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A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

Abstract Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor...

Nature 16h ago

On the Duke--Erd\H{o}s--R\"odl Problem at the One-Third Threshold

Announce Type: cross Abstract: Let $G$ be an $n$-vertex graph with $e(G)\ge n^2/ k$. We prove a self-contained internal short-cycle core theorem at the threshold $k\le n^{1/3}$: the graph $G$ contains a subgraph $H_6$ with $\Omega(n^2/ k^3)$ edges in which every two distinct edges lie together on a cycle of length at most $6$ contained in $H_6$, and a subgraph $H_8$ with $\Omega(n^2/k^2)$ edges in which every two distinct edges lie together on a cycle of length at most $8$ contained in...

arXiv CS 2d ago

Bill aims to end H-1B route to Green Cards & cut OPT: What the new act proposes

US lawmaker Chip Roy has introduced a bill aimed to overhaul the H-1B hiring programme titled “American White-Collar Worker Jobs Act of 2026”. Among other changes, the bill seeks to end the use of H-1B visas as a pathway to permanent residency ( Green Card) and eliminates the Optional Practical Training (OPT) program to prioritize employment opportunities for American STEM professionals. Publishing an official release, the Republican lawmaker said that the proposed legislation "would reform...

Times of India 4d ago

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis

Abstract Clonal haematopoiesis (CH) activates inflammation and increases the risk of atherosclerosis1,2. Whether lifestyle alters CH clone expansion or the phenotypic programming of CH mutant cells, thereby affecting atherosclerosis, is unknown. Here, in humans and mice and across mutations in Jak2, Tet2, Trp53 and Dnmt3a, we demonstrate mutation-dependent responses to sleep and exercise in CH and show that mutant cells are uniquely sensitive to lifestyle.

Nature 16h ago

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.

Nature 16h ago

Four lines that 'layoff email' from Meta Leadership has for those on H-1B visa

Meta has initiated another round of significant layoffs, impacting nearly 8,000 employees globally, with notifications starting in Singapore. While many are let go, over 7,000 will transition to AI initiatives. The company is providing immigration guidance and severance packages, including 16 weeks' pay plus two weeks per service year, and 18 months of COBRA coverage for affected staff.

Times of India 13d ago

Whole-genome duplication shaped cell-type evolution in the vertebrate brain

Abstract The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show...

Nature 16h ago

Light-induced quantum friction of carbon nanotubes in water

Abstract Friction slows down moving objects at both macroscopic and microscopic scales1. At the electronic level, quantum friction describes direct transfer of momentum between a liquid and the electrons of a solid2. Owing to its microscopic nature, this phenomenon remains experimentally challenging to capture3.

Nature 16h ago

Trump's US$100,000 H-1B visa fee is unlawful, US judge rules

Trump's US$100,000 H-1B visa fee is unlawful, US judge rules White House spokeswoman Taylor Rogers in a statement said the Trump administration is confident the US district judge's order will be reversed on appeal. BOSTON: A federal judge on Monday (Jun 8) struck down a US$100,000 fee US President Donald Trump imposed on new H-1B visas for highly skilled foreign workers, concluding that it constituted an unlawful tax Congress never authorised. US District Judge Leo Sorokin in Boston issued...

Channel News Asia 1d ago

Erd\H{o}s Rado Sunflower Theorem for Shifted Families

Combinatorics [Submitted on 1 Jun 2026 (v1), last revised 8 Jun 2026 (this version, v2)] Title:Erdős Rado Sunflower Theorem for Shifted Families View PDF HTML (experimental)Abstract:Let $f(k,s)$ denote the minimum integer $m$ such that any family $\mathcal{F}$ consisting of $k$-sized sets of cardinality at least $m$ always contain a sunflower of size $s$. The Erdős-Rado Sunflower Conjecture states that for every $s >2$, there is an constant $C=C(s)$ such that $f(k,s) \leq C^k$.

arXiv CS 1d ago