Design of an optical passive semi-athermalization zoom lens.

Traditional zoom lenses cannot clearly image during the entire zoom process when the ambient temperature changes and needs to focus frequently at middle focal length positions. An innovative design method called the optical passive semi-athermalization (OPSA) design for zoom optical systems is proposed which, based on the difference in the focusing sensitivity of the focusing group at short and long focal length positions, seeks out sensitive groups that have a greater impact on the imaging quality at the short focal position. By changing the temperature characteristics of the temperature-sensitive lenses in these groups, an OPSA zoom optical system can be realized, which exhibits a compact structure and excellent imaging quality. Under the ambient temperature of -40∘ C to +60∘ C, the OPSA zoom lens needs to refocus only once at the long focal length position, which can ensure an image clearly during the entire zoom process. Remarkably, this innovative method not only mitigates the frequent focusing challenges in traditional zoom lenses, but also contributes to the diminutive size.

Protein Structure Inspired Drug Discovery.

Drug discovery starts with known function, either of a compound or a protein, in-turn prompting investigations to probe 3D structure of the compound-protein interface. As protein structure determines function, we hypothesized that unique 3D structural motifs represent primary information denoting unique function that can drive discovery of novel agents. Using a physics-based protein structure analysis platform developed by us, designed to conduct computationally intensive analysis at supercomputing speeds, we probed a high-resolution protein x-ray crystallographic library developed by us. We selected 3D structural motifs whose function was not otherwise established, that offered environments supporting binding of drug-like chemicals and were present on proteins that were not established therapeutic targets. For each of eight potential binding pockets on six different proteins we accessed a 60 million compound library and used our analysis platform to evaluate binding. Using eight-day colony formation assays acquired compounds were screened for efficacy against human breast, prostate, colon and lung cancer cells and toxicity against human bone marrow stem cells. Compounds selectively inhibiting cancer growth segregated to two pockets on separate proteins. The compound, Dxr2-017, exhibited selective activity against human melanoma cells in the NCI-60 cell line screen, had an IC50 of 19 nM against human melanoma M14 cells in our eight-day assay, while over 2100-fold higher concentrations inhibited stem cells by less than 30%. We show that Dxr2-017 induces anoikis, a unique form of programmed cell death in need of targeted therapeutics. The predicted target protein for Dxr2-017 is expressed in bacteria, not in humans. This supports our strategy of focusing on unique 3D structural motifs. It is known that functionally important 3D structures are evolutionarily conserved. Here we demonstrate proof-of-concept that protein structure represents high value primary data to support discovery of novel therapeutics. This approach is widely applicable.

Optical design of a visible/short-wave infrared common-aperture optical system with a long focal length and a wide field-of-view.

Addressing the urgent need for long-distance dim target detection with a wide field-of-view and high sensitivity, this paper proposes a visible and short-infrared dual-band common-aperture optical system characterized by a broad field and extended focal length. To achieve system miniaturization and high-sensitivity target detection, the visible and infrared optical systems share a Ritchey-Chretien primary and secondary mirror. The primary optical path is segmented into visible light (0.45-0.75 µm) and short-wave infrared (SWIR) (2-3 µm) bands by a dichroic spectral splitter prism. The SWIR optical system utilizes four short-wave cooled infrared detectors, and wide-field stitching is achieved using a field-of-view divider. While ensuring the high cold-shield efficiency of cooled infrared detectors, this common-aperture optical system delivers visible and SWIR dual-band images with expansive fields, elongated focal lengths, and sizable apertures. The visible-light optical system has a focal length of 277 mm, a field-of-view of 2.3∘×2.3∘, and an entrance pupil diameter of 130 mm. Meanwhile, the SWIR optical system features a focal length of 480 mm, a field-of-view of 2.26∘×1.8∘ and an entrance pupil diameter of 160 mm. The design outcomes suggest that the imaging quality of the optical system approaches the diffraction limit. This visible/SWIR common-aperture optical system exhibits high sensitivity, a large field-of-view, compact structure, and excellent imaging quality, thereby meeting the requirements for long-distance dim target detection and imaging.

Oleaginous Microalga Coccomyxa subellipsoidea as a Highly Effective Cell Factory for CO2 Fixation and High-Protein Biomass Production by Optimal Supply of Inorganic Carbon and Nitrogen.

Microalgae used for CO2 biofixation can effectively relieve CO2 emissions and produce high-value biomass to achieve "waste-to-treasure" bioconversion. However, the low CO2 fixation efficiency and the restricted application of biomass are currently bottlenecks, limiting the economic viability of CO2 biofixation by microalgae. To achieve high-efficient CO2 fixation and high-protein biomass production, the oleaginous microalga Coccomyxa subellipsoidea (C. subellipsoidea) was cultivated autotrophically through optimizing inorganic carbon and nitrogen supply. 0.42 g L-1 NaHCO3 supplemented with 2% CO2 as a hybrid carbon source resulted in high biomass concentration (3.89 g L-1) and productivity (318.33) with CO2 fixation rate 544.21 mg L-1 d-1 in shake flasks. Then, used in a 5-L photo-fermenter, the maximal protein content (60.93% DW) in batch 1, and the highest CO2 fixation rate (1043.95 mg L-1 d-1) with protein content (58.48% DW) in batch 2 of repeated fed-batch cultures were achieved under 2.5 g L-1 nitrate. The relative expression of key genes involved in photosynthesis, glycolysis, and protein synthesis showed significant upregulation. This study developed a promising approach for enhancing carbon allocation to protein synthesis in oleaginous microalga, facilitating the bioconversion of the fixed carbon into algal protein instead of oil in green manufacturing.

Itraconazole-Induced the Activation of Adenosine 5'-Monophosphate (Amp)-Activated Protein Kinase Inhibits Tumor Growth of Melanoma via Inhibiting ERK Signaling.

Itraconazole, an effective broad-spectrum antifungal drug, has been well established for its anticancer activity in cancers including melanoma. However, details concerning its underlying mechanism in melanoma are unclear. This work investigated the function of itraconazole-induced 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα) in melanoma progression through ERK signaling. The AMPKα level in melanoma tissues and cells was assessed by RT-qPCR and western blot. Survival analysis of patients with melanoma based on the AMPKα expression level was performed according to TCGA database. Melanoma cell proliferation, migration, and invasion were examined using CCK-8, colony formation, wound healing, and Transwell assays. A xenograft tumor model was established to examine the effect of itraconazole on tumor growth in vivo. The AMPKα mRNA and protein levels were reduced in melanoma tissues and cells. A low expression of AMPKα indicated a poor prognosis. Functionally, itraconazole restrained melanoma cell proliferation, migration, and invasion by upregulating AMPKα. Itraconazole activated AMPK signaling and inhibited ERK signaling in melanoma cells. Activation of ERK signaling reversed the effect of itraconazole on cellular process in melanoma. Moreover, itraconazole-induced AMPKα inhibited melanoma tumor growth in vivo by inhibiting ERK signaling. Itraconazole-induced AMPKα inhibits the progression of melanoma by inhibition of ERK signaling.

Biotechnological advances for improving natural pigment production: a state-of-the-art review.

In current years, natural pigments are facing a fast-growing global market due to the increase of people's awareness of health and the discovery of novel pharmacological effects of various natural pigments, e.g., carotenoids, flavonoids, and curcuminoids. However, the traditional production approaches are source-dependent and generally subject to the low contents of target pigment compounds. In order to scale-up industrial production, many efforts have been devoted to increasing pigment production from natural producers, via development of both in vitro plant cell/tissue culture systems, as well as optimization of microbial cultivation approaches. Moreover, synthetic biology has opened the door for heterologous biosynthesis of pigments via design and re-construction of novel biological modules as well as biological systems in bio-platforms. In this review, the innovative methods and strategies for optimization and engineering of both native and heterologous producers of natural pigments are comprehensively summarized. Current progress in the production of several representative high-value natural pigments is also presented; and the remaining challenges and future perspectives are discussed.

Mixotrophic Chlorella pyrenoidosa as cell factory for ultrahigh-efficient removal of ammonium from catalyzer wastewater with valuable algal biomass coproduction through short-time acclimation.

To achieve ultrahigh-efficient ammonium removal and valuable biomass coproduction, Chlorella-mediated short-time acclimation was implemented in photo-fermentation. The results demonstrated short-time acclimation of mixotrophic Chlorella pyrenoidosa could significantly improve NH4+ removal and biomass production in shake flasks. After acclimation through two batch cultures in 5-L photo-fermenter, the maximum NH4+ removal rate (1,400 mg L-1 d-1) were achieved under high NH4+ level (4,750 mg L-1) in batch 3. In 50-L photo-fermenter, through one batch acclimated culture, the maximum NH4+ removal rate (2,212 mg L-1 d-1) and biomass concentration (58.4 g L-1) were achieved in batch 2, with the highest productivities of protein (5.56 g L-1 d-1) and total lipids (5.66 g L-1 d-1). The hypothetical pathway of nutrients assimilation in mixotrophic cells as cell factory was proposed with detailed discussion. This study provided a novel strategy for high-ammonium wastewater treatment without dilution, facilitating the algae-based "waste-to-treasure" bioconversion process for green manufacturing.

Functional Attributes and Anticancer Potentialities of Chico (Pachycereus Weberi) and Jiotilla (Escontria Chiotilla) Fruits Extract.

Mexico has a great diversity of cacti, however, many of their fruits have not been studied in greater depth. Several bioactive compounds available in cacti juices extract have demonstrated nutraceutical properties. Two cactus species are interesting for their biologically active pigments, which are chico (Pachycereus weberi (J. M. Coult.) Backeb)) and jiotilla (Escontria chiotilla (Weber) Rose)). Hence, the goal of this work was to evaluate the bioactive compounds, i.e., betalains, total phenolic, vitamin C, antioxidant, and mineral content in the extract of the above-mentioned P. weberi and E. chiotilla. Then, clarified extracts were evaluated for their antioxidant activity and cytotoxicity (cancer cell lines) potentialities. Based on the obtained results, Chico fruit extract was found to be a good source of vitamin C (27.19 ± 1.95 mg L-Ascorbic acid/100 g fresh sample). Moreover, chico extract resulted in a high concentration of micronutrients, i.e., potassium (517.75 ± 16.78 mg/100 g) and zinc (2.46 ± 0.65 mg/100 g). On the other hand, Jiotilla has a high content of biologically active pigment, i.e., betaxanthins (4.17 ± 0.35 mg/g dry sample). The antioxidant activities of clarified extracts of chico and jiotilla were 80.01 ± 5.10 and 280.88 ± 7.62 mg/100 g fresh sample (DPPH method), respectively. From the cytotoxicity perspective against cancer cell lines, i.e., CaCo-2, MCF-7, HepG2, and PC-3, the clarified extracts of chico showed cytotoxicity (%cell viability) in CaCo-2 (49.7 ± 0.01%) and MCF-7 (45.56 ± 0.05%). A normal fibroblast cell line (NIH/3T3) was used, as a control, for comparison purposes. While jiotilla extract had cytotoxicity against HepG2 (47.31 ± 0.03%) and PC-3 (53.65 ± 0.04%). These results demonstrated that Chico and jiotilla are excellent resources of biologically active constituents with nutraceuticals potentialities.

Overall survival prediction of non-small cell lung cancer by integrating microarray and clinical data with deep learning.

Non-small cell lung cancer (NSCLC) is one of the most common lung cancers worldwide. Accurate prognostic stratification of NSCLC can become an important clinical reference when designing therapeutic strategies for cancer patients. With this clinical application in mind, we developed a deep neural network (DNN) combining heterogeneous data sources of gene expression and clinical data to accurately predict the overall survival of NSCLC patients. Based on microarray data from a cohort set (614 patients), seven well-known NSCLC biomarkers were used to group patients into biomarker- and biomarker+ subgroups. Then, by using a systems biology approach, prognosis relevance values (PRV) were then calculated to select eight additional novel prognostic gene biomarkers. Finally, the combined 15 biomarkers along with clinical data were then used to develop an integrative DNN via bimodal learning to predict the 5-year survival status of NSCLC patients with tremendously high accuracy (AUC: 0.8163, accuracy: 75.44%). Using the capability of deep learning, we believe that our prediction can be a promising index that helps oncologists and physicians develop personalized therapy and build the foundation of precision medicine in the future.

In vitro anti-inflammatory effects of curcumin on mast cell-mediated allergic responses via inhibiting FcεRI protein expression and protein kinase C delta translocation.

Allergy is a hypersensitivity reaction when exposed to certain environmental substances. It shows high relation between immunoglobulin E (IgE) binding to a specific receptor (FcεRI), pro-inflammatory cytokines, and mediators with allergic inflammation responses. Curcumin is a yellow pigment isolated from the turmeric. Curcumin possesses antioxidant and anti-inflammatory properties as well as exhibits significant chemopreventive activity. This study was aimed to investigate the in vitro assessment of the regulation of curcumin on allergic inflammatory responses on rat basophil leukemia (RBL)-2H3 and human pre-basophils (KU812) cell lines. Curcumin showed the activity against histamine and ß-hexosaminidase releases from both IgE-mediated and A23187-induced cells degranulation. The morphological observation also confirmed that curcumin inhibits cells degranulation. IgE-mediated allergic responses and significantly induced mast cells intracellular reactive oxygen species (ROS) production. Curcumin reduced ROS production from IgE-mediated or A23187-induced cells degranulation. Curcumin also successfully reduced FcεRI expressions and some pro-inflammatory cytokines, such as interleukin (IL)-4 and IL-13. Furthermore, curcumin inhibited protein kinase C (PKC)-δ translocation from cytosolic to particulate. These results suggested that curcumin can alleviate both the IgE-mediated and calcium ionosphere A23187-stimulated allergic responses through reducing the release of the allergic mediators.

The mixed culture of microalgae Chlorella pyrenoidosa and yeast Yarrowia lipolytica for microbial biomass production.

Microbial biomass which mostly generated from the microbial processes of bacteria, yeasts, and microalgae is an important resource. Recent concerns in microbial biomass production field, especially microbial lipid production for biofuel, have been focused towards the mixed culture of microalgae and yeast. To more comprehensive understanding of the mixed culture for microbial biomass, mono Chlorella pyrenoidosa, mono Yarrowia lipolytica and the mixed culture were investigated in the present work. Results showed that the mixed culture achieved significantly faster cell propagation of microalga and yeast, smaller individual cell size of yeast and higher relative chlorophyll content of microalga. The mixed culture facilitated the assimilation of carbon and nitrogen and drove the carbon flow to carbohydrate. Besides higher lipid yield (0.77 g/L), higher yields of carbohydrates (1.82 g/L), protein (1.99 g/L) and heating value (114.64 kJ/L) indicated the microbial biomass harvested from the mixed culture have more potential utilization in renewable energy, feedstuff, and chemical industry.

Efficient resource recycling from liquid digestate by microalgae-yeast mixed culture and the assessment of key gene transcription related to nitrogen assimilation in microalgae.

To determine the feasibility of microalgae-yeast mixed culture using the liquid digestate of dairy wastewater (LDDW) for biofuels and single cell protein (SCP) production, the cell growth, nutrient removal and outputs evaluation of the mono and mixed culture of Chlorella vulgaris and Yarrowia lipolytica in LDDW were investigated by adding glycerol as carbon source. The results showed that the mixed culture could enhance the biological utilization efficiency of nitrogen and phosphorus, and obtain higher yield of biomass (1.62 g/L), lipid (0.31 g/L), protein (0.51 g/L), and higher heating value (34.06 KJ/L). Compared with the mono culture of C. vulgaris, a decline of the transcription level in nitrate reductase and glutamine synthetase II genes in C. vulgaris was observed in the mixed culture when ammonia was sufficient. The results suggest the possibility of using the mixed culture for the efficient treatment of LDDW and resources recycling.

Metabolomic profiling of Rhodosporidium toruloides grown on glycerol for carotenoid production during different growth phases.

Carotenoid production from three strains of Rhodosporidium toruloides grown on glycerol was studied. A time-dependent metabolomics approach was used to understand its metabolism on glycerol and mechanism for carotenoid production in three strains during different growth phases (1, 4, 7, and 12 days). Strain CBS 5490 was the highest carotenoid producer (28.5 mg/L) and had a unique metabolic profile. In this strain, metabolites belonging to the TCA cycle and amino acids were produced in lower amounts, as compared to the other strains. On the other hand, it produced the highest amounts of carotenoid and fatty acid metabolites. This indicated that the lower production of the TCA cycle and amino acid metabolites promoted energy and metabolic flux toward the carotenoid and fatty acid synthesis metabolic pathways. This study shows that metabolomic profiling is a useful tool to gain insight into the metabolic pathways in the cell and to shed light on the different molecular mechanisms between strains.

[Energy accumulation and caloric value in yield-forming process of different rice cultivars].

Based on the determination of dry matter and caloric value, this paper studied the characteristics of energy accumulation and the dynamics of caloric value in the yield-forming process of rice cultivars Shanyou 63 ( three-line hybrid rice) , Liangyou 2186 (two-line hybrid rice) , and IR64 (conventional rice). The results showed that at fully grain-maturing stage, the amount of dry matter in Shanyou 63, Liangyou 2186 and IR64 was 1926. 38 g x m(2), 1933.80 g x m(-2) and 1842.30 g x m(-2), and that of accumulated energy was 31,137.05 kJ x m(-2) 31 060.63 kJ x m(-2) and 30 454.89 kJ x m(-2) , respectively, showing no significant difference among the cultivars. In the process of grain filling, the apparent transformation ratio of energy in Shanyou 63, Liangyou 2186 and IR64 was about 38. 95% , 28. 38% and 32. 66% , respectively, implying that the energy flow in Shanyou 63 and IR 64 was smoother than that in Liangyou 2186, and the output of energy from stem to the sink of grain was blocked in Liangyou 2186. The ratio of energy partitioning to the sink of grain was 53. 03% , 46. 43% and 50. 11% for Shanyou 63, Liangyou 2186 and IR64, respectively, showing the energy partitioning heterosis in three-line hybrid rice Shanyou 63. As for the caloric value, it had no significant difference among the three cultivars, but decreased in the order of leaf> grain > sheath > stem > root, ranging from 16.81-17.25 kJ x g(-1) , 15.89-16.54 kJ x g (-1) 14.33-15.49 kJ x g(-1) , 14.23-15.15 kJ x g , and 11.51-13.25 kJ x g(-1), respectively. It was also shown that there was a significant positive correlation of caloric value with carbon content, chlorophyll a content, and nitrogen content in rice plant, with the determination coefficient R(2) being 0.609, 0.471 and 0.485, respectively.

Host heterogeneous ribonucleoprotein K (hnRNP K) as a potential target to suppress hepatitis B virus replication.

BACKGROUND: Hepatitis B virus (HBV) infection results in complications such as cirrhosis and hepatocellular carcinoma. Suppressing viral replication in chronic HBV carriers is an effective approach to controlling disease progression. Although antiviral compounds are available, we aimed to identify host factors that have a significant effect on viral replication efficiency. METHODS AND FINDINGS: We studied a group of hepatitis B carriers by associating serum viral load with their respective HBV genomes, and observed a significant association between high patient serum viral load with a natural sequence variant within the HBV enhancer II (Enh II) regulatory region at position 1752. Using a viral fragment as an affinity binding probe, we isolated a host DNA-binding protein belonging to the class of heterogeneous nuclear ribonucleoproteins--hnRNP K--that binds to and modulates the replicative efficiency of HBV. In cell transfection studies, overexpression of hnRNP K augmented HBV replication, while gene silencing of endogenous hnRNP K carried out by small interfering RNAs resulted in a significant reduction of HBV viral load. CONCLUSION: The evidence presented in this study describes a wider role for hnRNP K beyond maintenance of host cellular functions and may represent a novel target for pharmacologic intervention of HBV replication.

[Cellular ultrastructural changes of bone marrow of patients with hemorrhagic fever with renal syndrome].

BACKGROUND: To observe cytopathogenic effect of Hantaan virus (HV) on cultured human bone marrow cells. METHODS: Light and transmission electron microscopy and direct immunofluorescent technique were applied to study cellular structure especially ultrastructural changes of bone marrow cells from patients with Hantaan virus infection. Bone marrow cells of one healthy volunteer were also studied as control. RESULTS: The antigen of HV was found in bone marrow cells of 20 of 27 HFRS patients by the aid of direct immunofluorescent technique. It was found that the granulocytes had the highest percentage of HV antigen positive cells (76%), followed by monocytes (65%), lymphocytes (40%), megakaryocytes (20%) and the lowest was found in erythrocytes (3.7%). The injury of cell membrane after infection with HV was significantly more severe than that in the control group under the light and electron microscopy. CONCLUSION: This study demonstrated that HV could attack human bone marrow cells and cause cytopathogenic effect on them.