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In this instalment of Career pathways, James White and Wenjing Du reflect on the importance of recruiting the right people, staying excited and making work and home life coexist.

This study employs in situ cryo-ET to visualize basal body formation and ciliogenesis in multiciliated mouse cells, revealing how the remodeling of microtubule-inner proteins (e.g., CEP41) ensures precise ciliary assembly.

An endohedral metallofullerene–polymer layer, which features ultrafast electron extraction and in situ encapsulation, improves the efficiency and stability of perovskite solar cells.

Lipid droplets (LDs) and endosomes play crucial roles in cellular processes, yet their interplay is poorly understood. Here, the authors develop an LD-specific probe, AP1-coumarin, and reveal dynamic interactions between LDs and endosomes, regulating lipid homeostasis.

Blue QD-LEDs suffer from poor operational stability due to the carrier accumulation at transport layers. Here, the authors propose a strategy to mitigate the hole accumulation driven oxidation in hole transport layer, effectively elongating the operational lifetime of blue QD-LEDs.

There is growing evidence indicating the different roles of natural UHRF1 inhibitory protein STELLA in mouse-derived cells from its human ortholog. Here, the authors report the differences of hSTELLA versus mSTELLA in inhibiting the maintenance or de novo DNA methylation functions of UHRF1 in human cancer cells, and lipid nanoparticle-delivered mSTELLA reversing cancer-specific DNA hypermethylation thereby impairing colorectal cancer tumorigenicity.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

Sympathetic innervation of brown and white adipose tissue is shown to be promoted by zinc released from thermogenic adipocytes, revealing a positive feedback mechanism for regulation of thermogenesis and thereby energy expenditure.

The removal of ethane from ethylene is of importance in the petrochemical industry, but similar physicochemical properties of these molecules makes separation a challenging task. Here, the authors demonstrate that a robust octahedral calix[4]resorcinarene-based porous organic cage can separate high-purity ethylene from ethane/ethylene mixtures.

Speleothems from the Savanna region in Brazil documents the occurrence of an unprecedented long-term drought driven by anthropogenic forcing. Staring in the 1970´s the current drought is the most severe that has struck the region in the past 700 years.

Proteases of the caspase family are important regulators of apoptosis. Here, Zhang et al. present a genetically encoded protein biosensor that fluoresces if cleaved by caspase-3-like proteases, allowing real-time measurements of apoptosis in cells.

The metabolic switch of tumours to aerobic glycolysis can allow them to meet their increasing energetic demands. Here, the authors show that AKT1 regulates this switch through the phosphorylation of malic enzyme 2 (ME2) preventing mitochondrial translocation. In turn this pushes the cell from mitochondrial metabolism to glycolysis, promoting tumour growth.

Low-cost targeted approach to construct haplotype-resolved assemblies is needed to facilitate population genetic studies. Here, the authors demonstrate assembling high-quality MHC haplotypes with CRISPR-based enrichment and long-read sequencings.

The p53 homologue TAp73 is frequently overexpressed in tumours, suggesting it provides an advantage to cancer cells. Yang and colleagues have investigated the role of TAp73 in tumour cell proliferation and showed that TAp73, but not p53, is a transcriptional activator of glucose-6-phosphate dehydrogenase. Increased expression of this gene promotes the pentose phosphate pathway flux, leading to enhanced biosynthesis and antioxidant defence, both of which have been shown to support optimal cell proliferation and tumour formation.

The sequencing and assembly of the highly polymorphic oyster genome through a combination of short reads and fosmid pooling, complemented with extensive transcriptome analysis of development and stress response and proteome analysis of the shell, provides new insight into oyster biology and adaptation to a highly changeable environment.

Lung adenocarcinomas can convert to squamous cell carcinomas, which is associated with cancer progression and therapy resistance. Here, Gao et al. identify YAP as an essential barrier for this phenotypic conversion through ZEB2-mediated DNP63 repression.

An effective expansion system for therapeutic megakaryocyte-biased hematopoietic stem cells has not been developed. Here the authors present a microniche-based system that supports scalable expansion of human Mk-biased HSCs and identify their immune phenotype.

Cancer cells preferentially use aerobic glycolysis to generate ATP, consuming glucose in the process. The tumour suppressor p53 is now shown to suppress glucose consumption by inhibiting the pentose phosphate pathway (PPP). Tumour-associated p53 mutations lack this inhibitory effect.

The proapoptotic protein Siva1 has been shown to inhibit the tumour suppressor p53, however, it remains unclear how this activity is mediated. Here the authors show that Siva1 is an E3 ubiquitin ligase which inhibits p53 by promoting the degradation of ARF.

The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern and early assessment would be vital. Here, the authors show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission.

Mutant p53 protein is stabilized by direct binding to 2-HG produced by malic enzyme 2, resulting in enhanced tumour growth.

Li et al. report a non-metabolic role of NADPH as an inhibitor of HDAC3, thus linking NADPH levels with the epigenetic state of a cell.

Cellular responses to mechanical stimulation have emerged as an important area of research. Here, the authors use cryoprotectant to control the pore size and mechanical properties of porous scaffolds without changing the scaffold composition to allow for the study of cellular mechano-responsiveness in 3D.

The authors uncover new mutations in an enzyme from the purine synthesis pathway that cause resistance to leukemia therapy, and reveal a new mechanism by which they affect drug metabolism.

Imaging and sequencing approaches are combined to show that extrachromosomal DNA (ecDNA) in cancer is circular and has unique chromatin structure that amplifies oncogene output.

TAp73 is a structural homolog of the tumor suppressor p53. Here they show that TAp73 is critical for promoting glycolysis as it stimulates the transcriptional expression of liver type of phosphofructokinase-1 (PFKL), which catalyzes the committed step in glycolysis.

Evidence for a link between cellular senescence and metabolic regulation is provided, through the observation that p53 represses the expression of malic enzymes, thereby regulating NADPH, lipid and glutamine metabolism; in turn, this repression further activates p53, promoting cellular senescence.

NLRC5 facilitates cardiac repair by orchestrating autophagy through CAVIN1 degradation and CAV1/ATG12-5 modulation, positioning NLRC5 as a therapeutic target to mitigate post-MI damage and enhance recovery.

p53 regulates the metabolism of ammonia by repressing genes of the urea cycle that function to eliminate excess ammonia.

Characterization of macrophage polarization into different functional phenotypes is valuable for further investigation of gout pathogenesis, as well as for a better disease management. In this study the authors found that altered macrophage polarization exists in various stages of gouty inflammation. Macrophages in acute gout were polarized into M1 at an early stage and into M2 at later stages while the macrophages in chronic gout were generally polarized towards M2. The number of M1 rose with the progression of inflammation. Early increase of M2 was observed, which might be generated directly from M0.

The changes of global gaseous pollutants during the COVID-19 pandemic in early 2020 were retrieved from Chinese ultraviolet–visible hyperspectral satellite instrument through a series of remote sensing algorithm optimizations.