Dissolved inorganic carbon budget of two alpine catchments in the central Tibetan Plateau: Glaciation matters.

Dissolved inorganic carbon (DIC) fluxes account for over one-third of the total carbon transported in most rivers. The DIC budget for glacial meltwater of the Tibetan Plateau (TP), however, is still poorly understood, despite the fact, the TP has the largest glacier distribution outside of the Poles. In this study, the Niyaqu and Qugaqie catchments in the central TP were selected to examine the influence of glaciation on the DIC budget in vertical evasion (CO2 exchange rate at the water-air interface) and lateral transport (sources and fluxes) from 2016 to 2018. Significant seasonal variation in DIC concentration was found in the glaciated Qugaqie catchment, but was absent in the not glaciated Niyaqu catchment. δ13CDIC showed seasonal changes for both catchments, with more depleted signatures during the monsoon season. The average CO2 exchange rates in river water of Qugaqie were ~8 times lower compared to Niyaqu with values of -1294.6 ± 438.58 mg/m2/h and -163.4 ± 581.2 mg/m2/h, respectively, indicating that proglacial rivers can act as a substantial CO2 sink due to CO2 consumption by chemical weathering. DIC sources were quantified via the MixSIAR model using δ13CDIC and ionic ratios. During the monsoon season, the contribution from carbonate/silicate weathering driven by atmospheric CO2 was 13-15 % lower, while biogenic CO2 involved in chemical weathering was 9-15 % higher, indicating a seasonal control on weathering agents. Carbonate dissolution driven by H2SO4/HNO3 was the most important contributor to DIC in both catchments (40.7 ± 2.2 % in Niyaqu and 48.5 ± 3.1 % in Qugaqie). The net CO2 consumption rate in the not glaciated Niyaqu catchment was close to 0 (-0.07 ± 0.04 × 105 mol/km2/y), indicating the carbon sink effect caused by chemical weathering in this area was weak. The net CO2 consumption rate in the glaciated Qugaqie catchment, however, was much lower than that in the not glaciated catchment with a value of -0.28 ± 0.05 × 105 mol/km2/y. This study highlights that chemical weathering in small glaciated catchments of the central TP plays an active role in releasing CO2 to the atmosphere.

Lenalidomide attenuates IMQ-induced inflammation in a mouse model of psoriasis.

Psoriasis is a type of chronic autoimmune-mediated inflammatory skin condition in which clinical manifestations are characterized by erythema and scaly changes, with complex pathogenesis and ease of relapse, and it is difficult to cure. Lenalidomide (Len) is a structural analog of thalidomide, which belongs to the second generation of immunomodulators and has the functions of tumor killing, immune regulation, anti-angiogenesis and regulation of the myeloma microenvironment. In the current experiment, we investigated the therapeutic effect of transdermal application of Len on the pathological changes of imiquimod (IMQ)-induced skin irritations and inflammation in psoriatic-like mice. The in vivo results revealed that Len nanoemulsion-based gels markedly reduced the IMQ-induced Psoriasis Area Severity Index (PASI) score, spleen-to-body weight index and CD4 protein expression in the derma of mice and improved IMQ-induced skin inflammatory cell infiltration. Transcriptome sequencing was intended to obtain the differentially expressed genes among the skin of Con mice and the skin of IMQ mice, and then, the GO enrichment classification and KEGG pathway analysis of the significant genes was executed to obtain major signaling pathways in the pathogenesis of the psoriasis mouse model. It was found that the PI3K/AKT signaling pathway was a major pathway in the pathogenesis of psoriasis in a mouse model induced by IMQ. The immunohistochemical results confirmed that Len could modulate the protein expression of AKT and NF-κB in skin. In conclusion, the protective effect of transdermal administration of Len may be related to the inhibition of the PI3K/AKT signaling pathway and its downstream NF-κB pathway against IMQ-induced psoriasis in mice.

LncRNA SOX2OT Knockdown Alleviates Lipopolysaccharide-Induced Damage of PC12 Cells by Regulating miR-331-3p/Neurod1 Axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) serve as crucial regulators in the pathogenesis of spinal cord injury (SCI). However, the role of lncRNA SOX2 overlapping transcript (SOX2OT) in SCI remains to be well revealed. METHODS: An SCI rat model was established and assessed by the Basso-Beattie-Bresnahan (BBB) method. An SCI PC12 cell model was established through lipopolysaccharide (LPS) treatment. Quantitative real-time polymerase chain reaction assay was used for SOX2OT, miR-331-3p, and neurogenic differentiation 1 (Neurod1) mRNA levels. Cell counting kit-8 assay and flow cytometry analysis were performed for cell viability and apoptosis, respectively. Enzyme-linked immunosorbent assay was performed for the levels of inflammatory cytokines. The production of superoxide dismutase and malondialdehyde was determined with relevant kits. Dual-luciferase reporter and RNA immunoprecipitation assays were conducted for the relationships among SOX2OT, miR-331-3p, and Neurod1. Western blot assay was employed for protein levels. RESULTS: SOX2OT was elevated in SCI rat and cell models. SOX2OT knockdown relieved the injury of SCI in SCI rat model. Moreover, the suppressive role in PC12 cell viability and the promotional roles in apoptosis, inflammation, and oxidative stress mediated by LPS were all restored by silencing SOX2OT. For mechanism analysis, SOX2OT was identified as a sponge of miR-331-3p to positively regulate Neurod1 expression. Inhibition of miR-331-3p reversed the effect of SOX2OT knockdown on LPS-induced PC12 damage. Overexpression of miR-331-3p protected PC12 cells from LPS-induced damage by binding to Neurod1. In addition, SOX2OT knockdown relieved PC12 cell injury by inactivation of Janus kinase-signal transducer and activator of transcription pathway. CONCLUSIONS: SOX2OT promoted PC12 cell injury through modulating miR-331-3p/Neurod1 axis and activating Janus kinase-signal transducer and activator of transcription pathway.

ICG-loaded photodynamic chitosan/polyvinyl alcohol composite nanofibers: Anti-resistant bacterial effect and improved healing of infected wounds.

Photodynamic antimicrobial chemotherapy (PACT) has advantages of strong targeting, low resistance to drugs. Electrospinning nanofibers is favorable for wound healing. The combination of PACT and electrospinning nanofibers is appropriate for wound healing, especially infected wound. In our study, indocyanine green (ICG) as photosensitizer had obvious inhibition effects on two antibiotic-resistant bacteria, Methicillin-resistant Staphylococcus aureus (MRSA) and Meropenem-resistant Pseudomonas aeruginosa (MRPA). The optimized electrospinning solution consisted of 2% (w/v) chitosan and 7% (w/v) PVA. The nanofibers observed by scanning electron microscope showed a three-dimensional cross-network with smooth surface, the water absorption ratio of the nanofibers was up to 210%. Fourier transform infrared spectrum and X-ray diffraction showed that the intermolecular hydrogen bonding happened between chitosan and PVA in electrospinning process, which was favorable for the formation of nanofibers. ICG released rapidly from the surface of the nanofibers first and then released continuously. The photodynamic nanofibers could inhibit the bacteria and decreased the F4/80 expression of MRSA-infected rats. The improved effects of wound healing were evaluated with the morphology, wound healing radio, the increased expression of cluster of differentiation 31 (CD31), the decreased level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The photosensitizer-loaded electrospinning nanofibers provide a novel promising option for treatment of infected wound.

Preparation of hydroxylated lecithin complexed iodine/carboxymethyl chitosan/sodium alginate composite membrane by microwave drying and its applications in infected burn wound treatment.

Improving the antibacterial properties of membrane wound dressings of natural polymers is crucial. Iodine is an important safe inorganic antibacterial agent, but was confined in the composition with polymer membranes due to the challenges of homogeneity and stability during drying. In the present work, iodine was complexed with hydroxylated lecithin (HL) to improve its stability and complexing efficiency for the composition with carboxymethly chitosan/sodium alginate. With the aid of microwave drying, hydroxylated lecithin complexed iodine/carboxymethly chitosan/sodium alginate (HLI/CMCS/SA) composite membranes with homogeneously distributions of HLI, high contents of activated iodine, good mechanical and swelling properties, proper water vapor permeability, pH controllable iodine release and excellent antibacterial properties were prepared. The composite membranes exhibited high repairing efficiencies for the infection of a rat model of the seawater immersed wound infection of deep partial-thickness burns. This novel antibacterial composite membrane can be potentially used as a high performance wound dressing for treating and repairing open trauma infections.

Highly efficient treatment of aerobic vaginitis with simple acidic buffered gels: The importance of pH and buffers on the microenvironment of vaginas.

Aerobic vaginitis (AV) leads to uterus deep infection or preterm birth. Antibacterial agents are not optimal therapeutics of AV. Here, we report a series of temperature-sensitive in situ forming acidic buffered gels for topical treatment of AV, involving lactate, acetate, and citrate gels at pH 3.5, 5.0, and 6.5. AV rat models were prepared following vaginal infection with Staphylococcus aureus and Escherichia coli. In vitro/in vivo studies of the buffered gels were performed compared with ofloxacin gels and blank gels. All the buffered gels showed the lower in vitro antibacterial activities than ofloxacin gels but the better in vivo anti-S. aureus effects and similar anti-E. coli effects. The buffered gels improved Lactobacillus growth in the vaginas. Both the healthy rat vaginal pH and the pH of rat vaginas treated with the buffered gels were about 6.5 though the AV rat models or ones treated with ofloxacin gels still remained at the high pH more than 7.0. After treatments with the buffered gels, the vaginal smears changed to a clean state nearly without aerobic bacteria, the vaginal tissues were refreshed, and the immunoreactions were downregulated. The acidic buffered gels bring rapid decrease of local vaginal pH, high antibacterial activities, improvement of probiotics, and alleviation of inflammation. They are simple, highly efficient, and safe anti-AV formulations.

Distinct molecular and cellular contributions to stabilizing selectin-mediated rolling under flow.

Leukocytes roll on selectins at nearly constant velocities over a wide range of wall shear stresses. Ligand-coupled microspheres roll faster on selectins and detach quickly as wall shear stress is increased. To examine whether the superior performance of leukocytes reflects molecular features of native ligands or cellular properties that favor selectin-mediated rolling, we coupled structurally defined selectin ligands to microspheres or K562 cells and compared their rolling on P-selectin. Microspheres bearing soluble P-selectin glycoprotein ligand (sPSGL)-1 or 2-glycosulfopeptide (GSP)-6, a GSP modeled after the NH2-terminal P-selectin-binding region of PSGL-1, rolled equivalently but unstably on P-selectin. K562 cells displaying randomly coupled 2-GSP-6 also rolled unstably. In contrast, K562 cells bearing randomly coupled sPSGL-1 or 2-GSP-6 targeted to a membrane-distal region of the presumed glycocalyx rolled more like leukocytes: rolling steps were more uniform and shear resistant, and rolling velocities tended to plateau as wall shear stress was increased. K562 cells treated with paraformaldehyde or methyl-beta-cyclodextrin before ligand coupling were less deformable and rolled unstably like microspheres. Cells treated with cytochalasin D were more deformable, further resisted detachment, and rolled slowly despite increases in wall shear stress. Thus, stable, shear-resistant rolling requires cellular properties that optimize selectin-ligand interactions.

Regulatory Effect of HBV Integrated Fragment on PCNA Promoter.

H7C is a HBV integrated fragment isolated from a human hepatocellular carcinoma, containing the promoter of preS2 and the C-terminal truncated preS/S open reading frame. We have studied the effect of the 3'-truncated preS/S on human proliferating cell nuclear antigen (PCNA) promoter by co-transfection of the expression plasmids. Result showed that the product, pKSH7C-Hpa I, which contained the intact H7C and the flanking cellular sequences, stimulated the expression from PCNA promoter dose-dependently, and its effect was 1-2 folds higher than that on SV40 promoter. However, two subclones, pKSH7C-XHX and pKSH7C-XbH, which would not express preS/S, showed no stimulatory effect. Furthermore, when if the -45 bp ATF-like site was mutated, the activation effect became diminished. This showed that the ATF-like site might be important in mediating the transactivating process. This is the first report of the effect of a HBV integrated fragment on the promoter of a replicating protein factor.