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Due to a short flight time, the dual-axis rotational inertial navigation system carried by some launch vehicles or missiles is often only used for self-calibration and self-alignment. It is generally in the strap-down state rather than the rotation modulation state during flight. This wastes the precision potential of the navigation system. Therefore, a mode-switching strategy is proposed in this paper to improve the orbit injection accuracy of a launch vehicle. The rotational navigation system of the launch vehicle is in the near-platform mode or strap-down mode at different periods. It is switched in a timely manner to take advantage of the various modes. Numerical simulation and turntable experiment results show that compared with the traditional strap-down inertial mode, the mode-switching strategy can effectively improve the orbit accuracy of the launch vehicle by about 12% to 13% and hardly increases any costs.

Malaria remains a major public health and economic burden. The heterochromatin environment controls the silencing of genes associated with the fate of malaria parasites. Previous studies have demonstrated that a group of GC-rich ncRNAs (RUF6) is associated with the mutually exclusive expression of var genes, but the underlying mechanisms remain elusive. Here, through a series of genetic manipulation and genome-wide multiomics analysis, we have identified the plasmodial orthologue of RNA exosome-associated Rrp6 as an upstream regulator of RUF6 expression and revealed that the dysregulation of RUF6 upon Rrp6 knockdown triggered local chromatin alteration, thereby activating most heterochromatic genes via direct interaction of RUF6 and distal gene loci. This finding not only uncovered the in-depth mechanism of RUF6-mediated regulation of heterochromatic genes but also identified Rrp6 as a novel regulator of gene expression in human malaria parasites, which provides a new target for developing intervention strategies against malaria. The heterochromatin environment plays a central role in silencing genes associated with the malaria parasite’s development, survival in the host, and transmission to the mosquito vector. However, the underlying mechanism regulating the dynamic chromatin structure is not understood yet. Here, we have uncovered that Plasmodium falciparum Rrp6, an orthologue of eukaryotic RNA exosome-associated RNase, controls the silencing of heterochromatic genes. PfRrp6 knockdown disrupted the singular expression of the GC-rich ncRNA RUF6 family, a known critical regulator of virulence gene expression, through the stabilization of the nascent transcripts. Mechanistic investigation showed that the accumulation of the multiple RUF6 ncRNAs triggered local chromatin remodeling in situ , which activated their adjacent var genes. Strikingly, chromatin isolation by RNA purification analysis (ChIRP-seq) revealed that a remarkable RUF6 ncRNA had interacted with distal heterochromatin regions directly and stimulated a global derepression effect on heterochromatic genes, including all variant gene families and the sexual commitment-associated regulator ap2-g gene. Collectively, Rrp6 appears to conduct the epigenetic surveillance of heterochromatic gene expression through controlling RUF6 levels, thereby securing antigenic variation and sexual commitment of malaria parasites during the infection of the host. IMPORTANCE Malaria remains a major public health and economic burden. The heterochromatin environment controls the silencing of genes associated with the fate of malaria parasites. Previous studies have demonstrated that a group of GC-rich ncRNAs (RUF6) is associated with the mutually exclusive expression of var genes, but the underlying mechanisms remain elusive. Here, through a series of genetic manipulation and genome-wide multiomics analysis, we have identified the plasmodial orthologue of RNA exosome-associated Rrp6 as an upstream regulator of RUF6 expression and revealed that the dysregulation of RUF6 upon Rrp6 knockdown triggered local chromatin alteration, thereby activating most heterochromatic genes via direct interaction of RUF6 and distal gene loci. This finding not only uncovered the in-depth mechanism of RUF6-mediated regulation of heterochromatic genes but also identified Rrp6 as a novel regulator of gene expression in human malaria parasites, which provides a new target for developing intervention strategies against malaria.

Corporate overseas investment is a pivotal element of the Belt and Road Initiative (BRI). As an all-round opening-up strategy, the BRI has brought new ideas to international cooperation, and Chinese enterprises should seize this opportunity to promote global sustainable development. Adopting the data of Chinese listed enterprises from 2011-2020, this paper investigates the impact of the BRI on corporate overseas investment (COI) and its mechanisms via exploiting the difference-in-differences model (DID). Results show that the BRI has significantly facilitated the COI along the routes. We observe that the findings still hold after a series of robustness tests. Mechanism analysis verifies that tax incentives and credit environment improvement are the main channels by which BRI enhances COI. Heterogeneity results reveal that this initiative is more prominent for small and medium-sized enterprises and enterprises in dominant industries. The extensive analysis suggests that from a sustainable development perspective, the BRI facilitates more overseas investment of enterprises in polluting or high energy-consuming industries; the COI is more affected by BRI in regions with more stringent environmental regulations. This study provides empirical evidence for BRI construction and regional development.

ARID1A (the AT-rich interaction domain 1A, also known as BAF250a ) is one of the most commonly mutated genes in cancer 1 , 2 . The majority of ARID1A mutations are inactivating mutations and lead to loss of ARID1A expression 3 , which makes ARID1A a poor therapeutic target. Therefore, it is of clinical importance to identify molecular consequences of ARID1A deficiency that create therapeutic vulnerabilities in ARID1A -mutant tumors. In a proteomic screen, we found that ARID1A interacts with mismatch repair (MMR) protein MSH2. ARID1A recruited MSH2 to chromatin during DNA replication and promoted MMR. Conversely, ARID1A inactivation compromised MMR and increased mutagenesis. ARID1A deficiency correlated with microsatellite instability genomic signature and a predominant C>T mutation pattern and increased mutation load across multiple human cancer types. Tumors formed by an ARID1A-deficient ovarian cancer cell line in syngeneic mice displayed increased mutation load, elevated numbers of tumor-infiltrating lymphocytes, and PD-L1 expression. Notably, treatment with anti-PD-L1 antibody reduced tumor burden and prolonged survival of mice bearing ARID1A -deficient but not ARID1A -wild-type ovarian tumors. Together, these results suggest ARID1A deficiency contributes to impaired MMR and mutator phenotype in cancer, and may cooperate with immune checkpoint blockade therapy. Loss of mismatch-repair protein ARID1A in cancer correlates with high mutation load & checkpoint blockade response, complementing MSI-based prognosis.

Chronic wound healing is a complex and long-standing problem, that has been a major and critical clinical concern around the world for years. Recent advances in digital wound dressings open new possibilities for solving the problem. Here, we report a battery-free, fully permeable, skin-adhesive, stretchable electronic wound bandage (iSAFE) for intelligent wound management. This electronic bandage exhibits superior properties in multiple features and can be conformally adhered to the skin wound. In addition, the iSAFE can accurately assess the wound conditions in-situ and thus adaptively perform localized drug release. The results from both in vitro and in vivo studies on animals prove the validity of wound monitoring, wound healing boosting and intelligent closed-loop wound management. Clinical trials on patients across age 18 to 95 with various types of wounds are performed. These results all indicate the unique and universality of the reported technology for wound monitoring and management. Electronic wound bandages have to balance conformability and wound healing properties. Here, the authors develop a smart patch (iSAFE) using biomaterials with bioelectronics to facilitate permeability with waterproofing. This achieves intelligent wound management with real-time wound monitoring and active therapy.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods 1 – 3 . However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation) 4 – 8 . Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm −2  min −1 , 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices. Incorporation of a ‘liquid diode’ into a wearable electronic platform enhances comfort and stability by shunting away sweat as it accumulates.

Indian Hedgehog (IHH) signaling, a key regulator of skeletal development, is highly activated in cartilage and bone tumors. Yet deletion of Ptch1, encoding an inhibitor of IHH receptor Smoothened (SMO), in chondrocyte or osteoblasts does not cause tumorigenesis. Here, we show that Ptch1 deletion in mice Prrx1+mesenchymal stem/stromal cells (MSCs) promotes MSC proliferation and osteogenic and chondrogenic differentiation but inhibits adipogenic differentiation. Moreover, Ptch1 deletion led to development of osteoarthritis-like phenotypes, exostoses, enchondroma, and osteosarcoma in Smo-Gli1/2-dependent manners. The cartilage and bone tumors are originated from Prrx1+ lineage cells and express low levels of osteoblast and chondrocyte markers, respectively. Mechanistically, Ptch1 deletion increases the expression of Wnt5a/6 and leads to enhanced β-Catenin activation. Inhibiting Wnt/β-Catenin pathway suppresses development of skeletal anomalies including enchondroma and osteosarcoma. These findings suggest that cartilage/bone tumors arise from their early progenitor cells and identify the Wnt/β-Catenin pathway as a pharmacological target for cartilage/bone neoplasms. Bone and cartilage tumors are among the most common tumors in the skeleton, often affecting the limbs. Bone tumors, also called osteosarcomas, usually occur in growing children and teenagers, and they are often resistant to conventional chemo- and radio-therapies. Surgery is the only treatment option, but this can lead to long-lasting damage that impairs the quality of life of these patients. Thus, there is a need to find new drug targets for these diseases. Unfortunately, no good laboratory-based systems exist that mimic these human cancers, hindering research into these tumors. One way to create a laboratory-based model for cartilage tumors and osteosarcomas is to reproduce the signaling that is present in the human tumors in a mouse. A signaling pathway called Hedgehog signaling is overactive in human cartilage and bone tumors. The activity of this pathway can be increased by deleting a gene called Ptch1; but mice do not form tumors when this gene is deleted in their mature cartilage and bone cells. Now, Deng, Li et al. report that deleting Ptch1 in mesenchymal stem cells, early-stage cells that can give rise to cartilage and bone cells, generates a mouse model for osteosarcoma and cartilage tumors. The mice with these Ptch1 deficient cells developed tumors with overactive Hedgehog signaling in cartilage and bone. Deng, Li et al. also performed biochemical experiments to show that Hedgehog signaling turned on another signaling pathway called Wnt signaling. Treating the mice that had mesenchymal cells lacking Ptch1 with a drug that inhibits Wnt signaling reduced the growth of cartilage and bone tumors. These data suggest that deleting Ptch1 in mouse mesenchymal stem cells can mimic human cartilage tumors and osteosarcomas. More experiments will be needed to explain how the Hedgehog and Wnt signaling pathways interact in these tumors. Finally, further studies will need to investigate if inhibiting Wnt signaling might become a useful therapy for human patients with osteosarcoma in the future.

In the quest to connect bulk topological quantum numbers to measurable parameters in real materials, current established approaches often necessitate specific conditions, limiting their applicability. Here we propose and demonstrate an approach to link the non-trivial hierarchical bulk topology to the multidimensional partition of local density of states (LDOS), denoted as the bulk-LDOS correspondence. In finite-size topologically nontrivial photonic crystals, we observe the LDOS partitioned into three distinct regions: a two-dimensional interior bulk area, a one-dimensional edge region, and zero-dimensional corner sites. Contrarily, topologically trivial cases exhibit uniform LDOS distribution across the entire two-dimensional bulk area. Our findings provide a general framework for distinguishing topological insulators and uncovering novel aspects of topological directional band-gap materials, even in the absence of in-gap states. Current approaches to distinguish topological phases from topologically-trivial phases have limited general applicability. Here, in a photonic-crystal context, the authors demonstrate that in trivial structures the bulk local density of states (LDOS) extends all the way to the edges and corners, while in topological structures the bulk LDOS actually avoids the edges and corners.

In an experiment across China to test integrated soil–crop system management for rice, wheat and maize against current practice, improvements in grain yield are equivalent to high-input techniques, but nutrient use, nutrient loss and greenhouse gas emissions are lower than current practice. Locally optimized crop management Integrated soil–crop system management is a technique that aims to maximize yield and minimize environmental impact by adapting cropping systems to local conditions through optimal nutrient application, seasonal timing and the use of the best crop varieties. Fusuo Zhang and colleagues report the results of a China-wide test of this technique for the three main cereal crops — rice, wheat and maize. In comparisons with current practice and high input techniques, the authors find that the integrated system achieves yield improvements equivalent to high input techniques but with lower nutrient use, nutrient loss and greenhouse gas emissions than those found with the current practice. Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs 1 , 2 . Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil–crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha −1 ), 7.2 Mg ha −1 and 10.5 Mg ha −1 to 8.5 Mg ha −1 , 8.9 Mg ha −1 and 14.2 Mg ha −1 , respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment 3 show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil–crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.

Objectives To compare the image quality of three-dimensional breath-hold magnetic resonance cholangiopancreatography with deep learning-based compressed sensing reconstruction (3D DL-CS-MRCP) to those of 3D breath-hold MRCP with compressed sensing (3D CS-MRCP), 3D breath-hold MRCP with gradient and spin–echo (3D GRASE-MRCP) and conventional 2D single-shot breath-hold MRCP (2D MRCP). Methods In total, 102 consecutive patients who underwent MRCP at 3.0 T, including 2D MRCP, 3D GRASE-MRCP, 3D CS-MRCP, and 3D DL-CS-MRCP, were prospectively included. Two radiologists independently analyzed the overall image quality, background suppression, artifacts, and visualization of pancreaticobiliary ducts using a five-point scale. The signal-to-noise ratio (SNR) of the common bile duct (CBD), contrast-to-noise ratio (CNR) of the CBD and liver, and contrast ratio between the periductal tissue and CBD were measured. The Friedman test was performed to compare the four protocols. Results 3D DL-CS-MRCP resulted in improved SNR and CNR values compared with those in the other three protocols, and better contrast ratio compared with that in 3D CS-MRCP and 3D GRASE-MRCP (all, p < 0.05). Qualitative image analysis showed that 3D DL-CS-MRCP had better performance for second-level intrahepatic ducts and distal main pancreatic ducts compared with 3D CS-MRCP (all, p < 0.05). Compared with 2D MRCP, 3D DL-CS-MRCP demonstrated better performance for the second-order left intrahepatic duct but was inferior in assessing the main pancreatic duct (all, p < 0.05). Moreover, the image quality was significantly higher in 3D DL-CS-MRCP than in 3D GRASE-MRCP. Conclusion 3D DL-CS-MRCP has superior performance compared with that of 3D CS-MRCP or 3D GRASE-MRCP. Deep learning reconstruction also provides a comparable image quality but with inferior main pancreatic duct compared with that revealed by 2D MRCP. Key Points • 3D breath-hold MRCP with deep learning reconstruction (3D DL-CS-MRCP) demonstrated improved image quality compared with that of 3D MRCP with compressed sensing or GRASE. • Compared with 2D MRCP, 3D DL-CS-MRCP had superior performance in SNR and CNR, better visualization of the left second-level intrahepatic bile ducts, and comparable overall image quality, but an inferior main pancreatic duct.