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Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced β-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.

Abstract Testing of large‐sized specimens is becoming increasingly important in deep underground rock mechanics and engineering. In traditional mechanical loading, stresses on large‐sized specimens are achieved by large host frames and hydraulic pumps, which could lead to great investment. Low‐cost testing machines clearly always have great appeal. In this study, a new approach is proposed using thermal expansion stress to load rock specimens, which may be particularly suitable for tests of deep hot dry rock with high temperatures. This is a different technical route from traditional mechanical loading through hydraulic pressure. For the rock mechanics test system of hot dry rock that already has an investment in heating systems, this technology may reduce the cost of the loading subsystem by fully utilizing the temperature changes. This paper presents the basic principle and a typical design of this technical solution. Preliminary feasibility analysis is then conducted based on numerical simulations. Although some technical details still need to be resolved, the feasibility of this loading approach has been preliminarily confirmed.

Abstract Delta opioid receptor (δOR) plays a pivotal role in modulating human sensation and emotion. It is an attractive target for drug discovery since, unlike Mu opioid receptor, it is associated with low risk of drug dependence. Despite its potential applications, the pharmacological properties of δOR, including the mechanisms of activation by small-molecule agonists and the complex signaling pathways it engages, as well as their relation to the potential side effects, remain poorly understood. In this study, we use cryo-electron microscopy (cryo-EM) to determine the structure of the δOR-Gi complex when bound to a small-molecule agonist (ADL5859). Moreover, we design a series of probes to examine the key receptor-ligand interaction site and identify a region involved in signaling bias. Using ADL06 as a chemical tool, we elucidate the relationship between the β-arrestin pathway of the δOR and its biological functions, such as analgesic tolerance and convulsion activities. Notably, we discover that the β-arrestin recruitment of δOR might be linked to reduced gastrointestinal motility. These insights enhance our understanding of δOR’s structure, signaling pathways, and biological functions, paving the way for the structure-based drug discovery.

Abstract Understanding the mechanical characteristics of rocks when subjected to direct tension is crucial for assessing the stability of rock formations. Within the scope of this research, a series of tests was conducted using Tage tuff to assess the deformation behavior and crack extension of rock under direct tension. The axial, lateral, and shear strain fields as well as crack propagation, localized deformation behavior, and failure mode of the rocks were analyzed using three-dimensional digital image correlation method. The results showed that the axial strain fields on the specimen surface were heterogeneous, with different locations and localization occurring in the pre-peak stage, which was similar to the evolution of shear strain, whereas the lateral strain only showed slight changes. The crack extension direction was inferred, indicating that both tensile and shear stress occurred in the tests. Furthermore, different stress–strain responses were observed for the inside and outside of the localized bands. Then, the surface patterns of specimen failure were scanned and analyzed to assess the failure mode and residual strength of the specimen under direct tensile stress. Finally, the results of direct tension, uniaxial compression, and Brazilian split tests for Tage tuff were compared, and the complete stress–strain curve of uniaxial tension (UT) was simulated using a nonlinear-variable-compliance constitutive equation. This study provides a deeper understanding into the damage behavior of rocks under direct tension.

Abstract Plants NADP-malic enzymes (NADP-MEs) act as a class of oxidative decarboxylase to mediate malic acid metabolism in organisms. Despite NADP-MEs have been demonstrated to play pivotal roles in regulating diverse biological processes, the role of NADP-MEs involving in plant growth and development remains rarely known. Here, we characterized the function of rice cytosolic OsNADP-ME2 in regulating plant height. The results showed that RNAi silencing and knock-out of OsNADP-ME2 in rice results in a dwarf plant structure, associating with significant expression inhibition of genes involving in phytohormone Gibberellin (GA) biosynthesis and signaling transduction, but with up-regulation for the expression of GA signaling suppressor SLR1. The accumulation of major bioactive GA1, GA4 and GA7 are evidently altered in RNAi lines, and exogenous GA treatment compromises the dwarf phenotype of OsNADP-ME2 RNAi lines. RNAi silencing of OsNADP-ME2 also causes the reduction of NADP-ME activity associating with decreased production of pyruvate. Thus, our data revealed a novel function of plant NADP-MEs in modulation of rice plant height through regulating bioactive GAs accumulation and GA signaling, and provided a valuable gene resource for rice plant architecture improvement.

Landslides induced by reservoir inundation are common in Southwest China, negatively influencing hydropower stations. The Wunonglong hydropower station dam was constructed in the upper reaches of the Lancang River, accordingly causing the water level at the Lajinshengu slope to increase by 30 m. A tension crack with a visible depth of 8 m was observed in the upper sector of the Lajinshengu slope after reservoir impoundment for 170 d. In the following days, numerous cracks appeared on the surface of the slope, and the maximum displacement of the slope reached 3.22 m. Then, a large-scale active deformation body within the Lajinshengu slope formed with an area of 2.62 × 105 m2 and a volume of 1.65 × 107 m3. Detailed field investigations, on-site monitoring, and centrifugal model tests were carried out to analyze the surface features, deformation characteristics, and failure mechanism of the Lajinshengu slope. The results show that the slope is an ancient landslide, divided into two parts (i.e. zone A and zone B) by the gully. Zone B is a traction landslide caused by the displacement of zone A. The long-term inundation weakens the soft rock at the slope foot, intensifying the toppling of bedrock and consequently triggering the sliding of the overburden in zone A. The failure mode of the Lajinshengu slope is a typical case of toppling-sliding failure, and the underlying rock toppling drives the overlying sliding. In addition, early identification methods for toppling deformation covered by overburdened soil were proposed based on monitoring data and deformation signs.

In the context of repositories for nuclear waste, understanding the behavior of gas migration through clayey rocks with inherent anisotropy is crucial for assessing the safety of geological disposal facilities. The primary mechanism for gas breakthrough is the opening of micro-fractures due to high gas pressure. This occurs at gas pressures lower than the combined strength of the rock and its minimum principal stress under external loading conditions. To investigate the mechanism of microscale mode-I ruptures, it is essential to incorporate a multiscale approach that includes subcritical microcracks in the modeling framework. In this contribution, we derive the model from microstructures that contain periodically distributed microcracks within a porous material. The damage evolution law is coupled with the macroscopic poroelastic system by employing the asymptotic homogenization method and considering the inherent hydro-mechanical (HM) anisotropy at the microscale. The resulting permeability change induced by fracture opening is implicitly integrated into the gas flow equation. Verification examples are presented to validate the developed model step by step. An analysis of local macroscopic response is undertaken to underscore the influence of factors such as strain rate, initial damage, and applied stress, on the gas migration process. Numerical examples of direct tension tests are used to demonstrate the model's efficacy in describing localized failure characteristics. Finally, the simulation results for preferential gas flow reveal the robustness of the two-scale model in explicitly depicting gas-induced fracturing in anisotropic clayey rocks. The model successfully captures the common behaviors observed in laboratory experiments, such as a sudden drop in gas injection pressure, rapid build-up of downstream gas pressure, and steady-state gas flow following gas breakthrough.

Abstract In recent years, contrastive language‐image pre‐training (CLIP) has gained popularity for processing 2D data. However, the application of cross‐modal transferable learning to 3D data remains a relatively unexplored area. In addition, high‐quality, labelled point cloud data for Mechanical, Electrical, and Plumbing (MEP) scenarios are in short supply. To address this issue, the authors introduce a novel object detection system that employs 3D point clouds and 2D camera images, as well as text descriptions as input, using image‐text matching knowledge to guide dense detection models for 3D point clouds in MEP environments. Specifically, the authors put forth the proposition of a language‐guided point cloud modelling (PCM) module, which leverages the shared image weights inherent in the CLIP backbone. This is done with the aim of generating pertinent category information for the target, thereby augmenting the efficacy of 3D point cloud target detection. After sufficient experiments, the proposed point cloud detection system with the PCM module is proven to have a comparable performance with current state‐of‐the‐art networks. The approach has 5.64% and 2.9% improvement in KITTI and SUN‐RGBD, respectively. In addition, the same good detection results are obtained in their proposed MEP scene dataset.

Chemotherapy and radiotherapy in combination with sequence regimens are recognized as the current major strategy for suppressing postoperative tumor recurrence. However, systemic side effects and poor in-field cooperation of the two therapies seriously impair the therapeutic efficacy of patients. The combination of brachytherapy and chemotherapy through innovative biomaterials has proven to be an important strategy to achieve synergistic effects of radiotherapy and chemotherapy in-time and in-field. However, for postoperative chemoradiotherapy, as far as we know, there are few relevant reports. Herein, an injectable pH-responsive polypeptide-polysaccharide depot for concurrent in situ chemotherapy and brachytherapy was developed by encapsulating vincristine into iodine-125 radionuclide labeled hydrogel. This depot hydrogel was prepared by dynamic covalent bonds of Schiff base between aldehydeated hyaluronic acid and polyethylene glycol-polytyrosine. Therefore, this hydrogel enables smart response to tumor acidic microenvironment, rapid release of the encapsulated vincristine and an enhanced uptake effect by tumor cells, which significantly reduces IC50 of vincristine for the anaplasia Wilms' tumor cells in vitro. This depot hydrogel shows excellent stability and biocompatibility, and maintains for 14 days after in situ injection in a postoperative model of anaplasia Wilms' tumor. After injection at the cavity of tumor excision, responsively-released vincristine and the radioactive iodine-125 exerted excellent killing effects on residual tumor cells, inhibiting tumor relapse and liver metastasis of the recurrent tumor. Hence, this study proposes an effective therapeutic strategy for inhibiting anaplasia Wilms’ tumor recurrence, which provides a new approach for concurrent postoperative chemo-radiotherapy and a desirable guidance in regimen execution of pediatric refractory tumors.

Hypospadias is one of the most common congenital anomalies of the male urogenital system, and di(2-ethylhexyl) phthalate (DEHP), a widely used endocrine-disrupting chemical (EDC), is considered a significant risk factor for this condition. Mono-2-ethylhexyl phthalate (MEHP), the toxic active metabolite of DEHP, has been proven to affect penile development and ultimately result in the hypospadias phenotype. However, while it is acknowledged that hypospadias arises from the aberrant development of multiple penile tissues, the specific impact of MEHP on human foreskin tissue development and its underlying molecular mechanisms of action remain unclear. In this study, we constructed an in vitro toxicity assay for MEHP using human foreskin fibroblasts and employed high-throughput RNA sequencing to investigate the molecular mechanisms subserving the defects in cellular function. We subsequently conducted multi-omics data analysis using public databases to analyze key target genes, and identified MMP11 as a chief downstream gene responsible for the effects of MEHP on HFF-1 cell migration. Through molecular docking analysis and molecular biology experiments, we further demonstrated that the nuclear receptor PPAR-gamma was activated upon binding with MEHP, leading to the suppression of MMP11 expression. Additionally, we found that epigenetic modifications induced by MEHP were also involved in its pathogenic effects on hypospadias. Our research highlights the crucial role of impaired cellular proliferation and migration in MEHP-induced hypospadias. We identified the MEHP/PPAR-gamma/MMP11 pathway as a novel pathogenic mechanism, providing important potential targets for future preventive strategies with respect to hypospadias.

Ambient air pollution has been reported to be a risk factor for hypertensive disorders of pregnancy (HDP). Past studies have reported supportive evidence, but evidence from China is scarce and does not integrate the different periods of the pregnancy course. In this study, 1945 pregnant women with HDP and healthy pregnancies between 2016 and 2022 from the Renmin Hospital of Wuhan University registry network database were analysed. The geographic information, biological information and demographic information of the case were fused in the analysis. Machine learning methods were used to obtain the weight of the variable. Then, we used the generalized linear mixed model to evaluate the relationship between increased exposure to each pollutant at different periods of HDP and examined it in different groups. The results showed that SO2 had the predominate impact (12.65 %) on HDP compared with other air pollutants. SO2 exposure was associated with an increased risk of HDP. Increased unit SO2 concentrations were accompanied by an increased risk of HDP (OR = 1.33, 95 % CI: 1.13, 1.566), and the susceptible window for this effect was mainly in the first trimester (OR = 1.242, 95 % CI: 1.092, 1.412). In addition, SO2 exposure was associated with an increased risk of HDP in urban maternity (OR = 1.356, 95 % CI: 1.112, 1.653), obese maternity (OR = 3.58, 95 % CI: 1.608, 7.971), no higher education maternity (OR = 1.348, 95 % CI: 1.065, 1.706), nonzero delivery maternity (OR = 1.981, 95 % CI: 1.439, 2.725), maternal with first time maternity (OR = 1.247, 95 % CI: 1.007, 1.544) and other groups. In summary, SO2 exposure in early pregnancy is one of the risk factors for HDP, and the increased risk of HDP due to increased SO2 exposure may be more pronounced in obese, urban, low-education, and nonzero delivery populations.

The treat of climate warming is expected to increase the frequency and severity of droughts and significantly affect tree growth and distribution ranges, particularly in regions without monsoons. The distribution limits of tree species are highly susceptible to climate change. A deeper understanding of how tree species respond to climate across their distribution ranges is crucial for accurately predicting forest dynamics in the face of climate warming. Using tree ring width data from 586 trees at 19 sites spanning the northernmost and southernmost limits of Juniperus rigida (near-threatened, IUCN: NT), we assessed the growth responses of J. rigida to climate at different distribution range limits. We observed significant differences in tree-growth variability between the southern and northern populations of J. rigida, characterized by an increasing growth trend at the southern range limit, but a decreasing trend at the northern limit since 1996. Moreover, tree growth at their northern limit was hindered by high temperatures and SPEI during summer months, whereas it was constrained by low temperatures in March and precipitation in June at the southern limit. Particularly noteworthy is the increased sensitivity of growth to SPEI and precipitation in recent decades (1996–2018) compared to previous decades (1961–1995), particularly at their northern distribution edge. We therefore conclude that the growth of J. rigida trees at the southern limit could benefit from climate warming, while increasing warming and drought could limit tree growth or even cause tree mortality at the northern range limits. These findings may serve as an early warning for the growth and survival of J. rigida trees in open forests at their northern distribution edges in the face of future climate warming.

Revealing the matching relationship of “precipitation − vegetation” and its impact on sediment yield is of great scientific significance for controlling soil erosion and promoting coordinated environmental development. Based on GPM precipitation data and MODIS 250 m NDVI, the temporal distribution pattern and matching relationship between precipitation and vegetation within a year are analyzed, and the annual sediment yield index (ASYI) is constructed to reflect the sediment yield status of the basin. Furthermore, multiple regression analysis is conducted using precipitation, NDVI and its distribution parameters, as well as ASYI and actual sediment yield. The results show that (1) the inhibitory effect of vegetation on erosion varies little between years, while the fluctuation of precipitation distribution is more pronounced than that of vegetation; (2) the correlation between the constructed ASYI index and the actual sediment yield reaches 0.877, indicating that the index can well reflect the sediment yield; when fitting ASYI to sediment yield using a quadratic function, R2 reaches 0.9193; (3) there is a positive correlation between precipitation and sediment yield, but it is not necessarily that the larger the precipitation, the greater the sediment yield, and the annual distribution pattern of precipitation is the dominant factor affecting sediment yield; (4) the model which considering precipitation, NDVI, distribution parameters and ASYI, can achieve the best fit, and R2 reached 0.9129. In summary, the matching pattern of “precipitation − vegetation” within a year has a significant impact on sediment yield. When ASYI is greater than 1.63, the sediment yield will increase sharply. This paper provides a new perspective for studying the relationship and quantitative expression between precipitation and sediment yield. The proposed index can be easily applied to other regions due to its good operability.

The power grid’s geomagnetically induced currents (GIC) during geomagnetic storms, are associated with a broad and abrupt harmonic impact, with the potential for grid paralysis and extensive power outages in severe scenarios. Therefore, the harmonic characteristics of geomagnetically induced currents in China’s ultra-high voltage (UHV) AC/DC power grid are analyzed in this paper. Firstly, a harmonic equivalent model of transformer GIC is established, and the injection of harmonics into the UHV AC/DC power grid during GIC events is quantified. Secondly, a harmonic state-space model is established by combining the 12-pulse converter switching function theory with the exponential Fourier series. The harmonic transmission and dynamic coupling characteristics of GIC in the UHV AC/DC power grid are analyzed using the harmonic equivalent model of the main transformer GIC and the harmonic equivalent model of the converter transformer GIC. Finally, a harmonic simulation model of the UHV AC/DC power grid under GIC is constructed using PSCAD, and the distribution of harmonics in the UHV AC/DC power grid under GIC is calculated. The calculations indicate that with 30 A injected GIC in the sending end transformers, the 2nd harmonic current on the sending end network side alone is 61.45 A, and the 3rd harmonic voltage on the valve side is 8.57 kV. The characteristics of harmonic transmission in the power grid result in a 2nd harmonic current of 34.87 A on the receiving end network side. Simultaneously, the total harmonic distortion of the AC power grid at the sending end is 2.35 %, surpassing the permissible limit established by the national standard. Consequently, this issue should be prioritized by the relevant power authorities.

Abstract G protein-coupled receptors naturally oscillate between inactive and active states, often resulting in receptor constitutive activity with important physiological consequences. Among the class C G protein-coupled receptors that typically sense amino-acids and their derivatives, the calcium sensing receptor (CaSR) tightly controls blood calcium levels. Its constitutive activity has not yet been studied. Here, we demonstrate the importance of the inter-subunit disulfide bridges in maintaining the inactive state of CaSR, resulting in undetectable constitutive activity, unlike the other class C receptors. Deletion of these disulfide bridges results in strong constitutive activity that is abolished by mutations preventing amino acid binding. It shows that this inter-subunit disulfide link is necessary to limit the agonist effect of amino acids on CaSR. Furthermore, human genetic mutations deleting these bridges and associated with hypocalcemia result in elevated CaSR constitutive activity. These results highlight the physiological importance of fine tuning the constitutive activity of G protein-coupled receptors.

Abstract Low-temperature germination (LTG) is an important agronomic trait for rice (Oryza sativa). Japonica rice generally has greater capacity for germination at low temperatures than the indica subpopulation. However, the genetic basis and molecular mechanisms underlying this complex trait are poorly understood. Here, we report that OsUBC12, encoding an E2 ubiquitin-conjugating enzyme, increases low-temperature germinability in japonica, owing to a transposon insertion in its promoter enhancing its expression. Natural variation analysis reveals that transposon insertion in the OsUBC12 promoter mainly occurs in the japonica lineage. The variation detected in eight representative two-line male sterile lines suggests the existence of this allele introgression by indica-japonica hybridization breeding, and varieties carrying the japonica OsUBC12 locus (transposon insertion) have higher low-temperature germinability than varieties without the locus. Further molecular analysis shows that OsUBC12 negatively regulate ABA signaling. OsUBC12-regulated seed germination and ABA signaling mainly depend on a conserved active site required for ubiquitin-conjugating enzyme activity. Furthermore, OsUBC12 directly associates with rice SUCROSE NON-FERMENTING 1-RELATED PROTEIN KINASE 1.1 (OsSnRK1.1), promoting its degradation. OsSnRK1.1 inhibits LTG by enhancing ABA signaling and acts downstream of OsUBC12. These findings shed light on the underlying mechanisms of UBC12 regulating LTG and provide genetic reference points for improving LTG in indica rice.

Abstract G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive Gi/o sensors, we reveal specific properties of Gi/o protein-mediated responses triggered by GABAB, α2 adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the Gi/o protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment.

Introduction: Fine-wool sheep are the most common breed used by the wool industry worldwide. Fine-wool sheep have over a three-fold higher follicle density and a 50% smaller fiber diameter than coarse-wool sheep. Objectives: This study aims to clarify the underlying genetic basis for the denser and finer wool phenotype in fine-wool breeds. Method: Whole-genome sequences of 140 samples, Ovine HD630K SNP array data of 385 samples, including fine, semi-fine, and coarse wool sheep, as well as skin transcriptomes of nine samples were integrated for genomic selection signature analysis. Results: Two loci at keratin 74 (KRT74) and ectodysplasin receptor (EDAR) were revealed. Fine-scale analysis in 250 fine/semi-fine and 198 coarse wool sheep narrowed this association to one C/A missense variant of KRT74 (OAR3:133,486,008, P = 1.02E-67) and one T/C SNP in the regulatory region upstream of EDAR (OAR3:61,927,840, P = 2.50E-43). Cellular over-expression and ovine skin section staining assays confirmed that C-KRT74 activated the KRT74 protein and specifically enlarged cell size at the Huxley’s layer of the inner root sheath (P

Mycoviruses can alter the biological characteristics of host fungi, including change virulence or pathogenicity of phytopathogens and entomopathogenic fungi (EPF). However, most studies on the mycoviruses found in EPF have focused on the effects of the viruses on the virulence of host fungi towards insect pests, with relatively few reports on the effects to the host fungi with regard to plant disease resistance in hosts. The present study investigated the effects of the mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) virus infection on host biological characteristics, evaluated antagonistic activity of BbCV2 against two phytopathogenic fungi (Sclerotinia sclerotiorum and Botrytis cinerea), and transcriptome analysis was used to reveal the interactions between viruses and hosts. Our results showed that BbCV2 virus infection increased B. bassiana‘s growth rate, spore production, and biomass, it also enhanced the capacity of host fungi and their metabolic products to inhibit phytopathogenic fungi. BbCV2 virus infection reduced the contents of the two pathogens in tomato plants significantly, and transcriptome analysis revealed that the genes related to competition for ecological niches and nutrition, mycoparasitism and secondary metabolites in B. bassiana were significantly up-regulated after viral infection. These findings indicated that the mycovirus infection is an important factor to enhance the ability of B. bassiana against plant disease after endophytic colonization. We suggest that mycovirus infection causes a positive effect on B. bassiana against phytopathogens, which should be considered as a potential strategy to promote the plant disease resistance of EPF.

Abstract Self‐assembled peptides have been among the important biomaterials due to its excellent biocompatibility and diverse functions. Over the past decades, substantial progress and breakthroughs have been made in designing self‐assembled peptides with multifaceted biomedical applications. The techniques for quantitative analysis, including imaging‐based quantitative techniques, chromatographic technique and computational approach (molecular dynamics simulation), are becoming powerful tools for exploring the structure, properties, biomedical applications, and even supramolecular assembly processes of self‐assembled peptides. However, a comprehensive review concerning these quantitative techniques remains scarce. In this review, recent progress in techniques for quantitative investigation of biostability, cellular uptake, biodistribution, self‐assembly behaviors of self‐assembled peptide etc., are summarized. Specific applications and roles of these techniques are highlighted in detail. Finally, challenges and outlook in this field are concluded. It is believed that this review will provide technical guidance for researchers in the field of peptide‐based materials and pharmaceuticals, and facilitate related research for newcomers in this field.

According to the synaptic homeostasis hypothesis (SHY), sleep serves to renormalize synaptic connections that have been potentiated during the prior wake phase due to ongoing encoding of information. SHY focuses on glutamatergic synaptic strength and has been supported by numerous studies examining synaptic structure and function in neocortical and hippocampal networks. However, it is unknown whether synaptic down-regulation during sleep occurs in the hypothalamus, i.e., a pivotal center of homeostatic regulation of bodily functions including sleep itself. We show that sleep, in parallel with the synaptic down-regulation in neocortical networks, down-regulates the levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hypothalamus of rats. Most robust decreases after sleep were observed at both sites for AMPARs containing the GluA1 subunit. Comparing the effects of selective rapid eye movement (REM) sleep and total sleep deprivation, we moreover provide experimental evidence that slow-wave sleep (SWS) is the driving force of the down-regulation of AMPARs in hypothalamus and neocortex, with no additional contributions of REM sleep or the circadian rhythm. SWS-dependent synaptic down-regulation was not linked to EEG slow-wave activity. However, spindle density during SWS predicted relatively increased GluA1 subunit levels in hypothalamic synapses, which is consistent with the role of spindles in the consolidation of memory. Our findings identify SWS as the main driver of the renormalization of synaptic strength during sleep and suggest that SWS-dependent synaptic renormalization is also implicated in homeostatic control processes in the hypothalamus.

Abstract Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial‐mesenchymal transformation (EMT), thyroid differentiation‐related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor‐based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3‐mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3‐dependent manner. Finally, the METTL3‐14‐WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR‐SMARCA2‐TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

IntroductionScleroderma bovista can form symbiotic ectomycorrhizal fungi with hazel roots. The mechanism through which S. bovista promotes hazelnut growth remains unclear.MethodsThis study aimed to evaluate the effect of ectomycorrhizal fungus S. bovista on the growth and development of hazel roots and gene expression changes through comparative transcriptome analysis.ResultsAfter inoculation with S. bovista, the fungus symbiotically formed ectomycorrhiza with hazel roots. The fresh weights of the aboveground and underground parts of My treatment (inoculated with S. bovista and formed mycorrhiza) were much higher than those of the control, respectively. The length, project area, surface area, volume, forks, and diameter of the inoculated seedlings root were 1.13 to 2.48 times higher than those of the control. In the paired comparison, 3,265 upregulated and 1,916 downregulated genes were identified. The most significantly enriched Gene Ontology term for the upregulated Differentially Expressed Genes was GO:0005215 (transporter activity). Immunohistochemical analysis suggested that the expression levels of auxin and Auxin Response Factor9 were significantly increased by S. bovista after the formation of mycorrhizal fungi in hazelnut root tips.DiscussionThese results indicate that genes related to auxin biosynthesis, transport and signaling, and transport of nutrients may contribute to root development regulation in hazel ectomycorrhiza.

Autologous nerve transplantation (ANT) is currently considered the gold standard for treating long-distance peripheral nerve defects. However, several challenges associated with ANT, such as limited availability of donors, donor site injury, mismatched nerve diameters, and local neuroma formation, remain unresolved. To address these issues comprehensively, we have developed porous poly(lactic-co-glycolic acid) (PLGA) electrospinning fiber nerve guide conduits (NGCs) that are optimized in terms of alignment and conductive coating to facilitate peripheral nerve regeneration (PNR) under electrical stimulation (ES). The physicochemical and biological properties of aligned porous PLGA fibers and poly(3,4-ethylenedioxythiophene):polystyrene sodium sulfonate (PEDOT:PSS) coatings were characterized through assessments of electrical conductivity, surface morphology, mechanical properties, hydrophilicity, and cell proliferation. Material degradation experiments demonstrated the biocompatibility in vivo of electrospinning fiber films with conductive coatings. The conductive NGCs combined with ES effectively facilitated nerve regeneration. The designed porous aligned NGCs with conductive coatings exhibited suitable physicochemical properties and excellent biocompatibility, thereby significantly enhancing PNR when combined with ES. This combination of porous aligned NGCs with conductive coatings and ES holds great promise for applications in the field of PNR.

Abstract An increasing number of researchers have researched fixture layout optimization for thin-walled part assembly during the past decades. However, few papers systematically review these researches. By analyzing existing literature, this paper summarizes the process of fixture layout optimization and the methods applied. The process of optimization is made up of optimization objective setting, assembly variation/deformation modeling, and fixture layout optimization. This paper makes a review of the fixture layout for thin-walled parts according to these three steps. First, two different kinds of optimization objectives are introduced. Researchers usually consider in-plane variations or out-of-plane deformations when designing objectives. Then, modeling methods for assembly variation and deformation are divided into two categories: Mechanism-based and data-based methods. Several common methods are discussed respectively. After that, optimization algorithms are reviewed systematically. There are two kinds of optimization algorithms: Traditional nonlinear programming and heuristic algorithms. Finally, discussions on the current situation are provided. The research direction of fixture layout optimization in the future is discussed from three aspects: Objective setting, improving modeling accuracy and optimization algorithms. Also, a new research point for fixture layout optimization is discussed. This paper systematically reviews the research on fixture layout optimization for thin-walled parts, and provides a reference for future research in this field.

To investigate the specific creep behavior of ultra-deep buried salt during oil and gas exploitation, a set of triaxial creep experiments was conducted at elevated temperatures with constant axial pressure and unloading confining pressure conditions. Experimental results show that the salt sample deforms more significantly with the increase of applied temperature and deviatoric loading. The accelerated creep phase is not occurring until the applied temperature reaches 130 °C, and higher temperature is beneficial to the occurrence of accelerated creep. To describe the specific creep behavior, a novel three-dimensional (3D) creep constitutive model is developed that incorporates the thermal and mechanical variables into mechanical elements. Subsequently, the standard particle swarm optimization (SPSO) method is adopted to fit the experimental data, and the sensibility of key model parameters is analyzed to further illustrate the model function. As a result, the model can accurately predict the creep behavior of salt under the coupled thermo-mechanical effect in deep-buried condition. Based on the research results, the creep mechanical behavior of wellbore shrinkage is predicted in deep drilling projects crossing salt layer, which has practical implications for deep rock mechanics problems.

The modeling method of hydraulic fracturing fracture network combined with microseismic monitoring is currently a hot research topic. In the process of hydraulic fracturing production, previous studies have established a fracture model after fracturing based on the recorded source coordinates, earthquake time, and moment magnitude throughout the entire fracturing cycle, in order to evaluate the fracturing results. However, in the process of reservoir fracturing transformation, real-time evaluation of fracturing effect and provision of fracturing guidance are required. The method of establishing fracture models through long-term data collection is obviously not applicable. Nevertheless, existing research lacks efficient and direct 3D fracture network modeling methods based on microseismic events. To address these challenges, this study introduces a novel three-dimensional fracture network model reconstruction process, DEFME (Dimensionality Enhancement and Fracture Modeling of Microseismic Event Location Information), specifically tailored for datasets containing only the source coordinate information of microseismic events. This innovative process initially incorporates the improved DB-RANSAC (Density-Based Random Sample Consensus) method, introducing new regional microseismic event normal vector constraint information. It transforms the conventional DBSCAN(Density-Based Spatial Clustering of Applications with Noise) clustering algorithm into the NC-DBSCAN (Normal Vector Constraint-DBSCAN) method, combining normal vector constraints with density constraints for microseismic event point clustering. Finally, the Alpha-shape method is employed to extract contour information for each fracture, constructing a three-dimensional plane geometric model of the fracture. To validate the efficacy of the proposed processing workflow, synthetic data and public dataset are utilized. The corresponding results indicate that DEFME has successfully overcome noise interference and efficiently and accurately established a three-dimensional fracture network model based on microseismic events.

Abstract There are lots of researches on fixture layout optimization for large thin-walled parts. Current researches focus on the positioning problem, i.e., optimizing the positions of a constant number of fixtures. However, how to determine the number of fixtures is ignored. In most cases, the number of fixtures located on large thin-walled parts is determined based on engineering experience, which leads to huge fixture number and extra waste. Therefore, this paper constructs an optimization model to minimize the number of fixtures. The constraints are set in the optimization model to ensure that the part deformation is within the surface profile tolerance. In addition, the assembly gap between two parts is also controlled. To conduct the optimization, this paper develops an improved particle swarm optimization (IPSO) algorithm by integrating the shrinkage factor and adaptive inertia weight. In the algorithm, particles are encoded according to the fixture position. Each dimension of the particle is assigned to a sub-region by constraining the optional position range of each fixture to improve the optimization efficiency. Finally, a case study on ship curved panel assembly is provided to prove that our method can optimize the number of fixtures while meeting the assembly quality requirements. This research proposes a method to optimize the number of fixtures, which can reduce the number of fixtures and achieve deformation control at the same time.

Abstract Background Pelvic floor dysfunction (PFD) is an extremely widespread urogynecologic disorder, the prevalence of which increases with aging. PFD has severely affected women’s quality of life and has been called a social cancer. While previous studies have identified risk factors such as vaginal delivery and obesity for PFD, other reproductive factors, including age at menarche (AAMA), have been largely overlooked. Therefore, we used a Mendelian randomization (MR) study for the first time to investigate the potential causal relationship between reproductive factors and PFD. Methods We obtained summary statistics from genome-wide association studies (GWAS) for female genital prolapse (FGP), stress urinary incontinence (SUI), and five reproductive factors. Two-sample Mendelian randomization analysis (TSMR) was performed to explore the causal associations between these factors. The causal effects of reproductive factors on FGP and SUI were primarily estimated using the standard inverse variance weighting (IVW) method, with additional complementary and sensitivity analyses conducted using multiple approaches. A multivariate Mendelian randomization (MVMR) study was also conducted to adjust for pleiotropic effects and possible sources of selection bias and to identify independent exposure factors. Results Our findings revealed that advanced age at first sexual intercourse (AFS) and age at first birth (AFB) exhibited negative causal effects on both FGP and SUI. AAMA showed negative causal effects solely on FGP, while age at last live birth (ALB) and age at menopause (AAMO) did not demonstrate any causal effect on either FGP or SUI. And the MVMR results showed that AFB and AFS had independent negative causal effects on FGP and SUI, respectively. Conclusions This study, for the first time, investigates the causal relationship between reproductive factors and PFD. The results suggested a causal relationship between some reproductive factors, such as AFB and AFS, and PFD, but there were significant differences between FGPand SUI. Therefore, future studies should explore the underlying mechanisms and develop preventive measures for reproductive factors to reduce the disease burden of PFD.

Primary toppling usually occurs in layered rock slopes with large anti-dip angles. In this paper, the block toppling evolution was explored using a large-scale centrifuge system. Each block column in the layered model slope was made of cement mortar. Some artificial cracks perpendicular to the block column were prefabricated. Strain gages, displacement gages, and high-speed camera measurements were employed to monitor the deformation and failure processes of the model slope. The centrifuge test results show that the block toppling evolution can be divided into seven stages, i.e. layer compression, formation of major tensile crack, reverse bending of the block column, closure of major tensile crack, strong bending of the block column, formation of failure zone, and complete failure. Block toppling is characterized by sudden large deformation and occurs in stages. The wedge-shaped cracks in the model incline towards the slope. Experimental observations show that block toppling is mainly caused by bending failure rather than by shear failure. The tensile strength also plays a key factor in the evolution of block toppling. The simulation results from discrete element method (DEM) is in line with the testing results. Tensile stress exists at the backside of rock column during toppling deformation. Stress concentration results in the fragmented rock column and its degree is the most significant at the slope toe.

Great potential of underground gas/energy storage in salt caverns seems to be a promising solution to support renewable energy. In the underground storage method, the operating cycle unfortunately may reach up to daily or even hourly, which generates complicated pressures on the salt cavern. Furthermore, the mechanical behavior of rock salt may change and present distinct failure characteristics under different stress states, which affects the performance of salt cavern during the time period of full service. To reproduce a similar loading condition on the cavern surrounding rock mass, the cyclic triaxial loading/unloading tests are performed on the rock salt to explore the mechanical transition behavior and failure characteristics under different confinement. Experimental results show that the rock salt samples present a diffused shear failure band with significant bulges at certain locations in low confining pressure conditions (e.g. 5 MPa, 10 MPa and 15 MPa), which is closely related to crystal misorientation and grain boundary sliding. Under the elevated confinement (e.g. 20 MPa, 30 MPa and 40 MPa), the dilation band dominates the failure mechanism, where the large-size halite crystals are crushed to be smaller size and new pores are developing. The failure transition mechanism revealed in the paper provides additional insight into the mechanical performance of salt caverns influenced by complicated stress states.

Parasitoids are key regulators in ecological communities and widely used as agents in biocontrol programmes. The fall armyworm, Spodoptera frugiperda, recently invaded multiple continents and caused substantial economic losses in agriculture. Pyemotes zhonghuajia, a newly identified mite parasitoid, has shown potential for controlling various agricultural insect pests. Therefore, this study tested the performance of P. zhonghuajia in parasitising S. frugiperda. We also investigated the sublethal effects of parasitism by P. zhonghuajia on host fitness traits, transgenerational impacts, and cellular and humoral immunity. Our result showed that the fifth-instar larvae of S. frugiperda parasitised by 40 P. zhonghuajia were all dead (i.e., a lethal effect), while parasitism by 5 or 10 P. zhonghuajia was considered sublethal since many S. frugiperda survived to adulthood and produced offspring after mating. The sublethal influences from parasitism by P. zhonghuajia resulted in reduced pupal weight, adult emergence rate and fecundity, but increased developmental time and longevity. Parasitism at both lethal (40 mites) and sublethal (10 mites) levels impaired the cellular and humoral immunity of S. frugiperda. This study presents the first empirical evidence that mite parasitoids can negatively influence host immunity. Moreover, it provides insights into the biocontrol potential of mite parasitoids and their interactions with hosts.

Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis, whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer. Herein, we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy. The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin (DOX) formed by consecutive ultrasonication-induced β-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion, exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy, as well as simultaneous release of DOX to finally achieve effective anti-cancer effect. A stretchable bioadhesive is fabricated by copolymerization of α-thioctic acid and N, N-diacryloyl-l-lysine, and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions. The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing. Ultimately, in vivo animal studies substantiate the efficacy of our methodology, wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.

Bionic multi-legged robots with flexible bodies embody human ingenuity in imitating, learning, and exploring the natural world. In contrast to rigid-body robots, these robots with flexible bodies exhibit superior locomotive capabilities. The flexible body of the robot not only boosts the moving speed and walking stability but also enhances adaptability across complex terrains. This article focuses on the innovative design of flexible bodies. Firstly, the structural designs, including artificial spines and single/multi-axis articulation mechanisms, are outlined systematically. Secondly, the enhancement of robotic motion by flexible bodies is reviewed, examining the impact that body degrees of freedom, stiffness, and coordinated control between the body and limbs have on robotic motion. Thirdly, existing robotic control methods, organized by control architectures, are comprehensively overviewed in this article. Finally, the application prospects of bionic multi-legged robots with flexible bodies are offered, and the challenges that may arise in their future development are listed. This article aims to serve as a reference for bionic robot research.

Objectives: Optical coherence tomography (OCT) has recently been used in gynecology to detect cervical lesions in vivo and proven more effective than colposcopy in clinical trials. However, most gynecologists are unfamiliar with this new imaging technique, requiring intelligent computer-aided diagnosis approaches to help them interpret cervical OCT images efficiently. This study aims to (1) develop a clinically-usable deep learning (DL)-based classification model of 3D OCT volumes from cervical tissue and (2) validate the DL model’s effectiveness in detecting high-risk cervical lesions, including high-grade squamous intraepithelial lesions and cervical cancer. Method: The proposed DL model, designed based on the convolutional neural network architecture, combines a feature pyramid network (FPN) with texture encoding and deep supervision. We extracted, represent, and fused four-scale texture features to improve classification performance on high-risk local lesions. We also designed an auxiliary classification mechanism based on deep supervision to adjust the weight of each scale in FPN adaptively, enabling low-cost training of the whole model. Results: In the binary classification task detecting positive subjects with high-risk cervical lesions, our DL model achieved an 81.55% (95% CI, 72.70–88.51%) F1-score with 82.35% (95% CI, 69.13–91.60%) sensitivity and 81.48% (95% CI, 68.57–90.75%) specificity on the Renmin dataset, outperforming five experienced medical experts. It also achieved an 84.34% (95% CI, 74.71–91.39%) F1-score with 87.50% (95% CI, 73.20–95.81%) sensitivity and 90.59% (95% CI, 82.29–95.85%) specificity on the Huaxi dataset, comparable to the overall level of the best investigator. Moreover, our DL model provides visual diagnostic evidence of histomorphological and texture features learned in OCT images to assist gynecologists in making clinical decisions quickly. Conclusions: Our DL model holds great promise to be used in cervical lesion screening with OCT efficiently and effectively.

Three-dimensional gravity inversion is a process of obtaining the location, shape, and physical property parameters of underground anomaly sources using gravity anomaly data observed on the surface. In recent years, with the rapid development of data-driven methods, the application of deep learning (DL) to 3D gravity inversion has also attracted wide attention and achieved certain results. In this paper, based on the U-Net network, a three-dimensional gravity inversion method using an attention feature fusion mechanism is proposed. Using U-Net as the basic framework, the coarse-grained semantic features and fine-grained semantic features in the encoder and decoder are connected by long hops, and the global and local semantic features are aggregated through the attention feature fusion module, which avoids feature loss in the network training process. Compared with the inversion results of the U-Net network, the proposed method has a higher vertical resolution and effectively alleviates the influence of the skin effect on three-dimensional gravity inversion. Ablation experiments show that the attention feature fusion module is the key to improving the vertical resolution and prediction accuracy of inversion results. Noise experiments show that the inversion network in this study has a strong anti-noise ability and good generalization performance. The experimental results of the inversion network used in the prediction of the SAN Nicolas deposit in Mexico show that the inversion network can clearly predict the basic location and general shape of the sulfur deposit, and the results are in good agreement with the known geological data.

BackgroundThe claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied.MethodsWe evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats.ResultsWe found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test.ConclusionThese data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions.

IntroductionSclerotinia sclerotiorum is a known pathogen that harms crops and vegetables. Unfortunately, there is a lack of effective biological control measures for this pathogen. Bacillus velezensis 20507 has a strong antagonistic effect on S. Sclerotiorum; however, the biological basis of its antifungal effect is not fully understood.MethodsIn this study, the broad-spectrum antagonistic microorganisms of B. velezensis 20507 were investigated, and the active antifungal ingredients in this strain were isolated, purified, identified and thermal stability experiments were carried out to explore its antifungal mechanism.ResultsThe B. velezensis 20507 genome comprised one circular chromosome with a length of 4,043,341 bp, including 3,879 genes, 185 tandem repeats, 87 tRNAs, and 27 rRNAs. Comparative genomic analysis revealed that our sequenced strain had the closest genetic relationship with Bacillus velezensis (GenBank ID: NC 009725.2); however, there were significant differences in the positions of genes within the two genomes. It is predicted that B. velezensis 20507 encode 12 secondary metabolites, including difficidin, macrolactin H, fengycin, surfactin, bacillibactin, bacillothiazole A-N, butirosin a/b, and bacillaene. Results showed that B. velezensis 20507 produced various antagonistic effects on six plant pathogen strains: Exserohilum turcicum, Pyricularia oryzae, Fusarium graminearum, Sclerotinia sclerotiorum, Fusarium oxysporum, and Fusarium verticillioides. Acid precipitation followed by 80% methanol leaching is an effective method for isolating the antifungal component ME80 in B. velezensis 20507, which can damage the membranes of S. sclerotiorum hyphae and has good heat resistance. Using high-performance liquid chromatography, and Mass Spectrometry analysis, it is believed that fengycin C72H110N12O20 is the main active antifungal substance.DiscussionThis study provides new resources for the biological control of S. Sclerotiorum in soybeans and a theoretical basis for further clarification of the mechanism of action of B. velezensis 20507.

Abstract Background Stress urinary incontinence (SUI) is characterized by involuntary urine leakage in response to increased abdominal pressure, such as coughing, laughing, or sneezing. It significantly affects women’s quality of life and imposes a substantial disease burden. While pregnancy and childbirth have been previously identified as risk factors for SUI, educational attainment may also play a role. Therefore, this paper investigates the causal relationship between educational attainment and SUI using two-sample Mendelian randomization (TSMR) analysis, years of schooling (YOS), and college or university degree (CUD) as proxies. Methods Summary statistics of YOS, CUD, and SUI were obtained from genome-wide association studies (GWAS), and TSMR analysis was applied to explore potential causal relationships between them. Causal effects were mainly estimated using the standard inverse variance weighting (IVW) method, and complementary and sensitivity analyses were also performed using multiple methods. Results The results indicate that both YOS (OR = 0.994, 95% CI: 0.992–0.996; P = 7.764E-10) and CUD (OR = 0.987, 95% CI: 0.983–0.991; P = 1.217E-09) may have a negative causal effect on SUI. Conclusions Improving educational attainment may go some way towards reducing the risk of SUI. Therefore, it is important to increase efforts to improve the imbalance in educational development and safeguard women’s health.

Purpose – To address the problem that the current train operation mode that train selects one of several offline pre-generated control schemes before the departure and operates following the scheme after the departure, energy-saving performance of the whole metro system cannot be guaranteed. Design/methodology/approach – A cooperative train control framework is formulated to regulate a novel train operation mode. The classic train four-phase control strategy is improved for generating specific energy-efficient control schemes for each train. An improved brute force (BF) algorithm with a two-layer searching idea is designed to solve the optimisation model of energy-efficient train control schemes. Findings – Case studies on the actual metro line in Guangzhou, China verify the effectiveness of the proposed train control methods compared with four-phase control strategy under different kinds of train operation scenarios and calculation parameters. The verification on the computation efficiency as well as accuracy of the proposed algorithm indicates that it meets the requirement of online optimisation. Originality/value – Most existing studies optimised energy-efficient train timetable or train control strategies through an offline process, which has a defect in coping with the disturbance or delays effectively and promptly during real-time train operation. This paper studies an online optimisation of cooperative train control based on the rolling optimisation idea, where energy-efficient train operation can be realised once train running time is determined, thus mitigating the impact of unpredictable operation situations on the energy-saving performance of trains.

Abstract Background Ethylene inhibitor treatment of soybean promotes flower bud differentiation and early flowering, suggested that there is a close relationship between ethylene signaling and soybean growth and development. The short-lived ETHYLENE INSENSITIVE2 (EIN2) and ETHYLENE INSENSITIVE3 (EIN3) proteins play central roles in plant development. The objective of this study was carried out gene editing of EIL family members in soybeans and to examine the effects on soybean yield and other markers of growth. Methods and results By editing key-node genes in the ethylene signaling pathway using a multi-sgRNA-in-one strategy, we obtained a series of gene edited lines with variable edit combinations among 15 target genes. EIL3, EIL4, and EIN2L were editable genes favored by the T0 soybean lines. Pot experiments also show that the early flowering stage R1 of the EIL3, EIL4, and EIN2L triple mutant was 7.05 d earlier than that of the wild-type control. The yield of the triple mutant was also increased, being 1.65-fold higher than that of the control. Comparative RNA-seq revealed that sucrose synthase, AUX28, MADS3, type-III polyketide synthase A/B, ABC transporter G family member 26, tetraketide alpha-pyrone reductase, and fatty acyl-CoA reductase 2 may be involved in regulating early flowering and high-yield phenotypes in triple mutant soybean plants. Conclusion Our results provide a scientific basis for genetic modification to promote the development of earlier-flowering and higher-yielding soybean cultivars.

Deep learning (DL) has been widely applied to forecast the sales volume of household appliances with high accuracy. Unfortunately, in small towns, due to the limited amount of historical sales data, it is difficult to forecast household appliance sales accurately. To overcome the above-mentioned challenge, we propose a novel household appliance sales forecasting algorithm based on transfer learning, temporal convolutional network (TCN), long short-term memory (LSTM), and attention mechanism (called “TransTLA”). Firstly, we combine TCN and LSTM to exploit the spatiotemporal correlation of sales data. Secondly, we utilize the attention mechanism to make full use of the features of sales data. Finally, in order to mitigate the impact of data scarcity and regional differences, a transfer learning technique is used to improve the predictive performance in small towns, with the help of the learning experience from the megacity. The experimental outcomes reveal that the proposed TransTLA model significantly outperforms traditional forecasting methods in predicting small town household appliance sales volumes. Specifically, TransTLA achieves an average mean absolute error (MAE) improvement of 27.60% over LSTM, 9.23% over convolutional neural networks (CNN), and 11.00% over the CNN-LSTM-Attention model across one to four step-ahead predictions. This study addresses the data scarcity problem in small town sales forecasting, helping businesses improve inventory management, enhance customer satisfaction, and contribute to a more efficient supply chain, benefiting the overall economy.

Using computer vision technology to estimate pig live weight is an important method to realize pig welfare. But there are two key issues that affect pigs’ weight estimation: one is the uneven illumination, which leads to unclear contour extraction of pigs, and the other is the bending of the pig body, which leads to incorrect pig body information. For the first one, Mask R-CNN was used to extract the contour of the pig, and the obtained mask image was converted into a binary image from which we were able to obtain a more accurate contour image. For the second one, the body length, hip width and the distance from the camera to the pig back were corrected by XGBoost and actual measured information. Then we analyzed the rationality of the extracted features. Three feature combination strategies were used to predict pig weight. In total, 1505 back images of 39 pigs obtained using Azure kinect DK were used in the numerical experiments. The highest prediction accuracy is XGBoost, with an MAE of 0.389, RMSE of 0.576, MAPE of 0.318% and R2 of 0.995. We also recommend using the Mask R-CNN + RFR method because it has fairly high precision in each strategy. The experimental results show that our proposed method has excellent performance in live weight estimation of pigs.

Influenced by the clearance flow between stator and rotor, the operational performance and hydraulic performance of full cross-flow pump units are often worse than that of semi-cross-flow pumps. In order to explore the influence mechanism of clearance structural parameters on clearance flow and provide a reliable scientific support for the improvement of both external and internal characteristics of full cross-flow pump units, firstly, the optimization of the stator–rotor clearance structure was studied as research entry point and the radial inlet and outlet clearance width were taken to set up design variables. Secondly, to establish a comprehensive optimization objective function considering both the operational performance and the hydraulic performance of the pump, the information weight method was adopted by weighting four evaluation indexes, namely, head coefficient, efficiency coefficient, vortex average radial deflection coefficient and axial velocity uniformity coefficient, which were calculated by numerical simulation. Finally, the relevant optimization design analysis was carried out by establishing the response surface model, with the optimal objective value obtained by conducting the steepest-descent method. The results show that the response of the radial inlet and outlet clearance width coefficient between stator and rotor to the comprehensive objective function is not directly coupled and the influence of the radial inlet clearance width coefficient on the objective function is higher than that of the radial outlet clearance width coefficient. The parameter optimization outcomes are as follows: the width coefficient of radial inlet clearance between stator and rotor is 2.2 and that of radial outlet clearance is 3.6, in which case the disturbance effect of clearance flow on the mainstream flow pattern in the pump can be significantly reduced, with the export cyclic quantity of the guide vane obviously decreased and the outlet flow pattern of the pump unit greatly improved. Verified by the model test, the average lift of the pump unit was increased by about 7.6% and the maximum promotion of the unit efficiency reached 5.2%.

The Chinese crested (CC) duck is a unique indigenous waterfowl breed, which has a crest cushion that affects its survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed that genes related to tissue repair, immune function, and tumors were under strong positive selection, indicating that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We also assembled a Chinese spot-billed (Csp-b) duck genome, and detected the structural variations (SVs) in the genome assemblies of three ducks (i.e., CC duck, Csp-b duck, and Peking duck). Functional analysis revealed that several SVs were related to the immune system of CC ducks, further strongly suggesting that genetic compensation in the anti-tumor and immune systems supports the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.

Real-time automatic displacement monitoring of metro tunnels is vital for ensuring operational safety and contributes to carbon reduction goals by improving system efficiency. This study focuses on key monitoring elements such as displacement, settlement, convergence, and cracking. Through the analysis of continuous monitoring data, a real-time displacement monitoring model for metro tunnels based on robotic total stations is proposed. This model can timely identify potential risks, thereby ensuring the safe operation of tunnels and reducing carbon emissions from unnecessary maintenance operations, thereby reducing the carbon footprint of metro operations. This article takes the Jinan Metro Tunnel Displacement Real-time Monitoring Project in China as a case study and constructs a comprehensive monitoring framework using robotic total stations, intelligent automated deformation monitoring data collectors, and cloud servers. The implementation details of the project, displacement monitoring principles, monitoring system construction, and data analysis processes are elaborated in detail. Taking the monitoring data of Jinan Metro Line 2 from April 1, 2022, to May 31, 2023, as an example, the results show that the tunnel displacement is within the safe range, verifying the practical application value of the method proposed in this paper. It can effectively ensure the safe operation of the metro and promote sustainable development and low-carbon metro construction.

Highlights Responsive photonic nanorobots (RPNRs) simultaneously exhibit energetic magnetically-propelled swarming motions, bright stimuli-responsive structural colors, and photothermal conversion. The swarming RPNRs can actively navigate in complex environments and collectively map out local physicochemical conditions (e.g., pH, temperature, or glucose concentration) on the fly via their bright responsive structural colors. The swarming RPNRs can visualize an unknown target (e.g., tumor lesion) via motile-targeting mapping and then guide the external NIR light to initiate localized photothermal treatment.

A reasonable evaluation of unloading deformation characteristics is of great significance for the effective analysis of deformation and stability of surrounding rocks after underground excavation. In this study, the damage-controlled cyclic triaxial loading tests were conducted to investigate the pore compaction mechanism and its influences on the unloading deformation behavior of red sandstone, including Young's modulus, Poisson's ratio, volumetric strain, and irreversible strain. The experimental results show that the increases of volumetric and irreversible strains of rocks can be attributed to the compaction mechanism, which almost dominates the entire pre-peak deformation process. The unloading deformation consists of the reversible linear and nonlinear strains, and the irreversible strain under the influence of the porous grain structure. The pre-peak Young's modulus tends to increase and then decrease due to the influence of the unloading irreversible strain. However, it hardly changes with the increasing volumetric strain compaction under the influence of reversible nonlinear strain. Instead, the initial unloading tangent modulus is highly related to the volumetric strain, and clearly reflects the compaction state of red sandstone. Furthermore, both the reversible nonlinear and irreversible unloading deformations are independent of confining pressure. This study is beneficial for the theoretical modeling and prediction of cyclic unloading deformation behavior of red sandstone.

ABSTRACT: Longitudinal traits, such as milk production traits in dairy cattle, are featured by having phenotypic values at multiple time points, which change dynamically over time. In this study, we first imputed SNP chip (50–100K) data to whole-genome sequence (WGS) data in a Chinese Holstein population consisting of 6,470 cows. The imputation accuracies were 0.88 to 0.97 on average after quality control. We then performed longitudinal GWAS in this population based on a random regression test-day model using the imputed WGS data. The longitudinal GWAS revealed 16, 39, and 75 quantitative trait locus regions associated with milk yield, fat percentage, and protein percentage, respectively. We estimated the 95% confidence intervals (CI) for these quantitative trait locus regions using the logP drop method and identified 581 genes involved in these CI. Further, we focused on the CI that covered or overlapped with only 1 gene or the CI that contained an extremely significant top SNP. Twenty-eight candidate genes were identified in these CI. Most of them have been reported in the literature to be associated with milk production traits, such as DGAT1, HSF1, MGST1, GHR, ABCG2, ADCK5, and CSN1S1. Among the unreported novel genes, some also showed good potential as candidate genes, such as CCSER1, CUX2, SNTB1, RGS7, OSR2, and STK3, and are worth being further investigated. Our study provided not only new insights into the candidate genes for milk production traits, but also a general framework for longitudinal GWAS based on random regression test-day model using WGS data.