Miracle-dz/UniFAR-FTUs huggingface dataset:
Spitzer IRAC imaging photometric study of the massive star‐forming region AFGL 437

We present Spitzer Infrared Array Camera (IRAC) mid-infrared photometry on the massive star-forming region AFGL 437 (IRAS 03035+5819). From the IRAC colour-colour diagram, we identify several new embedded young stellar objects (YSOs) within 64 arcsec of the central compact cluster. Using the IRAC ratio images, we investigate the molecular outflows associated with the highly embedded YSO WK34 in the central cluster. We attribute the lobes seen (extended to ~0.16 pc in the north) in the ratio map to shocked molecular hydrogen emission. IRAC images reveal a large diffuse nebulosity associated with the central cluster and extending up to ~8.0 pc from south-west to north-east direction with its brightness gradually increasing from 3.6 to 8.0 μm. A dense boxcar-shaped nebula (more than 2.0 pc in size) situated to the south-west of the cluster shows molecular hydrogen emission that may have been caused by shock waves from the compact cluster sources. It seems that these sources are also responsible for the infrared-bright nebulosity. Using a 2D radiative transfer model, we derive from the spectral energy distributions (SEDs), the mass, age and luminosity of all the YSOs identified within the central cluster. The SED modelling shows that the driving engine of the outflows, WK34, appears to be massive but very young and deeply embedded. The weighted mean values of the masses and ages of the 21 YSOs derived from the model are in the range 1-10M ⊙ and 10 4.1-6.4 yr, respectively, while their luminosities are in the range of 10 0.47-3.48 L ⊙ .
Differential impact of GABAA receptors and gephyrin post-translational modifications on layer 2/3 pyramidal neuron responsiveness in vivo

A diverse set of GABAA receptors (GABAARs) enable synaptic plasticity adaptations at inhibitory postsynaptic sites in collaboration with the scaffolding protein gephyrin. Early studies helped to identify distinctions between GABAAR subtypes allocated within specific functional circuits, but their contribution to the changing dynamics of a microcircuit remains unclear. Here, using the whisker-barrel system in mouse, we assessed the contribution of specific synaptic GABAAR subtypes and gephyrin scaffolding changes to sensory processing in vivo. We monitored spontaneous and evoked Ca2+ transients in layer 2/3 pyramidal cells with the genetically encoded Ca2+ sensor RCaMP1.07. Using Gabra1 or Gabra2 global and conditional knockout mice, we uncovered that α1- and α2-GABAARs determine the sparseness of L2/3 pyramidal neuron encoding. In a cell-type dependent manner, α1-GABAARs and α2-GABAARs affected neuronal excitability and the reliability of neuronal responses after whisker stimulation. We also discerned that gephyrin with its diverse post-translational modifications (PTMs) shows preference for specific GABAAR subtype to facilitate microcircuit activity. Our results underscore the relevance of the diversity of GABAARs within a cortical microcircuit. Key points While GABAergic inhibition from interneuron subtypes regulates cortical microcircuit activity the molecular determinants have remain unclear. We demonstrate that specific-GABAA receptor subtypes contribute differentially to layer 2/3 neuronal activities in mouse barrel cortex. Importantly, we link the GABAAR contributions to the scaffolding properties of its important postsynaptic density protein gephyrin. We show that different PTMs on gephyrin determines neuronal excitability via GABAAR recruitment and modulation of inhibition within layer 2/3 neurons. Specifically, α1 and α2 subunits containing GABAA receptors, along with their scaffolding protein gephyrin determine the distribution of high, medium and low activity pyramidal neurons during sensory encoding, whereby controlling the total activity of cortical microcircuit.
Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI

Disentangling human brain connectivity requires an accurate description of neuronal trajectories. However, a detailed mapping of axonal orientations is challenging because axons can cross one another on a micrometer scale. Diffusion magnetic resonance imaging (dMRI) can be used to infer neuronal connectivity because it is sensitive to axonal alignment, but it has limited resolution and specificity. Scattered Light Imaging (SLI) and small-angle X-ray scattering (SAXS) reveal neuronal orientations with microscopic resolution and high specificity, respectively. Here, we combine both techniques to achieve a cross-validated framework for imaging neuronal orientations, with comparison to dMRI. We evaluate brain regions that include unidirectional and crossing fiber tracts in human and vervet monkey brains. We find that SLI, SAXS, and dMRI all agree regarding major fiber pathways. SLI and SAXS further quantitatively agree regarding fiber crossings, while dMRI overestimates the amount of crossing fibers. In SLI, we find a reduction of peak distance with increasing out-of-plane fiber angles, confirming theoretical predictions, validated against both SAXS and dMRI. The combination of scattered light and X-ray imaging can provide quantitative micrometer 3D fiber orientations with high resolution and specificity, enabling detailed investigations of complex tract architecture in the animal and human brain.
Differential Boric Acid and Water Transport in Type I and Type II Pores of Arabidopsis Nodulin 26-Intrinsic Proteins

Nodulin-26 intrinsic proteins (NIPs) are plant-specific multifunctional aquaporin-like channels that are phylogenetically and structurally segregated into three subfamilies: NIP I, II, and III. Each subfamily has a characteristic selectivity filter sequence (the “aromatic-arginine” region, or ar/R) that controls substrate transport specificity based on steric constraints, hydrophobicity, and the spatial orientation of hydrogen bonding moieties. All three NIP subfamilies transport metalloid hydroxides, both beneficial as well as toxic, but with different selectivities. Here we investigated the B, As, and water selectivity of representative Arabidopsis thaliana NIP I and II proteins as well as their ar/R mutants in transport assays as well as through B complementation analysis in the B sensitive nip5;1 mutant background. All NIP proteins, and their ar/R mutants, showed equal permeability to arsenite, but showed differences in boric acid and aquaporin activities that was linked to the amino acid at the helix 2 (H2) position of the ar/R filter (Ala for NIP II and Trp for NIP I). The presence of an alanine at this position in NIP II proteins enhances boric acid permeability and drastically reduces the aquaporin/water permeability of the channel. A NIP II structural model generated from the AlphaFold2 resource and evaluated by MD simulation shows that the alanine results in a wider ar/R pore that accommodates the trigonal boric acid molecule and may allow gating of the pore in a manner that affects water permeability. In contrast, NIP I proteins adopt a more classical aquaporin/glyceroporin arrangement in the ar/R that allows metalloid permeability, although with greater selectivity, as well as permeation by water.
Integrative multispecies omics reveals a hierarchy of cold-responsive network launched by circadian components in rosids

Elucidating regulators and molecular mechanisms underlying gene transcriptional and post-transcriptional co-regulatory network is key to understand plant cold responses. Previous studies were mainly conducted on single species and however, whether the regulators and mechanisms are conserved across species remains elusive. Here, we select three species that diverged at early evolution of rosids (93–115 million years ago) and integrate phylotranscriptome and regulome data to investigate cold-responsive regulators and their regulatory networks across rosids. First, we identify over ten thousand cold-responsive genes including differentially expressed genes (DEGs) and alternative splicing genes (DASGs) in each species. Among DEGs, a set of transcription factor (TF) families (AP2/ERF, MYB, WRKY, NAC, etc.) and RNA binding protein (RBP) families (Ribosomal, RRM, DEAD, Helicase_C, etc.) are conserved in cold responses in rosids. Compared to TFs, RBPs show a delayed cold-responsive pattern, likely suggesting a hierarchical regulation of DEGs and DASGs. Further, we identify 259 overlapping DE-DASG orthogroups between DEGs and DASGs and interestingly, pathway analysis on each dataset of DEGs, DASGs, and DE-DASGs coincidently shows an enrichment of circadian rhythm. Evidentially, many circadian components are cold-regulated differentially at both transcriptional and post-transcriptional level. Moreover, we reason 226 cold-responsive genes regulated by at least two of five circadian components (CCA1, LHY, RV4, RVE8, and RVE7) in rosids. Finally, we unveil a conserved hierarchical network in dynamic transcriptional and post-transcriptional regulation launched by circadian components in rosids. Together, our results provide insights into core regulators and mechanisms underlying cold-responsive network across rosids, despite a long evolutionary history.
Effect of long-range hopping and interactions on entanglement dynamics and many-body localization

We numerically investigate the dynamics of entanglement in a chain of spinless fermions with nonrandom but long-range hopping and interactions, and with random on-site energies. For moderate disorder in the absence of interactions, the chain hosts delocalized states at the top of the band which undergo a delocalization-localization transition with increasing disorder. We find an interesting regime in this noninteracting disordered chain where the long-time entanglement entropy scales as $S(t)\ensuremath{\sim}lnt$ and the saturated entanglement entropy scales with system size $L$ as $S(L,t\ensuremath{\rightarrow}\ensuremath{\infty})\ensuremath{\sim}lnL$. We further study the interplay of long-range hopping and interactions on the growth of entanglement and the many-body localization (MBL) transition in this system. We develop an analogy to higher-dimensional short-range systems to compare and contrast such behavior with the physics of MBL in a higher dimension.
Cortical control of chandelier cells in neural codes

Various cortical functions arise from the dynamic interplay of excitation and inhibition. GABAergic interneurons that mediate synaptic inhibition display significant diversity in cell morphology, electrophysiology, plasticity rule, and connectivity. These heterogeneous features are thought to underlie their functional diversity. Emerging attention on specific properties of the various interneuron types has emphasized the crucial role of cell-type specific inhibition in cortical neural processing. However, knowledge is still limited on how each interneuron type forms distinct neural circuits and regulates network activity in health and disease. To dissect interneuron heterogeneity at single cell-type precision, we focus on the chandelier cell (ChC), one of the most distinctive GABAergic interneuron types that exclusively innervate the axon initial segments (AIS) of excitatory pyramidal neurons. Here we review the current understanding of the structural and functional properties of ChCs and their implications in behavioral functions, network activity, and psychiatric disorders. These findings provide insights into the distinctive roles of various single-type interneurons in cortical neural coding and the pathophysiology of cortical dysfunction.
Hepatic perfusion as a new predictor of prognosis and mortality in critical care patients with acute-on-chronic liver failure

Background and aims Liver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score. Methods In this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF. Results The changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p < 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = −0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. −0.005; p = 0.015) and a lower mean value for the delta-PVv (−0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF. Conclusion This study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.
Enhancement of fluorescence and anti-tumor effect of ZnO QDs by La doping

ZnO quantum dots (QDs) have received much attention as biomarkers and drug delivery systems in cancer treatment, due to their low cost, ease of preparation, and pH-responsive degradation. However, its applications are limited by the low quantum yield and light absorption. In this work, a lanthanum-doped zinc oxide (La-ZnO) QDs-based drug delivery platform was constructed. The results show that 4% La doping is the most beneficial for improving the fluorescent properties of the ZnO QDs. After loading the drug, the cell activity was 15% at ZnO@DOX and 12% at La-ZnO@DOX. According to in vitro and in vivo experiment results, the La-ZnO QDs show enhancement of the antitumor effect. Dual enhancement of fluorescence and anti-tumor effects make La-ZnO QDs promising as a drug delivery system in cancer treatment.
Interactions between ecosystem services and land use in France: A spatial statistical analysis

The provision of ecosystem services (ESs) is driven by land use and biophysical conditions and is thus intrinsically linked to space. Large-scale ES models, developed to inform policy makers on ES drivers, do not usually consider spatial autocorrelation that could be inherent to the distribution of these ESs or to the modeling process. The objective of this study is to estimate the drivers of ecosystem services in France using statistical models and show how taking into account spatial autocorrelation improves the predictive quality of these models. We study six regulating ESs (habitat quality index, water retention index, topsoil organic matter, carbon storage, soil erosion control, and nitrogen oxide deposition velocity) and three provisioning ESs (crop production, grazing livestock density, and timber removal). For each of these ESs, we estimated and compared five spatial statistical models to investigate the best specification (using statistical tests and goodness-of-fit metrics). Our results show that (1) taking into account spatial autocorrelation improves the predictive accuracy of all ES models (ΔR 2 ranging from 0.13 to 0.58); (2) land use and biophysical variables (weather and soil texture) are significant drivers of most ESs; (3) forest was the most balanced land use for provision of a diversity of ESs compared to other land uses (agriculture, pasture, urban, and others); (4) Urban area is the worst land use for provision of most ESs. Our findings imply that further studies need to consider spatial autocorrelation of ESs in land use change and optimization scenario simulations.
Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study

Background Etanercept biosimilar recombinant human TNF-α receptor II: IgG Fc fusion protein (rhTNFR-Fc) has showed its efficacy and safety in Chinese patients with rheumatoid arthritis. However, data on rhTNFR-Fc's application in juvenile idiopathic arthritis (JIA) is limited. Methods A prospective, observational, multicenter study was performed at 6 institutes in China from July 2020 to December 2021. In a 24-week follow-up, patients with JIA including polyarticular JIA and enthesitis related arthritis received rhTNFR-Fc plus methotrexate (MTX) treatment. The primary outcome parameters were improvements of cJADAS-10 (clinical Juvenile Arthritis Disease Activity Score), and the secondary outcome parameter was an inactive disease. Results 60 patients completed at least 12-week follow-up, and 57 completed 24-week follow-up. They had high C reactive protein values (11.6 mg/L) and cJADAS-10 (14.6) at baseline. Thirteen patients had morning stiffness. 33 patients showed synovial thickening, and 34 showed bone marrow edemas on MRI. Ultrasonography demonstrated significant joint effusions in 43 patients. The cJADAS-10 sharply decreased from 14.66 at the baseline to 2.4 at 24 weeks of rhTNFR-Fc therapy, respectively (P < 0.01). About half of patients achieved inactive disease at 24 weeks of therapy. Compared with the baseline, the number of patients with morning stiffness, joint effusions, bone marrow edema and synovial thickening on MRI significantly decreased at 24 weeks. Adverse events were consistent with known side effects of biologic agents. Conclusions The present study indicated that the combination of rhTNFR-Fc and MTX significantly improve symptoms and disease activity of children with JIA. This study suggests etanercept biosimilar rhTNFR-Fc as an effective and safe therapy for children with JIA.
Clinical outcomes following pre-, pro- and synbiotic supplementation after caesarean birth or antibiotic exposure in the first week of life in term born infants: A systematic review of the literature

Background Caesarean section and early exposure to antibiotics disrupt the developing gastrointestinal microbiome, which is associated with long-term health effects. Objective The aim of this systematic review was to summarise the impact of prebiotics, probiotics, or synbiotics supplementation on clinical health outcomes of term infants born by caesarean section or exposed to antibiotics in the first week of life. Design A systematic search was performed in Medline and Embase from inception to August 2021. Title and abstract screening (n = 11,248), full text screening (n = 48), and quality assessment were performed independently by two researchers. Results Six RCTs studying caesarean born infants were included, group sizes varied between 32–193 with in total 752 children. No studies regarding supplementation after neonatal antibiotic exposure were found. Three studies administered a probiotic, one a prebiotic, one a synbiotic, and one study investigated a prebiotic and synbiotic. Several significant effects were reported at follow-up varying between 10 days and 13 years: a decrease in atopic diseases (n = 2 studies), higher immune response to tetanus and polio vaccinations (n = 2), lower response to influenza vaccination (n = 1), fewer infectious diseases (n = 2), and less infantile colic (n = 1), although results were inconsistent. Conclusions Supplementation of caesarean-born infants with prebiotics, probiotics, or synbiotics resulted in significant improvements in some health outcomes as well as vaccination responses. Due to the variety of studied products and the paucity of studies, no recommendations can be given yet on the routine application of prebiotics, probiotics, or synbiotics to improve health outcomes after caesarean section or neonatal antibiotic exposure.
Rituximab in patients with membranous nephropathy and kidney insufficiency

Introduction: Patients with membranous nephropathy and kidney insufficiency have an extremely high risk of progression to end-stage renal disease. Whether rituximab can effectively treat membranous nephropathy patients with renal dysfunction remains unknown at present. The aim of our study was to evaluate the effectiveness and safety of rituximab (RTX) in membranous nephropathy with kidney insufficiency. Methods: We retrospectively analyzed the clinical data of 35 membranous nephropathy patients with kidney insufficiency administered in the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2021. Patients were followed every 1–3 months for a total of 6 months. Clinical data were collected including anti-phospholipase A2 receptor antibody (anti-PLA2R antibody) quantification, 24-h urinary protein, serum albumin, and serum creatinine. The percentage of patients who achieved clinical remission was measured. Results: There were 7 (20%) patients who achieved complete or partial response at 6 months after RTX treatment. After 6 months of treatment, patients were clinically improved as evidenced by significant improvements in anti- PLA2R antibody titer [7.70 (5.72, 16.72) vs. 59.20 (17.70, 187.50) RU/ml, p < 0.001], 24-h urine protein [7.04 (4.43, 8.90) vs. 10.15 (4.83, 13.57) g/d, p < 0.001], serum albumin [30.55 (24.97, 33.27) vs. 21.40 (16.75, 25.00)g/L, p < 0.001], serum creatinine [99.50 (75.25, 140.25) vs. 152.00 (134.50, 232.50) µmol/L, p = 0.022], and estimated glomerular filtration rate (eGFR) [78.29 (50.15, 101.55) vs. 41.12 (26.53, 51.41) ml/min/1.73 m2, p = 0.045]. There were no significantly differences between responders and nonresponders in the baseline levels of anti-PLA2R antibodies, proteinuria, serum albumin, and renal function. After the RTX treatment, anti-PLA2R antibodies turned negative in all responders, but the antibody level persisted maintained positive in all but 5 nonresponders. The patients who achieved response maintained a stable kidney function during the study period, with eGFR 29.03 (28.76, 35.07) ml/min/1.73 m2 before rituximab treatment and 62.73 (62.34, 63.13) ml/min/1.73 m2 at the end of follow-up (p = 0.053). Conclusion: RTX therapy might be an alternative treatment in reducing proteinuria and maintaining stable renal function among membranous nephropathy patients even with kidney insufficiency.