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The Euphorbiaceae plant Euphorbia neriifolia L. is distributed widely in India, Thailand, Southeastern China, and Taiwan and used as a carminative and expectorant to treat several inflammation-related diseases, such as gonorrhoea, asthma, and cancer. In the course of our search for potential anti-inflammatory agents from the titled plant, 11 triterpenes from the stem of E. neriifolia were isolated and reported in our previous endeavor. Given its rich abundance in triterpenoids, the ethanolic extract in this follow-up exploration has led to the isolation of additional eight triterpenes, including six new euphanes—neritriterpenols H and J–N (1 and 3–7)—one new tirucallane, neritriterpenol I (2), and a known compound, 11-oxo-kansenonol (8). Their chemical structures were elucidated on the basis of spectroscopic data, including 1D- and 2D NMR, and HRESIMS spectra. The absolute stereochemistry of neritriterpenols was determined by single-crystal X-ray diffraction analysis, ICD spectra, and DP4+ NMR data calculations. Compounds 1–8 were also evaluated for their anti-inflammatory activity by using lipopolysaccharide (LPS)-stimulated IL-6 and TNF-α on RAW 264.7 macrophage cells. Intriguingly, the euphane-type triterpenes (1 and 3–8) showed an inhibitory effect on LPS-induced IL-6 but not on TNF-α, while tirucallane-type triterpene 2 showed strong inhibition on both IL-6 and TNF-α.

The coronavirus disease 2019 (COVID-19) pandemic continues to represent a challenge for public health globally since transmission of different variants of the virus does not seem to be effectively affected by the current treatments and vaccines. During COVID-19 the outbreak in Taiwan, the patients with mild symptoms were improved after the treatment with NRICM101, a traditional Chinese medicine formula developed by our institute. Here, we investigated the effect and mechanism of action of NRICM101 on improval of COVID-19-induced pulmonary injury using S1 subunit of the SARS-CoV-2 spike protein-induced diffuse alveolar damage (DAD) of hACE2 transgenic mice. The S1 protein induced significant pulmonary injury with the hallmarks of DAD (strong exudation, interstitial and intra-alveolar edema, hyaline membranes, abnormal pneumocyte apoptosis, strong leukocyte infiltration, and cytokine production). NRICM101 effectively reduced all of these hallmarks. We then used next-generation sequencing assays to identify 193 genes that were differentially expressed in the S1+NRICM101 group. Of these, three (Ddit4, Ikbke, Tnfaip3) were significantly represented in the top 30 enriched downregulated gene ontology (GO) terms in the S1+NRICM101 group versus the S1+saline group. These terms included the innate immune response, pattern recognition receptor (PRR), and Toll-like receptor signaling pathways. We found that NRICM101 disrupted the interaction of the spike protein of various SARS-CoV-2 variants with the human ACE2 receptor. It also suppressed the expression of cytokines IL-1β, IL-6, TNF-α, MIP-1β, IP-10, and MIP-1α in alveolar macrophages activated by lipopolysaccharide. We conclude that NRICM101 effectively protects against SARS-CoV-2-S1-induced pulmonary injury via modulation of the innate immune response, pattern recognition receptor, and Toll-like receptor signaling pathways to ameliorate DAD.

Abstract Inorganic nitrate production is critical in atmospheric chemistry that reflects the oxidation capacity and the acidity of the atmosphere. Here we use the oxygen anomaly of nitrate (Δ17O( $$\rm{NO}_{3}^{-}$$ NO 3 − )) in high-time-resolved (3 h) aerosols to explore the chemical mechanisms of nitrate evolution in fine particles during the winter in Nanjing, a megacity of China. The continuous Δ17O( $$\rm{NO}_{3}^{-}$$ NO 3 − ) observation suggested the dominance of nocturnal chemistry (NO3 + HC/H2O and N2O5 + H2O/Cl−) in nitrate formation in the wintertime. Significant diurnal variations of nitrate formation pathways were found. The contribution of nocturnal chemistry increased at night and peaked (72%) at midnight. Particularly, nocturnal pathways became more important for the formation of nitrate in the process of air pollution aggravation. In contrast, the contribution of daytime chemistry (NO2 + OH/H2O) increased with the sunrise and showed a highest fraction (48%) around noon. The hydrolysis of N2O5 on particle surfaces played an important role in the daytime nitrate production on haze days. In addition, the reaction of NO2 with OH radicals was found to dominate the nitrate production after nitrate chemistry was reset by the precipitation events. These results suggest the importance of high-time-resolved observations of Δ17O( $$\rm{NO}_{3}^{-}$$ NO 3 − ) for exploring dynamic variations in reactive nitrogen chemistry.

Aiming at providing an efficient hardware architecture for generalized spatial modulation (GSM) multiple-input multiple-output (MIMO) systems, in this paper a COordinate Rotation DIgital Computer (CORDIC) -based symbol detector is proposed. In the proposed detector, several CORDIC-based Givens rotation modules are conducted in parallel for the transmit antenna combinations (TACs) to facilitate QR-decomposition. After that, the proposed detector uses adders, shifters, and backward substitution mechanisms to currently estimate symbols for the corresponding TAC. At last, the estimated symbols and corresponding TAC index with the smallest distance measurement are chosen as the final solution. In particular, to achieve efficient hardware implementation, the architecture of the proposed detector has several features, including multiplication-free ranking mechanism, parallel CORDIC-based architectures, and shorter-bit-length multipliers. In addition, the overall architecture is pipelined to speed up the processing of the hardware. At last, computer simulations and hardware implementation are conducted under the configuration of four transmit, two active transmit, and four receive antennas. Simulation results reveal the proposed detector performs near to the optimal maximum likelihood (ML), but uses lower computational complexity. Additionally, the VLSI implementation results under the TSMC 90-nm CMOS technology show that the proposed hardware architecture requires 266K gates (KGEs), provides detection throughput 2.008 Gbps, works with pre-processing latency of 47 clock cycles, and has the hardware efficiency 7.54 (Mbps/KGEs) while operating at frequency 200.8 MHz. Moreover, implementation comparisons show the proposed architecture provides high throughput rate as well as hardware efficiency, and works with low pre-processing latency.

IntroductionKawasaki disease (KD) may increase the risk of myocardial infarction or sudden death. In children, delayed KD diagnosis and treatment can increase coronary lesions (CLs) incidence by 25% and mortality by approximately 1%. This study focuses on the use of deep learning algorithm-based KD detection from cardiac ultrasound images.MethodsSpecifically, object detection for the identification of coronary artery dilatation and brightness of left and right coronary artery is proposed and different AI algorithms were compared. In infants and young children, a dilated coronary artery is only 1-2 mm in diameter than a normal one, and its ultrasound images demonstrate a large amount of noise background-this can be a considerable challenge for image recognition. This study proposes a framework, named Scaled-YOLOv4-HarDNet, integrating the recent Scaled-YOLOv4 but with the CSPDarkNet backbone replaced by the CSPHarDNet framework.ResultsThe experimental result demonstrated that the mean average precision (mAP) of Scaled-YOLOv4-HarDNet was 72.63%, higher than that of Scaled YOLOv4 and YOLOv5 (70.05% and 69.79% respectively). In addition, it could detect small objects significantly better than Scaled-YOLOv4 and YOLOv5.ConclusionsScaled-YOLOv4-HarDNet may aid physicians in detecting KD and determining the treatment approach. Because relatively few artificial intelligence solutions about images for KD detection have been reported thus far, this paper is expected to make a substantial academic and clinical contribution.

Mesonaprocumbens Hemsley is a plant conventionally processed to provide popular food materials and herbal medicines in Asia. In this study, six triterpene acids, including five new ones (mesonaic acids D-H, 1–5), and one proximadiol-type sesquiterpene (7) were isolated from the methanolic extract of the air-dried M. procumbens. Chemical structures of 1‒7 were established by spectroscopic methods, especially 2D NMR techniques (1H–1H COSY, HSQC, HMBC, and NOESY) and HRESIMS. Concerning their biological activities, compounds 1, 2, 6, and 7 were examined manifesting high inhibition toward the pro-inflammatory NO production with EC50 values ranging from 12.88 to 21.21 µM, outrunning the positive control quercetin (24.12 µM). The mesoeudesmol B (7) identified from M. procumbens is the very first example, which exhibited high anti-inflammatory activity diminishing the level of the lipopolysaccharide-induced NO in RAW264.7 macrophage cells, thereby suppressing the secretion of pro-inflammatory cytokines TNF-α and IL-6 and the level of two critical downstream inflammatory mediators iNOS and COX-2.

This research explores the GPT-2 deep learning model for economic news generation and evaluation. After training GPT-2 by about 300,000 pieces of news with a total of 150 million words, 15 news articles are generated by GPT-2. Together with 15 real news articles written by journalists, 12 subjects were invited to judge the credibility of the 30 news articles with 1 to 5 scales. As a result, 8 subjects who graduated from economic-related major were more capable of discriminating the human- composed news (HCN) from the computer-generated news (CGN); while 4 subjects who graduated from non-economic related major had poor discriminating ability, and one was even unable to tell the HCN from the CGN. Among the 15 HCN articles, 1 was rated as non-genuine news, with an average credibility of 2.92, which is less than 3, due to lack of logic and strong subjectivity. Among the 15 CGN articles, 2 were rated as genuine news, with average credibility of 3.33, which is greater than 3, because the content is reasonable and the details are logical. After comparing these two articles with the corpus, it is found that the computer’s ability to substitute and retouch can deceive professionals. However, most of the CGN articles have been spotted, mainly because of obvious flaws in facts and incorrect digits such as dates and stock codes. The research also explores the possibility of automatically detecting computer-generated news using BERT-based neural network model. As a result, BERT had only 2 false predictions out of the above 30 news articles. Compared with the collective prediction by the 12 subjects with 5 errors, BERT performs better. Further large-scale experiments show that the effectiveness of BERT can reach an F-score of 0.96. (Article content in Chinese with English extended abstract)

Objectives: The resistance ofmcr-1-carrying Enterobacteriaceae to polymyxins, which are last-resort antibiotics, has raised great concern worldwide. In this study, four mcr-1-carrying plasmids isolated from Klebsiella pneumoniae clinical isolates were completely sequenced and the genome composition of the mcr-1-carrying plasmids was analysed. Methods: Antimicrobial resistance genes and antimicrobial susceptibility of fourmcr-1-carrying K. pneumoniae isolates were characterised. Comparison of mcr-1-carrying plasmids with closely related plasmids and analysis of the mcr-1 gene cassette were performed. Results: The genome composition of the fourmcr-1-carrying plasmids revealed the Tn6330 and Tn6390 cassettes embedded in two IncHI1-type plasmids, ΔTn6330 in an IncHI2-type plasmid, and mcr-1–pap2 in an IncX4-type plasmid. We also predicted the intermediate structures of the Tn6330 and Tn6390 cassettes. Conclusion: Dissemination of the colistin resistant genemcr-1 in Taiwan could have been driven by various plasmids and mobile gene cassettes. Evolution of the genetic environment has led to diversity in the mcr-1 gene among plasmids. This work sheds light on the urgent need for continued surveillance of the worldwide distribution of mcr-1 and evaluates the public-health risk of colistin resistance.

Four novel triterpene glycosides, taimordisins A–D (1–4), were discovered from fresh fruits of Taiwanese Momordica charantia. The chemical framework and relative stereochemistry of these four natural products were isolated, purified, and determined by using various separation and spectroscopy techniques. Each of them features a unique bicyclic-fused or trifuso-centro-fused ring system. Notably, 1 and 2 are cucurbitane-based compounds possessing a new C-24 and C-2″ carbon–carbon linkage with 5-hydroxy-2-(hydroxymethyl)tetrahydro-4H-pyran-4-one and 6-(hydroxymethyl)tetrahydro-4H-pyran-3,4,4-triol units, respectively, and represented an unprecedented molecular skeleton. In terms of biosynthesis, they all originate from a common precursor 3-hydroxycucurbita-5,24-dien-19-al-7,23-di-O-β-glucopyranoside. Of two sugar moieties, the one at 23-O-β-glucopyranoside grants each individual congener uniqueness likely through microbial symbiont-mediated intramolecular transformation into two major types of furo[2,3-b]pyranone and furo[3,2-c]pyranone derivatives. These new products possess desirable anti-inflammatory biological activities in addition to being generally regarded as safe.

Fossil fuel carbon dioxide (FFCO2) is a major source of atmospheric greenhouse gases that result in global climate change. Quantification of the atmospheric concentrations and emissions of FFCO2 is of vital importance to understand its environmental process and to formulate and evaluate the efficiency of carbon emission reduction strategies. Focusing on this topic, we summarized the state-of-the-art method to trace FFCO2 using radiocarbon (14C), and reviewed the 14CO2 measurements and the calculated FFCO2 concentrations conducted in the last two decades. With the mapped-out spatial distribution of 14CO2 values, the typical regional distribution patterns and their driving factors are discussed. The global distribution of FFCO2 concentrations is also presented, and the datasets are far fewer than 14CO2 measurements. With the combination of 14C measurements and atmospheric transport models, the FFCO2 concentration and its cross-regional transport can be well interpreted. Recent progress in inverse methods can further constrain emission inventories well, providing an independent verification method for emission control strategies. This article reviewed the latest developments in the estimation of FFCO2 and discussed the urgent requirements for the control of FFCO2 according to the current situation of climate change.

A phytochemical investigation of the leaves and twigs of Glycosmis pentaphylla (Rutaceae), collected in Vietnam, yielded three new compounds named glyfuran (1), glyphyllamide (2), and glyphyllazole (3), along with twenty-five known compounds (4–28). The structures of isolates were determined by IR, MS, NMR, and UV data analyses. In the anti-diabetic activity screening, (+)-isoaltholacton (4), glycoborinine (17), 2′,4′-dihydroxy-4,6′-dimethoxychalcone (24), and flavokawain A (25) simultaneously exhibited inhibition of dipeptidyl peptidase-4 (DPP4) and stimulation of the glucagon-like peptide-1 (GLP-1) secretion on the murine intestinal secretin tumor cell line (STC-1).

Abstract Larvae of the cosmopolitan family Limacodidae, commonly known as “slug” caterpillars, are well known because of the widespread occurrence of spines with urticating properties, a morpho‐chemical adaptive trait that has been demonstrated to protect the larvae from natural enemies. However, while most species are armed with rows of spines (“nettle” caterpillars), slug caterpillars are morphologically diverse with some species lacking spines and thus are nonstinging. It has been demonstrated that the evolution of spines in slug caterpillars may have a single origin and that this trait is possibly derived from nonstinging slug caterpillars, but these conclusions were based on limited sampling of mainly New World taxa; thus, the evolution of spines and other traits within the family remains unresolved. Here, we analyze morphological variation in slug caterpillars within an evolutionary framework to determine character evolution of spines with samples from Asia, Australia, North America, and South America. The phylogeny of the Limacodidae was reconstructed based on a multigene dataset comprising five molecular markers (5.6 Kbp: COI, 28S, 18S, EF‐1α, and wingless) representing 45 species from 40 genera and eight outgroups. Based on this phylogeny, we infer that limacodids evolved from a common ancestor in which the larval type possessed spines, and then slug caterpillars without spines evolved independently multiple times in different continents. While larvae with spines are well adapted to avoiding generalist predators, our results imply that larvae without spines may be suited to different ecological niches. Systematic relationships of our dataset indicate six major lineages, several of which have not previously been identified.

AIM: To evaluate the effects of visual perceptual learning on visual representation and binocular vision function of children with amblyopia. METHODS: A total of 94 cases(94 eyes)children with amblyopia admitted to the ophthalmology clinic of our hospital from January 2014 to December 2015 were selected for the study and were grouped according to the degrees of amblyopia, and they were given visual perceptual learning for 3mo. The clinical efficacy and perceptual level of eye position and poor visual acuity before and after treatment were compared among groups, and Pearson correlation coefficient was used to analyze the relationship between difference of poor visual acuity and difference of perceptual eye position before and after treatment in children with amblyopia. RESULTS: The total clinical effective rate of children with mild amblyopia was higher than that of children with moderate or severe amblyopia(PP>0.05). The perception level of eye position after treatment of children with amblyopia was significantly lower than that before treatment(PPPPPPr=0.371, PCONCLUSION: Visual perceptual learning can effectively improve the visual representation and binocular vision function of children with amblyopia, and it is suitable for the clinical treatment of children with amblyopia.

Mesona procumbens is a popular material used in foods and herbal medicines in Asia for clearing heat and resolving toxins. However, phytochemical research on this plant is very rare. In this study, eleven new diterpenoids, mesonols A-K (1–11), comprising seven ent-kauranes, three ent-atisanes, and one sarcopetalane, were isolated from its methanolic extract. Structural elucidation of compounds 1–11 was performed by spectroscopic methods, especially 2D NMR, HRESIMS, and X-ray crystallographic analysis. All isolates were assessed for their antiproliferative activity, and compounds 1–4 showed potential antiproliferative activities against A549, Hep-3B, PC-3, HT29, and U937 cancer cells, with IC50 values ranging from 1.97 to 19.86 µM. The most active compounds, 1 and 2, were selected for further investigation of their effects on cell cycle progression, apoptosis, and ROS generation in U937 human leukemia cancer cells. Interestingly, it was found that compounds 1 and 2 induced antiproliferative effects in U937 cells through different mechanisms. Compound 1 caused cell cycle arrest at the G2/M phase and subsequent cell death in a dose- and time-dependent manner. However, 2-mediated antiproliferation of U937 cells triggered ROS-mediated mitochondrial-dependent apoptosis. These results provide insight into the molecular mechanism involved in the antiproliferative activities of compounds 1 and 2 in U937 cells. Altogether, the study showed that new diterpenoid compounds 1 and 2 from M. procumbens are potent and promising anticancer agents.

Millettia pulchra is traditionally used for treating diseases, including joint pain, fever, anemia, and allergies. It is also a potential resource of natural flavonoid derivatives, which represents major constituents of this plant. This study aimed to isolate the major compounds from M. pulchra radix, develop and validate the HPLC-PDA method to determine their contents, and optimize its extraction. Four major flavonoid derivatives (karanjin, lanceolatin B, 2”,2”-dimethylpyrano-[5″,6″:7,8]-flavone, and pongamol) were isolated using silica gel column chromatography, crystallization techniques in large amounts with high purities (>95%). A simple, accurate high-performance liquid chromatography–photodiode array (HPLC–PDA) detection method has been developed and validated with significantly statistical impacts according to International Conference on Harmonization (ICH) guidelines. The Response Surface Methodology (RSM), Artificial Neural Network (ANN) models were employed to predictive performance and optimization of the extraction process. The optimized conditions for the extraction of major flavonoids were: extraction time (twice), solvent/material ratio (9.5), and ethanol concentration (72.5%). Our research suggests an effective method, which will be helpful for quality control in the pharmaceutical development of this species.

Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins O–R (1–4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC50 of 14.7 and 25.1 μM, respectively.

Plants of the genus Callicarpa are known to possess several medicinal effects. The constituents of the Taiwan endemic plant Callicarpa hypoleucophylla have never been studied. Therefore, C. hypoleucophylla was selected for our phytochemical investigation. Two new clerodane-type diterpenoids, named callihypolins A (1) and B (2), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant C. hypoleucophylla and then characterized. The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds 1–9 based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds 2–4 showed anti-inflammatory activity (9.52−32.48% inhibition at the concentration 10 μm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus Callicarpa but also highlight the possibility of developing anti-inflammatory agents from Callicarpa endemic species.

In folk medicine, Stahlianthus thorelii Gagnep. has been used to treat diseases related to inflammation, ulcers, and cancer. There are no reports concerning the chemical components and bioactivities of S. thorelii; thus, this study aims to explore the phytochemicals, quantify the main compounds, and test the anticancer activity of isolates from S. thorelii. Dried rhizomes were extracted with 95% ethanol and, then, partitioned, fractionated, and isolated. On the basis of the result of the antiproliferative activity of the fractions, seven isolates were yielded and were identified by spectroscopic analyses. The inhibition of cancer proliferation was determined by an MTT assay and the deployed IC50 to value their efficacy. Seven compounds containing one new C-benzylated dihydrochalcone derivative, thorechalcone A (1) and 2−7 were isolated from S. thorelii. In terms of the bioactivity, compounds 1 and 3 displayed promising antiproliferative activity (WiDr, A549, and HepG2), with IC50 values 3 and 4) was also validated. This study presented the isolations of antiproliferative potentials of new chalcone and known flavonoid derivatives from S. thorelii. The validated simple, accurate, and rapid HPLC method could be deployed for the quality control of herbal drugs.

Two new nitrogen-containing verticillene diterpenoids, cespilamides A and B (1 and 2), three new nitrogen-containing sesquiterpenoids, cespilamides C–E (3–5), and five new norverticillene and verticillene diterpenoids, cespitaenins A–E (6–10), were isolated from the Taiwanese soft coral Cespitularia taeniata. Compound 1 possesses an unusual oxazo ring system at C-10 while compound 2 displays an unprecedented C–C bond cleavage between C-10 and C-11 with an N-ethylphenyl group at C-10. Biogenetic pathways of 1 and 2 are proposed. The absolute configuration of 1 was confirmed by Mosher’s method and molecular mechanics calculations (MM2). The cytotoxicities of compounds 1–10 were evaluated against a small panel of human cancer cell lines.

Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells.

Six new dammarane-type saponins, gypenosides CP1-6 (1–6), along with 19 known compounds 7–25, were isolated and characterized from the aerial parts of Gynostemma pentaphyllum. Among these compounds, eight dammarane-type saponins, 2, 5, 6, 7, 11, 12, 13, and 15, exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).

Nine new derivatives of oleanane triterpenoids isolated from Fatsia polycarpa Hayata were synthesized through chemical transformations. Acetylation was effected by reaction with acetic anhydride in pyridine to afford compounds 1–5, while compound 6 was obtained using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) in CH2Cl2. The others derivatives 7–9 were obtained in reactions of the corresponding triterpenoids with EDC·HCl, 4-N,N-dimethylaminopyridine hydrochloride and 4-N,N-dimethylaminopyridine in CH2Cl2. The structures of 1–9 were elucidated from extensive spectroscopic and HRESIMS data, while the structure of 9 was further confirmed by X-ray diffraction analysis. The cytotoxic, anti-hepatitis B virus (HBV), antibacterial, hypoglycaemic and Wnt signaling activities of these derivatives were evaluated in vitro.

Three novel C19 homolignans, taiwankadsurins D (1), E (2) and F (4), and two new C18 lignans kadsuphilins N (3) and O (5) were isolated from the aerial parts of Taiwanese medicinal plant Kadsura philippinensis. The structures of compounds 1–5 were determined by spectroscopic analyses, especially 2D NMR techniques. The structure of compound 5 was further confirmed by X-ray crystallographic analysis. Compounds 1 and 2 have a 3,4-{1'-[(Z)-2''-methoxy-2''-oxoethylidene]}-pentano(2,3-dihydrobenzo[b]furano)-3-(2'''-methoxycarbonyl-2'''-hydroxy-2''',3'-epoxide) skeleton.

Four new 8-hydroxybriarane diterpenoids, frajunolides P–S (1–4), together with umbraculolide A, juncenolide C, junceellonoid A and juncin R, were isolated from the acetone extract of the gorgonian Junceella fragilis, collected from the southeast coast of Taiwan. Compound 1 contains an unusual pivaloyloxy group at C-2, while 3 is a rare compound having a chlorine atom on the olefinic carbon (C-6). The structures of the isolated compounds were established by extensive spectroscopic analysis, including 1D- and 2D-NMR, as well as HRMS data. Compound 1 was further confirmed by X-ray crystallographic analysis. In the anti-inflammatory test, compounds 1 and 2 exhibited moderate inhibition on superoxide anion generation and elastase release by human neutrophils in response to formylmethionylleucyl-phenylalanine/dihydrocytochalasin B (fMLP/CB).

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. The molecular mechanisms underlying the regulation of Grb7 remain unclear. Here, we revealed a novel negative post-translational regulation of Grb7 by the peptidyl-prolyl cis/trans isomerase, Pin1. Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. Indeed, we found that Pin1 exerts its peptidyl-prolyl cis/trans isomerase activity in the modulation of Grb7 protein stability in regulation of cell cycle progression at the G2-M phase. This study illustrates a novel regulatory mechanism in modulating Grb7-mediated signaling, which may take part in pathophysiological consequences.

Three new secoiridoid constituents, goncarin A−C (1–3), and a new derivative, goncarin A monoacetate (4), along with two known lignins, pinoresinol (5) and paulownin (6), were isolated from the seed of Gonocaryum calleryanum (Baill.) Becc. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy. The aim of this study was to identify the anti-inflammatory effects of compounds 1–6 on lipopolysaccharide (LPS)-stimulated murine macrophage cell lines (RAW 264.7). Following stimulation with LPS, elevated levels of nitric oxide (NO) production were detected in RAW 264.7 cells; however, pretreatment with compounds 1–6 significantly inhibited the production of NO (around 40–80%, p < 0.01–0.05), by suppressing the expression of inducible NO synthase (iNOS). In addition, LPS-stimulated tumor necrosis factor-α (TNF-α) production was significantly reduced by compounds 1–3 (25–40%, p < 0.01–0.05). These results suggested that compounds 1–3 may exert anti-inflammatory activity, and that compounds 1–3 may be considered a potential therapeutic for the treatment of inflammatory diseases associated with macrophage activation.

Four consecutive patients with chronic peripheral circumferential detachment developed vision-threatening complications requiring further treatment. All four cases had more than one previous vitreoretinal surgery; two cases had silicone oil intravitreally and three had crystalline lens removed. The main complications included chronic hypotony (1 case), rubeosis iridis (4 cases), intraocular hemorrhage (1 case), neovascular glaucoma (1 case), and cataract (1 case). Retinectomy with peripheral traction release and silicone oil infusion resulted in improvement or stabilization of visual function in all four cases.

Lemierre syndrome is an extremely rare disease characterized by oropharyngeal infection, septicemia, internal jugular vein thrombosis, and skip lesions. The most common causative pathogen is Fusobacterium necrophorum. We reported a 45-year-old woman who presented with left neck painful swelling and septicemia. Magnetic resonance imaging of the head and neck demonstrated venous thrombosis extending from the left internal jugular vein to the sigmoid sinus. During admission we discovered that the patient had uncontrolled diabetes mellitus. We also found a metastatic lesion through chest radiography. Klebsiella pneumoniae was cultivated from both blood samples and pus from deep neck spaces. Surgical drainage, early and adequate antibiotic treatment, anticoagulation, and strict control of blood glucose led to the patient's complete recovery. Because Lemierre syndrome is a forgotten disease in the era of antibiotics, awareness of the signs and symptoms of this disease is important because of its associated high mortality rate. This case illustrated that the presence of K pneumoniae can lead to Lemierre syndrome.

Phytochemical investigation of the acetone extract from the roots of Aphanamixis polystachya resulted in isolation of four new tetranortriterpenes (1–4) in addition to one protolimonoid (methyl-1ξ,7R-diacetoxy-23R,25-dihydroxy-20S,24R-21,24-epoxy-3,4-seco-apotirucall-4(28),14(15)-diene-3-oate (5)), five known limonoids (rohituka 3 (6), rohituka 7 (7), nymania 1 (8), rubrin G (9), prieurianin (10)) and a steroid (2,3-dihydroxy-5-pregnan-16-one (11)). Their structures were determined by spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Cytotoxic and anti-inflammatory activities of these compounds were evaluated. Compounds 4 and 5 showed significant inhibition against superoxide generation and elastase release by human neutrophils in response to (formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B) (FMLP/CB).

Children who speak one language at home and a different language at school may be at higher risk of falling behind in their academic achievement when schooling is disrupted. The present study examined the effects of COVID-19-related school disruptions on English language and literacy development among monolingual and bilingual children in the US. All children attended English-only schools that implemented varied forms of virtual and hybrid schooling during the pandemic. Pre-COVID-19 and during-COVID-19 examinations were conducted with 237 children (M(SD)[subscript age] = 7.78 (1.54) at Time 1) from relatively high SES homes, including 95 monolinguals, 75 Spanish-English and 67 Chinese-English bilinguals. The findings revealed different impacts of COVID-19 school disruptions on the present bilingual and monolingual participants. Specifically, between Time 1 and Time 2, monolingual children made age-appropriate improvements in all literacy measurements. Relative to monolinguals, both bilingual groups showed greater gains in vocabulary but lower gains in reading comprehension. Moreover, across groups, children's independent reading practices during COVID-19 were positively associated with children's literacy growth during the pandemic-related schooling disruptions. Taken together, these findings inform theoretical perspectives on learning to read in linguistically diverse children experiencing COVID-19-related schooling disruptions.

How do early bilingual experiences influence children's neural architecture for word processing? Dual language acquisition can yield common influences that may be shared across different bilingual groups, as well as language-specific influences stemming from a given language pairing. To investigate these effects, we examined bilingual English speakers of Chinese or Spanish, and English monolinguals, all raised in the US (N = 152, ages 5-10). Children completed an English morphological word processing task during fNIRS neuroimaging. The findings revealed both language-specific and shared bilingual effects. The language-specific effects were that Chinese and Spanish bilinguals showed principled differences in their neural organization for English lexical morphology. The common bilingual effects shared by the two groups were that in both bilingual groups, increased home language proficiency was associated with stronger left superior temporal gyrus (STG) activation when processing the English word structures that are most dissimilar from the home language. The findings inform theories of language and brain development during the key periods of neural reorganization for learning to read by illuminating experience-based plasticity in linguistically diverse learners.

Due to the implicit characteristics of learning disabilities (LDs), the diagnosis of students with learning disabilities has long been a difficult issue. Artificial intelligence techniques like artificial neural network (ANN) and support vector machine (SVM) have been applied to the LD diagnosis problem with satisfactory outcomes. However, special education teachers or professionals tend to be skeptical to these kinds of black-box predictors. In this study, we adopt the rough set theory (RST), which can not only perform as a classifier, but may also produce meaningful explanations or rules, to the LD diagnosis application. Our experiments indicate that the RST approach is competitive as a tool for feature selection, and it performs better in term of prediction accuracy than other rulebased algorithms such as decision tree and ripper algorithms. We also propose to mix samples collected from sources with different LD diagnosis procedure and criteria. By pre-processing these mixed samples with simple and readily available clustering algorithms, we are able to improve the quality and support of rules generated by the RST. Overall, our study shows that the rough set approach, as a classification and knowledge discovery tool, may have great potential in playing an essential role in LD diagnosis.

Morphological awareness, or sensitivity to units of meaning, is an essential component of reading comprehension development. Current neurobiological models of reading and dyslexia have largely been built upon phonological processing models, yet reading for meaning is as essential as reading for sound. To fill this gap, the present study explores the relation between children's neural organization for morphological awareness and successful reading comprehension in typically developing and impaired readers. English-speaking children ages 6-11 (N = 97; mean age = 8.6 years, 25% reading impaired) completed standard literacy assessments as well as an auditory morphological awareness task during functional near-infrared spectroscopy (fNIRS) neuroimaging, which included root (e.g., PERSON + al) and derivational (e.g., quick + LY) morphology. Regression analyses revealed that children's morphological awareness predicted unique variance in reading comprehension above and beyond demographic factors, vocabulary knowledge, and decoding ability. Neuroimaging analyses further revealed that children with stronger reading comprehension showed greater engagement of brain regions associated with integrating sound and meaning, including left inferior frontal, middle temporal, and inferior parietal regions. This effect was especially notable for the derivational morphology condition that involved manipulating more analytically demanding and semantically abstract units (e.g., un-, -ly, -ion). Together, these findings suggest that successful reading comprehension, and its deficit in dyslexia, may be related to the ability to manipulate morpho-phonological units of word meaning and structure. These results inform theoretical perspectives on literacy and children's neural architecture for learning to read.

Author(s): Chi-Lin Yu [sup.1] , Henry M. Wellman [sup.1] Author Affiliations: (1) grid.214458.e, 0000000086837370, University of Michigan, , Ann Arbor, MI, USA In a recent letter in this journal, Gough [...]

This study investigates the cross-linguistic transfer of literacy skills in Spanish-English, Chinese-English bilingual, and English monolingual children (N = 283, 5-10 years). Research question 1 examines English literacy and asks how phonological and morpho-semantic skills contribute to word reading as a function of children's language background. Structural equation modeling revealed contrasting bilingual effects: compared to English monolinguals, Spanish-English bilinguals relied more on phonological awareness in word reading, whereas Chinese-English bilinguals relied more on lexical knowledge. Research question 2 examines relations between bilinguals' heritage language proficiency and English literacy. Results revealed direct and indirect effects of heritage language meta-linguistic skills on English word reading. The study yields implications for reading theories and instructional practices in optimizing literacy in linguistically diverse children.

The possibility and nature of bilingual advantage for theory of mind (ToM), that is, young bilingual children outperforming their monolingual peers, have been discussed increasingly since the first research on the topic was published in 2003. Because accumulating evidence demonstrates a ToM advantage for bilingual individuals, in this article, we focus on how this advantage arises. We consider how current theoretical positions, including "executive function," "metalinguistic awareness," and "sociolinguistic awareness" accounts, explain such an advantage in young bilingual children. These theoretical accounts receive some, but only partial, support, so further research and theory are needed to understand comprehensively the relationship between bilingualism and ToM.

Phonological awareness is the stepping‐stone to learning to read as it helps children map language sounds onto letters. Theories of bilingualism posit that phonological awareness is a language‐common literacy skill. However, bilingual learners are also thought to build language‐specific representations. To illuminate common and specific dual‐language processes, we asked bilingual Spanish–English heritage language speakers (N = 60, Mage = 8.2) to complete a phonological sound‐matching task in Spanish and English during functional Near Infrared Neuroimaging (fNIRS). The left perisylvian activation was common across bilinguals' two languages, including similar active regions and functional connections. The findings further revealed language‐specific modulation of the system with more robust engagement of the temporal networks for Spanish and frontal networks for English. We interpret the results in the context of analytically demanding reading experiences in English and more informal home‐based Spanish language experiences typical of heritage language speakers. How do children's minds and brains develop to support literacy in two different languages? We asked school‐aged Spanish–English bilinguals to complete a phonological awareness task during neuroimaging. Similar brain regions supported phonological awareness across languages. Yet, communication, or functional connectivity, between brain regions differed across bilinguals' two languages. Findings suggest that similar cognitive and brain processes support literacy development in each of the two languages of young bilinguals. At the same time, there is evidence of language‐specific fine‐tuning of the brain's literacy systems; this allows children to develop literacy skills specific to each of their languages. [ABSTRACT FROM AUTHOR]