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In an article to study the effect of sizing agent and filler on the structural features of paper from the cellulose mass of the inner layer of the bark of mulberry tree branches, mechanical strength, absorbency and sorption properties were studied. Tensile strength was determined on a tensile testing machine by the force causing the destruction of the sample. Surface absorbency at one side wetting was determined by the method of Cobb(30), by determining the mass of water absorbed by the surface of the paper when wetting one side of the test sample. Sorption properties were studied on a high-vacuum setup with mercury gates and McBain quartz balances according to water vapor sorption data. It was found that the internal 2% sizing of the paper pulp with cherry tree resin glue contributes to the strengthening of the paper structure, which is confirmed by the values of mechanical strength and surface absorbency when unilaterally wetted with water, relative to the values obtained when sizing with pine oleoresin rosin glue. When using glue from cherry resin, it is advisable to add 2 g of kaolin to 100 g of pulp from the inner layer of the bark of mulberry tree branches, since the increase negatively affects mechanical strength and hydrophobicity., В статье для исследования влияния проклеивающего вещества и наполнителя на структурные особенности бумаги из целлюлозной массы внутреннего слоя коры веток тутового дерева изучены механическая прочность, впитывающая способность и сорбционные свойства. Прочность на разрыв при растяжении определяли на разрывной машине по усилию, вызывающему разрушение образца. Поверхностную впитываемость при одностороннем смачивании определяли по методу Кобб(30), путем определения массы воды, поглощенной поверхностью бумаги при смачивании одной стороны испытуемого образца. Сорбционные свойства исследовали на высоковакуумной установке с ртутными затворами и кварцевыми весами Мак-Бена по данным сорбции паров воды. Выявлено, что внутренняя 2%-ная проклейка бумажной массы клеем из живицы черешневого дерева способствует упрочнению структуры бумаги, что подтверждается значениями механической прочности и поверхностной впитываемостью при одностороннем смачивании водой, относительно значений, полученных при проклейке канифольным клеем из сосновой живицы. При использовании клея из живицы черешневого дерева целесообразно к 100 г целлюлозной массы из внутреннего слоя коры веток тутового дерева добавлять каолин в количестве 2 г, так как увеличение отрицательно влияет на механическую прочность и гидрофобность.

AimsTo assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists.Methods and resultsA European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9–12 December 2021 and 10–13 April 2022). All young cardiologists eligible to participate (ConclusionOnline evaluation of young cardiologists around the world showed a relatively low level of TOE skills and knowledge. Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and the EACVI certification for TOE were independently associated with a higher global score.

Microfluidic paper-based analytical devices (μPADs) are emerging as powerful analytical platforms in clinical diagnostics, food safety, and environmental protection because of their low cost and favorable substrate properties for biosensing. However, the existing top-down fabrication methods of paper-based chips suffer from low resolution (200 μm). Additionally, papers have limitations in their physical properties (e.g., thickness, transmittance, and mechanical flexibility). Here, we demonstrate a bottom-up approach for the rapid fabrication of heterogeneously controlled paper-based chip arrays. We simply print a wax-patterned microchip with wettability contrasts, enabling automatic and selective assembly of cellulose microfibers to construct predefined paper-based microchip arrays with controllable thickness. This paper-based microchip printing technology is feasible for various substrate materials ranging from inorganic glass to organic polymers, providing a versatile platform for the full range of applications including transparent devices and flexible health monitoring. Our bottom-up printing technology using cellulose microfibers as the starting material provides a lateral resolution down to 42 ± 3 μm and achieves the narrowest channel barrier down to 33 ± 2 μm. As a proof-of-concept demonstration, a flexible paper-based glucose monitor is built for human health care, requiring only 0.3 μL of sample for testing.

Background: Cognitive aids (CAs) are clinical tools guiding clinical decision-making during critical events in the operating room. They may counteract the adverse effects of stress on the non-technical skills of the attending clinician(s). Although most clinicians acknowledge the importance of CAs, their uptake in clinical practice seems to be lagging behind. This situation has led us to investigate which features of CAs may enhance their uptake. Therefore, in this systematic review we explored the optimums regarding the 1) timing to consult the CA, 2) person consulting the CA, 3) location of the CA in the operating room, 4) CA design (paper vs. electronic), 5) CA lay-out, 6) reader of the CA and 7) if the use of CAs in the form of decision support tools lead to improved outcome. Methods: Seven PICO-questions guided our literature search in 4 biomedical databases (MEDLINE, Embase, Web of Science and Google Scholar). We selected English-language randomized controlled trials (RCTs), observational studies and expert opinions discussing the use of cognitive aids during life-threatening events in the operating theatre. Articles discussing non-urgent or non-operating room settings were excluded. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We found 7 RCTs, 14 observational studies and 6 expert opinions. All trials were conducted in a simulation environment. The person who should trigger the use of a cognitive aid and the optimal timing of its initiation, could not be defined by the current literature. The ideal location of the cognitive aids remains also unclear. A favorable lay-out of an aid should be well-structured, standardized and easily readable. In addition, several potentially beneficial design features are described. RCT’s could not demonstrate a possible superiority of either electronic or paper-based aids. Both have their advantages and disadvantages. Furthermore, electronic decision support tools are potentially associated with an enhanced performance of the clinician. Likewise, the presence of a reader was associated with an improved performance of key steps in the management of a critical event. However, it remains unclear who should fulfill this role. Conclusion: Several features of the design or utilization of CAs may play a role in enhancing the uptake of CAs in clinical practice during the management of a critical event in the operating room. However, robust evidence supporting the use of a certain feature over another is lacking.

In the research of the review of this creative and innovation area that can benefit community and nation. The review that had been picked in this research was the paper. The aim of this review is to explain about the advantages or the benefits of paper and also the used of the paper, also the improvement of the nation by the helps of the paper production and innovation. The methods that we going to describe in this review was the involvement of the paper production in many fields, such as for individuals, schools, medical centre and so on. There are a lot of information and new knowledges that we going to present and cite in this review. The conclusion of this article review was to be making sure that everyone knows the important and the properties of the paper in our country.

We report the development of a distance-based paper analytical device combined with a hydrophilic bridge valve (B-dPAD) as a quantitative immunoassay method to monitor human interleukin-6 (IL-6) in human samples. Our device design features (i) a circular sample inlet zone, (ii) a circular capture zone with immobilized anti-IL-6 (anti-Ab

INTRODUCTION: Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression. RESULTS: In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2-32.4) and 28.7% (95% CI 15.8-43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5) and grade 3 or higher AE occurred in 18 pts (45%). CONCLUSIONS: Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients. ispartof: BREAST vol:64 pages:100-111 ispartof: location:Netherlands status: published

Telemedicine use surged during COVID-19, and a significant amount of recent research has relied solely on online surveys to assess patient perceptions. However, these surveys may be biased since they require an internet connection and digital literacy skills. We compare local perceptions of telemedicine visits in rural areas across two methods of data collection: online-only vs. paper surveys. We collected 100 paper and 108 online surveys in two rural counties with a total population of 10,000. The results show that significant differences exist in the demographics of people completing each type of survey and in the perceptions of telemedicine, with paper-based respondents generally demonstrating a higher degree of confidence in telemedicine. Ordered logistic regressions controlling for potentially influential underlying demographic characteristics (income, hours worked, and presence of children) show that paper-based respondents tend to have higher opinions of telemedicine, but that overall levels of comfort are similar across survey types.

Publisher Copyright: © 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. Background: Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication. Objectives: This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision-making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate-to-severe AD. Methods: Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two-round Delphi process, they reached full or partial consensus on 37 statements. Results: Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non-systemic therapy. Systemic therapy should achieve long-term disease control and reduce short-term interventions. Recommended are cyclosporine A for short-term use (all ages) and dupilumab or methotrexate for long-term use (ages ≥6 years). Consensus was not reached on the best long-term systemics for children aged 2–6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real-world data will become available. Conclusions: This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate-to-severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.

Uric acid (UA) is an important biomarker for many diseases. A sensitive point-of-care (POC) testing platform is designed for the digital quantification of salivary UA based on a colorimetric reaction on an easy-to-build smartphone-assisted microfluidic paper-based analytical device (SμPAD). UA levels are quantified according to the color intensity of Prussian blue on the SμPAD with the aid of a MATLAB code or a smartphone APP. A color correction method is specifically applied to exclude the light effect. Together with the engineering design of SμPADs, the background calibration function with the APP increases the UA sensitivity by 100-fold to reach 0.1 ppm with a linear range of 0.1-200 ppm. The assay time is less than 10 min. SμPADs demonstrate a correlation of 0.97 with a commercial UA kit for the detection of salivary UA in clinical samples. SμPADs provide a sensitive, fast, affordable, and reliable tool for the noninvasive POC quantification of salivary UA for early diagnosis of abnormal UA level-associated health conditions.

Food safety is an issue that cannot be ignored at any time because of the great impact of food contaminants on people's daily life, social production, and the economy. Because of the extensive demand for high-quality food, it is necessary to develop rapid, reliable, and efficient devices for food contaminant detection. Microfluidic paper-based analytical devices (μPADs) have been applied in a variety of detection fields owing to the advantages of low-cost, ease of handling, and portability. This review systematically discusses the latest progress of μPADs, including the fundamentals of fabrication as well as applications in the detection of chemical and biological hazards in foods, hoping to provide suitable screening strategies for contaminants in foods and accelerating the technology transformation of μPADs from the lab into the field.

ispartof: JOURNAL OF ENERGY CHEMISTRY vol:70 pages:492-501 status: published

Background Beryllium and its compounds are carcinogenicity, but the mechanisms through which this occurs have yet to be clarified. Accumulating evidence exists that long noncoding RNAs (lncRNAs) play an important role in occurrence and development of cancer. Aims and Methods To explore the carcinogenic mechanism of beryllium, human bronchial epithelial cells (16HBE) were treated with 50 μM beryllium sulfate (BeSO4) for 45 passages (~23 weeks). The expression levels of lncRNA SNHG7, SNHG11, SNHG15, MIR22HG, GMPS, and SIK1 were detected at passage 0 (P0), 15 (P15), 25 (P25), 35 (P35), and 45 (P45). Results The results indicated that enhanced cell proliferation, extensive clones in soft agar, protein expressions of up-regulated matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), proliferating cell nuclear antigen (PCNA), cyclin D1, and down-regulated p53 were all observed at the 45th passage in 16HBE cells. Thus, BeSO4-transformed 16HBE cells (T-16HBE) were established. Meanwhile, the study found that the expression of lncRNA SNHG11 was elevated during malignant transformation. Knockdown of SNHG11 in T-16HBE cells blocked cell proliferation, invasion, and migration, and decreased the protein levels of MMP9, MMP2, PCNA, cyclin D1, but increased p53. Conclusions The studies revealed that SNHG11 acts as an oncogene in the malignant transformation of 16HBE cells induced by BeSO4, which signifies progress in the study of the carcinogenic mechanism of beryllium.

Cypermethrin (CP) exhibits anti-androgenic effects through antagonism on androgen receptor (AR) activation. This study was to identify whether AR-mediated disabled 2 interacting protein (DAB2IP)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was involved in CP-induced mouse Sertoli cells (TM4) proliferation disorder. Real-Time Cell Analysis-iCELLigence system was to measure cell proliferation. Bioinformatic analyses were performed to identify AR-regulated genes. Quantitative Real-Time PCR and western blot were to detect the genes and proteins levels in AR-mediated DAB2IP/PI3K/AKT pathway. Results showed CP suppressed TM4 proliferation and the expression of AR. Activation of AR restored the inhibition efficacy of CP on TM4 proliferation. AR regulated DAB2IP expression and phosphorylation levels of PI3K and AKT in CP-exposed TM4 cells. In addition, knockdown of DAB2IP alleviated the inhibition efficacy of CP on cell proliferation and phosphorylation of PI3K and AKT. Taken together, AR was a modulator in CP-induced inhibition of Sertoli cells proliferation by negatively regulating DAB2IP/PI3K/AKT signaling pathway. The study may provide a new insight for the mechanisms of male reproductive toxicity induced by CP.

Publisher Copyright: © 2022, The Author(s). Direct fire, indirect heat, and extinguishing water cause great damage to cultural assets upon a fire disaster in a library or archive. Conservation and restoration of heat-damaged papers are particularly challenging due to the complexity and severity of the damage. Since valuable originals obviously cannot be used for the development of treatment methods and only to a limited extent for the analysis of the damage, it is necessary to produce model paper materials that have a high degree of similarity to fire-damaged papers, which was addressed in the present study. Three different heating methods were tested to produce model papers of different heating levels. Their altered optical, structural, and chemical properties were analyzed and compared with the results of original fire-damaged samples. The study points out pathways to enable the production of comparable sample materials. Heating between hot plates or in an oven produces papers that have properties quite similar to the originals in terms of surface area, paper structure, cellulose integrity, and interactions with water. Stack heating in the oven has proven to be a particularly effective manufacturing method for larger quantities of model papers.

The Near-Infrared Spectrograph (NIRSpec) is one of the four focal plane instruments on the James Webb Space Telescope. In this paper, we summarize the in-orbit performance of NIRSpec, as derived from data collected during its commissioning campaign and the first few months of nominal science operations. More specifically, we discuss the performance of some critical hardware components such as the two NIRSpec Hawaii-2RG (H2RG) detectors, wheel mechanisms, and the micro-shutter array. We also summarize the accuracy of the two target acquisition procedures used to accurately place science targets into the slit apertures, discuss the current status of the spectro-photometric and wavelength calibration of NIRSpec spectra, and provide the as measured sensitivity in all NIRSpec science modes. Finally, we point out a few important considerations for the preparation of NIRSpec science programs., STFC ERF

Funder: Deutsche Forschungsgemeinschaft; doi: http://dx.doi.org/10.13039/501100001659, For the growth of low-defect crack-free GaN heterostructures on large-area silicon substrates, compositional grading of AlGaN is a widely adapted buffer technique to restrict the propagation of lattice-mismatch induced defects and balance the thermal expansion mismatch-induced tensile stress. So far, a consolidation of the design strategy of such step-graded buffers has been impaired by the incomplete understanding of the effect of individual buffer design parameters on the mechanical and microstructural properties of the epilayers. Herein, we have analyzed a series of metal-organic chemical vapor deposition grown GaN/graded-AlGaN/AlN/Si heterostructures through in situ curvature measurements and post-growth x-ray diffraction (XRD). Our results reveal that in such epi structures, the GaN layer itself induces more compressive stress than the AlGaN buffer, but the underlying AlGaN layers dictate the magnitude of this stress. Furthermore, for a fixed AlGaN buffer thickness, the mean-stress accumulated during the GaN growth is found to be correlated with its structural properties. Specifically, one µm thick GaN layers that acquire 1.50 GPa or higher compressive mean-stress are seen to possess 20 2 ˉ 1 XRD ω-FWHM values less than 650 arc-sec. Also, the evolution of instantaneous stresses during the growth of the AlGaN layers is found to be a valuable indicator for buffer optimization, and composition difference between successive layers is established as a crucial criterion. The results also show that increasing the total buffer thickness (for a fixed number of steps) or increasing the number of steps (for a fixed total buffer thickness) may not always be beneficial. Irrespective of the buffer thickness, optimized high electron mobility transistor structures show similarly low sheet-resistance (∼350 Ω □)−1 and high mobility (∼2000 cm2 V−1 s −1) at room temperature.

Environmental toxic pollutants and pathogens that enter the ecosystem are major global issues. Detection of these toxic chemicals/pollutants and the diagnosis of a disease is a first step in efficiently controlling their contamination and spread, respectively. Various analytical techniques are available to detect and determine toxic chemicals/pathogens, including liquid chromatography, HPLC, mass spectroscopy, and enzyme-linked immunosorbent assays. However, these sensing strategies have some drawbacks such as tedious sample pretreatment and preparation, the requirement for skilled technicians, and dependence on large laboratory-based instruments. Alternatively, biosensors, especially paper-based sensors, could be used extensively and are a cost-effective alternative to conventional laboratory testing. They can improve accessibility to testing to identify chemicals and pollutants, especially in developing countries. Due to its low cost, abundance, easy disposal (by incineration, for example) and biocompatible nature, paper is considered a versatile material for the development of environmentally friendly electrochemical/optical (bio) sensor devices. This review presents an overview of sensing platforms constructed from paper, pointing out the main merits and demerits of paper-based sensing systems, their fabrication techniques, and the different optical/electrochemical detection techniques that they exploit.

Aldicarb, a carbamate pesticide banned in France since 2008, represents a persistent risk of human poisoning. There is no up-to-date picture of aldicarb intentional poisonings associated to detailed diagnosis and clinical management of cases to evaluate the effect of its ban on intoxication risk reduction, including suicide. This retrospective epidemiological study describes cases of suicidal intoxication from the Hauts-de-France region between 2012 and 2021 and illustrates this situation through one analytically documented case. 60 cases were collected, mostly presenting a pathognomonic symptomatology. Thirty-five victims presented a muscarinic syndrome (58.3%), 14 a nicotinic syndrome (23.3%), and 37 a central nervous system impairment (61.7%). Hospitalization was necessary for 44 cases (73.3%), with 2 fatal evolutions. Diagnosis was based on the blood cholinesterase activities. Among the 25 cases with toxicology results, 45.8% presented a moderate decrease of acetylcholinesterase activity, whereas 87.5% presented a strong decrease of butyrylcholinesterase activity. Blood or urine detection of aldicarb and its metabolites may be considered in therapeutic management, although their quantification is unlikely to change the emergency medical care. Our study updates epidemiology of aldicarb poisoning at a regional level, highlighting a persisting health threatening situation with banned pesticides. More than 65% of national cases occurred in this agricultural area, aldicarb remaining available from storage of previously purchased products. Robust evidence is presented that acute poisoning is an ongoing major global public health challenge. There is a need for continued international efforts in risk reduction, knowledge, and information strategies.

Dezocine, a dual agonist and antagonist of the μ-opioid receptor and κ-opioid receptor, is widely used as an analgesic in China. At present, there are few studies on anti-tumor effects of dezocine, most of which are used to treat cancer pain. However, it has recently been reported that dezocine can induce apoptosis of triple negative breast cancer cells. Dezocine may have some anti-tumor activity, but the effect and potential mechanism of dezocine in the treatment of other types of cancer remain to be fully studied. The purpose of the present study was to investigate the effect of dezocine on human Hela cervical carcinoma cells, and to elucidate the underlying molecular mechanisms. We performed CCK-8 assays, clone formation assays, xenograft, flow cytometry analysis, western blot and RNA-seq analysis to evaluate the effects of dezocine on Hela cells. In addition, the role of endoplasmic reticulum (ER) stress in dezocine-induced apoptosis was investigated using qPCR and western blot analysis. Dezocine inhibited Hela cell viability in dose-dependent and time-dependent manners, and notably did not achieve this effect by targeting the opioid receptors. Further mechanistic studies demonstrated that dezocine activated ER stress by upregulating the expression of GRP78, IRE1 and p-JNK, and that dezocine-induced apoptosis was attenuated when the ER stress pathway was blocked. Our results provide a foundation to support the redefinition of dezocine as a novel, adjuvant treatment for patients with cervical cancer, although further research will be required to support its application in clinical practice.

Background Mitochondrial dynamics is essential for the maintenance of healthy mitochondrial network. Emerging evidence suggests that mitochondrial dysfunction is closely linked to the pathogenesis of hepatic fibrogenesis following chronic liver injury. However, the role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in the context of liver fibrosis remains unclear. Methods and Results In this study, C57BL/6 mice were used to establish a model of liver fibrosis via oral gavage with CCl4 treatment for 8 weeks. Furthermore, mitochondrial fission intervention experiments were achieved by the mitochondrial division inhibitor 1 (Mdivi-1). The results demonstrated that chronic CCl4 exposure resulted in severe hepatic fibrogenesis and mitochondrial damage. By contrast, pharmacological inhibition of mitochondrial division by Mdivi-1 substantially reduced the changes of mitochondrial dynamics and finally prevented the deposition of extracellular matrix proteins. Mechanistically, excessive mitochondrial fission may activate hepatic stellate cells through RIPK1-MLKL-dependent hepatocyte death, which ultimately promotes liver fibrosis. Conclusion Our study imply that inhibiting Drp1-mediated mitochondrial fission attenuates CCl4-induced liver fibrosis and may serve as a therapeutic target for retarding progression of chronic liver disease.

The cardiotoxicity induced by arsenic trioxide (ATO) limits its clinical application in acute promyelocytic leukemia treatment. Sacubitril/valsartan (LCZ696) is an effective drug for the treatment of heart failure. In this study, we aimed to investigate the protective effect and mechanisms of LCZ696 against the ATO-induced cardiotoxicity in mice and H9c2 cells. We found that LCZ696 could alleviate the decrease of ejection fraction and fractional shortening induced by ATO, thereby improving mouse cardiac contractile function. LCZ696 could also reduce the myocardial enzyme, resist oxidative stress, mitigate myocardial fibrosis, and ameliorate myocardial structure, thereby alleviating myocardial damage caused by ATO. In addition, LCZ696 could significantly increase the cell viability and reduce the accumulation of reactive oxygen species in ATO-treated H9c2 cells. Besides, in vivo and in vitro studies have been found that LCZ696 could restore the expression of Bcl-2 and reduce Bax and Caspase-3 levels, inhibiting ATO-induced apoptosis. Meanwhile, LCZ696 decreased the levels of IL-1, IL-6, and TNF-α, alleviating the inflammatory injury caused by ATO. Furthermore, LCZ696 prevented NF-κB upregulation induced by ATO. Our findings revealed that LCZ696 has a considerable effect on preventing cardiotoxicity induced by ATO, which attributes to its capability to suppress oxidative stress, inflammation, and apoptosis.

Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders, and there are currently no Food and Drug Administration-approved drug therapies. It is of great interest to us that dimethyl fumarate (DMF) has been shown to have anti-inflammatory effects. The aim of this study was to investigate whether DMF could alleviate lipopolysaccharide(LPS)-induced ALI, and to explore its mechanism of action. Materials and methods We established a mice model of ALI with intratracheal instillation of LPS and intraperitoneal injection of DMF to treat ALI. The pathological damage and inflammatory response of lung tissues were observed by hematoxylin and eosin (H&E) staining, ELISA assay and western blot. ATP plus LPS was used for the establishment of ALI in vitro model, the therapeutic effects of DMF was explored by ELISA assay, RT-qPCR, western blot, and flow cytometry, and the therapeutic mechanisms of DMF was explored by administration of Brusatol (BT), a nuclear factor erythroid-2-related factor 2 (Nrf2) inhibitor. Results We found that intraperitoneal injection of DMF significantly reduced LPS-induced the pulmonary injury, pulmonary edema, and infiltration of inflammatory mediators. In LPS-induced ALI, NLRP3 inflammasome-mediated pyroptosis was markedly activated, followed by cleavage of caspase-1 and GSDMD. DMF inhibited the activation of the NLRP3 inflammasome and pyroptosis in both lung of ALI mice and ATP plus LPS-induced BEAS-2B cells. Mechanistically, DMF enhanced expressions of Nrf2, leading to inactivation of NLRP3 inflammasome and reduced pyroptosis in vivo and in vitro. Conversely, BT reduced the inhibitory effects of DMF on NLRP3 inflammasome and pyroptosis, and consequently blocked the improvement roles of DMF on ALI. Conclusions DMF could improve LPS-induced ALI via inhibiting NLRP3 inflammasome and pyroptosis, and that these effects were mediated by triggering Nrf2 expression, suggesting a therapeutic potential of DMF as an anti-inflammatory agent for ALI/ARDS treatment.

Objective The central objective of this study was to investigate the cumulative effects restraint stress and sodium arsenite on reproductive health in male rats. Methods Healthy male Wistar rats were allocated into 4 groups (n = 8). Animals in group 1 served as controls and did not subjected to any stress. Rats in groups 2, 3, and 4 were subjected to either restraint stress (5 h/day) or maintained on arsenic (25 ppm) via drinking water or both for 65 days. After completion of the experimental period, all the rats were analyzed for selected reproductive endpoints. Results Restraint stress or sodium arsenite treatment increased serum corticosterone levels, reduced testicular daily sperm count, epididymal sperm viability, motility, membrane integrity, and decreased testicular steroidogenic enzymes such as 3β- and 17β-hydroxysteroid dehydrogenases associated with reduced serum testosterone levels, deteriorated testicular architecture, and reduced activity levels of testicular superoxide dismutase and catalase accompanied by elevated lipid peroxidation levels. In rats subjected to restraint stress and sodium arsenite, a significant decrease in selected sperm qualitative and quantitative parameters, serum testosterone levels were observed as compared with rats subjected to sodium arsenite alone. A significant increase in the levels of lipid peroxidation with a concomitant decrease in the activities of antioxidant enzymes was observed in the testis of rats subjected to both restraint stress and sodium arsenite treatment as compared with sodium arsenite alone intoxicated rats. Surprisingly, serum corticosterone levels were significantly elevated in rats following both stressors as compared with arsenic alone treated rats. Analysis of atomic absorption spectroscopy revealed that the accumulation of arsenic in the testis of arsenic-treated and arsenic plus immobilization stress groups was significant as compared with controls. Conclusions Based on the findings, it can be concluded that deterioration of male reproductive health could be accelerated in arsenic intoxicated rats following restraint stress.

Acute lung injury has been reported following various chemotherapeutic agents administration. Several pathways for lung injury have been speculated however, the exact mechanism of the lung injury induced by methotrexate (MTX) is yet to be defined. The potential protective effect of Ginkgo biloba extract (GB), a Chinese herbal medicine, against MTX-induced lung injury is still not reported. Therefore, this study was performed to examine the possible implication of NLRP3 inflammasome and miRNA-21 in the pathogenesis of the MTX-induced lung injury as well as the protective role of GB in ameliorating the induced lung injury. Rats received GB (100 mg/kg/day, orally) for 10 days and MTX (20 mg/kg single dose, intraperitoneally) on the fifth day. MTX-induced lung injury was manifested by lung histopathology. MTX exhibited a marked increase in lung malondialdehyde beside a notable decrease in lung reduced glutathione. Moreover, MTX injection activated the lung NLRP3 inflammasome by significant upregulation of the NLRP3, ASC, caspase-1 lung mRNA expressions and protein levels in addition to lung NF-kBp65 protein expression, and miRNA-21 expression when compared with the normal control group. However, GB administration mitigated lung injury and inhibited the NLRP3 activation. This study is the first report to reveal the involvement of NLRP3 inflammasome in the pathogenesis of MTX-induced lung injury and also to show that the administration of GB alleviates the lung injury induced by MTX via suppressing the oxidative stress, restoring the antioxidant activity, blocking the NLRP3/ASC/Caspase-1 signaling and downregulating the NF-kBp65 protein expression ae well as miRNA-21 expression in lung tissue.

Drug-induced nephrotoxicity is a common problem in clinical medicine and the frequency of drug-related acute and chronic kidney dysfunction worldwide. One of them is anti-tuberculosis (TB) drugs that cause renal function impairment during TB treatment. Medicinal plants contain bioactive compounds that are capable for treating drug or toxin-induced renal disorders. The aim of the present study was to assess the protective effect of the ethanolic extract of Nigella sativa seeds (NS) against anti-TB drugs (ATDs) induced nephrotoxicity in Wistar albino rats. Rats were treated with ATDs for 12weeks (3 alternative days in a week). Supplementation with 125mg NS/kg, p.o. was administered to the experimental rats for 12weeks (3 alternative days in a week considering next day of ATDs treatment). The results demonstrated that NS treatment protected against renal damage induced by ATDs, as evidenced by the reduction in serum urea, creatinine, uric acid, urea nitrogen levels, pro-inflammatory markers (TNF-α and IL-6), whereas improvement in histological tubular and glomerular damage. In addition, NS enhanced the antioxidant enzyme activity (superoxide dismutase and catalase) and decreased the lipid peroxidation and glutathione level in the kidney. In conclusion, NS could reduce chronic nephritis in ATDs treated group through suppressing inflammation and oxidative stress. It suggests that NS can be used as supplementary preventive and protective drug against kidney injury during anti-TB treatment.

The membraneless-gas separation microfluidic paper-based analytical device (ML-GS μPAD), consisting of donor, spacer, and acceptor layers, was developed to monitor total ammonia in fish pond water. The principle of the analysis involved the addition of sodium hydroxide solution to the sample zone in the donor layer containing ammonia/ammonium, and the produced ammonia gas diffuses through the spacer to the detection zone in the acceptor layer containing red rose extract to produce a color change from pink to blue corresponding to the ammonia/ammonium concentration. Under optimum conditions, the proposed method provided good linearity of ammonia in the range concentration of 0-100 mg L

Nitroglycerin (NTG)—a nitric oxide–donating drug—is traditionally administered via the sublingual route to treat acute myocardial angina attacks. NTG also increases tumor blood flow and, consequently, cancer drug delivery to tumor cells. In the homologous recombination pathway, radiation-sensitive 52 (Rad52) plays a crucial role in DNA repair by promoting the annealing of complementary single-stranded DNA and stimulating radiation-sensitive 51 (Rad51) recombinase activity. Pemetrexed—a multitargeted antifolate agent—exhibits satisfactory clinical activity in wild-type nonsquamous non-small-cell lung cancer (NSCLC) cells. However, the synergistic activity of combination therapy with NTG and pemetrexed against NSCLC cells has not yet been clarified. In 2 NSCLC cell lines (i.e. lung squamous cell carcinoma H520 and lung adenocarcinoma H1975 cells), NTG reduced Rad52 expression; in addition, decreased phospho-AKT and phospho-ERK1/2 protein levels were observed. Enhancement of AKT or ERK1/2 activity through transfection with a constitutively active AKT (AKT-CA) vector or constitutively active mitogen-activated protein kinase kinase 1 (MKK1-CA) vector increased the Rad52 protein level and cell survival, which were suppressed by NTG. The knockdown of Rad52 expression by using small interfering RNA or by inhibiting AKT and ERK1/2 activity enhanced the cytotoxicity and cell growth inhibition induced by NTG. Moreover, NTG synergistically enhanced the cytotoxicity and cell growth inhibition induced by pemetrexed in NSCLC cells; these effects were associated with AKT and ERK1/2 inactivation and, consequently, Rad52 downregulation in H520 and H1975 cells. The results provide a rationale for combining NTG and pemetrexed in lung cancer treatment to improve lung cancer control.

Microfluidic paper-based analytical devices (μPADs) are emerging as prominent platform for disease detection, specifically in developing countries. This paper device offers simplicity and affordability not typically seen in centralized laboratory settings. However, detection limits in μPADs are inadequate and often require tests results to be read within a specific time interval to ensure accuracy. To overcome these challenges, we are developing an on-chip mass spectrometry (MS) detection strategy for immunoassays performed on paper substrates. Herein, we present our initial results from a proof-of-concept study toward the development of μPADs capable of storing immunoassay reagents within the confinements of the 3D device, automatic splitting of biofluid into four individual test zones, immuno-capture of disease biomarker, and on-chip MS detection of captured species. The reported study encourages the development of point-of-care and direct-to-customer testing using the disposable μPAD to collect samples, followed by sensitive analysis using portable mass spectrometers. We demonstrate this capability using malaria Plasmodium falciparum histidine-rich protein 2 (PfHRP2) antigen detection.

The use of natural nanocomponents for increasing the mechanical strength of paper in the aerodynamic method has been investigated. Milled bacterial cellulose and a fine fraction of sulphate bleached softwood cellulose formed during grinding (secondary fines) were used as nanocomponents. The treatment with nanocomponents was carried out while moistening the fibrous layer with the use of an anti-adhesive material providing uniform one sided application of substances in the form of a suspension on the paper surface. The growth of the indicators of the mechanical strength of paper occurred due to the formation of additional hydrogen bonds and an increase in the interfacial interaction between the fibrous layer of plant cellulose and the nanocomponent. It was found that the use of a suspension of bacterial cellulose is more promising due to the low consumption of the binder with a significant increase in the mechanical strength of the paper. The application of a bacterial cellulose coating layer on aerodynamically molded eucalyptus cellulose makes it possible to increase the mechanical strength of the paper to consumer requirements with the consumption of bacterial cellulose in an amount of 0.9% to 1.5% by weight of absolutely dry eucalyptus cellulose., Исследовано применение природных нанокомпонентов для повышения механической прочности бумаги при аэродинамическом способе формования. В качестве нанокомпонентов использовали измельченную бактериальную целлюлозу и мелкую фракцию сульфатной беленой хвойной целлюлозы, образующуюся в процессе размола (вторичную мелочь). Введение нанокомпонентов проводили при увлажнении волокнистого слоя с применением антиадгезионного материала, обеспечивающего равномерное одностороннее нанесение веществ в виде суспензии на поверхность бумаги. Рост показателей механической прочности бумаги происходил за счет образования дополнительных водородных связей и возрастания межфазного взаимодействия между волокнистым слоем из растительной целлюлозы и нанокомпонентами. Установлено, что использование суспензии бактериальной целлюлозы более перспективно из-за малого расхода при значительном повышении показателей механической прочности бумаги. Нанесение покровного слоя бактериальной целлюлозы на бумагу аэродинамического формования из сульфатной беленой эвкалиптовой целлюлозы позволяет повысить значение механической прочности бумаги до потребительских требований при расходе бактериальной целлюлозы в количестве от 0.9 до 1.5% к массе абсолютно сухой целлюлозы.

In this work, we present for the first time, a simplified fabrication of a laminated paper-based analytical device (LPAD) with a free-mobile app, Palette Cam, for image analysis. A filter paper is cut in a rectangular shape (9 × 3 cm) and placed between a top laminating sheet with punched holes and a bottom laminating sheet. The holes allow accessibility of liquid on the paper. Thermal lamination is then employed to complete the fabrication of LPAD. Our simplified design reduces a tedious alignment of small pieces of paper to the holes. We demonstrated the LPAD with an analysis of salicylic acid in pharmaceutical products. Each 4 μL of ferric reagent and sample was dispensed on the LPAD. Smartphone was used to capture images. The RGB (red green blue) color intensity from the Palette Cam was converted into a logarithm color ratio. Our LPAD is simplified, cost-effective and able to be a portable device.

Pseudoestrogene bisphenol A (BPA) can be important ingredient of thermochromic inks, increasingly used materials in thermal printing paper, security printing, advertising, design and as temperature indicators in medicine and food industry. BPA mass fraction in thermochromic inks can be up to several percent. Hence, disposal of items with thermochromic prints pose a risk of environmental pollution. In this work BPA mass fraction was monitored during anaerobic degradation of papers with thermochromic prints in soil in both matrices: papers and soil. The degradation conditions simulated deeper layers of waste at a landfill site. Six types of papers with prints of thermochromic ink containing 2% of BPA were subjected to anaerobic degradation over up to 150 days.

This study proposes a method for the chamber disinfection of paper with biocide in the form of fine, volatile droplets using antifungal Rocima GT. This method provides a fungicidal effect, and within a short exposure time, a fungistatic one. At a concentration of 5% Rocima GT solution, the minimum treatment time to ensure the complete disinfection of paper was 15 min. The proposed method of disinfection by a chemical mist was less harmful to paper than disinfection using a swab saturated in a biocide solution. It was noted that when using Rocima GT at insufficient concentrations to inhibit fungal growth completely, Rocima GT can induce, as well as suppress, organic acid produced by Aspergillus niger depending on the concentration.

Acute liver failure (ALF), characterized by the quick occurrence of disorder in liver, is a serious liver injury with extremely high mortality. Therefore, we investigated whether diallyl trisulfide (DATS), a natural product from garlic, protected against ALF in mice and studied underlying mechanisms. In the present study, lipopolysaccharide (LPS) (10 μg·kg−1)/D-galactosamine (D-gal) (500 mg·kg−1) was intraperitoneally injected to ICR mice to induce ALF. The mice were orally administered 20-, 40-, or 80-mg·kg−1 DATS) 1 h before LPS/D-gal exposure. Serum biochemical analyses and pathological study found that DATS pretreatment effectively prevented the ALF in LPS/D-gal-treated mice. Mechanistically, pretreatment of DATS inhibited the increase of the numbers of CD11b+ Kupffer cells and other macrophages in the liver, the release of tumor necrosis factor-α into the blood, and Caspase-1 activation induced by LPS/D-gal treatment in mice. Furthermore, DATS inhibited the activation of Caspase-3, downregulation of Bcl-2/Bax ratio, and increase of TUNEL positive staining. Altogether, our findings suggest that DATS exhibits hepatoprotective effects against ALF elicited by LPS/D-gal challenge, which probably associated with anti-inflammation and anti-apoptosis.

A new and valid method was developed for the quantitative voltammetric analysis of midodrine hydrochloride (MID) in pharmaceutical tablets (Midodrine) and biological samples. The method is based on electro-oxidation of MID supported by both disposable pencil electrode (PE) and glassy carbon electrode (GCE). The analysis was carried out using cyclic voltammetry, differential pulse voltammetry (DPV), and square wave voltammetry (SWV) techniques. The proposed analytical method was validated according to ICH guidelines. MID was successively assayed at concentration ranges of 1.15–6.55 and 0.58–3.05 μg mL−1 at PE. Also, MID was successively assayed at concentration ranges of 1.15–5.28 and 2.86–27.6 μg mL−1 at GCE for DPV and SWV methods, respectively. The proposed method was successfully used for the analysis of MID in its dosage form and human urine with good recoveries of 99.66 ± 0.33, 99.8 ± 0.45 at PE and 99.8 ± 0.25, 98.7 ± 1.27 at GCE for the DPV and SWV methods, respectively. The suggested method could be applied to the studied drug in the quality control lab as well as in its pharmacokinetic studies.

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1β and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

Introduction The assessment of the risk of virus transmission through papers, such as postcards, is important. However, the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) on different types of papers is currently unknown. Investigation of the survival time of these viruses on different types of papers will provide insights into their risk of long-distance transport by postal items. Methods We evaluated the stability of SARS-CoV-2 and IAV, mixed with a culture medium, on the surface of postcards with various coatings, including plain paper (PP), inkjet paper (IP), and inkjet photo paper (IPP). The surface structure of each paper was microscopically assessed. Results The surface structures of PP, IP, and IPP varied greatly depending on the presence or absence, and type, of coat layer, regardless of the base material. IP and IPP surfaces were less conducive to virus survival than PP surfaces, because of the difference in surface shapes. The survival times of SARS-CoV-2 on each paper were approximately 59.8 (PP), 6.5 (IP), and 9.8 h (IPP), and significantly longer than those of IAV (10.3, 1.8, and 3.3 h, respectively). Conclusions The risk of SARS-CoV-2 transmission via paper, such as postcards, is significantly higher than that of IAV transmission. While PP, IP, and IPP have the same base material, their surface structures differ, which affects viral stability. The IP and IPP surfaces are less suitable for virus survival. This study provides novel insights into the risks of viral transmission via paper.

Contemporary exposure to PM2.5 has been reported to disrupt spermatogenesis. However, the subsequent toxicological responses and the mechanisms of male reproductive damage in offspring induced by maternal exposure to PM2.5 remain largely unknown. For the first time, this study aimed to explore the apoptotic response in spermatogenesis of male offspring following maternal exposure to PM2.5 and its mechanisms. The C57BL/6 mice with vaginal plugs were randomly divided into four groups. Mice in the PM2.5 groups were intratracheally exposed to PM2.5 (4.8 mg/kg body weight, 43.2 mg/kg body weight) during pregnancy (every 3 days, six times in total). The mice in the membrane control group were treated similarly to the PM2.5 groups, applying only PM2.5 sampling membrane, while mice in the control group were kept untreated. The results showed that maternal exposure to PM2.5 during pregnancy resulted in structural lesions of the testis, reduced numbers of primary spermatocytes and spermatids, decreased sperm count and quality, shortened diameter of seminiferous tubules, and reduced testosterone and ABP in the offspring testes. Furthermore, cell apoptosis was increased and protein expression of IRE-1/P-JNK/cleaved caspase-12/cleaved caspase-3 was activated. These findings suggested that maternal exposure to PM2.5 may affect spermatogenesis by increasing apoptosis through activation of UPR-mediated JNK apoptotic pathway in offspring testicles and by reducing testosterone secretion.

Acrylamide is a well-known neurotoxicant and carcinogen. Apart from industrial exposure, acrylamide is also found in different food products. The present study deals with in vivo experiment to test the protective effect of rutin against acrylamide induced toxicity in rats. The study was carried out on female rats with exposure of acrylamide at the dose of 38.27 mg/kg body weight, orally for 10 days followed by the therapy of rutin (05, 10, 20 and 40 mg/kg orally), for three consecutive days. All animals were sacrificed after 24 h of last treatment and various biochemical parameters in blood and tissue were investigated. Histopathology of liver, kidney and brain was also done. On administration of acrylamide for 10 days, neurotoxicity was observed in terms of decreased acetylcholinesterase activity and oxidative stress was observed in terms of increased lipid peroxidation, declined level of reduced glutathione, antioxidant enzymes (superoxide dismutase and catalase) in liver, kidney and brain. Acrylamide exposure increased the activities of serum transaminases, lipid profile, bilirubin, urea, uric acid and creatinine in serum indicating damage. Our experimental results conclude that rutin showed remarkable protection against oxidative DNA damage induced by acrylamide, which may be due to its antioxidant potential.

Target-responsive nanomaterials attract growing interest in the application of drug delivery, bioimaging, and sensing due to the responsive releasing of guest molecules by the smart molecule gate. However, it remains a challenge to develop smart nanomaterials with simple assembly and low nonspecific leakage starting from encapsulation strategies, especially in the sensing field. Herein, Au nanoclusters (Au NCs) were first grown on porous carbon derived from ZIF-8 (PCZIF) to be employed as nanocarriers. By employing the Au NCs as linkers and aptamer (Apta) double-strand hybrids (target Apta and SH-complementary DNA) as capping units, we reported the novel target-responsive nanomaterials of Apta/Au NCs-PCZIF/hemin through Au-S binding encapsulation for sensing assays. The Au-S binding encapsulation strategy simplified the packaging procedure and reduced non-target responsive leakage. As a proof, ochratoxin A (OTA) as a model target participates in the double-strand hybrid competitive displacement reaction and triggered Apta conformation switches from a coil to a G-quadruplex structure accompanied by the dissociation of the gatekeeper. Simultaneously, the released hemin can initiate a self-assembly to form G-quadruplex/hemin DNAzyme. Interestingly, owing to DNAzyme providing electron transfer mediators and peroxidase-like activity, we proposed an electrochemical/colorimetric dual-mode paper-based analytical device (PAD) that provided self-verification to enhance reliability and accuracy, benefiting from independent signal conversion and transmission mechanism. As a consequence, the proposed dual-mode PAD could achieve sensitive electrochemical detection and visual prediction of OTA in the range of 1 pg/mL to 500 ng/mL and 50 pg/mL to 500 ng/mL, respectively. The electrochemical detection limit for OTA was as low as 0.347 pg/mL (

The existence of pesticide residues in the hydrosphere, biosphere, and anthroposphere can cause acute or chronic diseases and deteriorate the environment. Therefore, efficient detection of pesticide residues is of great significance to prevent food poisoning, control food pollution, and protect human lives by recognizing their distribution and concentration. Herein, a novel smartphone-coupled three-layered paper-based microfluidic chip is proposed as a facile platform to detect the pesticides. The stereoscopic capillary-driven fluid transport is enabled by the three-layered microfluidic chip configuration. The detection mechanism is based on the enzyme inhibition reaction and the chromatic reaction. The detection results are obtained by a smartphone and figured out by colorimetric quantitative analysis. Taking advantages of the above merits, we demonstrate the utilization of this smartphone-coupled three-layered paper-based microfluidic chip for the effective analysis of typical pesticides (profenofo and methomyl). The linear ranges of profenofo and methomyl are 0.27-2.1 μmol L

The exact fabrication of precise three-dimensional structures for piezoresistive sensors necessitates superior manufacturing methods or tooling, which are accompanied by time-consuming processes and the potential for environmental harm. Herein, we demonstrated a method for

Neratinib is a pan-HER tyrosine kinase inhibitor newly approved by FDA in 2017 to treat HER2-positive breast cancer, but the phase III trial of neratinib showed that 96% of the patients taking neratinib experienced diarrhea. So far very few mechanistic studies explore neratinib-induced gastrointestinal (GI) toxicity. Hereby, we performed toxicity studies in mice to characterize the potential mechanism underlying this adverse effect. C57BL/6 J mice were separated into three groups A, B, C. Group A received vehicle; group B was orally dosed with 100 mg/kg neratinib once daily for 18 days. Group C was dosed with 100 mg/kg neratinib for 12 days and switched to vehicle for 6 days. Intestine and liver were collected for further analysis. Human intestine-derived cells were treated with neratinib in vitro. Our results showed that 12 days treatment of neratinib caused persistent histological damage in mouse GI tract. Both gene expression and activity of Cyp3a11, the major enzyme metabolizing neratinib in mice was reduced in small intestine. The gene expression of proinflammatory cytokines increased throughout the GI tract. Such damages were not recovered after 6 days without neratinib treatment. In addition, in vitro data showed that neratinib was potent in killing human intestine-derived cell lines. Based on such findings, we hypothesized that neratinib downregulates intestinal CYP3A enzyme to cause excessive drug disposition, eventually leading to gut injury.

Ayurvedic formulations are widely used and perceived as safer medicine and subjected to be self-prescribed. However, recent reports have demonstrated adulterating these drugs with toxic quantities of heavy metals. To study the magnitude of the problem in Indian-manufactured Ayurvedic medications, we randomly collected common over-the-counter Ayurvedic preparations from the licensed Ayurvedic shops in the local markets of Chandigarh in 2017. The samples were analyzed to identify and quantify eight metal ions, including mercury, arsenic, lead, cadmium, zinc, iron, copper, and chromium, using inductively coupled plasma mass spectrometry in Postgraduate Institute of Medical Education and Research, Chandigarh. The permissible limit set by the Food and Agriculture Organization/World Health Organization (FAO/WHO) for herbal medicines was followed to define the high metal concentrations. Out of 43 Ayurvedic preparations, 42 were analyzed. Heavy metals were detected in all formulations. The median (range) concentrations (in μg/g or mg/kg) of the metals were quantified as follows- mercury, 13.52 (0.00–61 095.99); arsenic, 0.00 (0.00–1038.83); lead, 1.40 (0.00–57.09); zinc, 84.2200 (26.48–22 519.03); iron, 1356.21 (128.24–136 835.25); copper, 17.1450 (0.00–12 756.86) and chromium, 20.9050 (0.00–2717.58). The metal contents above the FAO/WHO-mandated limit for zinc, mercury, arsenic, and lead were detected in 35, 29, 6, and 2 formulations, respectively. All medications contained detectable quantities of zinc and iron. Copper was detected in all except one. Cadmium was not found in any sample. Ayurvedic medications have a high prevalence of heavy metals. An evaluation of the sources of contamination and the necessary drug safety regulations are required.

The prevalence of diabetes has increased over the past years. Therefore, developing minimally invasive, user-friendly and cost-effective glucose biosensors is necessary especially in low-income and developing countries. Cellulose paper-based analytical devices have attracted the attention of many researchers due to affordability, not requiring trained personnel, and complex equipment. This paper describes a microfluidic paper-based analytical device for the detection of glucose in tear with the naked eye. The paper-based biosensor fabricated by laser CO2, and GOx/HRP enzymatic solution coupled with TMB was utilized as reagents. A sample volume of 10 µl was needed for the biosensor operation and the results were observable within 5 minutes. To evaluate the device performance, color intensity-based and distance-based results were analyzed by ImageJ and Tracker. Distance-based results showed a linear behavior in the range of 0.1–0.6 mM with an R2 = 0.967 and LOD of 0.2 mM. The results could be perceived by the naked eye without any need to further equipment or trained personnel in a relatively short time (3–5 minutes). Moreover, glucose concentration could be obtained non-invasively by tears collected by this µPAD.

Silicosis is a chronic irreversible pulmonary disease caused by the inhalation of silica crystals in occupational settings in most cases. Persistent inflammation in the alveolar space is considered to be the major reason for tissue damage and lung fibrogenesis. The mechanisms by which silica exposure activates immune cells are not well understood. Here, we employed an in vivo silicosis disease model by intratracheal instillation of a large dose of silica suspension in rats and explored the involvement of inflammasome activation. Marked leukocyte infiltration and edema were observed 3 days following silica exposure in treated animals compared to controls. Using this model, we compared the expression of inflammasome sensors (AIM2 and NLRP3) and effector protein (caspase-1) by western blot and immunohistochemical staining using the lung homogenates and lung tissue sections. Our results demonstrated that following acute silica exposure, AIM2, NLRP3 and caspase-1 expressions were increased in macrophages or/and lung epithelial cells compared to control animals. We also analyzed interleukin 1β expression using lung homogenates, and significant increase in interleukin 1β was observed in 3-day silica-exposed rats. The activation of inflammasome sensors AIM2 and NLRP3 suggested to us that blocking these activators may attenuate silica-associated tissue damage and inflammation.

This study develops a simple and low-cost 3D paper-based analytical device (3D PAD) for the detection of available phosphate in soil. Epoxy resin is presented as a new hydrophobic material for low-cost mass production of PADs using the screen-printing method. An optimized concentration of epoxy resin solution is screen printed onto Whatman filter paper no. 1 in an easy one-step process to create hydrophobic patterns on PADs. The epoxy resin is air dried at room temperature, without heating or UV curing. This method delivers high reproducibility, resolution, and stability, and the epoxy resin barrier is compatible with both organic solvents and aqueous solutions. The molybdenum blue method is used in this PAD to measure phosphate in a colorimetric assay. The developed 3D PAD attains a linear range of 0.5-40 mg L

Microfluidic paper-based analytical devices (μPADs) have attracted great attention as potential candidates for point-of-care testing (POCT). Nevertheless, only a limited number of μPADs expected to satisfy the standard of Clinical Laboratory Improvement Amendments (CLIA) waived tests as issued by the US Food and Drug Administration (FDA) have been reported. This work introduces a "traffic light type μPAD", enabling highly intuitive semi-quantitative equipment-free naked-eye readout with no need for calibration, subjective interpretation or calculation. Assay results are displayed as traffic light colours reporting 5 analyte concentration levels (green/greenyellow/yellow/yellowred/red). The device has been designed to never display all three colours simultaneously, eliminating any risk for misinterpretation. The mechanism relies on the modulation of sample flow through a network of paperfluidic channels modified with a hydrophobic to hydrophilic phase-switching substance responsive to H

Microfluidic paper-based analytical devices (microPADs) are emerging as simple-to-use, low-cost point-of-care testing platforms. Such devices are mostly fabricated at present by creating hydrophobic barriers using wax or photoresist patterning on porous paper sheets. Even though devices fabricated using these methods are used and tested with a wide variety of analytes, still they pose many serious practical limitations for low-cost automated mass fabrication for their widespread applicability. We present an affordable and simple two-step process - cut and heat (CH-microPADs) - for the selective fabrication of hydrophilic channels and reservoirs on a wide variety of porous media such as tissue/printing/filter paper and cloth types, such as cotton and polyester, by a lamination process. The technique presents many advantages as compared to existing commonly used methods. The devices possess excellent mechanical strength against bending, folding and twisting, making them virtually unbreakable. They are structurally flexible and show good chemical resistance to various solvents, acids and bases, presenting widespread applicability in areas such as clinical diagnostics, biological sensing applications, food processing, and the chemical industry. Fabricated paper media 96 well-plate CH-microPAD configurations were tested for cell culture applications using mice embryonic fibroblasts and detection of proteins and enzymes using ELISA. With a simple two-step process and minimal human intervention, the technique presents a promising step towards mass fabrication of inexpensive disposable diagnostic devices for both resource-limited and developed regions.