Browse Articles

Studying the expression levels of LncRNA-MEG3 and miR-147b in the serum of psoriasis patients with and without dyslipidemia

Abstract Psoriasis is a chronic systemic inflammatory skin disorder that is strongly associated with metabolic disorders, including obesity, insulin resistance, hypertension, and dyslipidemia. Dyslipidemia causes abnormalities in lipid profiles, such as elevated triglycerides or low density lipoprotein (LDL) levels. Measure maternally expressed gene 3 (MEG3) and microRNA-147b in serum of patients with and without dyslipidemia compared to healthy control. These measurements were compared with clinical characteristics, clinical parameters, and laboratory investigations. Serum expression levels of MEG3 and microRNA-147b, as non-coding RNA biomarkers, were measured across four equally subcategorized groups (patients with and without dyslipidemia ( N  = 66) and healthy controls with and without dyslipidemia ( N  = 66) using Polymerase Chain Reaction (PCR). Psoriatic patients exhibited a high significantly body mass index and elevated low-density lipoprotein levels compared with controls ( p  = 0.038,0.010) respectively, while fasting blood glucose was significantl at p  = 0.001. Fasting blood glucose and lipid parameters showed low levels in patients without dyslipidemia and high levels of high-density lipoprotein than those with dyslipidemia. Expression Level of MEG3 was significantly downregulated, whereas microRNA-147b was markedly upregulated in psoriatic patients ( p  < 0.0001). MEG3 expression was negatively correlated with disease severity indices and lipid levels and inversely correlated with microRNA-147b, which also negatively correlated with disease duration. MEG3 and miR-147b, as non-coding RNAs, may show differential expression among psoriasis patient subgroups and could be associated with disease-related parameters, but their value as markers of disease severity or prognosis remains to be confirmed.

Views of EU citizens on economic growth and implications for climate policy

Abstract Although economic growth remains a central objective in policymaking and political discourse, its compatibility with environmental sustainability is increasingly contested. Yet it remains unclear whether this debate is reflected in public opinion. We therefore undertake a cross-national survey of 16,781 people across 13 EU countries to assess citizens’ attitudes in this regard. We find that nearly 60% of citizens express pro-growth views, seeing economic growth as essential for a sustainable society. Of these, more than half hold a moderate and less than half a strong pro-growth view. Additionally, a third of respondents show indifference about growth, while less than 10% hold views that are sceptical about growth. Wealthier countries with less income inequality show lower support for economic growth. Pro-growth attitudes correlate positively with both self-enhancement and self-transcendence values, suggesting that citizens may view growth not only as a means for personal advancement but also as a pathway to collective wellbeing. Growth attitudes have no significant association with climate concern or climate policy support, suggesting a more nuanced picture than a traditional trade-off narrative.

Comparing clinical outcomes of rFSH versus rFSH+HP-hMG in women undergoing in vitro fertilization-embryo transfer in real‑world practice: a retrospective study

Abstract Clinical outcomes of combining recombinant follicle-stimulating hormone (rFSH) with highly purified human menopausal gonadotropin (HP-hMG) versus rFSH alone were compared in patients undergoing in vitro fertilization in a real-world setting. This retrospective cohort study analyzed patients who underwent ovarian stimulation with rFSH or rFSH + HP-hMG following a gonadotropin-releasing hormone antagonist protocol, followed by fresh or frozen embryo transfer (ET) at two centers in Korea. A total of 1,028 women were included: 329 underwent fresh ET (rFSH: n  = 78; rFSH + HP-hMG: n  = 251) and 699 underwent frozen ET (rFSH: n  = 250; rFSH + HP-hMG: n  = 449). Across both fresh and frozen ET group, patients receiving rFSH + HP-hMG were older and had lower anti-Müllerian hormone levels and antral follicle counts. Despite fewer oocytes retrieved in rFSH + HP-hMG group (fresh: 9.5 vs. 11.0; frozen: 16.3 vs. 20.6, both p  < 0.05), metaphase II oocyte rates and clinical pregnancy rates were comparable (fresh: 44.6 vs. 43.6%; frozen: 58.4 vs. 56.8%, both p  > 0.05). Notably, ovarian hyperstimulation syndrome incidence was significantly lower in rFSH + HP-hMG group among frozen ET patients (6.9 vs. 13.2%, p  < 0.01). These findings suggest that rFSH + HP-hMG achieves comparable clinical outcomes to rFSH alone despite less favorable prognostic characteristics that could affect clinical outcome, supporting its role as a clinically acceptable alternative stimulation option in routine practice.

Blockade of NKp46⁻ CCR6⁻ ILC3 autophagy protects against necrotizing enterocolitis by restoring energy metabolism balance in mice

Abstract Group 3 innate lymphoid cells (ILC3) are crucial in neonatal necrotizing enterocolitis (NEC); however, the underlying mechanisms remain elusive. Here, we identify NKp46⁻CCR6⁻ (double-negative, DN) ILC3s as the dominant pathogenic subset driving NEC via IL-17 A secretion, which disrupts intestinal barrier integrity. Mechanistically, Atg5 activates autophagy in DN ILC3s during NEC. Atg5 conditional knockout in RORγt⁺ cells mitigates NEC, reduces DN ILC3 accumulation and IL-17 A production. Atg5 deficiency also decreases HIF-1α chromatin accessibility and transcriptional activity, shifting DN ILC3 metabolism from glycolysis to fatty acid oxidation. Lipidomics reveals phosphatidylcholine as a key downstream metabolite of Atg5-mediated autophagy. Phosphatidylcholine supplementation suppresses DN ILC3-driven inflammation, restores metabolic homeostasis, elevates Clostridium abundance, and ameliorates NEC in mice. Importantly, human NEC tissues exhibit increased ILC3 proportions, autophagic activity, and IL-17 A/IL-22 secretion. Thus, we uncover an Atg5–autophagy–glycolipid metabolic axis in DN ILC3s that drives NEC pathogenesis, providing a promising therapeutic target for neonatal NEC.

Single-cell transcriptomics reveals anti-inflammatory effects of prednisolone on the hepatic niche in biliary atresia

Fully cove-edged bilayer nanographene with parallel displaced stacking

Multi-scale hybrid composites of erythritol/diatomite/GNP for enhanced thermal energy storage: experimental and machine learning optimization

Simultaneous dual-Raman-shift scanning-free stimulated Raman scattering microscopy for label-free biomolecular imaging

Atractylon inhibits hepatocellular carcinoma by inducing ferroptosis with increasing SLC39A14 expression

Novelty exploration-activated ensemble in the lateral hypothalamus confers analgesic and anxiolytic effects

Effects of guaiane sesquiterpenoids from the invasive species Ambrosia trifida on inflammatory bowel disease by targeting JAK2/STAT3 signaling

Rank-dependent control of tuft and BEST4 cell development in the intestine

Abstract Specialist intestinal epithelial cells are critical for barrier integrity and immune responses at the mucosal boundary, yet the pathways that govern their development are incompletely defined. Here, we identify an essential role for TNFRSF11A/RANK in shaping intestinal epithelial specialization in zebrafish. Using lineage trajectory analysis, we identify two tuft cell subtypes, including a subtype enriched for expression of genes required to produce pro-inflammatory leukotrienes. We show that RANK deficiency reduces the abundance of immune-regulatory tuft and BEST4 cells, increases goblet cell frequency, and promotes the accumulation of pro-inflammatory leukocytes in the gut. Functionally, we demonstrate that the number of cells expressing the BEST4 cell marker cftr expand following infection with a pandemic strain of Vibrio cholerae , and we show that RANK deficiency enhances fish susceptibility to host colonization by Vibrio , implicating this lineage in host defenses against an enteric pathogen. Together, our findings implicate RANK signaling in intestinal epithelial diversification and immune regulation.

Reinvestigation of a paternity case with three CODIS core STR inconsistencies using MPS-based multi‑marker analysis

Recurrent structural variation and recent turnover at the 17q21.31 locus in humans and great apes

Abstract The 17q21.31 locus in humans harbors several complex structural haplotypes including a ~ 970 kb inversion. Different inversion haplotypes have been associated with susceptibility to microdeletions causing Koolen-de Vries syndrome and variation in fecundity and recombination rates. Here, using 210 haplotype-resolved human genome assemblies and pangenome graph-based approaches we characterize 11 distinct structural haplotypes, several of which have not been previously described. Extending our analyses to a set of haplotype-resolved great-ape genomes, we characterize the structure of an independent inversion in chimpanzees which extends an additional 650 kb, encompasses 5 additional genes, and is ~2 million years younger than the human inversion. Using short read sequencing data we characterize 17q21.31 haplotype diversity worldwide in ~5174 individuals from 107 populations finding increased frequencies of KANSL1 duplication-containing haplotypes in both European and South Asian populations as well as 8 double recombination events between inverted and non-inverted haplotypes ranging in size from 20-180 kb. Finally, using 626 ancient Eurasian human genomes we show the frequency of haplotypes containing KANSL1 duplications has increased ~6-fold over the past 12 thousand years in Europe. Together, our results highlight the dynamics, complexity, and recurrent, independent evolution of a medically relevant locus across humans and great apes.

Tracing the origins and recurrence of the South Atlantic Anomaly: A 2000-year absolute paleointensity record from central South America

A robust characterization of geomagnetic field strength in the Southern Hemisphere over the past millennia is critical for understanding the (multi)centennial evolution of the South Atlantic Anomaly (SAA), one of the most prominent geomagnetic features at Earth’s surface. Yet, robust absolute paleointensity records remain scarce in this region, introducing significant uncertainty into geomagnetic field reconstructions. Here, we present 41 absolute archeointensity determinations obtained using the Thellier–Thellier method from central South America spanning the last two millennia. Combined with a selection of high-quality records from the same region, these new data yield virtual axial dipole moment values broadly consistent with the other few available Southern Hemisphere datasets but generally lower than those from Europe, indicating a persistent north–south asymmetry in geomagnetic field strength. A new global geomagnetic field model incorporating these new data suggests that the observed asymmetry reflects a persistently northward-shifted eccentric dipole. In addition, the model tentatively suggests a westward migration of a nondipolar low-intensity anomaly between 1 and 850 CE, from the Indian Ocean to northern South America, following a trajectory broadly similar to that of the modern SAA, which appears in the Indian Ocean after 1100 CE and progresses across Africa before reaching South America. These findings support the hypothesis of a recurrent large-scale geomagnetic pattern and highlight multiscale geodynamic control on geomagnetic field morphology, in which mantle and core processes interact to shape secular variation patterns on centennial to millennial timescales.

Improving forward identified hadron spectra in proton carbon collisions at 90 GeV/c using impact parameter dependent subcollision acceptance in PYTHIA 8 Angantyr

Precision-guided therapy in H3K27-altered diffuse midline glioma

Metabolic engineering of <i>Escherichia coli</i> for the biosynthesis of nylon 6 and nylon 6,6 monomers

Hexamethylenediamine (HMD), adipic acid, and ε-caprolactam (ε-CL) are essential C6 monomers used in the production of nylon 6,6 and nylon 6. Developing sustainable, bio-based routes to these compounds remains challenging due to pathway complexity. Here, we report a modular Escherichia coli platform for the de novo biosynthesis of all three monomers directly from glycerol. We divided the overall pathway into upstream and downstream modules, with the upstream module converting glycerol to adipic acid. To construct downstream module, two distinct strains were engineered to individually convert adipic acid into HMD or ε-CL. Both strains employed carboxylic acid reductases Macar from Mycobacteroides abscessus and Mmocar from Mycolicibacterium moriokaense , with the latter identified and validated in this work. Specifically, HMD biosynthesis incorporated aminotransferases PatA from E. coli , GabT from Streptomyces avermitilis , and the introduced Bcta from Burkholderia cenocepacia . ε-CL biosynthesis utilized a similar upstream pathway but relied critically on a lactamization step catalyzed by an HLadh–Smnox fusion enzyme containing a flexible linker for efficient NAD + regeneration. The common precursor, adipic acid, was produced by an upstream strain optimized through reverse β-oxidation pathway reconstruction, PaaJ engineering, and metabolic flux balancing, achieving a titer of 6.1 g/L. In fed-batch fermentation, cocultivation of the engineered strains with delayed inoculation enabled temporally coordinated conversion of glycerol to HMD (230.9 mg/L) and ε-CL (808.0 µg/L), representing low yet the highest titers reported to date. This work opens up the possibility of a unified, modular microbial platform for the sustainable production of nylon monomers from a renewable carbon source.

Increasing rail transit ridership by improving passenger ride comfort

Semaglutide slows epigenetic aging in a randomized trial of HIV-associated lipohypertrophy

Abstract Glucagon-like peptide-1 (GLP-1) receptor agonists have attracted interest as gerotherapeutics, yet clinical-trial evidence for their effects on biological aging is lacking. We report a post hoc exploratory epigenetic age analysis of a 32-week, randomized, double-blind, placebo-controlled phase 2b trial (NCT04019197) of semaglutide in adults with human immunodeficiency virus (HIV)-associated lipohypertrophy (semaglutide n  = 45; placebo n  = 39). The parent trial’s primary endpoint was change in visceral adipose tissue, with secondary cardiometabolic and body-composition endpoints; epigenetic aging was not pre-specified. To address this gap, we profiled peripheral-blood DNA methylation (DNAm) at baseline and week 32 to assess semaglutide versus placebo on first-, second-, and third-generation epigenetic aging measures. In adjusted analyses, semaglutide reduced epigenetic aging across multiple second- and third-generation clocks, including PhenoAge ( − 4.9 years/year, p  = 0.004), PCGrimAge ( − 3.1, p  = 0.007), GrimAge V2 ( − 2.3, p  = 0.009), OMICmAge ( − 2.2, p  = 0.009), RetroAge ( − 2.2, p  = 0.030), and DunedinPACE ( − 0.09 units, 9% slower, p  = 0.01). Systems-based clocks showed parallel reductions in inflammation, brain, and heart aging measures. The post hoc design, modest sample size, HIV-specific cohort, and 32-week follow-up limit generalizability. Prospective trials are needed to determine whether GLP-1 receptor agonists can be repurposed as gerotherapeutics.