Chiral Bisphosphine-Catalyzed Asymmetric Staudinger/aza-Wittig Reaction: An Enantioselective Desymmetrizing Approach to Crinine-Type Amaryllidaceae Alkaloids.

An unprecedented chiral bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction of 2,2-disubstituted cyclohexane-1,3-diones is reported, enabling the facile access of a broad range of cis-3a-arylhydroindoles in high yields with excellent enantioselectivities. The key to the success of this work relies on the first application of chiral bisphosphine DuanPhos to the asymmetric Staudinger/aza-Wittig reaction. An effective reductive system has been established to address the challenging PV═O/PIII redox cycle associated with the chiral bisphosphine catalyst. In addition, comprehensive experimental and computational investigations were carried out to elucidate the mechanism of the asymmetric reaction. Leveraging the newly developed chemistry, the enantioselective total syntheses of several crinine-type Amaryllidaceae alkaloids, including (+)-powelline, (+)-buphanamine, (+)-vittatine, and (+)-crinane, have been accomplished with remarkable conciseness and efficiency.

The effects of hyaluronan and proteoglycan link protein 1 (HAPLN1) in ameliorating spinal cord injury mediated by Nrf2.

Excessive inflammatory response and oxidative stress (OS) play an important role in the pathogenesis of spinal cord injury (SCI). Balance of inflammation and prevention of OS have been considered an effective strategy for the treatment of SCI. Hyaluronan and proteoglycan link protein 1 (HAPLN1), also known as cartilage link protein, has displayed a wide range of biological and physiological functions in different types of tissues and cells. However, whether HAPLN1 regulates inflammation and OS during SCI is unknown. Therefore, we aimed to examine whether HAPLN1 can have a protective effect on SCI. In this study, both in vitro and in vivo SCI models were established. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays were used. Western blotting and enzyme-linked immunosorbent assay were employed to assess the expression of proteins. Our results demonstrate that the administration of HAPLN1 promoted the recovery of motor neurons after SCI by increasing the Basso mouse scale score, increasing the numbers of motor neurons, and preventing apoptosis of spinal cord cells. Additionally, HAPLN1 mitigated OS in spinal cord tissue after SCI by increasing the content of superoxide dismutase SOD and the activity of glutathione peroxidase but reducing the levels of malondialdehyde. Importantly, we found that HAPLN1 stimulated the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and stimulated the expression of heme oxygenase-1 and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1, which mediated the attenuation of HAPLN1 in activation of the NOD-like receptor protein 3 (NLRP3) inflammasome by reducing the levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1ß. Correspondingly, in vitro experiments show that the presence of HAPLN1 suppressed the NLRP3 inflammasome and prevented cell injury against H2O2 in PC12 cells. These effects were mediated by the Nrf2/ARE pathway, and inhibition of Nrf2 with ML385 abolished the beneficial effects of HAPLN1. Based on these findings, we conclude that HAPLN1 inhibits the NLRP3 inflammasome through the stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, enhancing motor neuronal survival, and improving the recovery of nerve function after SCI.

Enhancing students' agency in learning anatomy vocabulary with a formative intervention design.

One of the major challenges for health science students is the rapid acquisition of a new vocabulary in anatomy comprising several hundred new words. Research has shown that vocabulary learning can be improved when students are directed to vocabulary strategies. This paper reported a study with a formative intervention design inspired by Vygotsky's method of double stimulation. In this design, the students were put in a structured situation that invited them to identify the challenges in learning anatomy and then provided them with active guidance and a range of anatomy vocabulary learning strategies that scaffolded them to work out a solution to the challenge and develop their individualized anatomy learning resources. The data were collected from surveys, pre and postquiz results, and group discussion transcripts. The results revealed students perceived one of the main challenges in learning anatomy was learning, memorizing, and remembering many new words. A key finding in our study was that the formative intervention enhanced students' agency in creating resources for learning anatomy vocabulary. In addition, the development of their understanding showed a recursive form: from concrete experiences to abstract concepts and then to concrete new practices.

The renal artery-aorta angle associated with renal artery plaque: a retrospective analysis based on CT.

PURPOSE: To investigate the relationship between renal artery anatomical configuration and renal artery plaque (RAP) based on 320-row CT. METHODS: The abdominal contrast-enhanced CT data from 210 patients was retrospectively analyzed. Among 210 patients, there were 118 patients with RAP and 92 patients with no RAP. The anatomical parameters between lesion group and control group were compared and analyzed by using t-test, χ2-test and logistic regression analysis. RESULTS: (1) There were statistical differences on age, hypertension, diabetes, hypertriglyceridemia and hypercholesterolemia between lesion group and control group. (2) The differences on the distribution and type and of RAP between lesion group and control group were statistically significant. The most common position was the proximal, and the most common type was calcified plaque. (3)There were significant statistical differences on the proximal diameter of renal artery and renal artery-aorta angle A between lesion group and control group. The differences on the other anatomical factors between two groups were not statistically significant. (4) The result of logistic regression analysis showed that right RAP was related to age, hypertension and right renal artery angle A (the AUC of ROC = 0.82), and left RAP was related to high serum cholesterol, age and left renal artery angle A(the AUC of ROC = 0.83). (5) The RAP was associated with renal artery-aorta angle A, but the differences on distribution, type stability of RAP between R1 (L1) group and R2 (L2) group were not statistically significant. CONCLUSIONS: The RAP was associated with age, hypertension, hypercholesterolemia and renal artery-aorta angle A. Adults which had the greater renal artery-aorta angle A and the other above risk factors may be at increased risk for RAP.

Aqueous phase synthesis of ion-imprinted cryogel for paper-based colorimetric detection of As(V) with high selectivity.

A novel hydrophilic As(V) ion-imprinted cryogel (IIC) was green prepared by cryogelation in aqueous environment which was coincident with the adsorption condition and can improve the specific recognition performance. The methacrylamido propyl trimethyl ammonium chloride (MPTAC) was selected as the functional monomer and the saturated adsorption capacity of the prepared IIC and NIC were 55.0 mg/g and 29.4 mg/g, and with high imprinting factor of 1.87. Additionally, the prepared IIC showed admirable reusability and high selectivity, and the recovery was in the range 81.2-97.9% with RSD range of 1.9-4.3%, which was similar to the value obtained by hydride generation atomic absorption spectrometry. IIC can be used as solid material for colorimetric detection at the ultraviolet wavelength of 858 nm without color interference of material matrix, in the range 5-200 µg/L (R2 = 0.990) with a detection limit of 0.970 µg/L. Obviously, this synthetic strategy provides a simple, efficient, and green method for the preparation of water-compatible ion-imprinted polymers providing selective separation and detection of trace As(V) in real complex samples.

Effect of Thermal Processing on the Metabolic Components of Black Beans on Ultra-High-Performance Liquid Chromatography Coupled with High-Field Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.

Optical frequency-to-time mapping using a phase-modulated frequency-shifting loop.

A real-time spectral analysis is demonstrated experimentally with a frequency-shifting loop that includes an electro-optic phase modulator. When a single-frequency laser seeds the loop, pulse doublets are emitted if the integer Talbot condition is satisfied. With a polychromatic seed, frequency-to-time mapping is demonstrated, namely the temporal output of the loop maps the spectral power of the seed, with a resolution of 400 kHz. Due to the phase modulation function, the mapping is shown to be nonlinear. The results are in agreement with the theoretical predictions of [H. Yang et al., J. Opt. Soc. Am. B37, 3162 (2020)JOBPDE0740-322410.1364/JOSAB.389801]. The extension to integrated systems for applications is discussed.

Chemical trigger-enabled bioconjugation reaction.

Development of conceptually novel and practically useful bioconjugation reactions has been an intense pursuit of chemical biology research. Herein, we report an unprecedented bioconjugation reaction that hinges on a chemical trigger-enabled inverse-electron-demand Diels-Alder (IEDDA) cycloaddition of trans-cycloheptene (TCH) with tetrazine. Unlike the conventional strain-promoted bioconjugation reactions that utilize built-in strained alkenes as reactants, the current one features a "trigger-release-conjugate" reaction model, in which a highly strained TCH species is released from a bench-stable bicyclic N-nitrosourea (BNU) derivative upon treatment with an external stimulus. It is noteworthy that the reactivity-stability balance of BNU derivatives could be tuned by manipulating their N-1 substituents. As a proof-of-concept case, this new chemical trigger-enabled IEDDA reaction has been applied to in vitro protein labeling and pretargeted cell imaging. This work opens a new avenue to utilize BNU derivatives as a new class of chemical reporters in bioconjugate chemistry.

Recent advances in the synthesis of plakortin-type polyketides.

Plakortin-type polyketides represent a growing family of sponge-derived marine natural products that display notable structural and biological diversity. In particular, a series of polycyclic plakortin polyketides, namely hippolachnin A and gracilioethers, have been identified in recent years, which attract immense interest from the synthetic community owing to their unique molecular architectures and promising biomedical potential. A number of elegant total syntheses of these targets and some synthetic studies have been performed through either bio-inspired or rationally designed strategies. This focused review aims to provide an up-to-date summary of the progress in the chemical synthesis of plakortin polyketides, with an emphasis on the key synthetic elements enabling the rapid assembly of their core skeletons.

Helium Protects Against Lipopolysaccharide-Induced Cardiac Dysfunction in Mice via Suppressing Toll-Like Receptor 4-Nuclear Factor κB-Tumor Necrosis Factor-Alpha/ Interleukin-18 Signaling.

The nonanesthetic noble gas helium (He) can protect many organs against ischemia and reperfusion injury, such as liver and heart. However, the role of He on cardiac dysfunction during sepsis is not clear. In this study, we established a lipopolysaccharide (LPS)-induced cardiac dysfunction mouse model to examine the influence of He on the impaired cardiac function, and further investigated the possible innate immune mechanisms that may be involved. LPS induced left ventricular dysfunction and cavity enlargement, as indicated by decreased percent ejection fraction, percent fractional shortening, left ventricular anterior wall thickness in systole, and left ventricular posterior wall thickness in systole, while increased left ventricular end-systolic diameter and left ventricular end-systolic volume. He improved the impaired left ventricular function and cavity enlargement in a dose-dependent manner, and it was beneficial at 1.0 mL/100 g. Mechanistically, He inhibited toll-like receptor 4 (TLR4) expression, reduced the phosphorylation of nuclear factor κB (NF-κB), and subsequently alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) expression in heart. Therefore, He protects against LPS-induced cardiac dysfunction in mice partially via inhibiting myocardial TLR4-NF-κB-TNF-α/IL-18 signaling.

An Algorithm Based on Text Position Correction and Encoder-Decoder Network for Text Recognition in the Scene Image of Visual Sensors.

Text recognition in natural scene images has always been a hot topic in the field of document-image related visual sensors. The previous literature mostly solved the problem of horizontal text recognition, but the text in the natural scene is usually inclined and irregular, and there are many unsolved problems. For this reason, we propose a scene text recognition algorithm based on a text position correction (TPC) module and an encoder-decoder network (EDN) module. Firstly, the slanted text is modified into horizontal text through the TPC module, and then the content of horizontal text is accurately identified through the EDN module. Experiments on the standard data set show that the algorithm can recognize many kinds of irregular text and get better results. Ablation studies show that the proposed two network modules can enhance the accuracy of irregular scene text recognition.

Polarization effects in nonlinear interference of down-converted photons.

We study polarization effects in the nonlinear interference of photons generated via frequency nondegenerate spontaneous parametric-down conversion. Signal and idler photons, which are generated in the visible and infrared (IR) range, respectively, are split into different arms of a nonlinear Michelson interferometer, and the interference pattern for signal photons is detected. Due to the effect of induced coherence, the interference pattern for the signal photons depends on the polarization rotation of idler photons, which are introduced by a birefringent sample. Based on this concept, we realize two new methods of measuring sample retardation in the IR range by using well-developed and inexpensive components for visible light. The methods' accuracy reaches specifications that are reported for industrial-grade optical elements. The developed IR polarimetry technique is relevant to material research, optical inspection, and quality control.

Pulse doublets generated by a frequency-shifting loop containing an electro-optic amplitude modulator.

We investigate theoretically and experimentally an all-fibered frequency-shifting loop which includes an electro-optic amplitude modulator (EOM) and an optical amplifier, and is seeded by a continuous-wave laser. At variance with frequency-shifted feedback lasers, or Talbot lasers, that contain an acousto-optic frequency shifter, the EOM creates at each round-trip two side-bands that recirculate inside the loop. Benefiting from the high modulation frequency of the EOM, a wide optical frequency comb up to 40 GHz is generated. We demonstrate an original double-pulse regime when the loop length is a multiple of the RF modulation wavelength applied to the modulator. The inter-pulse interval is governed by both the bias voltage and modulation depth of the EOM. Besides, some typical waveforms such as saw-tooth and rectangle are experimentally obtained by properly setting operating frequency, bias voltage and the RF power. The system is modeled by a linear interference model that takes the amplitude modulation function and loop delay into account. The model explains the formation of pulse doublets and reproduces well all the experimental waveforms. Furthermore, the un-seeded loop driven above threshold also generates mode-locked picosecond pulse doublets with a continuously adjustable delay up to the modulation period.

A Ratiometric Fluorescent Sensor for Cd2+ Based on Internal Charge Transfer.

This work reports on a novel fluorescent sensor 1 for Cd2+ ion based on the fluorophore of tetramethyl substituted bis(difluoroboron)-1,2-bis[(1H-pyrrol-2-yl)methylene]hydrazine (Me4BOPHY), which is modified with an electron donor moiety of N,N-bis(pyridin-2-ylmethyl)benzenamine. Sensor 1 has absorption and emission in visible region, at 550 nm and 675 nm, respectively. The long wavelength spectral response makes it easier to fabricate the fluorescence detector. The sensor mechanism is based on the tunable internal charge transfer (ICT) transition of molecule 1. Binding of Cd2+ ion quenches the ICT transition, but turns on the π - π transition of the fluorophore, thus enabling ratiometric fluorescence sensing. The limit of detection (LOD) was projected down to 0.77 ppb, which is far below the safety value (3 ppb) set for drinking water by World Health Organization. The sensor also demonstrates a high selectivity towards Cd2+ in comparison to other interferent metal ions.

Total synthesis and preliminary SAR study of (±)-merochlorins A and B.

A modular synthesis of merochlorins A and B, two naturally occurring antibiotics, has been achieved concisely from readily available building blocks in 4-6 steps. The key steps include the bio-inspired tandem phenol oxidative dearomatization/[5 + 2] and [3 + 2] cycloadditions to construct the tricyclic cores of the targets, and the intermolecular Diels-Alder reaction followed by dehydrogenative aromatization to assemble the remaining aromatic units. The antibacterial activities of merochlorins A, B and some advanced synthetic intermediates were also evaluated, which provided valuable information on the structure-activity relationship (SAR) of this class of new antibiotics.

A Cu2+-Selective Probe Based on Phenanthro-Imidazole Derivative.

A novel fluorescent Probe 1, based on phenanthro-imidazole has been developed as an efficient chemosensor for the trace detection of copper ions (Cu2+). Probe 1 demonstrated sensitive fluorescence quenching upon binding with Cu2+ through 1:1 stoichiometric chelation. The detection limit for Cu2+ ions was projected through linear quenching fitting to be as low as 2.77 × 10-8 M (or 1.77 ppb). The sensing response was highly selective towards Cu2+ with minimal influence from other common metal ions, facilitating the practical application of Probe 1 in trace detection.

Correlation between Traditional Chinese Medicine symptom patterns and serum concentration of zinc, iron, copper and magnesium in patients with hepatitis B and associated liver cirrhosis.

OBJECTIVE: To investigate the correlation between the patterns of Traditional Chinese Medicine (TCM) syndromes and the serum concentration of zinc, iron, copper and magnesium of patients with chronic hepatitis B (CHB) and hepatitis B virus (HBV)-induced liver cirrhosis. METHODS: A total of 86 patients were included in the study between March 1, 2009 and January 1, 2010. All were diagnosed with CHB or HBV-induced liver cirrhosis according to the diagnosis standard of the Chinese Medical Association. Fasting serum concentrations of zinc, iron, copper and magnesium were measured. Patients were classified into different patterns of TCM symptoms according to TCM theory and clinical experience. RESULTS: In the HBV-induced liver cirrhosis group, the mean zinc concentration in patients with the TCM pattern of stagnation of fluid-Dampness was lower than that in patients with obstruction of collaterals by Blood stasis (P < 0.034). In the CHB group, the mean magnesium concentration in patients with toxic Heat flourishing was significantly lower than that in those with Damp-Heat in the Liver and Gallbladder, and those with Liver depression and Spleen deficiency (P < 0.021). The concentrations of iron and copper showed little difference among the different TCM symptom patterns. CONCLUSION: The serum zinc and magnesium concentrations correlated with certain TCM patterns of symptoms in patients with HBV-induced liver cirrhosis and CHB. It may be helpful to interpret the pathogenic change in the TCM symptom patterns in liver cirrhosis and CHB, and also to conduct clinical treatment of the diseases based on identified TCM patterns.

Clinicopathological significance of RUNX3 gene hypermethylation in hepatocellular carcinoma.

Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors including hepatocellular carcinoma (HCC). However, the correlation between RUNX3 hypermethylation and incidence of HCC remains unclear. Here, we conducted a systematic review and meta-analysis aiming to comprehensively assess the potential role of RUNX3 hypermethylation in the pathogenesis of HCC. A detailed literature search was made from PubMed, EMBASE, and ISI web of knowledge to identify studies for related research publications. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed. Odds ratio (OR) was calculated and summarized, respectively. Final analysis of 821 HCC patients from 14 eligible studies was performed. We observed that RUNX3 hypermethylation was significantly higher in HCC than in normal liver tissue, the pooled OR from eight studies including 382 HCC and 161 normal liver tissue (OR = 39.32, 95 % confidence interval (CI) = 13.72-112.7, p < 0.00001). The pooled analysis showed significantly increased OR of RUNX3 hypermethylation (OR = 5.4, 95 % CI = 2.06-14.17, p < 0.00001) in HCC tissues and non-tumor liver tissues. In addition, statistically significant OR of RUNX3 hypermethylation was obtained from non-tumorous liver tissue of HCC patients and normal liver tissue (OR = 12.57, 95 % CI = 3.56-44.35, p < 0.0001). The results of this meta-analysis suggest that RUNX3 hypermethylation may be implicated in the pathogenesis of HCC. Thus, detection of RUNX3 hypermethylation may be a helpful and valuable biomarker for diagnosis of HCC.

[Prevention and treatment mechanism of qingxia therapy (based on yinchenhao decoction and dachengqi decoction) on hepatocyte apoptosis in rats with acute hepatic injury induced by lipopolysaccharide/D-galactosamine].

OBJECTIVE: To study the prevention and treatment mechanism of Qingxia therapy (based on Yinchenhao Decoction and Dachengqi Decoction) on hepatocyte apoptosis in rats with acute hepatic injury induced by lipopolysaccharide plus D-galactosamine (LPS/D-GalN). METHODS: The acute hepatic injury model was established by LPS/D-GalN and then intervened with Qingxia therapy. Serum liver function, PT and liver tissue pathology were observed, hepatocyte apoptosis index was detected by Tunel, protein expressions of BCL-2, BAX and Caspase-3 were detected by Western blotting. RESULTS: Qingxia therapy could significantly decrease serum ALT, AST and TBIL levels (P < 0.01 or 0.05), reduce hepatocyte necrosis and inflammatory cell infiltration. There were more apoptotic cells in model group, which had significant differences compared with Qingxia group and control group. Protein expressions of BAX and Caspase-3 in model group were significantly higher than those in control group and Qingxia group (P < 0.05), but BCL-2 protein expression in model group was lower (P < 0.05). CONCLUSION: Qingxia therapy can ameliorate the liver function and hepatic tissue pathology of rats with hepatic injury induced by LPS/D-GalN, alleviate hepatocyte apoptosis in rats, prevent and treat hepatocyte apoptosis by down-regulating the protein expressions of Caspase-3 and BAX, up-regulating the protein expression of BCL-2, and adjusting the balance of BCL-2/BAX.