Three-year clinical outcomes of the novel sirolimus-eluting bioresorbable scaffold for the treatment of de novo coronary artery disease: A prospective patient-level pooled analysis of NeoVas trials.

OBJECTIVES: We aimed to evaluate the long-term outcomes of the novel NeoVas sirolimus-eluting bioresorbable scaffold (BRS) for the treatment of de novo coronary artery disease. BACKGROUND: The long-term safety and efficacy of the novel NeoVas BRS are still needed to be elucidated. METHODS: A total of 1103 patients with de novo native coronary lesions for coronary stenting were enrolled. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death (CD), target vessel myocardial infarction (TV-MI), or ischemia-driven-target lesion revascularization (ID-TLR). RESULTS: A three-year clinical follow-up period was available for 1,091 (98.9%) patients. The cumulative TLF rate was 7.2% with 0.8% for CD, 2.6% for TV-MI, and 5.1% for ID-TLR. Additionally, 128 (11.8%) patient-oriented composite endpoint and 11 definite/probable stent thromboses (1.0%) were recorded. CONCLUSIONS: The extended outcomes of the NeoVas objective performance criterion trial demonstrated a promising 3-year efficacy and safety of the NeoVas BRS in low-risk patients with low complexity in terms of lesions and comorbidities.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

The kinetics of IgG subclasses and contributions to neutralizing activity against SARS-CoV-2 wild-type strain and variants in healthy adults immunized with inactivated vaccine.

Neutralizing antibody is an important indicator of vaccine efficacy, of which IgG is the main component. IgG can be divided into four subclasses. Up to now, studies analysing the humoral response to SARS-CoV-2 vaccination have mostly focused on measuring total IgG, and the contribution of specific IgG subclasses remains elusive. The aim of this study is to investigate the kinetics of neutralizing antibodies and IgG subclasses, and to explore their relationships in people vaccinated with inactivated COVID-19 vaccine. We conducted a prospective cohort study in 174 healthy adults aged 18-59 years old who were administrated 2 doses of CoronaVac 14 days apart and a booster dose 1 year after the primary immunization, and followed up for 15 months. Blood samples were collected at various time points after primary and booster immunization. We used live SARS-CoV-2 virus neutralizing assay to determine neutralizing ability against the wild-type strain and 4 variants (Beta, Gamma, Delta and Omicron) and ELISA to quantify SARS-CoV-2 RBD-specific IgG subclasses. The results showed that the 2-dose primary immunization only achieved low neutralizing ability, while a booster shot can significantly enhance neutralizing ability against the wild-type strain, Beta, Gamma, Delta and Omicron variants. IgG1 and IgG3 were the most abundant serum antibodies, and IgG2 and IgG4 were hardly detected at any time. The ratio of IgG1/IgG3 was positively associated with the neutralization ability. The underlying mechanism requires further exploration.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

Astramalabaricosides A-T, Highly Oxygenated Malabaricane Triterpenoids with Migratory Inhibitory Activity from Astragalus membranaceus var. mongholicus.

Twenty new malabaricane triterpenoids, astramalabaricosides A-T (1-20), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1-20 were characterized as glycosides with a highly oxygenated side chain, and 13-20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1-20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.

Bioactive phenylpropanoid derivatives from the fruits of Lycium ruthenicum Murr.

Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, α-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).

Treating green pea aphids, Myzus persicae, with azadirachtin affects the predatory ability and protective enzyme activity of harlequin ladybirds, Harmonia axyridis.

As a natural enemy of green peach aphids, harlequin ladybirds, Harmonia axyridis Pallas (Coleoptera: Coccinellidae), are also indirectly affected by azadirachtin. In this study, we evaluated the effects of ladybird exposure to azadirachtin through azadirachtin-treated aphids. About 2 mg/L azadirachtin treated aphid can deliver the azadirachtin to ladybird larvae in 12 and 24 h. And azadirachtin treatment affected the rate at which fourth instar larvae and adult ladybirds preyed on aphids. Furthermore, the antifeedant effect increased with increasing azadirachtin concentrations. Twelve hours after exposing fourth instar ladybird larvae to aphids treated with 10 mg/L azadirachtin, the antifeedant effect was 47.70%. Twelve hours after exposing adult ladybirds to aphids treated with 2 mg/L azadirachtin, the antifeedant effect was 67.49%. Forty-eight hours after exposing ladybird larvae to azadirachtin-treated aphids, their bodyweights were 8.37 ± 0.044 mg (2 mg/L azadirachtin), 3.70 ± 0.491 mg (10 mg/L azadirachtin), and 2.39 ± 0.129 mg (50 mg/L azadirachtin). Treatment with azadirachtin affected the ability of ladybirds to prey on aphids. The results indicated that the instant attack rate of ladybird larvae and adults and the daily maximum predation rate were reduced by azadirachtin treatment. Superoxide dismutase (SOD), peroxidase (POD), and peroxide (CAT) enzyme activities of ladybirds were affected after feeding on aphids treated with azadirachtin. Azadirachtin has certain antifeedant effects on ladybirds and affects the ability of ladybirds to prey on aphids and the activities of SOD, POD, and CAT enzymes, which results in inhibition of normal body development.

Azadirachtin directly or indirectly affects the abundance of intestinal flora of Spodoptera litura and the energy conversion of intestinal contents mediates the energy balance of intestine-brain axis, and along with decreased expression CREB in the brain neurons.

Azadirachtin is a good growth inhibitor for Lepidopteran larvae, but its effect on the brain neurons, intestinal flora and intestinal contents caused by the growth inhibition mechanism has not been reported yet. This study explored the mechanism of azadirachtin on the growth and development of Spodoptera litura larvae and brain neurons through three aspects: intestinal pathology observation, intestinal flora sequencing, and intestinal content analysis. The results showed that the treatment of azadirachtin led to the pathological changes in the structure of the midgut and the goblet cells in the intestinal wall cells to undergo apoptosis. Changes in the host environment of the intestinal flora lead to changes in the abundance value of the intestinal flora, showing an increase in the abundance value of harmful bacteria such as Sphingomonas and Enterococcus, as well as an increase in the abundance value of excellent flora such as Lactobacillus and Bifidobacterium. Changes in the abundance of intestinal flora will result in changes in intestinal contents and metabolites. The test results show that after azadirachtin treatment, the alkane compounds in the intestinal contents of the larvae are greatly reduced, and the number of the long carbon chain and multi-branched hydrocarbon compounds is increased, unsaturated fatty acids, silicon­oxygen compounds and ethers. The production of similar substances indicates that azadirachtin has an inhibitory effect on digestive enzymes in the intestines, which results in the inhibition of substance absorption and energy transmission, and ultimately the inhibition of larval growth and brain neurons.

Different lethal treatments induce changes in piperidine (1,1'-(1,2-ethanediyl)bis-) in the epidermal compounds of red imported fire ants and affect corpse-removal behavior.

Corpse-removal behavior of the red imported fire ant (RIFA) and the effects of lethal substances on RIFA signal communication were investigated in this study. The RIFA corpses, obtained through freezing, ether, 0.25 mg/L thiamethoxam, and starvation to death treatments, and naturally dead red fire ants were subjected to gas chromatography-mass spectrometry to identify the cuticular hydrocarbon profiles that had an effect on the corpse-removal behavior. The results showed that lethal toxic substances altered the epidermal compounds of RIFA and affected their corpse-removal behavior. Lethal toxic substances increased the number of worker touches with corpses and identification time of corpses. In addition, the content of piperidine (1,1'-(1,2-ethanediyl)bis-) on the surface of the corpse was different following the various treatments. Contamination with toxic substances resulted in the increased secretion of piperidine and led to increased identification time of corpses, number of touch with corpses, and total time for removal of corpses. Piperidine content was higher under conditions of natural death (4.67 ± 0.55%) and with thiamethoxam (10.43 ± 0.78%), freezing (0.83 ± 0.25%), and ether treatment (12.50 ± 0.70%) than under starvation treatment (0). The higher content of piperidine led to a longer number of touches with corpses and identification time. Piperidine compounds may be an element in warning information, which could affect the occurrence of different corpse-removal behaviors.

The major zeaxanthin dipalmitate derivatives from wolfberry.

Zeaxanthin dipalmitate (3) and two zeaxanthin dipalmitate derivatives, including one new compound (1), were obtained from wolfberry [the fruit of Lycium barbarum L. (Solanaceae)]. Their structures were unambiguously elucidated by spectroscopic analyses. Compound 2 is isolated from the genus Lycium for the first time, and its 1D/2D NMR data are firstly reported. All the compounds belong to carotenoids which are a kind of major bioactive constituents in wolfberry and are also responsible for wolfberry's red color.

Cycloartane-type triterpenoids from the root of Astragalus membranaceus var. mongholicus.

Three new (1-3) and 11 known (4-14) cycloartane-type triterpenoids were isolated from the root of Astragalus membranaceus var. mongholicus. Their structures were determined by spectroscopic analyses and chemical methods. Cycloartane-type triterpenoids are a class of major bioactive constituents in the root of A. membranaceus var. mongholicus, and the discovery of compounds 1-3 added new members of this kind of natural product. [Formula: see text].

Houttuynoid M, an Anti-HSV Active Houttuynoid from Houttuynia cordata Featuring a Bis-houttuynin Chain Tethered to a Flavonoid Core.

Houttuynoid M (1), a new houttuynoid, and the related known compound houttuynoid A (2) were isolated from Houttuynia cordata. Their structures were defined using NMR data analysis, HR-MSn experiment, and chemical derivatization. Houttuynoid M is the first example of a houttuynoid with a bis-houttuynin chain tethered to a flavonoid core. A putative biosynthetic pathway of houttuynoid M (1) is proposed. The anti-herpes simplex virus (anti-HSV) activities of 1 and 2 (IC50 values of 17.72 and 12.42 µM, respectively) were evaluated using a plaque formation assay with acyclovir as the positive control.

Bioactive Asarone-Derived Phenylpropanoids from the Rhizome of Acorus tatarinowii Schott.

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6-10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13-15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher's method, and quantum chemical calculations. Compounds 1-8 were present as enantiomers, and 1-5 were successfully resolved via chiral-phase HPLC. Compounds 1a/1b were the first cases of asarone-derived phenylpropanoids with an isopropyl C-3 side-chain tethered to a benzene core from nature. Hypoglycemic, antioxidant, and AChE inhibitory activities of 1-15 were assessed by the α-glucosidase inhibitory, ORAC, DPPH radical scavenging, and AChE inhibitory assays, respectively. All compounds except 3a showed α-glucosidase inhibitory activity. Compound 3b has the highest α-glucosidase inhibitory effect with an IC50 of 80.6 µM (positive drug acarbose IC50 of 442.4 µM). In the antioxidant assays, compounds 13-15 exhibited ORAC and DPPH radical scavenging activities. The results of the AChE inhibitory assay indicated that all compounds exhibited weak AChE inhibitory activities.

A microbial model of mammalian metabolism: biotransformation of 4,5-dimethoxyl-canthin-6-one using Cunninghamella blakesleeana CGMCC 3.970.

1. A filamentous fungus, Cunninghamella blakesleeana CGMCC 3.970, was applied as a microbial system to mimic mammalian metabolism of 4,5-dimethoxyl-canthin-6-one (1). Compound 1 belongs to canthin-6-one type alkaloids, which is a major bioactive constituent of a traditional Chinese medicine (the stems of Picrasma quassioides). 2. After 72 h of incubation in potato dextrose broth, 1 was metabolized to seven metabolites as follows: 4-methoxyl-5-hydroxyl-canthin-6-one (M1), 4-hydroxyl-5-methoxyl-canthin-6-one (M2), canthin-6-one (M3), canthin-6-one N-oxide (M4), 10-hydroxyl-4,5-dimethoxyl-canthin-6-one (M5), 1-methoxycarbonl-ß-carboline (M6), and 4-methoxyl-5-O-ß-D-glucopyranosyl-canthin-6-one (M7). 3. The structures of metabolites were determined using spectroscopic analyses, chemical methods, and comparison of NMR data with those of known compounds. Among them, M7 was a new compound. 4. The metabolic pathways of 1 were proposed, and the metabolic processes involved phase I (O-demethylation, dehydroxylation, demethoxylation, N-oxidation, hydroxylation, and oxidative ring cleavage) and phase II (glycosylation) reactions. 5. This was the first research on microbial transformation of canthin-6-one alkaloid, which could be a useful microbial model for producing the mammalian phase I and phase II metabolites of canthin-6-one alkaloids. 6. 1, M1-M5, and M7 are canthin-6-one alkaloids, whereas M6 belongs to ß-carboline type alkaloids. The strain of Cunninghamella blakesleeana can supply an approach to transform canthin-6-one type alkaloids into ß-carboline type alkaloids.

The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport.

Axonal transport of synaptic vesicles (SVs) is a KIF1A/UNC-104 mediated process critical for synapse development and maintenance yet little is known of how SV transport is regulated. Using C. elegans as an in vivo model, we identified SAM-4 as a novel conserved vesicular component regulating SV transport. Processivity, but not velocity, of SV transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. Gain-of-function mutations in the unc-104 motor domain, identified in this study, suppress the sam-4 defects by increasing processivity of the SV transport. Genetic analyses suggest that SAM-4, SYD-2/liprin-α and the KIF1A/UNC-104 motor function in the same pathway to regulate SV transport. Our data support a model in which the SV protein SAM-4 regulates the processivity of SV transport.

Rap2b promotes proliferation, migration, and invasion of lung cancer cells.

Rap2b, a member of the guanosine triphosphate-binding proteins, is widely up-regulated in many types of tumors. However, the functional role of Rap2b in tumorigenesis of lung cancer remains to be fully elucidated. In this study, we investigated the effect of Rap2b on the lung cancer malignant phenotype, such as cell proliferation and metastasis. We found that Rap2b could promote the abilities of lung cancer cell wound healing, migration, and invasion via increasing matrix metalloproteinase-2 enzyme activity. Furthermore, Rap2b overexpression could increase the phosphorylation level of extracellular signal-regulated protein kinases 1/2. In conclusion, our results suggested that Rap2b may be a potential therapeutic target for lung cancer.

Regulation of C. elegans presynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10.

Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the Caenorhabditis elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation, as well as positioning of, a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted colocalization of active zone and synaptic vesicles. SAM-10 functions coordinately with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations that: (1) mutations in either gene show similar defects in PLM neurons; and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation.

Microcystin-LR induces protein phosphatase 2A alteration in a human liver cell line.

Microcystin-LR (MC-LR) is a potent inhibitor of protein phosphatases 1 and 2A, and has potent hepatotoxicity and tumor promotion activity. Numerous studies on MC-LR toxicity have been conducted in rat hepatocytes, but few studies of the effects of microcystins on human hepatocytes have been done. In this study, HL7702 cells (a human normal liver cell line) were incubated in MC-LR for 24 h. The existence of MC-LR in HL7702 cells was confirmed. Furthermore, PP2A activity and the alteration of PP2A subunits were assessed. The results show that PP2A activity decreased from the concentration of 1 µM MC-LR, showing a concentration-dependent decline, to about 34% at 10 µM MC-LR. This activity undergone opposite change with alternations of phosphorylated Y307-PP2A/C and PP2A/C subunit but showed same change with the alteration of the ratio of methylated L309-PP2A/C to PP2A/C. B55α, a regulatory subunit of PP2A, was slightly increases in cells treated with the highest concentration of MC-LR (10 µM), and colocalized increasedly with rearranged-microtubules after 1 µM MC-LR exposure. However, the proportion of early apoptotic cells did not show any change at various concentration of MC-LR for 24 h. To our knowledge, this is the first report showing MC-LR-induced alteration of PP2A phosphatase in human cultured hepatocytes, and the mechanism of action seems to be similar as described before in vitro. The alteration of PP2A and microtubule seems to be the early event induced by MC-LR exposure.

Asymmetric double-winged multi-view clustering network for exploring diverse and consistent information.

In unsupervised scenarios, deep contrastive multi-view clustering (DCMVC) is becoming a hot research spot, which aims to mine the potential relationships between different views. Most existing DCMVC algorithms focus on exploring the consistency information for the deep semantic features, while ignoring the diverse information on shallow features. To fill this gap, we propose a novel multi-view clustering network termed CodingNet to explore the diverse and consistent information simultaneously in this paper. Specifically, instead of utilizing the conventional auto-encoder, we design an asymmetric structure network to extract shallow and deep features separately. Then, by approximating the similarity matrix on the shallow feature to the zero matrix, we ensure the diversity for the shallow features, thus offering a better description of multi-view data. Moreover, we propose a dual contrastive mechanism that maintains consistency for deep features at both view-feature and pseudo-label levels. Our framework's efficacy is validated through extensive experiments on six widely used benchmark datasets, outperforming most state-of-the-art multi-view clustering algorithms.