On the origin of the split main sequences of the young massive cluster NGC 1856

The detection of split main sequences (MSs) associated with young clusters ($\lesssim$600 Myr) has caught lots of attention. A prevailing scenario is that a bimodality of stellar rotation distribution drives the MS bifurcation. Nevertheless, the origin of the stellar rotation dichotomy remains unclear. Hypotheses involving tidally-locked binaries or blue straggler stars (BSSs) are proposed to explain the observed split MSs. This work examines if the long-term dynamical evolution of star clusters can produce the observed split MSs, through high-performance $N$-body simulation. As a prototype example, the young massive cluster NGC 1856 exhibits an apparent MS bifurcation. Our simulation reports that at the age of NGC 1856, tidally-locked binaries are fully mixed with single stars. This is consistent with the observation that there is no significant spatial difference between blue MS and red MS stars. However, we find that only high mass-ratio binaries can evolve to the tidally-locked phase at the age of the NGC 1856. These tidally-locked binaries will populate a much redder sequence than the MS of single stars rather than a blue MS, which is inconsistent with the hypothesis. The number of tidally-locked binaries cannot account for the observation. Our simulation shows that BSSs produced by binary interactions do populate the blue periphery in the color-magnitude diagram, and their spatial distribution shows a similar pattern of single stars. However, the number of BSSs does not fit the observation.Comment: 14 pages, 7 figures, 1 table; accepted for publication in Ap

VCL Challenges 2023 at ICCV 2023 Technical Report: Bi-level Adaptation Method for Test-time Adaptive Object Detection

This report outlines our team's participation in VCL Challenges B Continual Test_time Adaptation, focusing on the technical details of our approach. Our primary focus is Testtime Adaptation using bi_level adaptations, encompassing image_level and detector_level adaptations. At the image level, we employ adjustable parameterbased image filters, while at the detector level, we leverage adjustable parameterbased mean teacher modules. Ultimately, through the utilization of these bi_level adaptations, we have achieved a remarkable 38.3% mAP on the target domain of the test set within VCL Challenges B. It is worth noting that the minimal drop in mAP, is mearly 4.2%, and the overall performance is 32.5% mAP

Synthetic θ‐Defensin Antibacterial Peptide as a Highly Efficient Nonviral Vector for Redox‐Responsive miRNA Delivery

Synthetic cationic vectors have shown great promise for nonviral gene delivery. However, their cytotoxicity and low efficiency impose great restrictions on clinic applications. To push through this limitation, humanized peptides or proteins with cationic biocompatibility as well as biodegradation would be an excellent candidate. Herein, for the first time, we describe how an arginine‐rich humanized antimicrobial cyclopeptide, θ‐defensin, can be used as a synthetic cationic vector to load and deliver miRNA into bone mesenchymal stem cells with high efficiency and ultralow cytotoxicity, surpassing the efficiency of the commercial polyethylenimine (25 kD) and Lipofectamine 3000. To note, θ‐defensin can redox‐responsively release the loaded miRNA through a structural change: in extracellular oxidative environment, θ‐defensin has large β‐sheet structures stabilized by three disulfide linkages, and this special structure enables highly efficient delivery of miRNA by passing through cell membranes; in intracellular environment, redox‐responsive disulfide linkages are broken and the tight β‐sheet structures are destroyed, so that the miRNA can be released. Our results suggest that synthetic θ‐defensin peptides are a new class of nonviral gene vectors and this study may also provide a promising strategy to design smart‐responsive gene vectors with high efficiency and minimal toxicity.This study describes how an arginine‐rich humanized antimicrobial cyclopeptide, θ‐defensin, can be used as a synthetic cationic vector to load and deliver miRNA into bone mesenchymal stem cells with high efficiency and low cytotoxicity, surpassing the efficiency of the commercial polyethylenimine (25 kD) and Lipofectamine 3000.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141894/1/adbi201700001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141894/2/adbi201700001_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141894/3/adbi201700001-sup-0001-S1.pd

Acylhydrazine-based reticular hydrogen bonds enable robust, tough, and dynamic supramolecular materials

Supramolecular materials are widely recognized among the most promising candidates for future generations of sustainable plastics because of their dynamic functions. However, the weak noncovalent cross-links that endow dynamic properties usually trade off materials’ mechanical robustness. Here, we present the discovery of a simple and robust supramolecular cross-linking strategy based on acylhydrazine units, which can hierarchically cross-link the solvent-free network of poly(disulfides) by forming unique reticular hydrogen bonds, enabling the conversion of soft into stiff dynamic material. The resulting supramolecular materials exhibit increase in stiffness exceeding two to three orders of magnitude compared to those based on the hydrogen-bonding network of analogous carboxylic acids, simultaneously preserving the repairability, malleability, and recyclability of the materials. The materials also show high adhesion strength on various surfaces while allowing multiple surface attachment cycles without fatigue, illustrating a viable approach how robustness and dynamics can be merged in future material design

The role of tidal interactions in the formation of slowly rotating early-type stars in young star clusters

The split main sequences found in the colour-magnitude diagrams of star clusters younger than ~600 Myr are suggested to be caused by the dichotomy of stellar rotation rates of upper main-sequence stars. Tidal interactions have been suggested as a possible explanation of the dichotomy of the stellar rotation rates. This hypothesis proposes that the slow rotation rates of stars along the split main sequences are caused by tidal interactions in binaries. To test this scenario, we measured the variations in the radial velocities of slowly rotating stars along the split main sequence of the young Galactic cluster NGC 2422 (~90 Myr) using spectra obtained at multiple epochs with the Canada-France-Hawai'i Telescope. Our results show that most slowly rotating stars are not radial-velocity variables. Using the theory of dynamical tides, we find that the binary separations necessary to fully or partially synchronise our spectroscopic targets, on time-scales shorter than the cluster age, predict much larger radial velocity variations across multiple-epoch observations, or a much larger radial velocity dispersion at a single epoch, than the observed values. This indicates that tidal interactions are not the dominant mechanism to form slowly rotating stars along the split main sequences. As the observations of the rotation velocity distribution among B- and A-type stars in binaries of larger separations hint at a much stronger effect of braking with age, we discuss the consequences of relaxing the constraints of the dynamical tides theory.Comment: 14 pages, 10 figures, 2 tables, accepted for publication in MNRA

Molecular basis of ligand recognition and activation of human V2 vasopressin receptor.

Vasopressin type 2 receptor (V2R) belongs to the vasopressin (VP)/oxytocin (OT) receptor subfamily of G protein-coupled receptors (GPCRs), which comprises at least four closely related receptor subtypes: V1aR, V1bR, V2R, and OTR. These receptors are activated by arginine vasopressin (AVP) and OT, two endogenous nine-amino acid neurohypophysial hormones, which are thought to mediate a biologically conserved role in social behavior and sexual reproduction. V2R is mainly expressed in the renal collecting duct principal cells and mediates the antidiuretic action of AVP by accelerating water reabsorption, thereby playing a vital role in controlling water homeostasis. Moreover, numerous gain-of-function and loss-of-function mutations of V2R have been identified and are closely associated with human diseases, including nephrogenic syndrome of inappropriate diuresis (NSIAD) and X-linked congenital nephrogenic diabetes insipidus (NDI). Thus, V2R has attracted intense interest as a drug target. However, due to a lack of structural information, how AVP recognizes and activates V2R remains elusive, which hampers the V2R-targeted drug design. Here, we determined a 2.6 Å resolution cryo-EM structure of the full-length, G s -coupled human V2R bound to AVP (Fig. 1a; Supplementary information, Table S1). The G s protein was engineered based on mini-G s that was used in the crystal structure determination of the G s -coupled adenosine A 2A receptor (A 2A R) to stabilize the V2R–G s protein complex (Supplementary information, Data S1). The final structure of the AVP–V2R–G s complex contains all residues of AVP (residues 1–9), the Gα s Ras-like domain, Gβγ subunits, Nb35, scFv16, and the V2R residues from T31 to L339 8.57 (superscripts refer to Ballesteros–Weinstein numbering). The majority of amino acid side chains, including AVP, transmembrane domain (TMD), all flexible intracellular loops (ICLs) and extracellular loops (ECLs) except for ICL3 and G185–G188 in ECL2, were well resolved in the model, refined against the EM density map (Fig. 1a; Supplementary information, Figs. S1–3). The complex structure can provide detailed information on the binding interface between AVP and helix bundle of the receptor, as well as the receptor–G s interface

Multimodal transformer augmented fusion for speech emotion recognition

Speech emotion recognition is challenging due to the subjectivity and ambiguity of emotion. In recent years, multimodal methods for speech emotion recognition have achieved promising results. However, due to the heterogeneity of data from different modalities, effectively integrating different modal information remains a difficulty and breakthrough point of the research. Moreover, in view of the limitations of feature-level fusion and decision-level fusion methods, capturing fine-grained modal interactions has often been neglected in previous studies. We propose a method named multimodal transformer augmented fusion that uses a hybrid fusion strategy, combing feature-level fusion and model-level fusion methods, to perform fine-grained information interaction within and between modalities. A Model-fusion module composed of three Cross-Transformer Encoders is proposed to generate multimodal emotional representation for modal guidance and information fusion. Specifically, the multimodal features obtained by feature-level fusion and text features are used to enhance speech features. Our proposed method outperforms existing state-of-the-art approaches on the IEMOCAP and MELD dataset

Assisted reproductive technology and interactions between serum basal FSH/LH and ovarian sensitivity index

ObjectivesThis study aimed to investigate whether the FSH (follicle-stimulating hormone)/LH (Luteinizing hormone) ratio correlates with ovarian response in a cross-sectional retrospective study of a population with normal levels of anti-Müllerian hormone (AMH).MethodsThis was a retrospective cross‐sectional study with data obtained from medical records from March 2019 to December 2019 at the reproductive center in the Affiliated Hospital of Southwest Medical University. The Spearmans correlation test evaluated correlations between Ovarian sensitivity index (OSI) and other parameters. The relationship between basal FSH/LH and ovarian response was analyzed using smoothed curve fitting to find the threshold or saturation point for the population with mean AMH level (1.1<AMH<6μg/L). The enrolled cases were divided into two groups according to AMH threshold. Cycle characteristics, cycle information and cycle outcomes were compared. The Mann-Whitney U test was used to compare different parameters between two groups separated by basal FSH/LH in the AMH normal group. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to find the risk factor for OSI.ResultsA total of 428 patients were included in the study. A significant negative correlation was observed between OSI and age, FSH, basal FSH/LH, Gn total dose, and Gn total days, while a positive correlation was found with AMH, AFC, retrieved oocytes, and MII egg. In patients with AMH <1.1 ug/L, OSI values decreased as basal FSH/LH levels increased, while in patients with 1.1<AMH<6 ug/L, OSI values remained stable with increasing basal FSH/LH levels. Logistic regression analysis identified age, AMH, AFC, and basal FSH/LH as significant independent risk factors for OSI.ConclusionsWe conclude that increased basal FSH/LH in the AMH normal group reduces the ovarian response to exogenous Gn. Meanwhile, basal FSH/LH of 3.5 was found to be a useful diagnostic threshold for assessing ovarian response in people with normal AMH levels. OSI can be used as an indicator of ovarian response in ART treatment

Autologous Skin Fibroblast-Based PLGA Nanoparticles for Treating Multiorgan Fibrosis

Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast-targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic-co-glycolic) acid cores, these nanoparticles, termed fibroblast membrane-camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor-beta, interleukin (IL)-11, IL-13, and IL-17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof-of-concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad-spectrum therapy for fibrosis management.Peer reviewe

Fecal and serum metabolomic signatures and gut microbiota characteristics of allergic rhinitis mice model

BackgroundThe etiology of allergic rhinitis (AR) is complicated. Traditional therapy of AR still has challenges, such as low long-term treatment compliance, unsatisfactory therapeutic outcomes, and a high financial burden. It is urgent to investigate the pathophysiology of allergic rhinitis from different perspectives and explore brand-new possible preventative or treatment initiatives.ObjectiveThe aim is to apply a multi-group technique and correlation analysis to explore more about the pathogenesis of AR from the perspectives of gut microbiota, fecal metabolites, and serum metabolism.MethodsThirty BALB/c mice were randomly divided into the AR and Con(control) groups. A standardized Ovalbumin (OVA)-induced AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. We detected the serum IL-4, IL-5, and IgE by enzyme-linked immunosorbent assay (ELISA), evaluated the histological characteristics of the nasal tissues by the hematoxylin and eosin (H&E) staining, and observed the nasal symptoms (rubs and sneezes) to evaluate the reliability of the AR mouse model. The colonic NF-κB protein was detected by Western Blot, and the colonic histological characteristics were observed by the H&E staining to evaluate inflammation of colon tissue. We analyzed the V3 and V4 regions of the 16S ribosomal DNA (rDNA) gene from the feces (colon contents) through 16S rDNA sequencing technology. Untargeted metabolomics was used to examine fecal and serum samples to find differential metabolites. Finally, through comparison and correlation analysis of differential gut microbiota, fecal metabolites, and serum metabolites, we further explore the overall impact of AR on gut microbiota, fecal metabolites, and host serum metabolism and its correlation.ResultsIn the AR group, the IL-4, IL-5, IgE, eosinophil infiltration, and the times of rubs and sneezes were significantly higher than those in the Con group, indicating the successful establishment of the AR model. No differences in diversity were detected between the AR and Con groups. However, there were modifications in the microbiota’s structure. At the phylum level, the proportion of Firmicutes and Proteobacteria in the AR group increased significantly, while the proportion of Bacteroides decreased significantly, and the ratio of Firmicutes/Bacteroides was higher. The key differential genera, such as Ruminococcus, were increased significantly in the AR group, while the other key differential genera, such as Lactobacillus, Bacteroides, and Prevotella, were significantly decreased in the Con group. Untargeted metabolomics analysis identified 28 upregulated and 4 downregulated differential metabolites in feces and 11 upregulated and 16 downregulated differential metabolites in serum under AR conditions. Interestingly, one of the significant difference metabolites, α-Linoleic acid (ALA), decreased consistently in feces and serum of AR. KEGG functional enrichment analysis and correlation analysis showed a close relationship between differential serum metabolites and fecal metabolites, and changes in fecal and serum metabolic patterns are associated with altered gut microbiota in AR. The NF-κB protein and inflammatory infiltration of the colon increased considerably in the AR group.ConclusionOur study reveals that AR alters fecal and serum metabolomic signatures and gut microbiota characteristics, and there is a striking correlation between the three. The correlation analysis of the microbiome and metabolome provides a deeper understanding of AR’s pathogenesis, which may provide a theoretical basis for AR’s potential prevention and treatment strategies