Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis of Polyethylene with in-chain α,β-Unsaturated Ketone and Isolated Ketone Units by Pd-catalyzed Ring-opening Copolymerization of Cyclopropenones with Ethylene.

Although various functionalized units can be incorporated into polyolefins via transition-metal catalyzed coordination copolymerizations of non-functionalized olefins with polar functional monomers, the incorporated functional units are largely limited to C1 units from CO or carbene precursor or C2 units from vinyl monomers. Here we report the Pd-catalyzed copolymerization of ethylene with cyclopropenone, leading to incorporation of C3 units with functional groups in chain, that are α,β-unsaturated ketones. Coordination-insertion of the carbonyl group and ring opening of the strained three-membered ring is proposed as the key steps in the mechanism. Under a different condition an isolated ketone structure was afforded as the major carbonyl unit, which could be generated by the copolymerization of ethylene with in-situ formed CO from cyclopropenone.
CXCL1 stimulates migration and invasion in ER-negative breast cancer cells via activation of the ERK/MMP2/9 signaling axis

Chemokine (C-X-C motif) ligand 1 (CXCL1), a member of the CXC chemokine family, has been reported to be a critical factor in inflammatory diseases and tumor progression; however, its functions and molecular mechanisms in estrogen receptor α (ER)-negative breast cancer (BC) remain largely unknown. The present study demonstrated that CXCL1 was upregulated in ER-negative BC tissues and cell lines compared with ER-positive tissues and cell lines. Treatment with recombinant human CXCL1 protein promoted ER-negative BC cell migration and invasion in a dose-dependent manner, and stimulated the activation of phosphorylated (p)- extracellular signal-regulated kinase (ERK)1/2, but not p-STAT3 or p-AKT. Conversely, knockdown of CXCL1 in BC cells attenuated these effects. Additionally, CXCL1 increased the expression of matrix metalloproteinase (MMP)2/9 via the ERK1/2 pathway. Inhibition of MEK1/2 by its antagonist U0126 reversed the effects of CXCL1 on MMP2/9 expression. Furthermore, immunohistochemical analysis revealed a strong positive association between CXCL1 and p-ERK1/2 expression levels in BC tissues. In conclusion, the present study demonstrated that CXCL1 is highly expressed in ER-negative BC, and stimulates BC cell migration and invasion via the ERK/MMP2/9 pathway. Therefore, CXCL1 may serve as a potential therapeutic target in ER-negative BC.
Transcriptome Analysis of Differentially Expressed Genes Related to the Growth and Development of the Jinghai Yellow Chicken

The growth traits are important traits in chickens. Compared to white feather broiler breeds, Chinese local broiler breeds have a slow growth rate. The main genes affecting the growth traits of local chickens in China are still unclear and need to be further explored. This experiment used fast-growth and slow-growth groups of the Jinghai Yellow chicken as the research objects. Three males and three females with similar body weights were selected from the two groups at four weeks old and eight weeks old, respectively, with a total of 24 individuals selected. After slaughter, their chest muscles were taken for transcriptome sequencing. In the differentially expressed genes screening, all of the genes obtained were screened by fold change ≥ 2 and false discovery rate (FDR) < 0.05. For four-week-old chickens, a total of 172 differentially expressed genes were screened in males, where there were 68 upregulated genes and 104 downregulated genes in the fast-growth group when compared with the slow-growth group. A total of 31 differentially expressed genes were screened in females, where there were 11 upregulated genes and 20 downregulated genes in the fast-growth group when compared with the slow-growth group. For eight-week-old chickens, a total of 37 differentially expressed genes were screened in males. The fast-growth group had 28 upregulated genes and 9 downregulated genes when compared with the slow-growth group. A total of 44 differentially expressed genes were screened in females. The fast-growth group had 13 upregulated genes and 31 downregulated genes when compared with the slow-growth group. Through gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, many genes were found to be related to cell proliferation and differentiation, muscle growth, and cell division such as SNCG, MCL1, ARNTL, PLPPR4, VAMP1, etc. Real-time PCR results were consistent with the RNA-Seq data and validated the findings. The results of this study will help to understand the regulation mechanism of the growth and development of Jinghai Yellow chicken and provide a theoretical basis for improving the growth rate of Chinese local chicken breeds.
Three new steroidal components from the roots of reineckia carnea

Abstract A new coprostanol glycoside, 26-trihydroxy-16, 22-dioxo-3β-[(α-L-rhamnopyranosyl)oxy]-5β-cholestan-1β-yl O-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranoside (1) (25S)-5β-spirostan-1β,2β,3β, 4β,5β, 6β-hexol (2), a new C-22 steroidal lactone saponin, (20 R)-16β-trihydroxy-3β-[(α-L-rhamnopyranosyl)oxy]-1β-[(O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl)oxy]-5β-pregnane-20-oic acid γ-lactone (3) along with two known pregnane glycosides (4 and 5) were obtained from the roots of Reineckia carnea. Their structures were determined by 1 D, 2 D NMR, IR and MS data analysis. In addition, the cytotoxic activities in HT-29, HCT116, H1299 and A549 tumor cells of the isolated compounds (1 − 5) were determined by the MTT method. The results showed that only compound 1 exhibited weak effect against these cells with IC50 values ranging from 63.36 μM to 105.01 μM.
Biomass co-pyrolysis: Effects of blending three different biomasses on oil yield and quality

In the present study, pyrolysis and co-pyrolysis of sugarcane bagasse, poppy capsule pulp, and rice husk were conducted in a fixed bed reactor at 550⁰C in nitrogen atmosphere. The moisture (5%–8%), ash (4%–17%), volatile matter (60%–76%), and fixed carbon analyses (11%–24%) of the utilized biomass were conducted. The decomposition behavior of biomasses due to the heat effect was investigated by thermogravimetric analysis/differential thermal analysis . In the pyrolysis of biomasses separately, the highest bio-oil yield was obtained with sugarcane bagasse (27.4%). In the co-pyrolysis of the binary blends of biomass, the highest bio-oil yield was obtained with the rice husk and sugarcane bagasse blends. While the mean bio-oil yield obtained with the separate pyrolysis of these two biomasses was 23.9%, it was observed that the bio-oil yield obtained with the co-pyrolysis of biomass blends was 28.4%. This suggested a synergistic interaction between the two biomasses during pyrolysis. It was observed that as the total ash content in the biomasses used in the pyrolysis increased, the bio-oil yield decreased, and the solid product content increased. Characterization studies of bio-oils were conducted by Fourier-transform infrared spectroscopy, gas chromatography–mass spectrometry (GC-MS), and hydrogen-1 nuclear magnetic resonance analyses. Results of these studies revealed that, all bio-oils were mainly composed of aliphatic and oxygenated compounds. The calorific values of bio-oils were determined by calorimeter bomb. Based on the GC-MS, the bio-oils with high fatty acid and its ester content also had high calorific values. The highest calorific value was 29.68 MJ kg-1, and this was obtained by pyrolysis of poppy capsule and sugarcane bagasse blend.
Autophagy induction by the pathogen receptor NECTIN4 and sustained autophagy contribute to peste des petits ruminants virus infectivity

ABSTRACT Macroautophagy/autophagy is an essential cellular response in the fight against intracellular pathogens. Although some viruses can escape from or utilize autophagy to ensure their own replication, the responses of autophagy pathways to viral invasion remain poorly documented. Here, we show that peste des petits ruminants virus (PPRV) infection induces successive autophagic signalling in host cells via distinct and uncoupled molecular pathways. Immediately upon invasion, PPRV induced a first transient wave of autophagy via a mechanism involving the cellular pathogen receptor NECTIN4 and an AKT-MTOR-dependent pathway. Autophagic detection showed that early PPRV infection not only increased the amounts of autophagosomes and LC3-II but also downregulated the phosphorylation of AKT-MTOR. Subsequently, we found that the binding of viral protein H to NECTIN4 ultimately induced a wave of autophagy and inactivated the AKT-MTOR pathway, which is a critical step for the control of infection. Soon after infection, new autophagic signalling was initiated that required viral replication and protein expression. Interestingly, expression of IRGM and HSPA1A was significantly upregulated following PPRV replication. Strikingly, knockdown of IRGM and HSPA1A expression using small interfering RNAs impaired the PPRV-induced second autophagic wave and viral particle production. Moreover, IRGM-interacting PPRV-C and HSPA1A-interacting PPRV-N expression was sufficient to induce autophagy through an IRGM-HSPA1A-dependent pathway. Importantly, syncytia formation could facilitate sustained autophagy and the replication of PPRV. Overall, our work reveals distinct molecular pathways underlying the induction of self-beneficial sustained autophagy by attenuated PPRV, which will contribute to improving the use of vaccines for therapy. Abbreviations: ACTB: actin beta; ANOVA: analysis of variance; ATG: autophagy-related; BECN1: beclin 1; CDV: canine distemper virus; Co-IP: coimmunoprecipitation; FIP: fusion inhibitory peptide; GFP: green fluorescent protein; GST: glutathione S-transferase; HMOX1: heme oxygenase 1; hpi: hours post infection; HSPA1A: heat shock protein family A (Hsp70) member 1A; HSP90AA1: heat shock protein 90 kDa alpha (cytosolic), class A member 1; IFN: interferon; IgG: immunoglobulin G; INS: insulin; IRGM: immunity related GTPase M; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PI3K: phosphoinositide-3 kinase; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; SDS: sodium dodecyl sulfate; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; UV: ultraviolet.
Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study

Purpose The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 PanNETs and PanNECs is difficult in clinical practice. Materials and Methods Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. Results Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. Conclusion Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.
A successful history: probiotics and their potential as antimicrobials

ABSTRACT Introduction: Probiotics are living, non-pathogenic microorganisms (bacteria) that enter through diet in the human body, live during their passage through the gastrointestinal (GI) tract and are beneficial to health. They have become popular in recent years as a way of improving human health through nutrition. This review aims to discuss the efficacy of probiotics for the supportive therapy of certain clinical conditions, especially infectious diseases, as reported in a number of studies, even though some concerns about their safety still remain. Areas covered: This paper will review the history of probiotics, from ancient ages to date, and the evolution of their use in clinical practice. The study is based on both personal professional experience of the authors and a comprehensive literature analysis, including old documents from libraries, searching the related biological and clinical data on Scopus, Web of Science, PubMed, EMBASE, also using the ‘cited by’ and ‘similar articles’ options available in PubMed. Expert opinion: Not all researchers agree about the safety and real efficacy of probiotics in common conditions, especially infective diseases. However, the use of probiotics for clinical conditions that may be improved by consumption of these dietary supplements should be considered as a possible supportive therapy in select patients.
Dexamethasone loaded Laponite®/porous calcium phosphate cement for treatment of bone defects

In this research, nanocomposite porous calcium phosphate cements (CPCs) consisting of dexamethasone (DEX) loaded Laponite® nanoplates (LAP) (DEX-LAP) were fabricated and the effects of sodium bicarbonate (NaHCO3) as the foaming agent on the physical, mechanical, and biological characteristics of DEX-LAP loaded CPCs were investigated. Our findings showed that DEX-LAP encapsulation significantly reduced the final setting time (1.5 times) of CPCs and accelerated the total transformation of tricalcium phosphate to hydroxyapatite. Moreover, DEX-LAP nanoplates meaningfully enhanced the compressive strength (4 fold) and compressive modulus (4 fold) of cement. Additionally, incorporation of 6% foaming agent noticeably reduced setting time of cement to less than 10 min due to the enhanced surface area in contact with cement paste. Encapsulation of DEX within the LAP nanoplates and consequently loading of DEX-LAP nanoplates in the CPCs resulted in the significantly reduced burst release of DEX. Finally, the results also illustrated that the presence of interconnected micropores and DEX-LAP nanoplates in the CPC improved MG63 cell proliferation. These findings suggest that the porous DEX-LAP/CPC can potentially be developed as bone grafts for bone defects.
Multi-Target β-Protease Inhibitors from Andrographis paniculata: In Silico and In Vitro Studies

Natural products derived from plants play a vital role in the discovery of new drug candidates, and these are used for novel therapeutic drug development. Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties. β-amyloid is a microscopic brain protein whose significant aggregation is detected in mild cognitive impairment and Alzheimer’s disease (AD) brains. The accumulation of β-amyloid disrupts cell communication and triggers inflammation by activating immune cells, leading to neuronal cell death and cognitive disabilities. The proteases acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta secretase-1 (BACE-1) have been reported to be correlated with the synthesis and growth of β-amyloid plaques in the brains of AD patients. In the present study, the phenolic compounds from A. paniculata and S. paniculata that have been reported in the literature were selected for the current investigation. Furthermore, we employed molecular docking and molecular dynamics studies of the phenolic compounds with the proteins AChE, BChE, and BACE-1 in order to evaluate the binding characteristics and identify potent anti-amyloid agents against the neurodegenerative diseases such as AD. In this investigation, we predicted three compounds from A. paniculata with maximum binding affinities with cholinesterases and BACE-1. The computational investigations predicted that these compounds follow the rule of five. We further evaluated these molecules for in vitro inhibition activity against all the enzymes. In the in vitro investigations, 3,4-di-o-caffeoylquinic acid (5281780), apigenin (5280443), and 7-o-methylwogonin (188316) were found to be strong inhibitors of AChE, BChE, and BACE-1. These findings suggest that these compounds can be potent multi-target inhibitors of the proteases that might cumulatively work and inhibit the initiation and formation of β-amyloid plaques, which is a prime cause of neurotoxicity and dementia. According to our knowledge, these findings are the first report on natural compounds isolated from A. paniculata as multi-target potent inhibitors and anti-amyloid agents.
Protective effect of ginsenoside Rg1 on attenuating anti-GBM glomerular nephritis by activating NRF2 signalling

Abstract Background/Aim Ginsenoside Rg1 exerts a beneficial effect in many kidney diseases. But little work has been done to confirm whether ginsenoside Rg1 could also exert a protective effect on anti-glomerular basement membrane (anti-GBM) glomerular nephritis (GN). We aimed to explore the role of ginsenoside Rg1 in attenuating anti-GBM GN in vitro and in vivo and investigate the mechanism under its action. Methods Interleukin-1β (IL-1β) treated podocytes were used as a cell model. A total of 20 mice were used to build the Anti-GBM GN mice model. Real-time PCR analysis (RT-PCR), Western blot analysis and ELISA assay were conducted to detect related indicators in this study. The statistical analysis was performed using GraphPad Prism software 6.0. Results Ginsenoside Rg1 attenuates IL-1β-induced inflammation and apoptosis in podocytes. NRF2 expression can be inhibited by IL-1β, whereas reversed by ginsenoside Rg1. NRF2 inhibitor ML385 can significantly reverse the effects of ginsenoside Rg1 on inflammation and apoptosis induced by IL-1β, and block the inhibitory effect of ginsenoside Rg1 on IL-1β activated MAPK pathway. In addition, ginsenoside Rg1 could improve anti-GBM GN injury in vivo. Conclusion Ginsenoside Rg1 inhibits the anti-GBM GN damage through regulating NRF2 pathway in vitro and in vivo. Our findings provide new insight and mechanism of ginsenoside Rg1 to prevent anti-GBM GN.
Effects of surgical treatment for classical trigeminal neuralgia with concomitant persistent facial pain.

PURPOSE Classical trigeminal neuralgia with concomitant persistent facial pain responds poorly to conservative treatment. The authors describe the effects of microvascular decompression and radiofrequency thermocoagulation for patients with classical trigeminal neuralgia and concomitant persistent facial pain. CASE REPORT Case 1 was a 61-year-old man with dull, continuous, aching pain in the left maxillary and mandibular molar area. Case 2 was a 68-year-old woman with aching pain in the maxillary right molar. Case 3 was a 67-year-old woman with severe pain in the right upper lip and maxillary right second premolar. Case 4 was a 42-year-old man with orofacial pain of 14 months' duration. Cases 1 and 2 underwent radiofrequency thermocoagulation and reported good relief of symptoms. Cases 3 and 4 underwent microvascular decompression and attained excellent relief. CONCLUSION Microvascular decompression may be more effective than radiofrequency thermocoagulation for patients with classical trigeminal neuralgia with concomitant persistent facial pain.
Patisiran Pharmacokinetics, Pharmacodynamics, and Exposure‐Response Analyses in the Phase 3 APOLLO Trial in Patients With Hereditary Transthyretin‐Mediated (hATTR) Amyloidosis

Hereditary transthyretin‐mediated (hATTR) amyloidosis is an inherited, rapidly progressive, life‐threatening disease caused by deposition of abnormal transthyretin protein. Patisiran is an RNA interference therapeutic comprising a novel, small interfering ribonucleic acid (ALN‐18328) formulated in a lipid nanoparticle targeted to inhibit hepatic transthyretin protein synthesis. The lipid nanoparticle also contains 2 novel lipid excipients (DLin‐MC3‐DMA and PEG2000‐C‐DMG). Here we report patisiran pharmacokinetics (PK), pharmacodynamics (PD), and exposure‐response analyses from the phase 3 APOLLO trial, in which patients with hATTR amyloidosis with polyneuropathy were randomized 2:1 to receive patisiran 0.3 mg/kg or placebo intravenously every 3 weeks over 18 months. In patisiran‐treated patients, mean maximum reduction in serum transthyretin level from baseline was 87.8%. Patisiran PK exposure was stable following chronic dosing. There were no meaningful differences in PK exposure, serum transthyretin reduction, and efficacy (change from baseline in modified Neuropathy Impairment Score+7) across all subgroups analyzed (age, sex, race, body weight, genotype status of valine‐to‐methionine mutation at position 30 [V30M] and non‐V30M, prior use of tetramer stabilizers, mild/moderate renal impairment, and mild hepatic impairment). transthyretin reduction and efficacy were similar across the interpatient PK exposure range for ALN‐18328. There was no trend in the incidence of adverse events or serious adverse events across the interpatient PK exposure range for all 3 analytes. Incidence of antidrug antibodies was low (3.4%) and transient, with no impact on PK, PD, efficacy, or safety. The patisiran dosing regimen of 0.3 mg/kg every 3 weeks is appropriate for all patients with hATTR amyloidosis.
Identification of Safety and Quality Parameters for Preparation of Jellyfish Based Novel Food Products

Edible jellyfish are mainly consumed and marketed in Southeastern Countries, generally produced by a multi-phase drying process, using mixtures of salt and alum. Recently, jellyfish have become very attractive also for Western food markets. They are novel food in Europe and no recognized handling/processing steps have been set up yet. Moreover, no specific food safety and quality parameters are available. In this study, we identified a set of safety and quality parameters for jellyfish, based on standards and process hygiene criteria used in Europe for other products. These assays were tested on three different jellyfish preparations that can be used as raw materials for subsequent food processing. All jellyfish samples revealed the absence of pathogens (Salmonella spp. and Listeria monocytogenes), Enterobacteriaceae and Pseudomonas spp. , even if a limited presence of Staphylococci was observed. No biogenic amine histamine was detected and negligible levels of total volatile basic nitrogen (TVB-N) were revealed. Total bacterium, yeast and mold counts were negligible or undetectable by conventional accredited methods, and conversely the results were higher when optimized saline conditions were used. This study, for the first time, established a set of quality and safety parameters necessary for first-operations and subsequent processing of jellyfish as novel food. Highlights: Jellyfish can represent a novel food in Europe. Identification of safety and quality parameters for jellyfish food products. Saline conditions are essential for improving safety and quality assessment of jellyfish as food.