Synthesis and evaluation of L-quebrachitol derivatives against platelet aggregation.

Thrombosis plays an important role in the occurrence and development of cardiovascular and cerebrovascular diseases that contribute to high mortality and morbidity in patients. L-(-)-Quebrachitol (QCT), a natural product, was first isolated from quebracho bark. It can inhibit PAF receptor and decrease gastric damage induced by indomethacin, as a drug against platelet aggregation. Here, five QCT derivatives were synthesized and investigated for their inhibitory effects on platelet aggregation. Among them, compound 3a showed anticoagulant effects comparable to aspirin, while compound 4b showed dose-independent inhibitory activities in rats that were stronger than aspirin.

Transcriptome analysis endoplasmic reticulum-stress response in Litopenaeus vannamei hemocytes.

Numerous studies have proved that endoplasmic reticulum (ER)-stress is an important cause of aquatic animal diseases. Therefore, for effectively preventing and controlling aquatic animal diseases, a systematic and in-depth understanding of the environmental stress response in aquatic animals is necessary. In present study, the influence of ER-stress in Litopenaeus vannamei was investigated using Illumina HiSeq based RNA-Seq. Comparing to the cDNA library of hemocytes treated with DMSO in L. vannamei, 286 unigenes were significantly upregulated and 473 unigenes were significantly down-regulated in the Thapsigargin treated group. KEGG analysis indicated that the differentially expressed genes (DEGs) are mainly related to ER-stress, immune as well as metabolism. Besides the classical ER-stress response pathways, the regulation of cell cycle and DNA replication are also important measures of ER-stress response. It has been suggested that the influence of ER-stress on immune genes might be an important factor in environmental stress inducing shrimp disease. Our investigation exhibited that immune-related DEG Prophenoloxidase activating enzyme 2 (LvPPAE2) roled in anti-pathogen immunity of shrimp. This study provides a solid foundation for uncovering the environmental adaptation response and especially its relationship with L. vannamei immune system.

A IFI27 gene contributes to ER-stress mediated apoptosis and benefits for white spot syndrome virus infection in Litopenaeus vannamei.

The interplay between virus and host has been one of the hot spot in virology, and it is also the important aspect of revealing the mechanism of virus infection. Increasing studies revealed that several key molecules took part in the process of virus-host interaction. White spot syndrome virus (WSSV) has been proved to affect several physiological processes of the host cells, especially apoptosis. While the relationship between them still remains unclear. In this study, a IFI27 gene (LvIFI27) of Litopenaeus vannamei was cloned. It is indicated that LvIFI27 was induced upon endoplasmic reticulum (ER)-stress and unfolded protein response activator Thapsigargin. Unlike human IFI27 locating to mitochondria, LvIFI27 lied to ER, and was involved in cell apoptosis process. Moreover, results of cumulative mortality analysis showed that LvIFI27 might contributed to WSSV proliferation by promoting apoptosis during the process of viral infection. Findings in this study enriched our understanding of the relationship between WSSV infection and ER-stress mediated apoptosis.

Transcriptome analysis of the influence of high plant protein based diet on Trachinotus ovatus liver.

Seeking out fish meal (FM) alternatives is an important requirement for aquaculture all over the world. And most practitioners believe that the plant protein is most potential for FM surrenal. While high plant protein feed caused some common problems in aquatic livestock: the absorption rate and growth rate are decreased, and even caused digestive tract inflammation. In present study, the inflence of high plant protien feed in Trachinotus ovatus was investigated using illumina HiSeqTM2000 based RNA-Seq. By comparing the two groups of cDNA libraries developed from high plant protien based diet or FM based diet fed T. ovatus livers, 836 unigenes were significantly upregulated, and 345 were significantly down regulated. KEGG analysis indicated that the differentially expressed genes (DEGs) are mainly metabolic-related genes. It was found that more than 28 DGEs beloned to the protein metabolism and absorption, lipid biosynthesis or other metabolic pathways. It indicated that high plant protein based diet had broad effects on metabolism on T. ovatus. There were also more DEGs belong to immune-related signaling pathways, include genes were involved in pathpathogen resistance and genes related to immunity system. These DEGs provided useful clues to explore the mechanisms that high plant protein based diet caused side effects on T. ovatus. These results improved our current understanding of the response of high plant protein based diet in T. ovatus, and outstanding the reasons of the side effect caused by high protein based diet.

A Litopenaeus vannamei TRIM32 gene is involved in oxidative stress response and innate immunity.

Tripartite motif (TRIM) family proteins are named by the presence of tripartite motifs in their amino terminal domains. Apart from the amino terminal, their carboxyl terminal contain variable domains which mediate diverse functions of the TRIM proteins. It had been found that TRIM proteins played important roles in distinct biological processes, such as innate immunity, anti-tumor immunity, cell cycle regulation and so on. In the present study, we cloned a TRIM32 (LvTRIM32) gene from Litopenaeus vannamei. LvTRIM32 was highly expressed in hemocytes, gills and epidermis, and subcellular localization analysis indicated that it was widely distributed in S2 cells. In vitro ubiquitination assays indicated that LvTRIM32 had E3 ubiquitin ligase activity. Results of real-time RT-PCR assay showed that LvTRIM32 was induced in shrimp hemocytes upon oxidative stress. It was also proved that the promoter activity of LvTRIM32 was enhanced by NF-E2-related factor, and knocked-down expression of LvTRIM32 depressed the expression of malic enzyme and epoxide hydrolase. Downregulated LvTRIM32 suppressed the cumulative mortality of shrimp under oxidative stress. Moreover, it was found that LvTRIM32 could be induced in shrimp hemocytes upon immunostimulation, and downregulated LvTRIM32 increased the cumulative mortality of shrimp infected with white spot syndrome virus (WSSV) or Vibrio alginolyticus. Collecting results suggested that LvTRIM32 was a member of shrimp antioxidant stress system, and it was also involved in WSSV- or V. alginolyticus-infection resistance.

Identification and functional characterization of a C-type lectin gene from Litopenaeus vannamei that is associated with ER-stress response.

C-type lectins (CTLs), which bind carbohydrates in a Ca2+-dependent manner, are involved in many cellular activities, especially immunity. CTLs play important roles in both the antibacterial and the antiviral immune response and are also associated with autoimmunity. Several CTLs have been investigated in crustaceans, primarily with respect to their function in the immune response. In this study, we cloned a novel CTL gene (LvCTLU) from Litopenaeus vannamei. LvCTLU is involved in microbe agglutination and phagocytosis. Downregulating LvCTLU increased the cumulative mortality of L. vannamei after Vibrio parahemolyticus infection. Similar to other reported CTLs, LvCTLU also had antiviral properties. Downregulation of LvCTLU also increased the cumulative mortality of L. vannamei after infection with white spot syndrome virus. More importantly, LvCTLU expression was induced by the unfolded protein response (UPR), which is the key pathway in the endoplasmic reticulum (ER)-stress response of eukaryotic organism. Our results suggested that this protein might be involved in the shrimp ER-stress response. Reporter gene assay indicated that LvCTLU was regulated by X-box-binding protein 1, which is the key transcription factor in the UPR. Our study thus revealed that LvCTLU plays vital roles in both the anti-pathogen immune response and the ER-stress response.

[Advances of transforming growth factor-ß inhibitors].

Transforming growth factor-ß is an important cytokine with various bioactivities, including embryonic development, wound healing, chemotaxis and cell cycle regulation. Epithelial-mesenchymal transition (EMT) is the main pathway of tumor cell to obtain the ability of invasion and metastasis. The TGF-ß is the key factor known to induce EMT in cancer cells and plays an important role in the process. In recent years, some progress has been obtained. Some TGF-ß inhibitors have approved in the market or in clinical trials. TGF-ß inhibitors can play an important role on the treatment of tumors, glaucoma, liver and kidney fibrosis disease and scar repair. Novel TGF-ß inhibitors reported in recent years were reviewed in this article.

[Study on Archaeological Lime Powders from Taosi and Yinxu Sites by FTIR].

Archaeological lime powders samples from Taosi and Yinxu sites, natural limestone and experimentally prepared lime mortar were investigated by means of Fourier transform infrared spectrometry (FTIR) to identify the raw material of lime powders from Taosi and Yinxu sites. Results show that ν2/ν4 ratio of calcite resulted from carbonation reaction of man-made lime is around 6.31, which is higher than that of calcite in natural limestone and reflects the difference in the disorder of calcite crystal structure among the natural limestone and prepared lime mortar. With additional grinding, the values of v2 and ν4 in natural limestone and prepared lime mortar decrease. Meanwhile, the trend lines of ν2 versus ν4 for calcite in experimentally prepared lime mortar have a steeper slope when compared to calcite in natural limestone. These imply that ν2/ν4 ratio and the slope of the trend lines of ν2 versus ν4 can be used to determine the archaeological man-made lime. Based on the experiment results, it is possible that the archaeological lime powder from Taosi and Yinxu sites was prepared using man-made lime and the ancient Chinese have mastered the calcining technology of man-made lime in the late Neolithic period about 4 300 years ago.

[Ilizarov technique combined with center of rotation dome-shaped osteotomy for the treatment of juvenile distal femoral valgus deformity].

OBJECTIVE: To investigate the effect of Ilizarov technique combined with rotational center dome-shaped osteotomy in the treatment of juvenile distal femoral valgus deformity. METHODS: A retrospective study was conducted to analyze the clinical data of 11 patients with valgus deformity of the distal femur who had been admitted and followed up completely from January 2016 to October 2020. There were 7 males and 4 females. The 6 patients were on the right side and 5 patients were on the left side. The age ranged from 10 to 14 years old. The center of roration of angulation(CORA) was identified at the distal femur deformity, and dome-shaped osteotomy was performed with the CORA as the midpoint. The annular external fixator was installed according to the needle threading principle of Ilizarov external fixation, and the distal femur was cut off. The valgus deformity under visual inspection of the distal femur was corrected immediately, and the external fixator was fixed and maintained. The residual deformity and shortening were corrected according to the force line and length of the lower limbs suggested by the weight-bearing full-length anteroposterior and lateral X-rays of both lower limbs. RESULTS: All 11 patients were followed up for 13 to 25 months. The time of wearing external fixator was 12 to 17 weeks. In the last follow-up, both lower limbs were measured by the weight-bearing full-length anteroposterior and lateral X-rays, and the length of both lower limbs of 11 patients were equal, and the deformities were corrected. The score of hospital for special surgery (HSS) was used to evaluate the knee function, all of which were excellent. CONCLUSION: The Ilizarov technique was applied in the treatment of distal femoral valgus deformity in adolescents using a rotating central dome-shaped osteotomy. Visual femoral valgus deformity was corrected immediately during the operation. After the operation, residual deformities and shortening were dynamically adjusted and corrected according to the force line and shortening degree of lower extremities indicated by the weight-bearing anteroposterior and lateral radiographs of both lower limbs, with minimal damage and fast recovery.

Discovery of a small molecular compound simultaneously targeting RXR and HADC: design, synthesis, molecular docking and bioassay.

Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for anti-cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we have designed and synthesized a novel compound which targets both RXR and HADC. This dual-targeting agent is derived from bexarotene and suberoylanilide hydroxamic acid (SAHA), prototypical RXR agonist and HDAC inhibitor, respectively. Molecular docking studies demonstrate that this agent has a relatively strong affinity to RXR and HADC. Importantly, it presents the potentials of activation of RXR and inhibition of HDAC in both cell-free and whole-cell assays, and displays anti-proliferative effect on representative cancer cell lines and drug-resistant cancer cell lines.