Miracle-dz/UniFAR-FTUs huggingface dataset:
Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients

In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 μg GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD65-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC < 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8+ T cells activation. Patients with poorer clinical response had higher baseline levels of GAD65-induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment. Clinical Trial Registration clinicaltrials.gov, identifier NCT02352974.
Decoding the Temporal Dynamics of Covert Spatial Attention Using Multivariate EEG Analysis: Contributions of Raw Amplitude and Alpha Power

Attention can be oriented in space covertly without the need of eye movements. We used multivariate pattern classification analyses (MVPA) to investigate whether the time course of the deployment of covert spatial attention leading up to the observer’s perceptual decision can be decoded from both EEG alpha power and raw activity traces. Decoding attention from these signals can help determine whether raw EEG signals and alpha power reflect the same or distinct features of attentional selection. Using a classical cueing task, we showed that the orientation of covert spatial attention can be decoded by both signals. However, raw activity and alpha power may reflect different features of spatial attention, with alpha power more associated with the orientation of covert attention in space and raw activity with the influence of attention on perceptual processes.
Functional MRI-Specific Alterations in Executive Control Network in Mild Cognitive Impairment: An ALE Meta-Analysis

Background: Mild cognitive impairment (MCI) is regarded as a transitional stage between normal aging and Alzheimer's disease (AD) dementia. MCI individuals with deficits in executive function are at higher risk for progressing to AD dementia. Currently, there is no consistent result for alterations in the executive control network (ECN) in MCI, which makes early prediction of AD conversion difficult. The aim of the study was to find functional MRI-specific alterations in ECN in MCI patients by expounding on the convergence of brain regions with functional abnormalities in ECN. Methods: We searched PubMed, Embase, and Web of Science to identify neuroimaging studies using methods including the amplitude of low frequency fluctuation/fractional amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in MCI patients. Based on the Activation Likelihood Estimation algorithm, the coordinate-based meta-analysis and functional meta-analytic connectivity modeling were conducted. Results: A total of 25 functional imaging studies with MCI patients were included in a quantitative meta-analysis. By summarizing the included articles, we obtained specific brain region changes, mainly including precuneus, cuneus, lingual gyrus, middle frontal gyrus, posterior cingulate cortex, and cerebellum posterior lobe, in the ECN based on these three methods. The specific abnormal brain regions indicated that there were interactions between the ECN and other networks. Conclusions: This study confirms functional imaging specific abnormal markers in ECN and its interaction with other networks in MCI. It provides novel targets and pathways for individualized and precise interventions to delay the progression of MCI to AD.
Nutritional Characterization of Diacylglycerols in Rats

ジアシルグリセリン (DG) は, 血清トリアシルグリセリン (TG) の上昇を抑制する脂質である。 1, 3-DGと1, 2-DGから成るDGの栄養学的特徴を, ラットで検討した。 DGとTGの間には, 消化及び代謝過程において, 明らかな違いが認められた。 結果は次の通りである。 (1) 小腸内において, DGからはTGの消化物中にはほとんど見られなかった1-モノアシルグリセリンが生成した。 (2) DG投与後には, TGと比較して多量の脂肪酸が小腸から門脈へ放出された。 (3) DG摂取は, 肝臓での脂肪酸のβ酸化を促進し, ケトン体を尿中へ放出させた。 (4) ラットにおいて, DG投与後の酸素消費量は, TG投与後に比べて増加した。 これらの結果から, DGはエネルギーとして利用されやすく, そのためTGと比較して体脂肪として蓄積しにくいものと考えられた。
Iron-Catalyzed Oxidation of 1-Phenylethanol and Glycerol With Hydrogen Peroxide in Water Medium: Effect of the Nitrogen Ligand on Catalytic Activity and Selectivity

The iron(II) complexes [Fe(bpy)3](OTf)2 (bpy = 2,2'-bipyridine; OTf = CF3SO3) (1) and [Fe(bpydeg)3](OTf)2 (bpydeg = N4,N4-bis(2-(2-methoxyethoxy)ethyl) [2,2'-bipyridine]-4,4'-dicarboxamide) (2), the latter being a newly synthesized ligand, were employed as catalyst precursors for the oxidation of 1-phenylethanol with hydrogen peroxide in water, using either microwave or conventional heating. With the same oxidant and medium the oxidation of glycerol was also explored in the presence of 1 and 2, as well as of two similar iron(II) complexes bearing tridentate ligands, i.e., [Fe(terpy)2](OTf)2 (terpy = 2, 6-di(2-pyridyl)pyridine) (3) and [Fe(bpa)2](OTf)2 (bpa = bis(2-pyridinylmethyl)amine) (4): in most reactions the major product formed was formic acid, although with careful tuning of the experimental conditions significant amounts of dihydroxyacetone were obtained. Addition of heterocyclic amino acids (e.g., picolinic acid) increased the reaction yields of most catalytic reactions. The effect of such additives on the evolution of the catalyst precursors was studied by spectroscopic (NMR, UV-visible) and ESI-MS techniques.
Cruzipain and Its Physiological Inhibitor, Chagasin, as a DNA-Based Therapeutic Vaccine Against Trypanosoma cruzi

Chagas disease caused by the protozoan parasite Trypanosoma cruzi is endemic in 21 Latin American countries and the southern United States and now is spreading into several other countries due to migration. Despite the efforts to control the vector throughout the Americas, currently, there are almost seven million infected people worldwide, causing ~10,000 deaths per year, and 70 million people at risk to acquire the infection. Chagas disease treatment is restricted only to two parasiticidal drugs, benznidazole and nifurtimox, which are effective during the acute and early infections but have not been found to be as effective in chronic infection. No prophylactic or therapeutic vaccine for human use has been communicated at this moment. Here, we evaluate in a mouse model a therapeutic DNA vaccine combining Cruzipain (Cz), a T. cruzi cysteine protease that proved to be protective in several settings, and Chagasin (Chg), which is the natural Cz inhibitor. The DNAs of both antigens, as well as a plasmid encoding GM-CSF as adjuvant, were orally administrated and delivered by an attenuated Salmonella strain to treat mice during the acute phase of T. cruzi infection. The bicomponent vaccine based on Salmonella carrying Cz and Chg (SChg+SCz) was able to improve the protection obtained by each antigen as monocomponent therapeutic vaccine and significantly increased the titers of antigen- and parasite-specific antibodies. More importantly, the bicomponent vaccine triggered a robust cellular response with interferon gamma (IFN-γ) secretion that rapidly reduced the parasitemia during the acute phase and decreased the tissue damage in the chronic stage of the infection, suggesting it could be an effective tool to ameliorate the pathology associated to Chagas disease.
Circular RNA Signature in Lung Adenocarcinoma: A MiOncoCirc Database-Based Study and Literature Review

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a structure of covalently closed continuous loops, which can regulate gene expression by acting as a microRNA sponge or through other mechanisms. Recent studies have identified that the expression of candidate circRNAs are dysregulated in various tumors and hence are considered as promising diagnostic or therapeutic targets across cancer types. However, the expression and function of circRNAs in lung adenocarcinoma (LUAD) remains unclear. In this article, we investigated the expression of circRNAs in LUAD via MiOncoCirc, which is the first and comprehensive database characterizing circRNAs across >2,000 cancer samples using an exome capture RNA sequencing. We identified seven abnormally expressed circRNAs in LUAD, including circCDR1-AS, circHIPK3, circFNDC3B, circPCMTD1, circRHOBTB3, circFAM13B, and circMAN1A2, as well as conducted a literature review about the function and features of these circRNAs. Previous studies have demonstrated that circCDR1-AS, circMAN1A2, and circHIPK3 were upregulated and significantly correlated with a poor survival, or promoted the tumor progression in lung cancer, whereas other circRNAs have not been fully explored. Besides, we reviewed all the publications regarding circRNAs and LUAD, and noticed that the dysregulation of these circRNAs impacts the development of LUAD through a variety of regulatory mechanisms. In conclusion, the underlying mechanisms of aberrant expression and functions of circRNAs in LUAD are worthy of being further investigated.
Bone Histology of the Non-Iguanodontian Ornithopod Jeholosaurus shangyuanensis and Its Implications for Dinosaur Skeletochronology and Development

ABSTRACT Bone histology has provided valuable information on the life history of dinosaurs, and the presence of growth lines provides useful information for age estimation, growth variation, and the reconstruction of paleobehavior. Here, we present new data recovered from five individuals of the non-iguanodontian ornithopod dinosaur Jeholosaurus shangyuanensis from the Early Cretaceous Jehol Biota. These specimens, ranging in body length from 16 to 62 cm, represent early juvenile, late juvenile, and subadult ontogenetic stages. The bones of Jeholosaurus mainly consist of fibrolamellar tissue, which is similar to that of other non-iguanodontian ornithopods; however, parallel-fibered bone and lamellar bone tissues were also deposited in early juvenile through subadult individuals, suggesting relatively slow growth rates. Parallel-fibered bone is only regionally present in the juvenile but is well developed throughout the outermost cortex of the subadult. Skeletochronology indicates that these specimens range in age from one to five years old. Analyzing bone tissue distribution and lines of arrested growth (LAGs) in these specimens, we estimate that Jeholosaurus reached sexual maturity at two to four years old. The largest individual (IVPP V15939) displays an apparently higher growth rate during the first two years, which is abruptly reduced in the following years, suggesting a distinct growth pattern that may be related to sexual dimorphism or variable environmental conditions. Finally, the largest specimen displays parallel-fibered bone tissue but lacks an external fundamental system (EFS) near the periphery, suggesting that it was still growing but was approaching somatic maturity at death.
Sources of Cryptocurrency Value Systems: The Case of Bitcoin

ABSTRACT Cryptocurrencies are a hotly debated topic because it is not clear why they should be valued as they are. Bitcoin, by far the most prominent cryptocurrency, currently trades around $9,500 USD. “Why is Bitcoin valuable? ” is a question often heard but seldom answered well. It is not the legal tender of any nation, nor does it represent anything of physical or intrinsic value. Some people attribute its value to its scarcity, others to its anonymity, and others to its immutability, all of which are created and managed by a computer algorithm. Current theories fail to explain Bitcoin’s value, or it is not immediately apparent how they might explain it. We are therefore motivated to investigate the sources of cryptocurrency value through the emergent value systems of the Bitcoin community. We use concourse theory and Q-methodology to discover five types of Bitcoin value systems that are complementary and coexisting facets of a collective whole, each type being its own internally consistent “theory” of value, and therefore our typology avoids simplistic generalizations about cryptocurrencies and the motivations behind those involved. We named the types: Fintech, Libertarians, Purists, Average Joe, and Gentrifier. Of interest, four of the five types we identified appear not to value Bitcoin for its monetary or market value, despite what is usually assumed. Instead, Bitcoin is associated with its potential as an alternative currency that may be used to exchange value, to mitigate various forms of risk, or as a force for social and cultural change. These five types may also underlie broader digital innovation processes and provide a basis from which to understand them.
Effect of Fermented Peanut Shell on Production Performance,Carcass Traits,Meat Quality and Economic Benefits of Fattening Pigs

This experiment was conducted to investigate the effect of fermented peanut shell on production performance,carcass traits,meat quality and economic benefits of fattening pigs.100 fattening pigs(Duroc×Landrace×Yorkshire)with an average weight of 50 kg were randomly divided into 5groups with 4replicates per group and 5pigs per replicate.The control group was fed with corn-concentrates-based feed,groups 1to 4were fed with the basal diets supplemented with10%fermented peanut shell,20% fermented peanut shell,30% fermented peanut shell and 15%fermentation of corn stalk,respectively.The trial lasted for 66 days.The results showed that ADFI in control group,group 2and group 3were significantly higher than that in group 1and group 4(P0.05),ADG in control group and group 3 were significantly higher than that in group 1and group 4(P0.05),there was no significant difference in F/G among all groups(P0.05). Diarrhea frequencies in groups 1to 4were extremely significantly lower than that in control group(P0.01). There were no significant differences in carcass quality,slaughter rate,backfat thickness and eye muscle area among all groups(P0.05),lean meat percentage in group2 was significantly lower than that in control group and group 1(P0.05). There were no significant differences in marbling,meat color,tenderness,intramuscular fat,water loss and cooked meat percentage among all groups(P0.05),water losses in groups 1to 4were lower than that in control group,but the differences were not significant(P0.05). According to the economic benefit analysis showed that in pig from 50 to 90kg,average profit of each pig in control group was 47.60 yuan,average profits of each pig in groups 1to 4were respectively 56.40,60.40,78.80 and 58.80 yuan,while group 3was optimal.Based on the analysis of the above result,the fermented peanut shell had no bad effect on growth performance,carcass traits and meat quality of pigs,and it could effectively reduce the diarrhea frequency of pigs,improve the system of hydraulic of pork,when the fermented peanut shells were appropriatly applied in pigs feed,which could effectively reduce the breeding cost,and improve the economic benefit.
Nonlinear Optical Microscopy: From Fundamentals to Applications in Live Bioimaging

A recent challenge in the field of bioimaging is to image vital, thick, and complex tissues in real time and in non-invasive mode. Among the different tools available for diagnostics, nonlinear optical (NLO) multi-photon microscopy allows label-free non-destructive investigation of physio-pathological processes in live samples at sub-cellular spatial resolution, enabling to study the mechanisms underlying several cellular functions. In this review, we discuss the fundamentals of NLO microscopy and the techniques suitable for biological applications, such as two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG-THG), and coherent Raman scattering (CRS). In addition, we present a few of the most recent examples of NLO imaging employed as a label-free diagnostic instrument to functionally monitor in vitro and in vivo vital biological specimens in their unperturbed state, highlighting the technological advantages of multi-modal, multi-photon NLO microscopy and the outstanding challenges in biomedical engineering applications.
A search of 10 unpaired domestic pig knees (Sus scrofa domestica) reveals no incidence of the anterolateral ligament (ALL)

Abstract. The anterolateral ligament (ALL) has been distinctly characterized in the human knee, so there has been a resulting search for animal models with this ligament. Sus scrofa domestica, the domestic pig, has many biomechanical qualities similar to those of human knees, so this study searched for incidence of the ALL in 10 separate specimen knees. The anatomic dissection yielded no identification of an ALL structure in any of the specimens examined. However, the knees did possess other identifiable structures on the anterolateral aspect of the knee, including the lateral collateral ligament (LCL), tibialis anterior tendon (TAT), and lateral retinaculum (LR). These were harvested and tested to determine if their biomechanical properties compensated for the lack of the ALL. The TAT had the largest average Young's modulus, followed by the LCL, and then the LR. The LR had the longest average end of toe region, followed by the TAT, and then the LCL. The properties of these anterolateral structures, the lifestyle, and the evolutionary path of S. scrofa likely offer insight as to why this species might lack an ALL. This study concludes that S. scrofa does not serve as an animal study model for the anterolateral ligament.
Alternating sequences of future and past behavior encoded within hippocampal theta oscillations

Representing the past and the future Adaptive behavior requires the ability to analyze experience both prospectively and retrospectively. How can forward-ordered neural activity facilitate the storage or expression of reverse-ordered sequences? Wang et al. used multitetrode recordings from many individual hippocampal CA1 neurons in rats while simultaneously recording field potentials expressing theta oscillations. Spatial representation in the place cell network oscillated between forward and backward sweeps within each theta oscillation. Backward replay was associated with theta peaks, whereas forward replay was associated with theta troughs. Most cells fell into one category, but some corresponding to deep-layer neurons showed bimodular responses. Backward replay was driven by entorhinal inputs, whereas forward replay was evoked by CA3 inputs. These are important insights into the underlying basis of coding future and past experiences. Science, this issue p. 247 Hippocampal place cell firing sequences represent future and past experiences. Neural networks display the ability to transform forward-ordered activity patterns into reverse-ordered, retrospective sequences. The mechanisms underlying this transformation remain unknown. We discovered that, during active navigation, rat hippocampal CA1 place cell ensembles are inherently organized to produce independent forward- and reverse-ordered sequences within individual theta oscillations. This finding may provide a circuit-level basis for retrospective evaluation and storage during ongoing behavior. Theta phase procession arose in a minority of place cells, many of which displayed two preferred firing phases in theta oscillations and preferentially participated in reverse replay during subsequent rest. These findings reveal an unexpected aspect of theta-based hippocampal encoding and provide a biological mechanism to support the expression of reverse-ordered sequences.
Genome Analysis of a Marine Bacterium Halomonas sp. and Its Role in Nitrate Reduction under the Influence of Photoelectrons

The solar light response and photoelectrons produced by widespread semiconducting mineral play important roles in biogeochemical cycles on Earth’s surface. To explore the potential influence of photoelectrons generated by semiconducting mineral particles on nitrate-reducing microorganisms in the photic zone, a marine heterotrophic denitrifier Halomonas sp. strain 3727 was isolated from seawater in the photic zone of the Yellow Sea, China. This strain was classified as a Halomonadaceae. Whole-genome analysis indicated that this strain possessed genes encoding the nitrogen metabolism, i.e., narG, nasA, nirBD, norZ, nosB, and nxr, which sustained dissimilatory nitrate reduction, assimilatory nitrate reduction, and nitrite oxidation. This strain also possessed genes related to carbon, sulfur, and other metabolisms, hinting at its substantial metabolic flexibility. A series of microcosm experiments in a simulative photoelectron system was conducted, and the results suggested that this bacterial strain could use simulated photoelectrons with different energy for nitrate reduction. Nitrite, as an intermediate product, was accumulated during the nitrate reduction with limited ammonia residue. The nitrite and ammonia productions differed with or without different energy electron supplies. Nitrite was the main product accounting for 30.03% to 68.40% of the total nitrogen in photoelectron supplement systems, and ammonia accounted for 3.77% to 8.52%. However, in open-circuit systems, nitrite and ammonia proportions were 26.77% and 11.17%, respectively, and nitrogen loss in the liquid was not observed. This study reveals that photoelectrons can serve as electron donors for nitrogen transformation mediated by Halomonas sp. strain 3727, which reveals an underlying impact on the nitrogen biogeochemical cycle in the marine photic zone.
A Single Second Shell Amino Acid Determines Affinity and Kinetics of Linagliptin Binding to Type 4 Dipeptidyl Peptidase and Fibroblast Activation Protein

Drugs targeting type 4 dipeptidyl peptidase (DPP‐4) are beneficial for glycemic control, whereas fibroblast activation protein alpha (FAP‐α) is a potential target for cancer therapies. Unlike other gliptins, linagliptin displays FAP inhibition. We compared biophysical and structural characteristics of linagliptin binding to DPP‐4 and FAP to better understand what differentiates linagliptin from other gliptins. Linagliptin exhibited high binding affinity (KD) and a slow off‐rate (koff) when dissociating from DPP‐4 (KD 6.6 pM; koff 5.1×10−5 s−1), and weaker inhibitory potency to FAP (KD 301 nM; koff>1 s−1). Co‐structures of linagliptin with DPP‐4 or FAP were similar except for one second shell amino acid difference: Asp663 (DPP‐4) and Ala657 (FAP). pH dependence of enzymatic activities and binding of linagliptin for DPP‐4 and FAP are dependent on this single amino acid difference. While linagliptin may not display any anticancer activity at therapeutic doses, our findings may guide future studies for the development of optimized inhibitors.