Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension.

BACKGROUND: This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT). METHODS: According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin-eosin staining, and senescence-associated ß-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified. RESULTS: In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration. CONCLUSIONS: ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

Phylogeography and evolutionary dynamics analysis of porcine delta-coronavirus with host expansion to humans.

From 2003 onwards, three pandemics have been caused by coronaviruses: severe acute respiratory syndrome coronavirus (SARS-CoV); middle east respiratory syndrome coronavirus (MERS-CoV); and, most recently, SARS-CoV-2. Notably, all three were transmitted from animals to humans. This would suggest that animals are potential sources of epidemics for humans. The emerging porcine delta-coronavirus was reported to infect children. This is a red flag that marks the ability of PDCoV to break barriers of cross-species transmission to humans. Therefore, we conducted molecular genetic analysis of global clade PDCoV to characterize spatiotemporal patterns of viral diffusion and genetic diversity. PDCoV was classified into three major lineages, according to distribution and phylogenetic analysis of PDCoV. It can be inferred based on the analysis results of the currently known PDCoV strains that PDCoV might originate in Asia. We also selected six special spike amino acid sequences to align and analyze to find seven significant mutation sites. The accumulation of these mutations may enhance dynamic movements, accelerating spike protein membrane fusion events and transmission. Altogether, our study offers a novel insight into the diversification, evolution, and interspecies transmission and origin of PDCoV and emphasizes the need to study the zoonotic potential of the PDCoV and comprehensive surveillance and enhanced biosecurity precautions for PDCoV.

[Mineral nitrogen accumulation and its spatial distribution in soils in dense planting dwarf rootstock apple orchard on the Weibei dry plateau, Northwest China]. / æ¸­åŒ—æ—±å¡¬çŸ®ç §å¯†æ¤è‹¹æžœå›­åœŸå£¤çŸ¿è´¨æ°®ç§¯ç´¯ä¸Žç©ºé—´åˆ†å¸ƒç‰¹å¾.

With the rapid development of dense apple tree plantings with the dwarf rootstock cultivation method, determining accumulation and distribution characteristics of soil mineral nitrogen in densely planted orchards with dwarf rootstock is important to enable scientific fertilization of apple orchards. We investigated densely planted apple orchards with dwarf rootstocks and different plant ages (6 a, 9 a, and 12 a). We collected soil samples under trees, between trees, between rows, and at the midpoints between the trees and rows, and examined the accumulation and distribution characteristics of nitrate, ammonium, and mineral nitrogen. The cumulative amount of nitrate in the 0-300 cm soil layer increased with plant age. The difference between orchards with different plant ages was significant and showed the trend 6 a<9 a<12 a. The cumulative amount of nitrate increased from 1729 kg·hm-2 to 3771 kg·hm-2 with increasing plant age. The ammonium content was low for orchards of all plant ages and had little effect on the accumulation and spatial distribution of mineral nitrogen. There were two accumulation peaks of nitrate nitrogen in the vertical direction. The depth of soil layer where the second accumulation peak was located decreased from 180 cm to 220 cm with increasing plant age. In the horizontal direction, soil nitrate nitrogen content between rows increased from 27 mg·kg-1 to 138 mg·kg-1 with increasing plant age, representing a more than 400% increase. The difference between orchards with different plant ages was significant. In summary, excessive usage of nitrogen fertilizer and serious leaching of nitrate were problematic in all orchards with different ages. Less nitrogen fertilizer should be applied, and anti-seepage measures should be used at the fertilization location to prevent the leaching of nitrate to deep layers.

Berberine mitigates high glucose-induced podocyte apoptosis by modulating autophagy via the mTOR/P70S6K/4EBP1 pathway.

AIMS: This study aimed to investigate the characteristics and mechanism of autophagy on podocyte apoptosis under high glucose (HG) conditions and further explore the effect of berberine on podocyte autophagy, apoptosis and the potential mechanism. MATERIALS AND METHODS: The levels of LC3II/I in podocytes stimulated with HG were detected at 0, 2, 4, 8, 12, 24, 36 and 48 h by western blotting. CCK-8 was used to detect the viability of podocytes. The level of autophagy was detected by western blotting, transmission electron microscopy and immunofluorescence. Podocyte apoptosis was analysed by using Hoechst staining, western blotting, annexin V/propidium iodide dual staining, and confocal microscopy. Then, podocytes were transfected with siRNA to silence mTOR, and the expression levels of proteins and mRNA involved in the mTOR/P70S6K/4EBP1 pathway were further investigated by western blotting and qRT-PCR. KEY FINDINGS: In this study, we found significantly reduced LC3II/LC3I and increased p62 in podocytes stimulated with HG for 24 h, and the level of autophagy reached a minimum at 24 h. Berberine restored podocyte viability and significantly attenuated HG-mediated inhibition of autophagy, as evidenced by the increased expression of LC3II/LC3I, the number of autophagosomes and the inhibition of p62. Moreover, berberine counteracted HG-induced podocyte apoptosis and injury, which was negatively correlated with the autophagy effect. Notably, silencing mTOR with siRNA augmented the inhibition of P70S6k and 4EBP1 phosphorylation, which was similar to the effect of berberine. SIGNIFICANCE: Berberine activates podocyte autophagy by inhibiting the mTOR/P70S6K/4EBP1 signaling pathway, thereby alleviating podocyte apoptosis.

Chiral-aminoquinoline-based fluorescent pH probe with large stokes shift for bioimaging.

The aminoquinoline derivatives, (R)- and (S)-2-phenyl-2-(quinolin-6-ylamino)ethan-1-ol (R-PEO and S-PEO), were synthesized by a tandem one-pot three-step CN coupling method where Smiles rearrangement was the key procedure. The selected compound R-PEO showed a significant fluorescence enhancement with a turn-on ratio over 98-fold and enabled the real time determination of proton concentration in acidic solution. The fluorescence intensity of R-PEO exhibited strong pH-dependent performance with a large Stokes shift (115nm) and responded linearly to minor pH change within the range of 3.8-6.0. With the help of 1H NMR spectrum, we also confirmed the protonation of the quinoline unit should be the proposed reaction. Compared with the conjugated acid of N-hexylquinolin-6-amine (NQA), the conjugated acid of R-PEO shows significant planar intramolecular charge transfer (PICT) character. Furthermore, biological imaging proved that R-PEO probe can be used to monitor the pH change of S. cerevisiae in vivo.

Neuroprotective properties of Madecassoside from Centella asiatica after hypoxic-ischemic injury.

Madecassoside is one of increasingly used constituent of Centella asiatica, a frequently prescribed crude drug in South eastern Asia and China for wound healing. In the present experiment, it exposes the neuroprotective nature of Madecassoside in GT1-7 cell lines, further, which the antioxidant activities are performed. The cellular toxicity was assessed using 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay with increased cell viability with IC50 2.5µg/ml. the regulation of antioxidant levels showed changes in madecassoside treated cell lysate viz., SOD assay. Also, the antioxidative assays confirmed the negligible cellular damage caused to the GT1-7 cell lines. Hence, the results advocate that the current antioxidant and antitumor activity be justified by the high concentration of phenolic constituents, primarily the triterpene present in the C. asiatica.

LncRNAs: new players in gliomas, with special emphasis on the interaction of lncRNAs With EZH2.

Gliomas are the most common primary malignancy in the brain, accounting for 50-60%. Despite all the efforts of cytoreductive surgery in combination with intense chemoradiotherapy, glioma remains an incurable disease. Recent studies have shown that long noncoding RNAs (lncRNAs) are involved in the pathology of gliomas. LncRNAs are involved in many cellular processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. In this review we focus on the dysregulation of lncRNAs in gliomas. We also address that epigenetic modification such as DNA methylation and microRNAs interact with lncRNAs in gliomas. In addition, the interaction of lncRNAs with signaling pathways in gliomas is discussed systematically, with particular emphasis on the interaction of lncRNAs with EZH2. Such approaches provide valuable insights into the potential future applications of lncRNAs in the treatment of gliomas.

[Controlling effects of dual mulching on soil moisture in an apple orchard].

To investigate the controlling effects of dual mulching on soil moisture in an apple orchard on the Weibei rainfed highland, soil moisture in the 0-600 cm soil profile of the apple orchard was measured under four mulching treatments (plastic film plus straw, plastic film and straw mulches, as well as a non-mulching control) , and meanwhile the apple yield and branch growth increment were analyzed statistically. Results showed that the dual mulching treatment had the best effect on soil moisture conservation, and the soil water storage in such a soil profile was 6.7% higher than the control treatment. Long-term dual mulching could effectively alleviate soil desiccation occurring in deep soil layer in the region, and the monthly averaged soil water storage in stable layer (240-600 cm) was 64.22 mm higher than that of the control treatment. Both plastic film plus straw and plastic film mulches were able to reduce the temporal fluctuation of soil moisture in shallow soil (0-60 cm) and enhance the temporal stability of soil moisture in the layer. Compared with the single mulching treatments, the dual mulching treatment could effectively decrease the vertical variation of soil moisture in the profile and improve the stability of the vertical soil moisture distribution. The apple yield under the dual mulching treatment was evidently increased by 48.2%, as compared with the control treatment. All the analyses showed that dual mulching had more advantages in controlling soil moisture and improving apple yield than single mulching.

TET family proteins: new players in gliomas.

DNA methylation at the 5-position of cytosine (5mC) in the mammalian genome has emerged as a pivotal epigenetic event that plays important roles in development, aging and disease. The three members of the TET protein family, which convert 5mC to 5-hydroxymethylcytosine, has provided a potential mechanism resulting in DNA demethylation and maintaining cellular identity. Recent studies have shown that epigenetic modifications play a key role in the regulation of the molecular pathogenesis of gliomas. In this review we focus on demonstrating the TET proteins in DNA demethylation and transcriptional regulation of different target genes. In addition, we address the role of TET proteins in gliomas. This review will provide valuable insights into the potential targets of gliomas, and may open the possibility of novel therapeutic approaches to this fatal disease.

[Characteristics of soil moisture in artificial impermeable layers].

For the problem of low water and fertilizer use efficiency caused by nitrate nitrogen lea- ching into deep soil layer and soil desiccation in dryland apple orchard, characteristics of soil moisture were investigated by means of hand tamping in order to find a new approach in improving the water and fertilizer use efficiency in the apple orchard. Two artificial impermeable layers of red clay and dark loessial soil were built in soil, with a thickness of 3 or 5 cm. Results showed that artificial impermeable layers with the two different thicknesses were effective in reducing or blocking water infiltration into soil and had higher seepage controlling efficiency. Seepage controlling efficiency for the red clay impermeable layer was better than that for the dark loessial soil impermeable layer. Among all the treatments, the red clay impermeable layer of 5 cm thickness had the highest bulk density, the lowest initial infiltration rate (0.033 mm · min(-1)) and stable infiltration rate (0.018 mm · min(-1)) among all treatments. After dry-wet alternation in summer and freezing-thawing cycle in winter, its physiochemical properties changed little. Increase in years did not affect stable infiltration rate of soil water. The red clay impermeable layer of 5 cm thickness could effectively increase soil moisture content in upper soil layer which was conducive to raise the water and nutrient use efficiency. The approach could be applied to the apple production of dryland orchard.

[Allelopathic effects of Artemisia sacrorum population in typical steppe based on niche theory].

By using modified Levins niche width index and Pianka niche overlap index, this paper analyzed the ecological competition between constructive and dominant species in a typical steppe. The stem- and leaf extracts from the constructive species (Artemisia sacrorum) were utilized to study their allelopathic potential on the seed germination and plant growth of the dominant species (Stipa bungeana, Thymus mongolicus, S. grandis, and Leymus secalinus), and the ecological position of A. sacrorum in the steppe succession. In the steppe, S. bungeana had the widest niche width (0.99), followed by T. mongolicus (0.94), A. sacrorum (0.82), S. grandis (0.76), and L. secalinus (0.73). The niche overlap value between A. sacrorum and S. bungeana, S. bungeana and T. mongolicus, T. mongolicus and S. grandis, and A. sacrorum and T. mongolicus was 0.90, 0.95, 0.94, and 0.86, respectively. The allelopathic effects of A. sacrorum extracts varied with their concentration. For the seed germination, root growth, and shoot growth of the dominant species, A. sacrorum extracts showed a trend of promoting at low concentrations and inhibiting at high concentrations. The extracts of A. sacrorum had a stronger promotion effect on the root growth of S. bungeana than on that of T. mongolicus, but a stronger inhibition effect on the shoot growth of T. mongolicus than on that of S. bungeana. Methanol extracts had stronger allelopathic effects than aqueous extracts. The high niche overlap between A. sacrorum and S. bungeana, and T. mongolicus and S. grandis indicated that the steppe community would continue succession to S. bungeana, while A. sacrorum population was only an important transitional stage during the succession. The allelopathic effect of A. sacrorum played a driving role in the succession process.

[Food security in 'Grain for Green Project' area of North Shaanxi based on households].

This paper analyzed the food production by the households in the counties with high population (Mizhi County) and low population (Wuqi County) in North Shaanxi, and studied the food security and its affecting factors in the two counties by using minimum cropland area per capita and Cobb-Douglass production function methods. The results demonstrated that the food production in low population county could meet the basic standard of food security, while that in high population county could not. Cultivated area and investment in agricultural technology were the major factors affecting food security; labor force, labor quality, and grain subsidy also had positive effects on food production. The current technology and labor quality did not reach their potential for food production. This region needed to increase grain production area to reach the minimum standard of 0.14 bm2 per capita, put much stress on labor force training, and formulate appropriate following policies for 'Grain for Green' to realize the food security strategy.

Synthesis, X-ray crystal structures and optical properties of novel substituted pyrazoly 1,3,4-oxadiazole derivatives.

Novel pyrazoly 1,3,4-oxadiazole derivatives were synthesized and characterized by (1)H NMR, IR, HRMS and X-ray diffraction analysis. UV-vis absorption and fluorescence properties of these compounds in different solutions showed that the maximum absorption wavelength was not significantly changed in different solvents; however, maximal emission wavelength was red-shifted with the increase of solvent polarity. Absorption λ(max) and emission λ(max) was less correlated with substituent groups on aryl rings.

The synthesis, X-ray crystal structure and optical properties of novel 5-aryl-3-ferrocenyl-1-pyridazinyl-pyrazoline derivatives.

A series of novel 5-aryl-3-ferrocenyl-1-pyridazinyl pyrazoline derivatives was synthesized by the reaction of ferrocenyl chalcone and 3-chloro-6-hydrazinylpyridazine in 10-65% yields. The compounds were characterized using IR, (1)H NMR, HRMS spectroscopic techniques and representative compounds 3c and 4c were assigned based on the X-ray crystallographic structure. The absorption and fluorescence characteristics of the compounds were investigated in chloroform, tetrahydrofuran and acetonitrile, respectively. The results showed that the absorption maxima of the compounds varied from 323 to 327 nm depending on the groups bonded to benzene and pyridazine ring. The maximum emission spectra of compounds in CHCl(3) were dependent on groups in pyridazine ring in which a strong donating-electron group such as propoxyl group on pyridazine ring in N-1 position of pyrazoline made the emission wavelength of 4a-4e small red shifte than that of compounds 3a-3e with chlorine group. The intensity of absorption and fluorescence was also correlated with substituent on aryl ring in C-5 position of pyrazoline. In addition, the absorption spectra of these compounds changed very little, but the fluorescence spectra had much change with increasing solvent polarity.

[Effects of different patterns surface mulching on soil properties and fruit trees growth and yield in an apple orchard].

Taking a nine-year-old Fuji apple orchard in Loess Plateau as test object, this paper studied the effects of different patterns surface mulching (clean tillage, grass cover, plastic film mulch, straw mulch, and gravel mulch) on the soil properties and fruit trees growth and yield in this orchard. Grass cover induced the lowest differentiation of soil moisture profile, while gravel mulch induced the highest one. In treatment gravel mulch, the soil moisture content in apple trees root zone was the highest, which meant that there was more water available to apple trees. Surface mulching had significant effects on soil temperature, and generally resulted in a decrease in the maximum soil temperature. The exception was treatment plastic film mulch, in which, the soil temperature in summer exceeded the maximum allowable temperature for continuous root growth and physiological function. With the exception of treatment plastic film mulch, surface mulching increased the soil CO2 flux, which was the highest in treatment grass cover. Surface mulching also affected the proportion of various branch types and fruit yield. The proportion of medium-sized branches and fruit yield were the highest in treatment gravel mulch, while the fruit yield was the lowest in treatment grass cover. Factor analysis indicated that among the test surface mulching patterns, gravel mulch was most suitable for the apple orchards in gully region of Loess Plateau.

The synthesis, X-ray crystal structure and optical properties of novel 1-ferrocenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)ethanone derivatives.

A series of novel 1-ferrocenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)ethanone derivatives was synthesized by the reaction of 3-substituted-1H-1,2,4-triazole-5-thiol and chloroacetyl ferrocene in the presence of sodium hydride and potassium iodide at reflux. The structures of the new compounds were determined by IR and (1)H NMR spectroscopy and HRMS. The structure of compound 5c was established by X-ray crystallography. UV-vis absorption and fluorescence spectra were recorded in ethanol and dichloromethane. The results showed that compounds 5a-g display similar absorptions ranging from 300 to 500nm and maximal emission bands are about 566nm. The intensity of fluorescence and maximal emission bands are dependent on the groups bonded to triazole rings.

2-[5-(1,3-Benzodioxol-5-yl)-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thia-zole.

In the title compound, [Fe(C(5)H(5))(C(24)H(18)N(3)O(2)S)], the pyrazoline ring adopts a twist conformation. The thia-zole ring forms dihedral angles of 83.7 (2) and 34.4 (2)° with the benzene ring of the benzodioxole ring and the fused phenyl ring, respectively. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯π inter-action. The crystal packing features inter-molecular C-H⋯N, C-H⋯O hydrogen bonds and weak C-H⋯π inter-actions.

Synthesis, single-crystal characterization and preliminary biological evaluation of novel ferrocenyl pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives.

A series of novel ferrocenyl pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives was synthesized and characterized by 1H NMR, 13C NMR, IR, HRMS and X-ray diffraction analysis. Preliminary evaluation of biological applications showed that the compounds 6c and 6f inhibit the growth of A549 cells in dosage-dependent manners through cell cycle arrest.

4-(o-Tolyl-amino)-benzaldehyde.

In the title compound, C(14)H(13)NO, the dihedral angle between the aromatic rings is 49.64 (18)°. The crystal structure is stabilized by N-H⋯O, C-H⋯O and C-H⋯π hydrogen bonds.

4-(p-Tolyl-amino)-benzaldehyde.

In the title compound, C(14)H(13)NO, the dihedral angle between the aromatic rings is 66.08 (9)°. Chains are formed along the b axis through inter-molecular N-H⋯O hydrogen bonds. The crystal structure is further stabilized by C-H⋯π inter-actions.