Room-temperature magnetoresistance in an all-antiferromagnetic tunnel junction.

Antiferromagnetic spintronics1-16 is a rapidly growing field in condensed-matter physics and information technology with potential applications for high-density and ultrafast information devices. However, the practical application of these devices has been largely limited by small electrical outputs at room temperature. Here we describe a room-temperature exchange-bias effect between a collinear antiferromagnet, MnPt, and a non-collinear antiferromagnet, Mn3Pt, which together are similar to a ferromagnet-antiferromagnet exchange-bias system. We use this exotic effect to build all-antiferromagnetic tunnel junctions with large nonvolatile room-temperature magnetoresistance values that reach a maximum of about 100%. Atomistic spin dynamics simulations reveal that uncompensated localized spins at the interface of MnPt produce the exchange bias. First-principles calculations indicate that the remarkable tunnelling magnetoresistance originates from the spin polarization of Mn3Pt in the momentum space. All-antiferromagnetic tunnel junction devices, with nearly vanishing stray fields and strongly enhanced spin dynamics up to the terahertz level, could be important for next-generation highly integrated and ultrafast memory devices7,9,16.

HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.

Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement and bulbar-associated dysfunction. The presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, supports an autoimmune basis. In this study, a multicentric human leukocyte antigen (HLA) study of 87 anti-IgLON5 patients revealed a stronger association with HLA-DQ than HLA-DR. Specifically, we identified a predisposing rank-wise association with HLA-DQA1*01:05∼DQB1*05:01, HLA-DQA1*01:01∼DQB1*05:01 and HLA-DQA1*01:04∼DQB1*05:03 in 85% of patients. HLA sequences and binding cores for these three DQ heterodimers were similar, unlike those of linked DRB1 alleles, supporting a causal link to HLA-DQ. This association was further reflected in an increasingly later age of onset across each genotype group, with a delay of up to 11 years, while HLA-DQ-dosage dependent effects were also suggested by reduced risk in the presence of non-predisposing DQ1 alleles. The functional relevance of the observed HLA-DQ molecules was studied with competition binding assays. These proof-of-concept experiments revealed preferential binding of IgLON5 in a post-translationally modified, but not native, state to all three risk-associated HLA-DQ receptors. Further, a deamidated peptide from the Ig2-domain of IgLON5 activated T cells in two patients, compared with one control carrying HLA-DQA1*01:05∼DQB1*05:01. Taken together, these data support a HLA-DQ-mediated T-cell response to IgLON5 as a potentially key step in the initiation of autoimmunity in this disease.

Magnetic-Field Response and Giant Electric-Field Modulation of Cu2S.

Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.

Close Intimacy between PtIn Clusters and Zeolite Channels for Ultrastability toward Propane Dehydrogenation.

Propane dehydrogenation (PDH) serves as a pivotal intentional technique to produce propylene. The stability of PDH catalysts is generally restricted by the readsorption of propylene which can subsequently undergo side reactions for coke formation. Herein, we demonstrate an ultrastable PDH catalyst by encapsulating PtIn clusters within silicalite-1 which serves as an efficient promoter for olefin desorption. The mean lifetime of PtIn@S-1 (S-1, silicalite-1) was calculated as 37317 h with high propylene selectivity of >97% at 580 °C with a weight hourly space velocity (WHSV) of 4.7 h-1. With an ultrahigh WHSV of 1128 h-1, which pushed the catalyst away from the equilibrium conversion to 13.3%, PtIn@S-1 substantially outperformed other reported PDH catalysts in terms of mean lifetime (32058 h), reaction rates (3.42 molpropylene gcat-1 h-1 and 341.90 molpropylene gPt-1 h-1), and total turnover number (14387.30 kgpropylene gcat-1). The developed catalyst is likely to lead the way to scalable PDH applications.

HINT2 protects against pressure overload-induced cardiac remodelling through mitochondrial pathways.

Histidine triad nucleotide-binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2-overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload-induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling.

The disordered C terminus of ALKBH5 promotes phase separation and paraspeckles assembly.

Paraspeckles (PS) are nuclear structures scaffolded by the long noncoding RNA NEAT1 and protein components such as NONO and SFPQ. We previously found that the upregulation of RNA N6-methyl-adenosine (m6A) demethylase ALKBH5 facilitates hypoxia-induced paraspeckle assembly through erasing m6A marks on NEAT1, thus stabilizing it. However, it remains unclear how these processes are spatiotemporally coordinated. Here we discover that ALKBH5 specifically binds to proteins in PS and forms phase-separated droplets that are incorporated into PS through its C-terminal intrinsically disordered region (cIDR). Upon exposure to hypoxia, rapid ALKBH5 condensation in PS induces m6A demethylation of NEAT1, which further facilitates PS formation before the upregulation of ALKBH5 expression. In cells expressing ALKBH5 lacking cIDR, PS fail to be formed in response to hypoxia, accompanied with insufficient m6A demethylation of NEAT1 and its destabilization. We also demonstrate that ALKBH5-cIDR is indispensable for hypoxia-induced effects such as cancer cell invasion. Therefore, our study has identified the role of ALKBH5 in phase separation as the molecular basis of the positive feedback loop for PS formation between ALKBH5 incorporation into PS and NEAT1 stabilization.

PhyloAcc-GT: A Bayesian Method for Inferring Patterns of Substitution Rate Shifts on Targeted Lineages Accounting for Gene Tree Discordance.

An important goal of evolutionary genomics is to identify genomic regions whose substitution rates differ among lineages. For example, genomic regions experiencing accelerated molecular evolution in some lineages may provide insight into links between genotype and phenotype. Several comparative genomics methods have been developed to identify genomic accelerations between species, including a Bayesian method called PhyloAcc, which models shifts in substitution rate in multiple target lineages on a phylogeny. However, few methods consider the possibility of discordance between the trees of individual loci and the species tree due to incomplete lineage sorting, which might cause false positives. Here, we present PhyloAcc-GT, which extends PhyloAcc by modeling gene tree heterogeneity. Given a species tree, we adopt the multispecies coalescent model as the prior distribution of gene trees, use Markov chain Monte Carlo (MCMC) for inference, and design novel MCMC moves to sample gene trees efficiently. Through extensive simulations, we show that PhyloAcc-GT outperforms PhyloAcc and other methods in identifying target lineage-specific accelerations and detecting complex patterns of rate shifts, and is robust to specification of population size parameters. PhyloAcc-GT is usually more conservative than PhyloAcc in calling convergent rate shifts because it identifies more accelerations on ancestral than on terminal branches. We apply PhyloAcc-GT to two examples of convergent evolution: flightlessness in ratites and marine mammal adaptations, and show that PhyloAcc-GT is a robust tool to identify shifts in substitution rate associated with specific target lineages while accounting for incomplete lineage sorting.

Deep Brain Stimulation for Refractory Status Dystonicus in Children: Multicenter Case Series and Systematic Review.

OBJECTIVE: We sought to better understand the workflow, outcomes, and complications of deep brain stimulation (DBS) for pediatric status dystonicus (SD). We present a systematic review, alongside a multicenter case series of pediatric patients with SD treated with DBS. METHODS: We collected individual data regarding treatment, stimulation parameters, and dystonia severity for a multicenter case series (n = 8) and all previously published cases (n = 77). Data for case series were used to create probabilistic voxelwise maps of stimulated tissue associated with dystonia improvement. RESULTS: In our institutional series, DBS was implanted a mean of 25 days after SD onset. Programming began a mean of 1.6 days after surgery. All 8 patients in our case series and 73 of 74 reported patients in the systematic review had resolution of their SD with DBS, most within 2 to 4 weeks of surgery. Mean follow-up for patients in the case series was 16 months. DBS target for all patients in the case series and 68 of 77 in our systematic review was the globus pallidus pars interna (GPi). In our case series, stimulation of the posterior-ventrolateral GPi was associated with improved dystonia. Mean dystonia improvement was 32% and 51% in our institutional series and systematic review, respectively. Mortality was 4% in the review, which is lower than reported for treatment with pharmacotherapy alone (10-12.5%). INTERPRETATION: DBS is a feasible intervention with potential to reverse refractory pediatric SD and improve survival. More work is needed to increase awareness of DBS in this setting, so that it can be implemented in a timely manner. ANN NEUROL 2023.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

GAS5 promotes cytarabine induced myelosuppression via inhibition of hematopoietic stem cell differentiation.

Cytarabine (Ara-C) is widely used in the induction chemotherapy for acute myeloid leukemia (AML). Association between LncRNA GAS5 genetic polymorphism and the recovery of hematopoietic function after Ara-C-based chemotherapy is observed. This study aimed to identify whether intervention of GAS5 expression and GAS5 genotype affect Ara-C-induced inhibition of hematopoietic stem cells (HSCs) differentiation. In this study, cord blood-derived CD34+ cells were cultured in vitro, and a cell model of myelosuppression was established by treatment of CD34+ cells with Ara-C. The effect of GAS5 overexpression, Ara-C treatment, and GAS5 rs55829688 genotype on the hematopoietic colony-forming ability of CD34+ cells was assessed using methylcellulose-based colony forming unit assay. GAS5 overexpression slowed down the proliferation of cord blood-derived CD34+ cells significantly (p < 0.05) and decreased their ability to form hematopoietic colonies in vitro. Ara-C significantly reduced the hematopoietic colony-forming ability of CD34+ cells in vitro (p < 0.0001), and overexpressing GAS5 further decreased the number of hematopoietic colonies. GAS5 expression was higher in CD34+ cells than in CD34- cells, and positively correlated with GATA1 mRNA expression in CD34+ cells in vitro culture. However, GAS5 genotype had no effect on the total number of hematopoietic colonies formed from cord blood-derived CD34+ cells. In conclusion, our study highlights that GAS5 inhibited the in vitro proliferation and reduced the hematopoietic colony-forming ability of cord blood-derived CD34+ cells, with the most pronounced effect observed on CFU-GEMM formation. GAS5 also enhanced the inhibitory effect of Ara-C on the in vitro hematopoietic ability of CD34+ HSCs.

Association Between Remnant Cholesterol and Risk of Hyperuricemia: A Cross-Sectional Study.

Remnant cholesterol (RC) is closely related to metabolic diseases. Our study aims to explore the relationship between RC and hyperuricemia. This cross-sectional study included 14 568 adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018 in the United States. RC is calculated by subtracting high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) from total cholesterol (TC). Hyperuricemia is defined by serum uric acid (SUA) levels≥7 mg/dl in men and≥6 mg/dl in women. The independent association between RC and hyperuricemia was evaluated. As the quartile range of RC levels increases, the prevalence of hyperuricemia also rises (7.84% vs. 13.71% vs. 18.61% vs. 26.24%, p<0.001). After adjusting for confounding factors, the fourth quartile of RC was associated with an increased risk of hyperuricemia compared with the first quartile (OR=2.942, 95% CI 2.473-3.502, p<0.001). Receiver Operating Characteristic (ROC) analysis shows that RC outperforms other single lipid indices in hyperuricemia. Further Restricted Cubic Splines (RCS) analysis suggests a nonlinear relationship between RC levels and hyperuricemia. Elevated RC levels were found to be linked to hyperuricemia. Further studies on RC hold promise for both preventing and addressing hyperuricemia.

Neck circumference as an additional predictor of cardiovascular disease mortality: A multi-center prospective population-based study in northeastern China.

BACKGROUND AND AIMS: This study aimed to assess the potential of neck circumference (NC) and neck-to-height ratio (NHR) as predictors of future cardiovascular disease (CVD) mortality in a general population from Northeastern China. METHODS: A multi-center prospective study was conducted in Northeastern China, involving 18, 796 participants. The associations between NC or NHR and the incidence of overall CVD mortality, stroke mortality, and coronary heart disease (CHD) mortality were examined using multivariate Cox regression models. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. Reclassification analyses were conducted to determine the incremental predictive value of NC or NHR. RESULTS: NC was significantly associated with the risk of CVD mortality, independent of other anthropometric measurements for obesity. Individuals in the highest quartile of NC had a 1.83-fold (95% CI 1.29 to 2.61) and a 2.40-fold (95% CI 1.45 to 4.00) higher risk of overall CVD mortality and CHD mortality, respectively. Larger NC was significantly related to a heightened risk of ischemic stroke mortality, although no such association was observed with hemorrhagic stroke mortality. Furthermore, the risk of overall CVD mortality, stroke mortality, and CHD mortality increased by approximately 1.21 to 1.25 times per 1-SD change in NC. Similar findings were observed for NHR. The percentages of correct classification of overall CVD mortality improved by 12.1% and 16.3% after the addition of NC or NHR into established models, respectively. CONCLUSIONS: NC and NHR might be promising predictors of CVD mortality, with higher values indicating greater risk.

Oral immunization with recombinant L. lactis expressing GCRV-II VP4 produces protection against grass carp reovirus infection.

The hemorrhagic disease causing by grass carp reovirus (GCRV) infection, is associated with major economic losses and significant impact on aquaculture worldwide. VP4 of GCRV is one of the major outer capsid proteins which can induce an immune response in the host. In this study, pNZ8148-VP4/L. lactis was constructed to express recombinant VP4 protein of GCRV, which was confirmed by the Western-Blot and enzyme-linked immunosorbent assay. Then we performed the oral immunization for rare minnow model and the challenge with GCRV-II. After oral administration, pNZ8148-VP4/L. lactis can continuously reside in the intestinal tract to achieve antigen presentation. The intestinal and spleen samples were collected at different time intervals after immunization, and the expression of immune-related genes was detected by real-time fluorescence quantitative PCR. The results showed that VP4 recombinant L. lactis could induce complete cellular and humoral immune responses in the intestinal mucosal system, and effectively regulate the immunological effect of the spleen. The immunogenicity and the protective efficacy of the oral vaccine was evaluated by determining IgM levels and viral challenge to vaccinated fish, a significant level (P < 0.01) of antigen-specific IgM with GCRV-II neutralizing activity was able to be detected, which provided a effective protection in the challenge experiment. These results indicated that an oral probiotic vaccine with VP4 expression can provide effective protection for grass carp against GCRV-II challenge, suggesting a promising vaccine strategy for fish.

Enhanced Calcium Signal Induces NK Cell Degranulation but Inhibits Its Cytotoxic Activity.

Although the mechanism of NK cell activation is still unclear, the strict calcium dependence remains the hallmark for lytic granule secretion. A plethora of studies claiming that impaired Ca2+ signaling leads to severely defective cytotoxic granule exocytosis accompanied by weak target cell lysis has been published. However, there has been little discussion about the effect of induced calcium signal on NK cell cytotoxicity. In our study, we observed that small-molecule inhibitor UNC1999, which suppresses global H3K27 trimethylation (H3K27me3) of human NK cells, induced a PKD2-dependent calcium signal. Enhanced calcium entry led to unbalanced vesicle release, which resulted into fewer target cells acquiring lytic granules and subsequently being killed. Further analyses revealed that the ability of conjugate formation, lytic synapse formation, and granule polarization were normal in NK cells treated with UNC1999. Cumulatively, these data indicated that induced calcium signal exclusively enhances unbalanced degranulation that further inhibits their cytotoxic activity in human NK cells.

A preliminary study on short- and medium-chain chlorinated paraffins in duck farms: Concentrations, distribution, and dietary exposure risks.

Chlorinated paraffins (CPs) in poultry feed and the farm environment might bioaccumulate in poultry eggs. Unlike chickens, which are mostly raised in cages, ducks are commonly raised free range. This would expose ducks to CPs in the environment. However, information on the presence of CPs on duck farms is scarce. In the present study, samples of duck eggs, duck feathers, poultry feed, and soil were collected from 25 duck farms in South China. Forty-eight congener groups of short- and medium-chain CPs (SCCPs and MCCPs) were detected in the samples. Interestingly, relatively high concentrations of SCCPs and MCCPs were found in the duck feathers. The median concentrations of SCCPs and MCCPs in the duck eggs, feathers, feed and soil were: 46 and 18 ng/g wet weight, 2460 and 992 ng/g, 103 and 47 ng/g, and 24 and 10 ng/g dry weight, respectively. The dominant groups of SCCPs and MCCPs were C10Cl6-7 and C14Cl7-8, respectively. The close relationship between duck feathers and poultry feed indicated that the duck feathers might act as a bioindicator for the exposure of ducks to CPs. The margin of exposure approach was used to assess the health risk, with the results showing that the consumption of duck eggs posed a low risk to different age groups from exposure to SCCPs and MCCPs.

Interfacial electron transfer of perylenes: Influence of the anchor binding mode.

Interfacial electron transfer (IET) through saturated single-linker and dual-linker groups from a perylene chromophore into nanostructured TiO2 films was studied by ultrafast spectroscopy. Perylene chromophores with one and two propanoic acid linker groups in the peri and ortho positions were investigated. In comparison to previously studied perylenes bound via unsaturated acrylic acid linkers, the chromophores with saturated linkers showed bi-exponential IET dynamics. Two distinct transfer times were observed that indicate the presence of two concurrent binding modes. A comparison between ortho- and peri-substituted sensitizers resulted in slower IET dynamics and weaker electronic coupling for ortho substitution. Finally, IET from sensitizers with saturated linker groups is neither promoted nor hindered by a second linker group. This indicates that only one of the two linkers binds covalently to the surface. This study reveals the importance of the anchor-binding mode and design considerations of the linker for regulating IET.

Actigraph-based quantification of sleep in children with dystonia undergoing deep brain stimulation.

OBJECTIVE: Dystonia is among the most common pediatric movement disorders and can manifest with a range of debilitating symptoms, including sleep disruptions. The duration and quality of sleep are strongly associated with quality of life in these individuals and could serve as biomarkers of dystonia severity and the efficacy of interventions such as deep brain stimulation (DBS). Thus, this study investigated sleep duration and its relationship to disease severity and DBS response in pediatric dystonia. METHODS: Actigraphs (wearable three-axis accelerometers) were used to record multiday sleep data in 22 children with dystonia, including 6 patients before and after DBS implantation, and age- and sex- matched healthy controls. Data were preprocessed, and metrics of sleep duration and quality were extracted. Repeated-measures statistical analyses were used. RESULTS: Children with dystonia slept less than typically developing children (p = 0.009), and shorter sleep duration showed trending correlation with worse dystonia severity (r = -0.421, p = 0.073). Of 4 patients who underwent DBS and had good-quality data, 1 demonstrated significantly improved sleep (p < 0.001) postoperatively. Reduction in dystonia severity strongly correlated with increased sleep duration after DBS implantation (r = -0.965, p = 0.035). CONCLUSIONS: Sleep disturbances are an underrecognized marker of pediatric dystonia severity, as well as the effectiveness of interventions such as DBS. They can serve as objective biomarkers of disease burden and symptom progression after treatment.

Salvianolic acid B alleviates autoimmunity in Treg-deficient mice via inhibiting IL2-STAT5 signaling.

Regulatory T cell (Treg) deficiency leads to immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which is a CD4+ T cell-driven autoimmune disease in both humans and mice. Despite understanding the molecular and cellular characteristics of IPEX syndrome, new treatment options have remained elusive. Here, we hypothesized that salvianolic acid B (Sal B), one of the main active ingredients of Salvia miltiorrhiza, can protect against immune disorders induced by Treg deficiency. To examine whether Sal B can inhibit Treg deficiency-induced autoimmunity, Treg-deficient scurfy (SF) mice with a mutation in forkhead box protein 3 were treated with different doses of Sal B. Immune cells, inflammatory cell infiltration, and cytokines were evaluated by flow cytometry, hematoxylin and eosin staining and enzyme-linked immunosorbent assay Kits, respectively. Moreover, RNA sequencing, western blot, and real-time PCR were adopted to investigate the molecular mechanisms of action of Sal B. Sal B prolonged lifespan and reduced inflammation in the liver and lung of SF mice. Moreover, Sal B decreased plasma levels of several inflammatory cytokines, such as IL-2, IFN-γ, IL-4, TNF-α, and IL-6, in SF mice. By analyzing the transcriptomics of livers, we determined the signaling pathways, especially the IL-2-signal transducer and activator of transcription 5 (STAT5) signaling pathway, which were associated with Treg deficiency-induced autoimmunity. Remarkably, Sal B reversed the expression of gene signatures related to the IL-2-STAT5 signaling pathway in vitro and in vivo. Sal B prolongs survival and inhibits lethal inflammation in SF mice through the IL-2-STAT5 axis. Our findings may inspire novel drug discovery efforts aimed at treating IPEX syndrome.

A new secondary metabolite from the marine-derived fungus Phomopsis lithocarpus FS508.

Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid (1) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2, 3 and 12 showed significant anti-inflammatory activities.

Evidence for Topological Magnon-Phonon Hybridization in a 2D Antiferromagnet down to the Monolayer Limit.

Topological phonons and magnons potentially enable low-loss, quantum coherent, and chiral transport of information and energy at the atomic scale. Van der Waals magnetic materials are promising to realize such states due to their recently discovered strong interactions among the electronic, spin, and lattice degrees of freedom. Here, we report the first observation of coherent hybridization of magnons and phonons in monolayer antiferromagnet FePSe3 by cavity-enhanced magneto-Raman spectroscopy. The robust magnon-phonon cooperativity in the 2D limit occurs even in zero magnetic field, which enables nontrivial band inversion between longitudinal and transverse optical phonons caused by the strong coupling with magnons. The spin and lattice symmetry theoretically guarantee magnetic-field-controlled topological phase transition, verified by nonzero Chern numbers calculated from the coupled spin-lattice model. The 2D topological magnon-phonon hybridization potentially offers a new route toward quantum phononics and magnonics with an ultrasmall footprint.