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Objective. The aim was to detect effects of blue light on reducing the adverse effect of heat stress in thermal manipulation (TM) of broiler embryos by subjecting embryos to heat stress during incubation development. Methods. Eggs were assigned to four treatments in which the TM (thermal manipulation) was exposed to 40°C for 4 h daily during five successive days, if TM was operated. The treatments were (1) normal temperature with white lighting group (37°C+W), (2) normal temperature with blue lighting group (37°C+B), (3) thermal manipulation with white lighting group (40°C+W), and (4) thermal manipulation with blue lighting group (40°C+B). Results. Blue light significantly lowered MDA and corticosterone concentrations in the embryonic liver. Additionally, the damage of embryonic liver tissue caused by heat stress could be reduced by blue light. HSPs and HSFs gene expression of chicken liver were modulated by blue light significantly, whereas the effects were different, respectively. Moreover, blue light modulated liver antioxidant enzyme activity and their gene expression in embryonic liver significantly. However, blue light did not exert significant effects on body weight, late hatch rectal temperature and tibia length of hatched chicks. Conclusions. The results suggest that monochromatic blue light can reduce the content of MDA and corticosterone of broiler embryos in heat stress and increase the relative expression of SOD and CAT genes. Moreover, the monochromatic blue light may reduce the metabolic heat production of broilers during the embryonic stage, thus reducing the damage of broilers due to heat stress during the embryonic heat acclimation stage.

Nitrogen availability might play an essential role in plant diseases by enhancing fungal cell growth and influencing the expression of genes required for successful pathogenesis. Nitrogen availability could modulate secondary metabolic pathways as evidenced by the significant differential expression of several core genes involved in mycotoxin biosynthesis and genes encoding polyketide synthase/nonribosomal peptide synthetases, cytochrome P450 and carbohydrate-active enzymes in Fusarium sacchari, grown on different nitrogen sources. A combined analysis was carried out on the transcript and metabolite profiles of regulatory metabolic processes and the virulence of Fusarium sacchari grown on various nitrogen sources. The nitrogen regulation of the gibberellin gene cluster included the metabolic flux and multiple steps of gibberellin synthesis. UHPLC-MS/MS-based metabolome analysis revealed the coordination of these related transcripts and the accumulation of gibberellin metabolites. This integrated analysis allowed us to uncover additional information for a more comprehensive understanding of biological events relevant to fungal secondary metabolic regulation in response to nitrogen availability.

Posaconazole (POS) is a novel antifungal agent, which has been repurposed as an anti-tumor drug for its potential inhibition of Hedgehog signaling pathway. Hedgehog pathway is reported to be abnormally activated in embryonal rhabdomyosarcoma (ERMS), this study aimed to reveal whether POS could inhibit Hedgehog signaling pathway in ERMS. Following POS treatment, XTT viability assay was used to determine the cell proliferation of ERMS cell lines. Protein changes related to Hedgehog signaling, cell cycle and autophagy were detected by Western blot. The cell cycle distribution was analyzed by flow cytometry. Moreover, a subcutaneous tumor mouse model of ERMS was established to assess the anti-tumor effect of POS. POS was found to inhibit tumor progression by inducing G0/G1 arrest and autophagy of RD, RMS-YM, and KYM-1 cells dose-dependently. Western blot demonstrated that POS downregulated the expressions of SMO, Gli1, c-Myc, CDK4, and CDK6, while upregulated the expressions of autophagy-related proteins. Immunofluorescence microscopy revealed a significant increase of LC3B puncta in POS-treated ERMS cells. Furthermore, POS treatment led to a significant inhibition of tumor growth in mice bearing ERMS. Our findings could provide a theoretical basis and have important clinical implications in developing POS as a promising agent against ERMS by targeting Hedgehog pathway.

Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time- and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.

The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×106), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.

Nitroxoline is considered to be an effective treatment for the urinary tract infections. Recently, it has been found to be effective against several cancers. However, few studies have examined the anti-tumor activity of nitroxoline in bladder cancer. The purpose of the study was to reveal the possible mechanisms how nitroxoline inhibited bladder cancer progression. In vitro assay, we demonstrated that nitroxoline inhibited bladder cancer cell growth and migration in a concentration-related manner. Western blot analysis demonstrated that nitroxoline downregulated the expressions of epithelial mesenchymal transition (EMT)-related proteins. Furthermore, treatment with nitroxoline in the C3H/He mice bladder cancer subcutaneous model resulted in significant inhibition of tumor growth. Moreover, the percentage of myeloid-derived suppressor cells (MDSC) in peripheral blood cells significantly decreased after treatment of nitroxoline. Taken together, our results suggested that nitroxoline may be used as a potential drug for bladder cancer.

Wenfeng Lin,1,* Chaoming Li,1,2,* Naijin Xu,1,3 Masami Watanabe,1,4 Ruizhi Xue,1 Abai Xu,2 Motoo Araki,1 Ruifen Sun,5 Chunxiao Liu,2 Yasutomo Nasu,1 Peng Huang1,2,6 1Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan; 5Center for Scientific Research, Yunnan University of Chinese Traditional Medicine, Kunming, People’s Republic of China; 6Okayama Medical Innovation Center, Okayama University, Okayama, Japan*These authors contributed equally to this workCorrespondence: Peng HuangDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, JapanTel + 81-86-235-7997Fax +81-86-235-7884Email huangpeng509@gmail.comPurpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men’s health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment.Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation.Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9± 1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96± 1.88)% compared with (0.99± 0.10)% in PBS group, revealing the enhanced immune response against PCa.Conclusion: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.Keywords: prostate cancer, PLGA, indocyanine green, resiquimod, photothermal therapy, immunotherapy

Yiming Zhang,1,2,* Binshen Chen,1,2,* Naijin Xu,3 Peng Xu,1,2 Wenfeng Lin,1– 3 Chunxiao Liu,1,2 Peng Huang1– 3 1Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Key Laboratory of Inflammatory and Immune Diseases, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan*These authors contributed equally to this workCorrespondence: Peng Huang; Chunxiao LiuDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of ChinaTel +86-20-62782726Fax +86-20-62782725Email huangpeng509@gmail.com; Liuchx888@hotmail.comBackground: Castration-resistant prostate cancer (CRPC) is still considered incurable, even though the mechanisms of CRPC had been extensively researched. Studies have demonstrated that exosomes in the tumor microenvironment contribute to prostate cancer development and progression. However, the role of exosomes in the process of CRPC progression has not yet been determined.Methods: Co-culturing and exosome treatment assays combined with in vitro and in vivo assays were performed to determine the function of exosomes in the transformation of androgen-dependent prostate cancer (ADPC) cells into androgen-independent cells. Then, the mRNA expression profiles of ADPC cells and ADPC cells co-cultured with androgen-independent prostate cancer (AIPC) cell-derived exosomes were studied using microarrays. After silencing the expression of heme oxygenase-1 (HMOX1), Western blotting, quantitative real-time PCR, immunohistochemistry (IHC) studies, and MTS assay were used to confirm the mechanisms of exosome participation in CRPC progression.Results: The results showed that ADPC cells acquired tolerance for androgen deprivation due to the exosome-mediated communication between cells. AIPC cell-derived exosomes promoted the transformation of ADPC cells into androgen-independent cells in vivo and in vitro. Microarray analysis revealed that HMOX1 in ADPC cells was up-regulated after treatment with AIPC cell-derived exosomes. Further results showed that HMOX1 is overexpressed in human AIPC specimens and protects ADPC cells from androgen deprivation.Conclusions: Our findings revealed that exosomes contribute to CRPC progression via promoting the transition of prostate cancer cells into an androgen-independent growth stage by activating HMOX1.Keywords: prostate cancer, castration resistance, exosomes, heme oxygenase-1

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.

Glaucocalyxin A (GLA), a major component isolated from Rabdosia japonica, has been proven to show anti-bacterial and anti-tumor biological characteristics according to previous studies. However, its potential effect on bladder cancer remains unknown. The present research aims to investigate the underlying mechanism in treating bladder cancer in vivo and in vitro. Cell proliferation was analyzed by CCK-8 assay and colony formation. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of the cell cycle and apoptosis-related proteins were detected by western blotting and immunofluorescence staining. Meanwhile, the in vivo study was performed to evaluate the anti-tumor effect on a UMUC3 subcutaneous tumor of NOD/SCID mice model. GLA suppressed colony-formation ability, triggered G2/M arrest and promoted apoptosis of UMUC3 cells in a dose-dependent manner. Furthermore, western blotting showed that GLA downregulated the expressions of PI3K p85, p-Akt, Bcl-2, CDK1, Cyclin B1 whereas upregulated the levels of PTEN, Bax, Cleaved Caspase-3. In vivo, GLA at a dosage of 20 mg/kg significantly inhibited tumor growth compared with the control group by intraperitoneal injection. These results suggested that GLA-related G2/M arrest and apoptosis in UMUC3 cells were mediated by a suppressed PI3K/Akt signaling pathway, which regulated p21Waf1/Cip1 as well as intrinsic caspase cascade. Collectively, our observations could help to develop new drugs targeting the PI3K/Akt pathway for the treatment of bladder cancer.

Background: Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC), posing a threat to the prognosis of patients. Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for the treatment of multiple tumors. Here we aimed to investigate whether NTX suppresses the growth of drug-resistant UBC in vitro and in vivo and the underlying mechanism at the molecular level. Methods: The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. The drug effects on cell proliferation were measured by XTT assay. Cell cycle distribution was analyzed by PI/RNase staining, while apoptosis was assessed by Hoechst 33342 and Annexin V-FITC/PI staining. The expressions of proteins related to STAT3 signaling, cell cycle, and apoptosis were detected by western blotting. Subcutaneous xenograft models of T24/DOX and T24/CIS were established to determine the in vivo anti-tumor effect of NTX. Results: T24/DOX and T24/CIS cells were resistant to DOX and CIS respectively, but they were sensitive to NTX in a time- and dose-dependent manner. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Furthermore, western blotting showed that NTX downregulated the expressions of phosphorylated STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibits the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced G0/G1 arrest, apoptosis, and P-gp reversal in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Conclusion: Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC. Citation Format: WENFENG LIN, Jingkai Sun, Takuya Sadahira, Motoo Araki, Masami Watanabe, Yasutomo Nasu, Peng Huang. Reposition of the antibiotic nitroxoline as a novel STAT3 inhibitor for drug-resistant urothelial bladder cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA037.

In this study, the mechanical behaviours of thick-walled hollow functionally graded material (FGM) cylinder subjected to uniform pressures at inner and outer surfaces are proposed. The hollow FGM cylinder has variable geometric profile, thickness and material properties like elastic modulus and mass density are all assumed to vary radially according to exponentially-varying functions in radial direction. With the help of the infinitesimal elasticity theory and plane strain assumption, analytic solutions of stress and deformation are proposed. Numerical example is given to show the performance between FEM and homogeneous cylinder. Finally, summary and the future work are presented at the end of the paper.

Bufalin, one of the active ingredients of the Chinese drug Chan su, exhibits significant antitumor activity against various cancer types. However, the role of bufalin in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that bufalin inhibited cell proliferation, blocked the cell cycle in the G2/M phase, and reduced the metastasis of human RCC ACHN cells via the upregulation of p21waf/cip1 and E-cadherin and the downregulation of cyclin dependent kinase 1, cyclin B1, N-cadherin, and hypoxia-inducible factor-1α (HIF-1α). Further mechanistic study revealed that bufalin reduced the expression of phosphorylated (phospho)-Akt and phospho-mammalian target of rapamycin (mTOR). Moreover, HIF-1α expression may be regulated through the inhibition of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR signaling pathway. Thus, the present results suggest that bufalin induces cell cycle arrest and suppresses metastasis; this process may be associated with the PI3K/Akt/mTOR signaling pathway. Accordingly, it is suggested that bufalin is a therapeutic agent for RCC.

Although the approach using non-thermal plasma (NTP) for deNOx has been studied for over 15 years, how to achieve higher removal efficiency with lower cost is still a barrier for its industrial application. In order to investigate the impact of the argon additive on electron density, energy and nitric oxide reduction process in plasma, the spectrum of the dielectric barrier discharge at atmospheric pressure in a coaxial reactor was measured using the monochromater with high resolution. The comparative experiments for NO reduction were carried out simultaneously in N2/O2/NO plasma stream with and without argon, respectively. The nitrogen molecular spectrum which is attributed to the energy level transition (C3pi(u)-->B3pi(g)) was compared in the wavelength range 300-480 nm and the electron density and temperature were determined based on the relative intensities and Stark broadening width of spectral lines. The spectrum results indicated that the argon additive could enhance the intensity of emissive spectrum of plasma, thus the electron concentration as well as the energy was increased, and finally prompted the ionization rate to produce active N, O and O3. The results of NO reduction showed that NO conversion efficiency increased in the range of 10%-30% with 5% addition of argon in stream comparing with the condition without argon additive. This study will play a positive role in the industrial application of dielectric barrier discharge deNOx reactor.

A novel low-complexity iterative receiver for coded multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing (OFDM) systems is proposed in this letter. The soft-in soft-out (SISO) detector is simply a parallel interference cancellation (PIC)–maximum ratio combining (MRC) operation. However, system performance would be degraded because of ignoring the existence of the residual interference from other transmit antennas. In our scheme, the log likelihood ratios (LLRs) of encoded bits after channel decoding are multiplied by a constant factor to achieve a performance gain. The constant factor is optimized according to the extrinsic information transfer (EXIT) chart. Simulation results show that the proposed iterative receiver can significantly improve the system performance and converge to the matched filter bound (MFB) with low computational complexity at high signal-to-noise ratios (SNRs).

Software framework is a very important approach to realize software reuse and improve the software quality. In this paper, we firstly introduce a new software framework named QFusion to complete cross-platform desktop software development, which is based on function plug-in module. The QFusion framework can realize information interaction by use of event bus, data bus and service, which can separate the graphical user interfaces (GUI) from data processing completely. Based on the framework-related develop process, the complexity is largely reduced. Secondly, we give the practice of QFusion framework in modern military field to implement the feature extraction and data processing algorithm. Benefit from the QFusion framework, the signal processing task is completed by the collaboration among three groups, including data generation plug-in development group, data processing plug-in development group and GUI plug-in development group, respectively. Finally, the signal processing results are presented to prove the validity of the QFusion framework, which lays a solid foundation for solving the practical problem in engineering application.

In this paper, a turbo like transceiver for multiple input multiple output (MIMO) orthogonal frequency division multiplexing (OFDM) system is presented. At the transmitter, convolutionally coded and modulated symbols are encoded by a only one cycle (OOC) space time encoder. At the receiver, a sub- optimal receiver performs two successive decisions, achieved by a maximum a posteriori probability (MAP) detector and a soft-input soft-output (SISO) channel decoder through an iterative process. At each iteration, extrinsic information is exchanged between the detector and the decoder. Simulation results show the iterative receiver offers performance gain over non-iterative receiver and the OOC space time encoder can get performance gains on the fast fading channel.

Bell lab layered space-time (BLAST) architecture can achieve a tight lower bound on the MIMO channel capacity with a simple transmit structure. It is very attractive because of its capacity ability. However, detection methods for BLAST face two problems: some are high complexity, such as Maximum Likelihood detection; some bear error propagation, which lead to poor performance, such as MMSE SIC method. In this paper, an omni-direction ZF BLAST receiver is presented. Simple omni- direction QR factorization and new detection criteria are performed. Without ordering for cancellation makes the complexity of this scheme very low. Simulation results show that performance of this scheme is prior to that of Bi-direction method presented in (7). Keywords-MIMO; BLAST; full diversity; zero-forcing.

The paper consider a scheme combining transmit antenna selection (TAS) and space time turbo trellis codes (ST-turbo-TCs), which is referred to as the ST-turbo-TCs/TAS scheme. We choose two transmit antennas, which maximizes the signal-to-noise ratio (SNR) at the receiver, to transmit the baseline ST-Turbo-TCs signals designed for two transmit antennas. Our simulation shows that this scheme can achieve significant performance gains with an increasing number of transmit antenna available for selection. In addition, this scheme does not have increasing complexity for increasing performance gains, and does not need a particular code design for a large number of transmit antennas.