Effects of swine manure dilution with lagoon effluent on microbial communities and odor formation in pit recharge systems.

Pit recharge systems (PRS) control odor by managing organic solids in swine manure. However, there needs to be more understanding of PRS's effect on the microbiome composition and its impact on odor formation. A study was conducted to understand how recharge intervals used in PRS impact manure microbiome and odor formation.

Pan-cancer analysis reveals multifaceted roles of retrotransposon-fusion RNAs.

Transposon-derived transcripts are abundant in RNA sequences, yet their landscape and function, especially for fusion transcripts derived from unannotated or somatically acquired transposons, remains underexplored. Here, we developed a new bioinformatic tool to detect transposon-fusion transcripts in RNA-sequencing data and performed a pan-cancer analysis of 10,257 cancer samples across 34 cancer types as well as 3,088 normal tissue samples. We identified 52,277 cancer-specific fusions with ~30 events per cancer and hotspot loci within transposons vulnerable to fusion formation.

Crif1 deficiency in dopamine neurons triggers early-onset parkinsonism.

Mitochondrial dysfunction has been implicated in Parkinson's Disease (PD) progression; however, the mitochondrial factors underlying the development of PD symptoms remain unclear. One candidate is CR6-interacting factor1 (CRIF1), which controls translation and membrane insertion of 13 mitochondrial proteins involved in oxidative phosphorylation. Here, we found that CRIF1 mRNA and protein expression were significantly reduced in postmortem brains of elderly PD patients compared to normal controls.

Evaluation of Actual Ventilation Rates and Efficiency in Research-Scale Pig Houses Based on Ventilation Configurations.

Accurate ventilation control is crucial for maintaining a healthy and productive environment in research-specialized pig facilities. This study aimed to evaluate actual ventilation rates and ventilation efficiency by investigating different inlet and exhaust configurations. The research was conducted in two pig rooms, namely pig room A and pig room B, in the absence of animals and workers to focus solely on evaluating the ventilation system's performance.

Impact of Bacillus subtilis on manure solids, odor, and microbiome.

A study was conducted to determine the effectiveness of supplementing swine manure with Bacillus subtilis (BS) to improve digestion of manure solids and lower odor emission. Large bioreactors (400 L) with manure (100 L) were treated with commercially available BS at a rate of 1% manure volume by either directly pouring or surface spraying the manure with inoculum. Manure physicochemical properties, gas emissions, and microbiome were monitored.

Pyruvate Prevents Dopaminergic Neurodegeneration and Motor Deficits in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopamine(DA)rgic neurons in the substantia nigra of the midbrain, and primarily causes motor symptoms. While the pathological cause of PD remains uncertain, oxidative damage, neuroinflammation, and energy metabolic perturbation have been implicated. Pyruvate has been shown neuroprotective in animal models for many neurological disorders, presumably owing to its potent anti-oxidative, anti-inflammatory, and energy metabolic properties.

Functional Characterization of Arylalkylamine -Acetyltransferase, a Pivotal Gene in Antioxidant Melatonin Biosynthesis from .

Arylalkylamine N-acetyltransferase (AANAT) is a pivotal enzyme in melatonin biosynthesis that catalyzes the conversion of serotonin to N-acetylserotonin. Homologs of animal AANAT genes are present in animals, but not in plants. An AANAT homolog was found in Chlamydomonas reinhardtii, but not other green algae.

Molecular Regulation of Antioxidant Melatonin Biosynthesis by Brassinosteroid Acting as an Endogenous Elicitor of Melatonin Induction in Rice Seedlings.

Gibberellic acid (GA) was recently shown to induce melatonin synthesis in rice. Here, we examined whether brassinosteroids (BRs) also induce melatonin synthesis because BRs and GA show redundancy in many functions. Among several plant hormones, exogenous BR treatment induced melatonin synthesis by twofold compared to control treatment, whereas ethylene, 6-benzylaminopurine (BA), and indole-3-acetic acid (IAA) showed negligible effects on melatonin synthesis.

Phytomelatonin as a signaling molecule for protein quality control via chaperone, autophagy, and ubiquitin-proteasome systems in plants.

Physiological effects mediated by melatonin are attributable to its potent antioxidant activity as well as its role as a signaling molecule in inducing a vast array of melatonin-mediated genes. Here, we propose melatonin as a signaling molecule essential for protein quality control (PQC) in plants. PQC occurs by the coordinated activities of three systems: the chaperone network, autophagy, and the ubiquitin-proteasome system.

Exogenous Gibberellin Treatment Enhances Melatonin Synthesis for Melatonin-Enriched Rice Production.

Melatonin production is induced by many abiotic and biotic stressors; it modulates the levels of many plant hormones and their signaling pathways. This study investigated the effects of plant hormones on melatonin synthesis. Melatonin synthesis in rice seedlings was significantly induced upon exogenous gibberellin 3 (GA) treatment, while it was severely decreased by GA synthesis inhibitor paclobutrazol.

Phase I and scintigraphy studies to evaluate safety, tolerability, pharmacokinetics, and lung deposition of inhaled GDC-0214 in healthy volunteers.

Several inflammatory cytokines that promote inflammation and pathogenesis in asthma signal through the Janus kinase 1 (JAK1) pathway. This phase I, randomized, placebo-controlled trial assessed the pharmacokinetics and safety of single and multiple ascending doses up to 15 mg twice daily for 14 days of a JAK1 inhibitor, GDC-0214, in healthy volunteers (HVs; n = 66). Doses were administered with a dry powder, capsule-based inhaler.

A Novel Pyrazolo[3,4-]pyrimidine Induces Heme Oxygenase-1 and Exerts Anti-Inflammatory and Neuroprotective Effects.

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin-1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells.

The Potential and Limitations of Precision Oncology: Lessons Learned from Whole-Exome Sequencing in an Exceptional Response to Everolimus in Advanced Renal Cell Carcinoma.

Through elucidating the genetic mechanisms of drug sensitivity, precision medicine aims to improve patient selection and response to therapy. Exceptional responders are patients that exhibit exquisite and durable responses to targeted therapy, providing a rare opportunity to identify the molecular basis of drug sensitivity. We identified an exceptional responder to everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR) pathway, in a patient with advanced renal cell carcinoma.

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo-controlled study.

Methods: Patients who had moderately to severely active SLE while receiving background standard therapy were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily.

Meta-analysis identifies the effect of dietary multi-enzyme supplementation on gut health of pigs.

Gut health though is not well defined the role of gastrointestinal tract is vital if an animal must perform well. Apart from digestion, secretion, and absorption gut is harbored with consortium of microbiota which plays a key role in one's health. Enzymes, one of the alternatives for antibiotics with beneficial effects on digestion and consistency of food and its effect on gut health.

Comprehensive analysis of microbial dynamics linked with the reduction of odorous compounds in a full-scale swine manure pit recharge system with recirculation of aerobically treated liquid fertilizer.

It is believed that the generation of odorous materials in manure-slurry pits during the storage can be reduced by recirculating aerobically treated liquid fertilizer (ATLF) to a manure-pit recharge system (PRS). However, the biological mechanisms for reduction of those problematic compounds remain poorly understood. In this study, the links between microbial evolution and changes in chemical composition and odorous compounds were analyzed where swine-manure slurry was stored in a full-scale PRS.

Suppression of Rice Cryptochrome 1b Decreases Both Melatonin and Expression of Brassinosteroid Biosynthetic Genes Resulting in Salt Tolerance.

We investigated the relationship between the blue-light photoreceptor cryptochrome (CRY) and melatonin biosynthesis by generating RNA interference (RNAi) transgenic rice plants that suppress the gene (). The resulting RNAi rice lines expressed less mRNA, but not or mRNA, suggesting that the suppression is specific to . The growth of RNAi rice seedlings was enhanced under blue light compared to wild-type growth, providing phenotypic evidence for impaired CRY function.

Swine manure dilution with lagoon effluent impact on odor reduction and manure digestion.

Manure management systems have a major impact on odor from swine operations. A study was conducted to compare deep-pit manure management systems to flushing barn manure management systems for odor reduction and organic matter degradation. Bioreactors were used to mimic manure management systems in which manure and lagoon effluent were loaded initially, and subsequent manure was added daily at 5% of its storage capacity (1 L).

A novel pyrazolo [3,4-d] pyrimidine, KKC080106, activates the Nrf2 pathway and protects nigral dopaminergic neurons.

The transcription factor nuclear factor-erythroid 2-related factor-2 (Nrf2) is known to induce neuroprotective and anti-inflammatory effects and is considered to be an excellent molecular target for drugs related to neurodegenerative disease therapy. Nrf2 activators previously tested in clinical trials were electrophilic, causing adverse effects due to non-selective and covalent modification of cellular thiols. In order to circumvent this issue, we constructed and screened a chemical library consisting of 241 pyrazolo [3,4-d] pyrimidine derivatives and discovered a novel, non-electrophilic compound: 1-benzyl-6-(methylthio)-N-(1-phenylethyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine (KKC080106).

Hypoxia Pretreatment Promotes Chondrocyte Differentiation of Human Adipose-Derived Stem Cells via Vascular Endothelial Growth Factor.

Background: Human adipose tissue-derived stem cells (ADSCs) are attractive multipotent stem cell sources with therapeutic potential in various fields requiring repair and regeneration, such as acute and chronically damaged tissues. ADSC is suitable for cell-based therapy, but its use has been hampered due to poor survival after administration. Potential therapeutic use of ADSC requires mass production of cells through in vitro expansion.

Effects of Light Quality and Phytochrome Form on Melatonin Biosynthesis in Rice.

Light is an important factor influencing melatonin synthesis in response to cadmium treatment in rice. However, the effects of light quality on, and the involvement of phytochrome light receptors in, melatonin production have not been explored. In this study, we used light-emitting diodes (LEDs) to investigate the effect of light wavelength on melatonin synthesis, and the role of phytochromes in light-dependent melatonin induction in rice.

Simultaneous Suppression of Two Distinct Serotonin -Acetyltransferase Isogenes by RNA Interference Leads to Severe Decreases in Melatonin and Accelerated Seed Deterioration in Rice.

Serotonin -acetyltransferase () is the penultimate enzyme in the melatonin biosynthetic pathway, in which serotonin is converted into -acetylserotonin () in plants. To date, two isogenes with low amino acid sequence homologies have been identified. Their single suppression in rice has been reported, but their double suppression in rice has not yet been attempted.

Influence of Baseline Cardiovascular Comorbidities on Mortality after Androgen Deprivation Therapy for Metastatic Prostate Cancer.

Few studies have assessed the benefits of androgen deprivation therapy (ADT) in men with metastatic prostate cancer (PC; mPC) at an old age or with major cardiovascular conditions. A retrospective cohort consisted of 3835 men with newly diagnosed mPC from the Taiwan Cancer Registry of 2008-2014. Among them, 2692 patients received only ADT in the first year after the cancer diagnosis, and 1143 patients were on watchful waiting.