Miracle-dz/UniFAR-FTUs huggingface dataset:
The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.
Safety of Dabigatran as an Anticoagulant: A Systematic Review and Meta-Analysis

Background: Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor which was developed as an alternative to vitamin K antagonists (VKAs). However, the safety of dabigatran remains controversial so far. In this study, we aimed to compare the risk of bleeding, fatal adverse events, and the all-cause mortality of dabigatran with those of the control group by a systematic review and meta-analysis of randomized controlled trials. Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Medline, Embase, Wanfang database, Clinical trial, China National Knowledge Infrastructure Chinese Scientific Journal database (VIP), and Chinese Biological Medicine database (CBM), for clinical trials on conventional treatments compared with dabigatran, published between January 2014 and July 2020. The reported outcomes, including the endpoints of primary safety, were systematically investigated. Results: Seven RCTs (n = 10,743) were included in the present systematic review. Compared to the control groups, dabigatran was not associated with an increased risk of major bleeding (relative risk [RR] 0.86, 95% confidence interval [CI]: 0.61 to 1.21, p = 0.06), intracranial hemorrhage (RR 0.89, 95% CI: 0.58 to 1.36, p = 0.41), fatal adverse reactions (RR 0.87, 95% CI: 0.65 to 1.17, p = 0.66), all-cause mortality (RR 0.88, 95% CI: 0.70 to 1.11, p = 0.45, I2 = 0%), and significantly reduced risk of clinically relevant non-major bleeding (RR 0.96, 95% CI: 0.65 to 1.42, p = 0.0007). However, dabigatran is associated with an increased risk of gastrointestinal (GI) bleeding (RR 1.78, 95% CI: 1.02 to 3.13, p = 0.05). Conclusion: Dabigatran has a favorable safety profile in terms of major bleeding, intracranial hemorrhage, and life-threatening events, among other safety outcomes. The present study suggested that dabigatran may be a suitable alternative to VKAs as an oral anticoagulant. However, more data are necessary to clarify the incidence of other adverse events and serious adverse reactions.
Early Drug Development and Evaluation of Putative Antitubercular Compounds in the -Omics Era

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. According to the WHO, the disease is one of the top 10 causes of death of people worldwide. Mycobacterium tuberculosis is an intracellular pathogen with an unusually thick, waxy cell wall and a complex life cycle. These factors, combined with M. tuberculosis ability to enter prolonged periods of latency, make the bacterium very difficult to eradicate. The standard treatment of TB requires 6–20months, depending on the drug susceptibility of the infecting strain. The need to take cocktails of antibiotics to treat tuberculosis effectively and the emergence of drug-resistant strains prompts the need to search for new antitubercular compounds. This review provides a perspective on how modern -omic technologies facilitate the drug discovery process for tuberculosis treatment. We discuss how methods of DNA and RNA sequencing, proteomics, and genetic manipulation of organisms increase our understanding of mechanisms of action of antibiotics and allow the evaluation of drugs. We explore the utility of mathematical modeling and modern computational analysis for the drug discovery process. Finally, we summarize how -omic technologies contribute to our understanding of the emergence of drug resistance.
Circulating Myeloid Regulatory Cells: Promising Biomarkers in B-Cell Lymphomas

The monocyte/macrophage lineage has been shown to be involved in the promotion of a protumoral tumor microenvironment and resistance to treatment in B cell lymphomas. However, it is still poorly described at the single cell level, and tissue samples are not easily accessible. Thus, a detailed analysis of the circulating myeloid cell compartment in the different B lymphomas is needed to better understand the mechanisms of resistance to treatment and identify at risk patients. In this Perspective, we review current knowledge on the phenotypic and functional description of the circulating monocytic lineage in B cell lymphomas and provide first insights into the heterogeneity of these cell populations in health and lymphoma, using mass cytometry. Indeed, the monocytic compartment is a continuum more than distinct subpopulations, as demonstrated by our high-resolution approach, explaining the sometimes confusing and contradictory conclusions on the prognostic impact of the different populations, including monocytes and monocytic myeloid derived suppressor cells (M-MDSC). By identifying S100A9high monocytic cells as a potential biomarker in diffuse large B cell lymphoma (DLBCL) in this proof-of-concept preliminary study including a limited number of samples, we underline the potential of circulating myeloid regulatory cells as diagnostic and prognostic biomarkers in B-cell lymphomas.
Hybrid-Model-Based Deep Reinforcement Learning for Heating, Ventilation, and Air-Conditioning Control

Buildings account for a large proportion of the total energy consumption in many countries and almost half of the energy consumption is caused by the Heating, Ventilation, and air-conditioning (HVAC) systems. The model predictive control of HVAC is a complex task due to the dynamic property of the system and environment, such as temperature and electricity price. Deep reinforcement learning (DRL) is a model-free method that utilizes the “trial and error” mechanism to learn the optimal policy. However, the learning efficiency and learning cost are the main obstacles of the DRL method to practice. To overcome this problem, the hybrid-model-based DRL method is proposed for the HVAC control problem. Firstly, a specific MDPs is defined by considering the energy cost, temperature violation, and action violation. Then the hybrid-model-based DRL method is proposed, which utilizes both the knowledge-driven model and the data-driven model during the whole learning process. Finally, the protection mechanism and adjusting reward methods are used to further reduce the learning cost. The proposed method is tested in a simulation environment using the Australian Energy Market Operator (AEMO) electricity price data and New South Wales temperature data. Simulation results show that 1) the DRL method can reduce the energy cost while maintaining the temperature satisfactory compared to the short term MPC method; 2) the proposed method improves the learning efficiency and reduces the learning cost during the learning process compared to the model-free method.
To Go or Not to Go: Degrees of Dynamic Inhibitory Control Revealed by the Function of Grip Force and Early Electrophysiological Indices

A critical issue in executive control is how the nervous system exerts flexibility to inhibit a prepotent response and adapt to sudden changes in the environment. In this study, force measurement was used to capture “partial” unsuccessful trials that are highly relevant in extending the current understanding of motor inhibition processing. Moreover, a modified version of the stop-signal task was used to control and eliminate potential attentional capture effects from the motor inhibition index. The results illustrate that the non-canceled force and force rate increased as a function of stop-signal delay (SSD), offering new objective indices for gauging the dynamic inhibitory process. Motor response (time and force) was a function of delay in the presentation of novel/infrequent stimuli. A larger lateralized readiness potential (LRP) amplitude in go and novel stimuli indicated an influence of the novel stimuli on central motor processing. Moreover, an early N1 component reflects an index of motor inhibition in addition to the N2 component reported in previous studies. Source analysis revealed that the activation of N2 originated from inhibitory control associated areas: the right inferior frontal gyrus (rIFG), pre-motor cortex, and primary motor cortex. Regarding partial responses, LRP and error-related negativity (ERNs) were associated with error correction processes, whereas the N2 component may indicate the functional overlap between inhibition and error correction. In sum, the present study has developed reliable and objective indices of motor inhibition by introducing force, force-rate and electrophysiological measures, further elucidating our understandings of dynamic motor inhibition and error correction.
Soil Disturbance Affects Plant Productivity via Soil Microbial Community Shifts

Recent advances in climate research have discovered that permafrost is particularly vulnerable to the changes occurring in the atmosphere and climate, especially in Alaska where 85% of the land is underlain by mostly discontinuous permafrost. As permafrost thaws, research has shown that natural and anthropogenic soil disturbance causes microbial communities to undergo shifts in membership composition and biomass, as well as in functional diversity. Boreal forests are home to many plants that are integral to the subsistence diets of many Alaska Native communities. Yet, it is unclear how the observed shifts in soil microbes can affect above ground plant communities that are relied on as a major source of food. In this study, we tested the hypothesis that microbial communities associated with permafrost thaw affect plant productivity by growing five plant species found in Boreal forests and Tundra ecosystems, including low-bush cranberry and bog blueberry, with microbial communities from the active layer soils of a permafrost thaw gradient. We found that plant productivity was significantly affected by the microbial soil inoculants. Plants inoculated with communities from above thawing permafrost showed decreased productivity compared to plants inoculated with microbes from undisturbed soils. We used metagenomic sequencing to determine that microbial communities from disturbed soils above thawing permafrost differ in taxonomy from microbial communities in undisturbed soils above intact permafrost. The combination of these results indicates that a decrease in plant productivity can be linked to soil disturbance driven changes in microbial community membership and abundance. These data contribute to an understanding of how microbial communities can be affected by soil disturbance and climate change, and how those community shifts can further influence plant productivity in Boreal forests and more broadly, ecosystem health.
Tolerance of Tetraselmis tetrathele to High Ammonium Nitrogen and Its Effect on Growth Rate, Carotenoid, and Fatty Acids Productivity

Microalgae can use either ammonium or nitrate for its growth and vitality. However, at a certain level of concentration, ammonium nitrogen exhibits toxicity which consequently can inhibit microalgae productivity. Therefore, this study is aimed to investigate the tolerance of Tetraselmis tetrathele to high ammonium nitrogen concentrations and its effects on growth rate, photosynthetic efficiency (Fv/Fm), pigment contents (chlorophyll a, lutein, neoxanthin, and β-carotene), and fatty acids production. Experiments were performed at different ammonium nitrogen concentrations (0.31–0.87 gL−1) for 6 days under a light source with an intensity of 300 μmol photons m−2 s−1 and nitrate-nitrogen source as the experimental control. The findings indicated no apparent enhancement of photosynthetic efficiency (Fv/Fm) at high levels of ammonium nitrogen (NH4+-N) for T. tetrathele within 24 h. However, after 24 h, the photosynthetic efficiency of T. tetrathele increased significantly (p < 0.05) in high concentration of NH4+-N. Chlorophyll a content in T. tetrathele grown in all of the different NH4+-N levels increased significantly compared to nitrate-nitrogen (NO3-N) treatment (p < 0.05); which supported that this microalgal could grow even in high level of NH4+-N concentrations. The findings also indicated that T. tetrathele is highly resistant to high ammonium nitrogen which suggests T. tetrathele to be used in the aquaculture industry for bioremediation purpose to remove ammonium nitrogen, thus reducing the production cost while improving the water quality.
Changes in Community Composition Induced by Experimental Warming in an Alpine Meadow: Beyond Plant Functional Type

Climate warming exerts profound effects on plant community composition. However, responses to climate warming are often reported at the community and functional type levels, but not at the species level. To test whether warming-induced changes are consistent among community, functional type, and species levels, we examined the warming-induced changes at different levels in an alpine meadow from 2015 to 2018. The warming was achieved by deploying six (open top) chambers [including three non-warmed chambers and three warmed chambers; 15 × 15 × 2.5 m (height) for each] that resulted in a small increase in mean annual temperature (0.3–0.5°C, varying with years) with a higher increase during the non-growing season (0.4–0.6°C) than in the growing season (0.03–0.47°C). The results show that warming increased plant aboveground biomass but did not change species richness, or Shannon diversity and evenness at the community level. At the functional type level, warming increased the relative abundance of grasses from 3 to 16%, but decreased the relative abundance of forbs from 89 to 79%; relative abundances of sedges and legumes were unchanged. However, for a given functional type, warming could result in contrasting effects on the relative abundance among species, e.g., the abundances of the forb species Geranium pylzowianum, Potentilla anserine, Euphrasia pectinate, and the sedge species Carex atrofusca increased in the warmed (compared to the non-warmed) chambers. More importantly, the difference in species identity between warmed and non-warmed chambers revealed warming-induced species loss. Specifically, four forb species were lost in both types of chambers, one additional forb species (Angelica apaensis) was lost in the non-warmed chambers, and two additional species (one forb species Saussurea stella and one sedge species Blysmus sinocompressus) were lost in the warmed chambers. Consequently, changes at the species level could not be deduced from the results at the community or functional type levels. These data indicate that species-level responses to climate changes must be more intensively studied. This work also highlights the importance of examining species identity (and not only species number) to study changes of community composition in response to climate warming.
Disruption of Glutamate Transport and Homeostasis by Acute Metabolic Stress

High-affinity, Na+-dependent glutamate transporters are the primary means by which synaptically released glutamate is removed from the extracellular space. They restrict the spread of glutamate from the synaptic cleft into the perisynaptic space and reduce its spillover to neighboring synapses. Thereby, glutamate uptake increases the spatial precision of synaptic communication. Its dysfunction and the entailing rise of the extracellular glutamate concentration accompanied by an increased spread of glutamate result in a loss of precision and in enhanced excitation, which can eventually lead to neuronal death via excitotoxicity. Efficient glutamate uptake depends on a negative resting membrane potential as well as on the transmembrane gradients of the co-transported ions (Na+, K+, and H+) and thus on the proper functioning of the Na+/K+-ATPase. Consequently, numerous studies have documented the impact of an energy shortage, as occurring for instance during an ischemic stroke, on glutamate clearance and homeostasis. The observations range from rapid changes in the transport activity to altered expression of glutamate transporters. Notably, while astrocytes account for the majority of glutamate uptake under physiological conditions, they may also become a source of extracellular glutamate elevation during metabolic stress. However, the mechanisms of the latter phenomenon are still under debate. Here, we review the recent literature addressing changes of glutamate uptake and homeostasis triggered by acute metabolic stress, i.e., on a timescale of seconds to minutes.
Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis

Introduction Late stage clinical trials in non-alcoholic steatohepatitis (NASH) are currently required by the FDA to use liver biopsy as a primary endpoint. The well-reported limitations with biopsy, such as associated risks and sampling error, coupled with patient preference, are driving investigation into non-invasive alternatives. MRI-derived biomarkers proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) are gaining traction as emerging alternatives to biopsy for NASH. Our aim was to explore the correlations between cT1 and PDFF (from LiverMultiScan®), with the histological components on the NAFLD-NASH spectrum in a large cohort of cross-sectional data, in order to calibrate the measurement to histology, and to infer what might constitute a clinically meaningful change when related to the FDA’s criteria. Materials and Methods In a retrospective analysis of data combined from three previously published observational NASH studies, in which adult participants who underwent liver biopsy on suspicion of NAFLD or NASH and had an MRI scan measuring cT1 and PDFF (LiverMultiScan®, Perspectum Ltd, UK), associations between imaging biomarkers and histology were tested using Spearman’s rank correlation coefficient (rs), and further exploration of the relationships between the imaging variables and histology were performed using linear regression. Results N = 264 patients with mean age of 54 (SD:9.9), 39% female, and 69% with BMI ≥ 30kg.m−2 were included in the analysis. cT1 and PDFF both correlated with all features of the NAFLD activity score (NAS). cT1 was also positively correlated with Kleiner-Brunt fibrosis. Partial correlations, adjusting for steatosis, revealed cT1 correlated with inflammation and fibrosis, whereas PDFF did not, and both were still associated with the NAS, but correlation was weaker with PDFF than cT1. An estimated difference of 88 ms in cT1, or 21% relative difference in PDFF was related to a two-point difference in overall NAS. Conclusion The correlations between cT1 and PDFF with the histopathological hallmarks of NASH demonstrate the potential utility of both cT1 and PDFF as non-invasive biomarkers to detect a pharmacodynamic change in NASH, with cT1 showing superiority for detecting changes in inflammation and fibrosis, rather than liver fat alone.
An Integrative Pharmacology-Based Approach for Evaluating the Potential Effects of Purslane Seed in Diabetes Mellitus Treatment Using UHPLC-LTQ-Orbitrap and TCMIP V2.0

Portulaca oleracea L. , known as the “vegetable for long life,” is an annual succulent herb that is widely distributed worldwide. Many clinical and experimental studies have demonstrated that purslane seed (MCXZ) can be used as an adjunctive and alternative therapy for the treatment of diabetes mellitus (DM). However, the underlying active constituents and pharmacological mechanisms through which MCXZ exerts effects in DM remain unclear. In the present study, we confirmed that MCXZ treatment resulted in hypoglycemic activity, lowering the fasting blood glucose and glycated hemoglobin levels in streptozotocin-induced diabetic mice. Then, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was used to systematically analyze the chemical profile of MCXZ, resulting in the identification of 84 constituents, including 31 organic acids and nine flavonoids. Finally, the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine was employed to analyze the key active components of MCXZ and the molecular mechanisms through which these components acted in DM. Ten key active compounds were identified based on the topological importance of their corresponding putative targets within the known DM-associated therapeutic target network of known MCXZ putative targets. Functionally, these candidate targets play critical anti-hyperlipidemia, anti-hyperglycemia, immunity regulation, and inflammatory roles involving DM-related pathways, such as the vascular endothelial growth factor (VEGF) signaling pathway and Fc gamma R-mediated phagocytosis, which indicated that MCXZ exhibited anti-diabetic activity through multi-faced actions.
The Role of Lipophagy in the Development and Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction) associated liver disease (MAFLD), is, with a global prevalence of 25%, the most common liver disorder worldwide. NAFLD comprises a spectrum of liver disorders ranging from simple steatosis to steatohepatitis, fibrosis, cirrhosis and eventually end-stage liver disease. The cause of NAFLD is multifactorial with genetic susceptibility and an unhealthy lifestyle playing a crucial role in its development. Disrupted hepatic lipid homeostasis resulting in hepatic triglyceride accumulation is an hallmark of NAFLD. This disruption is commonly described based on four pathways concerning 1) increased fatty acid influx, 2) increased de novo lipogenesis, 3) reduced triglyceride secretion, and 4) reduced fatty acid oxidation. More recently, lipophagy has also emerged as pathway affecting NAFLD development and progression. Lipophagy is a form of autophagy (i.e. controlled autolysosomal degradation and recycling of cellular components), that controls the breakdown of lipid droplets in the liver. Here we address the role of hepatic lipid homeostasis in NAFLD and specifically review the current literature on lipophagy, describing its underlying mechanism, its role in pathophysiology and its potential as a therapeutic target.