Genomic and transcriptomic studies on flavonoid biosynthesis in Lagerstroemia indica.

BACKGROUND: Lagerstroemia indica is a widely cultivated ornamental woody shrub/tree of the family Lythraceae that is used as a traditional medicinal plant in East Asia and Egypt. However, unlike other ornamental woody plants, its genome is not well-investigated, which hindered the discovery of the key genes that regulate important traits and the synthesis of bioactive compounds. RESULTS: In this study, the genomic sequences of L. indica were determined using several next-generation sequencing technologies. Altogether, 324.01 Mb sequences were assembled and 98.21% (318.21 Mb) of them were placed in 24 pseudo-chromosomes. The heterozygosity, repeated sequences, and GC residues occupied 1.65%, 29.17%, and 38.64% of the genome, respectively. In addition, 28,811 protein-coding gene models, 327 miRNAs, 552 tRNAs, 214 rRNAs, and 607 snRNAs were identified. The intra- and interspecies synteny and Ks analysis revealed that L. indica exhibits a hexaploidy. The co-expression profiles of the genes involved in the phenylpropanoid (PA) and flavonoid/anthocyanin (ABGs) pathways with the R2R3 MYB genes (137 members) showed that ten R2R3 MYB genes positively regulate flavonoid/anthocyanin biosynthesis. The colors of flowers with white, purple (PB), and deep purplish pink (DPB) petals were found to be determined by the levels of delphinidin-based (Dp) derivatives. However, the substrate specificities of LiDFR and LiOMT probably resulted in the different compositions of flavonoid/anthocyanin. In L. indica, two LiTTG1s (LiTTG1-1 and LiTTG1-2) were found to be the homologs of AtTTG1 (WD40). LiTTG1-1 was found to repress anthocyanin biosynthesis using the tobacco transient transfection assay. CONCLUSIONS: This study showed that the ancestor L. indica experienced genome triplication approximately 38.5 million years ago and that LiTTG1-1 represses anthocyanin biosynthesis. Furthermore, several genes such as LiDFR, LiOMTs, and R2R3 LiMYBs are related to anthocyanin biosynthesis. Further studies are required to clarify the mechanisms and alleles responsible for flower color development.

Growth of Scenedesmus obliquus on anaerobic soybean wastewater using different wasted organics for high biomass production and nutrients recycling.

The microalgae culture in mixing sewage with different characteristics may significantly improve biomass production and nutrients recycling efficiency. In this study, three waste organic wastewater including molasses, alcohol and glycerol wastewater were mixed with anaerobic soybean wastewater as mediums for microalgae culture. The optimal mixture of molasses, alcohol and glycerol wastewater was at an initial carbon-nitrogen ratio of 7:1, 5:1 and 10:1, improving biomass production by 60.4%, 31.3% and 68.7%, respectively. The removal efficiencies of organics, ammonia nitrogen and phosphorus at optimal mixture were 54.8-62.4%, 79.5-99.1% and 49.3-61.5%, and the removal rates increased by 340-630%, 27.5-66.3% and 36.3-70.2% compared to the blank culture. In addition, the culture in mixed wastewater increased lipids contrast by 0.7-1.3 times, while achieving higher saturation in fatty acids. The results suggested that microalgae culture using mixed wastewater was a strategy for high biomass production and nutrients recycling efficiency.

Lessons on Drug Development: A Literature Review of Challenges Faced in Nonalcoholic Fatty Liver Disease (NAFLD) Clinical Trials.

NAFLD is the most common chronic liver disease worldwide, occurring in both obese and lean patients. It can lead to life-threatening liver diseases and nonhepatic complications, such as cirrhosis and cardiovascular diseases, that burden public health and the health care system. Current care is weight loss through diet and exercise, which is a challenging goal to achieve. However, there are no FDA-approved pharmacotherapies for NAFLD. This review thoroughly examines the clinical trial findings from 22 drugs (Phase 2 and above) and evaluates the future direction that trials should take for further drug development. These trialed drugs can broadly be categorized into five groups-hypoglycemic, lipid-lowering, bile-pathway, anti-inflammatory, and others, which include nutraceuticals. The multitude of challenges faced in these yet-to-be-approved NAFLD drug trials provided insight into a few areas of improvement worth considering. These include drug repurposing, combinations, noninvasive outcomes, standardization, adverse event alleviation, and the need for precision medicine with more extensive consideration of NAFLD heterogenicity in drug trials. Understandably, every evolution of the drug development landscape lies with its own set of challenges. However, this paper believes in the importance of always learning from lessons of the past, with each potential improvement pushing clinical trials an additional step forward toward discovering appropriate drugs for effective NAFLD management.

Pyrolysis of Aesculus chinensis Bunge Seed with Fe2O3/NiO as nanocatalysts for the production of bio-oil material.

The rapid thermal cracking technology of biomass can convert biomass into bio-oil and is beneficial for industrial applications. Agricultural and forestry wastes are important parts of China's energy, and their high-grade utilization is useful to solve the problem of energy shortages and environmental pollution. To the best of our knowledge, the impact of nanocatalysts on converting biowastes for bio-oil has not been studied. Consequently, we examined the production of bio-oil by pyrolysis of Aesculus chinensis Bunge Seed (ACBS) using nanocatalysts (Fe2O3 and NiO catalysts) for the first time. The pyrolysis products of ACBS include 1-hydroxy-2-propanone (3.97%), acetic acid (5.42%), and furfural (0.66%). These chemical components can be recovered for use as chemical feedstock in the form of bio-oil, thus indicating the potential of ACBS as a feedstock to be converted by pyrolysis to produce value-added bio-oil. The Fe2O3 and NiO catalysts enhanced the pyrolysis process, which accelerated the precipitation of gaseous products. The pyrolysis rates of the samples gradually increased at DTGmax, effectively promoting the catalytic cracking of ACBS, which is beneficial to the development and utilization of ACBS to produce high valorization products. Combining ACBS and nanocatalysts can change the development direction of high valorization agricultural and forestry wastes in the future.

Conversion from spermatogonia to spermatocytes: Extracellular cues and downstream transcription network.

Spermatocyte (spc) formation from spermatogonia (spg) differentiation is the first step of spermatogenesis which produces prodigious spermatozoa for a lifetime. After decades of studies, several factors involved in the functioning of a mouse were discovered both inside and outside spg. Considering the peculiar expression and working pattern of each factor, this review divides the whole conversion of spg to spc into four consecutive development processes with a focus on extracellular cues and downstream transcription network in each one. Potential coordination among Dmrt1, Sohlh1/2 and BMP families mediates Ngn3 upregulation, which marks progenitor spg, with other changes. After that, retinoic acid (RA), as a master regulator, promotes A1 spg formation with its helpers and Sall4. A1-to-B spg transition is under the control of Kitl and impulsive RA signaling together with early and late transcription factors Stra8 and Dmrt6. Finally, RA and its responsive effectors conduct the entry into meiosis. The systematic transcription network from outside to inside still needs research to supplement or settle the controversials in each process. As a step further ahead, this review provides possible drug targets for infertility therapy by cross-linking humans and mouse model.

KIFC1 is essential for acrosome formation and nuclear shaping during spermiogenesis in the lobster Procambarus clarkii.

In order to study the function of kinesin-14 motor protein KIFC1 during spermatogenesis of Procambarus clarkii, the full length of kifc1 was cloned from testes cDNA using Rapid-Amplification of cDNA Ends (RACE). The deduced KIFC1 protein sequence showed the highest similarity between Procambarus clarkii and Eriocheir senensis (similarity rate as 64%). According to the results of in situ hybridization (ISH), the kifc1 mRNA was gathered in the acrosome location above nucleus in the mid- and late-stage spermatids. Immunofluorescence results were partly consistent with the ISH in middle spermatids, while in the late spermatids the KIFC1 was distributed around the nucleus which had large deformation and formed four to six nuclear arms. In the mature sperm, KIFC1 and microtubules were distributed around the sperm, playing a role in maintaining the sperm morphology and normal function. Overexpression of P. clarkii kifc1 in GC1 cells for 24 hours resulted in disorganization of microtubules which changed the cell morphology from circular and spherical into fusiform. In addition, the overexpression also resulted in triple centrosomes during mitosis which eventually led to cell apoptosis. RNAi experiments showed that decreased KIFC1 protein levels resulted in total inhibition of spermatogenesis, with only mature sperm found in the RNAi-testis, implying an indispensable role of KIFC1 during P. clarkii spermiogenesis.

Enhancement of hypothalamic STAT3 acetylation by nuclear receptor Nur77 dictates leptin sensitivity.

Leptin, an anorexigenic hormone in the hypothalamus, suppresses food intake and increases energy expenditure. Failure to respond to leptin will lead to obesity. Here, we discovered that nuclear receptor Nur77 expression is lower in the hypothalamus of obese mice compared with normal mice. Injection of leptin results in significant reduction in body weight in wild-type mice but not in Nur77 knockout (KO) littermates or mice with specific Nur77 knockdown in the hypothalamus. Hypothalamic Nur77 not only participates in leptin central control of food intake but also expands leptin's reach to liver and adipose tissues to regulate lipid metabolism. Nur77 facilitates signal transducer and activator of transcription 3 (STAT3) acetylation by recruiting acetylase p300 and disassociating deacetylase histone deacetylase 1 (HDAC1) to enhance the transcriptional activity of STAT3 and consequently modulates the expression of downstream gene Pomc in the hypothalamus. Nur77 deficiency compromises response to leptin in mice fed a high-fat diet. Severe leptin resistance in Nur77 KO mice with increased appetite, lower energy expenditure, and hyperleptinemia contributes to aging-induced obesity. Our study opens a new avenue for regulating metabolism with Nur77 as the positive modulator in the leptin-driven antiobesity in the hypothalamus.

Molecular regulation of hypothalamus-pituitary-gonads axis in males.

The hypothalamic-pituitary-gonadal axis (HPG) plays vital roles in reproduction and steroid hormone production in both sexes. The focus of this review is upon gene structures, receptor structures and the signaling pathways of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The hormones' functions in reproduction as well as consequences resulting from mutations are also summarized. Specific characteristics of hormones such as the pulsatile secretions of GnRH are also covered. The different regulators of the HPG axis are introduced including kisspeptin, activin, inhibin, follistatin, androgens and estrogen. This review includes not only their basic information, but also their unique function in the HPG axis. Here we view the HPG axis as a whole, so relations between ligands and receptors are well described crossing different levels of the HPG axis. Hormone interactions and transformations are also considered. The major information of this article is depicted in three figures summarizing the current discoveries on the HPG axis. This article systematically introduces the basic knowledge of the HPG axis and provides information of the current advances relating to reproductive hormones.

The apoptotic function analysis of p53, Apaf1, Caspase3 and Caspase7 during the spermatogenesis of the Chinese fire-bellied newt Cynops orientalis.

BACKGROUND: Spontaneous and stress-induced germ cell apoptosis during spermatogenesis of multicellular organisms have been investigated broadly in mammals. Spermatogenetic process in urodele amphibians was essentially like that in mammals in spite of morphological differences; however, the mechanism of germ cell apoptosis in urodele amphibians remains unknown. The Chinese fire-belly newt, Cynops orientalis, was an excellent organism for studying germ cell apoptosis due to its sensitiveness to temperature, strong endurance of starvation, and sensitive skin to heavy metal exposure. METHODOLOGY/PRINCIPAL FINDINGS: TUNEL result showed that spontaneous germ cell apoptosis took place in normal newt, and severe stress-induced apoptosis occurred to spermatids and sperm in response to heat shock (40°C 2 h), cold exposure (4°C 12 h), cadmium exposure (Cd 36 h), and starvation stress. Quantitative reverse transcription polymerase chain reactions (qRT-PCR) showed that gene expression of Caspase3 or Caspase7 was obviously elevated after stress treatment. Apaf1 was not altered at its gene expression level, and p53 was significantly decreased after various stress treatment. Caspase assay demonstrated that Caspase-3, -8, -9 enzyme activities in newt testis were significantly elevated after heat shock (40°C 2 h), cold exposure (4°C 12 h), and cadmium exposure (Cd 36 h), while Caspase3 and Caspase8 activities were increased with Caspase9 significantly decreased after starvation treatment. CONCLUSIONS/SIGNIFICANCE: Severe germ cell apoptosis triggered by heat shock, cold exposure, and cadmium exposure was Caspase3 dependent, which probably involved both extrinsic and intrinsic pathways. Apaf1 may be involved in this process without elevating its gene expression. But starvation-induced germ cell apoptosis was likely mainly through extrinsic pathway. p53 was probably not responsible for stress-induced germ cell apoptosis in newt testis. The intriguing high occurrence of spermatid and sperm apoptosis probably resulted from the sperm morphology and unique reproduction policy of Chinese fire-belly newt, Cynops orientalis.