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Injectable hydrogels derived from natural extracellular matrices exhibit excellent adhesion to endothelial cells in vitro and are ideal for many biomedical applications. However, their applicability in vivo is limited by the risk of infection or immunogenicity, and the current injectables also suffer from degradation, viscosity, and drug release. In this study, a multifunctional hydrogel scaffold (COB hydrogels) was constructed by incorporating bioactive glass nanoparticles with a Schiff base crosslinking-based hydrogel composed of carboxymethyl chitosan and oxidized cellulose. The incorporation of nanoparticles not only shortened the gelation time of the COB hydrogels, but also enhanced the performance of the hydrogel in terms of function, such as drug loading capacity. The prepared hydrogels also have self-healing ability, injectability, drug loading and sustained release, antibacterial properties and biocompatibility. In addition, given their no cytotoxicity and mild inflammation in vivo, the hydrogel scaffolds will be important for tissue engineering and drug delivery applications.

Although immune checkpoint blockers (ICBs) have revolutionized the treatment of many cancers, only less than 30% of patients respond to any ICB as a monotherapy. Estrogens, produced by the adipose tissue in the mammary glands, are immunomodulators in the tumor microenvironment (TME). Estrogens suppress anti-tumor immunity and activate immunosuppression through the estrogen receptor α (ERα) in the immune cells but activate anti-tumor immunity through ERβ. Genistein (GEN) is a biologically active isoflavone and is structurally similar to estradiol (E2). However, in contrast to E2, GEN binds preferentially to ERβ. Here we studied if GEN combined with ERα inhibitor fulvestrant (Fulv) alters response to anti-PD1 therapy in ERα negative, ERβ positive E0771 mouse mammary tumors. Syngeneic C57BL/6 mice were fed either a control (CON) diet or GEN supplemented diet for 5 weeks and then allografted E0771 mammary tumor cell into the 4th mammary fat pad. When tumors reached an average size of 16mm2, mice in both diet groups were further divided into 4 sub-groups treated with: 1) anti-PD1 (150µg or 100µg every 3 days for a total of 3 doses), 2) Fulv (1mg) once weekly, 3) anti-PD1+Fulv or 4) IgG control group. We found that three doses of 150µg of anti-PD1 alone effectively reduced tumor growth in the CON (p=0.0005) group and its efficacy was notably weakened in the GEN group (p=0.04).. Combination with Fulv did not improve PD1 response. These findings suggest that when using a highly effective anti-PD1 dose, GEN may reduce rather than improve the response, and anti-ERα does not add to anti-PD1’s effect in control of GEN group. A suboptimal dose (100 µg) of anti-PD1 alone did not inhibit E0771 tumor growth in mice fed CON diet, but in the GEN group the tumor inhibition by anti-PD1 alone almost reached statistical significance (p=0.057). The combination of suboptimal PD1+Fulv significantly reduced tumor growth compared with IgG (p=0.04) or Fulv (p=0.02). During GEN feeding, anti-PD1+Fulv was even more potent in inhibiting tumor growth when compared with IgG group (p=0.02) and Fulv group (p=0.007). Thus, when anti-PD1 alone is not effective, either Fulv or GEN will improve responsiveness to anti-PD1. In the suboptimal anti-PD1 dose experiment, GEN feeding increased CD8+ T cells (P=0.04) and decreased CD4+Foxp3+ cells (p=0.01) in the TME. Further, GEN reduced the proportion of immunosuppressive MDSC cells (CD3-CD11B+Ly6Ghigh6Clow) in the PD1+ Fulv group (p=0.01) in the Peyer’s patches. In vitro experiments showed that both GEN and Fulv, and especially their combination, inhibited the E0771 cells proliferation, indicating that these two treatments can also directly suppress the growth of ERα negative but ERβ positive breast cancer cells. Taken together, the data show that anti-estrogens and GEN in the diet may improve response to anti-PD1 therapy, possibly both through activation of tumor immune response and inhibition of tumor cell proliferation and induction of tumor cell death. Citation Format: Fabia de Oliveira Andrade, Vivek Verma, Ester Molina Hoyo, Karla Andrade de Oliveira, Pal Koak, Lu Jin, Leena Hilakivi-Clarke. Effects of isoflavone genistein, combined with anti-estrogen fulvestrant, on anti-PD1 therapy response against E0771 mammary tumors in mice [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-06-05.

Estrogen receptor positive (ER+) breast cancer is the most common subtype among all breast cancers and is responsible for most breast cancer related deaths. Endocrine therapies, such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI), often given in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, are initially effective but the majority of advanced ER+ breast cancers eventually become refractory to endocrine therapies. Therefore, understanding the underlying molecular mechanisms that enable or promote resistance to endocrine therapies may lead to novel therapeutic targets. Cancer cells consume greater quantities of glucose to meet their energy and anabolic demands to support cell growth and proliferation. In this study, we used breast cancer cell models that are endocrine therapy sensitive and resistant and investigated the metabolites by growing the cells in the presence of the stable glucose isotope, UC13-Glucose. We measured the C13-labelled metabolites of glycolysis and the TCA cycle. Glucose consumption was higher in endocrine therapy resistant MCF7/LCC9 (LCC9) cells compared with parental MCF7 (MCF7) and estrogen independent, endocrine therapy sensitive MCF7/LCC1 (LCC1) cells. Notably, in LCC9 cells the m+4 and m+6 isotopomer of C-13 labelled citrate was absent with a concurrent high succinate:fumarate ratio. Furthermore, in LCC9 cells, most of the fumarate was unlabeled suggesting that fumarate was not generated from glucose. These results suggest that the TCA cycle is impaired in LCC9 cells and the conversion of succinate to fumarate is dysregulated. Succinate dehydrogenase (SDH) enzyme is responsible for reversible catalytic conversion of succinate to fumarate. SDH is a multimeric protein comprised of four different subunits and SDH assembly factor 2 (SDHAF2), which is a tumor suppressor gene. Comparable SDH enzyme activity was observed in LCC9 and LCC1 cells. Intriguingly, when SDH activity was inhibited using dimethylmalonate, the LCC9 cells were re-sensitized to both Fulvestrant and 4-hydroxytamoxifen. Succinate accumulation was accompanied with HIF 1-alpha stabilization and SDH inhibition led to lower levels of HIF1-alpha. This indicated that SDH may function in the conversion of fumarate to succinate in LCC9 cells. Our study further investigates the source of fumarate in LCC9 cells. Overall, this study suggests that targeting succinate metabolism may help to restore sensitivity to Fulvestrant and tamoxifen in endocrine therapy resistance in ER+ breast cancer cells. Citation Format: Anil Yadav, Karla Andrade de Oliveira, Lu Jin, Robert Clarke, Surojeet Sengupta. Impaired Succinate Metabolism Supports Endocrine Therapy Resistance in ER Positive Breast Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-11-11.

Endocrine therapy can lead to nutrient deprivation by reducing glucose and glutamine uptake and total cellular ATP production. The ability of cells to bypass this metabolic stress is fundamental to how they regulate BC growth and acquire endocrine resistance. Sirtuins (SIRTs) are NAD+-dependent deacylases and regulate a widerange of intracellular processes including metabolism. SIRT3, activated by calorie restriction, modulates mitochondrial adaptation to low energy input. It has a key role in mitochondrial integrity and function, regulating cell survival, death and metabolic pathways, regulating the shift to amino-acid and fatty-acid catabolism. SIRT3 can maintain ROS levels at the appropriate levels for sustaining a proliferative phenotype, preventing apoptosis and promoting carcinogenesis. A role of SIRT3 in epigenetic regulation has also been reported. We used Differential Dependency Network analysis to compare the wiring of the SIRTs and key metabolism-related genes in matched antiestrogen- sensitive vs. resistant breast cancer (BC) cells, which identified several novel signaling hubs including CDKN2A (p16), linking SIRT3 to cell proliferation. The ability of SIRTs to sense and respond to changes in energy, coupled with their deacetylase/deacylase functions, could provide a mechanism for the cell to rewire signaling and maintain a newly acquired drug-resistant phenotype. Using endocrine sensitive (LCC1) and resistant (LCC9) BC cells, we confirmed the higher expression of SIRT3 in LCC9, compared to LCC1 cells. Upregulation of SIRT3 expression within 24 hrs of Fulvestrant (ICI 1 µM) treatment (p=0.0176) in LCC1 was shown, but no effect was observed in LCC9 cells. Conversely, treatment with 17β-estradiol (E2- 10 nM) did not significantly affect SIRT3 expression in either LCC1 or LCC9 cells. Inhibition of SIRT3 acitivity, using the LC0296 inhibitor (15 µM), reduced growth rate in LCC1 and SIRT3-silenced LCC9 cells under treatment with ICI (1 nM and 1 µM, respectively) (p< 0.0001, p< 0.001 respectively). Treatment with SIRTUIN 3 inhibitor and ICI induced apoptosis in LCC1 and SIRT3-silenced LCC9 cells compared to the untreated control and ICI only treated cells (p< 0.001). The combination SIRT3 inhibitor (15 µM) plus ICI (0.5 µM) increased ROS production in LCC9-SIRT3 silenced cells in 24 hours of treatment compared to the untreated control and ICI only treated cells (p< 0.001). SIRT3 inhibitor (15 µM) decreased LCC1 cell spheroid formation (p< 0.05), however it didn’t show additive effect to the effect of ICI (0.5 µM) in the same conditions. The combination of SIRT3 inhibitor (15 µM) and ICI (1 µM) reduced the growth of LCC9 SIRT3-silenced cells in detached condition compared to untreated control and ICI only treated cells (p< 0.001). The results show that SIRT3 may have a role in Fulvestrant response in BC cells; the mechanism is under investigation in our laboratory. Citation Format: Karla Andrade de Oliveira, Surojeet Sengupta, Lu Jin, Fabia de Oliveira Andrade, Melike Ozgu-Onal, Anil Yadav, Robert Clarke. Inhibition of Sirtuin 3 Sensitizes Breast Cancer Cells to Fulvestrant [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-11-08.

Purpose Contracts and trust are two prominent governance mechanisms in buyer–supplier exchanges, yet controversy persists regarding the interplay between contracts and trust. This study aims to provide a new perspective to understand the debate by differentiating between- from within-dyad effects of contracts–trust relationships. Design/methodology/approach Based on survey data of 250 Chinese buyer–supplier relationships collected over two time periods, this study used two-level hierarchical linear modeling (HLM) with repeated measures to test the influence of contracts (trust) on trust (contracts) over time. Findings The authors find that for major buyer–supplier exchanges, contracts and trust tend to complement each other when comparing across dyads, but they likely substitute for each other in within-dyad settings. Research limitations/implications First, to illustrate the dynamic interactions between contracts and trust, this study collected data at two time periods and assumed continuous linear relationships of time with both contracts and trust. Further research should collect multiple waves of data to explore the complex, varying changes that arise over time. Second, this study’s findings are based on buyer–supplier relationships in China, whose unique cultural features may limit the generalizability of the results to other settings. Practical implications Channel managers can structure exchanges by devising detailed contracts that align incentives and demonstrate commitment, which helps build trust in a relationship. Channel managers should also pay special attention to the contingency effects of their transactional and relational features. Originality/value This study offers the first explicit test of the dynamic contracts–trust relationship, thereby establishing a more refined understanding of interplay between contracts and trust.

In order to reduce the environmental pollution caused by plastic packaging, the development of biodegradable high-performance packaging materials has become a research hotspot. Cellulose is a promising food packaging material, but it usually lacks sufficient ultraviolet (UV) shielding property and mechanical strength. In this work, rectorite microplates were incorporated into the cellulose matrix by a facile blending method to fabricate the composite films. The structure and properties of the composite films were characterized by FT-IR, X-ray diffraction, scanning electron microscopy, UV-vis and mechanical properties test etc. The results indicated that rectorite microplates were uniformly distributed in the cellulose matrix. The blocking percentages for UVA and UVB for the cellulose/rectorite composite film with 14 wt% rectorite content (RCRF-14) could reach as high as 97.8 % and 96.0 %, respectively, showing a good UV shielding property. Meanwhile, the addition of rectorite obviously improved the mechanical properties and decreased the water vapor and oxygen permeabilities of the cellulose film, showing a potential application as a sustainable food packaging material.

This paper explores the windmilling operational boundary and aerodynamic characteristics of an axial wide-chord fan rotor according to the zero-torque characteristic. The interesting results show the radial profiles of the aerodynamic parameters at the rotor exit nearly collapse to the same curve for different windmilling speeds, which indicate that windmilling flow has a strong similarity. Meanwhile, there are three different operating modes along the blade span. The formation mechanism and evolution process of the tip leakage flow at the windmill are also analyzed. The reversal of the pressure difference will generate two kinds of tip leakage flows in opposite directions. A clear blockage zone appears near the blade tip under the joint action of the two kinds of tip leakage flows. Finally, this study proposes a mathematical model to predict the windmilling speed of a high-bypass-ratio turbofan based on the aerodynamic similarity of windmilling flow and the one-dimensional semiempirical windmilling mass flow function. This can be applied to the early stages of high-bypass-ratio turbofan development and can evaluate safety characteristics during engine windmilling operations.

One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune tolerant microenvironment. To determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1), NeuT/ATTAC mice, a conditional model of mammary fibrosis that we recently developed, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab, and drug response was monitored by tumor development, imaging mass cytometry, immunohistochemistry and tumor gene expression by RNAseq. Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1 and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors.

A high-precision networking method for a modular deployable antenna with ultramultiple modules is proposed to solve the problem of achieving an accurate formation of the structure of a large-aperture modular deployable space antenna. In accordance with the general requirements for the deployment surface of deployable antennas, the structure composition and deployment principle of a deployable antenna are analyzed, and the topological law of a hexagonal prism modular structure is expounded. On the basis of basic theories of differential geometry, analytical geometry, and robotics, the mathematical model of an envelope circle and that of its center are established. Then, a networking model of structure that includes 61 modules in the fully deployed state is established. Finally, the established model is verified via a numerical simulation method, and the influence law of structural parameters on networking characteristics is analyzed and studied. Simulation results show that the networking method can realize an accurate connection of multiple modules. The networking method for the structure of a modular deployable antenna proposed in this study can provide a reference for research on basic theory of a deployable antenna’s mechanism and related engineering applications.

The rapid expansion of the fast fashion industry brings about environmental concerns such as dyestuffs-related water pollutions and waste textiles. Conventional wastewater-disposal strategies emphasize the optimization of photocatalytic activity to improve pollutant degradation efficiency, while the absorptivity, recyclability and sustainability of photocatalysts are always ignored. The overproduced textiles are still in urgent of being recycled and reutilized in eco-friendly approaches. In this work, a scalable dyeing technology is employed to achieve green and sustainable reutilization of waste textiles. The functionalized TiO2/reduced graphene oxide wool fabrics show excellent sustainability, remarkable adsorbing capacity and enhanced photocatalytic performance. By taking advantage of these properties, we develop an integrated strategy of night-time adsorption and day-time photodegradation which could significantly optimize the dyestuffs degradation efficiency. The concept of waste textiles reutilization and wastewater treatment in this work provides practical potential for efficient and sustainable environmental remediation. Graphical abstract Concept of waste textiles reutilization and wastewater treatment.

Lu, Jin-Rong, Yu, Feng-Ming, Lei, Lei, Zhang, Ying, Zhao, Qi (2023): A new species of Helvella (Helvellaceae, Pezizomycetes) within the H. macropus group from China. Phytotaxa 601 (3): 212-222, DOI: 10.11646/phytotaxa.601.3.2, URL: http://dx.doi.org/10.11646/phytotaxa.601.3.2

Helvella guttata Q. Zhao & J.R. Lu sp. nov Fig. 1, 2 Index Fungorum number: IF 900384; Faces of Fungi number: FoF 14372. Etymology: Guttata refers to its guttata hymenium surface. Holotype: CHINA, Yunnan Province, Lushui County, Luzhuang, alt. 900 m, 26 Aug. 2009, Qing Cai 274 (HKAS 67836). Diagnosis: Similar to Helvella macropus but differs in its constantly mottled hymenium, and larger subellipsoid to subfusiform ascospores. Sexual morph: Pileus shallowly cupulate to discoid, 0.3–1 cm high, 1–2.5 cm broad, hymenium even, brown to dark brown, constantly mottled with patches of paler pigmentation when fresh, brownish when dried, receptacle surface villose to densely pubescent, greyish, light brown to dark brown when fresh, becoming greyish brown to dark brown when dried. Stipe 1–6 cm long, 0.2–0.5 cm diam, terete, internally solid, villose to densely pubescent, concolorous with the receptacle surface. Medullary excipulum 200–350 μm broad, of textura intricata, hyaline, composed of 3–7 μm diam hyphae, walls thickened, J-. Ectal excipulum 90–180 μm broad, of textura angularis, brown, terminal cells 18–40 × 7–13 μm, blue in cotton blue, J-. Stipitipellis 140–250 μm, of textura angularis, hyaline, terminal cells 18–28 × 7–15 μm, blue in cotton blue, J-. Asci arising from croziers, 8-spored, subcylindrical to clavate, with apex rounded, 200–300 × 14–22 μm, J- in Melzer’s reagent, blue in cotton blue. Paraphyses filiform, 3–4 μm dia., slightly exceeding the asci, apex enlarged, 7–10 μm dia., brown, blue in cotton blue, J-. Ascospores [80/4/2, in H 2 O] (20–)21–27.5(–28) × (11–)11.5–15(–16) μm [Q = 1.56–2.16, Q m = 1.78 ± 0.18)], subellipsoid to subfusoid, smooth-walled under the light microscope, uniguttulate, with large central globose to broadly ellipsoidal oil droplet. Asexual morph: Undetermined. Habitat: Scattered or gregarious on the ground, under Quercus spp. forest. Distribution: Currently only known in southwestern China. Material examined: CHINA, Yunnan Province, Lushui County, under Quercus sp. forest, alt. 1000 m, 26 Aug. 2009, Ting Guo 56 (HKAS 69046), same location, 6 Aug. 2010, Ting Guo 150 (HKAS 69546); Lijiang City, under Quercus sp. forest, alt. 2600 m, 20 Aug. 2010, Qi Zhao 1012 (HKAS 69733); Tibet, Bomi County, under Quercus sp. forest, alt. 2700 m, 30 Jun. 2014, Qi Zhao 2079 (HKAS 87759). Notes: Morphologically, H. guttata and H. macropus both share cupulate pileus, villose receptacle, and stipe surface, and subfusiform ascospores. However, the latter species never possess mottled apothecia, and the hymenium or receptacle surface is usually light to medium brown or greyish brown. In microstructure, H. macropus has slenderer ascospores than H. guttata. In phylogeny, H. guttata is the sister of H. macropus, which has relatively high statistical support (Fig. 1). The comparison of H. guttata with its phylogenetic relatives (H. ephippioides, H. fibrosa, and H. macropus) in fibrosa–macropus lineage is shown in Table 2., Published as part of Lu, Jin-Rong, Yu, Feng-Ming, Lei, Lei, Zhang, Ying & Zhao, Qi, 2023, A new species of Helvella (Helvellaceae, Pezizomycetes) within the H. macropus group from China, pp. 212-222 in Phytotaxa 601 (3) on pages 216-217, DOI: 10.11646/phytotaxa.601.3.2, http://zenodo.org/record/8141752

Helvella macropus (Pers.) P. Karst., 1871, Bidrag Känn. Finl. Natur. Folk. 19: 37 Figure 1, 3 Index Fungorum number: IF 237869; Faces of Fungi number: FoF 08727. Sexual morph: Pileus cupulate, shallowly cupulate to discoid, 0.5–2cm high, 1–4.5 cm broad, hymenium even, greyish brown to brown when fresh, brownish when dried, receptacle surface villose to densely pubescent, light to medium brown or greyish brown when fresh, becoming grey brown when dried. Stipe 3–7 cm long, 0.2–1 cm diam, terete to slightly sulcate, but never with ribs, internally solid, villose to densely pubescent, concolorous with the receptacle surface. Medullary excipulum 200–240 μm broad, of textura intricata, hyaline, composed of 3–4 μm broad hyphae, walls thickened, J-. Ectal excipulum 110–230 μm broad, of textura angularis, hyaline, terminal cells 16–35 × 7–24 μm, blue in cotton blue, J +. Stipitipellis 110–260 μm, of textura angularis, hyaline, terminal cells 20–40 × 9–14 μm, blue in cotton blue, J +. Asci arising from croziers, 8-spored, subcylindrical to clavate, with apex rounded, 220–260 × 14–19 μm, J- in Melzer’s reagent, blue in cotton blue. Paraphyses filiform, 4–5 μm broad, slightly exceeding the asci, apex enlarged, 6–11 μm broad, brown, blue in cotton blue, J-. Ascospores [40/2/2, in H 2 O] (19.5–)20–24(–24.5) × (9.5–)10–12 μm [Q = 1.90–2.35, Q m = 2.16 ± 0.14)], fusoid to subfusoid, smooth-walled to under the light microscope, triguttulate or unigutulate. Asexual morph: Undetermined. Habitat: Scattered or gregarious on the ground, under Quercus sp. or Pinus sp. forests. Distribution: Widely distributed in north temperate Eurasia and North America (Dissing 1966, Häffner 1987, Abbott & Currah 1997). Material examined: AUSTRIA, Klein Walsertal, Waldst ̧ck hinter dem Sport und Studienheim Marburg, 6 Jul. 2014, Flavus Popa K6 A59 (HKAS 84891), Flavus Popa K6 AA2 (HKAS 84895). GERMANY, Hessen, Wooghölle, 6 Jun., 2014, Flavus Popa K6085 (HKAS 84887), Flavus Popa K63 A2 (HKAS 84893). CHINA, Hubei Province, Shennongjia County, on the ground, under Pinus armandii forest, alt. 1700 m, 13 Sep. 2015, Qi Zhao 1497 (HKAS 78756). Notes: Morphologically, H. macropus is similar to H. fibrosa, H. cupuliformis and H. rivularis, which have cupulate pileus with villose to densely pubescent, light to medium brown or greyish brown receptacle surface (Dissing 1966, Häffner 1987, Abbott & Currah 1997), but the latter three species have ellipsoid ascospores. Our phylogeny confirms the existence of at least four species of the H. macropus morphospecies complex, i.e., H. guttata, H. macropus s.s., H. fibrosa, and H. ephippioides. These four species can be well distinguished according to the characteristics mentioned in Table 2., Published as part of Lu, Jin-Rong, Yu, Feng-Ming, Lei, Lei, Zhang, Ying & Zhao, Qi, 2023, A new species of Helvella (Helvellaceae, Pezizomycetes) within the H. macropus group from China, pp. 212-222 in Phytotaxa 601 (3) on page 217, DOI: 10.11646/phytotaxa.601.3.2, http://zenodo.org/record/8141752, {"references":["Dissing, H. (1966) The genus Helvella in Europe with special emphasis on the species found in Norden. Dansk Botanisk Arkiv 25: 1 - 172.","Haffner, J. (1987) Die Gattung Helvella: Morphologie und Taxonomie. Beihefte zur Zeitschrift fur Mykologie 7: 1 - 165.","Abbott, S. P. & Currah, R. S. (1997) The Hevellaceae: systematic revision and occurrence in northern and northwestern North America. Mycotaxon 62: 1 - 125."]}

Key to the species in Helvella macropus group 1 Apothecium cupuliform......................................................................................................................................................................2 1’ Apothecium ephippioid.............................................................................................................................................. H. ephippioides 2 Ascospores elliptic................................................................................................................................................................ H. fibrosa 2’ Ascospores subelliptic, fusiform to subfusiform................................................................................................................................3 3 Hymenium brown to dark brown, constantly mottled with patches of paler pigmentation................................................ H. guttata 3’ Hymenium mouse-grey, grey-beige or greyish brown.................................................................................................... H. macropus, Published as part of Lu, Jin-Rong, Yu, Feng-Ming, Lei, Lei, Zhang, Ying & Zhao, Qi, 2023, A new species of Helvella (Helvellaceae, Pezizomycetes) within the H. macropus group from China, pp. 212-222 in Phytotaxa 601 (3) on page 220, DOI: 10.11646/phytotaxa.601.3.2, http://zenodo.org/record/8141752

Aiming at the urgent need for the development of space deployable antenna with large aperture and a high storage rate, a new configuration of a multifold rib modular deployable antenna mechanism is proposed. The overall structure scheme design of the antenna is carried out, and the structure composition of the module, the principle of structural topology transformation, and the scheme of mechanism deployment and locking are expounded. According to the shape and constraint relationship of the structure deployment and folded state, and based on basic theory of robotics, calculation and the analysis of key structural parameters and the included angle of rib units are carried out, and the parameterized mathematical model is established. The detailed structural design is carried out, and then the complex structures such as the center beam assembly, diagonal beam assembly, and outer beam assembly are introduced in detail. The kinematic simulation of the mechanism is carried out by using ADAMS software, and the variation law of the motion parameters is analyzed. Finally, the prototype of a hexagonal prism single-module principle is developed, and a deployment function test and verification are carried out. The simulation and test results show that the proposed mechanism can realize the motion change from folded to deployed, and no problems such as interference or clamping are observed in deployment, which verifies the correctness and the feasibility of the structural scheme and principle. Moreover, the proposed new configuration scheme not only retains the characteristics of modular structure, such as good universality and easy expansion, but also has a high storage rate and structure efficiency rate. The research results have a high reference value and relevance for basic theoretical research and the engineering application of a space deployable antenna.

Metabolomics provides an unprecedented window on diverse plant secondary metabolites that represent a potentially critical niche dimension in tropical forests underlying co-existence. Here, we used untargeted metabolomics to evaluate the chemical composition of 358 tree species and its relationship to phylogeny and variation in light environment, soil nutrients, and insect-herbivore leaf damage in a tropical rain forest plot. We found that tree species that co-occur locally are less chemically similar than random, and that local chemical dispersion and metabolite diversity reduce herbivory, especially that of specialist insect herbivores. Our results suggest that plant secondary metabolites have the potential to mediate plant-herbivore interactions in a manner consistent with diversity maintenance at the community scale.

Supplementary Materials and Methods

Supplementary Figure S1. Epitope mapping of clones A-D by alanine scanning mutagenesis. Supplementary Figure S2. Analysis of the selectivity of ET1402L1 (clone B) towards AFP158. Supplementary Figure S3. Analysis of the potential risk for cross-presentation of AFP158 by normal cells. Supplementary Figure S4. Co-incubation of AFP-CAR T cells with antigen-positive cells induces production and release of cytokines. Supplementary Figure S5. AFP-CAR T cells can penetrate laminin-rich Matrigel and specifically kill AFP+/A2+ cells in vitro. Supplementary Figure S6. Representative quality control tests performed on each batch of AFP-CAR T cells manufactured for in vivo studies. Supplementary Figure S7. T cell subset analysis to determine distribution of TNaive, TCM TEM, and TEffector cell populations. Supplementary Figure S8. Analysis of human CD3+ T cells in Hep G2 s.c. tumors from i.v.- treated mice. Supplementary Figure S9. Determination of the number of AFP158/HLA-A*02:01 complexes expressed on the surface of liver cancer cells. Supplementary Table S1. Chimeric mouse IgG1 antibody binding affinity to AFP158/HLAA* 02:01.

Figure Legends for Sup. Figures 1-9 and Sup. Table 1

Purpose: The majority of tumor-specific antigens are intracellular and/or secreted and therefore inaccessible by conventional chimeric antigen receptor (CAR) T-cell therapy. Given that all intracellular/secreted proteins are processed into peptides and presented by class I MHC on the surface of tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide–MHC complexes can be targets for CAR T-cell therapy against solid tumors.Experimental Design: We generated a fully human chimeric antigen receptor, ET1402L1-CAR (AFP-CAR), with exquisite selectivity and specificity for the AFP158–166 peptide complexed with human leukocyte antigen (HLA)-A*02:01.Results: We report that T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01+/AFP+ while sparing cells from multiple tissue types that were negative for either expressed proteins. In vivo, intratumoral injection of AFP-CAR T cells significantly regressed both Hep G2 and AFP158-expressing SK-HEP-1 tumors in SCID-Beige mice (n = 8 for each). Moreover, intravenous administration of AFP-CAR T cells in Hep G2 tumor-bearing NSG mice lead to rapid and profound tumor growth inhibition (n = 6). Finally, in an established intraperitoneal liver cancer xenograft model, AFP-CAR T cells showed robust antitumor activity (n = 6).Conclusions: This study demonstrates that CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response. Our approach expands the spectrum of antigens available for redirected T-cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy. Clin Cancer Res; 23(2); 478–88. ©2016 AACR.

PDF file - 388K, GRP78 promotes survival signaling schematic

Patient/tumor characteristics of human breast cancer tissue microarrays.

PDF file - 78K, Cell surface GRP78 localization does not mediate the cells anti-estrogen responsiveness

Relationship between IRF1 and ATG7 in human tissue microarrays.

PDF file - 46K, Elevated LC3-II protein levels are observed in anti-estrogen resistant cell lines

Efficient knockdown of IRF1 using siRNA.

Interferon regulatory factor-1 (IRF1) is a tumor suppressor that regulates cell fate in several cell types. Here, we report an inverse correlation in expression of nuclear IRF1 and the autophagy regulator ATG7 in human breast cancer cells that directly affects their cell fate. In mice harboring mutant Atg7, nuclear IRF1 was increased in mammary tumors, spleen, and kidney. Mechanistic investigations identified ATG7 and the cell death modulator beclin-1 (BECN1) as negative regulators of IRF1. Silencing ATG7 or BECN1 caused estrogen receptor-α to exit the nucleus at the time when IRF1 nuclear localization occurred. Conversely, silencing IRF1 promoted autophagy by increasing BECN1 and blunting IGF1 receptor and mTOR survival signaling. Loss of IRF1 promoted resistance to antiestrogens, whereas combined silencing of ATG7 and IRF1 restored sensitivity to these agents. Using a mathematical model to prompt signaling hypotheses, we developed evidence that ATG7 silencing could resensitize IRF1-attenuated cells to apoptosis through mechanisms that involve other estrogen-regulated genes. Overall, our work shows how inhibiting the autophagy proteins ATG7 and BECN1 can regulate IRF1-dependent and -independent signaling pathways in ways that engender a new therapeutic strategy to attack breast cancer. Cancer Res; 75(6); 1046–55. ©2015 AACR.

Silencing ATG7 and BECN1 induces IRF1 expression independently of ROS.

PDF file - 132K, Representative Western blot images of data quantified in Table 1

Nuclear IRF1 is induced following ATG7 and BECN1 knockdown.

dnIRF1 blocks ICI sensitivity in LCC1 cells.

Model ranges, their range, and description.

Knockdown of IRF1 alters BECN1 and IGF1R/mTOR expression.

Supplementary figure legends

In this paper, the impact and mechanism of natural water constituents (humic acid, nitrate, iron and chloride ions) on the photodegradation of bisphenol A (BPA) was investigated in aqueous media under simulated UV light irradiation. Results suggested that the contributions of ·OH, 1O2, O2.− and BPA* to BPA photodegradation in pure water were 13.4%, 7.7%, 22.9% and 47.9%, respectively, indicating that direct photodegradation other than self-sensitized photodegradation was the main reaction pathway. Furthermore, the presence of humic acid (HA), nitrate, iron and chloride ions showed different impacts on BPA photodegradation. NO- 3 and NO- 2 both showed inhibitory effect but due to different ROS (reactive oxidization species). In the presence of HA, it was light-screening-induced direct photolysis not quenching effect dominated over the inhibited BPA photodegradation. The photodegradation of BPA was significantly enhanced by the addition of iron because iron-assisted indirect photolysis controlled the degradation process through promoting the production of ·OH and H2O2. Chloride had a dual effect on BPA photodegradation depending on the different concentration levels. Additionally, a simple linear model revealed that the interaction of these factors also significantly impacted BPA photodegradation. In natural water, the decreased photolytic rate of BPA was mainly attributed to triple-excited dissolved organic matter (3DOM*) and indirect photolysis was the primary transformation pathway of BPA. Finally, the detection of photolysis products including nitrate and chlorinated products suggested the possibility of increasing ecological risk of BPA photodegradation.