Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel pituitary actions of GnRH in teleost: The link between reproduction and feeding regulation

Gonadotropin-releasing hormone (GnRH), as a vital hypothalamic neuropeptide, was a key regulator for pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the vertebrate. However, little is known about the other pituitary actions of GnRH in teleost. In the present study, two GnRH variants (namely, GnRH2 and GnRH3) and four GnRH receptors (namely, GnRHR1, GnRHR2, GnRHR3, and GnRHR4) had been isolated from grass carp. Tissue distribution displayed that GnRHR4 was more highly detected in the pituitary than the other three GnRHRs. Interestingly, ligand–receptor selectivity showed that GnRHR4 displayed a similar and high binding affinity for grass carp GnRH2 and GnRH3. Using primary culture grass carp pituitary cells as model, we found that both GnRH2 and GnRH3 could not only significantly induce pituitary reproductive hormone gene (GtHα, LHβ, FSHβ, INHBa, secretogranin-2) mRNA expression mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways but also reduce dopamine receptor 2 (DRD2) mRNA expression via the Ca2+/CaM/CaMK-II pathway. Interestingly, GnRH2 and GnRH3 could also stimulate anorexigenic peptide (POMCb, CART2, UTS1, NMBa, and NMBb) mRNA expression via AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways in grass carp pituitary cells. In addition, food intake could significantly induce brain GnRH2 mRNA expression. These results indicated that GnRH should be the coupling factor to integrate the feeding metabolism and reproduction in teleost.
Planck 2015 results. XVII. Constraints on primordial non-Gaussianity

The Planck nominal mission cosmic microwave background (CMB) maps yield unprecedented constraints on primordial non-Gaussianity (NG). Using three optimal bispectrum estimators, separable template-fitting (KSW), binned, and modal, we obtain consistent values for the primordial local, equilateral, and orthogonal bispectrum amplitudes, quoting as our final result fNL^local= 2.7+/-5.8, fNL^equil= -42+/-75, and fNL^ortho= -25+\-39 (68% CL statistical). NG is detected in the data; using skew-C_l statistics we find a nonzero bispectrum from residual point sources, and the ISW-lensing bispectrum at a level expected in the LambdaCDM scenario. The results are based on comprehensive cross-validation of these estimators on Gaussian and non-Gaussian simulations, are stable across component separation techniques, pass an extensive suite of tests, and are confirmed by skew-C_l, wavelet bispectrum and Minkowski functional estimators. Beyond estimates of individual shape amplitudes, we present model-independent, 3-dimensional reconstructions of the Planck CMB bispectrum and thus derive constraints on early-Universe scenarios that generate primordial NG, including general single-field models of inflation, excited initial states (non-Bunch-Davies vacua), and directionally-dependent vector models. We provide an initial survey of scale-dependent feature and resonance models. These results bound both general single-field and multi-field model parameter ranges, such as the speed of sound, c_s \geq 0.02 (95% CL), in an effective field theory parametrization, and the curvaton decay fraction r_D \geq 0.15 (95% CL). The Planck data significantly limit the viable parameter space of the ekpyrotic/cyclic scenarios. The amplitude of the 4-point function in the local model tauNL < 2800 (95% CL). These constraints represent the highest precision tests to date of physical mechanisms for the origin of cosmic structure.
A novel method of heterogeneous combat network disintegration based on deep reinforcement learning

Modern war is highly dependent on intelligent, unmanned combat systems. Since many intelligent, unmanned combat systems have network attributes, it is meaningful to research combat systems from the perspective of complex network. Heterogeneous network provides a suitable model to describe real combat network. Previous studies of combat network only concentrate on homogeneous networks. However, on the real battlefield, military networks are composed of a large number of heterogeneous nodes and edges with different functions. In the paper, a superior, intelligent, heterogeneous combat network disintegration strategy (HDGED) are obtained by DQN, which embeds heterogeneous networks into a low-dimensional representation vector as input, rather than ignore the differences of the nodes and their connections. A method of heterogeneous graph embedding is first introduced, which adopts type encoding and aggregation. Besides, a normalized combat capability index was designed, which could assess the performance of the dynamic heterogeneous combat networks. On this basis, HDGED was experimented on networks with uneven node combat capabilities and the results show that HDGED has improved disintegration effectiveness for heterogeneous networks of different sizes compared with traditional methods. Our work provides a new approach to realize the disintegration of heterogeneous combat networks by deep reinforcement learning, which is of great significance for optimizing the command operation process, and deserves further study.
An analysis of African Swine Fever consequences on rural economies and smallholder swine producers in Haiti

African Swine Fever (ASF) causes high mortality and often results in strict culling policies for affected pigs and international market restrictions. It took more than 25 years for swine inventories in Haiti and the Dominican Republic to recover from an ASF outbreak that took place from 1978 to 1984. The 2021 outbreaks in the Dominican Republic and Haiti pose threats to animal health, livestock markets, and producer livelihoods. A partial equilibrium Haitian pig sector model (HPM-2021) was developed to assess the economic impacts of a 2021 Haitian ASF outbreak of a similar size to the 1980s outbreak. The dynamic model examines ASF impacts from 2021 to 2024, through 100 iterations of stochastic supply shocks, and three specific demand shocks. Recovery alternatives are assessed through 2030, and outbreaks and recovery outcomes are compared to a baseline reflecting 2019 trends. The analysis includes economic effects on national pork and maize in Haiti, the Dominican Republic, the rest of the Caribbean, and the rest of the world. Findings demonstrate higher vulnerabilities of the traditional sector to ASF-related disruptions. The inflated prices generated by pork production shortfalls are an opportunity to accelerate income growth for remaining traditional pig producers. When there is no consumer avoidance, the production losses caused by ASF generate high prices and contribute to a minimum of 49% increase in traditional sector revenue, and a minimum of 2.22% revenue growth in the commercial sector from the 2019 base year. Nevertheless, the potential for consumer avoidance of pork cause prices to decrease and offset those gains by as much as 90% in the traditional sector and 44% in the commercial sector. Smaller commercial sector impacts derive from different elasticities. ASF-induced high prices also lead to increased consumer expenditure losses by up to 200% over the outbreak period. Nevertheless, consumer expenditures tend to recover instantaneously with ASF eradication. Due to persisting demand shocks, producers will earn up to 0.3% lower than baseline levels income from 2027 to 2030. Few models evaluate the economic impacts of health response policies in less developed countries like Haiti. HPM-2021 results highlight ASF impacts on prices, which can benefit certain producers and disincentivize on-farm disease reporting. Slow recovery and consumer avoidance of pork are detrimental to long-term swine industry survival, producer livelihoods, and the overall rural economy.
The economic impact of porcine reproductive and respiratory syndrome outbreak in four Chinese farms: Based on cost and revenue analysis

The economic impact after the outbreak of porcine reproductive and respiratory syndrome (PRRS) has been proven to be tremendous for pig production worldwide. However, the economic impact of the disease is not well understood in China. In our previous study, we acquired and analyzed the main production data (the number of weaned piglets, health costs, delayed marketing age, etc.) from the management system before and after the PRRS outbreaks occurring in November 2014, March 2015, December 2016, and February 2017. This study aimed to analyze and quantify the economic losses of the four PRRS outbreaks in Chinese herds. A straightforward approach was used to calculate additional costs and decreased revenues based on the PRRS-induced production deficiencies by average cost-of-production indices calculated from annual estimates of costs between 2014 and 2017. The results showed that economic losses varied between ¥668.14 and ¥1004.43 per sow in breeding herds from the outbreaks to regain the basic performance, with an average of ¥822.75 per sow, and the mean costs in the fattening herds (including nursery pigs) were ¥601.62 per sow, ranging from ¥318.64 to ¥937.14. Overall, the economic impact of PRRS on the whole herd was ¥1424.37 per sow. The majority of the losses were due to the reduction in the number of weaned piglets for breeding herds, and the increased feed cost (occupying 44.88%) was the primary source of loss for fattening herds. Our study fills the gap in knowledge of PRRS economics in China, enriches the data for veterinary economics, and re-stresses the necessity for producers and veterinarians to control PRRS effectively.
Lung ultrasound to guide the administration of exogenous pulmonary surfactant in respiratory distress syndrome of newborn infants: A retrospective investigation study

Background Respiratory distress syndrome (RDS) is a common disease that seriously endangers the life and safety of newborns, especially premature infants. Exogenous pulmonary surfactant (PS) is the specific agent for the treatment of neonatal RDS. Lung ultrasound (LUS) has been successfully used in the diagnosis of RDS, but its value in guiding the application of PS is still unclear. This paper explored whether the application of PS under LUS monitoring has some advantages, including (1) decreasing the misdiagnosis rate of RDS and decreasing probability of using PS, and (2) reducing the dose of PS without reducing the therapeutic effect. Methods This study included two parts. Part 1: To decide whether the LUS is good to differentiate RDS from other lung diseases in the premature infants. All patients who were diagnosed with RDS and required PS treatment based on conventional criteria were routinely examined by LUS. Then, according to LUS findings, we decided whether they needed to receive PS treatment. Part 2: To see the dose reduction of surfactant is applicable. In RDS patients diagnosed based on LUS presentation and treated with Curosurf (Chiesi Pharmaceutical, Parma, Italy), the dose of Curosurf was compared with that recommended by the European RDS management guidelines. Results (1) Since March 2017, 385 newborn infants admitted to our neonatal intensive care unit met the traditional diagnostic criteria of RDS. Of these, only 269 cases were diagnosed with RDS and needed PS treatment according to LUS manifestations. The other 116 infants who did not meet the criteria for ultrasound diagnosis of RDS did not receive PS supplementation but obtained good outcomes, that is LUS findings decreased a misdiagnosis rate of RDS by 30.1% and subsequently resulted in a 30.1% reduction in PS use. (2) Among the 269 RDS patients diagnosed based on LUS findings, 148 were treated with Curosurf (another 121 RDS infants who received domestic PS treatment were not included in the study group), and the average dose was 105.4 ± 24.3 mg/kg per time, which is significantly lower than the dose of 200 mg/kg per time recommended by the European RDS guidelines. (3) The mortality rate of RDS patients was 0%, and no patients had ventilator-associated pneumonia or bronchopulmonary dysplasia in this study. Conclusion LUS can decrease the misdiagnosis rate of RDS, thereby decreasing the probability of using PS and decreasing the dose of PS, and can help RDS infants to achieve better outcomes.
Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC

The mitotic kinesin Eg5 has emerged as a potential anti-mitotic target for the purposes of cancer chemotherapy. Whether clinical resistance to these inhibitors can arise is unclear. We exploited HCT116 cancer cell line to select resistant clones to S-trityl-L-cysteine (STLC), an extensively studied Eg5 loop-L5 binding inhibitor. The STLC resistant clones differed in their resistance to other loop-L5 binding inhibitors but remained sensitive to the ATP class of competitive Eg5 specific inhibitors. Eg5 is still necessary for bipolar spindle formation in the resistant clones since the cells were sensitive to RNAi mediated depletion of Eg5. One clone expressing Eg5(T107N), a dominant point mutation in the P-loop of the ATP binding domain of the motor, appeared to be not only resistant but also dependent on the presence of STLC. Eg5(T107N) expression was associated also with resistance to the clinical relevant loop-L5 Eg5 inhibitors, Arry-520 and ispinesib. Ectopic expression of the Eg5(T107N) mutant in the absence of STLC was associated with strong non-exchangeable binding to microtubules causing them to bundle. Biochemical assays showed that in contrast to the wild type Eg5-STLC complex, the ATP binding site of the Eg5(T107N) is accessible for nucleotide exchange only when the inhibitor is present. We predict that resistance can be overcome by inhibitors that bind to other than the Eg5 loop-L5 binding site having different chemical scaffolds, and that allostery-dependent resistance to Eg5 inhibitors may also occur in cells and may have positive implications in chemotherapy since once diagnosed may be beneficial following cessation of the chemotherapeutic regimen.
Potential applications for multifunctional microalgae in soil improvement

Soil is the basis of agricultural production, and the quality of soil directly affects crop quality and yield. Microalgae can carry out photosynthesis, carbon and nitrogen fixation, and produce large amounts of valuable biomass coupled with wastewater treatment. Also, microalgae can produce plant hormones and other high-value products, which can promote plant growth, improve soil fertility, soil ecological health, and control crop diseases. This research reviews the characteristics of microalgae in improving soil health, discusses the situation of microalgae in controlling soil pollutants, elaborates on the technical application of microalgae in alleviating soil problems, and proposes potential applications of microalgae in ecological environment. Also, resource utilization of multifunctional microalgae is discussed, to provide a theoretical basis for the application of microalgae in soil improvement.
The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside

Despite efficient repair, DNA damage inevitably accumulates with time affecting proper cell function and viability, thereby driving systemic aging. Interventions that either prevent DNA damage or enhance DNA repair are thus likely to extend health- and lifespan across species. However, effective genome-protecting compounds are largely lacking. Here, we use Ercc1 Δ/− and Xpg −/− DNA repair-deficient mutants as two bona fide accelerated aging mouse models to test propitious anti-aging pharmaceutical interventions. Ercc1 Δ/− and Xpg −/− mice show shortened lifespan with accelerated aging across numerous organs and tissues. Previously, we demonstrated that a well-established anti-aging intervention, dietary restriction, reduced DNA damage, and dramatically improved healthspan, strongly extended lifespan, and delayed all aging pathology investigated. Here, we further utilize the short lifespan and early onset of signs of neurological degeneration in Ercc1 Δ/− and Xpg −/− mice to test compounds that influence nutrient sensing (metformin, acarbose, resveratrol), inflammation (aspirin, ibuprofen), mitochondrial processes (idebenone, sodium nitrate, dichloroacetate), glucose homeostasis (trehalose, GlcNAc) and nicotinamide adenine dinucleotide (NAD+) metabolism. While some of the compounds have shown anti-aging features in WT animals, most of them failed to significantly alter lifespan or features of neurodegeneration of our mice. The two NAD+ precursors; nicotinamide riboside (NR) and nicotinic acid (NA), did however induce benefits, consistent with the role of NAD+ in facilitating DNA damage repair. Together, our results illustrate the applicability of short-lived repair mutants for systematic screening of anti-aging interventions capable of reducing DNA damage accumulation.
Development and validation of a novel prognosis prediction model for patients with myelodysplastic syndrome

Background Somatic mutations are widespread in patients with Myelodysplastic Syndrome (MDS) and are associated with prognosis. However, a practical prognostic model for MDS that incorporates somatic mutations urgently needs to be developed. Methods A cohort of 201 MDS patients from the Gene Expression Omnibus (GEO) database was used to develop the model, and a single-center cohort of 115 MDS cohorts from Northwest China was used for external validation. Kaplan-Meier analysis was performed to compare the effects of karyotype classifications and gene mutations on the prognosis of MDS patients. Univariate and multivariate Cox regression analyses and Lasso regression were used to screen for key prognostic factors. The shinyapps website was used to create dynamic nomograms with multiple variables. The time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) were used to evaluate the model’s discrimination, accuracy and clinical utility. Results Six risk factors (age, bone morrow blast percentage, ETV6, TP53, EZH2, and ASXL1) were considered as predictor variables in the nomogram. The nomogram showed excellent discrimination, with respective the area under the ROC curve (AUC) values of 0.850, 0.839, 0.933 for the training cohort at 1 year, 3 years and 5 years; 0.715, 0.802 and 0.750 for the testing cohort at 1 year, 3 years and 5 years; and 0.668, 0.646 and 0.731 for the external validation cohort at 1 year, 3 years and 5 years. The calibration curves and decision curve showed that the nomogram had good consistency and clinical practical benefit. Finally, a stratified analysis showed that MDS patients with high risk had worse survival outcomes than patients with low risk. Conclusion We developed a nomogram containing six risk factors, which provides reliable and objective predictions of prognosis for MDS patients.
Post-Disruptive Runaway Electron Beam in COMPASS Tokamak

For ITER-relevant runaway electron studies, such as suppression, mitigation, termination and/or control of runaway beam, obtaining the runaway electrons after the disruption is important. In this paper we report on the first achieved discharges with post-disruptive runaway electron beam, entitled "runaway plateau", in the COMPASS tokamak. The runaway plateau is produced by massive gas injection of argon. Almost all of the disruptions with runaway electron plateaus occurred during the plasma current ramp-up phase. Comparison between the Ar injection discharges with and without plateau has been done for various parameters. Parametrisation of the discharges shows that COMPASS disruptions fulfill the range of parameters important for the runaway plateau occurrence. These parameters include electron density, electric field, disruption speed, effective safety factor, maximum current quench electric field. In addition to these typical parameters, the plasma current value just before the massive gas injection surprisingly proved to be important.
Immunomodulatory potential of secretome from cartilage cells and mesenchymal stromal cells in an arthritic context: From predictive fiction toward reality

The purpose of the present study is to predict by bioinformatics the activity of the extracellular vesicle (EV)-embedded micro RNA (miRNAs) secreted by cartilage cells (CCs), adipose tissue-derived- (ASCs), and bone marrow-derived stem cells (BMSCs) and verify their immunomodulatory potential supporting our bioinformatics findings to optimize the autologous cell-based therapeutic strategies for osteoarthritis (OA) management. Cells were isolated from surgical waste tissues of three patients who underwent total hip replacement, expanded and the EVs were collected. The expression of EV-embedded miRNA was evaluated with the QuantStudio 12 K Flex OpenArray® platform. Mientournet and ingenuity pathway analysis (IPA) were used for validated target prediction analysis and to identify miRNAs involved in OA and inflammation. Cells shared the expression of 325 miRNAs embedded in EVs and differed for the expression of a small number of them. Mienturnet revealed no results for miRNAs selectively expressed by ASCs, whereas miRNA expressed by CCs and BMSCs were putatively involved in the modulation of cell cycle, senescence, apoptosis, Wingless and Int-1 (Wnt), transforming growth factor beta (TGFβ), vascular endothelial growth factor (VEGF), Notch, Hippo, tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), insulin like growth factor 1 (IGF-1), RUNX family transcription factor 2 (RUNX2), and endochondral ossification pathways. Cartilage homeostasis, macrophages and T cells activity and inflammatory mediators were identified by IPA as targets of the miRNAs found in all the cell populations. Co-culture tests on macrophages and T cells confirmed the immuno-modulatory ability of CCs, ASCs, and BMSCs. The study findings support the rationale behind the use of cell-based therapy for the treatment of OA.
Apoptosis-associated speck-like protein containing a CARD-mediated release of matrix metalloproteinase 10 stimulates a change in microglia phenotype

Inflammation contributes to amyloid-β and tau pathology in Alzheimer’s disease (AD). Microglia facilitate an altered immune response that includes microgliosis, upregulation of inflammasome proteins, and elevation of matrix-metalloproteinases (MMPs). Studies of cerebrospinal fluid (CSF) and blood in dementia patients show upregulation of two potential biomarkers of inflammation at the cellular level, MMP10 and apoptosis-associated speck-like protein containing a CARD (ASC). However, little is known about their relationship in the context of brain inflammation. Therefore, we stimulated microglia cultures with purified insoluble ASC speck aggregates and MMP10 to elucidate their role. We found that ASC specks altered microglia shape and stimulated the release of MMP3 and MMP10. Furthermore, MMP10 stimulated microglia released additional MMP10 along with the inflammatory cytokines, tumor-necrosis factor-α (TNFα), Interleukin 6 (IL-6), and CXCL1 CXC motif chemokine ligand 1 (CXCL1). A broad-spectrum MMP inhibitor, GM6001, prevented TNFα release. With these results, we conclude that MMP10 and ASC specks act on microglial cells to propagate inflammation.