Cloud-based data management system for automatic real-time data acquisition from large-scale laying-hen farms

: Management of poultry farms in China mostly relies on manual labor. Since such a large amount of valuable data for the production process either are saved incomplete or saved only as paper documents, making it very difficult for data retrieve, processing and analysis. An integrated cloud-based data management system (CDMS) was proposed in this study, in which the asynchronous data transmission, distributed file system, and wireless network technology were used for information collection, management and sharing in large-scale egg production. The cloud-based platform can provide information technology infrastructures for different farms. The CDMS can also allocate the computing resources and storage space based on demand. A real-time data acquisition software was developed, which allowed farm management staff to submit reports through website or smartphone, enabled digitization of production data. The use of asynchronous transfer in the system can avoid potential data loss during the transmission between farms and the remote cloud data center. All the valid historical data of poultry farms can be stored to the remote cloud data center, and then eliminates the need for large server clusters on the farms. Users with proper identification can access the online data portal of the system through a browser or an APP from anywhere worldwide

Human Domain Antibodies to Conserved Epitopes on HER2 Potently Inhibit Growth of HER2-Overexpressing Human Breast Cancer Cells In Vitro

The FDA approval of two anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, and an antibody-drug conjugate, trastuzumab emtansine, has transformed clinical practice for HER2-positive cancers. However, not all patients respond to therapy, and the majority of responders eventually develop resistance. In addition, cardiotoxicity is a major safety concern for their clinical use. Thus, there remains a need for the discovery and development of novel classes of HER2-targeted therapeutics with high efficacy and specificity. In this study, we report the identification and characterization of fully human single-domain antibodies (dAbs) targeting HER2 epitopes that are highly conserved among various species and non-overlapping with those of trastuzumab and pertuzumab. An Fc-fusion protein of the best binder demonstrated much higher inhibitory activity against HER2-amplified human breast cancer cell lines than trastuzumab and pertuzumab. Unlike the latter, however, it did not have an effect on gastric and ovarian cancer cell lines with HER2 overexpression. The dAb-Fc fusion protein showed poor pharmacokinetics in mice, thus limiting its potential for therapeutic use. It could be useful as an agent for the exploration of functionally important conserved structures on HER2 with implications for the design of novel therapeutics and elucidation of mechanisms of HER2-mediated tumorigenesis

NIR molecule induced self-assembled nanoparticles for synergistic in vivo chemo-photothermal therapy of bladder cancer

Bladder cancer (BC) is one of the commonest malignancies in the urinary system. Bladder cancer is divided into non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) according to the depth of invasion. Besides, the prognosis of MIBC remains poor. Surgical resection combined with radiotherapy or chemotherapy is the standard treatment for MIBC. However, the major obstacle that hinders successful chemotherapy is its lack of tumor targeting. Here, we fabricated nanoparticles that respond to near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome challenges of bladder cancer treatment. IR780 and Doxorubicin (DOX)were loaded into albumin nanoparticles (IR780-DOX@Albumin NPs). In the process of IR780-DOX@Albumin NPs synthesis, the near-infrared molecule IR780 was used as the assembly molecular bridge. Under irradiation, the nanoparticles were decomposed due to the degradation of IR780 while the release of DOX increased. Nanoparticles can be ingested by tumor cells in a short time. The IR780- DOX@Albumin NPs were sensitive to near-infrared laser irradiation. Near-infrared laser irradiation can promote the release of the drugs from the nanoparticles and induce a photothermal effect, thus destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, IR780-DOX@Albumin NPs can greatly increase the concentration of chemotherapeutic drugs in tumor cells. This study combines photothermal therapy and chemotherapy to treat MIBC, so as to avoid chemotherapy resistance, reduce the toxicity to normal cells, and achieve the purpose of improving the treatment of MIBC

Adeno-associated virus-mediated expression of activated factor V (FVa) for hemophilia phenotypic correction

Adeno-associated virus (AAV) gene therapy has been successfully applied in hemophilia patients excluding patients with inhibitors. During the coagulation pathway, activated factor V (FVa) functions downstream as a cofactor of activated factor X (FXa) to amplify thrombin generation. We hypothesize that the expression of FVa via gene therapy can improve hemostasis of both factor IX and FVIII deficiencies, regardless of clotting factor inhibitor. A human FVa (hFVa) expression cassette was constructed, and AAV8 vectors encoding hFVa (AAV8/TTR-hFVa) were intravenously administrated into mice with hemophilia A and B with or without FVIII inhibitors. Hemostasis, including hFVa level, activated partial thromboplastin time (aPTT), tail clip, and the saphenous vein bleeding assay (SVBA), was evaluated. In hemophilia B mice, a dose of 4 × 1013 vg/kg AAV8/TTR-hFVa vectors achieved a complete phenotypic correction over 28 weeks. In hemophilia A mice, hemostasis improvement was also achieved, regardless of FVIII inhibitor development. In vivo hemostasis efficacy was confirmed by tail clip and SVBA. Interestingly, while minimal shortening of aPTT was observed at a lower dose of AAV8 vectors, hemostasis improvement was still achieved via in vivo bleeding assays. Collectively, FVa-based AAV gene therapy shows promise for hemostasis correction in hemophilia, regardless of inhibitor development and no potential risk for thrombosis

Xanthine quartets on Au(111)

The quartet of xanthine (X), a purine base ubiquitously distributed in most human body tissues and fluids, has been for the first time fabricated and visualized, as the first alternative purine quartet besides the known guanine (G)-quartet. The X-quartet network is demonstrated to be the most stable phase on Au(111). Unlike guanine, the fabrication of the X-quartets is not dependent on the presence of metal atoms, which makes it the first metal-free purine quartet. The X-quartet holds great promise to potentially construct artificial new DNA quadruplexes for genetic regulation and antitumor therapy. Moreover, both the X-quartet itself and the quartet networks favor homochirality, suggesting homochiral xanthine oligomers and the networks may have been formed as the precursors of the pristine oligonucleotides on primitive Earth

Second generation androgen receptor antagonist, TQB3720 abrogates prostate cancer growth via AR/GPX4 axis activated ferroptosis

Purpose: Prostate cancer (PCa) poses a great threat to humans. The study aimed to evaluate the potential of TQB3720 in promoting ferroptosis to suppress prostate cancer, providing a theoretical basis for PCa therapy.Methods: PCa cells and nude mice models were divided into TQB3720, enzalutamide (ENZ), and control groups. Sulforhodamine B assay, colony formation assessment, organoids culture system, and the CCK8 assay were used for detecting proliferation. Western blot assay was processed to detect the expression of androgen receptor (AR), ferroptosis, and apoptosis-related genes. Flow cytometry was applied to measure the intracellular ROS levels. ELISA was performed to determine the cellular oxidized glutathione (GSSG) and malondialdehyde (MDA) levels. RT-qPCR was conducted to detect the mRNA expression of genes in AR signaling. BODIPYTM™ 581/591 was processed for detection of intracellular lipid peroxidation levels. The interaction of AR with other translational factor complex proteins was explored using Co-immunoprecipitation (Co-IP), and the chromatin immunoprecipitation (ChIP) assay was performed to detect the binding of AR-involved translational complex to downstream genes promoter. Luciferase reporter assay was conducted to examine the translation activity of GPX4 promoter, and immunohistochemistry (IHC) was conducted to analyze the levels of c-MYC, Ki-67 and AR in TQB3720-treated cancer tissues.Results: Here, we found TQB3720 inhibits the growth of prostate cancer in vitro and in vivo. TQB3720 treatment induced intracellular levels of GSSG and MDA significantly, by which hints AR antagonist caused ferroptosis-related cell death. Moreover, molecular evidence shown TQB3720 regulates downstream of AR signaling by binding AR resulting in inhibition of AR entry into the nucleus. Additional, we also proved that TQB3720 abrogates the interaction between AR and SP1 and leads to decrease GPX4 transcription.Conclusion: TQB3720 promotes ferroptosis in prostate cancer cells by reducing the AR/SP1 transcriptional complex binding to GPX4 promoter. As a result, it is suggested to be a potential drug for clinic prostate cancer treatment

Image-guided percutaneous renal cryoablation for stage 1 renal cell carcinoma with high surgical risk

Background: This study was undertaken to evaluate the feasibility, safety, and therapeutic effects of percutaneous renal cryoablation under local anesthesia with conscious sedation for patients who have unresectable stage 1 (T1NoMo) renal cell carcinoma (RCC) in high surgical risk. Methods: Eighteen patients who were not candidates for surgery underwent primary cryosurgery guided by gray-scale ultrasound. Contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computed tomography (CT) were performed to evaluate treatment at completion. Results: The mean follow-up period was 26.8 months (range, 12–56 months). All tumors were biopsied before cryosurgery. Seventeen tumors remained free of enhancement during follow-up period. No major complications associated with cryoablation procedures were found though two instances of subcapsular hematomas, one of retroperitoneal errhysis and one of nausea, were seen after cryoablation. One patient had a local recurrence of tumor and received additional cryoablation. Local tumor control rate was 100 % of T1NoMo tumors including the recurrence case who underwent additional cryoablation. Conclusions: Percutaneous cryoablation can be recommended as a feasible, safe, and promising therapy for the treatment of renal tumor, especially those unresectable stage 1 RCC, with a low risk of complications

The influence of mass media on countryside leisure visit behaviour compared to the influence of childhood socialization: a structural model of relationships.

Those involved with the management of the countryside have an imperative to understand the drivers of behaviour towards it. This is particularly so, since the UK population is largely urban-based and yet still retains an attachment to green open spaces and engagement with the pastoral scene (DEFRA, 2009; Natural England, 2016). The media has been recognised as playing an important role in sustaining this attachment but its relative influence compared to the role of the family, other social groups and education is less well understood in this context. The aim of this research is to provide a measure of the influences that underpin this attachment, specifically to develop a better understanding of the role of mass media as a component of the socializing factors which influence attitudes towards leisure behaviour in the countryside. The measurement and exploration of these influences is based upon a pilot study, followed by a survey of 2775 respondents, in six urban centres in England during 2011 and 2012. The data was analysed in order to investigate the relative role of developmental and mass media influences on countryside leisure behaviour. The cognitive and emotional processes that catalyse these relationships were also evaluated. A structural model of relationships was then developed, which provided predictive measures of the formative influences upon countryside leisure behaviour. Three key findings emerged from the research. The first confirmed that interest in countryside leisure may be derived from early socialization influences but significantly there are sub-groups for whom this early experience is irrelevant. These sub-groups developed their interest in countryside in later adulthood, inspired by the cultural discourse of rural themes represented in the media. Secondly the research identified that the relative influence of early exposure to countryside interests from family and friends is weaker than the direct effect of media on current countryside visit behaviour. Thirdly the predictive relationship suggests that countryside knowledge, the normative and control influences of others and the media, work largely through emotional rather than cognitive processes in their effect upon countryside visit behaviour. A further outcome of the research identified a control influence upon attitudes and engagement with the countryside, driven by pragmatic considerations of countryside as a resource for housing and infrastructure needs. The significant findings from this research make a contribution to knowledge regarding the processes that influence countryside leisure attitudes and behaviour. Specifically, it confirms the importance of developing media strategy that reflects the emotional bond that people have with the countryside and targeting robust market segments, differentiated by media responsiveness and developmental influences. An effective media strategy is particularly important for those sections of the population, who have had little encouragement to engage with the countryside during childhood but are, in adulthood, responsive to its portrayal in the media