Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue distribution and integrated pharmacokinetic properties of major effective constituents of oral Gegen-Qinlian decoction in mice

Gegen-Qinlian decoction (GQD) is a classic traditional Chinese medicine (TCM) formula. GQD is effective against colon or liver-related diseases including ulcerative colitis, non-alcoholic fatty liver, and type 2 diabetes. In this study, a liquid chromatography-tandem mass spectrometry method was developed, validated, and then applied to reveal the tissue distribution and integrated pharmacokinetic properties of major effective constituents of oral GQD in mice. The established method was quick, sensitive, and accurate enough to analyze GQD constituents in plasma and tissue homogenate samples quantitatively. According to their concentrations in the portal vein, systemic circulation, liver and colon samples of the mice after oral administration of GQD, the concentration-time curves of the constituents were respectively plotted. The results showed that daidzein, baicalin, and baicalein had relatively high exposure levels in the livers, while puerarin, berberine, epiberberine, coptisine, palmatine, jatrorrhizine, magnoflorine, glycyrrhizic acid, and glycyrrhetinic acid were enriched in the colons. Given that these constituents have significant biological activity, they could be regarded as the major effective constituents of GQD in treating colon or liver-related diseases, respectively. In addition, the integrated pharmacokinetic properties of GQD were studied. The GQD “integrated constituent” reached peak concentration at 4.0 h in the portal vein, the systemic circulation, the livers, and the colons, with half-lives of 1.5–4.1 h and mean retention time of 4.5–6.3 h, respectively. Furthermore, the concentration of the GQD “integrated constituent” in the colons was approximately 10 times higher than that in the livers, both of which were much higher than that in the systemic circulation, indicating its accumulation in these tissues, especially in the colons. In conclusion, the tissue distribution and integrated pharmacokinetic properties of oral GQD were revealed in the study. The results of the tissue distribution study would contribute to identifying the major target tissues and effective constituents of GQD, while the results of the integrated pharmacokinetic study would help to explain the pharmacokinetic properties of oral GQD as a whole.
A systemic review of taxanes and their side effects in metastatic breast cancer

Taxanes-containing chemotherapy constitutes an essential backbone for both early and metastatic breast cancer (mBC). However, the two major taxane drugs—paclitaxel and docetaxel—have distinct safety profiles. In this review, we summarize the safety outcome and management following treatment with both taxanes from selected clinical trials. We utilized PubMed to perform literature search before April 2021. Five phase III randomized controlled trials with reports of individual taxane adverse events (AEs) were included in this review. Grade 3/4 AEs were summarized and discussed extensively. The rates of grade 3/4 neutropenia were higher with docetaxel than with paclitaxel. For non-hematologic grade 3/4 AEs, peripheral neuropathy was more frequent with paclitaxel while fluid retention was more frequent with docetaxel. Compared to paclitaxel, docetaxel had a higher rate of grade 3/4 gastrointestinal AEs. Grade 3/4 myalgia were generally comparable between the two taxanes. Except for neutropenia, the incidence rate of grade 3/4 AEs of taxanes was generally manageable. Peripheral neuropathy was more common with paclitaxel while grade 3/4 neutropenia was more common with docetaxel.
Transareolar uniportal thoracoscopic extended thymectomy for patients with myasthenia gravis

Background Transareolar uniportal thoracoscopic extended thymectomy (TUTET) has not been previously reported. We attempted to assess the feasibility and safety of TUTET for male myasthenia gravis (MG) patients. Patients and methods From February 2013 to February 2020, 46 men with MG underwent TUTET. All patients were followed up for 12–84 months postoperatively by clinic visits or telephone/e-mail interviews. Results All surgeries were completed successfully, with an average operation time of 72.6 min. The mean length of transareolar uniportal incision was 3.0 ± 0.4 cm, and the mean postoperative cosmetic score was 3.1 ± 0.5 at discharge. Three months postoperatively, no patients had an apparent surgical scar on the chest wall or complained of postoperative pain. Substantial amelioration of the disease was achieved in a short period, and several benefits were clear. At the 1-year follow-up, all patients showed a good cosmetic effect and high satisfaction. Conclusions TUTET is an effective and safe way for men with MG. The uniportal incision is hidden in the areola with sound cosmetic effects. We believe that TUTET is an acceptable procedure for extended thymectomy.
Inhibitory Control Development: A Network Neuroscience Perspective

As one of the core executive functions, inhibition plays an important role in human life through development. Inhibitory control is defined as the ability to suppress actions when they are unlikely to accomplish valuable results. Contemporary neuroscience has investigated the underlying neural mechanisms of inhibitory control. The controversy started to arise, which resulted in two schools of thought: a modulatory and a network account of inhibitory control. In this systematic review, we survey developmental mechanisms in inhibitory control as well as neurodevelopmental diseases related to inhibitory dysfunctions. This evidence stands against the modulatory perspective of inhibitory control: the development of inhibitory control does not depend on a dedicated region such as the right inferior frontal gyrus (rIFG) but relies on a more broadly distributed network.
HAS 1: A natural product from soil-isolated Streptomyces species with potent activity against cutaneous leishmaniasis caused by Leishmania tropica

Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war and the significant displacement of refugees aggravated the spread of this ailment into several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria, Leishmania tropica is identified as one of the most aggressive and endemic identified species, causing localized or generalized lesions, often chronic or relapsing. Pentavalent antimonial drugs are currently used as first line treatment against CL. Nonetheless, these drugs exhibit several limitations, including the repetitive painful injections, high cost, poor availability, and mainly systemic toxicity. Besides, the emergence of acquired parasitic resistance hinders their potency, stressing the need for new therapies to combat CL. Natural products (NPs) epitomize a valuable source in drug discovery. NPs are secondary metabolites (SMs) produced by plants, sponges, or a wide variety of organisms, including environmental microorganisms. The EMR is characterized by its immense biodiversity, yet it remains a relatively untapped area in drug discovery. NPs of the region were explored over the last 2 decades, but their discoveries lack biogeographical diversity and are limited to the Red Sea. Here, we isolated previously uncultured environmental soil-dwelling Streptomyces sp. HAS1, from Hasbaya region in southeast Lebanon. When fermented in one of our production media named INA, HAS1 produced a crude extract with significant potency against a clinical Leishmania tropica isolate. Using bio-guided fractionation, the bioactive compound was purified and the structure was elucidated by NMR and LC-HRMS. Our findings establish NPs as strong candidates for treating Leishmania tropica and further dwells on the importance of these natural sources to combat microbial infections.
Antibacterial activity of peptaibols from Trichoderma longibrachiatum SMF2 against gram-negative Xanthomonas oryzae pv. oryzae, the causal agent of bacterial leaf blight on rice

Bacterial leaf blight caused by Gram-negative pathogen Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive bacterial diseases on rice. Due to the resistance, toxicity and environmental issues of chemical bactericides, new biological strategies are still in need. Although peptaibols produced by Trichoderma spp. can inhibit the growth of several Gram-positive bacteria and plant fungal pathogens, it still remains unclear whether peptaibols have anti-Xoo activity to control bacterial leaf blight on rice. In this study, we evaluated the antibacterial effects of Trichokonins A (TKA), peptaibols produced by Trichoderma longibrachiatum SMF2, against Xoo. The in vitro antibacterial activity analysis showed that the growth of Xoo was significantly inhibited by TKA, with a minimum inhibitory concentration of 54 μg/mL and that the three TKs in TKA all had remarkable anti-Xoo activity. Further inhibitory mechanism analyses revealed that TKA treatments resulted in the damage of Xoo cell morphology and the release of intracellular substances, such as proteins and nucleic acids, from Xoo cells, suggesting the damage of the permeability of Xoo cell membrane by TKA. Pathogenicity analyses showed that the lesion length on rice leaf was significantly reduced by 82.2% when treated with 27 μg/mL TKA. This study represents the first report of the antibacterial activity of peptaibols against a Gram-negative bacterium. Thus, TKA can be of a promising agent in controlling bacterial leaf blight on rice.
Production of beneficial lignans in heterologous host plants

COPYRIGHT © 2022 Koyama, Murata, Horikawa and Satake. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Opinion PUBLISHED 11 October 2022 DOI 10.3389/fpls.2022. 1026664
Overestimation of maximal aerobic speed by the Université de Montréal track test and a 1500-m-time trial in soccer

Introduction: Maximal aerobic speed (MAS), usually measured by cardiopulmonary exercise testing (CPET) on a treadmill, is gaining popularity in soccer to determine aerobic performance. Several field tests are used to estimate MAS, although, gold standard methods are still not clarified. Therefore, this work aims 1) to compare two different CPET based methods to assess MAS and 2) to investigate the convergent validity of two common field tests to estimate MAS in soccer. Methods: Thirteen trained male soccer players completed an CPET on a treadmill to determine two VO2-kinetic based definitions of MAS (MASPlateau = speed at onset of VO2-plateau = gold standard; MAS30s = first speed of 30-s-interval of VO2max), the Université de Montreal Track Test (UMTT; VUMTT = speed of the last stage), and a 1500-m-time trial (1500-m-TT; V1500m = average speed). MASPlateau, MAS30s, VUMTT, and V1500m were compared using ANOVA. Additionally, limits of agreement analysis (LoA), Pearson’s r, and ICC were calculated between tests. Results: MAS30s, VUMTT, and V1500m significantly overestimated MASPlateau by 0.99 km/h (ES = 1.61; p < 0.01), 1.61 km/h (ES = 2.03; p < 0.01) and 1.68 km/h (ES = 1.77; p < 0.01), respectively, with large LoA (-0.21 ≤ LoA≤3.55), however with large-to-very large correlations (0.65 ≤ r ≤ 0.87; p ≤ 0.02; 0.51 ≤ ICC≤ 0.85; p ≤ 0.03). Discussion: The overestimation and large LoA of MASPlateau by all estimates indicate that 1) a uniform definition of MAS is needed and 2) the UMTT and a 1500-m-TT seem questionable for estimating MAS for trained soccer players on an individual basis, while regression equations might be suitable on a team level. The results of the present work contribute to the clarification of acquisition of MAS in soccer.
A study of interactive robot architecture through the practical implementation of conversational android

This study shows an autonomous android robot that can have a natural daily dialogue with humans. The dialogue system for daily dialogue is different from a task-oriented dialogue system in that it is not given a clear purpose or the necessary information. That is, it needs to generate an utterance in a situation where there is no clear request from humans. Therefore, to continue a dialogue with a consistent content, it is necessary to essentially change the design policy of dialogue management compared with the existing dialogue system. The purpose of our study is to constructively find out the dialogue system architecture for realizing daily dialogue through implementing an autonomous dialogue robot capable of daily natural dialogue. We defined the android’s desire necessary for daily dialogue and the dialogue management system in which the android changes its internal (mental) states in accordance to the desire and partner’s behavior and chooses a dialogue topic suitable for the current situation. The developed android could continue daily dialogue for about 10 min in the scene where the robot and partner met for the first time in the experiment. Moreover, a multimodal Turing test has shown that half of the participants had felt that the android was remotely controlled to some degree, that is, the android’s behavior was humanlike. This result suggests that the system construction method assumed in this study is an effective approach to realize daily dialogue, and the study discusses the system architecture for daily dialogue.
Clinical tooth segmentation based on local enhancement

The tooth arrangements of human beings are challenging to accurately observe when relying on dentists’ naked eyes, especially for dental caries in children, which is difficult to detect. Cone-beam computer tomography (CBCT) is used as an auxiliary method to measure patients’ teeth, including children. However, subjective and irreproducible manual measurements are required during this process, which wastes much time and energy for the dentists. Therefore, a fast and accurate tooth segmentation algorithm that can replace repeated calculations and annotations in manual segmentation has tremendous clinical significance. This study proposes a local contextual enhancement model for clinical dental CBCT images. The local enhancement model, which is more suitable for dental CBCT images, is proposed based on the analysis of the existing contextual models. Then, the local enhancement model is fused into an encoder–decoder framework for dental CBCT images. At last, extensive experiments are conducted to validate our method.
Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention

Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in neurological diseases, including intracerebral hemorrhage (ICH). Microglia are activated to acquire either pro-inflammatory or anti-inflammatory phenotypes. After the onset of ICH, pro-inflammatory mediators produced by microglia at the early stages serve as a crucial character in neuroinflammation. Conversely, switching the microglial shift to an anti-inflammatory phenotype could alleviate inflammatory response and incite recovery. This review will elucidate the dynamic profiles of microglia phenotypes and their available shift following ICH. This study can facilitate an understanding of the self-regulatory functions of the immune system involving the shift of microglia phenotypes in ICH. Moreover, suggestions for future preclinical and clinical research and potential intervention strategies are discussed.
Imputation to whole-genome sequence and its use in genome-wide association studies for pork colour traits in crossbred and purebred pigs

Imputed whole-genome sequence (WGS) has been proposed to improve genome-wide association studies (GWAS), since all causative mutations responsible for phenotypic variation are expected to be present in the data. This approach was applied on a large number of purebred (PB) and crossbred (CB) pigs for 18 pork color traits to evaluate the impact of using imputed WGS relative to medium-density marker panels. The traits included Minolta A*, B*, and L* for fat (FCOL), quadriceps femoris muscle (QFCOL), thawed loin muscle (TMCOL), fresh ham gluteus medius (GMCOL), ham iliopsoas muscle (ICOL), and longissimus dorsi muscle on the fresh loin (FMCOL). Sequence variants were imputed from a medium-density marker panel (61K for CBs and 50K for PBs) in all genotyped pigs using BeagleV5.0. We obtained high imputation accuracy (average of 0.97 for PBs and 0.91 for CBs). GWAS were conducted for three datasets: 954 CBs and 891 PBs, and the combined CBs and PBs. For most traits, no significant associations were detected, regardless of panel density or population type. However, quantitative trait loci (QTL) regions were only found for a few traits including TMCOL Minolta A* and GMCOL Minolta B* (CBs), FMCOL Minolta B*, FMCOL Minolta L*, and ICOL Minolta B* (PBs) and FMCOL Minolta A*, FMCOL Minolta B*, GMCOL Minolta B*, and ICOL Minolta B* (Combined dataset). More QTL regions were identified with WGS (n = 58) relative to medium-density marker panels (n = 22). Most of the QTL were linked to previously reported QTLs or candidate genes that have been previously reported to be associated with meat quality, pH and pork color; e.g., VIL1, PRKAG3, TTLL4, and SLC11A1, USP37. CTDSP1 gene on SSC15 has not been previously associated with meat color traits in pigs. The findings suggest any added value of WGS was only for detecting novel QTL regions when the sample size is sufficiently large as with the Combined dataset in this study. The percentage of phenotypic variance explained by the most significant SNPs also increased with WGS compared with medium-density panels. The results provide additional insights into identification of a number of candidate regions and genes for pork color traits in different pig populations.
Extracting work from correlations

We consider the problem of extracting work from isolated quantum systems composed of $n$ subsystems. In this scenario the work can be naturally divided into two contributions: a local contribution from each subsystem, and a global contribution originating from correlations between subsystems. Here we focus on the latter and consider quantum systems which are locally thermal, thus from which work can only be extracted from correlations. We derive bounds on the extractable work for general quantum states, separable states, and states with fixed entropy. Our results show that while entanglement gives an advantage for small quantum systems, this gain vanishes for a large number of subsystems.
Phosphorus retention and agronomic efficiency of refined manure-based digestate—A review

Digestate, a by-product from anaerobic digestion of organic materials such as animal manure, is considered a suitable plant fertilizer. However, due to its bulkiness and low economic value, it is costly to transport over long distances and store for long periods. Refinement processes to valorize digestate and facilitate its handling as a fertilizer include precipitation of phosphorus-rich mineral compounds, such as struvite and calcium phosphates, membrane filtration methods that concentrate plant nutrients in organic products, and carbonization processes. However, phosphorus retention efficiency in output products from these processes can vary considerably depending on technological settings and characteristics of the digestate feedstock. The effects of phosphorus in plant fertilizers (including those analogous or comparable to refined digestate products) on agronomic productivity have been evaluated in multiple experiments. In this review, we synthesized knowledge about different refinement methods for manure-based digestate as a means to produce phosphorus fertilizers, thereby providing the potential to increase phosphorus retention in the food production chain, by combining information about phosphorus flows in digestate refinement studies and agronomic fertilizer studies. It was also sought to identify the range, uncertainty, and potential retention efficiency by agricultural crops of the original phosphorus amount in manure-based digestate. Refinement chains with solid/wet phase separation followed by struvite or calcium phosphate precipitation or membrane filtration of the wet phase and carbonization treatments of the solid phase were included. Several methods with high potential to extract phosphorus from manure-based wet phase digestate in such a way that it could be used as an efficient plant fertilizer were identified, with struvite precipitation being the most promising method. Synthesis of results from digestate refinement studies and agronomic fertilizer experiments did not support the hypothesis that solid/wet separation followed by struvite precipitation, or any other refinement combination, results in higher phosphorus retention than found for unrefined digestate. Further studies are needed on the use of the phosphorus in the solid phase digestate, primarily on phosphorus-rich soils representative of animal-dense regions, to increase understanding of the role of digestate refinement (particularly struvite precipitation) in phosphorus recycling in agricultural systems.
Clinal variation as a tool to understand climate change

Clines are observable gradients that reflect continuous change in biological traits of species across geographical ranges. Clinal gradients could vary at geographic scales (latitude and altitude). Since clinal variations represent active genomic responses at the population level they (clines) provide an immense power to address questions related to climatic change. With the fast pace of climate change i.e. warming, populations are also likely to exhibit rapid responses; at both the phenotypic and genotypic levels. We seek to understand how clinal variation could be used to anticipate climatic responses using Drosophila, a pervasively used inter-disciplinary model system owing to its molecular repertoire. The genomic information coupled with the phenotypic variation greatly facilitates our understanding of the Drosophilidae response to climate change. We discuss traits associated with clinal variation at the phenotypic level as well as their underlying genetic regulators. Given prevailing climatic conditions and future projections for climate change, clines could emerge as monitoring tools to track the cross-talk between climatic variables and organisms.