The present study was designed to determine whether sulfur dioxide (SO2) could be endogenously produced in adipocyte and served as a novel adipocyte-derived inflammatory inhibitor. SO2 was detected in adipose tissue using high-performance liquid chromatography with fluorescence detection. SO2 synthase aspartate aminotransferase (AAT1 and AAT2) mRNA and protein expressions in adipose tissues were measured. For in vitro study, 3T3-L1 adipocytes were cultured, infected with adenovirus carrying AAT1 gene or lentivirus carrying shRNA to AAT1, and then treated with tumor necrosis factor-α (TNF-α). We found that endogenous SO2/AAT pathway existed in adipose tissues including perivascular, perirenal, epididymal, subcutaneous and brown adipose tissue. AAT1 overexpression significantly increased SO2 production and inhibited TNF-α-induced inflammatory factors, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) secretion from 3T3-L1 adipocytes. By contrast, AAT1 knockdown decreased SO2 production and exacerbated TNF-α-stimulated MCP-1 and IL-8 secretion. Mechanistically, AAT1 overexpression attenuated TNF-α-induced IκBα phosphorylation and degradation, and nuclear factor-κB (NF-κB) p65 phosphorylation, while AAT1 knockdown aggravated TNF-α-activated NF-κB pathway, which was blocked by SO2. NF-κB inhibitors, PDTC or Bay 11-7082, abolished excessive p65 phosphorylation and adipocyte inflammation induced by AAT1 knockdown. This is the first report to suggest that endogenous SO2 is a novel adipocyte-derived inflammatory inhibitor.

Escherichia coli NusA, an essential component of the RNA polymerase elongation complex, is involved in transcriptional elongation, termination, anti-termination, cold shock and stress-induced mutagenesis. In this study, we demonstrated that NusA can self-assemble into oligomers under heat shock conditions and that this property is largely determined by the C-terminal domain. In parallel with the self-assembly process, NusA also acquires chaperone activity. Furthermore, NusA overexpression results in the enhanced heat shock resistance of host cells, which may be due to the chaperone activity of NusA. Our results suggest that E. coli NusA can act as a protector to prevent protein aggregation under heat stress conditions in vitro and in the NusA-overexpressing strain. We propose a new hypothesis that NusA could serve as a molecular chaperone in addition to its functions as a transcription factor. However, it remains to be further investigated whether NusA has the same function under normal physiological conditions.

Macrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model. Using immunofluorescence, flow cytometry, RT-qPCR, and western blot assays, we found that low-level laser therapy altered the polarization state to a M2 tendency. A greater number of neurons survived in the pare injury site, which was accompanied by higher BBB scores in the LLLT group. Furthermore, low-level laser therapy elevated expression of interleukin 4 (IL-4) and interleukin 13 (IL-13). Results from this study show that low-level laser therapy has the potential for reducing inflammation, regulating macrophage/microglia polarization, and promoting neuronal survival. These beneficial effects demonstrate that low-level laser therapy may be an effective candidate for clinical treatment of spinal cord injury.

Previous studies showed that mutation of folC caused decreased expression of the dihydropteroate synthase encoding gene folP2 in Mycobacterium tuberculosis (M. tuberculosis). We speculated that mutation of folC in M. tuberculosis might affect the susceptibility to sulfamethoxazole (SMX). To prove this, 53 clinical isolates with folC mutations were selected and two folC mutants (I43A, I43T) were constructed based on M. tuberculosis H37Ra. The results showed that 42 of the 53 clinical isolates (79.2%) and the two lab-constructed folC mutants were more sensitive to SMX. To probe the mechanism by which folC mutations make M. tuberculosis more sensitive to SMX, folP2 was deleted in H37Ra, and expression levels of folP2 were compared between H37Ra and the two folC mutants. Although deletion of folP2 resulted in increased susceptibility to SMX, no difference in folP2 expression was observed. Furthermore, production levels of para-aminobenzoic acid (pABA) were compared between the folC mutants and the wild-type strain, and results showed that folC mutation resulted in decreased production of pABA. Taken together, we show that folC mutation leads to decreased production of pABA in M. tuberculosis and thus affects its susceptibility to SMX, which broadens our understanding of mechanisms of susceptibilities to antifolates in this bacterium.

This study presents a parametric analysis of the steady-state temperature elevation in rat skin models due to millimeter wave exposure at frequencies from 6-100 GHz. The statistical data of the thickness of skin layers, namely epidermis, dermis, dermal white adipose tissue, and panniculus carnosus, were measured for the first time using the excised tissues of real male Sprague-Dawley rats. Based on the precise structure obtained from the histological analysis of rat skin, we solve the bioheat transfer equation to investigate the effects of changes in parameters, such as body parts and thermal constants, on the absorbed power density and temperature elevation of biological tissues. Owing to the notably thin dermal white adipose tissue layer, the surface temperature elevation in the rat head and dorsal skin at 6-100 GHz is 52.6-32.3% and 83.3-58.8% of the average values of different human skin models, respectively. Our results also reveal that the surface temperature elevation of rat skin may correlate with the tissue thickness and deep blood perfusion rates.

Diacetyl, a high value product that can be extensively used as a food ingredient, could be produced from the non-enzymatic oxidative decarboxylation of α-acetolactate during 2,3-butanediol fermentation. In this study, the 2,3-butanediol biosynthetic pathway in Enterobacter cloacae subsp. dissolvens strain SDM, a good candidate for microbial 2,3-butanediol production, was reconstructed for diacetyl production. To enhance the accumulation of the precursor of diacetyl, the α-acetolactate decarboxylase encoding gene (budA) was knocked out in strain SDM. Subsequently, the two diacetyl reductases DR-I (gdh) and DR-II (budC) encoding genes were inactivated in strain SDM individually or in combination to decrease the reduction of diacetyl. Although the engineered strain E. cloacae SDM (ΔbudAΔbudC) was found to have a good ability for diacetyl production, more α-acetolactate than diacetyl was produced simultaneously. In order to enhance the nonenzymatic oxidative decarboxylation of α-acetolactate to diacetyl, 20 mM Fe(3+) was added to the fermentation broth at the optimal time. In the end, by using the metabolically engineered strain E. cloacae SDM (ΔbudAΔbudC), diacetyl at a concentration of 1.45 g/L was obtained with a high productivity (0.13 g/(L·h)). The method developed here may be a promising process for biotechnological production of diacetyl.

Heterosis refers to the phenomenon in which hybrid progeny show superior performance relative to their parents. Early maize ear development shows strong heterosis in ear architecture traits and greatly affects grain yield. To explore the underlying molecular mechanisms, genome-wide proteomics of immature ears of maize hybrid ZD909 and its parents were analyzed using tandem mass tag (TMT) technology. A total of 9,713 proteins were identified in all three genotypes. Among them, 3,752 (38.6%) proteins were differentially expressed between ZD909 and its parents. Multiple modes of protein action were discovered in the hybrid, while dominance expression patterns accounted for 63.6% of the total differentially expressed proteins (DEPs). Protein pathway enrichment analysis revealed that high parent dominance proteins mainly participated in carbon metabolism and nitrogen assimilation processes. Our results suggested that the dominant expression of favorable alleles related to C/N metabolism in the hybrid may be essential for ZD909 ear growth and heterosis formation. Integrated analysis of proteomic and quantitative trait locus (QTL) data further support our DEP identification and provide useful information for the discovery of genes associated with ear development. Our study provides comprehensive insight into the molecular mechanisms underlying heterosis in immature maize ears from a proteomic perspective.

We performed this meta-analysis to examine the diagnostic accuracy of MRI for the diagnosis of anterior cruciate ligament (ACL) injury in comparison to arthroscopy. We also compared the diagnostic accuracy of MRI with magnetic field intensities (MFI) greater than or equal to 1.5T with those below 1.5T, in addition to different MRI sequences. Studies relevant to the diagnosis of ACL injury by MRI and arthroscopy were analyzed. Computer and manual retrieval were carried out on studies published between January 1, 2006 and May 31, 2016. Twenty-one papers were included. Neither threshold nor non-threshold effects were present (p = 0.40, p = 0.06). The pooled sensitivity (SE), specificity (SP), positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) with 95% confidence interval (CI) were 87% (84-90%), 90% (88-92%), 6.78 (4.87-9.44), 0.16 (0.13-0.20) and 44.70 (32.34-61.79), respectively. The area under the curve (AUC) was 0.93. The risk of publication bias was negligible (p = 0.75). In conclusion, examination by MRI is able to provide appreciable diagnostic performance. However, the principle, which states that the higher the MFI, the better the diagnostic accuracy, could not be verified. Additionally, conventional sequences (CSs) associated with proton density-weighted imaging (PDWI) are only slightly better than CSs alone, but not statistically different.

Prohibitin 2 (PHB2), as a conserved multifunctional protein, is traditionally localized in the mitochondrial inner membrane and essential for maintenance of mitochondrial function. Here, we investigated the role of PHB2 in human rhabdomyosarcoma (RMS) RD cells and found substantial localization of PHB2 in the nucleolus. We demonstrated that PHB2 knockdown inhibited RD cell proliferation through inducing cell cycle arrest and suppressing DNA synthesis. Meanwhile, down-regulation of PHB2 also induced apoptosis and promoted differentiation in fractions of RD cells. In addition, PHB2 silencing led to altered nucleolar morphology, as observed by transmission electron microscopy, and impaired nucleolar function, as evidenced by down-regulation of 45S and 18S ribosomal RNA synthesis. Consistently, upon PHB2 knockdown, occupancy of c-Myc at the ribosomal DNA (rDNA) promoter was attenuated, while more myoblast determination protein 1 (MyoD) molecules bound to the rDNA promoter. In conclusion, our findings suggest that nucleolar PHB2 is involved in maintaining nucleolar morphology and function in RD cells by regulating a variety of transcription factors, which is likely to be one of the underlying mechanisms by which PHB2 promotes tumor proliferation and represses differentiation. Our study provides new insight into the pathogenesis of RMS and novel characterizations of the highly conserved PHB2 protein.

Tibial dyschodroplasia (TD) is a most common pathological condition in many avian species that is characterized by failure of growth plate (GP) modeling that leads to the persistence of avascular lesion in the GP. Tetramethylpyrazine (TMP) is widely used to treat neurovascular disorders and pulmonary hypertension, but no report is available about promoting effect of TMP against TD. Therefore, a total of 210 broiler chicks were equally divided into three groups; Control, TD and TMP. During the experiment mortality rate, chicken performance indicators (daily weight, average daily feed intake, average daily weight gain and feed conversion ratio), tibia bone indicators (weight, length, width of tibial and the size of GP) in addition to gene expression of HIF-1α and VEGF were examined. The results showed that TMP administration restore the GP width, increase growth performance, and mitigated the lameness in broiler chickens. The expression of HIF-1α and VEGF increased significantly in TD affected thiram induced chicks. Whereas, TMP treatment down-regulated HIF-1α and VEGF genes and proteins expressions. The present study demonstrates that the TMP plays an important role in angiogenesis during the impairment and recovery of GP in TD via regulation of the HIF-1α/VEGF signaling pathway in chickens.

The aim of the study was to investigate the role of endogenous sulfur dioxide (SO2)/ aspartate aminotransferase 1 (AAT1) pathway in stretch-induced excessive collagen expression and its mechanism. The mechanical stretch downregulated SO2/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-β1 (TGF- β1) expression and phosphorylation of Smad2/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- β1 expression and phosphorylation of Smad2/3 induced by stretch. Mechanistically, SB431542, a TGF-β1/Smad2/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO2 content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO2 derivatives inhibited activation of TGF- β1/Smad2/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO2/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-β1/Smad2/3 pathway.

Due to the lack of a proper imaging approach, a veracious pH map of normal and abnormal cell is still rare. In this work, we presented a rhodamine-salicylaldehyde combination (Rh-SA2) as a novel pH probe, which has dual sensitive units for both acidic and basic environment. This dual sensitive probe acts like a chameleon in living cells and offers the doubling guarantees for endocellular pH mapping. Moreover, a quantitative measurement of cellular pH changes was allowed and the endocellular pH values under drug-associated stimuli were also investigated.

The plant glutathione peroxidase (GPX) family consists of multiple isoenzymes with distinct subcellular locations, tissue-specific expression patterns and environmental stress responses. In this study, 13 putative GPXs from the genome of Gossypium hirsutum (GhGPXs) were identified and a conserved pattern among plant GPXs were exhibited, besides this they also responded to multiple environmental stresses and we predicted that they had hormone responsive cis-elements in their promoter regions. Most of the GhGPXs on expression in yeast can scavenge H2O2. Our results showed that different members of the GhGPX gene family were co-ordinately regulated under specific environmental stress conditions, and suggested the importance of GhGPXs in hormone treatments and abiotic stress responses.

Huang-Lian-Jie-Du-Tang (HLJDT), a traditional formula with four TCM herbs, has been used for hundred years for different diseases. The current study aimed to assess the inhibitory activity of HLJDT against H1N1 neuraminidase (NA-1), and identify potent NA-1 inhibitors from its plasma profile. The in vitro NA-1 study has shown that the water extract of HLJDT potently inhibited NA-1 (IC50 = 112.6 μg/ml; Ki = 55.6 μg/ml) in a competitive mode. The IC50 values of the water extracts of its four herbs were as follows: Coptidis Rhizoma, 96.1 μg/ml; Phellodendri Chinensis Cortex, 108.6 μg/ml; Scutellariae Radix, 303.5 μg/ml; Gardeniae Fructus, 285.0 μg/ml. Thirteen compounds found in the plasma profile of HLJDT were also identified as potent NA-1 inhibitors, which included jatrorrhizine, palmatine, epiberberine, geniposide, oroxylin A, berberine, coptisine, baicalein, wogonoside, phellodendrine, wogonin, oroxylin A-7-O-glucuronide and baicalin (sorted in ascending order by their IC50 values). Their inhibitory activities were consistent with molecular docking analysis when considering crystallographic water molecules in the ligand-binding pocket of NA-1. Our current findings suggested that HLJDT can be used as a complementary medicine for H1N1 infection and its potent active compounds can be developed as NA-1 inhibitors.

This study aimed to explore whether and how L-cystathionine had any regulatory effect on the inflammatory response in THP-1-derived macrophages cultured in vitro under oxidized low-density lipoprotein (ox-LDL) stimulation. The human monocyte line THP-1 cell was cultured in vitro and differentiated into macrophages after 24 hours of PMA induction. Macrophages were pretreated with L-cystathionine and then treated with ox-LDL. The results showed that compared with the controls, ox-LDL stimulation significantly upregulated the expression of THP-1-derived macrophage MCP-1 by enhancing NF-κB p65 phosphorylation, nuclear translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL group, 0.3 mmol/L and 1.0 mmol/L L-cystathionine significantly inhibited the expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3 mmol/L and 1.0 mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation of the NF-κB p65 protein, as well as the DNA binding activity and DNA binding level of NF-κB with the MCP-1 promoter, which resulted in a reduced THP-1-derived macrophage MCP-1 generation. This study suggests that L-cystathionine could inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL via inhibition of NF-κB p65 phosphorylation, nuclear translocation, and binding of the MCP-1 promoter sequence after entry into the nucleus.

Microspheres with magnetic-fluorescent functions have received attention due to fluorescent tracking and target positioning. To improve the accuracy of optical imaging and the fluorescent tracking of drug release, it is essential to enhance the fluorescent intensity of microparticles. Magnetic-fluorescent bifunctional poly lactic-co-glycolic acid (PLGA) Janus microspheres [PLGA/TbLa3(Bim)12]//[PLGA/Fe3O4] with double chambers were fabricated with the double-needle electrospraying method. The fluorescent drug TbLa3(Bim)12 with dual rare earth ions was encapsulated in one chamber, while Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) were simultaneously encapsulated in another chamber. In comparison, magnetic-fluorescent PLGA composite microspheres PLGA/TbLa3(Bim)12/Fe3O4 were also prepared, which encapsulated fluorescent drugs TbLa3(Bim)12 with dual rare earth (RE) ions and Fe3O4 MNPs in one chamber. The fluorescent intensity at 542 nm of Janus microspheres was about three times higher than that of composite microspheres due to a decrease in contact between fluorescent-labeling RE drug and MNPs. The fluorescent intensities of Janus microspheres with different contents of Fe3O4 MNPs and TbLa3(Bim)12 were investigated. Furthermore, the magnetic properties, thermostability, cell toxicity and hemolytic properties of Janus microspheres were also assayed to conduct a tentative exploration of their bioapplication. The Janus microspheres provide many opportunities for application in biofields such as drug delivery.

Rickettsiales bacteria in arthropods play a significant role in both public health and arthropod ecology. However, the extensive genetic diversity of Rickettsiales endosymbionts of arthropods is still to be discovered. In 2016, 515 arthropods belonging to 9 species of four classes (Insecta, Chilopoda, Diplopoda and Arachnida) were collected in Serbia. The presence and genetic diversity of Rickettsiales bacteria were evaluated by characterizing the 16S rRNA (rrs), citrate synthase (gltA) and heat shock protein (groEL) genes. The presence of various Rickettsiales bacteria was identified in the majority of tested arthropod species. The results revealed co-circulation of five recognized Rickettsiales species including Rickettsia, Ehrlichia and Wolbachia, as well as four tentative novel species, including one tentative novel genus named Neowolbachia. These results suggest the remarkable genetic diversity of Rickettsiales bacteria in certain arthropod species in this region. Furthermore, the high prevalence of spotted fever group Rickettsia in Ixodes ricinus ticks highlights the potential public health risk of human Rickettsia infection.

Here we report two novel red emission fluorescent probes for the highly sensitive and selective detection of monoamine oxidase (MAO) with large Stokes shift (227 nm). Both of the probes possess solid state fluorescence and can accomplish the identification of MAO on test papers. The probe MAO-Red-1 exhibited a detection limit down to 1.2 μg mL(-1) towards MAO-B. Moreover, the cleavage product was unequivocally conformedby HPLC and LCMS and the result was in accordance with the proposed oxidative deamination mechanism. The excellent photostability of MAO-Red-1 was proved both in vitro and in vivo through fluorescent kinetic experiment and laser exposure experiment of confocal microscopy, respectively. Intracellular experiments also confirmed the low cytotoxity and exceptional cell imaging abilities of MAO-Red-1. It was validated both in HeLa and HepG2 cells that MAO-Red-1 was capable of reporting MAO activity through the variation of fluorescence intensity.