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Plants employ dynamic molecular networks to control development in response to environmental changes, yet the underlying mechanisms are largely unknown. Here we report the identification of two rice leucine-rich repeat receptor-like kinases, Thermo-Sensitive Genic Male Sterile 10 (TMS10) and its close homolog TMS10-Like (TMS10L), which redundantly function in the maintenance of the tapetal cell layer and microspore/pollen viability under normal temperature conditions with TMS10 playing an essential role in higher temperatures (namely, 28 °C). tms10 displays male sterility under high temperatures but male fertility under low temperatures, and the tms10 tms10l double mutant shows complete male sterility under both high and low temperatures. Biochemical and genetic assays indicate that the kinase activity conferred by the intracellular domain of TMS10 is essential for tapetal degeneration and male fertility under high temperatures. Furthermore, indica or japonica rice varieties that contain mutations in TMS10, created by genetic crosses or genome editing, also exhibit thermo-sensitive genic male sterility. These findings demonstrate that TMS10 and TMS10L act as a key switch in postmeiotic tapetal development and pollen development by buffering environmental temperature changes, providing insights into the molecular mechanisms by which plants develop phenotypic plasticity via genotype–environment temperature interaction. TMS10 may be used as a genetic resource for the development of hybrid seed production systems in crops.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1 , Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation. The authors of this manuscript identify that Gpr54 activation by its natural ligand Kisspeptin-10 can abrogate bone resorption. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase, which causes Dusp18 to dephosphorylate Src at Tyr 416.

The mammalian BREAST CANCER 2 ( BRCA2 ) gene is a tumor suppressor that plays a crucial role in DNA repair and homologous recombination (HR). Here, we report the identification and characterization of OsBRCA2 , the rice orthologue of human BRCA2 . Osbrca2 mutant plants exhibit normal vegetative growth but experience complete male and female sterility as a consequence of severe meiotic defects. Pairing, synapsis and recombination are impaired in osbrca2 male meiocytes, leading to chromosome entanglements and fragmentation. In the absence of OsBRCA2, localization to the meiotic chromosome axes of the strand-invasion proteins OsRAD51 and OsDMC1 is severely reduced and in vitro OsBRCA2 directly interacts with OsRAD51 and OsDMC1. These results indicate that OsBRCA2 is essential for facilitating the loading of OsRAD51 and OsDMC1 onto resected ends of programmed double-strand breaks (DSB) during meiosis to promote single-end invasions of homologous chromosomes and accurate recombination. In addition, treatment of osbrca2-1 seedlings with mitomycin C (MMC) led to hypersensitivity. As MMC is a genotoxic agent that creates DNA lesions in the somatic cells that can only be repaired by HR, these results suggest that OsBRCA2 has a conserved role in DSB repair and HR in rice.

Abstract Owing to its constant exposure to the external environment and various stimuli, skin ranks among the organs most vulnerable to manifestations of aging. Preventing and delaying skin aging has become one of the prominent research subjects in recent years. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential. MSC-derived extracellular vesicles (MSC-EVs) are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior. Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory, anti-oxidative stress, and wound healing promoting abilities. This review presents the latest progress of MSC-EVs in delaying skin aging. It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts, reducing the expression of matrix metalloproteinases, resisting oxidative stress, and regulating inflammation. We then briefly discuss the recently discovered treatment methods of MSC-EVs in the field of skin anti-aging. Moreover, the advantages and limitations of EV-based treatments are also presented. Graphical Abstract Graphical Abstract

This research aimed to comparatively evaluate the influences of root restriction (RR) cultivation and traditional cultivation (RC) on grape berry skin metabolomics using a non-targeted metabolomics method. Two-hundred-and-ninety-one metabolites were annotated and the kinetics analyses showed that berry skin metabolome is stage- and cultivation-dependent. Our results showed that RR influences significantly the metabolomes of berry skin tissues, particularly on secondary metabolism, and that this effect is more obvious at pre-veraison stage, which was evidenced by the early and fast metabolic shift from primary to secondary metabolism. Altogether, this study provided an insight into metabolic adaptation of berry skin to RR stress and expanded general understanding of berry development.

‘General requirements for the production of extracellular vesicles derived from human stem cells’ is the first guideline for stem cells derived extracellular vesicles in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the general requirements, process requirements, packaging and labelling requirements and storage requirements for preparing extracellular vesicles derived from human stem cells, which is applicable to the research and production of extracellular vesicles derived from stem cells. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that the publication of this guideline will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardisation of extracellular vesicles derived from human stem cells.

Deep Learning (DL) compilers typically load a DL model and optimize it with intermediate representation.Existing DL compiler testing techniques mainly focus on model optimization stages, but rarely explore bug detection at the model loading stage. Effectively testing the model loading stage requires covering diverse usages of each DL operator from various DL libraries, which shares a common objective with DL library testing, indicating that the embedded knowledge in DL library tests is beneficial for testing the model loading stage of DL compilers. In this work, we propose OPERA to extract such domain knowledge from the test inputs for DL libraries. OPERA constructs diverse tests from the various test inputs for DL libraries (including the test inputs documented in DL libraries and those generated by recent fuzzers). In addition, it incorporates a diversity-based test prioritization strategy to migrate and execute those test inputs that are more likely to detect diverse bugs earlier. We considered three sources of tests in DL libraries for migration and used eight frontends from three DL compilers (e.g., TVM, TensorRT, and OpenVINO) for evaluation. OPERA detected 170 previously unknown bugs in total, 90 of which have been confirmed/fixed by developers, demonstrating the effectiveness of such the migration-based idea. The test prioritization strategy in OPERA improves testing efficiency with migrated tests by 11.9%~47.4% on average compared to general test prioritization strategies.

Celastrol, a natural bioactive ingredient derived from Tripterygium wilfordii Hook F, exhibits significant broad-spectrum anticancer activities for the treatment of a variety of cancers including liver cancer, breast cancer, prostate tumor, multiple myeloma, glioma, etc. However, the poor water stability, low bioavailability, narrow therapeutic window, and undesired side effects greatly limit its clinical application. To address this issue, some strategies were employed to improve the anticancer efficacy and reduce the side-effects of celastrol. The present review comprehensively focuses on the various challenges associated with the anticancer efficiency and drug delivery of celastrol, and the useful approaches including combination therapy, structural derivatives and nano/micro-systems development. The specific advantages for the use of celastrol mediated by these strategies are presented. Moreover, the challenges and future research directions are also discussed. Based on this review, it would provide a reference to develop a natural anticancer compound for cancer treatment.

Photoacoustic tomography (PAT), also known as optoacoustic tomography, is an attractive imaging modality that provides optical contrast with acoustic resolutions. Recent progress in the applications of PAT largely relies on the development and employment of ultrasound sensor arrays with many elements. Although on-chip optical ultrasound sensors have been demonstrated with high sensitivity, large bandwidth, and small size, PAT with on-chip optical ultrasound sensor arrays is rarely reported. In this work, we demonstrate PAT with a chalcogenide-based micro-ring sensor array containing 15 elements, while each element supports a bandwidth of 175 MHz (−6 dB) and a noise-equivalent pressure of 2.2 mPaHz −1/2 . Moreover, by synthesizing a digital optical frequency comb (DOFC), we further develop an effective means of parallel interrogation to this sensor array. As a proof of concept, parallel interrogation with only one light source and one photoreceiver is demonstrated for PAT with this sensor array, providing images of fast-moving objects, leaf veins, and live zebrafish. The superior performance of the chalcogenide-based micro-ring sensor array and the effectiveness of the DOFC-enabled parallel interrogation offer great prospects for advancing applications in PAT. The authors report a highly sensitive chalcogenide-based micro-ring sensor array for photoacoustic tomography and develops a compatible parallel interrogation means by synthesizing a digital optical frequency comb. Imaging is demonstrated on fast-moving objects, leaf veins, and live zebrafish.