A strategy to reduce the byproduct glucose by simultaneously producing levan and single cell oil using an engineered Yarrowia lipolytica strain displaying levansucrase on the surface.

Currently, levan is attracting attention due to its promising applications in the food and biomedical fields. Levansucrase synthesizes levan by polymerizing the fructosyl unit in sucrose. However, a large amount of the byproduct glucose is produced during this process. In this paper, an engineered oleaginous yeast (Yarrowia lipolytica) strain was constructed using a surface display plasmid containing the LevS gene of Gluconobacter sp. MP2116. The levansucrase activity of the engineered yeast strain reached 327.8 U/g of cell dry weight. The maximal levan concentration (58.9 g/l) was achieved within 156 h in the 5-liter fermentation. Over 81.2 % of the sucrose was enzymolyzed by the levansucrase, and the byproduct glucose was converted to 21.8 g/l biomass with an intracellular oil content of 25.5 % (w/w). The obtained oil was comprised of 91.3 % long-chain fatty acids (C16-C18). This study provides new insight for levan production and comprehensive utilization of the byproduct in levan biosynthesis.

Health Effects of Peptides Extracted from Deer Antler.

Deer antler is widely used as a nutraceutical in Asian countries. In the past decades, deer antler peptides (DAPs) have received considerable attention because of their various biological properties such as antioxidant, anti-inflammatory, anti-bone damage, anti-neurological disease, anti-tumor and immunomodulatory properties. This review describes the production methods of DAPs and the recent progress of research on DAPs, focusing on the physiological functions and their regulatory mechanisms.

Peptides Isolated from Amphibian Skin Secretions with Emphasis on Antimicrobial Peptides.

The skin of amphibians is a tissue with biological functions, such as defense, respiration, and excretion. In recent years, researchers have discovered a large number of peptides in the skin secretions of amphibians, including antimicrobial peptides, antioxidant peptides, bradykinins, insulin-releasing peptides, and other peptides. This review focuses on the origin, primary structure, secondary structure, length, and functions of peptides secreted from amphibians' skin. We hope that this review will provide further information and promote the further study of amphibian skin secretions, in order to provide reference for expanding the research and application of amphibian bioactive peptides.

Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne.

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Association of Serum Magnesium with Insulin Resistance and Type 2 Diabetes among Adults in China.

Magnesium is an essential mineral for the human body and a cofactor or activator for more than 300 enzymatic reactions, including blood glucose control and insulin release. Diabetes is a well-known global burden of disease with increasing global prevalence. In China, the prevalence of diabetes in adults is higher than the global average. Evidence shows that magnesium is a predictor of insulin resistance and diabetes. However, the majority of studies focus on dietary magnesium instead of serum magnesium concentration. We study the correlation of serum magnesium levels with insulin resistance and Type 2 diabetes. In this prospective cohort study, we included 5044 participants aged 18 years and older without insulin resistance (IR) and diabetes at the baseline from China Health and Nutrition Survey (CHNS). A fasting blood sample was taken for the measurement of both types of magnesium, fasting blood glucose, hemoglobin A1c (HbA1c), and fasting insulin. The homeostatic model (HOMA-IR) was calculated. Demographic characteristics of participants, and risk factors such as intensity of physical activities, smoking status, drinking habit, and anthropometric information were recorded. IR was defined as HOMA-IR ≥ 2.5, and Type 2 diabetes mellitus was defined as fasting plasma glucose ≥ 7.0 mmol/L or HbA1c ≥ 6.5%, or a self-reported diagnosis or treatment of diabetes. A total of 1331 incident insulin resistance events and 429 incident diabetic events were recorded during an average follow-up of 5.8 years. The serum magnesium concentration was categorized into quintiles. After adjusting for relevant covariates, the third quintile of serum magnesium (0.89−0.93 mmol/L) was correlated with 29% lower risk of incident insulin resistance (hazard ratio = 0.71, 95% CI 0.58, 0.86) and with a lower risk of Type 2 diabetes. Multivariable-adjusted hazard ratios (95% confidence intervals) for insulin resistance were compared with the lowest quintile of serum magnesium (<0.85). We found similar results when evaluating serum magnesium as a continuous measure. Restricted cubic spline (RCS) curves showed a nonlinear dose−response correlation in both serum magnesium levels and insulin resistance, and in serum magnesium levels and Type 2 diabetes. Lower serum magnesium concentration was associated with a higher risk of insulin resistance and diabetes.

Hematological changes in patients with COVID­19 (Review).

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.

[Thrombopoietin promotes megakaryopoiesis via protecting bone marrow endothelial function in patients undergoing chemotherapy for hematological malignancies].

OBJECTIVE: To explore whether thrombopoietin (TPO) can rescue megakaryopoiesis by protecting bone marrowderived endothelial progenitor cells (BM-EPCs) in patients receiving chemotherapy for hematological malignancies. METHODS: Bone marrow samples were collected from 23 patients with hematological malignancies 30 days after chemotherapy and from 10 healthy volunteers. BM-EPCs isolated from the samples were identified by staining for CD34, CD309 and CD133, and their proliferation in response to treatment with TPO was assessed using CCK8 assay. DiL-Ac-LDL uptake and FITC-UEA-I binding assay were performed to evaluate the amount of BM-EPCs from the subjects. Tube-formation and migration experiments were used for functional assessment of the BM-EPCs. The BM-EPCs with or without TPO treatment were co-cultured with human megakaryocytes, and the proliferation of the megakaryocytes was detected with flow cytometry. RESULTS: Flow cytometry indicated that the TPO-treated cells had high expressions of CD34, CD133, and CD309. CCK8 assay demonstrated that TPO treatment enhanced the proliferation of the BM-EPCs, and the optimal concentration of TPO was 100 µg/L. Double immunofluorescence assay indicated that the number of BM-EPC was significantly higher in TPO-treated group than in the control group. The TPO-treated BM-EPCs exhibited stronger tube-formation and migration abilities (P < 0.05) and more significantly enhanced the proliferation of co-cultured human megakaryocytes than the control cells (P < 0.05). CONCLUSIONS: TPO can directly stimulate megakaryopoiesis and reduce hemorrhage via protecting the function of BM-EPCs in patients following chemotherapy for hematological malignancies.

Long noncoding RNA TP73-AS1 accelerates the epithelial ovarian cancer via epigenetically repressing p21.

Evidence has indicated the important roles of long non-coding RNAs (lncRNAs) in the human cancer biology, providing potential targets for cancer intervention. However, the expression profile and function of lncRNA TP73-AS1 in human epithelial ovarian cancer (EOC) remain to be investigated. In the EOC specimens and cell lines, TP73-AS1 was identified to be significantly up-regulated. EOC patients with high TP73-AS1 expression had poor survival rate. The gain and loss of functional assay uncovered that TP73-AS1 promoted the proliferation, invasion and reduced the apoptosis of EOC cells in vitro. And, the knockdown of TP73-AS1 inhibited the tumor growth in vivo. By using chromatin immunoprecipitation and luciferase reporter assay, we identified TP73-AS1 epigenetically repressed p21 via recruiting EZH2. In conclusion, this finding supports that TP73-AS1 promotes the EOC progression via epigenetically repressing p21, serving as a prognosis predictor for EOC patients.

Suppressing autophagy protects photoreceptor cells from light-induced injury.

Autophagy, a conserved cellular self-degradation process, not only serves to protect cells at critical times during development and nutrient stress, but also contributes to cell death. Photoreceptor cells are unique neurons which when directly exposed to the light, transduces light stimuli into visual signal. However, intense light exposure can be cytotoxic to the retina. So far, the precise mechanism underlying retina light injury remains unknown, and the effective therapy is still unavailable. Here, we found that visible light exposure activated the mitogen-activated protein kinases (MAPK) pathway and led to remarkable autophagy in photoreceptor cells (661W cells). Directly blocking autophagy with 3MA or LY294002 markedly attenuated light-induced death in 661W cells. Among the activated downstream factors of MAPK pathway, ERK, not JNK or p-38, played a critical role in light-induced death mechanism. Inhibiting the activation of ERK with its specific inhibitor PD98059 significantly suppressed light-induced autophagy and protected 661W cells from light injury. These results indicate that autophagy is an essential event in light-induced photoreceptor death and that directly blocking autophagy or suppressing autophagy by inhibiting the ERK pathway could effectively attenuates light-induced damage. These observations may have a potential application in the treatment of retinal light injury.

Rapamycin attenuates visible light-induced injury in retinal photoreceptor cells via inhibiting endoplasmic reticulum stress.

An extended exposure of the retina to visible light may lead to photochemical damage in retinal photoreceptor cells. The exact mechanism of retinal light damage remains unknown, and an effective therapy is still unavailable. Here, we demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), markedly protected 661W photoreceptor cells from visible light exposure-induced damage at the nanomolar level. We also observed by transmission electron microscopy that light exposure led to severe endoplasmic reticulum (ER) stress in 661W cells as well as abnormal endomembranes and ER membranes. In addition, obvious upregulated ER stress markers were monitored by western blot at the protein level and by quantitative reverse transcription-polymerase chain reaction (RT-PCR) at the mRNA level. Interestingly, rapamycin pretreatment significantly suppressed light-induced ER stress and all three major branches of the unfolded protein response (UPR), including the RNA-dependent protein kinase-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) pathways both at the protein and mRNA levels. Additionally, the inhibition of ER stress by rapamycin was further confirmed with a dithiothreitol (DTT; a classical ER stress inducer)-damaged 661W cell model. Meanwhile, our results also revealed that rapamycin was able to remarkably inhibit the activation of mTOR and its downstream factors eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), p-4EBP1, p70, p-p70, and phosphorylated ribosomal protein S6 kinase (p-S6K) in the light-injured 661W cells. Thus, these data indicate that visible light induces ER stress in 661W cells; whereas the mTOR inhibitor, rapamycin, effectively protects 661W cells from light injury through suppressing the ER stress pathway.