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An applied example is also provided to demonstrate proof of concept. We conclude with recommendations for practitioners when the asymptotic correction works well under different conditions and also future directions.Quality fish feed is the prime need for successful aquaculture. Feed qualities determine the fish flesh quality including appearance, color, odor, flavor, texture, nutritive value, and shelf-life. Nowadays, consumers are very much concerned about various issues regarding way of fish farming, types of feed ingredients used etc. The current study was conducted to assess the heavy metal contents and nutritional composition of some selected commercial fish feeds used in Bangladesh. The major heavy metal concentrations and proximate composition (moisture, crude protein, crude lipid, ash, crude fiber, and carbohydrate) of the collected feed samples were analyzed. The results showed that the feeds contained a number of heavy metals in varying proportions. The highest concentrations (mg/kg) of heavy metals such as lead (Pb), cadmium (Cd), chromium (Cr), copper (Cu), and zinc (Zn) analyzed in fish feed samples were 0.189, 0.027, 1.023, 0.303, and 1.468, respectively. There were significant differences between the nutritive values provided by feed companies and the values observed in this finding. The present study recommends that adequate measures are required to be taken by commercial fish feed manufacturers to ensure the nutritional quality of feed as well as to avoid the contamination of feed from heavy metals. Otherwise, fish and human, the ultimate consumer, may be predisposed to the assimilation and accumulation of the assessed heavy metals.Biomonitoring of synanthropic species provides evidence about effects of the pollution in human environment. In the present study, tibia and tarsometatarsal bones were extracted from feral pigeons (Columba livia), found either deceased, or experimentally captured in the lofts of houses in Bratislava, Slovakia. Concentrations of mercury (tarsometatarsus), lead, iron, and zinc (tibia) were analyzed, along with sex and plumage pattern, wing, and tarsometatarsal length. In order to estimate age, lines of arrested growth (LAGs) were used. Results show no significant differences in heavy metal accumulation depending on sex or plumage pattern. However, age-related tarsometatarsus length was correlated to Hg, Pb, and Fe bone level accumulation. Thus, bigger or older pigeons with longer tarsometatarsal bones had higher Hg, Pb, and Fe concentrations. Higher heavy metal concentrations (mainly Fe and Zn) were also present in bones of older deceased individuals with completed LAG. These findings point to chronic accumulation of heavy metals in feral pigeons during their life in polluted environments.Plastidial Δ12 fatty acid desaturase (FAD6) is a key enzyme for linoleic acid (LA) and α-linolenic acid (ALA) biosynthesis. Chia (Salvia hispanica L.) is a revived omega-3 plant source that is richest in ALA level. In this study, based on the RACE method, one full-length cDNA sequence encoding FAD6, named ShFAD6, was isolated from chia. There exist three alternative transcription start sites and five alternative poly(A) tailing sites in ShFAD6. The 5'UTR of ShFAD6 contains a purine-stretch of 44 bp. ShFAD6 has an ORF of 1335 bp encoding a 444 aa protein of 51.33 kDa. ShFAD6 contains a conserved Delta12-FADS-like domain together with three strong trans-membrane helices and three histidine motifs. There also exists a chloroplast transmit peptide in ShFAD6 N-terminal. Phylogenetic analyses validated its identity of dicot FAD6 protein and suggested some critical evolutionary features of plant FAD6 genes. selleck chemical Heterologous yeast expression confirmed the catalytic activity of ShFAD6. The qRT-PCR assay showed that ShFAD6 is mainly expressed in leaves, stems, flowers, buds and early-stage seeds, and also responded to various stresses and hormone treatments. Under Sclerotinia infection, qRT-PCR and fluorescence imaging illustrated the possible correlation of ShFAD6 expression and photosynthesis. This study provides insight for further function study of ShFAD6 in oil quality improvement in staple oilseed crops as well as stress response and adaptation in plants.

PD-L1 expression predicts response to immune checkpoint inhibitors in renal cell carcinomas (RCC), but has also been suggested to be linked to poor patient outcome.

We analyzed PD-L1 in > 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8

cytotoxic cells.

At a cut-off level of 5% PD-L1 positive tumor cells, PD-L1 positivity was seen in 6.3% of 633 clear cell RCC (ccRCC), 18.2% of 165 papillary RCC, 18.8% of 64 chromophobe RCC, and 41.7% of 103 oncocytomas. In ccRCC, PD-L1 positivity was significantly linked to high ISUP (p < 0.0001), Fuhrman (p < 0.0001), Thoenes grade (p < 0.0001), distant metastasis (p = 0.0042), short recurrence-free (p < 0.0001), and overall survival (p = 0.0002). Intratumoral CD8

lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; p < 0.0001). PD-L positive immune cells were seen in 8.2% of all RCC and 13.9% of papillary RCC. In ccRCC, PD-L1 positive immune cells were linked to high numbers of tumor-infiltrating CD8

cells (p < 0.0001), high ISUP (p < 0.0001), Fuhrman (p = 0.0027), and Thoenes grade (p < 0.0001), and poor tumor-specific survival (p = 0.0280).

These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.

These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.Circadian rhythms are ubiquitous phenomena that recur daily in a self-sustaining, entrainable, and oscillatory manner, and orchestrate a wide range of molecular, physiological, and behavioral processes. Circadian clocks are comprised of a hierarchical network of central and peripheral clocks that generate, sustain, and synchronize the circadian rhythms. The functioning of the peripheral clock is regulated by signals from autonomic innervation (from the central clock), endocrine networks, feeding, and other external cues. The critical role played by circadian rhythms in maintaining both systemic and tissue-level homeostasis is well established, and disruption of the rhythm has direct consequence for human health, disorders, and diseases. Circadian oscillations in both pharmacokinetics and pharmacodynamic processes are known to affect efficacy and toxicity of several therapeutic agents. A variety of modeling approaches ranging from empirical to more complex systems modeling approaches have been applied to characterize circadian biology and its influence on drug actions, optimize time of dosing, and identify opportunities for pharmacological modulation of the clock mechanisms and their downstream effects.