Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of low-protein diet on the intestinal morphology, digestive enzyme activity, blood urea nitrogen, and gut microbiota and metabolites in weaned pigs

ABSTRACT This study investigated the effects of low-protein diet supplemented with Lysine (Lys), Methionine (Met), Threonine (Thr), and Tryptophan (Trp) on small intestine morphology, enzyme activity, blood urea nitrogen, and gut microbiota and metabolites in weaned piglets. Eighteen weaned pigs weighing an average of 9.57 kg received one of three treatments: a normal protein diet with 20% crude protein (CP, diet [NP]), a moderately reduced protein diet with 17% CP (MP), or a low-protein diet with 14% CP (LP). All three diets were supplemented with Lys, Met, Thr and Trp to meet essential amino acid requirements for post-weaned piglets according to the NRC (2012). Following a 45 d study period, piglets on the LP and MP diets demonstrated atrophic small intestinal morphology, with decreased villus heights and lower ratios of villus height to crypt depth (p < 0.05); pepsin activity in the stomach was also reduced in these two groups (p < 0.05). Increased plasma cholesterol and decreased blood urea nitrogen presented in the MP and LP groups compared with the NP group (p < 0.05). Overall, gastrointestinal hormones were not affected by dietary protein levels with the exception of reduced somatostatin levels in the MP and LP groups. Jejunum and colon microbiota were not affected at either the phyla or genera level in any of the diets. Colonic ammonia nitrogen concentration was reduced in MP and LP groups. Dietary protein level had no effect on short chain fatty acids or biogenic amines. Our data suggest that reducing dietary protein levels by 3% (MP) or 6% (LP) in weaned pigs has the potential to decrease nitrogen emissions and impaired digestive capacity. Therefore, dietary protein level cannot be reduced by more than 3% in consideration of maladaptive changes to small intestinal morphology and pepsin activity in weaned piglets.
HMGA2 regulates acute myeloid leukemia progression and sensitivity to daunorubicin via Wnt/β-catenin signaling

Acute myeloid leukemia (AML) is a malignant disease with an increasing prevalence in adults and children. However, valuable molecular diagnostic research is rare. In the present study, plasmids silencing and overexpressing high-mobility group AT-hook 2 (HMGA2) were respectively transfected in HL60 and NB4 cells. The effects of HMGA2 on AML cell viability, apoptosis, migration and invasion were determined by preforming MTT, flow cytometry, wound scratch and Transwell assays, respectively. Genes associated with apoptosis and Wnt signaling were evaluated by reverse transcription-quantitative (RT-q)-PCR and western blotting. AML cell sensitivity to daunorubicin (DNR) and the regulatory effects of the Wnt signaling pathway via HMGA2 following treatment with the agonist LiCl or antagonist XAV939 were detected by MTT, RT-qPCR and western blot analysis. The results revealed that the expression of HMGA2 was elevated more so in HL60, KG1, U937, Kasumi-1, THP-1 and K562 cells than in NB4 cells. Silencing HMGA2 suppressed cell viability, migration and invasion, enhanced cell apoptosis and sensitivity to DNR, and almost restored the DNR inhibitory function that was promoted by LiCl treatment. In addition, low expression of HMGA2 attenuated X-linked inhibitor of apoptosis and Bcl-2 mRNA and protein levels, and upregulated the expression of Bax and cleaved-caspase-3. Furthermore, silencing HMGA2 not only decreased Wnt and non-phospho-β-catenin expressions, but also partially reversed the increased expressions of these proteins induced by LiCl treatment. On the other hand, overexpression of HMGA2 exhibited the opposite results after transfection in NB4 cells. The results of the present study demonstrated that HMGA2 played important roles in driving AML progression and chemosensitivity in HL60 and NB4 cells, potentially by activating the Wnt/β-catenin signaling pathway. Therefore, it was suggested that HMGA2 may be a promising molecular marker for AML diagnosis.
Cargo Sorting at the trans-Golgi Network for Shunting into Specific Transport Routes: Role of Arf Small G Proteins and Adaptor Complexes

The trans-Golgi network (TGN) is responsible for selectively recruiting newly synthesized cargo into transport carriers for delivery to their appropriate destination. In addition, the TGN is responsible for receiving and recycling cargo from endosomes. The membrane organization of the TGN facilitates the sorting of cargoes into distinct populations of transport vesicles. There have been significant advances in defining the molecular mechanism involved in the recognition of membrane cargoes for recruitment into different populations of transport carriers. This machinery includes cargo adaptors of the adaptor protein (AP) complex family, and monomeric Golgi-localized γ ear-containing Arf-binding protein (GGA) family, small G proteins, coat proteins, as well as accessory factors to promote budding and fission of transport vesicles. Here, we review this literature with a particular focus on the transport pathway(s) mediated by the individual cargo adaptors and the cargo motifs recognized by these adaptors. Defects in these cargo adaptors lead to a wide variety of diseases.
The Respiratory Burst Oxidase Homolog D (RbohD) Cell and Tissue Distribution in Potato–Potato Virus Y (PVYNTN) Hypersensitive and Susceptible Reactions

The respiratory burst oxidase homolog D (RbohD) acts as a central driving force of reactive oxygen species signaling in plant cells by integrating many different signal transduction pathways in plants, including incompatible interactions with pathogens. This study demonstrated the localization and distribution of RbohD in two types of potato–potato virus Y (PVY) interactions: Compatible and incompatible (resistant). The results indicated a statistically significant induction of the RbohD antigen signal in both interaction types. In the hypersensitive response (resistant reaction) of potato with a high level of resistance to the potato tuber necrotic strain of PVY (PVYNTN), RbohD localization followed by hydrogen peroxide (H2O2) detection was concentrated in the apoplast. In contrast, in the hypersensitive response of potato with a low resistance level to PVYNTN, the distribution of RbohD was concentrated more in the plant cell organelles than in the apoplast, resulting in the virus particles being present outside the inoculation area. Moreover, when compared to mock-inoculated plants and to the hypersensitive response, the PVYNTN-compatible potato interaction triggered high induction in the RbohD distribution, which was associated with necrotization. Our findings indicated that RbohD and hydrogen peroxide deposition was associated with the hypersensitive response, and both were detected in the vascular tissues and chloroplasts. These results suggest that the RbohD distribution is actively dependent on different types of PVY NTN-potato plant interactions. Additionally, the RbohD may be involved in the PVYNTN tissue limitation during the hypersensitive response, and it could be an active component of the systemic signal transduction in the susceptible host reaction.
Effect of ammonium to nitrite ratio on reactor performance and microbial population structure in anammox reactors

ABSTRACT Anaerobic ammonium oxidation (anammox) presents an efficient alternative for conventional nitrogen removal process. In this study, the effect of varying Substrate (ammonium to nitrite) ratios on reactor performance and microbial community structures within three anaerobic sequencing batch reactors (ASBRs) was investigated. Three 1 L ASBRs (Reactors 1, 2 and 3) were operated under similar operational conditions. By varying the ammonium to nitrite ratios, a significant variation in nitrogen removal was observed after 170 days of operation: nitrogen removal efficiencies of 67.17 ± 7.29%, 57.13 ± 11.18% and 56.26 ± 17.05% in Reactors 3, 2 and 1 respectively were achieved. Similarly, using quantitative PCR, an overall variation in the population of anammox bacteria, ammonia oxidizing bacteria (AOB), Nitrospira and copy numbers of nirS, hzo and hzs genes were observed with varying degrees of expression. High throughput sequencing analysis further showed a shift in microbial community structure with an overall increase in population of Planctomycetia from 0.76% to (3%, 25% and 26%) and Betaproteobacteria from 5.38% to (19%, 21% and 43%) within Reactors 1, 2 and 3, respectively. In conclusion, different substrates ratio showed a significant influence on the overall nitrogen removal rate as well as the abundances of the different microbial groups. GRAPHICAL ABSTRACT
The Learning Curve of Subaxial Cervical Pedicle Screw Placement: How Can We Avoid Neurovascular Complications in the Initial Period?

BACKGROUND Despite the biomechanical benefits of subaxial cervical pedicle screw (CPS) placement, possible neurovascular complications, including vertebral artery and nerve root injury, are of great concern. We have demonstrated many times the safety and efficacy of CPS deployments, even when using freehand technology. OBJECTIVE To analyze the learning curve of CPS placement to determine the number of cases necessary for assuring safe CPS placement and to identify a reasonable accuracy rate. METHODS From March 2012 to August 2018, a single surgeon performed posterior cervical fusion surgery using CPS placement on 162 consecutive patients. We classified whole surgical periods, 6 years, into 4 periods. We analyzed the screw breach rate, lateral mass screw conversion (LMSC) rate, and reposition rate. We also compared the CPS placement accuracy in the initial 15, 20, and 30 patients with the other 147, 142, and 132 patients, respectively, to assess the number of procedures necessary to reach the learning curve plateau and to identify a reasonable accuracy rate. RESULT The total number of planned CPS placements was 979. Our learning curve showed that the breach rate plateaus at 3% to 4%. The necessary numbers for safe and accurate CPS placement during learning curve were 30 patients and 170 screws. None of the patients undergoing CPS developed a neurologic or vascular complication. CONCLUSION By following our 5 safety steps, the steady state for safety and accuracy can be reached without neurovascular complications even in the initial period of the learning curve.
Pharmacological characterization of the calcium influx pathways involved in nitric oxide production by endothelial cells

ABSTRACT Objective: To characterize the calcium influx pathways implicated in the sustained elevation of endothelial intracellular calcium concentration, required for the synthesis and release of relaxing factors. Methods: We evaluated the effect of the newly synthesized pyrazole derivatives, described as selective inhibitors for ORAI (BTP2/Pyr2 and Pyr6) and TRPC3 (Pyr3 and Pyr10) channels, upon endothelium- and extracellular calcium-dependent relaxations stimulated by acetylcholine and thapsigargin, in pre-constricted rat thoracic aortic rings. Results: Acetylcholine and thapsigargin responses were completely reverted by Pyr2 and Pyr6 (1 to 3μM). Pyr3 (0.3 to 3μM) caused a rapid reversal of acetylcholine (6.2±0.08mg.s−1) and thapsigargin (3.9±0.25mg.s−1) relaxations, whereas the more selective TRPC3 blocker Pyr10 (1 to 3μM) had no effect. The recently described TRPC4/5 selective blocker, ML204 (1 to 3μM), reverted completely acetylcholine relaxations, but minimally thapsigargin induced ones. Noteworthy, relaxations elicited by GSK1016790A (TRPV4 agonist) were unaffected by pyrazole compounds or ML204. After Pyr2 and Pyr6 pre-incubation, acetylcholine and thapsigargin evoked transient relaxations similar in magnitude and kinetics to those observed in the absence of extracellular calcium. Sodium nitroprusside relaxations as well as phenylephrine-induced contractions (denuded aorta) were not affected by any of pyrazole compounds (1 to 3μM). Conclusion: These observations revealed a previously unrecognized complexity in rat aorta endothelial calcium influx pathways, which result in production and release of nitric oxide. Pharmacologically distinguishable pathways mediate acetylcholine (ORAI/TRPC other than TRPC3/TRPC4 calcium-permeable channels) and thapsigargin (TRPC4 not required) induced calcium influx.
Computational Methods for Extremal Steklov Problems

We develop a computational method for extremal Steklov eigenvalue problems and apply it to study the problem of maximizing the $p$th Steklov eigenvalue as a function of the domain with a volume constraint. In contrast to the optimal domains for several other extremal Dirichlet- and Neumann-Laplacian eigenvalue problems, computational results suggest that the optimal domains for this problem are very structured. We reach the conjecture that the domain maximizing the $p$th Steklov eigenvalue is unique (up to dilations and rigid transformations), has $p$-fold symmetry, and has at least one axis of symmetry. The $p$th Steklov eigenvalue has multiplicity 2 if $p$ is even and multiplicity 3 if $p\geq3$ is odd.
Isoflavones and postmenopausal bone health: a viable alternative to estrogen therapy?

OBJECTIVE The rapidly growing postmenopausal population in the United States, and this population's high incidence and prevalence of osteoporosis and related morbidity and mortality herald an enormous public health burden for the coming decades. Estrogen replacement has been the mainstay of therapy for the prevention and treatment of osteoporosis in this estrogen-deficient population. However, long-term compliance with estrogen therapy generally is poor, and there are numerous concerns regarding its safety. The phytoestrogens are nonsteroidal plant-derived compounds that exhibit estrogenic activity at several sites. The isoflavones are one class of phytoestrogens derived largely from soy-based products. International popularity for menopausal therapy regimens containing isoflavones is growing rapidly. In this article, we review the existing data on isoflavones and postmenopausal bone health. DESIGN A review of interventional trials examining isoflavones and bone in animals and humans. RESULTS The data point to a reduction in bone resorption resulting from isoflavone/ipriflavone intake. CONCLUSIONS The data on naturally occurring isoflavones are very limited but suggest that including them in the diet results in reduction in bone resorption caused by estrogen deficiency. The extensive data on ipriflavone, a synthetic isoflavone derivative, suggest that it is a useful and safe alternative to estrogen therapy in treating existing low bone mass or osteoporosis in postmenopausal women. Further studies are warranted to examine the utility of ipriflavone as a preventive agent, as well as the clinical efficacy of the naturally occurring isoflavones.
Lasers in Surgery and Medicine

Kamila Pasternak‐Mnich,* Barbara Ziemba, Aleksandra Szwed, Karolina Kopacz, Marek Synder, Maria Bryszewska, and Jolanta Kujawa Department of Medical Rehabilitation, Faculty of Health Sciences, Medical University of Lodz, 251 Pomorska St., 92‐213, Lodz, Poland Department of Clinical Genetic, Medical University of Lodz, 251 Pomorska St., 92‐213, Lodz, Poland Department of General Biophysics, University of Lodz, 141/143 Pomorska St., 90‐236, Lodz, Poland “DynamoLab” Academic Laboratory of Movement and Human Physical Performance, Medical University of Lodz, 251 Pomorska St., 92‐213, Lodz, Poland Medical Faculty, Clinic of Orthopedics and Pediatric Orthopedics, Medical University of Lodz, 251 Pomorska St., 92‐213, Lodz, Poland
An Interbank Market Network Model based on Bank Credit Lending Preference

An interbank market network model based on bank credit lending preference is built in this paper to explain the formation mechanism of interbank market network structure. As well, we analyze the impact of credit lending risk preference on network topology structure, which includes degree distribution, network clustering coefficient, average shortest path length and network efficiency. Simulation results demonstrate that the accumulation degree follows dual power law distribution with credit lending risk preference parameter value equal or greater than 1, while the accumulation degree follows power law distribution with credit lending risk preference parameter value smaller than 1. The interbank market network shows small world topology property. With the increasing of bank credit lending risk preference, the average shortest path length decreases but network efficiency improves, which enhances the stability of the network.
The Cdk1/Cdk2 homolog CDKA;1 controls the recombination landscape in Arabidopsis

Significance Cyclin-dependent kinases are the main drivers of the mitotic cell cycle. Here, we show that the activity of the main cell-cycle regulator in the model plant Arabidopsis, CDKA;1, also governs one of the most important processes in meiosis: the formation of meiotic cross-overs. We show that CDKA;1 activity especially affects the major class of meiotic cross-overs, known as class I cross-overs. We find that lowering kinase activity leads to a progressive loss of cross-overs, of which cross-overs near the chromosome ends are the last to disappear. Conversely, an increase of kinase activity increases the rate of cross-over formation. Little is known how patterns of cross-over (CO) numbers and distribution during meiosis are established. Here, we reveal that cyclin-dependent kinase A;1 (CDKA;1), the homolog of human Cdk1 and Cdk2, is a major regulator of meiotic recombination in Arabidopsis. Arabidopsis plants with reduced CDKA;1 activity experienced a decrease of class I COs, especially lowering recombination rates in centromere-proximal regions. Interestingly, this reduction of type I CO did not affect CO assurance, a mechanism by which each chromosome receives at least one CO, resulting in all chromosomes exhibiting similar genetic lengths in weak loss-of-function cdka;1 mutants. Conversely, an increase of CDKA;1 activity resulted in elevated recombination frequencies. Thus, modulation of CDKA;1 kinase activity affects the number and placement of COs along the chromosome axis in a dose-dependent manner.
A First‐in‐Human Phase I Study of GC1118, a Novel Anti‐Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors

Abstract Lessons Learned. GC1118 is a novel fully human anti‐epidermal growth factor receptor (EGFR) antibody with unique binding epitopes and different ligand‐binding inhibitory activity compared with cetuximab or panitumumab. GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. Skin toxicities were more common and diarrhea was less frequent compared with other anti‐EGFR antibodies. Background. GC1118 is a novel monoclonal antibody targeting epidermal growth factor receptor (EGFR) with more potent ligand inhibition than cetuximab or panitumumab. We conducted a first‐in‐human, phase I study of GC118 in patients with refractory solid tumors. Methods. In the dose escalation part, GC1118 was administered on days 1, 8, 15, and 22, followed by a 2‐week rest, during which dose‐limiting toxicities (DLTs) were evaluated. In the expansion part, patients were enrolled into three cohorts (Cohort 1 [C1], patients with colorectal cancer [CRC] without prior anti‐EGFR treatment; Cohort 2 [C2], patients with CRC with tumors resistant to anti‐EGFR therapy; Cohort 3 [C3], EGFR‐overexpressing gastric cancer). Results. In the dose escalation part, 24 patients were treated at five dose levels: 0.3, 1.0, 3.0, 4.0, and 5.0 mg/kg. In the 5.0 mg/kg cohort, two patients experienced DLTs (skin toxicities). The maximum‐tolerated dose (MTD) was 4.0 mg/kg. Common adverse events were skin toxicities. In the expansion part, 39 patients were enrolled. In Cohort 1, stable disease (SD) was observed in 58%; in Cohort 2, partial response (PR) 17% and SD 8%; in Cohort 3, PR 8% and SD 17%. Conclusion. GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti‐EGFR antibodies might be advantageous for further development.
Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD

ABSTRACT Introduction: Despite stimulants being highly efficacious in short-term randomized controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of novel non-stimulant options are currently in the pipeline for the treatment of attention-deficit/hyperactivity disorder (ADHD). Areas covered: The authors conducted a systematic review of RCTs registered in ClinicalTrials.gov in the past 5 years (January 2014 and February 2019), supplemented by searches in PubMed, Web of Science, and drug manufacturer websites to find recent RCTs on novel non-stimulant ADHD medications. Expert opinion: The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), Mazindol, and Molindone hydrochloride (SPN-810). Given the high effect size found in RCTs of stimulants in terms of efficacy on ADHD core symptoms, it is unlikely that these novel agents will show better efficacy than stimulants, at the group level. However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a ‘one size fits all’ to a ‘precision medicine’ approach.
The Shape of the Concentration–Response Association between Fine Particulate Matter Pollution and Human Mortality in Beijing, China, and Its Implications for Health Impact Assessment

Background: Studies found approximately linear short-term associations between particulate matter (PM) and mortality in Western communities. However, in China, where the urban PM levels are typically considerably higher than in Western communities, some studies suggest nonlinearity in this association. Health impact assessments (HIA) of PM in China have generally not incorporated nonlinearity in the concentration–response (C-R) association, which could result in large discrepancies in estimates of excess deaths if the true association is nonlinear. Objectives: We investigated nonlinearity in the C-R associations between with PM with aerodynamic diameter ≤2. 5μm (PM2.5) and mortality in Beijing, China, and the sensitivity of HIA to linearity assumptions. Methods: We modeled the C-R association between PM2.5 and cause-specific mortality in Beijing, China (2009–2012), using generalized linear models (GLM). PM2.5 was included through either linear, piecewise-linear, or spline functions to investigate evidence of nonlinearity. To determine the sensitivity of HIA to linearity assumptions, we estimated PM2.5-attributable deaths using both linear- and nonlinear-based C-R associations between PM2.5 and mortality. Results: We found some evidence that, for nonaccidental and circulatory mortality, the shape of the C-R association was relatively flat at lower concentrations of PM2.5, but then had a positive slope at higher concentrations, indicating nonlinearity. Conversely, the shape for respiratory mortality was positive and linear at lower concentrations of PM2.5, but then leveled off at the higher concentrations. Estimates of excess deaths attributable to short-term PM2.5 exposure were, in some cases, very sensitive to the linearity assumption in the association, but in other cases robust to this assumption. Conclusions: Our results demonstrate some evidence of nonlinearity in PM2.5–mortality associations and that an assumption of linearity in this association can influence HIAs, highlighting the importance of understanding potential nonlinearity in the PM2.5–mortality association at the high concentrations of PM2.5 in developing megacities like Beijing. https://doi.org/10.1289/EHP4464