Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus.

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.

A nanobody inhibiting porcine reproductive and respiratory syndrome virus replication via blocking self-interaction of viral nucleocapsid protein.

Porcine reproductive and respiratory syndrome (PRRS) is a serious global pig industry disease. Understanding the mechanism of viral replication and developing efficient antiviral strategies are necessary for combating with PRRS virus (PRRSV) infection. Recently, nanobody is considered to be a promising antiviral drug, especially for respiratory viruses. The present study evaluated two nanobodies against PRRSV nucleocapsid (N) protein (PRRSV-N-Nb1 and -Nb2) for their anti-PRRSV activity in vitro and in vivo. The results showed that intracellularly expressed PRRSV-N-Nb1 significantly inhibited PRRSV-2 replication in MARC-145 cells (approximately 100%). Then, the PRRSV-N-Nb1 fused with porcine IgG Fc (Nb1-pFc) as a delivering tag was produced and used to determine its effect on PRRSV-2 replication in porcine alveolar macrophages (PAMs) and pigs. The inhibition rate of Nb1-pFc against PRRSV-2 in PAMs could reach >90%, and it can also inhibit viral replication in vivo. Epitope mapping showed that the motif Serine 105 (S105) in PRRSV-2 N protein was the key amino acid binding to PRRSV-N-Nb1, which is also pivotal for the self-interaction of N protein via binding to Arginine 97. Moreover, viral particles were not successfully rescued when the S105 motif was mutated to Alanine (S105A). Attachment, entry, genome replication, release, docking model analysis, and blocking enzyme-linked immunosorbent assay (ELISA) indicated that the binding of PRRSV-N-Nb1 to N protein could block its self-binding, which prevents the viral replication of PRRSV. PRRSV-N-Nb1 may be a promising drug to counter PRRSV-2 infection. We also provided some new insights into the molecular basis of PRRSV N protein self-binding and assembly of viral particles.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes serious economic losses to the swine industry worldwide, and there are no highly effective strategies for prevention. Nanobodies are considered a promising novel approach for treating diseases because of their ease of production and low costing. Here, we showed that PRRSV-N-Nb1 against PRRSV-N protein significantly inhibited PRRSV-2 replication in vitro and in vivo. Furthermore, we demonstrated that the motif Serine 105 (S105) in PRRSV-N protein was the key amino acid to interact with PRRSV-N-Nb1 and bond to its motif R97, which is important for the self-binding of N protein. The PRRSV-N-Nb1 could block the self-interaction of N protein following viral assembly. These findings not only provide insights into the molecular basis of PRRSV N protein self-binding as a key factor for viral replication for the first time but also highlight a novel target for the development of anti-PRRSV replication drugs.

Mobile phone problem use and depressive symptoms: the mediating role of social support and attitude to aging among Chinese older adults.

BACKGROUND: Little is known about mobile phone problem use (MPPU) among older adults. This study investigated critical factors affecting MPPU and filled the gap between MPPU and depressive symptoms in older people. METHODS: A cross-sectional study was conducted in community (n = 376) with questionnaires of Multidimensional Scale of Perceived Social Support (MSPSS), Geriatric Depression Scale (GDS-15), Attitudes to Aging Questionnaire (AAQ) and Mobile Phone Problem Use Scale (MPPUS). RESULTS: 80.9% of older people used smartphones and spend less than three hours on mobile phone per day. The average MPPU score of Chinese elderly is greater than the cut off to 41. Female (ß = -0.11, P = 0.037), living with spouse (ß = -0.17, P = 0.03), and late marriage age (ß = -0.16, P = 0.007) are less likely to develop MPPU. The relationship between MPPU and depressive symptoms was partially mediated by social support and attitude to aging. CONCLUSION: Elderly people generally have higher MPPU scores. MPPU was associated with depressive symptoms, through social support and attitude to aging.

In Situ Lignin Adhesion for High-Performance Bamboo Composites.

Bamboo composite is an attractive candidate for structural materials in applications such as construction, the automotive industry, and logistics. However, its development has been hindered due to the use of harmful petroleum-derived synthetic adhesives or low-bonding biobased adhesives. Herein, we report a novel bioadhesion strategy based on in situ lignin bonding that can process natural bamboo into a scalable and high-performance composite. In this process, lignin bonds the cellulose fibrils into a strong network via a superstrong adhesive interface formed by hydrogen bonding and nanoscale entanglement. The resulting in situ glued-bamboo (glubam) composite exhibits a record-high shear strength of ∼4.4 MPa and a tensile strength of ∼300 MPa. This in situ lignin adhesion strategy is facile, highly scalable, and cost-effective, suggesting a promising route for fabricating strong and sustainable structural bamboo composites that sequester carbon and reduce our dependence on petrochemical-based adhesives.

Effect of Calcination Atmosphere on the Performance of Cu/Al2O3 Catalyst for the Selective Hydrogenation of Furfural to Furfuryl Alcohol.

The selective hydrogenation of the biomass platform molecule furfural (FAL) to produce furfuryl alcohol (FA) is of great significance to alleviate the energy crisis. Cu-based catalysts are the most commonly used catalysts, and their catalytic performance can be optimized by changing the preparation method. This paper emphasized the effect of calcination atmosphere on the performance of a Cu/Al2O3 catalyst for the selective hydrogenation of FAL. The precursor of the Cu/Al2O3 catalyst prepared by the ammonia evaporation method was treated with different calcination atmospheres (N2 and air). On the basis of the combined results from the characterizations using in situ XRD, TEM, N2O titration, H2-TPR and XPS, the Cu/Al2O3 catalyst calcined in the N2 atmosphere was more favorable for the dispersion and reduction of Cu species and the reduction process could produce more Cu+ and Cu0 species, which facilitated the selective hydrogenation of FAL to FA. The experimental results showed that the N2 calcination atmosphere improved the FAL conversion and FA selectivity, and the FAL conversion was further increased after reduction. Cu/Al2O3-N2-R exhibited the outstanding performance, with a high yield of 99.9% of FA after 2 h at 120 °C and an H2 pressure of 1 MPa. This work provides a simple, efficient and economic method to improve the C=O hydrogenation performance of Cu-based catalysts.

Construction of Nanofibrillar Networked Wood Aerogels Derived from Typical Softwood and Hardwood: A Comparative Study on the In Situ Formation Mechanism of Nanofibrillar Networks.

The construction of networks within natural wood (NW) lumens to produce porous wood aerogels (WAs) with fascinating characteristics of being lightweight, flexible, and porous is significant for the high value-added utilization of wood. Nonetheless, how wood species affect the structure and properties of WAs has not been comprehensively investigated. Herein, typical softwood of fir and hardwoods of poplar and balsa are employed to fabricate WAs with abundant nanofibrillar networks using the method of lignin removal and nanofibril's in situ regeneration. Benefiting from the avoidance of xylem ray restriction and the exposure of the cellulose framework, hardwood has a stronger tendency to form nanofibrillar networks compared to softwood. Specifically, a larger and more evenly distributed network structure is displayed in the lumens of balsa WAs (WA-3) with a low density (59 kg m-3), a high porosity (96%), and high compressive properties (strain = 40%; maximum stress = 0.42 MPa; height retention = 100%) because of the unique structure and properties of WA-3. Comparatively, the specific surface area (SSA) exhibits 25-, 27-, and 34-fold increments in the cases of fir WAs (WA-1), poplar WAs (WA-2), and WA-3. The formation of nanofibrillar networks depends on the low-density and thin cell walls of hardwood. This work offers a foundation for investigating the formation mechanisms of nanonetworks and for expanding the potential applications of WAs.

Temperature and strain simultaneous sensing measurement based on an all-fiber Mach-Zehnder interferometer and fiber Bragg grating.

We designed and fabricated what we believe to be a novel dual-parameter fiber optic sensor for simultaneous measurement of temperature and strain, which was composed of a femtosecond laser inscribed fiber Bragg grating (FBG), three segments of a single-mode fiber (SMF), and two segments of a multimode fiber (MMF), forming a SMF-MMF-FBG-MMF-SMF structure. The FBG and Mach-Zehnder interferometer (MZI) were present in this structure so that the changes of the temperature and strain parameters can be sensed by the shifts of the reflection center wavelength of the FBG and the interference valley wavelength of the MZI. We simulated the light field distribution of the sensor structure, compared the shapes of the interference spectra formed by the MZI structure with different sensing arm lengths of 25, 35, and 45 mm, and analyzed the spectra in the spatial frequency domain. The simulation results showed that the interference spectrum of the MZI structure with a 25 mm length sensing arm was clearer and more suitable for the experiment. The experimental results showed that the temperature sensitivity of the FBG and MZI was 14.81 and 43.54 pm/°C in the range of 80°C to 240°C, and the strain sensitivity was 1.49 and -2.58 pm/µÎµ in the range of 0 to 1200 µÎµ, with a high linearity and excellent repeatability. The sensor is economical, sensitive, and convenient to fabricate, and exhibits promising applications in the fields of biochemical medical detection and industrial production monitoring.

Dopamine Functionalized Polyethylene Glycol for Improving Stability of Gold Nanoparticles against Reactive Oxygen Species in Serum.

PEGylation is the most effective antifouling method for the surface modification of gold nanoparticles (AuNPs). However, thiol-terminated polyethylene glycol (PEG) ligands tethered on the AuNPs are instable in serum and can detach from the AuNP surface, resulting in a significant reduce of their antifouling properties. Herein, it is reported that reactive oxygen species (ROS) is a major factor causing the detachment of PEG ligands from AuNP surfaces. By covalently backfilling dopamine-functionalized PEG on the AuNPs, the stability of PEG ligands on AuNP surface and the antifouling ability of AuNPs can be effectively improved. Tuning the balance between ROS and dopamine-functionalized PEG can be used as a new strategy to control the self-assembly of AuNPs and serum proteins.

Generation of frequency 32-tupling millimeter-wave based on a dual-parallel polarization modulator.

A scheme to generate a frequency 32-tupling millimeter wave (mm-wave) is proposed, enabled by two dual-parallel polarization modulators (DP-PolMs) in cascade. By properly controlling the amplitude and the phase shift of the radio-frequency (RF) driving signal applied to two DP-PolMs, the main optical components at the output of the DP-PolM are ±16th order optical sidebands and the central carrier. After the central carrier is canceled by the polarization multiplexing structure, the ±16th order optical sidebands are beaten in the photodetector; then the frequency 32-tupling mm-wave can be achieved. The optical sideband suppression ratio (OSSR) and the radio-frequency spurious suppression ratio (RFSSR) of the generated signal are 52 and 47 dB in simulation, which are consistent with the theoretical analysis values 53.7 and 47.7 dB. The influence on the OSSR and RFSSR of the generated signal by the key parameters of devices deviating from the theoretical analysis value i are investigated.

Opioid-free anesthesia compared to opioid anesthesia for laparoscopic radical colectomy with pain threshold index monitoring: a randomized controlled study.

BACKGROUND: Few studies have investigated the depth of intraoperative analgesia with non-opioid anesthesia. This study evaluated whether opioid-free anesthesia can provide an effective analgesia-antinociception balance monitored by the / pain threshold index in laparoscopic radical colectomy. METHODS: We enrolled 102 patients undergoing laparoscopic radical colectomy with general anesthesia. Participants were randomly allocated into two groups to receive opioid-free anesthesia (group OFA) with dexmedetomidine (loading dose with 0.6 µg·kg-1 for 10 min and then 0.5 µg·kg-1·h-1 continuous infusion) and sevoflurane plus bilateral paravertebral blockade (0.2 µg·kg-1 dexmedetomidine and 0.5% ropivacaine 15 ml per side) or opioid-based anesthesia (group OA) with remifentanil, sevoflurane, and bilateral paravertebral blockade (0.5% ropivacaine 15 ml per side). The primary outcome variable was pain intensity during the operation, as assessed by the pain threshold index with the multifunction combination monitor HXD- I. Results were analyzed using repeated measures analysis of variance and Student's t-test. The secondary outcomes were wavelet index, lactic levels, and blood glucose concentration during the operation. The visual analog scale (VAS), rescue analgesic consumption, and side-effects of opioids after surgery were further assessed. RESULTS: One hundred and one patients were included in the analysis. Analysis revealed that the intraoperative pain threshold index readings were not significantly different between the groups from incision to the end of the operation (P = 0.06). Furthermore, similar changes in the brain wavelet index readings were observed in the OFA and OA groups. There was no statistical difference in VAS scores between the groups (P > 0.05); however, non-opioid anesthesia did reduce the rescue analgesic consumption after operation (P < 0.05). In the OFA group, the blood glucose levels increased by 20% compared to baseline and were significantly higher than those in the OA group (P < 0.001). The incidences of postoperative nausea and vomiting, urine retention, intestinal paralysis and pruritus were not significantly different from those in the OA group (P > 0.05). CONCLUSIONS: This study suggests that compared to the opioid anesthesia regimen, our opioid-free anesthesia regimen achieved an equally effective intraoperative pain threshold index in laparoscopic radical colectomy. The incidence of opioid-related adverse reactions was not different between regimens, and intraoperative blood glucose levels were higher with opioid-free anesthesia. TRIAL REGISTRATION: ChiCTR1900021223, 02/02/2019, Title: " Opioid-free anesthesia in laparoscopic surgery: a randomized controlled trial ". Website: hppts:// www.chictr.ogr.cn.

Research on Multi-Level Scheduling of Mine Water Reuse Based on Improved Whale Optimization Algorithm.

Aiming at the problem of the inefficiency of coal mine water reuse, a multi-level scheduling method for mine water reuse based on an improved whale optimization algorithm is proposed. Firstly, the optimization objects of mine water reuse time and reuse cost are used to establish the optimal scheduling model of mine water. Secondly, in order to overcome the defect that the whale optimization algorithm (WOA) is prone to local convergence, the opposition-based learning strategy is introduced to speed up the convergence speed, the Levy flight strategy is used to enhance the ability of the algorithm to jump out of the local optimization, the nonlinear convergence factor is used to balance the global and local search ability, and the adaptive inertia weight is used to improve the optimization accuracy of the algorithm. Finally, the improved whale optimization algorithm (IWOA) is applied to the mine water optimization scheduling model with multiple objects and constraints. The results show that the reuse efficiency of the multi-level scheduling method of mine water reuse is increased by 30.2% and 31.9%, respectively, in the heating and nonheating seasons, which can significantly improve the reuse efficiency of mine water and realize the efficient utilization of mine water reuse deployment. At the same time, experiments show that the improved whale optimization algorithm has higher convergence accuracy and speed, which proves the feasibility and superiority of its improvement strategies.

PHLDA3 promotes lung adenocarcinoma cell proliferation and invasion via activation of the Wnt signaling pathway.

The PHLDA3 gene encodes a small 127 amino acid protein with a pleckstrin homology (PH)-only domain. The expression and significance of PHLDA3 in lung cancer remain unclear. Here, we investigated the role of PHLDA3 in tumor proliferation and invasion in lung adenocarcinoma. Immunohistochemistry and immunoblotting analyses were used to assess PHLDA3 expression in lung cancer tissues, and its correlation with clinicopathological factors in lung cancer. Plasmids encoding PHLDA3 and small interfering RNA against PHLDA3 were used to regulate the expression of PHLDA3 in lung cancer cells. Furthermore, the effects of PHLDA3 on lung cancer cell proliferation and invasion were investigated using the MTS, colony formation, Matrigel invasion, and wound healing assays. Co-immunoprecipitation analysis and inhibitors of both the Wnt signaling pathway and GSK3ß were used to explore the regulatory mechanisms underlying the role of PHLDA3 in lung cancer cells. PHLDA3 was found to be overexpressed in lung cancer tissues, and its expression was correlated with poor outcomes in lung adenocarcinoma patients. PHLDA3 expression promoted the proliferation, invasion, and migration of lung cancer cells. Overexpression of PHLDA3 activated the Wnt signaling pathway and facilitated epithelial-mesenchymal transition. Inhibition of Wnt signaling pathway activity, using XAV-939, reversed the effects of PHLDA3 overexpression in lung cancer cells; moreover, PHLDA3 could bind to GSK3ß. Inhibition of GSK3ß activity, using CHIR-99021, restored the proliferative and invasive abilities of PHLDA3 knockdown cells. Our findings demonstrate that PHLDA3 is highly expressed in lung adenocarcinomas and is correlated with poor outcomes. Furthermore, it promotes the proliferation and invasion of lung cancer cells by activating the Wnt signaling pathway.

Wood Ionic Cable.

The combination of good stability, biocompatibility, and high mechanical strength is attractive for bio-related material applications, but it remains challenging to simultaneously achieve these properties in a single, ionically conductive material. Here a "wood" ionic cable, made of aligned wood nanofibrils, demonstrating a combination of biocompatibility, high mechanical strength, high ionic conductivity, and excellent stability is reported. The wood ionic cable possesses excellent flexibility and exhibits high tensile strength up to 260 MPa (in the dry state) and ≈80 MPa (in the wet state). The nanochannels within the highly aligned cellulose nanofibrils and the presence of negative charges on the surfaces of these nanochannels, originating from the cellulose hydroxyl groups, provide new opportunities for ion regulation at low salt concentrations. Ion regulation in turn enables the wood ionic cable to have unique nanofluidic ionic behaviors. The Na+ ion conductivity of the wood ionic cable can reach up to ≈1.5 × 10-4 S cm-1 at low Na+ ion concentration (1.0 × 10-5 mol L-1 ), which is an order of magnitude higher than that of bulk NaCl solution at the same concentration. The scalable, biocompatible wood ionic cable enables novel ionic device designs for potential ion-regulation applications.

Plateletpheresis-associated lymphopenia in frequent platelet donors.

More than 1 million apheresis platelet collections are performed annually in the United States. After 2 healthy plateletpheresis donors were incidentally found to have low CD4+ T-lymphocyte counts, we investigated whether plateletpheresis causes lymphopenia. We conducted a cross-sectional single-center study of platelet donors undergoing plateletpheresis with the Trima Accel, which removes leukocytes continuously with its leukoreduction system chamber. We recruited 3 groups of platelet donors based on the total number of plateletpheresis sessions in the prior 365 days: 1 or 2, 3 to 19, or 20 to 24. CD4+ T-lymphocyte counts were <200 cells per microliter in 0/20, 2/20, and 6/20 donors, respectively (P = .019), and CD8+ T-lymphocyte counts were low in 0/20, 4/20, and 11/20 donors, respectively (P < .001). The leukoreduction system chamber's lymphocyte-extraction efficiency was ∼15% to 20% for all groups. Immunophenotyping showed decreases in naive CD4+ T-lymphocyte and T helper 17 (Th17) cell percentages, increases in CD4+ and CD8+ effector memory, Th1, and regulatory T cell percentages, and stable naive CD8+ and Th2 percentages across groups. T-cell receptor repertoire analyses showed similar clonal diversity in all groups. Donor screening questionnaires supported the good health of the donors, who tested negative at each donation for multiple pathogens, including HIV. Frequent plateletpheresis utilizing a leukoreduction system chamber is associated with CD4+ and CD8+ T-cell lymphopenia in healthy platelet donors. The mechanism may be repeated extraction of these cells during plateletpheresis. The cytopenias do not appear to be harmful.

Asymmetric population of momentum distribution by quasi-periodically driving a triangular optical lattice.

Ultracold atoms in periodical-driven optical lattices enable us to investigate novel band structures and explore the topology of the bands. In this work, we investigate the impact of the ramping process of the driving signal and propose a simple but effective method to realize desired asymmetric population in momentum distribution by controlling the initial phase of the driving signal. A quasi-momentum oscillation along the shaking direction in the frame of reference co-moving with the lattice is formed, causing the formation of the mix of ground energy band and first excited band in laboratory frame, within the regime that the driving frequency is far less than the coupling frequency between ground band and higher energy bands. This method avoids the construction of intricate lattices or complex control sequence. With a triangular lattice, we experimentally investigate the influence of the initial phase, frequency, amplitude of the driving signal on the population difference and observe good agreement with our theoretical model. This provides guidance on how to load a driving signal in driven optical lattice experiment and also potentially supplies a useful tool to form a qubit that can be used in quantum computation.

Viewing heterospecific facial expressions: an eye-tracking study of human and monkey viewers.

Common facial expressions of emotion have distinctive patterns of facial muscle movements that are culturally similar among humans, and perceiving these expressions is associated with stereotypical gaze allocation at local facial regions that are characteristic for each expression, such as eyes in angry faces. It is, however, unclear to what extent this 'universality' view can be extended to process heterospecific facial expressions, and how 'social learning' process contributes to heterospecific expression perception. In this eye-tracking study, we examined face-viewing gaze allocation of human (including dog owners and non-dog owners) and monkey observers while exploring expressive human, chimpanzee, monkey and dog faces (positive, neutral and negative expressions in human and dog faces; neutral and negative expressions in chimpanzee and monkey faces). Human observers showed species- and experience-dependent expression categorization accuracy. Furthermore, both human and monkey observers demonstrated different face-viewing gaze distributions which were also species dependent. Specifically, humans predominately attended at human eyes but animal mouth when judging facial expressions. Monkeys' gaze distributions in exploring human and monkey faces were qualitatively different from exploring chimpanzee and dog faces. Interestingly, the gaze behaviour of both human and monkey observers were further affected by their prior experience of the viewed species. It seems that facial expression processing is species dependent, and social learning may play a significant role in discriminating even rudimentary types of heterospecific expressions.

An evidence-based etiology study of synovial cyst of knee cruciate ligament: a real or pseudo-cyst.

PURPOSE: Synovial cyst of knee cruciate ligament (SCKCL) is a rare condition but can cause severe knee pain. The understanding of its etiology is relatively poor. This current study aimed to elucidate the pathogenesis of SCKCL based on a series of histo- and cytopathological examination. METHODS: Ten SCKCL patients who underwent arthroscopy were enrolled, among five patients claimed past knee injury. Hematoxylin & eosin staining was conducted to the cyst wall tissue sections and Papanicolaou staining to the cyst fluid smear. Prussian blue staining was employed to both the wall section and fluid smear. Immumohistochemical staining for mesothelial cells (MC), epithelial cells (CK), vascular endothelial cells (CD31), monocytes (CD68), and hematogenous stem cells (CD117) were taken to elucidate the possible involvement of various cell types in the development of SCKCL. RESULTS: No erythrocyte was discovered in the fluid; however, Prussian blue stained hemosiderin particles were found in the cyst wall and fluid, suggesting past hemorrhage in all patients. Abundant lymphocytes and plasmocytes were observed in the cyst wall and fluid. In addition, the cyst lining was infiltrated with abundant CD68(+) monocytes while only few MC(+) mesothelial cells were sporadically observed in four samples. The cyst submucosa was also diffused with abundant CD68(+) monocytes and proliferated capillaries stained with CD31. CD117-positve hematogenous stem cells were sporadically observed in eight specimens. CONCLUSION: Our findings provided evidence that SCKCL is not a mature synovial cyst but rather an inflammatory pseudo-cyst. It may have resulted from past minor hemorrhage and intra-ligament chronic inflammation.

Odd-skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and ß-catenin.

The odd-skipped related 1 (OSR1) gene encodes a zinc-finger transcription factor. The expression and significance of OSR1 in human tumors remains unclear. We found that OSR1 was downregulated in lung cancers, and its expression was correlated with poor differentiation. Overexpression of OSR1 by OSR1 gene transfection into H1299 cells (H1299-OSR1) inhibited the proliferation and invasion of lung cancer cells. Knockdown of OSR1 with small interfering (si)RNA against OSR1 in A549 cells (A549-siOSR1) enhanced the proliferation and invasion of lung cancer cells. Western blot analysis showed that the expression level of GSK3ß increased, while that of p-GSK3ß, nuclear ß-catenin, cyclin D1, c-Myc and matrix metallopeptidase 7 significantly decreased in the H1299-OSR1 cells, and this pattern was reversed in the A549-siOSR1 cells compared to that in the control cells. Furthermore, upregulation of sex-determining region Y-box 9 (SOX9) by SOX9 gene transfection increased the expression of ß-catenin, which was inhibited by OSR1. The mRNA and protein expression levels of SOX9 and ß-catenin were reduced in H1299-OSR1 cells and increased in A549-siOSR1 cells. In conclusion, the expression of OSR1 was more reduced in lung cancer tissues than in normal lung tissues, and was correlated with poor differentiation. OSR1 downregulated the activity of the Wnt signaling pathway by suppressing the expression of SOX9 and ß-catenin.

B7-H4 is Predictive of Poor Prognosis in Patients with Gastric Cancer.

BACKGROUND Recently, some studies were performed to evaluate the relevance of B7-H4 and gastric cancer (GC) prognosis. However, the results remained controversial. Therefore, we performed the present meta-analysis. MATERIAL AND METHODS We performed a systematic search in PubMed and Web of Science databases. All data were extracted and reviewed from each eligible study independently by 2 investigators. The strength of association between B7-H4 and GC prognosis was assessed by computing odds ratio (OR) with its corresponding 95% confidence interval (CI). RESULTS Six studies that evaluated the association between B7-H4 and GC prognosis were included. The results showed a statistically significant association of B7-H4 and GC prognosis (OR=1.63, 95%CI=1.30-2.03). Furthermore, we conducted subgroup analysis based on source of B7-H4; the results from blood (OR=1.71; 95%CI, 1.09-2.68) and tissue (OR=1.60; 95%CI, 1.03-2.07) indicated B7-H4 was significantly associated with poor prognosis. CONCLUSIONS This meta-analysis suggests that GC patients with high B7-H4 have poor prognosis.

iTRAQ based quantitative proteomics approach validated the role of calcyclin binding protein (CacyBP) in promoting colorectal cancer metastasis.

Keeping continuity with our previous study that revealed direct correlations between CRC metastasis and enhanced CacyBP protein levels, here we attempt to improve our understanding of the mechanisms involved within this enigmatic process. Overexpression of CacyBP (CacyBP-OE) in primary CRC cell and its knock down (CacyBP-KD) in the metastatic CRC cells revealed (through phenotypic studies) the positive impact of the protein on metastasis. Additionally, two individual 4-plex iTRAQ based comparative proteomics experiments were carried out on the CacyBP-OE and CacyBP-KD cells, each with two biological replicates. Mining of proteomics data identified total 279 (63.80% up-regulated and 36.20% down-regulated) proteins to be significantly altered in expression level for the OE set and in the KD set, this number was 328 (48.78% up-regulated and 51.22% down-regulated). Functional implications of these significantly regulated proteins were related to metastatic phenotypes such as cell migration, invasion, adhesion and proliferation. Gene ontology analysis identified integrin signaling as the topmost network regulated within CacyBP-OE. Further detection of caveolar mediated endocytosis in the top hit list correlated this phenomenon with the dissociation of integrins from the focal adhesion complex which are known to provide the traction force for cell movement when transported back to the leading edge. This finding was further supported by the data obtained from CacyBP-KD data set showing down-regulation of proteins necessary for integrin endocytosis. Furthermore, intracellular calcium levels (known to influence integrin mediated cell migration) were found to be lowered in CacyBP-KD cells indicating decreased cell motility and vice versa for the CacyBP-OE cells. Actin nucleation by ARP-WASP complex, known to promote cell migration, was also identified as one of the top regulated pathways in CacyBP-OE cells. In short, this study presents CacyBP as a promising candidate biomarker for CRC metastasis and also sheds light on the underlying molecular mechanism by which CacyBP promotes CRC metastasis.