The characteristics and the multiple functions of integrin ß1 in human cancers.

Integrins, which consist of two non-covalently linked α and ß subunits, play a crucial role in cell-cell adhesion and cell-extracellular matrix (ECM) interactions. Among them, integrin ß1 is the most common subunit and has emerged as a key mediator in cancer, influencing various aspects of cancer progression, including cell motility, adhesion, migration, proliferation, differentiation and chemotherapy resistance. However, given the complexity and sometimes contradictory characteristics, targeting integrin ß1 for therapeutics has been a challenge. The emerging understanding of the mechanisms regulating by integrin ß1 may guide the development of new strategies for anti-cancer therapy. In this review, we summarize the multiple functions of integrin ß1 and signaling pathways which underlie the involvement of integrin ß1 in several malignant cancers. Our review suggests the possibility of using integrin ß1 as a therapeutic target and highlights the need for patient stratification based on expression of different integrin receptors in future clinical studies.

Role of cancer-educated mesenchymal stromal cells on tumor progression.

The malignant tumor is the main cause of human deaths worldwide. Current therapies focusing on the tumor itself have achieved unprecedented benefits. Various pro-tumorigenic factors in the tumor microenvironment (TME) could abolish the effect of cancer therapy. Mesenchymal stromal cells (MSCs) are one of the substantial components in the tumor microenvironment, contributing to tumor progression. However, MSCs are not inherently tumor-promoting. Indeed, they acquire pro-tumorigenic properties under the education of the TME. We herein review how various elements in the TME including tumor cells, immune cells, pro-inflammatory factors, hypoxia, and extracellular matrix influence the biological characteristics of MSCs through complex interactions and demonstrate the underlying mechanisms. We also highlight the importance of tumor-associated mesenchymal stromal cells (TA-MSCs) in promoting tumor progression. Our review gives a new insight into the TA-MSCs as a potential tumor therapeutic target. It is anticipated that subverting MSCs education will facilitate the outbreak of therapeutic strategies against tumors.

Multiresonant Nonlocal Metasurfaces.

Optical metasurfaces supporting localized resonances have become a versatile platform for shaping the wavefront of light, but their low quality (Q-) factor modes inevitably modify the wavefront over extended momentum and frequency space, resulting in limited spectral and angular control. In contrast, periodic nonlocal metasurfaces have been providing great flexibility for both spectral and angular selectivity but with limited spatial control. Here, we introduce multiresonant nonlocal metasurfaces capable of shaping the spatial properties of light using several resonances with widely disparate Q-factors. In contrast to previous designs, the narrowband resonant transmission punctuates a broadband resonant reflection window enabled by a highly symmetric array, achieving simultaneous spectral filtering and wavefront shaping in the transmission mode. Through rationally designed perturbations, we realize nonlocal flat lenses suitable as compact band-pass imaging devices, ideally suited for microscopy. We further employ modified topology optimization to demonstrate high-quality-factor metagratings for extreme wavefront transformations with large efficiency.

The RUBY reporter enables efficient haploid identification in maize and tomato.

In vivo haploid induction has been extended from maize to monocotyledonous plants like rice, wheat, millet and dicotyledonous plants such as tomato, rapeseed, tobacco and cabbage. Accurate identification of haploids is a crucial step of doubled haploid technology, where a useful identification marker is very pivotal. R1-nj is an extensively used visual marker for haploid identification in maize. RFP and eGFP have been shown to be feasible in identifying haploid. However, these methods are either limited to specific species, or require specific equipment. It still lacks an efficient visual marker that is practical across different crop species. In this study, we introduced the RUBY reporter, a betalain biosynthesis system, into maize and tomato haploid inducers as a new marker for haploid identification. Results showed that expression of RUBY could result in deep betalain pigmentation in maize embryos as early as 10 days after pollination, and enabled 100% accuracy of immature haploid embryo identification. Further investigation in tomato revealed that the new marker led to deep red pigmentation in radicles and haploids can be identified easily and accurately. The results demonstrated that the RUBY reporter is a background-independent and efficient marker for haploid identification and would be promising in doubled haploid breeding across different crop species.

Genome-wide association and genomic prediction for resistance to southern corn rust in DH and testcross populations.

Southern corn rust (SCR), caused by Puccinia polysora Underw, is a destructive disease that can severely reduce grain yield in maize (Zea mays L.). Owing to P. polysora being multi-racial, it is very important to explore more resistance genes and develop more efficient selection approaches in maize breeding programs. Here, four Doubled Haploid (DH) populations with 384 accessions originated from selected parents and their 903 testcross hybrids were used to perform genome-wide association (GWAS). Three GWAS processes included the additive model in the DH panel, additive and dominant models in the hybrid panel. As a result, five loci were detected on chromosomes 1, 7, 8, 8, and 10, with P-values ranging from 4.83×10-7 to 2.46×10-41. In all association analyses, a highly significant locus on chromosome 10 was detected, which was tight chained with the known SCR resistance gene RPPC and RPPK. Genomic prediction (GP), has been proven to be effective in plant breeding. In our study, several models were performed to explore predictive ability in hybrid populations for SCR resistance, including extended GBLUP with different genetic matrices, maker based prediction models, and mixed models with QTL as fixed factors. For GBLUP models, the prediction accuracies ranged from 0.56-0.60. Compared with traditional prediction only with additive effect, prediction ability was significantly improved by adding additive-by-additive effect (P-value< 0.05). For maker based models, the accuracy of BayesA and BayesB was 0.65, 8% higher than other models (i.e., RRBLUP, BRR, BL, BayesC). Finally, by adding QTL into the mixed linear prediction model, the accuracy can be further improved to 0.67, especially for the G_A model, the prediction performance can be increased by 11.67%. The prediction accuracy of the BayesB model can be further improved significantly by adding QTL information (P-value< 0.05). This study will provide important valuable information for understanding the genetic architecture and the application of GP for SCR in maize breeding.

Hylocereus undatus flower extract suppresses OVA-induced allergic asthma in BALb/c mice by reducing airway inflammation and modulating gut microbiota.

Asthma is a chronic allergic respiratory disease with limited treatment options. Emerging findings indicate an important interaction between the gut microbiota and the lungs, and that the development of asthma causes changes in the gut environment. Hylocereus undatus flower (HUF) is a traditional Chinese medicine used in the treatment of pulmonary and intestinal diseases. Our previous studies have demonstrated significant anti-asthmatic and anti-inflammatory activity, but the exact mechanism has not been elucidated. In the current study, we validated the potential therapeutic asthma properties of HUF in vivo using an ovalbumin-induced allergic asthma mouse model. We found that HUF treatment significantly reduced the key features of allergic asthma, including an elevated respiratory rate, inflammatory cell accumulation, airway inflammation, and the expression of pro-inflammatory molecules. Histological analysis of mouse lungs showed that HUF attenuated lung inflammatory cell infiltration. Periodic acid-Schiff staining confirmed the reduced mucus secretion in lung mucosa, and Masson's staining confirmed the reduced collagen deposition in the lungs after HUF treatment. Western blot and immunohistochemistry confirmed that HUF increased lung SIRT1 and reduced p38MAPK, NF-κBp65, and caspase-1 proteins. 16 S rDNA sequencing showed that HUF improved the endostasis of the disrupted gut microbiota composition in asthmatic mice. Surprisingly, an inflammatory response was found in the gut of asthmatic mice, along with alterations in inflammation-associated SIRT1 and caspase-1 proteins, and HUF was able to ameliorate these lesions. In conclusion, these findings suggest that HUF may be a new drug candidate for the treatment of allergic asthma.

Inhibition of CCCTC Binding Factor-Programmed Cell Death Ligand 1 Axis Suppresses Emergence of Chemoresistance Induced by Gastric Cancer-Derived Mesenchymal Stem Cells.

Background: Gastric cancer (GC) is the third leading cause of cancer-associated deaths worldwide. Stromal cells, especially mesenchymal stem cells (MSCs), play significant roles in the development of therapy resistance depending on their paracrine function. The PD-1/PD-L1 crosstalk between cancer and immune cells has been well studied. Emerging evidence suggests that PD-L1 also contributes to tumor resistance to therapy. Methods: Cell survival and apoptosis were assessed using CCK-8, colony formation, and flow cytometry assays. Protein alterations were analyzed via Western blot. Gene knockdown and overexpression were achieved with siRNA/shRNA and lentiviral infection, respectively. Drug effects on tumors in vivo were assessed with xenografts in nude mice. In addition, GC patient samples after chemotherapy treatment were collected to observe the relationship between chemotherapy effect and CTCF or PD-L1. Results: In response to 5-fluorouracil or paclitaxel treatment, GCMSC-CM enhanced the cell viability and decreased the apoptosis rate. Furthermore, blocking PD-L1 or CTCF in GC cells prevented GCMSC-induced drug resistance accompanied by a decline in cell stemness. Consistent with these in vitro observations, mice treated with GCMSC-CM showed a lower sensitivity to 5-fluorouracil. In addition, high expression of CTCF and PD-L1 was associated with poor chemotherapy progression in the clinic. Conclusion: Study results demonstrate a mechanism where GCMSC-CM promotes GC chemoresistance by upregulating CTCF-PD-L1 and provide strong evidence in support of targeting CTCF-PD-L1 signaling as a strategy to prevent resistance in the clinic.

CD39 - A bright target for cancer immunotherapy.

The ATP-adenosine pathway functions as a key modulator of innate and adaptive immunity within the tumor microenvironment, and cancer immune evasion largely involves the generation of high amounts of immunosuppressive extracellular adenosine (eADO). Consequently, inhibition of eADO-generating enzymes and/or eADO receptors can effectively restore the antitumor immunity of multiple immune cells. With several clinical strategies currently being explored to modulating the eADO pathway in patients with cancer, recent clinical data with antagonists targeting CD73 and A2A receptor have demonstrated a promising therapeutic potential in cancer. Recent findings reveal that the ectonucleotidase CD39, the limiting enzyme been viewed as "immunological switch", converts ATP-driven pro-inflammatory milieu to an anti-inflammatory state mediated by adenosine. Owing to its superior feature of CD39 antagonism that rely not only on preventing the accumulation of adenosine but also on the stabilization of extracellular ATP to restore antitumor immunity, several inhibitors and clinical trials based on CD39 are being evaluated. Consequently, there is currently a focus on understanding the role of CD39 in governing immunity and how therapeutic strategies targeting this pathway alter the antitumor potential. We herein review the impact of CD39 on tumor microenvironment with a focus on treatment preference. Additionally, we also discuss the implication for rational combination therapies, molecular regulation, as well as potential limitations.

LncRNA AK077216 affects the survival of colorectal adenocarcinoma patients via miR-34a.

BACKGROUND AND STUDY AIMS: It has been reported that long non-coding RNA (lncRNA) AK077216 involves in osteoclastogenesis and bone resorption. Our preliminary data has revealed that AK077216 was downregulated in colorectal adenocarcinoma (CRA) and it was closely correlated with miR-34a. This study was carried out to explore the role of AK077216 in CRA with a focus on its interactions with miR-34a. PATIENTS AND METHODS: Paired CRA and non-tumor tissues collected from 66 CRA patients were subjected to RNA preparations, followed by RT-qPCRs to determine the expression levels of AK077216 and miR-34a. The interactions between AK077216 and miR-34a were analyzed with overexpression assays. Transwell assays were carried out to explore the roles of AK077216 and miR-34a in regulating CRA cell invasion and migration. RESULTS: AK077216 was downregulated in CRA tissues compared to that in non-tumor tissues of CRA patients. During a 5-year follow-up, patients with lower expression levels of AK077216 in CRA tissues showed significantly lower overall survival. MiR-34a was upregulated in CRA tissues and inversely correlated with AK077216. Overexpression of AK077216 decreased the expression levels of miR-34a, while overexpression of miR-34a did not affect the expression of AK077216. Overexpression of AK077216 inhibited CRA cell migration and invasion, while overexpression of miR-34a accelerated cancer cell migration and invasion and attenuated the effects of overexpression on AK077216 on cell behaviors. CONCLUSION: Therefore, AK077216 may inhibit CRA cell migration and invasion by downregulating miR-34a.

ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.

In higher plants, the generation and release of viable pollen from anthers is vital for double fertilization and the initiation of seed development. Thus, the characterization of genes related to pollen development and anther dehiscence in plants is of great significance. The F-box protein COI1 plays a crucial role in the jasmonate (JA) signaling pathway and interacts with many JAZ family proteins in the presence of jasmonoyl-isoleucine (JA-Ile) or coronatine (COR). The mutation of AtCOI1 in Arabidopsis leads to defective anther dehiscence and male sterility (MS), although COI has not been shown to affect fertility in Zea mays (maize). Here we identified two genes, ZmCOI2a and ZmCOI2b, that redundantly regulate gametophytic male fertility. Both ZmCOI2a and ZmCOI2b are highly homologous and constitutively expressed in all tissues tested. Subcellular localization revealed that ZmCOI2a and ZmCOI2b were located in the nucleus. The coi2a coi2b double mutant, generated by CRISPR/Cas9, had non-dehiscent anthers, delayed anther development and MS. In addition, coi2a coi2b male gametes could not be transmitted to the next generation because of severe defects in pollen germination. The JA content of coi2a coi2b anthers was unaltered compared with those of the wild type, and the exogenous application of JA could not rescue the fertility defects of coi2a coi2b. Transcriptome analysis showed that the expression of genes involving the JA signaling transduction pathway, including ZmJAZ3, ZmJAZ4, ZmJAZ5 and ZmJAZ15, was affected in coi2a coi2b. However, yeast two-hybrid assays showed that ZmJAZs interacted with ZmCOI1s, but not with ZmCOI2s. In conclusion, ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.

Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth.

The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy.

G6PD-NF-κB-HGF Signal in Gastric Cancer-Associated Mesenchymal Stem Cells Promotes the Proliferation and Metastasis of Gastric Cancer Cells by Upregulating the Expression of HK2.

Background: Tumor-associated stromal cells have been widely recognized for their tumor-promoting capability involving paracrine signaling. However, the underlying mechanism and the effects of the molecules in the glycolysis pathway in gastric cancer-associated mesenchymal stem cells (GCMSCs) and gastric cancer cells on tumor progression remain unclear. Methods: The expression of hepatocyte growth factor (HGF) in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by enzyme-linked immunosorbent assay (ELISA). The effect of HGF derived from GCMSCs on the proliferation, metastasis, and HK2 expression of gastric cancer cells was evaluated in vitro and in vivo. The effects of G6PD on the production of HGF in mesenchymal stem cells (MSCs) were analyzed by immunoblotting. Results: HGF derived from GCMSCs promoted glycolysis, proliferation, and metastasis of gastric cancer by upregulating c-Myc-HK2 signal. The progression of the disease induced by GCMSCs decelerated in the absence of HK2. The expression of G6PD activated NF-κB signaling and stimulated the production of HGF in GCMSCs. Blocking HGF derived from GCMSCs decreased proliferation, metastasis, and angiogenesis of gastric cancer cells in vivo. Conclusions: GCMSCs highly expressed G6PD and facilitated the progression of gastric cancer through the G6PD-NF-κB-HGF axis coordinates. Blocking HGF derived from GCMSCs is a potential new therapeutic target for the treatment of gastric cancer.

Gastric cancer mesenchymal stem cells inhibit natural killer cell function by up-regulating FBP1.

INTRODUCTION: The dysfunction of natural killer (NK) cells has been widely reported in malignancies, including in solid tumours. Gastric cancer mesenchymal stem cells (GCMSCs) are one of the vital elements of stromal cells in the tumour environment (TME) which possess immunosuppressive activity. This study aimed to determine whether GCMSCs are involved in the inhibition of NK cell immune function and explore its underlying mechanism. MATERIAL AND METHODS: CD107a and perforin expression of GCMSCs conditioned medium (GCMSCs-CM)-primed NK cells were detected by flow cytometry. To determine NK cell cytotoxicity, the CytoTox96 Non-Radioactive Cytotoxicity Assay kit was used. Glucose uptake and lactate production assay were performed to evaluate the metabolism state of NK cells treated with GCMSCs-CM. The expression of FBP1 in NK cells was analysed by immunoblotting. RESULTS: GCMSCs inhibited the degranulation capacity, perforin production and cytotoxicity of NK cells. GCMSCs-CM restrained NK cell glucose uptake and lactate production, thus weakening their glycolytic metabolism. FBP1 expression of NK cells was upregulated in the presence of GCMSCs-CM. Using FBP1 inhibitor could reverse the dysfunctional state of NK cells. CONCLUSIONS: This study indicated that GCMSCs could exert immunosuppressive effects on NK cells by up-regulating FBP1 expression, opening up new avenues for NK cell-based GC immunotherapy.

Chemical reactions of organic compounds in supercritical water gasification and oxidation.

Supercritical water is a benign reaction medium to convert organic matters through supercritical water gasification and supercritical water oxidation into flammable gaseous and harmless substances, respectively. This work systematically summarizes main chemical reactions of some typical organic compounds in supercritical water with or without oxidant for the first time. These compounds include hydrocarbons, proteins, cellulose, lignins, phenols, alcohols, aldehydes, ketones, organic acids, and some N-, Cl-, Br-, F-, S- and P-containing organic matters. Their main conversion pathways, reaction processes, intermediate products, final products and influence factors are analyzed deeply. This information helps to understand and predict corresponding reaction mechanisms and to better achieve objective products in supercritical water gasification and supercritical water oxidation.

Gastric cancer mesenchymal stem cells regulate PD-L1-CTCF enhancing cancer stem cell-like properties and tumorigenesis.

Rationale: Mesenchymal stem cells (MSCs) have been the focus of many studies because of their abilities to modulate immune responses, angiogenesis, and promote tumor growth and metastasis. Our previous work showed that gastric cancer MSCs (GCMSCs) promoted immune escape by secreting of IL-8, which induced programmed cell death ligand 1 (PD-L1) expression in GC cells. Mounting evidence has revealed that PD-L1 expression is related to intrinsic tumor cell properties. Here, we investigated whether GCMSCs maintained a pool of cancer stem cells (CSCs) through PD-L1 signaling and the specific underlying molecular mechanism. Methods: Stem cell surface markers, aldehyde dehydrogenase (ALDH) activity, migration and sphere formation abilities were tested to evaluate the stemness of GC cells. PD-L1-expressing lentivirus and PD-L1 specific siRNA were used to analyze the effects of PD-L1 on GC cells stemness. Annexin V/PI double staining was used to assess apoptosis of GC cells induced by chemotherapy. Co-Immunoprecipitation (Co-IP) and Mass spectrometry were employed to determine the PD-L1 binding partner in GC cells. PD-L1Negative and PD-L1Positive cells were sorted by flow cytometry and used for limiting dilution assays to verify the effect of PD-L1 on tumorigenic ability in GC cells. Results: The results showed that GCMSCs enhanced the CSC-like properties of GC cells through PD-L1, which led to the resistance of GC cells to chemotherapy. PD-L1 associated with CTCF to contribute to the stemness and self-renewal of GC cells. In vivo, PD-L1Positive GC cells had greater stemness potential and tumorigenicity than PD-L1Negative GC cells. The results also indicated that GC cells were heterogeneous, and that PD-L1 in GC cells had different reactivity to GCMSCs. Conclusions: Overall, our data indicated that GCMSCs enriched CSC-like cells in GC cells, which gives a new insight into the mechanism of GCMSCs prompting GC progression and provides a potential combined therapeutic target.

Differential expression of EphA5 protein in gastric carcinoma and its clinical significance.

The aim of the present study was to evaluate ephrin type-A receptor 5 (EphA5) expression and its clinicopathological significance in gastric cancer. Gastric cancer tissues were analyzed by immunohistochemistry. The association between EphA5 expression and clinicopathological parameters, human epidermal growth factor receptor 2 (HER2) status and Ki-67 proliferation index was statistically analyzed. EphA5 expression was detected in all non-tumor gastric epithelia but was differentially expressed among gastric cancer samples. EphA5 was negatively expressed in 30/110 (27.3%) and positively expressed in 80/110 (72.3%) samples from patients with gastric cancer. EphA5 expression was significantly associated with Lauren classification (P=0.032), lymph node metastasis (P<0.001), HER2 expression (P=0.020) and Ki-67 expression (P=0.005). No significant association was determined between EphA5 expression and age, sex, primary location, depth of invasion and Tumor-Node-Metastasis stage. The present data indicated that EphA5 is differentially expressed in gastric cancer. EphA5 may therefore be a potential therapeutic target and may have clinical utility as a marker for lymph node metastasis in gastric cancer.

Illusion Optics: Disguising with Ordinary Dielectric Materials.

Illusion devices are usually designed using transformation optics. Here, a new method is proposed to achieve optical illusions without external devices by elaborately manipulating the scattering potential of an object. In contrast to the conventional transformation optics method, which completely replaces one object by the image of another object using complementary\restoring media and a superlens, the method described here is more of a cosmetic operation for an object, which modifies the scattering pattern of the object to mimic another object by exchanging their scattering potentials in two symmetrical areas in the wave vector domain. Only positive isotropic nonmagnetic materials are introduced in the present method, which is impossible using the conventional method because superlenses require negative-index materials. Both numerical simulations and experimental demonstrations are used to verify the performance of the illusion devices of this method.

Ni-Ru/CeO2 Catalytic Hydrothermal Upgrading of Water-Insoluble Biocrude from Algae Hydrothermal Liquefaction.

Hydrothermal liquefaction (HTL) of algae is a promising crude bio-oil (biocrude) production technology, which can convert wet algae into water-insoluble biocrude and other coproducts. In this work, algae HTL at 350°C and 20 min was conducted to obtain water-insoluble biocrude (B1), which was then hydrothermally upgraded at 450°C, 60 min, or with added H2 and/or homemade catalyst (i.e., Ni-Ru/CeO2 or Ni/CeO2) for the first time. The characteristics (e.g., yield, elemental component, energy recovery, and molecular and functional group compositions) of upgraded water-insoluble biocrude (B2) as well as light biocrude thereof were analyzed comprehensively. The results show that Ni-Ru/CeO2+H2 led to the highest yield and HHV (higher heating value), the best elemental compositions quality of B2, and the largest fraction and the best light of light biocrude in B2. Ni-Ru/CeO2+H2 had good catalytic desulfurization effect and could transform high-molecular-weight compounds into low-molecular-weight compounds in B1 upgrading. At the condition above, 46.2% of chemical energy in the initial algae could be recovered by B2, while average 54.9% of chemical energy in B2 was distributed in its light biocrude (hexane-soluble) portion. On the whole, Ni-Ru/CeO2+H2 can be considered as the optimal additive in all tested cases.