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In comparison to the well-developed electrochemical transformations of thiophenols, the electrochemical modification of peptides and proteins through cysteine remains rather underdeveloped. Here the authors report an electro-induced umpolung approach that enables the efficient functionalization/macrocyclization of cysteine-containing peptides.

Li et al. report that co-delivering a dominant negative fragment of p53 (p53DD) greatly enhances precise editing efficiencies for prime editing and cytosine base editing in human pluripotent stem cells, without compromising the genome-wide safety.

Existing optogenetic methods to induce calcium mobilisation lack selectivity and specificity. Here, the authors design and engineer a single-component light-operated calcium channel to provide optical control over calcium signals and calcium-dependent physiological responses: LOCa.

Efficient and multiplex precise editing in human pluripotent stem cells (hPSCs) remains a significant challenge. Here, the authors established a robust and inducible prime editing platform, termed ‘iPE-Plus’, for efficient and controllable multiplex editing in hPSCs.

While the shortwave infrared (SWIR) region has potential for bioimaging applications, stable and biocompatible SWIR absorbers/emitters are challenging to access. Here, the authors report the approach of crystal-aided aggregate synthesis for the development of J-aggregates for in vivo bioimaging.

Here the authors identify a role of GPAT4 in endocardial and myocardial development through maintaining ER homeostasis. GPAT4 deficiency triggers ER stress, ER-mitochondrial dysfunction, and activation of the cGAS-STING-type I IFN response, leading to severe heart malformation.

How plasma membrane Orai Ca²⁺ channels are activated by STIM proteins to activate Ca²⁺signals is still not fully known. Here the authors show that a nexus region located at the Orai1 C-terminus allows channel gating without a direct interaction of STIM1 with the channel pore.

STIM1, the endoplasmic reticulum calcium sensor, is activated in response to calcium store depletion and translocates to the ER–plasma membrane junctions to activate Orai1 channels. Here the authors present a new model of unimolecular coupling between STIM1 and Orai1 whereby STIM1 dimers may be involved in crosslinking Orai1 channels.

The production of the anticancer drug paclitaxel depends on the extraction of the intermediate baccatin III from Taxus species. This Review highlights recent progress in genome-level analysis of paclitaxel and baccatin III biosynthesis based on sequenced Taxus genomes to guide the future discovery of biosynthesis genes.

Here the authors use cryo-electron microscopy to provide insights into fatty acid recycling by an acyl-acyl carrier protein (ACP) synthesizing enzyme, showing a transition from a hexameric to tetrameric form in the process of acyl-ACP production.

Depletion of calcium from intracellular stores induces interaction between the endoplasmic reticulum STIM1 protein and the plasma membrane ORAI1 channel that facilitates cellular calcium entry. Here Ma et al. characterize a STIM1 gain-of-function mutant and propose a conformational switch that controls ORAI1 gating.

STIM proteins are key regulators of intracellular Ca²⁺ signalling. Here, Wang et al. demonstrate that subtle differences between STIM1 and its close homologue STIM2 have profound consequences for their ability to gate Orai1 Ca²⁺channels, thus revealing the basis for their distinct physiological functions.

A small molecule, CGI1746, was identified to block ferroptosis acting through the sigma-1 receptor, a chaperone primarily at endoplasmic reticulum–mitochondria contacts to mediate calcium transfer.

The intermembrane complexes mediating calcium signals are crucial but poorly understood. Here the authors identify a Phe-His pair in the calcium-sensing STIM1 protein that controls both activation and pairing of STIM1 with Orai channels to generate calcium signals

Dual-specificity phosphatases regulate several processes associated with carcinogenesis. Here the authors show that inhibition of the dual-specificity phosphatase DUSP18 improves the activity of tumor-infiltrating CD8 T cells, enhancing response to immune checkpoint blockade in preclinical models of colorectal cancer.

Bacillus thuringiensis (Bt) is an important bioinsecticide, but high-level resistance has been rapidly evolving in agricultural pests. Here, Guo et al. show that the MAPK cascade can be activated by enhanced upstream insect hormone signals to counter Bt virulence in the diamondback moth.

The NEMO series of genetically encoded calcium indicators report calcium activity in neuronal and non-neuronal cells with high signal-to-baseline ratio, which is shown in neuronal culture, slice preparations, in vivo and in planta.

Determining the triboelectric charge and energy density of dielectric materials is generally limited by many factors, failing to reflect their intrinsic behaviour. Here, a standardized strategy is proposed employing contact-separation TENG and supressing air-breakdown to assess max triboelectric charge and energy densities leading to an updated triboelectric series.

Plutella xylostella endures Bt toxins with no performance costs. This study reveals how, depending on the presence of the toxin, this insect modifies MAPK phosphorylation to modulate the transcription factor FTZ-F1 binding, to up- or down- regulate Bt receptors or non-receptor (resistant) paralogs.

Hydrogen-rich superhydrides are promising high-temperature superconductors which have been observed only at pressures above 170 GPa. Here the authors show that CeH₉ can be synthesized at 80-100 GPa with laser heating, and is characterized by a clathrate structure with a dense 3-dimensional atomic hydrogen sublattice.

Through a proteomic analysis of ER–PM junctions, Zhou and colleagues and Wang and colleagues discover that the transmembrane protein STIMATE is a positive regulator of STIM localization and function, thereby stimulating Ca²⁺ influx.

Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca²⁺ levels to maintain cellular Ca²⁺ balance. Here the authors find that the STIM1 luminal domain monomer has multiple Ca²⁺ - binding sites which set the threshold for physiological activation of STIM1 in cells.

Plasmid-encoded tet(X) genes from Escherichia coli in China confer high-level tigecycline resistance.