greatly higher level of Runx-2, compared with the negative control. Alkaline phosphatase activity was evidently observed after MSC were maintained in the presence of putrescine for 2 weeks. The phosphatase activity contrasted to the protein content in putrescine-treated MSC was significantly higher than that of the control cells (0.87±0.012 vs 0.52±0.010) (P<0.01), and also greatly higher than that of the positive control (0.83±0.029) (P=0.02). Oil red O staining showed that MSC treated by putrescine did not differentiate into adipoblasts. CONCLUSION: Putrescine can promote the proliferation and osteogenic differentiation of MSC, suggesting the potential application of putrescine as a novel inductive agent for in vitro osteogenesis of MSC.

[Slowly-adhered primary bone marrow mesenchymal stem cells may exhibit more potent immuno-regulatory activity].

OBJECTIVE: This study was to investigate the relationship between the adherent ability of freshly isolated MSCs with their inhibitory effect on lymphocyte activation. METHODS: Human bone marrow mononucleated cells were maintained in culture for 48 hours, the attached and the non-attached cells were then cultured separately and the adherent cells were collected and passaged. Cellular surface markers were analyzed with flow cytometry. Alkaline phosphatase activity and the intracellular lipid droplets were measured by histological staining, the in vitro osteogenesis and adipogenesis were identified. One-way mixed lymphocyte reaction was used to evaluate the suppressive activity of the adherent cells on lymphocyte proliferation, the prostaglandin E2 level in supernatant of cultured cells was detected by ELISA. RESULTS: Some cells attached to the plastic after the bone marrow mononucleated cells were allowed to adhere for 48 hours. The slowly-attached cells were fibroblast-like in morphology, homogenously positive for CD44 and CD73 and negative for CD31 and CD45. They could be coaxed into osteoblasts and adipoblasts under the standard inductive conditions. These cells were able to inhibit lymphocyte proliferation in mixed lymphocyte reaction and their effect was more potent than those from the adherent cells appeared within 48 hours. The concentration of prostaglandin E-2 in the supernatants of the slowly-adhered cells was significantly higher than that in the MSCs cultured with the traditional method (90.8 ± 10.37 ng/ml vs 70.2 ± 8.98 ng/ml) (P < 0.01). CONCLUSIONS: The MSCs exist in the marrow mononucleated cells after adherent culture for 48 hours, and the MSCs may exhibit more potently inhibitory activity on lymphocyte activation.

[Exploration of conditions for releasing microvesicle from human bone marrow mesenchymal stem cells].

The release of microvesicles(MV) is one of the critical mechanisms underlying the angiogenesis-promoting activity of mesenchymal stem cells(MSC). This study was aimed to explore the appropriate condition under which MSC releases MV. Bone marrow samples from 5 healthy adults were collected, and MSC were isolated, culture-expanded and identified. MSC at passage 5 were suspended in medium without or medium with 10% fetal(FCS) calf serum and seeded into culture dishes. The culture was separately maintained in hypoxia (1% oxygen) or normoxia (around 20% oxygen), and 20 dishes of cells (2×10(6)/dish) were used for each group. The supernatants were collected for MV harvesting. The cell number was counted with trypan blue exclusion test and the protein contents in the MV were determined. MV were identified by observation under an electron microscope. The surface markers on MV were analyzed by flow cytometry. MTT test was performed to observe the pro-proliferative activity of MV that were added into the culture of human umbilical cord vein endothelial cells at a concentration of 10 µg/ml. The results showed that the majority of MV released by MSC were with diameters of less than 100 nm, and MV took the featured membrane-like structure with a hypodense center. They expressed CD29, CD44, CD73 and CD105, while they were negative for CD31 and CD45. The increase multiples of the adherent trypan blue-resistant cells cultured in normoxia with serum, in normoxia without serum, in hypoxia with serum and hypoxia in the absence of serum were 4.05 ± 0.73, 1.77 ± 0.48, 5.80 ± 0.65 and 3.69 ± 0.85 respectively, and the estimated protein contents per 10(8) cells were 463.48 ± 138.74 µg, 1604.07 ± 445.28 µg, 2389.64 ± 476.75 µg and 3141.18 ± 353.01 µg. MTT test showed that MV collected from MSC in hypoxia seemed to promote the growth of endothelial cells more efficiently than those from cells in normoxia. It is concluded that hypoxia can enhance the release of microvesicles from MSC, and cultivation of MSC in hypoxia and medium without serum may provide an appropriate condition for MV harvesting.

Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo.

Although mesenchymal stem cells (MSCs) have been increasingly trialed to treat a variety of diseases, the underlying mechanisms remain still elusive. In this study, human umbilical cord (UC)-derived MSCs were stimulated by hypoxia, and the membrane microvesicles (MVs) in the supernatants were collected by ultracentrifugation, observed under an electron microscope, and the origin was identified with the flow cytometric technique. The results showed that upon hypoxic stimulus, MSCs released a large quantity of MVs of ~100 nm in diameter. The MVs were phenotypically similar to the parent MSCs, except that the majority of them were negative for the receptor of platelet-derived growth factor. DiI-labeling assay revealed that MSC-MVs could be internalized into human UC endothelial cells (UC-ECs) within 8 h after they were added into the culture medium. Carboxyfluorescein succinimidyl ester-labeling technique and MTT test showed that MSC-MVs promoted the proliferation of UC-ECs in a dose-dependent manner. Further, MVs could enhance in vitro capillary network formation of UC-ECs in a Matrigel matrix. In a rat hindlimb ischemia model, both MSCs and MSC-MVs were shown to improve significantly the blood flow recovery compared with the control medium (P<0.0001), as assessed by laser Doppler imaging analysis. These data indicate that MV releasing is one of the major mechanisms underlying the effectiveness of MSC therapy by promoting angiogenesis.

Two evaluation budgets for the measurement uncertainty of glucose in clinical chemistry.

BACKGROUND: Measurement uncertainty characterizes the dispersion of the quantity values attributed to a measurand. Although this concept was introduced to medical laboratories some years ago, not all medical researchers are familiar with it. Therefore, the evaluation and expression of measurement uncertainty must be highlighted using a practical example. METHODS: In accordance with the procedure for evaluating and expressing uncertainty, provided by the Joint Committee for Guides in Metrology (JCGM), we used plasma glucose (Glu) as an example and defined it as the measurand. We then analyzed the main sources of uncertainty, evaluated each component of uncertainty, and calculated the combined uncertainty and expanded uncertainty with 2 budgets for single measurements and continuous monitoring, respectively. RESULTS: During the measurement of Glu, the main sources of uncertainty included imprecision, within-subject biological variance (BV(w)), calibrator uncertainty, and systematic bias. We evaluated the uncertainty of each component to be 1.26%, 1.91%, 5.70%, 0.42%, and -2.87% for within-run imprecision, between-day imprecision, BV(w), calibrator uncertainty, and systematic bias, respectively. For a single specimen, the expanded uncertainty was 7.38% or 6.1±0.45 mmol/L (κ=2); in continuous monitoring of Glu, the expanded uncertainty was 13.58% or 6.1±0.83 mmol/L (κ=2). CONCLUSIONS: We have demonstrated the overall procedure for evaluating and reporting uncertainty with 2 different budgets. The uncertainty is not only related to the medical laboratory in which the measurement is undertaken, but is also associated with the calibrator uncertainty and the biological variation of the subject. Therefore, it is helpful in explaining the accuracy of test results.