Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

Unveiling the Role of Water in Heterogeneous Photocatalysis of Methanol Conversion for Efficient Hydrogen Production.

Water molecules, which act as both solvent and reactant, play critical roles in photocatalytic reactions for methanol conversion. However, the influence of water on the adsorption of methanol and desorption of liquid products, which are two essential steps that control the performance in photocatalysis, has been well under-explored. Herein, we reveal the role of water in heterogeneous photocatalytic processes of methanol conversion on the platinized carbon nitride (Pt/C3N4) model photocatalyst. In situ spectroscopy techniques, isotope effects, and computational calculations demonstrate that water shows adverse effects on the adsorption of methanol molecules and desorption processes of methanol oxidation products on the surface of Pt/C3N4, significantly altering the reaction pathways in photocatalytic methanol conversion process. Guided by these discoveries, a photothermal-assisted photocatalytic system is designed to achieve a high solar-to-hydrogen (STH) conversion efficiency of 2.3 %, which is among the highest values reported. This work highlights the important roles of solvents in controlling the adsorption/desorption behaviours of liquid-phase heterogeneous catalysis.

PTPN3 acts as a tumor suppressor and boosts TGF-ß signaling independent of its phosphatase activity.

TGF-ß controls a variety of cellular functions during development. Abnormal TGF-ß responses are commonly found in human diseases such as cancer, suggesting that TGF-ß signaling must be tightly regulated. Here, we report that protein tyrosine phosphatase non-receptor 3 (PTPN3) profoundly potentiates TGF-ß signaling independent of its phosphatase activity. PTPN3 stabilizes TGF-ß type I receptor (TßRI) through attenuating the interaction between Smurf2 and TßRI. Consequently, PTPN3 facilitates TGF-ß-induced R-Smad phosphorylation, transcriptional responses, and subsequent physiological responses. Importantly, the leucine-to-arginine substitution at amino acid residue 232 (L232R) of PTPN3, a frequent mutation found in intrahepatic cholangiocarcinoma (ICC), disables its role in enhancing TGF-ß signaling and abolishes its tumor-suppressive function. Our findings have revealed a vital role of PTPN3 in regulating TGF-ß signaling during normal physiology and pathogenesis.

Full-length transcriptome sequencing and transgenic tobacco revealed the key genes in the chlorogenic acid synthesis pathway of Sambucus chinensis L.

Chlorogenic acid is a key chemical in antioxidation and antisepsis. Sambucus chinensis L. is an herbaceous plant rich in chlorogenic acid and a potential genetic resource for breeding high-chlorogenic acid plants. However, there are few studies on the synthesis pathway of chlorogenic acid in S. chinensis. Our study found chlorogenic acid accumulation in S. chinensis to be organ-specific, higher in leaves and buds but lower in roots, stems and fruits. A total number of 546,844 CCS (circular consensus sequence), including 402,767 full-length nonchimeric (FLNC) and 39 annotated sequences related to the synthesis of chlorogenic acid, was obtained by single-molecule real-time sequencing technology (SMRT). qRT-PCR showed that a number of key genes involved in chlorogenic acid synthesis were differentially expressed in various tissues of S. chinensis. Transgenic tobacco revealed that ectopic expression of the HCT homologous gene HCT-45178 increased the content of chlorogenic acid. Our results should be the first report of full-length transcriptome data of S. chinensis, which help to understand the basis of chlorogenic acid synthesis and provide a novel strategy for breeding tobacco cultivars with higher levels of chlorogenic acid.

Diagnosis and genetic analysis of a case with Bardet-Biedl syndrome caused by compound heterozygous mutations in the BBS12 gene.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.

Coordination Chemistry Engineered Polymeric Carbon Nitride Photoanode with Ultralow Onset Potential for Water Splitting.

Construction of an intimate film/substrate interface is of great importance for a photoelectrode to achieve efficient photoelectrochemical performance. Inspired by coordination chemistry, a polymeric carbon nitride (PCN) film is intimately grown on a Ti-coated substrate by an in situ thermal condensation process. The as-prepared PCN photoanode exhibits a record low onset potential (Eonset ) of -0.38 V versus the reversible hydrogen electrode (RHE) and a decent photocurrent density of 242 µA cm-2 at 1.23 VRHE for water splitting. Detailed characterization confirms that the origin of the ultralow onset potential is mainly attributed to the substantially reduced interfacial resistance between the Ti-coated substrate and the PCN film benefitting from the constructed interfacial sp2 N→Ti coordination bonds. For the first time, the ultralow onset potential enables the PCN photoanode to drive water splitting without external bias with a stable photocurrent density of ≈9 µA cm-2 up to 1 hour.

Systematic analysis of CCCH zinc finger family in Brassica napus showed that BnRR-TZFs are involved in stress resistance.

BACKGROUND: CCCH zinc finger family is one of the largest transcription factor families related to multiple biotic and abiotic stresses. Brassica napus L., an allotetraploid oilseed crop formed by natural hybridization between two diploid progenitors, Brassica rapa and Brassica oleracea. A systematic identification of rapeseed CCCH family genes is missing and their functional characterization is still in infancy. RESULTS: In this study, 155 CCCH genes, 81 from its parent B. rapa and 74 from B. oleracea, were identified and divided into 15 subfamilies in B. napus. Organization and syntenic analysis explained the distribution and collinearity relationship of CCCH genes, the selection pressure and evolution of duplication gene pairs in B. napus genome. 44 diploid duplication gene pairs and 4 triple duplication gene groups were found in B. napus of CCCH family and the segmental duplication is attributed to most CCCH gene duplication events in B. napus. Nine types of CCCH motifs exist in B. napus CCCH family members, and motif C-X7/8-C-X5-C-X3-H is the most common and a new conserved CCH motif (C-X5-C-X3-H) has been identified. In addition, abundant stress-related cis-elements exist in promoters of 27 subfamily IX (RR-TZF) genes and their expression profiles indicated that RR-TZF genes could be involved in responses to hormone and abiotic stress. CONCLUSIONS: The results provided a foundation to understand the basic characterization and genes evolution of CCCH gene family in B. napus, and provided potential targets for genetic engineering in Brassicaceae crops in pursuit of stress-tolerant traits.

Protective effects of astaxanthin on lipopolysaccharide-induced inflammation in bovine endometrial epithelial cells†.

Astaxanthin (AST), a natural antioxidant carotenoid, has been shown to exert anti-inflammatory effects. However, to our knowledge, no study has specifically addressed the potential protective effects of AST against bovine endometritis. The purpose of this study was to examine whether treatment with AST could protect endometrial epithelial cells against lipopolysaccharide (LPS)-induced inflammatory injury. Treatment of bovine endometrial (BEND) epithelial cell line with AST reduced LPS-induced production of interleukin-6 and tumor necrosis factor-alpha, increased the cellular activity of superoxide dismutase and catalase, decreased the proportion of apoptotic cells, and promoted the production of insulin-like growth factor and epithelial growth factor. The effects of AST were mediated through the downregulation of B-cell lymphoma 2 (Bcl-2) associated X, apoptosis regulator (Bax), and cleaved caspase-3 and through the upregulation of Bcl-2. Moreover, AST significantly increased the expression of the tight junction proteins (TJP) claudin, cadherin-1, and TJP1, which play an essential role in the maintenance of host endometrial defense barrier against pathogen infection. Collectively, these results demonstrated that treatment with AST protected against oxidative stress, prevented cell apoptosis, promoted BEND cells viability, and increased the production of growth factors, in addition to activating the endometrial defense barrier. Therefore, AST is a promising therapeutic agent for the prevention and treatment of endometritis. This finding is of utmost importance in the present times when the excessive use of antibiotics has resulted in the development of antibiotic-resistant bacteria.

Reddish GaN:ZnO photoelectrode for improved photoelectrochemical solar water splitting.

Efficient light harvesting is one of the key prerequisites in improving the solar conversion efficiency for photoelectrochemical water splitting. As classic semiconductors for water splitting, the solid state solution GaN:ZnO based photoanodes exhibit poor water splitting efficiency mainly limited by its light absorption. To overcome this bottleneck, here we report that phosphorus modification shifts the absorption edge of GaN:ZnO from 480 nm to the red end of 650 nm and also leads to one order of magnitude increase of the carrier concentration. Further, taking the surface phosphate groups as anchors, cobalt can be adsorbed, leading to the in situ formation of cobalt phosphate as a cocatalyst for water oxidation, which results in drastically improved photocurrent density and stability. This work highlights the significance of phosphorization treatment in extending the light harvest and changing the surface reaction kinetics for an efficient solar conversion process.

Using ß-ocimene to increase the artemisinin content in juvenile plants of Artemisia annua L.

OBJECTIVE: The anti-malarial drug, artemisinin, is harvested from the leaves of adult Artemisia annua L. plants. As its concentration in juvenile plants is very low, the present study aimed to assess if the airborne signaling molecule, ß-ocimene, could be used to enhance artemisinin accumulation in juvenile A. annua plants. RESULTS: Application of exogenous ß-ocimene increased artemisinin accumulation in A. annua. Treatment with 10 µM ß-ocimene for 4 days resulted in juvenile plants accumulating artemisinin contents of up to 25 mg/g (2.5%) of dry weight. The expression levels of key genes encoding enzymes involved in both precursor biosynthetic pathways and artemisinin biosynthetic pathways induced by ß-ocimene were upregulated. Glandular secretory trichome (GST) size and density increased by 49.2% and 38.2%, respectively, along with the upregulation of genes associated with GST development. CONCLUSION: ß-ocimene enhances artemisinin accumulation in juvenile A. annua plants by modulating artemisinin biosynthetic pathways and GST development.

Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-ß signaling.

Smad7 is a negative feedback product of TGF-ß superfamily signaling and fine tunes a plethora of pleiotropic responses induced by TGF-ß ligands. However, its noncanonical functions independent of TGF-ß signaling remain to be elucidated. Here, we show that Smad7 activates signal transducers and activators of transcription 3 (STAT3) signaling in maintaining mouse embryonic stem cell pluripotency in a manner independent of the TGF-ß receptors, yet dependent on the leukemia inhibitory factor (LIF) coreceptor glycoprotein 130 (gp130). Smad7 directly binds to the intracellular domain of gp130 and disrupts the SHP2-gp130 or SOCS3-gp130 complex, thereby amplifying STAT3 activation. Consequently, Smad7 facilitates LIF-mediated self-renewal of mouse ESCs and is also critical for induced pluripotent stem cell reprogramming. This finding illustrates an uncovered role of the Smad7-STAT3 interplay in maintaining cell pluripotency and also implicates a mechanism involving Smad7 underlying cytokine-dependent regulation of cancer and inflammation.

Molten-Salt-Mediated Synthesis of an Atomic Nickel Co-catalyst on TiO2 for Improved Photocatalytic H2 Evolution.

Atomic co-catalysts offer high potential to improve the photocatalytic performance, of which the preparation with earth-abundant elements is challenging. Here, a new molten salt method (MSM) is designed to prepare atomic Ni co-catalyst on widely studied TiO2 nanoparticles. The liquid environment and space confinement effect of the molten salt leads to atomic dispersion of Ni ions on TiO2 , while the strong polarizing force provided by the molten salt promotes formation of strong Ni-O bonds. Interestingly, Ni atoms are found to facilitate the formation of oxygen vacancies (OV) on TiO2 during the MSM process, which benefits the charge transfer and hydrogen evolution reaction. The synergy of atomic Ni co-catalyst and OV results in 4-time increase in H2 evolution rate compared to that of the Ni co-catalyst on TiO2 prepared by an impregnation method. This work provides a new strategy of controlling atomic co-catalyst together with defects for efficient photocatalytic water splitting.

Understanding the Roles of Oxygen Vacancies in Hematite-Based Photoelectrochemical Processes.

Oxygen vacancy (VO ) engineering is an effective method to tune the photoelectrochemical (PEC) performance, but the influence of VO on photoelectrodes is not well understood. Using hematite as a prototype, we herein report that VO functions in a more complicated way in PEC process than previously reported. Through a comprehensive analysis of the key charge transfer and surface reaction steps in PEC processes on a hematite photoanode, we clarify that VO can facilitate surface electrocatalytic processes while leading to severe interfacial recombination at the semiconductor/electrolyte (S-E) interface, in addition to the well-reported improvements in bulk conductivity. The improved bulk conductivity and surface catalysis are beneficial for bulk charge transfer and surface charge consumption while interfacial charge transfer deteriorates because of recombination through VO -induced trap states at the S-E interface.

The TOR signaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA.

Pseudouridine (Ψ) has been identified in various types of RNAs, including mRNA, rRNA, tRNA, snRNA, and many other noncoding RNAs. We have previously shown that RNA pseudouridylation, like DNA and protein modifications, can be induced by stress. For instance, growing yeast cells to saturation induces the formation of Ψ93 in U2 snRNA. Here, we further investigate this inducible RNA modification. We show that switching yeast cells from nutrient-rich medium to different nutrient-deprived media (including water) results in the formation of Ψ93 in U2 snRNA. Using gene deletion/conditional depletion as well as rapamycin treatment, we further show that the TOR signaling pathway, which controls cell entry into stationary phase, regulates Ψ93 formation. The RAS/cAMP signaling pathway, which parallels the TOR pathway, plays no role in this inducible modification.

Long-range RNA pairings contribute to mutually exclusive splicing.

Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks.

An Integrated Strategy towards Enhanced Performance of the Lithium-Sulfur Battery and its Fading Mechanism.

To fulfil the potential of Li-S batteries (LSBs) with high energy density and low cost, multiple challenges need to be addressed simultaneously. Most research in LSBs has been focused on the sulfur cathode design, although the performance is also known to be sensitive to other parameters such as binder, current collector, separator, lithium anode, and electrolyte. Here, an integrated LSB system based on the understanding of the different roles of binder, current collector, and separator is developed. By using the cross-linked carboxymethyl cellulose-citric acid (CMC-CA) binder, Toray carbon paper current collector, and reduced graphene oxide (rGO) coated separator, LSBs achieve a high capacity of 960 mAh g-1 after 200 cycles (2.5 mg cm-2 ) and 930 mAh g-1 after 50 cycles (5 mg cm-2 ) at 0.1 C. Moreover, the failure mechanism at a high sulfur loading with characteristics of fast capacity decay and infinite charging is discussed. This work highlights the synergistic effect of different components and the challenges towards more reliable LSBs with high sulfur loading.

SUMO Modification Reverses Inhibitory Effects of Smad Nuclear Interacting Protein-1 in TGF-ß Responses.

SNIP1 (Smad nuclear interacting protein 1) is a transcription repressor for the TGF-ß and NF-κB signaling pathways through disrupting the recruitment of co-activator p300. However, it is unclear how the functions of SNIP1 in the TGF-ß signaling pathway are controlled. Our present studies show that SNIP1 is covalently modified by small ubiquitin-like modifier (SUMO) in vitro and in vivo at three lysine sites: Lys5, Lys30, and Lys108, with Lys30 being the major SUMO modification site. SUMOylation of SNIP1 is enhanced by SUMO E3 ligase PIAS proteins and inhibited by SUMO proteases SENP1/2. Furthermore, we find that SUMOylation of SNIP1 attenuates its inhibitory effect in TGF-ß signaling because the SUMO-conjugated form of SNIP1 exhibits impaired ability to disrupt the formation of Smad complex and the interaction between p300 and Smads. Subsequently, SUMOylation of SNIP1 leads to the loss of SNIP1-mediated inhibition on expression of the TGF-ß target genes PAI-1 and MMP2 and eventually enhances TGF-ß-regulated cell migration and invasion.

Liver X receptor ß increases aquaporin 2 protein level via a posttranscriptional mechanism in renal collecting ducts.

Liver X receptors (LXRs) including LXRα and LXRß are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRß but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRß regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRß-/- mice exhibited a reduced response to desmopressin (dDAVP) stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin. AQP2 protein abundance in the renal inner medulla was significantly reduced in LXRß-/- mice but with little change in AQP2 mRNA levels. In vitro studies showed that AQP2 protein levels were elevated upon LXR agonist treatment in both primary cultured mouse inner medullary duct cells (mIMCD) and the mIMCD3 cell line with stably expressed AQP2. In addition, LXR agonists including TO901317 and GW3965 failed to induce AQP2 gene transcription but diminished its protein ubiquitination in primary cultured mIMCD cells, thereby inhibiting its degradation. Moreover, LXR activation-induced AQP2 protein expression was abolished by the protease inhibitor MG132 and the ubiquitination-deficient AQP2 (K270R). Taken together, the present study demonstrates that activation of LXRß increases AQP2 protein levels in the renal collecting ducts via a posttranscriptional mechanism. As such, LXRß represents a key regulator of body water homeostasis.

[Optogenetic activation of dorsal hippocampal astrocytic Rac1 blocks the learning of associative memory].

Rac1 belongs to the family of Rho GTPases, and plays important roles in the brain function. It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology. However, the effect of its dynamic activation in regulating physiological function remains unclear. Recently, a photoactivatable analogue of Rac1 (PA-Rac1) has been developed, allowing the activation of Rac1 by the specific wavelength of light in living cells. Thus, we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optical stimulation. Primary culture of hippocampal astrocytes was infected with the recombinant AAV-PA-Rac1 or AAV-PA-Rac1-C450A. Real-time fluorescence imaging showed that the cell membrane of the astrocyte expressing PA-Rac1 protruded near the light spot, while the astrocyte expressing PA-Rac1-C450A did not. We injected AAV-PA-Rac1 and AAV-PA-Rac1-C450A into dorsal hippocampus to investigate the role of the activation of Rac1 in regulating the associative learning. With optical stimulation, the PA-Rac1 group, rather than the PA-Rac1-C450A group, showed slower learning curve during the fear conditioning compared with the control group, indicating that activating astrocytic Rac1 blocks the formation of contextual memory. Our data suggest that the activation of Rac1 in dorsal hippocampal astrocyte plays an important role in the associative learning.

Anti-Interleukin-1 Beta/Tumor Necrosis Factor-Alpha IgY Antibodies Reduce Pathological Allergic Responses in Guinea Pigs with Allergic Rhinitis.

This study aims to determine whether the combined blockade of IL-1ß and TNF-α can alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-α IgY treatment group; (4) the 0.1% anti-IL-1ß IgY treatment group; (5) the 0.1% combined anti-IL-1ß and TNF-α IgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright's staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P < 0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P < 0.05) in the combined 0.1% anti-IL-1ß- and TNF-α IgY-treated guinea pigs. The data suggest that topical blockade of IL-1ß and TNF-α could reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.