In vitro antiviral activity of germacrone against porcine parvovirus.

Porcine parvovirus (PPV) infections can lead to significant losses to the swine industry by causing reproductive failure in pigs. Germacrone has been reported to efficiently suppress the replication of influenza virus. In this report, the antiviral activity of germacrone on PPV in swine testis (ST) cells was investigated. Here, we show for the first time that germacrone protects cells from PPV infection and suppresses the synthesis of viral mRNA and protein. Furthermore, we show that germacrone inhibits PPV replication at an early stage in a dose-dependent manner. These findings suggest that germacrone is a potential candidate for anti-PPV therapy.

Evaporation issues of acoustically levitated fuel droplets.

Fuel droplet evaporation is essential to the generation of flammable mixtures in thermal engines. Generally, liquid fuel is injected directly into the hot, high-pressure atmosphere to form scattered droplets. Many investigations on droplet evaporation have been conducted with techniques involving the influence of boundaries, such as suspended wires. Ultrasonic levitation is a non-contact and non-destructive technology that can avoid the impact of hanging wire on droplet shape and heat transfer. Besides, it can simultaneously levitate multiple droplets and allow them to associate with each other or be used to study droplet instability behaviors. This paper reviews the influences of the acoustic field on levitated droplets, the evaporation characteristics of acoustically levitated droplets, and the prospects and limitations of ultrasonic suspension methods for droplet evaporation, which can serve as references for relevant studies.

A Biomimetic Basalt Fiber/Epoxy Helical Composite Spring with Hierarchical Triple-Helix Structures Inspired by the Collagen Fibers in Compact Bone.

The lightweight property of helical composite spring (HCS) applied in the transportation field has attracted more and more attention recently. However, it is difficult to maintain stiffness and fatigue resistance at the same time. Herein, inspired by collagen fibers in bone, a bionic basalt fiber/epoxy resin helical composite spring is manufactured. The collagen fibers consist of nanoscale hydroxyapatite (increases stiffness) and collagen molecules composed of helical amino acid chains (can increase fatigue resistance). Such a helical structure of intercalated crystals ensures that bone has good resistance to fracture. Specifically, we first investigated the effect of adding different contents of NS to basalt fibers on the stiffness and fatigue properties of an HCS. The results show that the optimal NS content of 0.4 wt% resulted in 52.1% and 43.5% higher stiffness and fatigue properties of an HCS than those without NS, respectively. Then, two braided fiber bundles (TS-BFB) and four braided fiber bundles (FS-BFB) were designed based on the helical structure of amino acid chains, and the compression tests revealed that the maximum load resistance of TS-BFB and FS-BFB was increased by 29.2% and 44%, respectively, compared with the conventional single fiber bundle (U-BFB). The superior mechanical performance of TS-BFB and FS-BFB is attributed to the more adequate bonding of 0.4 wt% NS to the epoxy resin and the multi-fiber bundles that increase the transverse fiber content of the spring. The findings in this work introduce the bionic collagen fiber structure into the design for an HCS and provide a new idea to improve the spring performance.

B7-H4 and HHLA2, members of B7 family, are aberrantly expressed in EGFR mutated lung adenocarcinoma.

BACKGROUND: In order to find new immune targets for lung cancer with different EGFR mutant status, we describe differential expression profiles of checkpoint molecules of the new discovery B7 family member to find new immune targets for lung cancer with different EGFR statuses. METHODS: We performed immunohistochemistry with antibodies of B7-H3, B7-H4, VISTA, B7-H6, HHLA2, IDO-1, PD-L1 and CD8 in lung adenocarcinoma tissues constructed from 372 cases in the discovery cohort and 231 cases in the validation set. The differential expression profiles of these indices in EGFR mutant and wild-type lung adenocarcinoma was described and compared. RESULTS: In the discovery cohort, the median IHC scores of B7-H4 and HHLA2 for the EGFR mutant group were significantly higher than those in the wild-type group (median score [interquartile range], mutant vs. wild type: 3.250 [0-7.000] vs. 5.000 [1.000-7.000], P = 0.045 for B7-H4; 8.000 [6.000-10.500] vs. 7.000 [5.000-8.630] P = 0.003 for HHLA2). Meanwhile, the median IHC scores of IDO-1 and PD-L1 in the wild-type group were significantly higher than those in the mutant group (median score [interquartile range], mutant vs. wild type: 1.000 [0-5.000] vs. 3.000 [0-8.500], P = 0.000 for IDO-1; 0 [0-3.500] vs. 3.000 [0-6.000], P = 0.000 for PD-L1). Results above was confirmed in the discovery cohort. The increased CD8 and decreased HHLA2 expression levels were associated with long disease-free survival in lung adenocarcinoma (P = 0.000 for CD8 expression and P = 0.004 for HHLA2 expression). CONCLUSIONS: B7-H4 and HHLA2 are promising immune targets for lung adenocarcinoma, especially for patients with EGFR mutation.

The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer.

Background: Immunotherapies targeting CTLA-4 and PD-1 have elicited promising responses in a variety of cancers. However, the relatively low response rates warrant the identification of additional immunosuppressive pathways. V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and is a valuable target in cancer immunotherapy. Methods: Here, we used single-cell RNA-seq to analyze the gene expression levels of 14897 cells from a breast cancer sample and its paired 7,320 normal cells. Then, we validated the protein expression of immune checkpoint molecules (VISTA, PD-1, PD-L1, TIGIT, TIM3, and LAG3) in 324 human breast cancer samples by immunohistochemistry and quantitative immunofluorescence (QIF) approaches. Results: Single cell RNA-seq results show a higher level of immune checkpoint VISTA expression in breast cancer tissue compared to adjacent normal tissue. We also found that VISTA expressed highest in breast cancer tissue than other immune-checkpoints. Immunohistochemical results showed that VISTA was detected with a membranous/cytoplasmic staining pattern in intratumoral immune cells and breast cancer cells. Additionally, VISTA was positively correlated with pathological grade, lymph node status and the levels of PD-1 according to the chi-square test or Fisher's test. Furthermore, VISTA expression was higher in CD68+ tumor-associated macrophages (TAMs) than in CD4+ T cells, CD8+ cytotoxic T cells or CD20+ B cells. Conclusions: These findings therefore support the immunoregulatory role of VISTA in breast cancer and indicate that targeting VISTA may benefit breast cancer immunotherapy.

Simulated High Altitude Helium-Oxygen Diving.

BACKGROUND: Experience with commercial heliox diving at high altitude is limited. The purpose of this study was to evaluate the effects of acute high-altitude exposure on fitness to dive and the safety of decompression after heliox diving while using U.S. Navy heliox decompression tables with Cross correction. METHOD: Four professional male divers were consecutively decompressed in a hypo- and hyperbaric chamber to altitudes of 3000 m (9842.5 ft), 4000 m (13,123.4 ft), and 5200 m (17,060.4 ft) during the 8-d study. The dive profiles tested were to 30 m (98.4 ft) for 60 min at all three altitudes and, in addition, a dive to 50 m (164 ft) for 60 min at 5200 m altitude. The decompression followed the U.S. Navy heliox decompression table. The safety of decompression was evaluated by precordial Doppler venous gas emboli (VGE) monitoring during the decompression stages and postdive monitoring of the divers for symptoms of decompression sickness (DCS). Effects of altitude exposure were measured as subjective rating and EEG signs of sleepiness and fatigue, clinical symptoms of high altitude disease, and fitness to dive. RESULTS: A total of 24 person-dives were conducted. There were no VGE detected during the decompression and no postdive symptoms of decompression illness. Both the EEG findings and subjective evaluation indicated increased sleepiness and fatigue at 3000 m, 4000 m, and 5200 m, all compared with the sea level baseline. During the diving phase, both the EEG findings and subjective evaluation scores returned to the baseline and the divers successfully completed diving. DISCUSSION: Diving at high altitude with a short acclimatization period appears safe despite divers exhibiting clinical symptoms and EEG signs of impairment by hypoxia at high altitude. Despite a small number of dives, the results of this study indicate that our application of U.S. Navy standard heliox decompression tables with Cross correction is effective and could be used for underwater constructions up to 5200 m altitude, with due caution.Shi L, Zhang Y, Tetsuo K, Shi Z, Fang Y, Denoble PJ, Li Y. Simulated high altitude helium-oxygen diving. Aerosp Med Hum Perform. 2017; 88(12):1088-1093.

[Prevention of Rhodiola-astragalus membranaceus compounds against simulated plateau hypoxia brain injury in rat].

OBJECTIVE: To observe the protective effects of Rhodiola-astragalus membranaceus mixture against brain damage during hypoxia under simulated plateau environment and the mechanisms maybe involved in. METHOD: Adult SD rats were randomly divided into 3 groups, which were normoxic control, simulated plateau hypoxia, and Rhodiola-astragalus membranaceus mixture pretreatment group. Rats in the latter two groups were exposed to simulated 8000 m altitude in a hypobaric chamber for 7 h. Water content, Na+, K(+)-ATPase activity and SOD activity in cerebral tissue, malondialdehyde (MDA) and lactic acid content in cerebral homogenate and serum were measured. RESULT: As compared with control group, cerebral water content was significantly higher in hypoxia group, while it was obviously lower in pretreatment group. MDA contents of hypoxia group both in cerebral homogenate and serum were higher than that of control group, while the pretreatment group they were both decreased obviously. Lactic acid content of hypoxia group in cerebral and in serum increased markedly and decreased drastically in pretreatment group compared to that of hypoxic group. CONCLUSION: Rhodiola-astragalus membranaceus mixture has preventive effects on hypoxic damage induced by simulated plateau environment. This prevention may be related to the antagonistic effect on membrane lipid peroxidation and the inhibition on the accumulation of lactic acid in brain tissue and serum.

HER2 status in molecular apocrine breast cancer: associations with clinical, pathological, and molecular features.

Molecular apocrine breast cancer (MABC) is a distinct subtype of breast cancer. The purpose of this study was to investigate the relationship between HER2 status and clinicopathologic characteristics of MABCs from Chinese Han cohort. A cohort of 90 MABC patients were enrolled. Immunohistochemical method was performed to analyze the molecular expression, and the human epidermal growth factor receptor 2 (HER2) amplification was verified by fluorescence in situ hybridization (FISH). By studying these 90 MABC cases, the majority of studied patients were premenopausal young women (median age 48 yr) with high grade tumors. We also found that MABCs had high positive expression rates of HER2, CK8, CD44, CD166, p53 and BRCA1, the elevated Ki-67 labeling index, and favorable prognosis. There was a significantly higher incidence of lymph node metastasis and lower CD166 positive rate in HER2-negative patients compared to HER2-positive patients (54.5% vs. 37.0%, P = 0.044 and 72.7% vs. 91.3%, P = 0.021, respectively). The CK5/6 and EGFR expression rates were significant higher in HER2-negative cases than in HER2-positive cases, suggesting that there is overlap between MABC with HER2-negative phenotype and basal-like breast cancer. In addition, HER2 positive was found to be significantly associated a poor overall survival in MABCs. In conclusion, HER2 are highly expressed, and HER2 positivity could be considered as a significant biomarker of poor prognosis in MABC. The results also suggest that a subtype tumor with distinct patterns of molecule expression depending on HER2 status presented in MABC.