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Here the authors report new human fossils from Tam Pà Ling cave, Laos, consisting of a cranial and a tibial fragment, dated to 68–86 thousand years ago. This find confirms that Homo sapiens were present in Southeast Asia by this time and the shape of the fossils indicates they may have descended from non-local populations.

Doan et al. show that loss of cardiac NAD⁺ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

Preclinical studies indicate that myeloproliferative neoplasms (MPN) may be sensitive to the estrogen receptor modulator, tamoxifen. Here, the authors present a phase II clinical trial reporting the efficacy of tamoxifen in MPN and analysis of peripheral haematopoietic stem cells to identify potential predictive signatures of responders.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

TnpB and IscB nucleases use transposon-encoded guide RNAs to target genomic sequences for cleavage, thereby favouring copying and spreading of transposable elements.

Preclinical molecular models are useful that mimic a patient´s response to targeted therapy. Here, the authors establish an in vivo inducible RNAi-mediated gene silencing system in patient-derived xenograft models of acute leukemia to identify individual vulnerabilities and therapeutic targets.

Florfenicol amine hijacks intrinsic resistance in Mycobacterium abscessus, highlighting that antimicrobial resistance mechanisms can be harnessed for antibiotic activation.

Glacially transported igneous rocks eroded from the deep interior of ice-covered East Antarctica constrain a remarkable episodic cooling and exhumation history that helps unravel its mysterious tectonic evolution over the last 500 million years.

Patterson, Firulyova, et al. report that TREM2 is a key regulator of foamy macrophage differentiation. Myeloid-specific deletion of Trem2 caused increased macrophage susceptibility to cholesterol-mediated toxicity and cell death and significantly attenuated atherosclerotic plaque progression in mice.

Thermally assisted magnetic scanning probe lithography is used to reversibly pattern magnetic anisotropy landscapes in a continuous exchange-bias system, where propagating spin waves are excited.

Natural salt lake brines contain various ions, making the selective extraction of KCl challenging. Here, the authors combine 3D covalent organic framework membranes with redox-mediated salinity gradient harvesting to enable the low-energy separation of anions and cations.

Minetti, Omrani et al. report that delayed intestinal regeneration results from protein homeostasis stress and can be improved by modulation of the polyamine pathway dynamics.

RNA-guided transcription factors arose repeatedly via the domestication of transposon-encoded tnpB genes, representing a parallel evolutionary path to CRISPR-Cas adaptive immunity.

Bacterial secretion systems are key to pathogenesis, as they secrete the many virulence factors needed for host colonization. Bioinformatic and functional analyses have identified a transport and assembly module (TAM) in proteobacteria that may be necessary for biogenesis of the autotransporter family of virulence factors.

Taxanes are natural products which bind beta-tubulin, stabilize microtubules and have a broad spectrum of anticancer activity. Here authors employ a computational binding site similarity screen and cell-based assays to reveal a SERM cross-reactivity between the estrogen receptor and the beta-tubulin taxane binding pocket.

In a mouse model of breast cancer, a low-protein diet induces engulfment activities and mTORC1 signalling in tumour-associated macrophages to suppress engulfment-dependent mTORC1 signalling in MYC-overexpressing cancer cells through cell competition, serving as an innate immune defence mechanism to slow tumour growth.

Evidence for the presence of Homo during the Middle Pleistocene is limited in continental Southeast Asia. Here, the authors report a hominin molar from Tam Ngu Hao 2 (Cobra Cave), dated to 164–131 kyr. They use morphological and paleoproteomic analysis to show that it likely belonged to a female Denisovan.

p50 is a constitutively produced NF-κB subunit that modulates the response to DNA damage. Here, the authors show that activation of ATR during S phase induces p50 interaction with BARD1 resulting in p50 mono-ubiquitination, facilitating cell cycle progression and promoting chromosome integrity.

Ferroptosis is a form of non-apoptotic cell death with unclear physiological relevance. Conrad and colleagues now report that unrestrained ferroptosis can lead to renal failure. They also identify a small molecule that limits ferroptosis in vivo.

The role of therapy in shaping the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single-cell RNA sequencing in PDAC samples before and after chemotherapy and suggest that chemotherapy may promote resistance to immunotherapy.

The cell of origin for high-grade serous carcinoma (HGSC) remains to be determined. Here, the authors characterize the different cell types and states of the mouse uterine tube and identify transitional pre-ciliated cells as a cancer-prone cell state, which could be targeted therapeutically.

Clinical correlative data and a plethora of preclinical studies of cancers have shown that both tumour-associated and metastasis-associated macrophages play an important role in promoting cancer. In this Perspective article, Cassetta and Pollard chronologically explore the evolution of our understanding of tumour-associated macrophage biology and enabling technologies.

Kathiriya et al. identify a cardiac progenitor lineage with expression of Tbx5 and anterior heart field-specific expression of Mef2c that bisects the intraventricular septum during development and show that alterations in this lineage lead to congenital heart defects in mice.

Understanding exciton dynamics in quantum dots is important for realizing their potential in optoelectronics. Here, the authors use femtosecond transient absorption microscopy to reveal ultrafast exciton transport, enhanced at larger interdot distance and taking place within hundreds of femtoseconds after generation.

The relationship between wound healing and cancer is intricate and complex. Here, the authors show that in breast cancer models an IL-6 driven co-expression of FAP and HO-1 in tumour-associated macrophages, similar to the wound healing response, facilitates migration and metastatic spread.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Conditional genetic ferret models enable ionocyte lineage tracing, ionocyte ablation and ionocyte-specific deletion of CFTR to elucidate the roles of pulmonary ionocyte biology and function during human health and disease.

A study shows that loss of memory precision associated with systems consolidation can be explained by neurogenesis-dependent reorganization of engram circuitry within the hippocampus over time.

The translocation assembly module (TAM) of Escherichia coli functions together with the BAM complex to mediate the rapid assembly of usher proteins, the molecular platform important for the biogenesis of bacterial fimbriae.

A study demonstrates that metabolic signalling and inflammatory cues associated with obesity selectively induce expression of PD-1 on tumour-associated macrophages to suppress anti-tumour immunity.

Dendritic cells (DC) are important regulators of both innate and adaptive immunity, but how the DC pool is homeostatically maintained in vivo is unclear. Here the authors show that combined deficiency of FLT3 and CSF1R impedes the differentiation of spleen macrophages of embryonic origin that are required for DC homeostasis.

Mouse and human tumour-associated macrophages express PD-1, which increases with cancer stage and induces decreased phagocytosis by macrophages; by contrast, PD-L1 removal increases phagocytosis in vivo, decreases tumour burden and increases survival of mice.

Exciton-polaritons are typically formed in organic systems when the molecules are confined between metallic or dielectric mirrors. Here, the authors reveal that interactions between excitons and moderately confined photonic states within the bare organic film can also lead to polariton formation, making them the primary photoexcitation.

Genetic screening identifies a rich catalogue of regulators of micronucleus formation.

Renal macrophages (RMs) can be of bone marrow or embryonic origin, but their abundance, fate and metabolic profiles in physiological and pathogenic settings are still unclear. Here the authors show, by characterizing these two RMs in multiple transgenic mouse lines, that they exhibit distinct dynamics, homeostasis, immune activity, and metabolic properties.

During early postnatal development in mammals, cardiomyocytes exit the cell cycle, losing their regenerative capacity. Here the authors show that, following myocardial infarction, loss of microRNA-128 promotes cardiomyocyte proliferation and cardiac regeneration in adult mice partly via enhancing the expression of the chromatin modifier SUZ12.

Oncolytic viruses (OV) and second mitochondrial activator of caspase (Smac)-mimetic compounds (SMC) synergistically kill cancer cells directly. Here, the authors show that SMC and OV therapies combination also synergize in vivo by promoting anticancer immunity through an increase in CD8⁺ T-cell response.

Alterations in glycosylation in tumours facilitate tumour progression. Here, the authors show that pancreatic ductal adenocarcinomas present increased sialylation, which stimulates the polarisation of monocytes via Siglec receptors, resulting in the generation of immune suppressive tumour associated macrophages.