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Abstract Gene drives are alleles that can bias the inheritance of specific traits in target populations for the purpose of modification or suppression. Here, we construct a homing suppression drive in the major urban malaria vector Anopheles stephensi targeting the female-specific exon of doublesex, incorporating two gRNAs and a nanos-Cas9 to reduce functional resistance and improve female heterozygote fitness. Our results show that the drive was recessive sterile in both females and males, with various intersex phenotypes in drive homozygotes. Both male and female drive heterozygotes show only moderate drive conversion, indicating that the nanos promoter has lower activity in A. stephensi than in Anopheles gambiae. By amplicon sequencing, we detect a very low level of resistance allele formation. Combination of the homing suppression drive and a vasa-Cas9 line boosts the drive conversion rate of the homing drive to 100%, suggesting the use of similar systems for population suppression in a continuous release strategy with a lower release rate than SIT or fsRIDL techniques. This study contributes valuable insights to the development of more efficient and environmentally friendly pest control tools aimed at disrupting disease transmission.

Abstract Using potentiometric testing, we investigated the zeta potential of shield muck curing materials’ particle surfaces, varying the concentration of metal ion complex. We analyzed the microscopic characteristics of shield muck curing products by using the electron microscopy, revealing the impact of metal ion complex on curing. Results showed that the metal ion complex significantly reduces the surface zeta potential of shield muck and conventional curing materials, with cement showing the most substantial effect, followed by shield muck, calcium carbonate, and calcium sulfate. The concentration of metal ion complex negatively correlates with the zeta potential within a range of 0 to 100 mmol/L. Comparing shield muck cured for 7 and 28 days, with and without metal ion complexes, indicated that metal ion complexes accelerate crystalline product formation, increasing the compressive strength of shield cinder cured products by over 35%. Fitted curves and empirical parameter equations of zeta potential and metal ion complex concentration align with experimental results. This study provides a reference for the efficient treatment and sustainable utilization of shield slag soil, holding significant practical engineering value.

Abstract In arid and semi-arid climates, native plants have developed unique strategies to survive challenging conditions. These adaptations often rely on molecular pathways that shape plant architecture to enhance their resilience. Date palms (Phoenix dactylifera) and mangroves (Avicennia marina) endure extreme heat and high salinity, yet the metabolic pathways underlying this resilience remain underexplored. Here, we integrate tissue imaging with spatial metabolomics to uncover shared and distinct adaptive features in these species. We found that mangrove roots accumulate suberin and lignin in meristematic tissues, this is unlike other plant species, where only the differentiation zones contain these compounds. Our metabolomic analysis shows that date palm roots are enriched in metabolites involved in amino acid biosynthesis, whereas compounds involved in lignin and suberin production were more abundant in mangrove roots. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed tissue- and species-specific metabolite distributions in root tissues. We identified common osmoprotectants accumulating in the exodermis/epidermis of date palm and mangrove root meristems, along with a unique metabolite highly abundant in the inner cortex of date palm roots. These findings provide valuable insights into stress adaptation pathways and highlight key tissue types involved in root stress response.

Abstract Enhancing crops productivity to ensure food security is one of the major challenges encountering agriculture today. A promising solution is the use of biostimulants, which encompass molecules that enhance plant fitness, growth, and productivity. The regulatory metabolite zaxinone and its mimics (MiZax3 and MiZax5) showed promising results in improving the growth and yield of several crops. Here, the impact of their exogenous application on soil and rice root microbiota was investigated. Plants grown in native paddy soil were treated with zaxinone, MiZax3, and MiZax5 and the composition of bacterial and fungal communities in soil, rhizosphere, and endosphere at the tillering and the milky stage was assessed. Furthermore, shoot metabolome profile and nutrient content of the seeds were evaluated. Results show that treatment with zaxinone and its mimics predominantly influenced the root endosphere prokaryotic community, causing a partial depletion of plant-beneficial microbes at the tillering stage, followed by a recovery of the prokaryotic community structure during the milky stage. Our study provides new insights into the role of zaxinone and MiZax in the interplay between rice and its root-associated microbiota and paves the way for their practical application in the field as ecologically friendly biostimulants to enhance crop productivity.

Abstract An improved method tailored for anisotropic soft soils is presented, integrating theoretical models and field data to calculate the grouting quantity required for tunnel foundations. Given the complexities of soil interactions, particularly under variable geological conditions, this approach incorporates nonlinear behaviors and empirical field data to improve accuracy. Our findings reveal that integrating these theoretical frameworks significantly enhances the understanding of stress–strain behavior during grouting, enabling precise calculations of both axial and vertical expansion. Validation against numerical simulations demonstrates the model’s reliability, highlighting the influence of soil types and grouting depths on expansion dynamics. This method not only helps mitigate risks in tunnel construction but also enhances foundation reinforcement strategies, driving progress in geotechnical engineering. It is particularly valuable for urban tunnel projects in complex geological conditions, where ensuring ground stability and safety is crucial.

Abstract Understanding the genetic basis of developmental delay (DD) and intellectual disability (ID) remains a considerable clinical challenge. This study evaluated the clinical application of trio whole exome sequencing (WES) in children diagnosed with DD/ID. The study comprised 173 children with unexplained DD/ID. The participants underwent trio-WES and their demographic, clinical, and genetic characteristics were evaluated. Based on their clinical features, the participants were classified into two groups for further analysis: a syndromic DD/ID group and a non-syndromic DD/ID group. The genetic diagnostic yield of the 173 children diagnosed with DD/ID was 49.7% (86/173). This included 58 pathogenic or likely pathogenic single nucleotide variants (SNVs) in 41 genes identified across 54 individuals (31.2%) through trio-WES. Among these, 22 SNVs had not been previously reported. Additionally, 30 copy number variations (CNVs) were detected in 36 individuals (20.8%). The diagnostic yield in the syndromic DD/ID group was higher than that in the non-syndromic DD/ID group (57.8% vs. 47.2%, P

Abstract Iron is an essential biomineral in the human body. Here, we describe a subset of iron-loaded cancer-associated fibroblasts, termed as FerroCAFs, that utilize iron to induce immunosuppression in prostate cancer and predict an unfavorable clinical outcome. FerroCAFs secrete myeloid cell-associated proteins, including CCL2, CSF1 and CXCL1, to recruit immunosuppressive myeloid cells. We report the presence of FerroCAFs in prostate cancer from both mice and human, as well as in human lung and ovarian cancers, and identify a conserved cell surface marker, the poliovirus receptor. Mechanistically, the accumulated iron in FerroCAFs is caused by Hmox1-mediated iron release from heme degradation. The intracellular iron activates the Kdm6b, an iron-dependent epigenetic enzyme, to induce an accessible chromatin state and transcription of myeloid cell-associated protein genes. Targeting the FerroCAFs by inhibiting the Hmox1/iron/Kdm6b signaling axis incurs anti-tumor immunity and tumor suppression. Collectively, we report an iron-loaded FerroCAF cluster that drives immunosuppression through an iron-dependent epigenetic reprogramming mechanism and reveal promising therapeutic targets to boost anti-tumor immunity.

Abstract The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans.

Abstract Monofluoroalkenes serve as nonhydrolyzable mimetics of amides and are frequently encountered in drug candidates. Herein we report a regio-, enantio-, and stereoselective NiH-catalyzed ipso- and migratory defluorinative olefin cross-coupling employing readily available olefins and gem-difluoroalkenes under mild conditions. This approach enables the efficient synthesis of a broad array of structurally diverse monofluoroalkenes bearing a tertiary allylic stereogenic center. Mechanistically, the challenging migratory defluorinative olefin cross-coupling process is successfully realized through a ligand relay catalytic strategy, enabling the formal C(sp3)–H/C(sp2)–F activation with high levels of regio-, stereo-, and enantiocontrol.

Abstract Excavation of subway tunnels in hard rock generates strong vibration waves that pose potential risks to the stability of surrounding structures. In this study, the discrete element method-finite difference method (DEM-FDM) coupling was adopted to build the model of tunnel structure-rock-pile, which was validated by field monitoring data. Then, the vibration response of piles under various pile-tunnel spacings was analyzed, revealing the occurrence of vibration peak rebound phenomena within certain distance ranges. The range of vibration effects was categorized. Furthermore, in shield tunneling construction, the energy induced by vibrations was mainly concentrated within the 50 Hz range. Low-frequency vibrations result in a wider effect range. The study also demonstrated that within a 1d (tunnel diameter) range of the pile-tunnel spacing, the vibration induced by shield tunneling construction had a more significant effect. As the pile-tunnel spacing increased, the piles transitioned from being subjected to bending forces to experiencing bending-shear forces. Finally, the vibration effects on the existing piles were evaluated under field working conditions. It also provided suggestions for construction based on the effects and laws of the pile dynamic response.

Abstract The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

Abstract Backgroud A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. Methods In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. Results Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p

Tens of minutes of training can significantly improve visual discriminability of human adults, and this fast perceptual learning (PL) effect is usually specific to the trained location, with little transfer to untrained locations. Although location specificity is generally considered as a hallmark of visual PL, it remains unclear whether it involves both facilitation of trained locations and suppression of untrained locations. Here we developed a novel experimental design to investigate the cognitive neural mechanism of location specificity of fast PL. Specifically, we manipulated attentional settings and recorded event-related potentials (ERPs) in both the training and tests. To get reliable location-specific PL effects on early ERPs, we adopted a new approach involving analysis of contralateral-minus-ipsilateral P1 (P1c-i). ERP results showed that tens of minutes of training not only increased the late P1c-i (~100–120 ms) evoked by targets at the trained location, but also decreased the early P1c-i (~75–95 ms) evoked by distractors at the untrained location, both of which were location specific. Moreover, comparison between the pretest and posttest revealed that the suppression effect of early P1c-i preserved even when the untrained location became target location, whereas the facilitation effect of late P1c-i appeared only when the trained location remained actively attended. These findings provide the first evidence that fast PL induces both location-specific facilitation and location-specific suppression at early stages of visual cortical processing. We speculate that while the facilitation effect indicates more efficient allocation of voluntary attention to the trained location induced by fast PL, the suppression effect may reflect learning-associated involuntary suppression of visual processing at the untrained location. Several confounding factors with regard to the early ERP effects of PL are discussed, and some important issues worth further investigation are proposed.

The use of strigolactone (SL) analogs as suicidal germination agents to control the seed banks of the parasitic weed Striga hermonthica has gained interest for field applications in recent years. However, concerns about the environmental safety of these SL analogs remain. In this study, we evaluated the mutagenic potential of two selected SL analogs, Methyl Phenlactonoate 3 (MP3) and Nijmegen-1, across concentrations ranging from 1.5 to 5000 μg per plate. We conducted this assessment using five histidine-deficient mutant tester strains of Salmonella typhimurium. After incubating the SL analogs with the tester strains, we observed no significant increase in the number of revertants, with and without the S9 mix, compared to both negative and positive laboratory controls. These results suggest that MP3 and Nijmegen-1 are non-mutagenic according to the bacterial reverse mutation test, supporting their potential as environmentally safe agents for managing Striga populations.

The model predictive control trajectory planner is a popular and effective robot local motion planner. However, it is challenging to satisfy real-time requirements and implement them on embedded platforms due to their high complexity of solving and reliance on optimization solvers. This letter reports a lightweight and efficient two-stage solving algorithm for the model predictive control planner. Firstly, the general form of the model predictive control local planning problem was specified and simplified by the motion primitives. Then, a two-stage solving method of multi-layer perceptron pre-solving and particle swarm optimization re-optimizing is developed after splitting the cost function into two pieces. An multi-layer perceptron neural network was designed and trained offline to learn the solution of the model predictive control local planner without considering obstacles after selecting the inputs and outputs. Next, to accomplish obstacle avoidance, the particle swarm optimization algorithm re-optimizes the trajectory based on the outputs of the neural network. The experiment results demonstrate that the multi-layer perceptron-particle swarm optimization algorithm can quickly and accurately solve local planning problems, guiding robots to complete global paths with the same efficiency as expert solvers. The average solving time has been reduced by over 90%, enabling the robot to increase its control frequency or adopt higher-quality complex motion primitives. The multi-layer perceptron-particle swarm optimization algorithm can also be used for various robots and motion primitives, with a wide range of potential applications.

Background: This study aims to identify key glycosyltransferases (GTs) in colorectal cancer (CRC) and establish a robust prognostic signature derived from GTs. Methods: Utilizing the AUCell, UCell, singscore, ssgsea, and AddModuleScore algorithms, along with correlation analysis, we redefined genes related to GTs in CRC at the single-cell RNA level. To improve risk model accuracy, univariate Cox and lasso regression were employed to discover a more clinically subset of GTs in CRC. Subsequently, the efficacy of seven machine learning algorithms for CRC prognosis was assessed, focusing on survival outcomes through nested cross-validation. The model was then validated across four independent external cohorts, exploring variations in the tumor microenvironment (TME), response to immunotherapy, mutational profiles, and pathways of each risk group. Importantly, we identified potential therapeutic agents targeting patients categorized into the high-GARS group. Results: In our research, we classified CRC patients into distinct subgroups, each exhibiting variations in prognosis, clinical characteristics, pathway enrichments, immune infiltration, and immune checkpoint genes expression. Additionally, we established a Glycosyltransferase-Associated Risk Signature (GARS) based on machine learning. GARS surpasses traditional clinicopathological features in both prognostic power and survival prediction accuracy, and it correlates with higher malignancy levels, providing valuable insights into CRC patients. Furthermore, we explored the association between the risk score and the efficacy of immunotherapy. Conclusion: A prognostic model based on GTs was developed to forecast the response to immunotherapy, offering a novel approach to CRC management.

Increased astrocytic lactoferrin (Lf) expression was observed in the brains of elderly individuals and Alzheimer's disease (AD) patients. Our previous study revealed that astrocytic Lf overexpression improved cognitive capacity by facilitating Lf secretion to neurons to inhibit β-amyloid protein (Aβ) production in APP/PS1 mice. Here, we further discovered that astrocytic Lf overexpression inhibited neuronal loss by decreasing iron accumulation and increasing glutathione peroxidase 4 (GPX4) expression in neurons within APP/PS1 mice. Furthermore, human Lf (hLf) treatment inhibited ammonium ferric citrate (FAC)-induced ferroptosis by chelating intracellular iron. Additionally, machine learning analysis uncovered a correlation between Lf and GPX4. hLf treatment boosted low-density lipoprotein receptor-related protein 1 (LRP1) internalization and facilitated its interaction with heat shock cognate 70 (HSC70), thereby inhibiting HSC70 binds to GPX4, and eventually attenuating GPX4 degradation and FAC-induced ferroptosis. Overall, astrocytic Lf overexpression inhibited neuronal ferroptosis through two pathways: reducing intracellular iron accumulation and promoting GPX4 expression via inhibiting chaperone-mediated autophagy (CMA)-mediated GPX4 degradation. Hence, upregulating astrocytic Lf expression is a promising strategy for combating AD.

The partial removal of lignin from bamboo materials, a prevalent method to soften the material for plastic forming. It increases bending toughness and improves forming quality, albeit at the expense of load-bearing capacity. This study employs an innovative approach using deep eutectic solvent pretreatment on bamboo green strips (BGS) to establish a balance between strength and toughness, resulting in a significant enhancement of the elastic modulus. The mechanical properties of the DES-treated BGS displayed notable improvements compared to bamboo timber strips (BTS) and bamboo yellow strips (BYS), which either showed no enhancement or suffered degradation after extended treatment durations. Notably, BGS treated for one hour exhibited increases of 8.22 % in flexural toughness and 33.45 % in elastic modulus, while strength diminished by a mere 5.72 %. Concurrently, its porosity increased by 29.36 %, predominantly in the mesopore range. In addition, the crystallinity of the treated BGS increased, whereas the grain size decreased. Silicon-aluminum compounds form on the outer surface of BGS, along with an increase in silicon oxide content, contributed to the observed improvements in stiffness and toughness. These works suggest a novel method for balancing modulus and strength of bamboo structural units, with potential applications in architecture, furniture and transportation sectors.

Using ANSYS/LS-DYNA finite element software, a rock RHT damage constitutive model is used to conduct numerical simulation experiments on the dynamic compression of coal SHPB under different strain rates for the Furong Baijiao coal in Yibin, Sichuan. Firstly, based on the determination method of RHT constitutive model parameters for relevant rocks and the RHT parameter values for Riedel concrete, the optimal parameters of the coal RHT dynamic compression constitutive model are determined through 3 levels of 27 sets of orthogonal experiments under different dynamic strain rates and sensitivity analysis of 13 uncertainty parameters. Secondly, based on the comparison and analysis of numerical simulation experiments and indoor experiments, it is found that the stress-strain curves obtained from the two types of experiments were in good agreement. The numerical simulation test results meet the two assumptions of one-dimensional stress and stress uniformity in SHPB compression test, and the numerical simulation test has a certain degree of reliability. Finally, the RHT damage constitutive model is used to explore the dynamic mechanical properties of coal energy evolution law during the asymptotic deformation and failure process: The research results indicate that the RHT damage constitutive model can better simulate the dynamic deformation and failure process of, and the corresponding mechanical properties and energy evolution process are consistent with the laboratory tests; The RHT model parameters of coal show an increasing trend with the increase of strain rate, and the sensitivity is greatly different. As the strain rate increases from 29.12 s−1 to 95.69 s−1, RHT parameters gc*、N、ft*、n and pco are most sensitive to the final simulation effect of coal, while the parameters pco、ξ、fs*、pco and Q0 are the least sensitive; With the increase of strain rate, the resistance to deformation of coal is obviously enhanced, the degree of fragmentation is more intense, and the peak compressive strength and dynamic strength factor DIF value increase exponentially; The dynamic energy evolution process of coal has obvious stages. Dynamic characteristic stress division based on the obvious stages of dynamic energy evolution process of coal. It is found that the corresponding characteristic energy increases first, then decreases, and then tends to be stable. The dynamic elastic energy storage capacity and limit energy storage capacity of coal should also be enhanced with the increase of strain rate.

Wear particles produced by joint replacements induce inflammatory responses that lead to periprosthetic osteolysis and aseptic loosening. However, the precise mechanisms driving wear particle-induced osteolysis are not fully understood. Recent evidence suggests that autophagy, a cellular degradation process, plays a significant role in this pathology. This study aimed to clarify the role of autophagy in mediating inflammation and osteolysis triggered by wear particles and to evaluate the therapeutic potential of zinc oxide nanoparticles (ZnO NPs).We incorporated ZnO into the prosthetic material itself, ensuring that the wear particles inherently carried ZnO, providing a targeted and sustained intervention. Our findings reveal that polymer wear particles induce excessive autophagic activity, which is closely associated with increased inflammation and osteolysis. We identified secretory autophagy as a key mechanism for IL-1β secretion, exacerbating osteolysis. Both in vitro and in vivo experiments demonstrated that ZnO-doped particles significantly inhibit autophagic overactivation, thereby reducing inflammation and osteolysis.In summary, this study establishes secretory autophagy as a critical mechanism in wear particle-induced osteolysis and highlights the potential of ZnO-doped prosthetic polymers for targeted, sustained mitigation of periprosthetic osteolysis.

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

Abstract Background Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. Methods We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. Results Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. Conclusions We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Abstract Background The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. Methods Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. Results The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. Conclusion Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. Simple summary The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Benzophenone ultraviolet light filters (BPs) are high-production-volume chemicals extensively used in personal care products, leading to widespread human exposure. Given their estrogenic properties, the potential health risks associated with exposure to BPs have become a public health concern. This review aims to summarize sources and pathways of exposure to BPs and associated health risks. Dermal exposure, primarily through the use of sunscreens, constitutes a major pathway for BP exposure. At a recommended application rate, dermal exposure of BP-3 via the application of sunscreens may reach or exceed the suggested reference dose. Other exposure pathways to BPs, such as drinking water, seafood, and packaged foods, contribute minimal to the overall dose. Inhalation is a minor pathway of exposure; however, its contribution cannot be ignored. Human exposure to BPs is an order of magnitude higher in North America than in Asia and Europe. Studies conducted on laboratory animals and cells have consistently demonstrated the toxic effects of BP exposure. BPs are estrogenic and elicit reproductive and developmental toxicities. Furthermore, neurotoxicity, hepatotoxicity, nephrotoxicity, and carcinogenicity have been reported from chronic BP exposure. In addition to animal and cell studies, epidemiological investigations have identified associations between BPs and couples' fecundity and other reproductive disorders, as well as adverse birth outcomes. Further studies are urgently needed to understand the risks posed by BPs on human health.

Shield tunnel backfill grouting is vital to stabilize tunnel settlement at a later stage; however, most shield tunnel backfill grouting designs lack a complete theoretical reference, and numerical simulations of the grouting process are rarely conducted. This study presents the fundamental theories of grout diffusion and pressure variation for backfill grouting during shield construction. Moreover, the numerical simulation methods coupled with discrete element methods (DEM) and finite difference methods (FDM) are achieved to simulate the process of grout injection from the grouting hole into the shield tail gap and generate grout pressure on the surrounding rock. The diffusion state of the grout in the shield tail gap and the squeezing effect on the surrounding rock under two shield tail disengagement modes are analyzed, as well as the impact of various grouting pressure on the surface settlement. The results indicated that the grout diffusion in the shield tail gap can be divided into three stages: the stage of diffusion with each grouting hole as the starting point, the stage of interconnection and contact of the grout injected in each grouting hole, and the final gap filling stage. Each of the three stages can be described using the proposed equation. During the grouting process, the grout is injected into the shield tail gap at a certain pressure, but the grout diffuses slowly to both sides and upwards, which causes a rapid rise of the principal stresses in the soil around the tunnel. After grouting is complete, the grout pressure gradually dissipates and stabilizes, and the principal stress decreases. In addition, backfill grouting can reduce surface settlement, but it does not affect its distribution width.

Abstract BRAF mutations are associated with a small number of hematologic malignancies, including hairy cell leukemia and histiocytic disorders. In addition, BRAF mutations have also been detected in low frequency in other B‐cell lymphomas, such as chronic lymphocytic leukemia and diffuse large B‐cell lymphoma, but never in mantle cell lymphoma (MCL). We present a case of a 69‐year‐old female with classic MCL harboring a BRAFN581S mutation. To our knowledge, this is the first reported case of any BRAF mutation in MCL.

Abstract The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

Abstract To advance the full potential of quantum networks one should be able to distribute quantum resources over long distances at appreciable rates. As a consequence, all components in such networks need to have large multimode capacity to manipulate photonic quantum states. Towards this end, a photonic quantum memory with a large multimode capacity, especially one operating at telecom wavelength, remains an important challenge. Here we optimize the preparation of atomic frequency combs and demonstrate a spectro-temporally multiplexed quantum memory in a 10-m-long cryogenically cooled erbium doped silica fibre. Our multiplexing storage has five spectral channels - each 10 GHz wide with 5 GHz separation - with up to 330 temporal modes in each, thus resulting in a simultaneous storage of 1,650 modes of heralded single photons with a 1000-fold increasing in coincidence detection rate with respect to single mode storage. Our results could pave the way for high speed quantum networks compatible with the infrastructure of fibre optical communication.

Skeletal muscle has a robust regeneration ability that is impaired by severe injury, disease, and aging, resulting in a decline in skeletal muscle function. Therefore, improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders. Owing to their significant role in tissue regeneration, implantation of M2 macrophages (M2Mø) has great potential for improving skeletal muscle regeneration. Here, we present a short-wave infrared (SWIR) fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2Mø transplantation. SWIR fluorescence imaging was employed to track implanted M2Mø in the injured skeletal muscle of mouse models. It is found that the implanted M2Mø accumulated at the injury site for two weeks. Then, SWIR fluorescence imaging of blood vessels showed that M2Mø implantation could improve the relative perfusion ratio on day 5 (1.09 ± 0.09 vs 0.85 ± 0.05; p = 0.01) and day 9 (1.38 ± 0.16 vs 0.95 ± 0.03; p = 0.01) post-injury, as well as augment the degree of skeletal muscle regeneration on day 13 post-injury. Finally, multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration. These results provide more in vivo details about M2Mø in skeletal muscle regeneration and confirm that M2Mø could promote angiogenesis and improve the degree of skeletal muscle repair, which will guide the research and development of M2Mø implantation to improve skeletal muscle regeneration.

microRNAs (miRNAs) influence many biological processes at the post-transcriptional level. However, the molecular characterization of miRNAs in the Myzus persicae response to Brassica yellows virus (BrYV) stress remains unclear. In this study, we present the results of miRNA profiling in Myzus persicae under two different treatments: treatment one (raised on turnip plants), and treatment two (raised on Arabidopsis thaliana). A total of 72 known and 113 novel mature miRNAs were identified in both non-viruliferous and viruliferous aphids, under treatment one. In treatment two, 72 known and 112 novel mature miRNAs were identified in BrYV-free aphids; meanwhile, 71 known and 115 novel miRNAs were identified in BrYV-carrying aphids. Moreover, eight upregulated and four downregulated miRNAs were identified in viruliferous aphids under treatment two, whereas only two miRNAs were differentially expressed under treatment one. These results indicated the relative BrYV level could influence miRNA expression in aphids. KEGG enrichment analysis showed the predicted genes targeted by differentially expressed miRNAs were primarily involved in Peroxisome, neuroactive ligand–receptor interaction, and metabolism of xenobiotics by cytochrome P450 pathways. Taken together, these findings reveal the effect of BrYV on miRNAs in Myzus persicae and provide key clues for further studies on the molecular mechanisms of BrYV transmission via aphids.

As the most widely distributed scavenger birds on the Qinghai-Tibetan Plateau, Himalayan vultures (Gyps himalayensis) feed on the carcasses of various wild and domestic animals, facing the dual selection pressure of pathogens and antibiotics and are suitable biological sentinel species for monitoring antibiotic resistance genes (ARGs). This study used metagenomic sequencing to comparatively investigate the ARGs and mobile genetic elements (MGEs) of wild and captive Himalayan vultures. Overall, the resistome of Himalayan vultures contained 414 ARG subtypes resistant to 20 ARG types, with abundances ranging from 0.01 to 1,493.60 ppm. The most abundant resistance type was beta-lactam (175 subtypes), followed by multidrug resistance genes with 68 subtypes. Decreases in the abundance of macrolide-lincosamide-streptogramin (MLS) resistance genes were observed in the wild group compared with the zoo group. A total of 75 genera (five phyla) of bacteria were predicted to be the hosts of ARGs in Himalayan vultures, and the clinical (102 ARGs) and high-risk ARGs (35 Rank I and 56 Rank II ARGs) were also analyzed. Among these ARGs, twenty-two clinical ARGs, nine Rank I ARG subtypes, sixteen Rank II ARG subtypes were found to differ significantly between the two groups. Five types of MGEs (128 subtypes) were found in Himalayan vultures. Plasmids (62 subtypes) and transposases (44 subtypes) were found to be the main MGE types. Efflux pump and antibiotic deactivation were the main resistance mechanisms of ARGs in Himalayan vultures. Decreases in the abundance of cellular protection were identified in wild Himalayan vultures compared with the captive Himalayan vultures. Procrustes analysis and the co-occurrence networks analysis revealed different patterns of correlations among gut microbes, ARGs, and MGEs in wild and captive Himalayan vultures. This study is the first step in describing the characterization of the ARGs in the gut of Himalayan vultures and highlights the need to pay more attention to scavenging birds.

Heterostructure engineering is crucial for enhancing gas sensing performance. However, achieving rapid response for room-temperature NO2 sensing through rational heterostructure design remains a challenge. In this study, a Bi2Se3/SnSe2 2D/2D heterostructure was synthesized by hydrothermal method for the rapid detection of NO2 at room temperature. By combining Bi2Se3 nanosheets with SnSe2 nanosheets, the Bi2Se3/SnSe2 sensor demonstrated and the lowest detection limit for NO2 a short response time (15 s) to 10 ppm NO2 at room temperature, reaches 25 ppb. Furthermore the sensor demonstrates significantly larger response to NO2 than to other interfering gases, including 10 ppm NO2, H2S, NH3, CH4, CO, and SO2,demonstrating its outstanding selectivity. And we discuss the mechanism of related performance enhancement.

Abstract 3D porous organic frameworks, which possess the advantages of high surface area and abundant exposed active sites, are considered ideal platforms to accommodate single atoms (SAs) and metal nanoclusters (NCs) in high‐performance catalysts; however, very little research has been conducted in this field. In the present work, a 3D porous organic framework containing Ni1 SAs and Nin NCs is prepared through the metal‐assisted one‐pot polycondensation of tetraaldehyde and hexaaminotriptycene. The single metal sites and metal clusters confined in the 3D space created a favorable micro‐environment that facilitated the activation of chemically inert CO2 molecules, thus promoting the overall photoconversion efficiency and selectivity of CO2 reduction. The 3D‐NiSAs/NiNCs‐POPs, as a CO2 photoreduction catalyst, demonstrated an exceptional CO production rate of 6.24 mmol g−1 h−1, high selectivity of 98%, and excellent stability. The theoretical calculations uncovered that asymmetrical interaction between Ni1 SAs and Nin NCs not only favored the bending of CO2 molecules and reducing the CO2 reduction energy, but also regulated the electronic structure of the catalyst leading to the optimal binding strength of intermediates.

Abstract Hypergolic propellants rely on fuel and oxidizer that spontaneously ignite upon contact, which fulfill a wide variety of mission roles in launch vehicles and spacecraft. Energy‐rich carboranes are promising hypergolic fuels, but triggering their energy release is quite difficult because of their ultrastable aromatic cage structure. To steer the development of carborane‐based high‐performance hypergolic material, carboranylthiolated compounds integrated with atomically precise copper clusters are presented, yielding two distinct isomers, Cu14B‐S and Cu14C‐S, both possessing similar ligands and core structures. With the migration of thiolate groups from carbon atoms to boron atoms, the ignition delay (ID) time shortened from 6870 to 3 ms when contacted with environmentally benign oxidizer high‐test peroxide (HTP, with a H2O2 concentration of 90%). The extraordinarily short ignition ID time of Cu14B‐S is ranking among the best of HTP‐active hypergolic materials. The experimental and theoretical findings reveal that benefitting from the migration of thiolate groups, Cu14B‐S, characterized by an electron‐rich metal kernel, displays enhanced reducibility and superior charge transfer efficiency. This results in exceptional activation rates with HTP, consequently inducing carborane combustion and the simultaneous release of energy. This fundamental investigation shed light on the development of advanced green hypergolic propulsion systems.

IntroductionHimalayan griffons (Gyps himalayensis), known as the scavenger of nature, are large scavenging raptors widely distributed on the Qinghai-Tibetan Plateau and play an important role in maintaining the balance of the plateau ecosystem. The gut microbiome is essential for host health, helping to maintain homeostasis, improving digestive efficiency, and promoting the development of the immune system. Changes in environment and diet can affect the composition and function of gut microbiota, ultimately impacting the host health and adaptation. Captive rearing is considered to be a way to protect Himalayan griffons and increase their population size. However, the effects of captivity on the structure and function of the gut microbial communities of Himalayan griffons are poorly understood. Still, availability of sequenced metagenomes and functional information for most griffons gut microbes remains limited.MethodsIn this study, metagenome sequencing was used to analyze the composition and functional structures of the gut microbiota of Himalayan griffons under wild and captive conditions.ResultsOur results showed no significant differences in the alpha diversity between the two groups, but significant differences in beta diversity. Taxonomic classification revealed that the most abundant phyla in the gut of Himalayan griffons were Fusobacteriota, Proteobacteria, Firmicutes_A, Bacteroidota, Firmicutes, Actinobacteriota, and Campylobacterota. At the functional level, a series of Kyoto Encyclopedia of Genes and Genome (KEGG) functional pathways, carbohydrate-active enzymes (CAZymes) categories, virulence factor genes (VFGs), and pathogen-host interactions (PHI) were annotated and compared between the two groups. In addition, we recovered nearly 130 metagenome-assembled genomes (MAGs).DiscussionIn summary, the present study provided a first inventory of the microbial genes and metagenome-assembled genomes related to the Himalayan griffons, marking a crucial first step toward a wider investigation of the scavengers microbiomes with the ultimate goal to contribute to the conservation and management strategies for this near threatened bird.

Abstract Background and Aims The effectiveness of immune checkpoint inhibitors (ICIs) in low programmed death ligand 1 (PD‐L1) expression in cervical cancer (CC) patients remains unknown. We aimed to evaluate the efficacy of ICIs in low PD‐L1 expression CC patients. Methods The study is an individual patient data (IPD)‐based meta‐analysis. IPD were compiled through KMSubtraction and IPDfromKM methodologies from high‐quality randomized clinical trials and single‐arm studies which reported overall survival (OS) or progression‐free survival (PFS) stratified by PD‐L1 expression. Kaplan−Meier curves and Cox regression analysis were employed to evaluate the survival benefits of ICIs. Results A total of eight studies and 1110 cases were included in the analysis. Within the low PD‐L1 expression subgroup, ICI combination therapy, but not ICI monotherapy, demonstrated significant OS benefits over non‐ICI treatment (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.36−1.04, p = 0.06). Concerning PFS, ICI monotherapy was associated with a negative effect compared to non‐ICI treatment (HR = 4.59, 95% CI: 2.32−9.07, p