Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrogen Source Matters: High NH4/NO3 Ratio Reduces Cannabinoids, Terpenoids, and Yield in Medical Cannabis

The N form supplied to the plant, ammonium (NH4+) or nitrate (NO3–), is a major factor determining the impact of N nutrition on plant function and metabolic responses. We have hypothesized that the ratio of NH4/NO3 supplied to cannabis plants affects the physiological function and the biosynthesis of cannabinoids and terpenoids, which are major factors in the cannabis industry. To evaluate the hypothesis we examined the impact of five supply ratios of NH4/NO3 (0, 10, 30, 50, and 100% N-NH4+, under a uniform level of 200 mg L–1 N) on plant response. The plants were grown in pots, under controlled environment conditions. The results revealed high sensitivity of cannabinoid and terpenoid concentrations and plant function to NH4/NO3 ratio, thus supporting the hypothesis. The increase in NH4 supply generally caused an adverse response: Secondary metabolite production, inflorescence yield, plant height, inflorescence length, transpiration and photosynthesis rates, stomatal conductance, and chlorophyll content, were highest under NO3 nutrition when no NH4 was supplied. Ratios of 10–30% NH4 did not substantially impair secondary metabolism and plant function, but produced smaller inflorescences and lower inflorescence yield compared with only NO3 nutrition. Under a level of 50% NH4, the plants demonstrated toxicity symptoms, which appeared only at late stages of plant maturation, and 100% NH4 induced substantial plant damage, resulting in plant death. This study demonstrates a dramatic impact of N form on cannabis plant function and production, with a 46% decrease in inflorescence yield with the increase in NH4 supply from 0 to 50%. Yet, moderate levels of 10–30% NH4 are suitable for medical cannabis cultivation, as they do not damage plant function and show only little adverse influence on yield and cannabinoid production. Higher NH4/NO3 ratios, containing above 30% NH4, are not recommended since they increase the potential for a severe and fatal NH4 toxicity damage.
Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo

Bacterial infections have become increasingly difficult to treat due to the occurrence of antibiotic-resistant strains. A promising strategy to increase the efficacy of therapy is to combine antibacterials with agents that decrease pathogen virulence via the modulation of the quorum sensing (QS). Lactonases inhibit acylated homoserine lactone (AHL)-mediated QS in Gram-negative bacteria, including the leading nosocomial pathogen Pseudomonas aeruginosa. Here we describe the characteristics of heterologously expressed YtnP lactonase from Bacillus paralicheniformis ZP1 (YtnP-ZP1) isolated from agricultural soil using the culture enrichment method. Purified YtnP-ZP1 hydrolyzed different AHLs with preference to substrates with long acyl residues as evaluated in assays with biosensors and HPLC. The enzyme showed good thermostability and activity in a wide temperature range. YtnP-ZP1 in 50 μg mL–1 concentration reduced the amount of P. aeruginosa-produced long-chain AHLs by 85%, while it hydrolyzed 50% of short-chain AHLs. Incubation of P. aeruginosa PAO1 with YtnP-ZP1 reduced its swarming motility and elastolytic activity without bactericidal effect. YtnP-ZP1 caused the inhibition of biofilm formation and disintegration of mature biofilms in P. aeruginosa PAO1 and multiresistant clinical strain BR5H that was visualized by crystal violet staining. The treatment with YtnP-ZP1 in concentrations higher than 25 μg mL–1 improved the survival of P. aeruginosa PAO1-infected zebrafish (Danio rerio), rescuing 80% of embryos, while in combination with tobramycin or gentamicin survival rate increased to 100%. The treatment of P. aeruginosa PAO1 biofilms on infected zebrafish tail wounds with 50 μg mL–1 YtnP-ZP1 and 2 × MIC tobramycin led to infection clearing in 2 days. The extensive toxicity studies proved YtnP-ZP1 was non-toxic to human cells and zebrafish. In conclusion, novel YtnP-ZP1 lactonase with its effective anti-virulence activity could be used to increase the efficacy of clinically approved antibiotics in clearing both systemic and biofilm-associated P. aeruginosa infections.
The Responses of Lactobacillus reuteri LR1 or Antibiotic on Intestinal Barrier Function and Microbiota in the Cecum of Pigs

This study aimed to investigate responses of the Lactobacillus reuteri or an antibiotic on cecal microbiota and intestinal barrier function in different stages of pigs. A total of 144 weaned pigs (Duroc × Landrace × Yorkshire, 21 days of age) were randomly assigned to the control group (CON, fed with a basal diet), the antibiotic group (AO, fed with basal diet plus 100 mg/kg olaquindox and 75 mg/kg aureomycin), and the L. reuteri group (LR, fed with the basal diet + 5 × 1010 CFU/kg L. reuteri LR1) throughout the 164-d experiment. A total of 45 cecal content samples (5 samples per group) from different periods (14th, 42th, and 164th days) were collected for 16S rRNA gene amplification. The results revealed that although LR and AO did not change the diversity of cecal microbiota in pigs, the abundance of some bacteria at the genus level was changed with age. The proportion of Lactobacillus was increased by LR in early life, whereas it was decreased by AO compared with the control group. The relative abundance of Ruminococcaceae was increased along with age. In addition, the gas chromatography results showed that age, not AO or LR, has significant effects on the concentrations of SCFAs in the cecum of pigs (P < 0.05). However, the mRNA expression of tight junction proteins zonula occluden-1 (ZO-1) and occludin were increased by AO in the cecum of pigs on day 14, while LR increased the mRNA expression of intestinal barrier-related proteins ZO-1, occludin, mucin-1, mucin-2, PG1-5, and pBD2 in the cecum of pigs on days 14 and 164 (P < 0.05). In conclusion, LR and AO have different effects on the intestinal barrier function of the cecum, and neither LR nor AO damaged the intestinal barrier function of pig cecum. In addition, LR and AO have little effects on cecal microflora in different stages of the pigs. The microflora and their metabolite SCFAs were significantly changed along with age. These findings provide important information to understand the homeostasis of the cecum of pigs after antibiotic or probiotic treatment.
Counterproductive Academic Behaviors and Academic Performance: A Meta-Analysis and a Path Analysis Model

Counterproductive academic behaviors (CAB) are a complex phenomenon that affects academic institutions in multiple geographical areas with different cultures, values, and social norms. The high incidence of CAB causes problems of critical importance that transcend the educational domain. The current study aims to contribute to the knowledge of the CAB consequences by focusing on its impact on academic performance (AP). For this purpose, a meta-analysis was conducted in order to examine the relationship between CAB, its facets, and AP. The results show that overall CAB and students' performance are negatively related with a true effect size of ρ = −0.40 (K = 231, N = 127,269). Particularly, absenteeism appeared to be the facet most strongly related to AP (ρ = −0.48, K = 117, N = 69,453). A meta-analytic path analysis model was carried out in order to test the predictive validity of CAB, students' personality characteristics, and intelligence on AP. Results show that conscientiousness and cognitive intelligence have a negative relationship with CAB (β = −0.28 and β = −0.20, respectively), and that conscientiousness, openness to experience, intelligence, and CAB can explain 58% of AP true variance. Meta-analyses of moderator variables and hierarchical meta-analyses are also presented. The implications for research and practice are discussed at the end.
Polyvinylpyrrolidone-Modified Taxifolin Liposomes Promote Liver Repair by Modulating Autophagy to Inhibit Activation of the TLR4/NF-κB Signaling Pathway

Taxifolin (TAX) is a hepatoprotective flavanol compound, which is severely limited by poor solubility and low bioavailability. Liposomes (Lips) are used as well-recognized drug carrier systems that improve the water solubility and bioavailability of drugs, but are easily damaged by gastric juice after oral administration, resulting in the release of drugs in the gastric juice. Therefore, it is important to find materials that modify liposomes and avoid the destruction of the liposomal phospholipid bilayer structure by the gastrointestinal environment. Taxifolin liposomes (TAX-Lips) were modified by polyvinylpyrrolidone-k30 (PVP-TAX-Lips) and manufactured using a thin-film hydration technique. Particle size (109.27 ± 0.50 nm), zeta potential (−51.12 ± 3.79 mV), polydispersity coefficient (PDI) (0.189 ± 0.007), and EE (84.7 ± 0.2%) of PVP-TAX-Lips were studied. In addition, the results of in vitro release experiments indicated that the cumulative release rates of TAX-Lips and PVP-TAX-Lips were 89.73 ± 5.18% and 65.66 ± 4.86% in the simulated gastric fluid after 24 h, respectively, while the cumulative release rates were 68.20 ± 4.98% and 55.66 ± 3.92% in the simulated intestinal fluid after 24 h, respectively. Moreover, PVP-TAX-Lips were able to reverse lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced acute liver injury (ALI) by inducing autophagy to inhibit the expression levels of the TLR4/NF-κB signaling pathway and inflammatory factors, which suggested that PVP-TAX-Lips played an important role in the prevention of ALI and also provided a promising drug delivery system for the application of TAX.
A Novel and Easy-to-Promote Prognostic Model for Patients With Uveal Melanoma

Purpose To establish an easy and widely applicable prognostic prediction model for uveal melanoma (UM) based on a Chinese population. Patients and Methods A total of 295 consecutive cases treated at the Eye & ENT Hospital of Fudan University were included as the primary cohort, and 256 cases were included in the validation cohorts from two external Caucasian databases. Clinicopathological data were collected retrospectively, and nomogram models were formulated based on multivariable analysis. The concordance index (C-index), AUC (area under the Receiver Operating Characteristic, ROC curve), and Brier score were calculated and compared. Results Based on the training cohort, a nomogram model was established with five relevant variables: age, tumor size, ciliary body involvement, non-spindle cell type and extra-scleral extension. The C-index was 0.737, the 3- and 5-year AUCs were 0.767 and 0.742, and the Brier scores for 3- and 5-year survival were 0.082 and 0.129, respectively, which showed superior prediction compared to that of the Tumor, Node and Metastasis staging system. The model also displayed good discrimination and calibration in the external validation cohorts. By risk stratification, patients could be divided into low- and high-risk groups, and the overall survival curves displayed significant differences in the training and validation cohorts. Conclusion Our nomogram model was simple and accurate at predicting the overall survival of patients with UM. It was established based on Asian patients and proved suitable for Caucasian patients; thus, it has a wide range of potential applications, especially for patients living in less medically developed countries and regions.
New Contribution to the Diversity of the Anaerobic Genus Metopus (Ciliophora, Armophorea), With Descriptions of Three New Marine Species

Armophorean ciliates constitute an important component of microeukaryotic community in anaerobic or hypoxic environments. Yet, their diversity remains poorly known due to under-sampling or the scarcity of knowledge. In this study, three metopid ciliates, i.e., Metopus paraes sp. n. , Metopus spiculatus sp. n. , and Metopus parapellitus sp. n. , collected from coastal sediments in Qingdao and Rizhao, China, were investigated using live observation, protargol staining, and molecular phylogenetic methods. M. paraes sp. n. can be distinguished by its long caudal cilia. M. spiculatus sp. n. resembles M. vestitus in many ways, but differs mainly in having a beak-like preoral dome end and a conspicuous tail. The most remarkable features of M. parapellitus sp. n. include an ovate body shape, caudal cilia located at the rear end and right posterior body, and an adoral zone that never extends onto the dorsal surface. Sequence divergences supported the species identification of these three species. Phylogenetic analyses confirmed that the Metopus is not monophyletic, and first revealed that all marine species of Metopus form a well-supported clade. The clustering of these marine forms with M. es (type species) is not rejected by the AU test, which infers that the marine clade represents the genus Metopus together with M. es.
Patient-Derived Organoid Serves as a Platform for Personalized Chemotherapy in Advanced Colorectal Cancer Patients

Background Addition of oxaliplatin to adjuvant 5-FU has significantly improved the disease-free survival and served as the first line adjuvant chemotherapy in advanced colorectal cancer (CRC) patients. However, a fraction of patients remains refractory to oxaliplatin-based treatment. It is urgent to establish a preclinical platform to predict the responsiveness toward oxaliplatin in CRC patients as well as to improve the efficacy in the resistant patients. Methods A living biobank of organoid lines were established from advanced CRC patients. Oxaliplatin sensitivity was assessed in patient-derived tumor organoids (PDOs) in vitro and in PDO-xenografted tumors in mice. Based on in vitro oxaliplatin IC50 values, PDOs were classified into either oxaliplatin-resistant (OR) or oxaliplatin-sensitive (OS) PDOs. The outcomes of patients undergone oxaliplatin-based treatment was followed. RNA-sequencing and bioinformatics tools were performed for molecular profiling of OR and OS PDOs. Oxaliplatin response signatures were submitted to Connectivity Map algorithm to identify perturbagens that may antagonize oxaliplatin resistance. Results Oxaliplatin sensitivity in PDOs was shown to correlate to oxaliplatin-mediated inhibition on PDO xenograft tumors in mice, and parallelled clinical outcomes of CRC patients who received FOLFOX treatment. Molecular profiling of transcriptomes revealed oxaliplatin-resistant and -sensitive PDOs as two separate entities, each being characterized with distinct hallmarks and gene sets. Using Leave-One-Out Cross Validation algorithm and Logistic Regression model, 18 gene signatures were identified as predictive biomarkers for oxaliplatin response. Candidate drugs identified by oxaliplatin response signature-based strategies, including inhibitors targeting c-ABL and Notch pathway, DNA/RNA synthesis inhibitors, and HDAC inhibitors, were demonstrated to potently and effectively increase oxaliplatin sensitivity in the resistant PDOs. Conclusions PDOs are useful in informing decision-making on oxaliplatin-based chemotherapy and in designing personalized chemotherapy in CRC patients.
Ebullition Regulated by Pressure Variations in a Boreal Pit Lake

Methane ebullition from lakes is an important contributor to atmospheric greenhouse gases. However, ebullition is typically sampled at intervals greater than the duration of ebullition events, limiting our understanding of the factors controlling this flux. Here, we present high-frequency ebullition data from a single site in a boreal pit lake during the open-water season between June 24 and 21 October 2018. We record ebullition every 30 min for the first 2 months, and then every minute for the next 2 months. During the 4-month period, 24 ebullition events were recorded. These events generally lasted 2–4 days in response to low atmospheric pressure systems. The peaks in ebullition corresponded to troughs in atmospheric pressure. We provide empirical equations that incorporate a pressure threshold to model the time-series of ebullition events. Minor and gradual variations in mud temperature had no apparent effect on the observed ebullition events.
Antibacterial Activity of Endophytic Bacteria Against Sugar Beet Root Rot Agent by Volatile Organic Compound Production and Induction of Systemic Resistance

The volatile organic compounds (VOCs) produced by endophytic bacteria have a significant role in the control of phytopathogens. In this research, the VOCs produced by the endophytic bacteria Streptomyces sp. B86, Pantoea sp. Dez632, Pseudomonas sp. Bt851, and Stenotrophomonas sp. Sh622 isolated from healthy sugar beet (Beta vulgaris) and sea beet (Beta maritima) were evaluated for their effects on the virulence traits of Bacillus pumilus Isf19, the causal agent of harvested sugar beet root rot disease. The gas chromatographymass spectrometry (GC-MS) analysis revealed that B86, Dez632, Bt851, and Sh622 produced 15, 28, 30, and 20 VOCs, respectively, with high quality. All antagonistic endophytic bacteria produced VOCs that significantly reduced soft root symptoms and inhibited the growth of B. pumilus Isf19 at different levels. The VOCs produced by endophytic bacteria significantly reduced swarming, swimming, and twitching motility by B. pumilus Isf19, which are important to pathogenicity. Our results revealed that VOCs produced by Sh622 and Bt851 significantly reduced attachment of B. pumilus Isf19 cells to sugar beetroots, and also all endophytic bacteria tested significantly reduced chemotaxis motility of the pathogen toward root extract. The VOCs produced by Dez632 and Bt851 significantly upregulated the expression levels of defense genes related to soft rot resistance. Induction of PR1 and NBS-LRR2 genes in sugar beetroot slices suggests the involvement of SA and JA pathways, respectively, in the induction of resistance against pathogen attack. Based on our results, the antibacterial VOCs produced by endophytic bacteria investigated in this study can reduce soft rot incidence.
The Common Effects of Sleep Deprivation on Human Long-Term Memory and Cognitive Control Processes

Sleep deprivation is known to have adverse effects on various cognitive abilities. In particular, a lack of sleep has been reported to disrupt memory consolidation and cognitive control functions. Here, focusing on long-term memory and cognitive control processes, we review the consistency and reliability of the results of previous studies of sleep deprivation effects on behavioral performance with variations in the types of stimuli and tasks. Moreover, we examine neural response changes related to these behavioral changes induced by sleep deprivation based on human fMRI studies to determine the brain regions in which neural responses increase or decrease as a consequence of sleep deprivation. Additionally, we discuss about the possibility that light as an environmentally influential factor affects our sleep cycles and related cognitive processes.
Partial Substation of Organic Fertilizer With Chemical Fertilizer Improves Soil Biochemical Attributes, Rice Yields, and Restores Bacterial Community Diversity in a Paddy Field

Conventional farming systems are highly reliant on chemical fertilizers (CFs), which adversely affect soil quality, crop production and the environment. One of the major current challenges of current agriculture is finding ways to increase soil health and crop yield sustainably. Manure application as a substitute for CF is an alternative fertilization strategy for maintaining soil health and biodiversity. However, little is known about the complex response of soil bacterial communities and soil nutrients to manure and CFs application. This study reports the response of soil nutrients, rice yield, and soil microbial community structure to 2 years of continuous manure and CFs application. The study consisted of six treatments: no N fertilizer control (Neg-Con); 100% CF (Pos-Con); 60% cattle manure (CM) + 40% CF (High-CM); 30% CM + 70% CF (Low-CM); 60% poultry manure (PM) + 40% CF (High-PM), and 30% PM + 70% CF (Low-PM). We used high-throughput sequencing of 16S ribosomal RNA gene amplicons to characterize the soil bacterial communities. Results revealed that the addition of manure significantly altered the soil bacterial community composition and structure; and enhanced the relative abundance of phyla Proteobacteria, Chloroflexi, Firmicutes, Acidobacteria, and Planctomycetes. Organic fertilizer treatments, particularly high CM and PM had the highest measured soil bacterial diversity of all treatments. Similarly, integrated application of manure and CFs increased the soil biochemical traits [i.e., pH, total N (TN), soil organic C (SOC), microbial biomass N (MBN), and microbial biomass C (MBC)] and rice grain yield. Average increases in SOC, TN, MBN, and MBC were 43.66, 31.57, 24.34, and 49.45%, respectively, over the years in the High-PM compared with Pos-Con. Redundancy analysis showed that the dominant bacteria phyla were correlated with soil pH, SOC, TN, and microbial biomass, but the relative abundance of Proteobacteria was strongly correlated with environmental factors such as soil pH, SOC, TN, and MBC. We employed a structural equation model to examine the relationship between microbial biomass, soil nutrients and grain yield among treatments. This analysis supported the hypothesis that soil nutrient content and availability directly affect rice grain yield while soil bacteria indirectly affect grain yield through microbial biomass production and nutrient levels. Overall, the findings of this research suggest that the integrated application of CF and manure is a better approach for improving soil health and rice yield.
Zoledronic Acid Targeting of the Mevalonate Pathway Causes Reduced Cell Recruitment and Attenuates Pulmonary Fibrosis

Background and aim: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreparable scarring of lung tissue, with most patients succumbing rapidly after diagnosis. The mevalonate pathway, which is involved in the regulation of cell proliferation, survival, and motility, is targeted by the bisphosphonate zoledronic acid (ZA). The aim of this study was to assess the antifibrotic effects of ZA and to elucidate the mechanisms by which potential IPF treatment occurs. Methods: A series of in vitro and in vivo models were employed to identify the therapeutic potential of ZA in treating IPF. In vitro transwell assays were used to assess the ability of ZA to reduce fibrotic-related immune cell recruitment. Farnesyl diphosphate synthase (FDPS) was screened as a potential antifibrotic target using a bleomycin mouse model. FDPS-targeting siRNA and ZA were administered to mice following the onset of experimentally-induced lung fibrosis. Downstream analyses were conducted on murine lung tissues and lung fluids including 23-plex cytokine array, flow cytometry, histology, Western blotting, immunofluorescent staining, and PCR analysis. Results: In vitro administration of ZA reduced myofibroblast transition and blocked NF-κB signaling in macrophages leading to impaired immune cell recruitment in a transwell assay. FDPS-targeting siRNA administration significantly attenuated profibrotic cytokine production and lung damage in a murine lung fibrosis model. Furthermore, ZA treatment of mice with bleomycin-induced lung damage displayed decreased cytokine levels in the BALF, plasma, and lung tissue, resulting in less histologically visible fibrotic scarring. Bleomycin-induced upregulation of the ZA target, FDPS, was reduced in lung tissue and fibroblasts upon ZA treatment. Confirmatory increases in FDPS immunoreactivity was seen in human IPF resected lung samples compared to control tissue indicating potential translational value of the approach. Additionally, ZA polarized macrophages towards a less profibrotic phenotype contributing to decreased IPF pathogenesis. Conclusion: This study highlights ZA as an expedient and efficacious treatment option against IPF in a clinical setting.