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Behçet’s syndrome is a chronic inflammatory disease with oral ulcers being the most common symptom. Here authors present results from a phase 2 randomized double-blind placebo-controlled clinical trial that shows that systemic low dose interleukin-2 could be safely administered to these patients, and the therapy may improve their quality of life.

Bicyclic peptides targeting integrin are promising drug candidates, yet achieving high selectivity for specific integrins remains challenging. Here, the authors design RGD-containing bicyclic peptides with a tryptathionine bridge, demonstrating that peptide 5j selectively targets integrin αvβ3, and induces αvβ3-targeted cytotoxicity by drug-peptide conjugates.

Ubiquitin-conjugating enzymes (E2s), including UBE2D3, are important regulator of cellular function and fate. Here the authors report that IFN-y driven upregulation of UBE2D3 is associated with impaired antigen presentation in pancreatic cancer, also showing that its targeting enhances antitumor immunity.

X. Du, W. Li, G. Li, C. Guo et al. report that dietary galactose regulates the cellular crosstalk between hepatocytes and CD8⁺ T cells via IGFBP-1 production and IGF-1 signalling, thereby modulating T cell exhaustion and antitumour immunity.

Enhanced mitophagy has been recognized as crucial mechanism to sustain cellular homeostasis in hypoxic tumors. Here, this group fabricates an azocalix[4]arene-modified supramolecular albumin nanoparticle codelivering hydroxychloroquine (HCQ) and sulfur-substituted methylated nile blue analog, capable of inducing cascaded oxidative stress via regulating mitophagy for hypoxic tumors treatment.

The CAPItello-291 phase 3 study reported that capivasertib (an AKT inhibitor) and fulvestrant (a selective estrogen receptor degrader) improved progression free survival in patients with HR-positive/HER2-negative advanced breast cancer. Here, the authors report the results of an extended Chinese cohort recruited as part of the original global CAPItello-291 study.

Systems with strong photon-photon interactions enable advanced quantum optical applications as well as the study of highly correlated light-matter states. Here the authors report strong coupling between single- and two-photon states in a superconducting circuit, enabling a new regime of nonlinear quantum optics.

Through a synthetic-bioinformatic natural product approach combined with peptide optimization, a nature inspired antibiotic, paenimicin, was identified from Paenibacillaceae family. Paenimicin features a dual-target mechanism of action and shows broad-spectrum activities against multi-drug-resistant pathogens both in vitro and in vivo.

A combination of adenovirus-vectored and subunit protein intranasal vaccine enhances immune response against SARS-CoV-2 variants in animal models and humans.

HER2 targeted therapy combined with chemotherapy represents a standard approach for treating HER2-positive metastatic breast cancer (MBC). Here the authors report the results of a phase II trial of the small molecule tyrosine kinase inhibitor pyrotinib plus docetaxel as a first-line treatment for HER2-positive MBC.

The haplotype-resolved genome of tetraploid modern rose, along with a variation map of 233 wild and cultivated Rosa accessions, reveals the complex genome composition of modern roses and elucidates the genomic bases of their origin and breeding.

Toxoplasma gondii acquires host cytosolic materials, yet the mechanism remains unknown. Wan et al. reveal the micropore as an essential organelle at the plasma membrane for endocytosis of host cytosolic proteins and biotin, and Golgi ceramide.

Fan et al. show that cTAGE5 is essential for adipogenesis and adipose tissue development. Mechanistically, cTAGE5 promotes pro-insulin receptor processing, which mediates actin cytoskeleton remodeling and lipolysis during the adipocyte differentiation.

Genome sequences of a deep-sea vent and a shallow-water mussel species are compared. The former has expanded gene families for protein stabilization and removal of toxic substances and has a more complex immune system.

The characteristics of the pores are vital for controlling the performance of covalent organic frameworks, but obtaining different chemical environments in different pores is challenging. Here, the authors report the development of covalent organic frameworks with differing pore environments.

The molecular mechanisms underlying relapse in pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients remain to be explored. Here, the authors characterise the chromatin accessibility landscape of B-ALL and identify subtype and drug response specific patterns.

Thermal instability is a critical bottleneck for bulk heterojunction organic solar cells. Here Yang et al. use barely 1 wt% of a polymer acceptor as an additive to simultaneously improve the device efficiency and thermal stability of several state-of-the-art organic photovoltaic systems at high temperatures.

Jellyfish plays an important ecological role in surface waters and the deep sea. Here the authors report genome sequences of two true jellyfish, Sanderia malayensis and Rhopilema esculentum, showing distinct homeobox gene clusters and sesquiterpenoid pathway.

NK-cell and γδ-T cell lymphoma share clinic-pathological features; however the driving mutations are largely unknown. Here the authors, using a combination of RNA-Seq analysis, targeted re-sequencing and functional analysis, identify frequent activating mutations in STAT3 and STAT5Bthat may be driver mutations in these diseases.

Osteosarcoma survival rates have been largely unchanged for several decades, and treatment response is variable. Here, the authors analyzed genomic, transcriptomic and epigenomic data from 121 osteosarcoma patients and identify subtypes related to treatment outcome.

Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.

The use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

The adult mammalian inner ear cells cannot regenerate nor proliferate. Here, the authors show that co-activation of Myc and NOTCH pathways can stimulate proliferation of inner ear sensory epithelial cells, which can be induced to become hair cell-like cells in vitro and in vivo.

Transposable elements, or ‘jumping genes’, constitute ~45% of the human genome. Sun et. al. report that jumping gene dysregulation is a pharmacologically targetable driver of cell death in neurodegenerative tauopathies, including Alzheimer’s disease.

Brain-wide axonal projections of single neurons have been extensively reconstructed without any functional characterization. The authors present a method that allows for developing a precise one-to-one map of both projection patterns and functional features of single neurons in mice.

Oxidative stress is closely linked with nonalcoholic steatohepatitis (NASH). Here, the authors show that palmitic acid stimulates NASH by inhibiting PRDX1 to increase oxidative stress, while rosmarinic acid improves NASH by activating PRDX1 to reduce oxidative stress.

In this work the authors report how human mesenchymal stem cells rapidly adapt to dynamic microenvironment through lipid raft in membrane microdomains that direct neurogenesis.

Human serum albumin (HSA) can be used as a drug delivery material for cancer therapy. Here, the authors report an HSA-based photothermal platform that improves drug loading and photothermal therapeutic performance in breast cancer mouse models.

Prime editors can mediate all twelve types of base substitutions and small insertions or deletions in living cells but its efficiency remains low. Here the authors introduce same-sense mutations into pegRNAs to increase base-editing efficiency and the pegRNA secondary structure was altered to increase indel-editing efficiency.

PTENα is an N-terminally extended isoform of PTEN, a gene frequently mutated in human cancers. Here the authors show that PTENα remains active in PTEN-mutant cancers and is associated with tumor immune escape by promoting tumor cell resistance to T cell cytotoxicity.

Doping carbon-based materials with nitrogen is effective for enhancing catalytic activity for oxygen reduction; however, directing nitrogen dopants to specific locations is difficult. Here the authors employ hydrogen-substituted graphdiyne as a matrix for nitrogen doping, leading to enhanced performance.

While hydrogen bonded organic frameworks are well covered in the scientific literature, halogen hydrogen-bonded organic framework (XHOF) remain less explored. Here, the authors demonstrate a highly stable diradical-based XHOF and demonstrate photoreduction of uranyl ions and high capacity of uranyl immobilization.

Jin et al. discover the accumulation of natural killer (NK) cells in the aged brains of humans and mice. Neuroblast senescence in the dentate gyrus augments NK cell cytotoxicity that impairs neurogenesis and cognition during normal brain aging.

Melatonin promotes EMT in trophoblast cells via GDF15-mediated activation of the SMAD2/3 pathway and partially induces the expression of GPX4 through GDF15 to enhance oxidative damage resistance in trophoblast cells.

Zhong and colleagues report that zebrafish leakytail (Lkt) promotes ciliogenesis by exporting prostaglandin E2 to upregulate cAMP synthesis. A human orthologue of Lkt, ABCC4, is also important for ciliogenesis in human retinal pigment epithelial cells.