Electrochemical Radical Tandem Difluoroethylation/Cyclization of Unsaturated Amides to Access MeCF2-Featured Indolo/Benzoimidazo [2,1-a]Isoquinolin-6(5H)-ones.

A metal-free electrochemical oxidative difluoroethylation of 2-arylbenzimidazoles was accomplished, which provided an efficient strategy for the synthesis of MeCF2-containing benzo[4,5]imidazo[2,1-a]-isoquinolin-6(5H)-ones. In addition, the method also enabled the efficient construction of various difluoroethylated indolo[2,1-a]isoquinolin-6(5H)-ones. Notably, this electrochemical synthesis protocol proceeded well under mild conditions without metal catalysts or exogenous additives/oxidants added.

Photopromoted Free Radical Silylation of 2-Aryl-2H-indazoles with Silanes.

Photoinduced silylation of silanes with 2-aryl-2H-indazoles was developed under mild conditions, which could efficiently result in diverse 3-silylated 2H-indazoles with good substrate scopes. A series of scaled-up to gram level and radical capture operations were performed in this system. Meanwhile, a bioactive molecule was tolerated well under typical conditions.

An ultrasensitive photoelectrochemical assay for tumor necrosis factor-alpha based on hollow CdS cubes as a signal generator and NiCo2O4-Au as a signal extinguisher.

Sensitive detection of tumor necrosis factor-alpha (TNF-α) in human serum is beneficial for finding cancer patients early due to overexpressed TNF-α being related to some cancers. Here, a photoelectrochemical (PEC) aptasensor was constructed for ultrasensitive TNF-α assay based on the signal generator of hollow CdS cubes (H-CdS) and the signal extinguishing activity of NiCo2O4-Au. In this work, compared with traditional solid CdS, H-CdS could greatly promote the PEC signal because its hollow structure could accelerate the separation of photogenerated charges, which also possesses abundant active sites and high light absorption capability. Moreover, H-CdS can be prepared facilely with Cd-based Prussian blue analogs as the precursor. Meanwhile, NiCo2O4-Au was fabricated and utilized as a signal extinguisher. In the presence of TNF-α, NiCo2O4-Au could be introduced onto the H-CdS modified electrode, producing competitive consumption of the electron donor effect, the p-n semiconductor quenching effect, and the mimetic enzymatic catalytic precipitation effect, which all can significantly reduce the PEC signal. Based on the signal extinguishing activity of NiCo2O4-Au and the signal generator of H-CdS, TNF-α can be detected sensitively with a lower detection limit (0.63 fg mL-1) and a wide linear range (1 fg mL-1- to 1 ng mL-1), which may have a potential application in the PEC bioanalysis field and the disease diagnostics field.

Clinicopathological Characteristics of Three Cases with Recurrent Orbital Solitary Fibrous Tumors: A Retrospective Study and Literature Review.

Objective: Solitary fibrous tumor (SFT) is a spindle cell neoplasm that rarely occurs in orbit. This study aimed to report the clinical, imaging, and pathological features of three patients with recurrent orbital SFTs. Methods: Clinical, imaging, and pathological data of the three patients were retrospectively reviewed, and the results were compared with those of previously reported cases with recurrent orbital SFT. Results: One female and two male patients (mean age, 54 years old) were included in this study. The present cases and literature review showed that the average time to recurrence in patients who aged under 50 years old was shorter than that in those who aged over 50 years old. The most common site for recurrent orbital SFT was the retrobulbar area of the orbit (23.8%). Imaging examinations showed consistent intensity of MRI signals before and after recurrence. Immunohistochemical results of all cases revealed the expressions of CD34. The mitotic rate increased in 4/8 cases, and the percentage of Ki-67-positive cells was elevated in 5/16 cases. Conclusion: These results suggested that young patients were more likely subjected to recurrent orbital SFT. The postoperative pathological diagnosis revealed that patients with recurrent orbital SFT had more nuclear abnormalities and mitotic activity, as well as a higher percentage of Ki-67-positive cells, indicating that orbital recurrent SFT tended to be malignant according to both morphological features and immunohistochemistry results.

Short-wavelength artificial light affects visual neural pathway development in mice.

Nearly all modern life depends on artificial light; however, it does cause health problems. With certain restrictions of artificial light emitting technology, the influence of the light spectrum is inevitable. The most remarkable problem is its overload in the short wavelength component. Short wavelength artificial light has a wide range of influences from ocular development to mental problems. The visual neuronal pathway, as the primary light-sensing structure, may contain the fundamental mechanism of all light-induced abnormalities. However, how the artificial light spectrum shapes the visual neuronal pathway during development in mammals is poorly understood. We placed C57BL/6 mice in three different spectrum environments (full-spectrum white light: 400-750 nm; violet light: 400 ± 20 nm; green light: 510 ± 20 nm) beginning at eye opening, with a fixed light time of 7:00-19:00. During development, we assessed the ocular axial dimension, visual function and retinal neurons. After two weeks under short wavelength conditions, the ocular axial length (AL), anterior chamber depth (ACD) and length of lens thickness, real vitreous chamber depth and retinal thickness (LLVR) were shorter, visual acuity (VA) decreased, and retinal electrical activity was impaired. The density of S-cones in the dorsal and ventral retinas both decreased after one week under short wavelength conditions. In the ventral retina, it increased after three weeks. Retinal ganglion cell (RGC) density and axon thickness were not influenced; however, the axonal terminals in the lateral geniculate nucleus (LGN) were less clustered and sparse. Amacrine cells (ACs) were significantly more activated. Green light has few effects. The KEGG and GO enrichment analyses showed that many genes related to neural circuitry, synaptic formation and neurotransmitter function were differentially expressed in the short wavelength light group. In conclusion, exposure to short wavelength artificial light in the early stage of vision-dependent development in mice delayed the development of the visual pathway. The axon terminus structure and neurotransmitter function may be the major suffering.

Recent advances in yeast genome evolution with stress tolerance for green biological manufacturing.

Green biological manufacturing is a revolutionary industrial model utilizing yeast as a significant microbial cell factory to produce biofuels and other biochemicals. However, biotransformation efficiency is often limited owing to several stress factors resulting from environmental changes or metabolic imbalance, leading to the slow growth of cells, compromised yield, and enhanced energy consumption. These factors make biological manufacturing competitively less economical. In this regard, minimizing the stress impact on microbial cell factories and strong robust performance have been an interesting area of interest in the last few decades. In this review, we focused on revealing the stress factors and their associated mechanisms for yeast in biological manufacturing. To improve yeast tolerance, rational and irrational strategies were introduced, and the molecular basis of genome evolution in yeast was also summarized. Furthermore, strategies of genome-directed evolution such as homology directed repair and nonhomologous end-joining, and the synthetic chromosome recombination and modification by LoxP-mediated evolution and their association with stress tolerance was highlighted. We hope that genome evolution provides new insights for solving the limitations of the natural phenotypes of microorganisms in industrial fermentation for the production of valuable compounds.

Functions of retinal astrocytes and Müller cells in mammalian myopia.

BACKGROUND: Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia is unknown. We aimed to explore the potential role and mechanism of retinal glial cells in form deprived myopia. METHODS: We adapted the mice form-deprivation myopia model by covering the right eye and left the left eye open for control, measured the ocular structure with anterior segment optical coherence tomography, evaluated changes in the morphology and distribution of retinal glial cells by fluorescence staining and western blotting; we also searched the online GEO databases to obtain relative gene lists and confirmed them in the form-deprivation myopia mouse retina at mRNA and protein level. RESULTS: Compared with the open eye, the ocular axial length (3.54 ± 0.006 mm v.s. 3.48 ± 0.004 mm, p = 0.027) and vitreous chamber depth (3.07 ± 0.005 mm v.s. 2.98 ± 0.006 mm, p = 0.007) in the covered eye became longer. Both glial fibrillary acidic protein and excitatory amino acid transporters 4 elevated. There were 12 common pathways in human myopia and anoxic astrocytes. The key proteins were also highly relevant to atropine target proteins. In mice, two common pathways were found in myopia and anoxic Müller cells. Seven main genes and four key proteins were significantly changed in the mice form-deprivation myopia retinas. CONCLUSION: Retinal astrocytes and Müller cells were activated in myopia. They may response to stimuli and secretory acting factors, and might be a valid target for atropine.

Enzyme-free fluorescence determination of uric acid by combining CdTe quantum dots with metal-organic framework for signal amplification.

The composite of CdTe quantum dots (QDs) with ZIF-8 was elaborately designed and synthesized as an enzyme-free fluorescent probe for the sensitive determination of uric acid (UA), based on the fluorescence detection property of CdTe QDs and the signal amplification function of ZIF-8. The structure and feature of the composite were characterized with transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, and fluorescence spectrometry. With adding UA to the composite, the emission of CdTe QDs reduced due to the inner filter and dynamic quenching effects of UA, and the adsorption ability of ZIF-8 toward UA promoted the response signal of CdTe QDs. On this basis, UA was quantified by the composite in the concentration range 0.05 to 10 µM with excitation/emission wavelength at 287/615 nm, and the detection limit of the composite toward UA was 32 nM. The reproducibility of the composite for determining UA was further evaluated, and the relative standard deviations were below 10.2%. The composite also exhibited the merits of enzyme-free analysis such as low testing cost, short analysis time (1 min), and loose pH condition (application in whole physiological pH range, 5.0 - 8.0). The composite was applied to the determination of UA in human urine with recoveries of spiked samples in the range 99 to 113%.

The effects of colour and temporal frequency of flickering light on variability of the accommodation response in emmetropes and myopes.

BACKGROUND: Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes. METHODS: We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz). RESULTS: Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes. CONCLUSIONS: These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.

Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection.

OBJECTIVE: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2-infected patients. METHODS: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse-transcription polymerase chain reaction (RT-PCR) assay. RESULTS: Twenty-one common-type and nine severe-type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. Fifty-eight samples from other patents were all negative. CONCLUSION: We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.

Relapsing viral keratoconjunctivitis in COVID-19: a case report.

BACKGROUND: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. CASE PRESENTATION: A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. CONCLUSIONS: In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.

A Zinc Metal-Organic Framework for Concurrent Adsorption and Detection of Uranium.

Uranium is one of the principal raw materials in the nuclear industry, but if released into the natural environment, it also poses latent health risks to mankind. Therefore, there is an urgent need to develop a strategy that can concurrently detect and adsorb uranium to realize the sustainable development of nuclear power and protect the environment. In this work, a fluorescent zinc-based metal-organic framework (HNU-50) was designed and synthesized for the effective detection and extraction of U(VI). The amide groups on N-pyridin-4-ylpyridine-4-carboxamide ligands and two uncoordinated carboxyl oxygen atoms on pyromellitic acid ligands in HNU-50 provide potential uranium-binding sites. Consequently, HNU-50 is competent of selectively and efficiently catching uranyl ions, achieving an optimum adsorption capacity of 632 mg/g. Additionally, the adsorption of U(VI) results in fluorescence quenching of HNU-50, thus allowing sensitive and selective detection of U(VI) by fluorescence change. Note that HNU-50 exhibits a considerably low detection limit of 1.2 × 10-8 M for U(VI) in aqueous solution, which is below the World Health Organization maximum pollution standards for potable water (6.3 × 10-8 M).

Effects of glyphosate on soybean metabolism in strains bred for glyphosate-resistance.

To produce high quality, glyphosate-resistant soybeans, we crossed Jinda 73 and glyphosate-resistant RR1 (Roundup Ready First Generation) (RR1) resulting in 34 hybrid strains. To determine the effects of glyphosate on soybean metabolism, we grew the two parents upto the seedling stage, and measured chlorophyll, soluble sugar, malondialdehyde (MDA), relative conductivity and proline. Then, we treated the plants with glyphosate and measured the same factors again. Results showed that the chlorophyll content of Jinda 73 and RR1 decreased after spraying glyphosate. Glyphosate increased the level of soluble sugar, MDA, relative conductivity and proline in Jinda 73, but had no significant effect on RR1. We determined glyphosate resistance of the parents and the 34 hybrid, offspring strains by documenting the growth response in the field after treatment with glyphosate. Results showed that 29 hybrid, offspring strains have complete glyphosate resistance. Polymerase chain reaction (PCR) shows that the strains which have complete resistance to glyphosate have imported the CP4 5-enolpyhruvylshikimate-3- phosphate synthase (CP4 EPSPS) gene successfully. We selected three high quality, glyphosate-resistant strains (F7-3, F7-16 and F7-21), which had higher protein and oil levels as compared with Jinda 73.

Neuroprotection and repair of 3'-blocking DNA ends by glaikit (gkt) encoding Drosophila tyrosyl-DNA phosphodiesterase 1 (TDP1).

Tyrosyl-DNA phosphodiesterase (TDP1) is a phylogenetically conserved enzyme critical for the removal of blocking lesions at the 3' ends of DNA or RNA. This study analyzes the Drosophila TDP1 gene ortholog glaikit (gkt) and its possible role(s) in the repair of endogenous DNA lesions and neuroprotection. To do so, we studied a homozygous PiggyBac insertion (c03958) that disrupts the 5' UTR of gkt. Protein extracts of c03958 flies were defective in hydrolyzing 3'-DNA-tyrosyl residues, demonstrating that gkt is the Drosophila TDP1. Although the mutant is generally healthy and fertile, females exhibit reduced lifespan and diminished climbing ability. This phenotype was rescued by neuronal expression of TDP1. In addition, when c03958 larvae were exposed to bleomycin, an agent that produces oxidative DNA damage, or topoisomerase I-targeted drugs (camptothecin and a noncamptothecin indenoisoquinoline derivative, LMP-776), survivors displayed rough eye patches, which were rescued by neuronal expression of TDP1. Our study establishes that gkt is the Drosophila TDP1 gene, and that it is critical for neuroprotection, normal longevity, and repair of damaged DNA.

MiR-204-5p may regulate oxidative stress in myopia.

The mechanisms underlying myopia remain not fully understood. We proposed to examine the function and underlying mechanisms of miR-204-5p in myopia development. The miR-204-5p expression level was assessed in the vitreous humor (VH) of a cohort consisting of 11 patients with high myopia (HM) and 16 control patients undergoing vitrectomy. Then the functional implications of miR-204-5p in ARPE-19 cells were assessed. Thioredoxin-interacting protein (TXNIP) was found as a possible target of miR-204-5p through mRNA sequencing, and its interaction with miR-204-5p was confirmed employing luciferase assay and western blotting. Furthermore, the miR-204-5p function in regulating oxidative stress was examined by measuring reactive oxygen species (ROS) accumulation. The results indicated a significant reduction of miR-204-5p in the VH of HM patients. Overexpression of miR-204-5p suppressed cell proliferation, migration, invasion, and apoptosis in ARPE-19 cells. The direct targeting of miR-204-5p on TXNIP has been confirmed, and its downregulation mediated the miR-204-5p impacts on ARPE-19 cells. Moreover, miR-204-5p overexpression significantly reduced ROS accumulation by targeting TXNIP. Our findings revealed the possible contribution of the miR-204-5p/TXNIP axis in myopia development by regulating oxidative stress, which may provide new targets to combat this prevalent and debilitating condition.

Stable dispersion of carbon nanotubes in a molten salt of KNO3-NaNO3-NaNO2-LiNO3-LiOH.

Carbon nanotubes (CNTs) have excellent mechanical and electrical properties; however, they suffer from dispersion problems in various applications. Traditional dispersing strategies of CNTs mostly use oxidation with strong acids or mechanical milling with high energy, which causes serious damage to the intrinsic structures and properties of CNTs. Therefore, it is important to develop new methods for dispersing CNTs without destroying their structures. This paper proposes to disperse CNTs in low-temperature molten salts composed of KNO3-NaNO3-NaNO2-LiNO3-LiOH. By adjusting the composition ratio of molten salts and alkaline, the interaction between charged ions and CNT electrons in the molten salt is studied. The alkaline molten salts can stably disperse CNTs and do not destroy their lengths, thereby offering better electric conductivity. This work will provide a new yet effective method for dispersing CNTs with high aspect ratios, which are important for the application of CNTs and other nanocarbons.

A highly sensitive SERS substrate of porous membrane-Ag NPs for kidney cancer detection.

BACKGROUND: The substrate employed in surface-enhanced Raman spectroscopy (SERS) constitutes an essential element in the cancer detection methodology. In this research, we introduce a three-dimensional (3D) structured SERS substrate that integrates a porous membrane with silver nanoparticles to enhance SERS spectral signals through the utilization of the aggregation effect of silver nanoparticles. This enhancement is crucial because accurate detection results strongly depend on the intensity of specific peaks in Raman spectroscopy. A highly sensitive SERS substrate can significantly improve the accuracy of detection results. RESULTS: We collected 66 plasma samples from individuals with kidney cancer and control individuals, including both bladder cancer patients and healthy individuals. Then, we utilized substrates with and without porous membranes to acquire the SERS spectra of the samples, enabling us to evaluate the enhancement effect of our SERS substrate. The spectral analysis demonstrated enhanced peak intensities in the experimental group (with porous substrate) compared to the control group (without porous substrate). The uniformity and reproducibility of the SERS substrate are also significantly enhanced, which is very helpful for improving the accuracy of detection results. Additionally, the Principal Component Analysis-Linear Discriminant Analysis algorithm (PCA-LDA) was employed to classify the SERS spectra of both groups. In the experimental group, the classification accuracy was 98.5 % for kidney cancer, and 83.3 % for kidney and bladder cancer. Compared to the control group, it improved by 3 % and 12.6 % respectively. SIGNIFICANT: This indicates that our 3D structured SERS substrate combined with multivariate statistical algorithms PCA-LDA can not only improve the accuracy of SERS detection technology in single cancer detection, but also has great potential in multiple cancer detection. This 3D structured SERS substrate is expected to become a new auxiliary means for cancer detection.

Review of molecular biological studies on acute lymphoblastic leukemia treated by modified shengmaiyin.

The objective was to explore the pharmacological mechanism of modified shengmaiyin (MSMY) in the treatment of acute lymphoblastic leukemia (ALL) by network pharmacology analysis. The effective components and predicted targets of MSMY were collected from TCMSP and Swiss target prediction databases, and the related targets of ALL were screened by GeneCards and DisGeNET. The core targets and related signaling pathways of MSMY active ingredients for the treatment of ALL were predicted by protein-protein interaction network (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. We identified 172 potential targets for the active components of MSMY, 538 disease targets associated with ALL, and 59 common gene targets. PPI network showed that 27 targets such as triptolide, RAC-alpha serine/threonine-protein kinase (AKT1), vascular endothelial growth factor A and Caspase-3 (CASP3) were the core targets. KEGG enrichment analysis related signaling pathways included cancer pathway, phosphatidylinositol 3 kinase, PI-3K/protein kinase B (PI3K-Akt) signaling pathway, apoptosis and mitogen-activated protein kinase (MAPK) signaling pathway and IL-17 signaling pathway. The effective active components and potential therapeutic targets of MSMY in the treatment of ALL were initially identified by comprehensive network pharmacology, which provides a theoretical basis for further study of the material basis and molecular mechanism of MSMY in the treatment of ALL.

Bifunctional ratiometric fluorescent probe for sensing anthrax spore biomarker and tetracycline at different excitation channels.

Multifunctional fluorescent probes have received increasing attention for the sake of atom economy and high-density integration. Herein, CdTe quantum dots (QDs) modified with Eu3+ were synthesized as the bifunctional ratiometric fluorescent probe for sensing two hazardous substances tetracycline (TC) and anthrax spore biomarker 2,6-dipicolinic acid (DPA) at different excitation channels, based on the discrepant excitation wavelengths of Eu3+ and the fluorescence quenching of CdTe QDs after interaction with them. Both DPA and TC enhanced the red emission of Eu3+ via antenna effect but caused the green emission of CdTe QDs to quench. Interestingly, the excitation wavelengths of Eu3+ after coordinating with DPA and TC were 275 and 386 nm, respectively. On this basis, CdTe QDs-Eu3+ achieved the bifunctional ratiometric detection of DPA (λex = 275 nm) and TC (λex = 386 nm) with different excitation channels. Both DPA and TC were selectively detected by CdTe QDs-Eu3+ with rapid response (DPA-1 min, TC-1 min) and high sensitivity (DPA-LOD 0.3 µM, TC-LOD 2.2 nM). CdTe QDs-Eu3+ were applied to analyzing DPA and TC in food, biological and environmental samples. Satisfactory spiked recoveries (80.0-119.0 %) and relative standard deviations (0.5-8.4 %) were obtained for measuring DPA and TC in these samples.