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Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5 + DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease and high mortality. The aetiology and pathogenesis of MDA5 + DM are still largely unknown. Here we describe the immune signatures of MDA5 + DM via single-cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in peripheral B and T cells and in affected lung tissue samples from one patient. We find strong peripheral antibody-secreting cell and CD8 + T cell responses as cellular immune hallmarks, and over-stimulated type I interferon signaling and associated metabolic reprogramming as molecular immune signature in MDA5 + DM. High frequency of circulating ISG15 + CD8 + T cells at baseline predicts poor one-year survival in MDA5 + DM patients. In affected lungs, we find profuse immune cells infiltration, which likely contributes to the pro-fibrotic response via type I interferon production. The importance of type I interferons in MDA5 + DM pathology is further emphasized by our observation in a retrospective cohort of MDA5 + DM patients that combined calcineurin and Janus kinase inhibitor therapy show superior efficacy to calcineurin inhibitor monotherapy. In summary, this study reveals key immune-pathogenic features of MDA5 + DM and provides a potential basis for future tailored therapies. Anti-melanoma differentiation-associated gene 5-positive dermatomyositis is a severe autoimmune disease with largely unknown aetiology. Here authors identify the key immune cell types that contribute to the disease phenotype and implicate type I interferons signalling in the patho-mechanism.

BackgroundAnti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive clinically amyopathic dermatomyositis (CADM) with pneumomediastinum (PNM) is a life-threatening condition. We aim to determine the prognostic factors affecting survival of patients with anti-MDA5 Ab-positive CADM complicated with PNM.MethodsWe retrospectively established a cohort of patients with anti-MDA5 Ab-positive CADM complicated with PNM from April 2013 to July 2019. Demographic data and clinical characteristics from medical records were analyzed and variables were compared between survivors and nonsurvivors. We performed univariate and multivariate survival analyses by Cox regression. Survival curves were depicted by the Kaplan–Meier method.ResultsAmong 133 patients with anti-MDA5 Ab-positive CADM, 20 were diagnosed with PNM. The cumulative estimated Kaplan–Meier survival rate was 85% at 1 week, 55% at 1 month, and 40% at 1 year. Univariate analysis indicated several factors associated with survival. Worse liver function (AST, p = 0.043; LDH, p = 0.002; TBIL, p = 0.038), higher CRP level (p = 0.044), higher HRCT score (p = 0.022), and using noninvasive positive pressure ventilation (NPPV) (p < 0.01) were associated with poor prognosis. In a multivariate Cox regression model, AST level and using NPPV were indicated to be independent predictors of poor prognosis.ConclusionIn this research, we found that the incidence rate of PNM in anti-MDA5 Ab-positive CADM was 15.5%, obviously higher than in classical DM. The application of noninvasive positive pressure ventilator (NPPV) and higher AST level were independent risk factors for survival.Key Points• Anti-MDA5 Ab-positive CADM complicated with PNM is a life-threatening condition with an incidence rate of 15.5%.• The application of NPPV and worse liver function were independent risk factors for survival of anti-MDA5 Ab-positive CADM patients complicated with PNM.

Macrophage activation syndrome (MAS) is frequently secondary to rheumatic diseases, with features including a cytokine storm and hemophagocytosis. Emapalumab is a monoclonal antibody that targets interferon-γ and has the ability to precisely regulate cytokines. This study aimed to investigate the efficacy and safety of low-dose emapalumab for patients with refractory MAS in the Chinese population. From January 2022 to July 2024, 9 patients with MAS secondary to adult-onset Still's disease (AOSD) or systemic lupus erythematosus (SLE) received low-dose emapalumab following no response to prior conventional therapies. The laboratory parameters, therapeutic response, and safety were assessed following low-dose emapalumab-based treatment. Of the nine MAS patients, 5 patients were secondary to AOSD and 4 patients were secondary to SLE. The overall response rate was 66.7% (6/9), 77.8% (7/9), 88.9% (8/9) and 88.9% (8/9) at week 1, 2, 4 and week 8, respectively. At the end of the follow-up period, up to 88.9% (8/9) of patients achieved complete remission. All patients demonstrated improvement or normalization of clinical manifestations and laboratory parameters. Notably, the median prednisone-equivalent dose for the patients was reduced by 85.5% during the treatment. Cytomegalovirus infection occurred in 33.9% (3/9) of patients, with no occurrence of serious adverse events reported. Our findings suggest that low-dose emapalumab may be a promising salvage option for refractory MAS in the Chinese population, but confirmation in larger prospective studies is required.

Obesity is a prevalent chronic disease worldwide. In this study, we screened lactic acid bacteria (LAB) suitable for fermenting Shenheling extract (SHLE) to enhance its anti-obesity efficacy and improve flavor. Using SHLE as the medium, a single strain was inoculated and the lactic acid bacteria suitable for growth in SHLE were preliminarily screened through a growth curve. The growth of the initially screened LAB was characterized in detail by the pH value, titration acidity and viable bacteria count. At the same time, appropriate LAB were selected with the lipase activity inhibition rate, α-glucosidase activity inhibition rate and a sensory evaluation as the response indicators. As a result, 6 of the 12 strains of lactic acid bacteria grew well in SHLE. The fermentation of five representative LAB could significantly improve the inhibition rate of the lipase activity of SHLE and maintain the inhibition rate of the α-glucosidase activity at a high level. In addition, fermentation removed the original flavors of SHLE such as grass, bitterness and cassia and added a sour taste, fruity aroma and cool taste. Among them, Lactobacillus fermentum grx08 and Lactobacillus rhamnosus hsryfm1301 gave SHLE a soft sour taste after fermentation. L. fermentum grx08, L. rhamnosus grx10 and hsryfm1301 imparted a moderately fruity aroma to SHLE after fermentation. In summary, L. fermentum grx08 and L. rhamnosus hsryfm1301 were the candidate strains for fermenting SHLE to produce good-flavored slimming functional drinks.

Objective: To explore the characteristics of metabolites in Shenheling (SHL) fermented by Lactobacillus fermentum. Methods: In this study, ultrahigh-performance liquid chromatography-quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-QE-MS) was used to qualitatively, quantitatively, and differentially analyze the metabolites of SHL before and after fermentation. Results: A total of 102 significant differential metabolites in nine categories were analyzed before and after fermentation. It mainly includes 29 terpenoids, 17 alkaloids, 14 organic acids and derivatives, 10 flavonoids, 9 phenylpropanoids, 6 phenols, 3 aromaticity, and 3 amino acid derivatives. Further screening found that the content of most active substances, such as alkaloids, organic acids, and flavonoids, increased significantly. These metabolites play an important role in improving the taste and efficacy of SHL. After fermentation, the contents of differential metabolites, such as panaquinquecol 2, ginsenoside Rh3, ginsenoside Rg3, dehydronuciferin, nicotinic acid, 5-hydroxytryptophan, azelaic acid, dihydrokaempferol, and chrysin, were increased, which increased the effects of antioxidation, anti-obesity, hypoglycemic, antibacterial, and improved immunity compared with those before fermentation. KEGG pathway analysis identified 10 metabolic pathways. Isoquinoline alkaloid biosynthesis, vitamin B6 metabolism, beta-alanine metabolism, nicotinate, and nicotinamide metabolism, purine metabolism, pantothenate and CoA biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism, citrate cycle (TCA cycle), phenylpropanoid biosynthesis, etc. Conclusions: Fermentation significantly changed the metabolites in SHL and played an important role in improving its taste, aroma quality, antioxidant, anti-obesity, and other health care functional components.

Several elastic scattering angular distributions of 12C from target nuclei of A≥ 39 are analyzed to extract the Woods-Saxon poten- tial parameters with the fixed imaginary potential and Coulomb radius parameters. Using the best fitted diffuseness parameters, the correlations of the real part parameters with A1/3 1 ＋ A1/3 2and incident energy are revealed, and the systematic Woods-Saxon potential parameters are presented for nucleus-nucleus interaction. The proposed potential parameters can reproduce not only the elastic scattering angular distributions induced by 12C, but also many elastic scattering angular distributions induced by the projectiles other than 12C, thus providing important inputs for the study of nuclear reactions of heavy-ion systems.

Experimental data of β--decay half-lives of nuclei with atomic number between 20 and 190 are investigated. A systematic formula has been proposed to calculateβ--decay half-lives of neutron-rich nuclei, with a particular consideration on shell and pair effects, the decay energy Q as well as the nucleon numbers （Z, N）. Although the formula has relatively few parameters, it reproduces the experimentalβ--decay half-lives of neutron-rich nuclei very well. The predicted half-lives for the r-process relevant nuclei obtained with the current formula serve as reliable input in the r-process model calculations.

Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression and plant development. Here, we identified 6,510 lncRNAs in Arabidopsis under normal or stress conditions. We found that the expression of natural antisense transcripts (NATs) that are transcribed in the opposite direction of protein-coding genes often positively correlates with and is required for the expression of their cognate sense genes. We further characterized MAS , a NAT-lncRNA produced from the MADS AFFECTING FLOWERING4 ( MAF4) locus. MAS is induced by cold and indispensable for the activation of MAF4 transcription and suppression of precocious flowering. MAS activates MAF4 by interacting with WDR5a, one core component of the COMPASS-like complexes, and recruiting WDR5a to MAF4 to enhance histone 3 lysine 4 trimethylation (H3K4me3). Our study greatly extends the repertoire of lncRNAs in Arabidopsis and reveals a role for NAT-lncRNAs in regulating gene expression in vernalization response and likely in other biological processes. Long non-coding RNAs regulate developmental transitions and stress responses in plants. Here Zhao et al. show that a non-coding antisense transcript MAS transcribed from the Arabidopsis MAF4 locus activates H3K4me3 deposition and MAF4 transcription to suppress precocious flowering.

In this Letter, we use the latest results from the Dark Energy Spectroscopic Instrument (DESI) survey to measure the Hubble constant. Baryon acoustic oscillation (BAO) observations released by the DESI survey, allow us to determine H0 from the first principles. Our method is purely data-driven and relies on unanchored luminosity distances reconstructed from Type Ia supernovae (SN Ia) data and H(z) reconstruction from cosmic chronometers. Thus, it circumvents calibrations related to the value of the sound horizon size at the baryon drag epoch or intrinsic luminosity of SN Ia. We find H0=68.4−0.8+1.0kms−1Mpc−1 at a 68% confidence level, which provides the Hubble constant at an accuracy of 1.3% with minimal assumptions. Our assessments of this fundamental cosmological quantity using the BAO data spanning the redshift range z = 0.51–2.33 agree very well with Planck's results and TRGB results within 1σ. This result is still in a 4.3σ tension with the results of the Supernova H0 for the Equation of State.

Transition metal dichalcogenide (TMDC) moiré superlattices, owing to the moiré flatbands and strong correlation, can host periodic electron crystals and fascinating correlated physics. The TMDC heterojunctions in the type-II alignment also enable long-lived interlayer excitons that are promising for correlated bosonic states, while the interaction is dictated by the asymmetry of the heterojunction. Here we demonstrate a new excitonic state, quadrupolar exciton, in a symmetric WSe 2 -WS 2 -WSe 2 trilayer moiré superlattice. The quadrupolar excitons exhibit a quadratic dependence on the electric field, distinctively different from the linear Stark shift of the dipolar excitons in heterobilayers. This quadrupolar exciton stems from the hybridization of WSe 2 valence moiré flatbands. The same mechanism also gives rise to an interlayer Mott insulator state, in which the two WSe 2 layers share one hole laterally confined in one moiré unit cell. In contrast, the hole occupation probability in each layer can be continuously tuned via an out-of-plane electric field, reaching 100% in the top or bottom WSe 2 under a large electric field, accompanying the transition from quadrupolar excitons to dipolar excitons. Our work demonstrates a trilayer moiré system as a new exciting playground for realizing novel correlated states and engineering quantum phase transitions. The authors observe the signatures of quadrupolar excitons in a WSe 2 -WS 2 -WSe 2 trilayer moiré superlattice, originating from the hybridization of the WSe 2 valence moiré flatbands. They further use electrostatic gating to reveal a hybridized interlayer Mott insulator state, with holes shared between the two WSe 2 layers but laterally confined in moiré superlattices.