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Hemiepiphytic figs killing their host trees is an ecological process unique to the tropics. Yet the benefits and adaptive strategies of their special life history remain poorly understood. We compared leaf phosphorus (P) content data of figs and palms worldwide, and functional traits and substrate P content of hemiepiphytic figs (Ficus tinctoria), their host palm and nonhemiepiphytic conspecifics at different growth stages in a common garden. We found that leaf P content of hemiepiphytic figs and their host palms significantly decreased when they were competing for soil resources, but that of hemiepiphytic figs recovered after host death. P availability in the canopy humus and soil decreased significantly with the growth of hemiepiphytic figs. Functional trait trade-offs of hemiepiphytic figs enabled them to adapt to the P shortage while competing with their hosts. From the common garden to a global scale, the P competition caused by high P demand of figs may be a general phenomenon. Our results suggest that P competition is an important factor causing host death, except for mechanically damaging and shading hosts. Killing hosts benefits hemiepiphytic figs by reducing interspecific P competition and better acquiring P resources in the P-deficient tropics, thereby linking the life history strategy of hemiepiphytic figs to the widespread P shortage in tropical soils.

Melanogenesis (melanin pigment production) in melanocytes is canonically stimulated by the alpha melanocyte stimulating hormone (αMSH), which activates the cyclic-AMP-mediated expression of the melanocyte inducing transcription factor (MITF) and its downstream melanogenic genes, including the principal rate-limiting melanogenic enzyme tyrosinase (TYR). Here, we report that interferon-gamma (IFNG; type II interferon), but not interferon-alpha (a type I interferon), induces a noncanonical melanogenic pathway in mouse and human melanocytic cells. Inhibition of IFNG pathway by the JAK1/2 inhibitor ruxolitinib or knocking out Stat1 gene abrogated the IFNG-induced melanogenesis. Interestingly, IFNG-induced melanogenesis was independent of MITF. IFNG markedly increased the TYR protein expression but did not affect the mRNA expression, suggesting a post-translational regulatory mechanism. In contrast, IFNG had no effect on the expression of other melanogenesis-related proteins, for example, tyrosinase-related protein 1 (TYRP1) and dopachrome tautomerase (DCT). Glycosidase digestion assays revealed that IFNG treatment increased the mature glycosylated form of TYR, but not its de novo synthesis. Moreover, cycloheximide chase assay showed that degradation of TYR was decreased in IFNG-treated cells. These results suggest that the IFNG-STAT1 pathway regulates melanogenesis via regulation of the post-translational processing and protein stability of TYR.

CTLA4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti–CTLA4 immunotherapy is highly effective at reactivating T-cell responses against melanoma, which is postulated to be due to targeting CTLA4 on T cells. Here, we report that CTLA4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-γ (IFNG) signaling activated the expression of the human CTLA4 gene in a melanocyte and melanoma cell–specific manner. Mechanistically, IFNG activated CTLA4 expression through JAK1/2-dependent phosphorylation of STAT1, which bound a specific gamma-activated sequence site on the CTLA4 promoter, thereby licensing CBP/p300-mediated histone acetylation and local chromatin opening. In melanoma cell lines, elevated baseline expression relied upon constitutive activation of the MAPK pathway. Notably, RNA-seq analyses of melanoma specimens obtained from patients who had received anti–CTLA4 immunotherapy (ipilimumab) showed upregulation of an IFNG-response gene expression signature, including CTLA4 itself, which correlated significantly with durable response. Taken together, our results raise the possibility that CTLA4 targeting on melanoma cells may contribute to the clinical immunobiology of anti–CTLA4 responses.Significance: These findings show that human melanoma cells express high levels of the immune checkpoint molecule CTLA4, with important possible implications for understanding how anti-CTLA4 immunotherapy mediates its therapeutic effects. Cancer Res; 78(2); 436–50. ©2017 AACR.

Supplementary Figure S1: CTLA4 mRNA expression in human tumor cell lines. Supplementary Figure S2: CTLA4 promoter analysis. Supplementary Figure S3: UCSC genome browser view of human CTLA4 locus. Supplementary Figure S4: Recruitment of STAT1 and POL II to CTLA4 promoter by IFNG treatment. Supplementary Figure S5: The effects of CBP inhibitors on CTLA4 expression. Supplementary Figure S6: Quantification of western blotting in Fig. 5H. Supplementary Figure S7: The effects of Ruxolitinib on expression of genes of IFNG signaling pathway.

The unique tripeptide structure of green fluorescent protein (GFP), a Ser-Tyr-Gly motif, generates the mature chromophore in situ to define the emission profiles of GFP. Here, we describe the rational design and discovery of a biomimetic fluorescent emitter, MBP, by mimicking the key structure of the Ser-Tyr-Gly motif. Through systematically tailoring the tripeptide, a family of four chromophores were engineered, while only MBP exhibited bright fluorescence in different fluid solvents with highly enhanced quantum yields. Distinct to previous hydrogen-bonding-induced fluorescence quenching of GFP chromophore analogues, the emission of MBP was only slightly decreased in protic solvents. Heteronuclear multiple bond correlation techniques demonstrated the fundamental mechanism for enhanced fluorescence emission owing to the synergy of the formation of the intramolecular hydrogen-bonding-ring structure and the self-restricted effect, which was further illustrated via theoretical calculations. This work puts forward an extraordinary approach toward highly emissive biomimicking fluorophores, which gives new insights into the emission mechanisms and photophysics of GFP-like chromophores.

Background: Elevated levels of inflammatory cytokines such as Interleukin (IL)-17A have been repeatedly linked with major depression in both animals and humans. Our recent double-blinded Randomized Placebo-controlled Trial (RCT) discovered significant efficacy of a traditional Chinese medicine substance, namely the Lycium barbarum polysaccharide (LBP), on reducing depressive symptoms among adolescents with subthreshold depression. Here, we further investigated whether the antidepressant property of LBP was associated with its anti-inflammatory effect on adolescents with subthreshold depression. Methods: In this 6-week RCT, we measured common cytokine levels from participants’ peripheral blood samples, both at baseline and at the end of the 6-week intervention with either LBP (intervention group, N=14) or placebo (control group, N=10). Independent t-tests were used to compare the change of cytokine levels between groups.Network-based analysis was applied to evaluate the systemic immune responses to the interventions. Results: The intervention and control groups were matched on demographic and clinical characteristics. As expected, the LBP group exhibited a greater reduction in IL-17A compared to the placebo group (t = -2.25, P = 0.04) after the 6-week interventions. Moreover, network-level analysis showed that LBP reduced the correlations and connectivity among cytokines (Z = 3.34, P < 0.01), which was in turn associated with improvement of depressive symptoms. Conclusions: Our findings demonstrated that 6-week repeated LBP administrations downregulated immune responses in adolescents with StD, which could be a key mechanistic pathway underpinning the antidepressant effect of LBP.

Imaging and tracking macrophage behaviors in vivo are essential to reveal its biological function and fate in various diseases. Small molecular probes suffer from poor macrophage targeting and retention, rapid clearance, and deficient metabolizing stability. To overcome these limitations, a variety of functional nanoprobes have been developed for targeted imaging of macrophages in divergent diseases such as cancer, atherosclerosis and obesity. Generally, nanoprobes are functionalized with targeting peptides, ligands or antibodies to fulfill high macrophage affinity. In this review, the most recent advances of nanoprobes for imaging macrophages in vivo and ex vivo are systematically summarized. The challenges and perspectives of precisely imaging macrophages with improved signal-to-background ratios via nanoprobes are further discussed.

In this work, the polyacrylonitrile monolayer/composite nanofibrous membranes were successfully fabricated at different processing parameters. As expected, compared with monolayer membranes, the composite membrane revealed high breaking strength, high breaking elongation, high porosity, and good filtration performance. The composite method used in this article also provides new ideas for designing filter materials.

In this paper, we investigate the impact of downside risk in the oil market on the expected stock returns in China’s A-share market, and find that downside risk positively influences the expected s...

Cytotoxic T Lymphocyte Antigen 4 (CTLA4) expressed on the surface of T cells is an important immunotherapeutic target in many cancers, including melanoma. However, we previously found highly upregulated expression of CTLA4 in BRAF/NRAS-mutant human melanoma cell lines and tissues. Although CTLA4 is almost entirely expressed intracellularly in melanoma cells, its intracellular functions have remained elusive. Ectopic expression of Ctla4 (Ctla4-ee) in mouse melanoma cell lines significantly promoted lung colonization in syngeneic mice as well as in immunocompromised mice, suggesting that Ctla4 had pro-tumorigenic effects independent of its extracellular immune checkpoint function. Proteomics analysis identified apoptosis to be a major affected pathway and we found that Ctla4 ectopic-expressing mouse melanoma cells (B2905-Ctla4-ee) were significantly resistant to doxorubicin-induced apoptosis as compared to empty vector (EV) controls. In a reciprocal experiment, knocking out CTLA4 in the Hs936T human melanoma cells, that exhibit high endogenous CTLA4 expression, showed significantly increased apoptosis than the parental cells. Moreover, significant upregulation of anti-apoptotic proteins (Bnip3, Birc6, Pak1, Mcl-1, Survivin, Rac1/Cdc42, Bcl-2, and Bnip3l) and downregulation of pro-apoptotic proteins (p53 and Bad) were observed in CTLA4-ee cells as compared to EV controls. CTLA4-ee cells also showed significantly higher invasion in Matrigel-coated Transwell assay. Interestingly, we also found that CTLA4 translocated to mitochondria, where it downregulated oxidative phosphorylation and increased glycolysis. These findings lead us to hypothesize that CTLA4 plays a significant role in regulating apoptosis and mitochondrial metabolic functions, leading to the promotion of melanoma progression and metastasis. Citation Format: Hasan Raza Kazmi, Xuan Mo, Bo Zhou, Sarah Preston Alp, Scott Gross, Hassaan Wajeeh, Carmen Merali, John Elrod, Jonathan Soboloff, Salim Merali, M. Raza Zaidi. Intracellular Ctla4 overexpression promotes melanoma progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2536.

Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be closely associated with poor tumour differentiation. Overexpression of GDF1 suppresses cell proliferation but strongly enhances tumour dissemination and metastasis. Ectopic expression of GDF1 can induce the dedifferentiation of hepatocellular carcinoma (HCC) cells into their ancestral lineages and reactivate a broad panel of cancer testis antigens (CTAs), which further stimulate the immunogenicity of HCC cells to immune-based therapies. Mechanistic studies reveal that GDF1 functions through the Activin receptor-like kinase 7 (ALK7)-Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signalling cascade and suppresses the epigenetic regulator Lysine specific demethylase 1 (LSD1) to boost CTA expression. GDF1-induced tumour lineage plasticity might be an Achilles heel for HCC immunotherapy. Inhibition of LSD1 based on GDF1 biomarker prescreening might widen the therapeutic window for immune checkpoint inhibitors in the clinic., Poorly differentiated hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis. Here the authors show that GDF1, a member of the TGF-β superfamily, is highly expressed in high-grade poorly differentiated HCC and is associated with tumor plasticity, and that GDF1-induced reexpression of cancer testis antigens could render tumors sensitive to immune checkpoint inhibition.

Melanogenesis (melanin pigment production) in melanocytes is canonically stimulated by the alpha-melanocyte stimulating hormone (αMSH), which activates the cyclic-AMP-mediated expression of the melanocyte inducing transcription factor (MITF) and its downstream melanogenic genes, including the principal rate-limiting melanogenic enzyme tyrosinase (Tyr). Here we report that interferon-gamma (IFNG; type II interferon), but not IFN-alpha (a type I interferon), induces a noncanonical melanogenic pathway. Inhibition of IFNG pathway by the JAK inhibitor ruxolitinib or knocking out Stat1 abrogated the IFNG-induced melanogenesis. Interestingly, IFNG-induced melanogenesis was independent of MITF. IFNG markedly increased the Tyr protein expression but did not affect the mRNA expression, suggesting a post-translational regulatory mechanism. In contrast, IFNG had no effect on the expression of other melanogenesis-related proteins, e.g. tyrosinase-related protein 1 (Tyrp1) and dopachrome tautomerase (Dct). Glycosidase digestion assays revealed that IFNG treatment increased the mature glycosylated form of Tyr, but not its de novo synthesis. Moreover, cycloheximide chase assay showed that degradation of Tyr was decreased in IFNG-treated cells. These results suggest that the IFNG-STAT1 pathway regulates melanogenesis via modulation of the post-translational processing and protein stability of Tyr.SIGNIFICANCEThe canonical pathway that controls melanogenesis in melanocytes is activated by the alpha melanocyte stimulating hormone (αMSH) via its receptor MC1R, which activates the cyclic-AMP-mediated expression of the melanocyte master regulator MITF and its downstream target genes involved in the melanogenic process. Here we report a novel non-canonical melanogenic pathway that is mediated via the Interferon-gamma cytokine signaling. We show that this non-canonical pathway is independent of MITF-mediated gene expression, but rather functions via post-translational modification of the principal melanogenic enzyme Tyrosinase.

SUMMARYInterferon-gamma (IFNG) has long been regarded as the flag-bearer for the anti-cancer immunosurveillance mechanisms. However, relatively recent studies have suggested a dual role of IFNG, albeit there is no direct experimental evidence for its potential pro-tumor functions. Here we providein vivoevidence that treatment of mouse melanoma cell lines with physiological levels of Ifng enhances their tumorigenicity and metastasis in lung colonization allograft assays performed in immunocompetent syngeneic host mice, but not in immunocompromised host mice. We also show that this enhancement is dependent on downstream signaling via Stat1 but not Stat3, providing evidence of an oncogenic function of Stat1 in melanoma. The experimental results suggest that melanoma cell-specific Ifng signaling modulates the tumor microenvironment and its pro-tumorigenic effects are dependent on the γδ T cells, as Ifng-enhanced tumorigenesis was inhibited in the TCR-δ knockout mice. Overall, these results show that Ifng signaling may have tumor-promoting effects in melanoma by modulating the immune cell composition of the tumor microenvironment.

With the development of the city and the increase of the population, the demand for transportation is increasing. The increases in transportation ways and demand have also brought certain energy and environmental problems to transportation construction. A good transportation environment and green travel experience have an important role in promoting the happiness of urban life and the sustainable development of society. Based on this, the following solutions are proposed for the construction and development of urban green transportation. First, as a guiding role, the government should formulate active transportation and green transportation policies to promote the reform of multiple public transportation methods. Second, as a leading role, the market can support a variety of the construction of green travel modes, which could encourage the development of shared bicycles and new energy vehicles. Third, as the main role of city, the citizens would like to choose green travel tools with the guidance in the conscious level. If we built green behavior into a fashionable business card of the city, green behavior will lead the city’s transportation construction and development.

The water-retaining capabilities of bleached chemical pulps treated by the oven-, air-, vacuum-, and freeze-drying modes were determined with use of a reliable the headspace gas chromatographic method (HS-GC) developed recently. The results showed that reliable water retention data could be determined by the HS-GC method only in the case of air-dried pulp. This result was supplemented by observations of the surface morphology of the fibers from these drying processes. The present HS-GC method can be used for checking the differences of wettability (at a given equilibration time) of pulp specimens from different drying modes.

The temperature shrinkage effect is a very important factor causing the cracking of super-long frame structures. Current design codes and recommendations for reinforced concrete (RC) structures consider the influence of the construction process on the temperature shrinkage effect by adopting a uniform reduction coefficient and neglect the influence of the construction method. However, different construction processes can vary the temperature stress of the structure. In this paper, under cooling action, the temperature stress of a one-layer, super-long frame structure with different quantities and indwelling times of post-cast strips is calculated with a spatial nonlinear simulation analysis program by adopting the degenerated spatial solid virtual laminated element method. With this approach, the internal force state of each construction stage during the construction process is accounted for in a nonlinear mechanical model of the structure. The results show that the quantity and the indwelling time of post-cast strips can effectively vary the temperature stress of the structure. Meanwhile, the quantity of the post-cast strips can have a more obvious effect than the indwelling time. Therefore, the construction process is an important factor affecting the temperature shrinkage effect of the structures. The research results can provide a valid reference for the design and construction of super-long frame structures.

We propose a novel architecture to handle the problem of multi-frame super-resolution (MFSR). The proposed framework is known as Enhanced Burst Super-Resolution (EBSR), which divides the MFSR problem into three parts: alignment, fusion, and reconstruction. We propose a Feature Enhanced Pyramid Cascading and Deformable convolution (FEPCD) module to align multiple low-resolution burst images in the feature level. And then the aligned features are fused by a Cross Non-Local Fusion (CNLF) module. Finally, the SR image is reconstructed by the Long Range Concatenation Network (LRCN). In addition, we build a cascading residual pathway structure (CR) to improve the performance. We conduct several experiments to analyze and demonstrate these modules. Our EBSR model won the champion in the real track and second place in the synthetic track in the NTIRE21 Burst Super-Resolution Challenge.

This paper reviews the NTIRE2021 challenge on burst super-resolution. Given a RAW noisy burst as input, the task in the challenge was to generate a clean RGB image with 4 times higher resolution. The challenge contained two tracks; Track 1 evaluating on synthetically generated data, and Track 2 using real-world bursts from mobile camera. In the final testing phase, 6 teams submitted results using a diverse set of solutions. The top-performing methods set a new state-of-the-art for the burst super-resolution task., NTIRE 2021 Burst Super-Resolution challenge report