Distribution of Propranolol in Periocular Tissues: A Comparison of Topical and Systemic Administration

Purpose: Oral propranolol has become a promising treatment of capillary hemangiomas (CHs) despite concerns of side effects associated with systemic beta-blockers. The objective of this study was to investigate the distribution of propranolol in periocular tissues and in plasma after topical application of propranolol as compared with intravenous and oral administration of propranolol. Methods: Each rabbit received propranolol as ophthalmic solution (1%) in one eye (1.5 mg dose), intravenous injection (1.5 mg dose), or commercially available propranolol oral solution (5 mg dose). The periocular tissues (e.g., eyelids and extraocular muscles) and blood were collected and assayed for propranolol. Results:After topical instillation of 1.5 mg propranolol, high amounts of propranolol were rapidly delivered to the eyelids and extraocular muscles (4−32 μg/g at 1 h after dosing). The drug in these tissues was slowly cleared, and significant amounts of the drug (\u3e0.4 μg/g) were still present at 24 h after the topical application. After oral administration of a clinically relevant dose of 5 mg propranolol, the drug concentrations in the periocular tissues were relatively low ( Conclusions: Topical administration can provide increased concentrations of propranolol in the periocular tissues and, thus, is superior to systemic administration for the treatment of periocular CH

The Role of Metagenomic Next-Generation Sequencing as a Promising Technology for Diagnosing HIV-TB Coinfection

The human immunodeficiency virus (HIV) pandemic has caused a resurgence of tuberculosis (TB), thus increasing morbidity and mortality. Moreover, HIV-TB coinfection leads to difficulties in diagnosis. Sputum smear microscopy, mycobacterial culture and GeneXpert MTB/RIF assays are generally endorsed to detect Mycobacterium tuberculosis ( M. tuberculosis ) in HIV-TB coinfection. However, these methods cannot diagnose TB in an accurate and timely manner, thus increasing the rates of HIV-associated morbidity and mortality in patients with TB. Hence, a considerable need exists for better diagnostic tools for patients with HIV-TB coinfection. Metagenomic next-generation sequencing (mNGS) is a novel detection platform widely used to assess infectious disease, antimicrobial resistance, the microbiome and human host gene expression. Herein, we summarize the advantages of mNGS for infectious disease diagnostics. We then assess the efficiency of mNGS in the detection of M. tuberculosis in different specimens and several cases of HIV-TB coinfection. We conclude that mNGS is an acceptable diagnostic method for HIV-TB coinfection, although limited research is available

Conjugated Quantum Dots Inhibit the Amyloid β (1–42) Fibrillation Process

Nanoparticles have enormous potential in diagnostic and therapeutic studies. We have demonstrated that the amyloid beta mixed with and conjugated to dihydrolipoic acid- (DHLA) capped CdSe/ZnS quantum dots (QDs) of size approximately 2.5 nm can be used to reduce the fibrillation process. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used as tools for analysis of fibrillation. There is a significant change in morphology of fibrils when amyloid β (1–42) (Aβ (1–42)) is mixed or conjugated to the QDs. The length and the width of the fibrils vary under modified conditions. Thioflavin T (ThT) fluorescence supports the decrease in fibril formation in presence of DHLA-capped QDs

Dynamics analysis of a novel two-translation parallel mechanism

In this paper, we take a novel two-translation parallel mechanism based on variable length parallelogram structure as the research object, and carry out the research on the dynamic characteristics of the mechanism. Based on the principle of virtual work, the dynamic model of the new two-translation parallel mechanism is established. By numerically solving the dynamic model, the dynamic behavior of the new mechanism with impact characteristics is found, which provides a theoretical basis for optimizing this new mechanism

Reliability Evaluation of NC Machine Tools considering Working Conditions

Reliability evaluation is the basis for reliability design of NC machine tools. Since traditional reliability evaluation methods do not consider the working conditions' effects on reliability, there is a great error of a result of a traditional method compared with an actual value. A new reliability evaluation model of NC machine tools is proposed based on the Cox proportional hazards model, which describes the mathematical relation between the working condition covariates and the reliability level of NC machine tools. Firstly, the coefficients of working condition covariates in the new reliability evaluation model are estimated by the partial likelihood estimation method; secondly, the working condition covariates which have no effects on the reliability of NC machine tools are eliminated by the likelihood ratio test; then parameters of the baseline failure rate function are estimated by the maximum likelihood estimation method. Thus, the reliability evaluation model of NC machine tool is obtained under different working conditions and the reliability level of NC machine tools is obtained. Case study shows that the proposed method could establish the relation between the working condition covariates and the reliability level of NC machine tools, and it would provide a new way for the reliability evaluation of NC machine tools

Carbon Dioxide and Water Electrolysis Using New Alkaline Stable Anion Membranes

The recent development and market introduction of a new type of alkaline stable imidazole-based anion exchange membrane and related ionomers by Dioxide Materials is enabling the advancement of new and improved electrochemical processes which can operate at commercially viable operating voltages, current efficiencies, and current densities. These processes include the electrochemical conversion of CO2 to formic acid (HCOOH), CO2 to carbon monoxide (CO), and alkaline water electrolysis, generating hydrogen at high current densities at low voltages without the need for any precious metal electrocatalysts. The first process is the direct electrochemical generation of pure formic acid in a three-compartment cell configuration using the alkaline stable anion exchange membrane and a cation exchange membrane. The cell operates at a current density of 140 mA/cm2 at a cell voltage of 3.5 V. The power consumption for production of formic acid (FA) is about 4.3–4.7 kWh/kg of FA. The second process is the electrochemical conversion of CO2 to CO, a key focus product in the generation of renewable fuels and chemicals. The CO2 cell consists of a two-compartment design utilizing the alkaline stable anion exchange membrane to separate the anode and cathode compartments. A nanoparticle IrO2 catalyst on a GDE structure is used as the anode and a GDE utilizing a nanoparticle Ag/imidazolium-based ionomer catalyst combination is used as a cathode. The CO2 cell has been operated at current densities of 200 to 600 mA/cm2 at voltages of 3.0 to 3.2 respectively with CO2 to CO conversion selectivities of 95–99%. The third process is an alkaline water electrolysis cell process, where the alkaline stable anion exchange membrane allows stable cell operation in 1 M KOH electrolyte solutions at current densities of 1 A/cm2 at about 1.90 V. The cell has demonstrated operation for thousands of hours, showing a voltage increase in time of only 5 μV/h. The alkaline electrolysis technology does not require any precious metal catalysts as compared to polymer electrolyte membrane (PEM) design water electrolyzers. In this paper, we discuss the detailed technical aspects of these three technologies utilizing this unique anion exchange membrane

Extracellular RNA in melanoma: Advances, challenges, and opportunities

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%–3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According to previous studies, extracellular RNAs (exRNAs) have been implicated in tumorigenesis and spread of melanoma. They can influence the proliferation, invasion and metastasis of melanoma by controlling the expression of target genes and can also influence tumor progression by participating in signal transduction mechanisms. Therefore, understanding the relationship between exRNA and malignant melanoma and targeting therapy is of positive significance for its prevention and treatment. In this review, we did an analysis of extracellular vesicles of melanoma which focused on the role of exRNAs (lncRNAs, miRNAs, and mRNAs) and identifies several potential therapeutic targets. In addition, we discuss the typical signaling pathways involved in exRNAs, advances in exRNA detection and how they affect the tumor immune microenvironment in melanoma

Analysis of Milling Quality of Reasonably Well Milled Rice with Three Different Grain Shapes

In order to explore changes in the milling quality of reasonably well milled rice with different grain shapes, the bran degree, milling degree and broken rice rate of short-grained (‘Jihong 6’), medium-grained (‘Daohuaxiang’) and long-grained (‘Yexiangyoulisi’, ‘Yexiang’ for short) brown rice were measured after milling at different temperatures and for different periods. The results showed that the bran degree decreased exponentially with an increase in milling pressure for ‘Jihong 6’ and ‘Daohuaxiang’ and an increase in milling time for ‘Yexiang’. For reasonably well milled rice with bran degree from 7.0% to 2.0%, as specified by China’s national standard GB/T 1354–2018, the percentage change in milling degree of ‘Jihong 6’, ‘Daohuaxiang’ and ‘Yexiang’ were approximately 5.03%, 2.98% and 0.18%, respectively, indicating that the milling degree of reasonably well milled rice did not change more significantly with increasing grain length. The broken rice rates of ‘Daohuaxiang’, ‘Jihong 6’ and ‘Yexiang’ increased by 5.32, 0.25 and 0.21 percentage points, respectively, and the white rice yields decreased by 1.38, 2.74 and 0.21 percentage points, respectively. The change in broken rice rate of ‘Yexiang’ for reasonably well milled rice was the smallest. The broken rice rates of ‘Daohuaxiang’, ‘Jihong 6’ and ‘Yexiang’ at bran degree of 0.10% increased by 10.36–4.77, 1.85–1.60, and 10.05–9.84 percentage points, respectively compared with those at bran degree from 7.0% to 2.0%, and the white rice yields decreased by 4.19–2.81, 7.02–4.28 and 10.65–10.44 percentage points, respectively. So, the effect of changes in broken rice rate at bran degree of 0.10% on white rice yield was more pronounced. ‘Daohuaxiang’ with bran degree of 2.10%–2.45% met germ retention rate of less than 20% for high-quality japonica rice specified in the national standard, while ‘Jihong 6’ and ‘Yexiang’ with bran degree from 7.0% to 2.0% did not meet this requirement. At bran degree from 7.0% to 2.0%, the whiteness of ‘Daohuaxiang’, ‘Jihong 6’ and ‘Yexiang’ increased by 6.65, 2.80 and 2.69 percentage points, respectively. There was no significant regular change in the breaking strength of the three rice varieties. The bran degree had a significant correlation with the degree of milling, whiteness and germ retention rate in reasonably well milled rice. As observed by scanning electron microscopy (SEM), the difference in thickness between the dorsal and ventral regions of ‘Yexiang’ was the smallest. When the bran degree was about 2.00%, the ventral aleurone layer of the three types of rice was almost entirely removed, while much of the aleurone layer was remained in the dorsal part. When the bran degree was about 0.10%, a small amount of the dorsal aleurone layer was retained for ‘Daohuaxiang’ and ‘Jihong 6’, while the dorsal aleurone layer of ‘Yexiang’ was completely removed. Therefore, the milling degree required for uniform whitening of brown rice and the processing quality vary with cultivar and grain shape

Case Report: Mycobacterium kansasii causing infective endocarditis explored by metagenomic next-generation sequencing

In this report, we describe the first case of infective endocarditis caused by Mycobacterium kansasii in a 45-year-old male patient who presented with a 10-day fever and decompensated cirrhosis. Despite negative results in blood culture and pathology, we employed metagenomic next-generation sequencing (mNGS) to analyze the genome sequences of both the host and microbe. The copy number variation (CNV) indicated a high risk of liver disease in the patient, which correlated with biochemical examination findings. Notably, M. kansasii sequences were detected in peripheral blood samples and confirmed through Sanger sequencing. Unfortunately, the patient’s condition deteriorated, leading to his demise prior to heart surgery. Nevertheless, we propose that mNGS could be a novel approach for diagnosing M. kansasii infection, particularly in cases where blood culture and pathology results are unavailable. It is important to consider M. kansasii infection as a potential cause of endocarditis and initiate appropriate anti-infection treatment

Comparative transcriptome analyses of immune responses to LPS in peripheral blood mononuclear cells from the giant panda, human, mouse, and monkey

Gram-negative bacteria are major pathogens that can cause illnesses in giant pandas. Lipopolysaccharides (LPS), components of Gram-negative bacteria, can activate immune responses in mammals (i.e., humans and mice) through recognition by toll-like receptors (TLRs). However, the giant pandas’ immune response to LPS stimulation and the differences between the giant panda and other mammals are not fully known. In this study, we administrated peripheral blood mononuclear cells (PBMCs) from giant pandas, humans, C57BL/6 mice, and rhesus monkeys by LPS treatment at 6 h followed by RNA sequencing (RNA-seq), respectively, with control of non-stimulation. KEGG analyses of differentially expressed genes (DEGs) pathways indicated that LPS could activate the classic signaling pathway of NF-κB in PBMCs from those four tested species. Thus, similar to the other three species, NF-κB is an LPS-responsive regulator of innate immune responses in giant pandas. Furthermore, the expression patterns of adapter genes, inflammatory cytokine genes, chemokines, interferon genes, cytokine genes related to cell growth and development, costimulatory molecules, Th1/Th2 cytokine genes, Th17 cytokine genes, Th9, and Th22 cytokine genes were compared among giant pandas and three other species. Our data indicated that in addition to the similar expression patterns of certain genes among giant pandas and other species, the unique expression pattern response to LPS in giant pandas was also discovered. Furthermore, Th9, Th17, and Th22 cells might be involved in the response to LPS in giant pandas at this tested time point. This study reveals that LPS-induced immune responses have different sensitivities and response timelines in giant pandas compared with other mammals. This study facilitates further understanding of the role of the TLR signaling pathway and the immune system in giant pandas, which might be helpful for disease prevention and protection