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Etoposide (VP-16) is used for the treatment of various cancers, including nasopharyngeal carcinoma (NPC); however, cancers develop resistance to this agent by promoting DNA repair. The DNA-PK (DNA-PKcs) catalytic subunit and poly(ADP-ribose) polymerase 1 (PARP1) mediate acquired resistance and poor survival in NPC cells exposed to DNA damaging agents. DNA repair can alter the sensitivity of NPC cells to DNA damaging agents, and these two enzymes function concomitantly in response to DNA damage in vivo. Therefore, we explored the relationship between DNA-PKcs and PARP1, which may affect NPC cell survival by regulating DNA repair after VP-16 treatment. We performed quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunoassays and found that DNA-PKcs knockdown downregulated the PARP1 and PAR expression. Conversely, PARP1 knockdown reduced DNA-PKcs activity, indicating the mutual regulation between DNA-PKcs and PARP1 in VP-16-induced DNA repair. Moreover, a combination treatment with olaparib (a PARP1 inhibitor) and NU7441 (a DNA-PKcs inhibitor) sensitized NPC cells to VP-16 in vitro and in vivo, suggesting that the combined treatment of olaparib, NU7441, and a DNA-damaging agent may be a successful treatment regimen in patients with NPC.

Background Previous studies have revealed obesity, nutrition, lifestyle, genetic and epigenetic factors may be risk factors for the occurrence and development of non-alcoholic fatty liver disease (NAFLD). However, the effect of total polyunsaturated fatty acid (PUFA) consumption on the risk of NAFLD is uncertain. Therefore, this study aimed to determine whether the total PUFA intake is independently associated with the risk of NAFLD and explore the threshold of PUFA intake better illustrate the correlation between them in Chinese Han adults. Methods The present study was a retrospective case–control study. A total of 534 NAFLD patients and 534 controls matched by gender and age in the same center were included in this study. Using a semi-quantitative food frequency questionnaire in a health examination center in China to collect information about dietary intake and calculate nutrient consumption. A multivariate logistic regression model was used to estimate the association between total PUFA daily intake and its quartile and the incidence of NAFLD. Results Multivariate analyses suggested a significant association between total PUFA intake and the occurrence of NAFLD. A non-linear relationship between total PUFA consumption and NAFLD risk was detected after adjusting for potential confounding factors. There was a significant connection between PUFA and the risk of NAFLD (OR: 1.32, 95% CI: 1.23–1.41, P Conclusions The relationship between total PUFA intake and NAFLD is non-linear. Total PUFA was positively related to the risk of NAFLD when PUFA intake is between 18.8 and 29.3 g/day among Chinese Han adults.

Some microbial-associated molecular patterns (MAMPs), like glucan oligosaccharides, can be recognized by pattern recognition receptors (PRRs) of plant to elicit further immunity response. In this study, a novel glycoside hydrolase family 55 β-1,3-glucanase (AcGluA) from Archangium sp. strain AC19 was cloned and expressed in Escherichia coli. Among the reported β-1, 3-glucanases from the glycoside hydrolase 55 family, the purified AcGluA exhibited the highest activity on laminarin at pH 6.0 and 60 °C with 112.3 U/mg. Activity of AcGluA was stable in the range of pH 4.0–9.0 and at temperatures below 60 °C. The Km and Vmax of AcGluA for laminarin were 3.5 mg/ml and 263.5 μmol/(ml·min). AcGluA hydrolyzed laminarin into a series of oligosaccharides, suggesting it was an endo-β-1,3-glucanase. The high dose of oligosaccharides (1600 mg/l) had conspicuous biocontrol efficacy on the defense of rice seedlings to Magnaporthe oryzae, which provided a new idea for the development of green biopesticide. Key points • The AcGluA was determined bacteria-derived β-1,3-glucanases in the GH55 family. • The AcGluA showed the highest activity towards laminarin among reported GH55 family. • The hydrolysates of laminarin showed conspicuous biocontrol efficacy to M. oryzae.

Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G (1-2) and 17��-carboxaldehyde-ent-kaur-18-oic acid (3), together with four known compounds (4���7). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.

Hyperalgesia, which often occurs in people suffering from alcohol use disorder, may drive excessive drinking and relapse. Emerging evidence suggests that the lateral habenula (LHb) may play a significant role in this condition. Previous research suggests that endocannabinoid signaling (eCBs) is involved in drug addiction and pain, and that the LHb contains core components of the eCBs machinery. We report here our findings in rats subjected to chronic ethanol vapor exposure. We detected a substantial increase in endocannabinoid-related genes, including Mgll and Daglb mRNA levels, as well as monoacylglycerol lipase (MAGL) protein levels, as well as a decrease in Cnr1 mRNA and type-1 cannabinoid receptor (CB1R) protein levels, in the LHb of ethanol-exposed rats. Also, rats withdrawing from ethanol exposure displayed hypersensitivity to mechanical and thermal nociceptive stimuli. Conversely, intra-LHb injection of the MAGL inhibitor JZL184, the fatty acid amide hydrolase inhibitor URB597, or the CB1R agonist WIN55,212-2 produced an analgesic effect, regardless of ethanol or air exposure history, implying that alcohol exposure does not change eCB pain responses. Intra-LHb infusion of the CB1R inverse agonist rimonabant eliminated the analgesic effect of these chemicals. Rimonabant alone elicited hyperalgesia in the air-, but not ethanol-exposed animals. Moreover, intra-LHb JZL184, URB597, or WIN55,212-2 reduced ethanol consumption in both homecages and operant chambers in rats exposed to ethanol vapor but not air. These findings suggest that LHb eCBs play a pivotal role in nociception and facilitating LHb eCBs may attenuate pain in drinkers.

Strain YIM 132242T, isolated from lichen collected from Pu’er, Yunnan Province, China, was short-rod-shaped, Gram-reaction-negative, aerobic, catalase- and oxidase-positive. Growth of the strain was occurred at 10–39 °C (optimum, 28–35 °C), at pH 4.0–10.0 (optimum, pH 7.0–8.0) and at salinities of 0–8% (w/v) NaCl (optimum, 0–2%). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YIM 132242T belonged to the genus Paracoccus and had the highest levels of sequence similarity to Paracoccus aerius KCTC 42845T (97.0% similarity), Paracoccus sediminis CMB17T (96.8% similarity), and Paracoccus fontiphilus MVW-1T (96.4% similarity). The major fatty acid was identified as C18:1 ω7c (77.6%). The predominant respiratory quinone was ubiquinone-10 (Q-10). Polar lipid analysis indicated the presence of phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), diphosphatidylglycerol (DPG), an unidentified lipid (L), and three unidentified phospholipids (PL1-PL3). Based on the draft genome sequence, the DNA G + C content of the strain was 67.1 mol%, and the values of average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) of strain YIM 132242T with Paracoccus aerius KCTC 42845T were 85.4% and 29.1%, respectively. On the basis of the data from this polyphasic characterization, strain YIM 132242T represents a novel species of the genus Paracoccus, for which the name Paracoccus lichenicola sp. nov. is proposed. The type strain is YIM 132242T (= KCTC 72463T = CGMCC1.17191T).

Six oxazolomycins (1–6) were isolated from the fermentation broth of a soil-borne bacterial strain, Streptomyces glaucus.

Metabolic reactions provide energy and metabolic substance for cell function. It was recently shown that metabolic reprogramming is a key regulator of cell pluripotency and differentiation. Although many evidences point to a metabolic "switch" toward mitochondrial respiration, the importance of glycolysis and mitochondrial respiration is still controversial. In this study, we differentiated two different neuronal cells and compared the glycolytic and metabolic profile before and after differentiation. The results showed a significant increase in glycolysis (includes basal glycolysis and glycolytic capacity) and mitochondrial respiration (includes mitochondrial basal respiration, adenosine triphosphate production, and mitochondrial respiration capacity) of both SY5Y and neural stem cells (NSCs) during neuronal differentiation, whereas their mitochondrial DNA copies remain unchanged. Antimycin, a mitochondrial inhibitor, reduced cell density of differentiated SY5Y cells. However, for differentiated NSCs, antimycin dedifferentiated the cells, resulted in a significant increase in cell density, and lowered oxidative stress. In conclusion, this study demonstrated that metabolic enhancement of glycolysis and mitochondrial respiration (rather than a "switch") are both important for neuronal differentiation, although only the blocking of mitochondrial respiration reverses the differentiation process.

A Gram-stain-positive, non-motile, aerobic, rod-shaped, golden yellow-pigmented actinobacterium, designated strain YIM 123512T, was isolated from soil sampled at Gaoligong Mountain, Yunnan Province, PR China. The strain grew at 10–40 °C (optimum, 28 °C), with 0–3.0 % (w/v) NaCl (optimum, 0–1.0 %) and at pH 5.0–11.0 (optimum, pH 7.0). The major menaquinone was MK-8(H4) and the major cellular fatty acids (>10 %) were identified as iso-C16 : 0 and C17 : 1 ω8c. Strain YIM 123512T had ll-2, 6-diaminopimelic acid as the diagnostic cell-wall diamino acid. The major polar lipids were found to be diphosphatidylglycerol, phosphatidylglycerol, two unknown phospholipids and one unknown lipid. The genomic DNA G+C content of strain YIM 123512T was 72.7 mol% based on its draft genome sequence. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain YIM 123512T appeared to be most closely related to Nocardioides halotolerans KCTC 19274T (97.7 % sequence similarity) and to belong to the genus Nocardioides . The sequence similarity values of strain YIM 123512T to other currently described type strains of the genus Nocardioides were less than 97.0 %. Based on the draft genome sequence, the novel strain showed an average nucleotide identity value of 80.2 % and a digital DNA–DNA hybridization value of 23.1 % with the reference strain N. halotolerans KCTC 19274T. The results of the polyphasic taxonomic study including phenotypic, chemotaxonomic and phylogenetic analyses show that strain YIM 123512T represents a novel species of the genus Nocardioides , for which the name Nocardioides flavescens sp. nov. is proposed. The type strain is YIM 123512T (=KCTC 49303T=CGMCC 4.7628T).

Msb2 is important for growth, conidia and sclerotia formation in Aspergillus flavus. Msb2 play negative roles in regulation of aflatoxins biosynthesis., Summary As a pathogenic fungus, Aspergillus flavus can produce carcinogenic aflatoxins (AFs), which poses a great threat to crops and animals. Msb2, the signalling mucin protein, is a part of mitogen‐activated protein kinase (MAPK) pathway which contributes to a range of physiological processes. In this study, the roles of membrane mucin Msb2 were explored in A. flavus by the application of gene disruption. The deletion of msb2 gene (Δmsb2) caused defects in vegetative growth, sporulation and sclerotia formation when compared to WT and complement strain (Δmsb2C) in A. flavus. Using thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC) analysis, it was found that deletion of msb2 down‐regulated aflatoxin B1 (AFB1) synthesis and decreased the infection capacity of A. flavus. Consistently, Msb2 responds to cell wall stress and osmotic stress by positively regulating the phosphorylation of MAP kinase. Notably, Δmsb2 mutant exhibited cell wall defect, and it was more sensitive to inhibitor caspofungin when compared to WT and Δmsb2C. Taking together, these results revealed that Msb2 plays key roles in morphological development process, stresses adaptation, secondary metabolism and pathogenicity in fungus A. flavus.

Bacterial non-enzymatic Mn(II) oxidation involving reactive oxygen species (ROS) (i.e. indirect oxidation), initially discovered from a marine alpha-proteobacterium, is believed to be of importance in controlling biogeochemical cycles. For soil-borne bacteria, however, evidence of indirect Mn(II) oxidation remains unclear. In this study, the indirect Mn(II) oxidation was evidenced in a soil-borne bacterium, Providencia sp. LLDRA6. First, with and without 50 mM of Mn(II) exposure for LLDRA6, 300 differentially expressed genes were found to be linked to Mn(II) exposure via transcriptome sequencing. Among them, an operon, responsible for phenylacetic acid catabolism, was sharply upregulated in transcription, drawing us a special attention since its transcriptional upregulation has recently shown to be important for withstanding ROS. Next, a fluorometric probe, 2′,7′-Dichlorofluorescin diacetate (DCFDA), was used to qualitatively detect ROS from cells, showing a distinct increase in fluorescence intensities of ROS during Mn(II) exposure. Further, concentrations of superoxide and hydrogen peroxide from cells were detected respectively with and without Mn(II) exposure, exhibiting that when Mn(II) oxidation occurred, superoxide concentration significantly increased but hydrogen peroxide concentration significantly decreased. Particularly, superoxide produced by LLDRA6 was proven to be the oxidant for Mn(II) in the formation of Mn oxides. Finally, we predicted links between phenylacetic acid metabolism pathway and ROS during Mn(II) exposure, proposing that the excessive ROS, generated in response to Mn(II) exposure, transcriptionally activate phenylacetic acid catabolism presumably by increasing concentrations of highly reactive oxepins.

In this study, various indium zinc tin oxide (IZTO) films were fabricated using co-sputtering to explore amorphous transparent conducting oxides as alternatives to crystalline indium tin oxide (ITO). Various Zn ratios were tuned to study their effects on the structural evolution of IZTO. Amorphous IZTO (aIZTO) films were obtained when the Zn concentration was higher than approximately 17 at.%. X-ray diffraction and transmission electron microscopy analyses indicated that amorphous structures were formed due to the high crystallization temperatures of IZTO and nanocrystalline In2Zn5O8, which also caused aIZTO to exhibit small band gaps. On average, 87% transmittance was achieved in the visible light range. The aIZTO films had substantially higher transmittance in the infrared region than the ITO films did. Samples with Zn ratios between approximately 17 at.% and 27 at.% exhibited resistivity (approximately 3 × 10−4 Ω-cm), mobility (7 cm2 V−1 s−1), and carrier concentrations (4 × 1021 cm−3) comparable to those of crystalline ITO. Thus, the aIZTO films are promising alternative TCO materials. The mechanisms of competition between the crystallinity, oxygen deficiency, high-mobility In2Zn5O8, and electron and hole generation rates were applied to shed light on the excellent electrical and transport properties of aIZTO films.

The c-myc oncogene is an important regulator for cell growth and differentiation, and its aberrant overexpression is closely related to the occurrence and development of various cancers. Thus, the suppression of c-myc transcription and expression has been investigated for cancer treatment. In this study, various new bisacridine derivatives were synthesized and evaluated for their binding with c-myc promoter G-quadruplex and i-motif. We found that a9 could bind to and stabilize both G-quadruplex and i-motif, resulting in the downregulation of c-myc gene transcription. a9 could inhibit cancer cell proliferation and induce SiHa cell apoptosis and cycle arrest. a9 exhibited tumor growth inhibition activity in a SiHa xenograft tumor model, which might be related to its binding with c-myc promoter G-quadruplex and i-motif. Our results suggested that a9 as a dual G-quadruplex/i-motif binder could be effective in both oncogene replication and transcription and become a promising lead compound for further development with improved potency and selectivity.

Heat stress negatively affects wheat production in many regions of the world. At present, sensitivity to heat stress remains one of the least understood aspects of wheat genetics and breeding, and measures for preventing heat stress are understudied. In this study, we used three cultivars of winter wheat (GY2018, SL02-1 and SY20) to evaluate the effect of heat stress at different days after anthesis (DAA) on yield and quality. Heat stability of the cultivars were analyzed and evaluated for the effects of two kinds of regulators on wheat under heat stress conditions. Heat treatment at 7 DAA led to the most substantial reduction in yield while GY2018 had the best heat stability with respect to yield, and demonstrated the most positive effects on several quality traits including protein content, sedimentation volume and glutenin and gliadin contents. Heat treatment at 14 DAA had the least reduction in yield, while SY20 had the best heat stability with respect to yield and heat treatment had minimal effects on quality. Heat treatment at 21 DAA had only a limited effect on yield, while SL02-1 had the best heat stability with respect to yield, but it showed the most negative effects on quality. Stable time at 14 DAA and protein content at 21 DAA can be used as indicators for detecting the stability of quality under heat stress. Among the three studied cultivars, SY20 was the most sensitive to heat stress with the stable time decreasing from 26.4 to 9.1 min, a higher sedimentation volume at 7 DAA, and a lower γ-gliadin content which increased 2.4-fold under high-temperature treatment. The addition of various regulators had different effects: potassium dihydrogen phosphate (KDP) was more protective of yield with heat stress at 7 DAA, while Duntianbao (DTB) had better effects on quality with heat stress at 21 DAA.

DNA damage response (DDR) pathways are crucial for the survival of cancer cells and are attractive targets for cancer therapy. Bloom syndrome protein (BLM) is a DNA helicase that performs important roles in DDR pathways. Our previous study discovered an effective new BLM inhibitor with a quinazolinone scaffold by a screening assay. Herein, to better understand the structure-activity relationship (SAR) and biological roles of the BLM inhibitor, a series of new derivatives were designed, synthesized, and evaluated based on this scaffold. Among them, compound 9h exhibited nanomolar inhibitory activity and binding affinity for BLM. 9h could effectively disrupt BLM recruitment to DNA in cells. Furthermore, 9h inhibited the proliferation of the colorectal cell line HCT116 by significantly triggering DNA damage in the telomere region and inducing apoptosis, especially in combination with a poly (ADP-ribose) polymerase (PARP) inhibitor. This result suggested a synthetic lethal effect between the BLM and PARP inhibitors in DDR pathways.

Previous studies have shown that the tumor necrosis factor-α (TNF-α) levels in serum and bone tissues formed in avascular necrosis of femoral head (ANFH) patients were higher than those of normal individuals, indicating TNF-α might play a role in the pathogenesis of ANFH. However, the underlying mechanisms remain unclear. Hematoxylin and eosin staining was performed to show the pathological changes of ANFH bone tissues. TNF-α expression in normal and ANFH tissues was examined by quantitative real-time polymerase chain reaction and western blot analyses. Osteoblast autophagy and apoptosis, as well as signaling pathways activation, were measured by their corresponding marker proteins. Osteoblast proliferation, autophagy, and apoptosis were evaluated using cell counting kit-8, transmission electron microscopy, and flow cytometry. The structures of bone tissues of ANFH were obviously damaged. TNF-α expression was significantly upregulated in ANFH bone tissues compared to normal tissues. Autophagy and apoptosis were remarkably promoted, and p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways were markedly activated in ANFH. Suppression of the p38 MAPK/NF-κB pathway significantly attenuated the TNF-α-induced autophagy, however, enhanced the TNF-α-induced apoptosis in osteoblasts. Increased TNF-α in ANFH regulated osteoblast autophagy and apoptosis by p38 MAPK/NF-κB signaling pathways, blocking the pathway by inhibitors exacerbated TNF-α-induced apoptosis through impairing autophagy flux.

Soil plays a crucial role in tea tree growth, however, only few studies have reported the responses of soil microorganisms to soil acidification in tea plantations and the negative regulation of soil acidification on tea tree growth. In this study, the soil samples from Tieguanyin tea tree plantation with different acidities were used as a material for rhizosphere soil microbial protein extraction. Data dependent acquisition (DDA) was used to establish the soil microbial protein data, whereas Data independent acquisition (DIA) was used for quantitative analyses to obtain the reduced abundance of soil protein in tea rhizosphere soil. Furthermore, the functional analysis of the obtained proteins was conducted, and the regulation map of microbial protein metabolism of rhizosphere soil was constructed. The results showed that a total of 2,741 microbial proteins were detected in the tea tree rhizosphere soil, and the molecular weight ranged from 2.64 to 338.33 kD, whereas the range of pI was from 3.78 to 12.15. Quantitative analyses of soil proteins showed that the abundance of 54 microbial proteins, including genetic signaling proteins, energy metabolism signaling proteins, soil antioxidant signaling proteins, and soil nutrient cycling signaling proteins, which are named according to their functions, was decreased. Based on these analyses, a metabolic regulation map of soil microbial proteomes was constructed, and the results suggested that as tea soil acidity increased, soil microbes released quorum-sensing proteins to trigger signaling proteins for survival. Under the regulation of signaling pathway proteins, signaling proteins activated the expression of specific signaling proteins in different metabolic pathways and then regulated the expression of proteins in different metabolic pathways, demonstrating a downregulated expression trend. Finally, this regulation resulted in a decrease of microbial energy metabolism and circulation capacity as well as the reproduction capacity and quantity. The change in microbial quantity and function led to the weakening of soil nutrient cycling capacity, the blocking of the absorption of nutrients in tea trees, and the stunting of the growth and the declining of the yield and quality of tea trees.

A novel actinobacterium, YIM 132087T, isolated from Lepraria sp. lichen collected from Yunnan province, south-west PR China. Cells are Gram-stain-positive, catalase-positive and oxidase-negative, aerobic, non-motile and short rod-shaped. Colonies are asporogenous, circular and white brown in colour. Optimal growth occured at 15−35 °C (optimum 28 °C), at pH 5.0−9.0 (optimum pH 6.0), and in the presence of 3% NaCl (w/v). The DNA G+C content of strain YIM 132087T based on the draft genome sequence was 71.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences suggested that strain YIM 132087T belonged to the genus Nakamurella and exhibited high levels of 16S rRNA gene sequence similarity with Nakamurella endophytica CGMCC 4.7038T (97.9%) and Nakamurella intestinalis NBRC 111844T (97.2%). The DNA–DNA hybridization values between strain YIM 132087T and its closest relatives are lower than 26%. Strain YIM 132087T had meso-diaminopimelic acid as the diagnostic cell-wall diamino acid, and MK-8(H4) as the predominant menaquinone. Predominant cellular fatty acids (> 10%) were iso-C16:0, iso-C15:0, C16:0 and anteiso-C15:0. The polar lipid profile were found to be diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, three unknown phospholipids, one unknown aminophospholipid and one unknown lipid. Based on phenotypic, phylogenetic and chemotaxonomic analysis, strain YIM 132087T belongs to the genus Nakamurella and represents a novel species of the genus Nakamurella, for which the name Nakamurella albus sp. nov., with type strain YIM 132087T (=CGMCC 4.7629T =NBRC 114017T), is proposed.

Candida rugosa lipase was immobilized in this study using CaCl2/CMC nanoparticles that yielded a lipase loading capacity of 127 mg/g, with better thermal stability and activity of 91.8%. The hydrolysis of racemic 2-phenylpropionic acid isopropyl ester by free and immobilized Candida rugosa lipase was investigated in the mixed organic-solvent composed of isooctane and methyl tert-butyl ether (9.5:0.5, V/V). The optimal conditions were 35 °C and pH 7.5 for free Candida rugosa lipase hydrolysis. We obtained (S)-2-phenylpropionic acid with 44.85% conversion, 95.75% enantiomeric excess and enantiomeric ratio of 112. The CaCl2/CMC nanoparticles immobilized Candida rugosa lipase possesses high enantioselectivity, with E = 237 at 40 °C and pH 7.5. It was efficiently reusable in four cycles and appropriately enhanced enantioselectivity within 120–240.

Background Pancreatic cancer (PC) is one of the most well-known malignancies with high mortality, but the underlying mechanism of PC remains unknown. Keratin17 (KRT17) expression has been reported in many malignancies, but its functions in PC are not clear. The aim of our study was to evaluate KRT17 expression and its potential role in PC. Methods The online databases GEPIA and THPA were used to identify KRT17 expression in tissues. Quantitative real-time PCR (qRT-PCR) was used to determine KRT17 expression in cell lines. Ki67 and ROS levels were detected by immunofluorescence assay and a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. KRT17 downregulation was induced by the small interfering RNA (siRNA) technique. Proliferation function was evaluated by colony formation assay and RTCA. Migration and invasion were evaluated by transwell migration assay. A Western blot assay was used to detect protein levels. Results KRT17 was overexpressed in PC tissues compared to that in normal tissues. The results showed that Ki67 and ROS levels were decreased in pancreatic cancer cells after transfection with siKRT17. After KRT17 downregulation in PC cell lines, cell viability functions, including proliferation, migration and invasion, and mTOR/S6K1 phosphorylation levels were attenuated. Conclusion KRT17 knockdown significantly inhibited proliferation, migration and invasion in pancreatic cancer cells.

A new monocyclic diterpenoid, cassipouryl formate, (1) together with three known diterpenoids (2−4) and five known sesquiterpenoids (5−9) were isolated from the twigs and leaves of Syzygium fluviatile. The new isolate was elucidated by various spectroscopic technologies. This was the first example of the chemical constituents from this species and the first report on the diterpenoids from genus Syzygium.

A Gram-stain-positive, yellow-pigmented, catalase-positive and oxidase-negative, strictly aerobic actinobacterium, designated strain YIM 131853T, was isolated from lichen collected from the South Bank of the Baltic Sea. The novel strain was non-spore-forming, short rod-shaped and motile with a single polar flagellum. The strain could grow at 4–37 °C (optimum, 28 °C), at pH 4.0–12.0 (pH 6.0) and at 0–3 % (w/v) NaCl (1 %). The DNA G+C content of strain YIM 131853T based on the draft genome sequence was 68.3 mol%. Predominant cellular fatty acids (>10 %) were identified as anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipid profile included diphosphatidylglycerol, dimannosyldiacylglycerol, three unknown glycolipids, two unknown phospholipids and one unknown lipid. Strain YIM 131853T had 2,4-diaminobutyric acid as the diagnostic cell-wall diamino acid, galactose and glucose as whole-cell sugars, and MK-10, MK-14, MK-13 and MK-12 as the major menaquinones. Although strain YIM 131853T exhibited a highest 16S rRNA gene sequence similarity (96.6 %) to Amnibacterium kyonggiense NBRC 109360T, phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain formed a tight lineage with Naasia aerilata NBRC 108725T (96.5 % 16S rRNA gene sequence similarity), which was the only species of genus Naasia . Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM 131853T should belong to the genus Naasia and represents a novel species of the genus Naasia , for which the name Naasia lichenicola sp. nov. is proposed. The type strain is YIM 131853T (=CGMCC 4.7565T=NBRC 113605T).

A new tetranorditerpenoid (1), two new labdane diterpenoids (2, 3), and nine known analogues (4-12) were isolated from the rhizomes of Amomum villosum var. xanthioides. Compound 1 is an unprecedented rearranged tetranorlabdane diterpenoid, featuring a 6/6/5 fused tricarbocyclic skeleton with an α,β-unsaturated cyclopentenone unit, while 2 is a structurally rare labdane diterpenoid carrying a five-membered cyclic anhydride moiety. Their structures and absolute configurations were established on the basis of spectroscopic data and the experimental and calculated ECD data. Compound 4 showed inhibitory activity against nitric oxide production, with an IC50 value of 2.4 μM, and also inhibited α-glucosidase activity (IC50 = 10.0 μM).

Heme oxygenase-1 (HO-1) is one of the most powerful cytoprotective proteins known. The goal of this study was to explore the effects of HO-1 in c-kit-positive cardiac cells (CPCs). LinNEG/c-kitPOS CPCs were isolated and expanded from wild-type (WT), HO-1 transgenic (TG), or HO-1 knockout (KO) mouse hearts. Compared with WT CPCs, cell proliferation was significantly increased in HO-1TG CPCs and decreased in HO-1KO CPCs. HO-1TG CPCs also exhibited a marked increase in new DNA synthesis during the S-phase of cell division, not only under normoxia (21% O2) but after severe hypoxia (1% O2 for 16 h). These properties of HO-1TG CPCs were associated with nuclear translocation (and thus activation) of Nrf2, a key transcription factor that regulates antioxidant genes, and increased protein expression of Ec-SOD, the only extracellular antioxidant enzyme. These data demonstrate that HO-1 upregulates Ec-SOD in CPCs and suggest that this occurs via activation of Nrf2, which thus is potentially involved in the crosstalk between two antioxidants, HO-1 in cytoplasm and Ec-SOD in extracellular matrix. Overexpression of HO-1 in CPCs may improve the survival and reparative ability of CPCs after transplantation and thus may have potential clinical application to increase efficacy of cell therapy.

Study on the form partitioning and content of heavy metals in soil particles with different sizes is crucial for preventing and controlling heavy metals pollution, but few studies regard soil contaminated by heavy metals as a homogeneous body. In this study (Fig. 1), goat manure, lime and phosphate were used to stabilize exogenous lead (Pb). These soil passivators’ differential effects on total Pb and Pb with different chemical forms in soil particles of different sizes as well as Pb immobilization in soil were investigated. By passivation experiment in laboratory for 45 days, the passivation effect of the single and combined application treatments on exogenous Pb and partitioning characteristics were analyzed and compared. The characterization method of fine sand microstructure and mineral composition analysis was used. The results showed that the single application of P5 and combined application of LP5 had optimum passivation efficiency. The content of DTPA-Pb was reduced with P5 by 65.27% and the percentage of available Pb decreased significantly in soil particles of the four sizes. The content of TCLP-Pb and available Pb (weak acid extraction and reducible Pb) significantly decreased by 71.60 and 25.12% respectively after the application of LP5 in the original soil. Furthermore, most of the total Pb was enriched in coarse sand and clay, while its content was lower in fine sand and silt. The combined application treatment of GL5 significantly increased the content of weak acid extractable and reducible Pb in fine sand, silty sand and clay. Through SEM and XRD analysis, it was found that the diffraction peak of P5 treatment groups might be related to the formation of insoluble Pb that contained compounds, which were mainly mineral components, including quartz, feldspar and mica, and LP showed a big potential in the study on passivation of heavy metal Pb-contaminated soil in the natural environment. In conclusion, further studies on the different dosage and metal-contamination levels as well as different combination forms of passivators should be considered under natural conditions, the selection of suitable passivators according to soil texture is of great significance for remediation of Pb-contaminated soil.

Lorcaserin is a serotonergic agonist specific to the 5-hydroxytryptamine 2c receptor (5-HT2CR) that is FDA approved for the long-term management of obesity with or without at least one weight-related comorbidity. Lorcaserin can restrain patients’ appetite and improve insulin sensitivity and hyperinsulinemia mainly through activating 5-HT2CR in the hypothalamus. It is known that the mCPP, a kind of 5-HT2CR agonist, decreases plasma insulin concentration in mice and previous research in our laboratory found that mCPP inhibited glucose-stimulated insulin secretion (GSIS) by activating 5-HT2CR on the β cells. However, the effect of lorcaserin on GSIS of pancreatic β cell has not been studied so far. The present study found that 5-HT2CR was expressed in both mouse pancreatic β cells and β-cell–derived MIN6 cells. Dose-dependent activation of 5-HT2CR by lorcaserin suppressed GSIS and SB242084 or knockdown of 5-HT2CR abolished lorcaserin’s effect in vitro. Additionally, lorcaserin also suppressed GSIS in high-fat diet (HFD)-fed mice in dose-dependent manner. Lorcaserin did not change insulin synthesis ATP content, but lorcaserin decrease cytosolic free calcium level [(Ca2+)i] in MIN6 cells stimulated with glucose and also inhibit insulin secretion and (Ca2+)i in MIN6 treated with potassium chloride. Furthermore, stimulation with the L-type channel agonist, Bay K8644 did not restore GSIS in MIN6 exposed to lorcaserin. Lorcaserin inhibits the cAMP generation of MIN6 cells and pretreatment with the Gα i/o inhibitor pertussis toxin (PTX), abolished lorcaserin-induced suppression of GSIS in β cells, while membrane-permeable cAMP analogue db-cAMP had same effect as PTX. These date indicated lorcaserin coupled to PTX-sensitive Gα i/o proteins in β cells reduced intracellular cAMP level and Ca2+ influx, thereby causing GSIS dysfunction of β cell. These results highlight a novel signaling mechanism of lorcaserin and provide valuable insights into the further investigation of 5-HT2CR functions in β-cell biology and it also provides guidance for the clinical application of lorcaserin.

Xiao-Hong Chen,1 Ding-Li Yu,2 Jiang-Tao Zhong,2 Shui-Hong Zhou,2 Jun Fan,3 Zhong-Jie Lu4 1Department of Otolaryngology, The Second Hospital of Jiaxing (The Second Affiliated Hospital, Jiaxing University), Jiaxing City, Zhejiang Province, 314000, People’s Republic of China; 2Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 4Department of Radiotherapy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Shui-Hong ZhouDepartment of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of ChinaTel +86-571-87236894Fax +86-571-87236895Email 1190051@zju.edu.cnPurpose: Hexokinase-II (HK-II) is the key enzyme in the first rate-limiting step of glycolysis that catalyzes the conversion of glucose to glucose-6-phosphate. Here, we examined the association between HK-II expression and radioresistance in laryngeal carcinoma and whether the inhibition of HK-II expression can enhance the radiosensitivity of these tumors.Methods: The effects of HK-II small interfering RNA (siRNA) on the radiosensitivity of Tu212 cells were examined in vitro and in vivo in a mouse model. Cells were irradiated using a 6-MV linear accelerator. The cell viability, cell survival, proliferation, apoptosis, and cell cycle of Tu212 cells were evaluated using trypan blue staining, colony formation assays, CCK-8 assays, and flow cytometry, respectively. Oxygen consumption, lactic acid production, glucose consumption, and the ATP level of Tu212 cells were also examined. The expression of glycolytic and regulatory enzymes involved in the tricarboxylic acid cycle was assessed using Western blotting.Results: The HK-II siRNA and X-ray combination treatment led to a significantly greater reduction of cell viability, inhibition of cell survival and proliferation, increased apoptosis, and increased G2 phase arrest compared to either treatment alone (all, P< 0.01). HK-II siRNA increased the oxygen consumption rate of cells, significantly inhibited lactic acid production and glucose consumption, and significantly suppressed the upregulation of HK-II, pyruvate kinase M2 (PKM2), pyruvate dehydrogenase (PDH), phosphofructokinase platelet (PFKP), lactate dehydrogenase (LD), and citrate synthase (CS) (all, P< 0.01).Conclusion: The inhibition of HK-II by siRNA enhances the radiosensitivity of laryngeal carcinoma Tu212 cells by inhibiting glycolysis and partially inhibiting oxidative phosphorylation.Keywords: laryngeal carcinoma, hexokinase-II, siRNA, radiosensitivity, Warburg effect

Biogas slurry, a byproduct of biogas plants, is considered a high-quality bio-organic fertilizer. Despite providing nutrients to crops, biogas slurry may contain a high concentration of heavy metals, leading to food safety problems and endangering human health if such metals are absorbed by plants. Therefore, biogas slurry should undergo systematic risk assessment prior to direct use on farmland to ensure its safety for soils and crops. In this study, the risk of applying biogas slurry in peanut cultivation was comprehensively evaluated. Based on nitrogen contents, different concentrations of biogas slurry were applied in peanut cultivation. The results achieved herein showed that the application of biogas slurry as a nutrient supplier in peanut cultivation would significantly affect the physical and chemical properties of soil and characteristics of the plant and the quality of peanuts. Although the heavy metal content of biogas slurry was within the permitted range, it had potential risks to human health and the environment. Principal component analysis (PCA) showed that biogas slurry was the primary source of heavy metals in soil. After the application of biogas slurry, the contents of As and Hg in the soil increased significantly, which were 11.12 and 26.67 times higher than those in the control soil. The contents of Cu, Zn, Pb, Cd, and As in peanut kernel samples under different levels of biogas slurry application were all lower than the maximum permissible limit set by the Standardization Administration of China. In contrast, the content of Hg in peanut kernels was higher than the maximum permissible limit value of 0.02 mg/kg. Peanut had a higher enrichment capacity of Cd and Zn and a higher migration capacity of Pb. The health risk assessment showed that the long-term consumption of peanuts grown with a high dosage of biogas slurry would be harmful to the health of children aged 2–6 years with a large consumption level.

Probiotic intake has been shown to improve certain physiological health indicators. We aimed to examine effects of Lactobacillus&nbsp, casei LTL1879, obtained from long-lived elderly volunteers, on blood biochemical, oxidative, and inflammatory markers and gut microbiota in twenty healthy, young volunteers. Volunteers were randomly divided into equal probiotic and placebo groups and changes in blood biochemical indicators, oxidative and inflammatory markers, and gut microbiota were examined after three weeks of probiotic intervention. The probiotic group’s antioxidant levels were significantly enhanced post-intervention. Total antioxidant capacity (T-AOC) levels were significantly increased (p &lt, 0.0001), while malondialdehyde (MDA) levels decreased (p &lt, 0.05), and total superoxide dismutase (T-SOD) levels increased, but with no significant difference. In addition, Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) levels were significantly up-regulated and down-regulated (p &lt, 0.05, respectively). Escherichia coli, Enterococcus, and Bacteroides expression was significantly reduced (p &lt, 0.05), while Clostridium leptum, Bifidobacterium, and Lactobacillus expression increased (p &lt, 0.05). Volunteer health status was quantified using principal components and cluster analysis, indicating that the probiotic group’s overall score was higher than that of the placebo group. The results of this pilot study suggest L. casei LTL 1879 can significantly improve specific immune, oxidative, and gut microbiota characteristics related to health factors.

A heavy element is a special character for high thermoelectric performance since it generally guarantees a low lattice thermal conductivity. Here, we unexpectedly found a promising thermoelectric performance in a two-dimensional semiconducting monolayer consisting of a light boron element. Using first-principles combined with the Boltzmann transport theory, we have shown that in contrast to graphene or black phosphorus, the boron monolayer has a low lattice thermal conductivity arising from its complex crystal of hexagonal vacancies. The conduction band with an intrinsic camelback shape leads to the high DOS and a high n-type Seebeck coefficient, while the highly degenerate valence band along with the small hole effective mass contributes to the high p-type power factor. As a result, we obtained the p-type thermoelectric figure of merit up to 0.96 at 300 K, indicating that the boron monolayer is a promising p-type thermoelectric material.

Acetaldehyde, the first metabolite of ethanol, is implicated in several of ethanol’s actions, including the reinforcing and aversive effects. The neuronal mechanisms underlying acetaldehyde’s aversive effect, however, are poorly understood. The lateral habenula (LHb), a regulator of midbrain monoaminergic centers, is activated by negative valence events. Although the LHb has been linked to the aversive responses of several abused drugs, including ethanol, little is known about acetaldehyde. We, therefore, assessed acetaldehyde’s action on LHb neurons in rats. The results showed that intraperitoneal injection of acetaldehyde increased cFos protein expression within the LHb and that intra-LHb infusion of acetaldehyde induced conditioned place aversion in male rats. Furthermore, electrophysiological recording in brain slices of male and female rats showed that bath application of acetaldehyde facilitated spontaneous firing and glutamatergic transmission. This effect of acetaldehyde was potentiated by an aldehyde dehydrogenase inhibitor, disulfiram, but attenuated by the antagonists of dopamine receptor subtype 1 (SCH23390) and subtype 2 (raclopride), and partly abolished by the pretreatment of dopamine or dopamine reuptake blocker (GBR12935). Moreover, application of acetaldehyde initiated a depolarizing inward current (IACD) and enhanced the hyperpolarizing-activated currents in LHb neurons. Bath application of Rp-cAMPs, a selective cAMP-PKA inhibitor attenuated acetaldehyde-induced potentiation of EPSCs and IACD. Finally, bath application of ZD7288, a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channels attenuated acetaldehyde-induced potentiation of firing, EPSCs, and IACD. These results show that acetaldehyde exerts its aversive property by exciting LHb neurons via multiple cellular mechanisms, and new treatments targeting the LHb may be beneficial for alcoholism. SIGNIFICANCE STATEMENT: Acetaldehyde has been considered aversive peripherally and rewarding centrally. However, whether acetaldehyde has a central aversive property is unclear. Here we report that acetaldehyde excites the LHb, a brain region associated with aversion and negative valence, through multiple cellular and molecular mechanisms. Intra-LHb acetaldehyde produces significant conditioned place aversion. These results suggest that acetaldehyde’s actions on the LHb neurons might contribute to its central aversive property and new treatments targeting the LHb may be beneficial for alcoholism.

The purpose of this study was to investigate the effects of dietary Selenohomolanthionine (SeHLan) on antioxidant status and immune response in canine parvovirus (CPV) vaccinated puppies. In this study, 30 weaned puppies were randomly divided into six groups: control group (–Se/–Vacc), immunization group (–Se/+Vacc), supplementation of sodium selenite group (SS/+Vacc, 0.35 mg/kg DM), low-dose SeHLan group (SeHLan-L/+Vacc, 0.35 mg/kg DM), mid-dose SeHLan group (SeHLan-M/+Vacc, 1.0 mg/kg DM), and high-dose SeHLan group (SeHLan-H/+Vacc, 2.0 mg/kg DM). The puppies were fed for 42 days and vaccinated with Vanguard Plus 5 on day 0 and day 21. Blood samples were collected on 7, 14, 21, 28, 35, 42 days post-immunization (PI) for determination of antioxidant indicators, lymphocyte proliferation index, serum cytokine concentration (IL-2, IL-4), canine polymorphonuclear neutrophils (PMN) phagocytic function, and the level of CPV antibody titers. The results showed that SeHLan supplementation raised the serum Se concentration and glutathione peroxidase (GSH-Px) activity in a dose-dependent manner (P < 0.05). It also increased the activity of serum superoxide dismutase (SOD) and decreased serum malondialdehyde (MDA) content, especially in SeHLan-M/+Vacc group (1.0 mg/kg DM) (P < 0.01). SeHLan supplementation significantly increased lymphocyte proliferation, IL-2, and IL-4 levels in canine serum, and enhanced phagocytosis of PMN in vaccinated puppies (P < 0.05). Moreover, SeHLan supplementation shortened the CPV antibody production time and increased the CPV antibody titers (P < 0.05). Of note, the beneficial effects of SeHLan were superior to those of SS. In conclusion, dietary SeHLan supplementation improved antioxidant activity, increased CPV antibody titers, and enhanced immune function in puppies after weaning. An appropriate dosage of SeHLan (1~2 mg/kg DM) may confer nutritional benefits in puppies.

Targeting endoplasmic reticulum (ER) stress, inflammation and metabolic dysfunctions may halt the pathogenesis of obesity and thereby reduce the prevalence of diabetes, cardiovascular disesases and cancers. The present study was designed to elucidate the mechnaisms by which plant-derived celastrol ameliorated inflammation and lipid accumulation in obesity. The mouse model of diet-induced obesity was induced by feeding high-fat diet for 3 months and subsequently intervented with celastrol for 21 days. Hepatic and adipose tissues were analysed for lipid accumulation, macrophage activation and biomarker expression. As result, celastrol effectively reduced body weight, suppressed ER stress, inflammation and lipogenesis while promoted hepatic lipolysis. RNA-sequencing revealed that celastrol-loaded nanomicelles restored the expression of 49 genes that regulate ER stress, inflammation and lipid metabolism. On the other hand, celastrol-PEG4-alkyne was synthesized for identifying celastrol-bound proteins in RAW264.7 macrophages. ER chaperone GRP78 was identified by proteomics approach for celastrol binding to the residue Cys41. Upon binding and conjugation, celastrol diminished the chaperone activity of GRP78 by 130-fold and reduced ER stress in palmitate-challenged cells, while celastrol analogue lacking quinone methide failed to exhibit anti-obesity effects. Thus, covalent GRP78 inhibition may induce the reprograming of ER signaling, inflammation and metabolism against diet-induced obesity.

A new monoterpenoid glycoside, together with seven known aliphatic acid derivatives, was isolated from the twigs and leaves of Syzygium fluviatile. Their structures were elucidated by means of NMR and HR-ESI-MS data and comparison with the reported values. This is the first example of a monoterpenoid glycoside from Syzygium plants.

To study the remediation effect of hydroxyapatite with different particle sizes, a field in situ experiment was carried out by adding conventional hydroxyapatite (0.25 mm) and microhydroxyapatite (3 μm) and nanohydroxyapatite (40 nm) to the contaminated soil and planting Elsholtzia splendens. The distribution and migration of copper (Cu) and cadmium (Cd) in soil were investigated after 4 years. The results show that the application of three different particle sizes of hydroxyapatite significantly raise the soil pH, total phosphorus, and soil organic carbon. Moreover, the addition of hydroxyapatite can reduce the EXC fraction of Cu and Cd by 73.7%–80.1% and 20.8%–35.2%, respectively. In addition, the concentrations of Cu and Cd in >2 mm, 0.25–2 mm, 0.053–0.25 mm, and

A novel Actinobacterium strain YIM 131861 T, was isolated from lichen collected from the South Bank Forest of the Baltic Sea, Germany. It was Gram-stain-positive, strictly aerobic, catalase positive and oxidase negative, yellow pigmented. Cells were motile with a polar flagellum, irregular rod shaped and did not display spore formation. The strain grew at 15 − 30 °C (optimum 25 °C), at pH 6.0 − 10.0 (optimum pH 7.0) and in the presence of 0 − 1.5% (w/v) NaCl (optimum 1%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain YIM 131861 T belonged to the genus Glaciibacter, and exhibited a high sequence similarity (96.4%) with Glaciibacter superstes NBRC 104264 T. The genomic DNA G + C content of strain YIM 131861 T was 68.2 mol%. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain YIM 131861 T and Glaciibacter superstes NBRC 104264 T were 73.2 and 19.9% based on the draft genome sequence. The cell-wall peptidoglycan type was B2γ and contained the 2, 4-diaminobutyric acid as the diagnostic amino acid. Whole cell sugars were galactose, rhamnose, ribose and glucose. It contained MK-12 and MK-13 as the predominant menaquinones. The major cellular fatty acids (> 10%) were identified as anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol and two unknown glycolipids. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM 131861 T should belong to the genus Glaciibacter and represents a novel species of the genus Glaciibacter, for which the name Glaciibacter flavus sp. nov. is proposed. The type strain is YIM 131861 T (= CGMCC 1.16588 T = NBRC 113572 T).

In our previous study, the chitosanase AqCoA and the chitooligosaccharides it produced were found to exhibit significant protective effects against fungal diseases. In this study, we enhanced the expression of AqCoA using the novel pMC-GAP that enables stable transformation of Escherichia coli, and built an integrated model based on the gene copy number, molecular chaperones, and protein production of AqCoA. In terms of gene dosage, the highest hydrolase activity was 0.32 U/ml in the strain with four copies, which was 1.78-fold higher than that of the strain with only one copy (0.18 U/ml). In addition, we found the chaperones such as PDI, ERO1, HAC1, YDJ1, SSE1, SSA4, and SSO2 improved protein expression. Furthermore, the PDI/ERO1, SSA4/SSE1, and YDJ1/SSO2 pairs synergistically increased the expression levels by 61%, 31%, and 42%, respectively. Finally, we investigated the combined effects of gene copy numbers and molecular chaperones on protein expression. The highest activity reached 2.32 U/ml in the strain with six integrated molecular chaperone expression cassettes and sixteen copies of the target gene, which was 13-fold higher than that of the control strain with only one copy (GAP-1AqCoA). Combined optimization of gene dosage and molecular chaperone combinations significantly increased the expression level of AqCoA, providing a powerful strategy to improve the expression of other heterologous proteins in P. pastoris.

MicroRNA (miRNA/miR)-124-3p has been extensively studied in tumor biology and stem cells. However, little is known regarding its functional roles in the differentiation of precartilaginous stem cells (PSCs) into nucleus pulposus-like cells (NPLCs). In the present study, using miRNA microarray screening, it was demonstrated that the miRNA expression profiles differed between rat primary PSCs and TGF-β1-induced differentiated NPLCs, and that miR-124-3p was significantly differentially expressed during the differentiation of PSCs to NPLCs. Furthermore, RT-qPCR analysis verified that miR-124-3p expression was decreased during PSC differentiation, with the lowest levels being detected at the later stages. Subsequent experiments revealed that miR-124-3p overexpression significantly decreased the expression of the extracellular matrix proteins, aggrecan and collagen type II, which was accompanied by a significant decrease in follistatin-related protein 1 (FSTL1) expression levels. Moreover, bioinformatics analysis indicated that FSTL1 was a potential target of miR-124-3p, which was additionally verified using luciferase reporter assays. Taken together, these data revealed a specific regulatory pathway of miR-124-3p, which negatively regulated its target gene, FSTL1, during the differentiation of PSCs to NPLCs, and suggested a functional role for miR-124-3p in the differentiation of PSCs.

Twelve phenolic compounds, including one new phloroglucinol derivative, were isolated from the leaves of Syzygium austroyunnanense. Their structures were elucidated based on the spectroscopic data and by comparison with the literature. All of compounds were firstly isolated from this species.

Emerging fungal phytodiseases are a food security threat and novel fungicides are in an urgent need. Herein, a series of isobutyrophenone derivatives were designed and synthesized. The derivatives exhibited excellent fungicidal activities against seven fungi. The structure-activity relationship (SAR) study indicated that the introduction of a bromo group at the position 3 or 5 of the phenyl ring, as well as esterification of the 4-hydroxy with a chloroacetyl group, could substantially increase the antifungal activity and spectrum of the compounds. Among all 23 compounds, 2-bromo-3-hydroxy-4-isobutyryl-6-methylphenyl 2-chloroacetate (12b) showed the highest fungicidal activity against all seven tested fungal pathogens with EC50 values ranging from 1.22 to 39.94 μg/mL and exhibited the most potent inhibition against class II fructose-1,6-bisphosphate aldolase with an IC50 of 3.63 μM. The lead compounds were proven to be safe to NIH3T3/293 T cells and silkworm larvae, and relatively stable under different harsh conditions. Detached fruit tests showed the practical potential of lead compounds for fruit (or plant) protection. Taken together, our results indicated that the isobutyrophenone derivatives could be further optimized and developed as advanced leads for new fungicides.

A heat-treatment-assisted approach towards scalable synthesis of mesoporous carbons by direct solid-solid mixing of microcrystalline cellulose (MCC) and nano-sized SiO2, subsequent pyrolysis and SiO2 removal process, was reported in this study. The obtained mesoporous carbon presented a well-defined mesopore structure with high surface area and large mesopore size. During synthesis, MCC underwent structural relaxation process before degradation, which could provide a capillarity condensation force inducing the imprint of mesopore on final carbons. Due to the proper structure, the as-prepared mesoporous carbon showed prominent performance as sulfur host for lithium-sulfur (Li-S) battery, exhibiting a high reversible capacity of 860 mA h g−1 at 0.5 C after 200 cycles, and exceptional rate capability with 600 mA h g−1 at 5.0 C.

Objective: Cyclin D1 was an important molecular involved in the pathological process of osteoarthritis (OA). The purpose of this study was to identify the effect and potential mechanism of Cyclin D1 for the proliferation and apoptosis of OA chondrocytes. Methods: We used polymerase chain reaction (PCR) method to identify the expression levels of Cyclin D1 and down-stream Wnt/β-catenin pathway-related genes in OA chondrocytes according to the grade of OA. Small interfering RNA (siRNA) or overexpression of Cyclin D1 were used to identify the role of Cyclin D1 in cell proliferation and apoptosis. Next, we used XAV-939 to inhibit the Wnt/β-catenin pathway and explore the relevant mechanism. Results: Cyclin D1 was significantly decreased with OA grade (p < .05). After siCyclin D1 transfection, the expression level of WNT3 and nuclear β-catenin were significantly increased, while Wnt10a and total β-catenin were not obviously changed. Co-cultured with XAV-939 and siCyclin D1 abolished the effects of siCyclin D1 on proliferation and apoptosis of OA chondrocytes (p < .05). Conclusions: Cyclin D1 regulated chondrocyte proliferation and apoptosis through Wnt3/β-catenin instead of Wnt10a/β-catenin signalling pathway.