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Abstract High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

Abstract The patterns of communication among different chondrocyte subtypes in human cartilage degeneration and regeneration help us understand the microenvironment of osteoarthritis and optimize cell-targeted therapies. Here, a single-cell transcriptome dataset of chondrocytes is used to explore the synergistic and communicative patterns of different chondrocyte subtypes. We collected 1600 chondrocytes from 10 patients with osteoarthritis and analyzed the active communication patterns for the first time based on network analysis and pattern recognition at the single-cell level. Manifold learning and quantitative contrasts were performed to analyze conserved and specific communication pathways. We found that ProCs (Proliferative chondrocytes), ECs (Effector chondrocytes), preHTCs (Prehypertrophic chondrocytes), HTCs (Hypertrophic chondrocytes), and FCs (Fibrocartilage chondrocytes) are more active in incoming and outgoing signaling patterns, which is consistent with studies on their close functional cooperation. Among them, preHTCs play multiple roles in chondrocyte communication, and ProCs and preHTCs have many overlapping pathways. These two subtypes are the most active among all chondrocyte subtypes. Interestingly, ECs and FCs are a pair of “mutually exclusive” subtypes, of which ECs are predominant in incoming patterns and FCs in outgoing patterns. The active signaling pathways of ECs and FCs largely do not overlap. COLLAGEN and LAMININ are the main pivotal pathways, which means they are very important in the repair and expansion of joint homeostasis. Notably, only preHTCs assume multiple roles (including sender, receiver, mediator, and influencer) and are involved in multiple communication pathways. We have examined their communication patterns from the perspective of cellular interactions, revealed the relationships among different chondrocyte subtypes, and, in particular, identified a number of active subtypes and pathways that are important for targeted therapy in the osteoarthritic microenvironment. Our findings provide a new research paradigm and new insights into understanding chondrocyte activity patterns in the osteoarthritic microenvironment.

Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors. Subsequently, OX1R, HIF-1α expression and localization, glucose uptake, glucose transporter 1 (GLUT1) expression and ATP content were measured. We further investigated the intracellular fate of glucose by measuring the gene expression of pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase (LDHA) and pyruvate dehydrogenase B (PDHB), as well as metabolite levels including lactate generation and mitochondrial pyruvate dehydrogenase (PDH) activity. The activity of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was also assessed. Our results showed that the expression of OX1R was predominantly located in the nucleus in HepG2 cells. Orexin A oxygen-independently promoted the mRNA and protein expression of HIF-1α as well as its nuclear accumulation in HepG2 cells and the elevated HIF-1α protein was associated, at least partly, with the activation of the PI3K/Akt/mTOR pathway. Orexin A stimulated GLUT1 expression, glucose uptake as well as ATP generation in HepG2 cells via OX1R acting through the HIF-1α pathway. Moreover, orexin A inhibited LDHA, PDK1 expression and lactate production, stimulated PDHB expression and PDH enzyme activity independent of HIF-1α. Our results indicated that orexin signaling facilitated the glucose flux into mitochondrial oxidative metabolism rather than glycolysis in HepG2 cells. These findings provide new insight into the regulation of glucose metabolism by orexin A in hepatocellular carcinoma cells.

Abstract Identifying influential nodes in real networks is significant in studying and analyzing the structural as well as functional aspects of networks. VoteRank is a simple and effective algorithm to identify high-spreading nodes. The accuracy and monotonicity of the VoteRank algorithm are poor as the network topology fails to be taken into account.Given the nodes’ attributes and neighborhood structure, this paper put forward an algorithm based on the Edge Weighted VoteRank (EWV) for identifying influential nodes in the network. The proposed algorithm draws inspiration from human voting behavior and expresses the attractiveness of nodes to their first-order neighborhood using the weights of connecting edges. Similarity between nodes is introduced into the voting process, further enhancing the accuracy of the method. Additionally, this EWV algorithm addresses the problem of influential node clustering by reducing the voting ability of nodes in the second-order neighborhood of the most influential nodes. The validity of the presented algorithm is verified through experiments conducted on 12 different real networks of various sizes and structures, directly comparing it with 7 competing algorithms.Empirical results indicate a superiority of the presented algorithm over the remaining seven competing algorithms with respect to node differentiation ability, effectiveness, and ranked list accuracy.

Abstract The generation of a substantial amount of construction waste (CW) poses significant challenges to the green transition of highway construction projects. However, the construction industry lacks integration of construction waste management (CWM) practices into the construction process. This paper aims to develop a calculation for assessing the performance of CWM to monitor its effectiveness in highway construction. Initially, this study utilizes the Site waste management plan (SWMP) as a foundation and develops a Construction Waste Management Performed Assessment Method (CWMPAM). The extension of CWM is incorporated into earned value management (EVM) to manage costs, schedules, and the performance of CWM within a unified framework. The functionality and sensitivity of CWMPAM and CWM-embedded EVM are validated through pilot testing and scenario analysis. The research results are computerized into a calculator to facilitate the practical application of CWM, and its validity is tested using random cases. CWMPAM and CWM-embedded EVM prove satisfactory in assessing and monitoring the execution and performance of CWM. The developed calculator simplifies the practical application of the outcomes. Essentially, the developed calculator represents a groundbreaking integration of CWM and construction management, enabling project managers to monitor and compare the CWM performance across different segments of highway construction. Not only does this contribute to the green transformation of highway projects, it also promotes high quality and sustainable development in the construction industry.

Abstract Prostate cancer (PCa) is one of the most important health problems among elderly men in China, with the increasing aging of the population. A cross-sectional survey was conducted in eastern China from 2022 to 2023. Recruitment included a total of 70,342 participants aged 60 or older. Social demographic information, such as individual factors like age, education levels and behavior habits, physical examination and laboratory tests results were collected. Age-standardized prevalence rates were estimated by a direct method with a standard population. T test and chi-square test were used to compare the statistical differences. Multivariate regression models were used to identify the risk factors of PCa. Overall, the crude and age-standardized PCa prevalence is 0.93% and 0.91%, respectively in eastern China. When we adjusted all the co-variables, it showed that high age, smoking, having a higher BMI and higher CA19-9 were associated with a higher risk for a prostate cancer diagnosis. Faced with the demographic transition, innovative strategies are needed to control and prevent PCa. Conducting early screening among male population in community health service centers in eastern of China, especially among a population with associated risk factors such as high age, obesity, and conducting community-based intervention programs might be helpful to address this increasingly significant health problem.

Abstract In order to obtain the pattern of variation of PM2.5concentrations in the atmosphere in Nanchang City, we build a Support Vector Regression(SVR) with modified Whale Optimization Algorithm(WOA) hybrid model (namely mWOA-SVR model) that can predict the PM2.5concentration. Firstly, according to the Pearson correlation coefficient (PCC) method to examine the dynamic relationship between air pollutants and meteorological factors together with them, PM10, SO2and CO were selected as air pollutant concentration characteristics, while daily maximum and minimum temperatures, and wind power levels were selected as meteorological characteristics; then, using modified WOA algorithm for parameter selection of SVR model, four sets of better parameter combinations were found; finally, the mWOA-SVR model was built by the four sets parameters to predict PM2.5concentration. The results show that the prediction accuracy of mixed mWOA-SVR model with pollutant concentration plus weather factors as the feature was higher than single pollutant concentration.

Abstract Light and DELLA proteins are central factors controlling seed germination which is critical for seed plant survival and agricultural production. However, the mechanisms underlying DELLA degradation under different light conditions during seed germination remain to be clarified. Here, it is reported that TIE1‐ASSOCIATED RING‐TYPE E3 LIGASE4 (TEAR4) and other TEARs redundantly promote DELLA degradation to positively regulate seed germination in Arabidopsis. The tear1/2/3/4/5/6 sextuple mutant displayed delayed seed germination under the white or PhyB‐dependent light condition, and nearly no seed germination under the PhyA‐dependent light condition. The DELLA protein REPRESSOR OF ga1‐3 (RGA) accumulated in tear1/2/3/4/5/6, and disruption of RGA and GA‐INSENSITIVE (GAI) in tear1/2/3/4/5/6 rescued defective seed germination. Far‐red (FR) light rapidly induced TEARs, and TEAR4 is shown to act as an E3 ligase. It is showed that both GA‐dependent and TEAR‐mediated DELLA degradation pathways are indispensable for PhyA‐dependent germination. It is found that TEAR homologs PpTEAR1 and PpTEAR2 from the moss Physcomitrium patens interacted with Arabidopsis DELLAs to promote their degradation, and overexpression of PpTEAR1 or PpTEAR2 completely rescued defective PhyA‐dependent seed germination in phya‐211. This findings demonstrate that TEARs act as critical players in fine‐tuning seed germination, and TEAR‐mediated DELLA degradation might be an ancient pathway conserved in plant kingdom.

The cervical uncinate process is a unique structure of the cervical spine that undergoes significant changes in its morphological characteristics with age, and these changes may be related to osteoporosis. This study aimed to observe the distribution of cancellous bone in the cervical uncinate process and its morphological features using micro-computed tomography (Micro-CT) to gain a deeper understanding of the morphological characteristics of the uncinate microstructure. We performed Micro-CT scans on 31 sets of C3-C7 vertebrae, a total of 155 intact bone samples, and subsequently used the measurement software with the Micro-CT system to obtain parameters related to the cancellous bone of the uncinate process. We found that the cancellous bone of the uncinate process was predominantly longitudinally cross-aligned and continuous with the cancellous bone within the vertebral body. Comparisons between the left and right sides of each parameter showed significant differences only in the bone surface area, and the peaks of each parameter were primarily concentrated in C4-C6. In this study, we found that the C5 uncinate process is the site of most significant stress in the cervical vertebrae, which leads to the earliest occurrence of osteoporosis, and this study provides experimental, theoretical bases for the prevention of cervical spondylosis and osteoporosis, and the diagnosis and treatment of related diseases.

Abstract Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups;

Abstract Variations in immune cell counts can trigger depressive symptoms, while physical activity effectively reduces the risk and severity of depressive symptoms. This study, based on the NHANES database, analyzes the relationship between neutrophil count and depressive symptoms and explores the moderating effect of physical activity on this relationship. Cross-sectional data from the NHANES database were extracted, including immune cell counts, PHQ-9 scores for self-assessment of depressive symptoms, and Global Physical Activity Questionnaire (GPAQ) scores (PA). The interrelations among physical activity, neutrophil count, and depressive symptoms were analyzed. After controlling for confounding factors, neutrophil count was found to have a significant role in identifying depressive symptoms with an odds ratio (OR) [95% Confidence Interval (CI)] = 1.13 [1.02, 1.251]; the moderating effect of physical activity on the impact of neutrophil count on depressive symptoms was statistically significant (coefficient = -0.0028, P

Abstract Intron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.

Abstract Despite of excellent thermal properties and high sputtering resistance, pure tungsten cannot fully satisfy the requirements for plasma facing materials in future high-duty cycle nuclear fusion reactions due to the coupled extreme environments, including the high thermal loads, plasma exposure, and radiation damage. Here, we demonstrated that tungsten-based composite materials fabricated using spark-plasma sintering (SPS) present promising solutions to these challenges. Through the examination of two model systems, i.e., tungsten-zirconium composite for producing porous tungsten near the surface and dispersoid-strengthened tungsten, we discussed both the strengths and limitations of the SPS-fabricated materials. Our findings point towards the need for future studies aimed at optimizing the SPS process to achieve desired microstructures and effective control of oxygen impurities in the tungsten-based composite materials.

Abstract This study compares the effectiveness of Conbercept and Aflibercept in treating neovascular age-related macular degeneration (nAMD). Conducted at the First Affiliated Hospital of Chongqing Medical University's Ophthalmology Department (May 2020–May 2023), this prospective study enrolled 159 nAMD patients. Participants were randomly divided into two groups: one receiving 0.5 mg Conbercept and the other 2 mg Aflibercept intravitreal injections. Over 12 months, the study, employing a Treat-and-Extend (T&E) regimen, assessed Best-Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT) changes and injection frequency. Of the 159 patients, 137 (149 eyes) completed the study. No significant age difference was found between the groups (P = 0.331). After 12 months, BCVA improved similarly in both groups (Conbercept: 52.8 ± 18.9, Aflibercept: 52.0 ± 19.7 letters; P = 0.820). CRT reduction was also comparable (Conbercept: 246.3 ± 82.8 µm, Aflibercept: 275.9 ± 114.3 µm; P = 0.079). Injection frequencies averaged 6.9 ± 0.7 (Conbercept) and 6.7 ± 0.7 (Aflibercept; P = 0.255). Subtype analysis revealed Type 1 MNV had higher baseline BCVA and lower CRT, with more frequent injections compared to other types. Both Conbercept and Aflibercept are clinically similar in efficacy for nAMD, with the T&E regimen proving therapeutically effective and potentially reducing patient costs. Anti-VEGF treatment efficacy varies across nAMD subtypes, indicating a potential benefit in tailored treatments for specific subtypes. Clinical trial registration number NCT05539235 (Protocol Registration and Results System).

Abstract Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.

Abstract Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and infertility. Early hormonal intervention is preventive, but excessive glucocorticoid poses risks. Developing reliable methods for early TART diagnosis and monitoring is crucial. The present study aims to formulate a scoring system to identify high-risk infertility through analysis of TART ultrasound features. Grayscale and power Doppler ultrasound were employed in this retrospective study to evaluate testicular lesions in male CAH patients. Lesion assessment encompassed parameters such as range, echogenicity, and blood flow, and these were subsequently correlated with semen parameters. Results of 49 semen analyzes from 35 patients demonstrated a notable inverse correlation between lesion scores and both sperm concentration (rs = − 0.83, P

Abstract Insufficient attention has been given to the recycling of excess urea despite its potential detrimental effects on soil nutrient equilibrium, geological structure, and crop health. In this study, corncob-derived porous biochar (CPB), which is rich in surface functional groups, was prepared from biomass corncob in two steps as an adsorbent to remove urea from wastewater. Compared with the typical carbonization and activation processes, this process resulted in a higher yield of CPB and an ultrahigh adsorption capacity for urea. Response surface analysis was utilized to determine the optimal carbonization conditions, which were found to be 500 °C for 6 h with a heating rate of 15 °C/min. The exceptional adsorption capability of CPB can be ascribed to its porous structure and significant presence of oxygen-containing functional groups, which facilitate a synergistic interaction of physisorption and chemisorption. This adsorption phenomenon aligns with the Harkins–Jura isotherm model and adheres to pseudo-second order kinetics. CPB demonstrates potential as an adsorbent for the elimination of urea from wastewater in an economical and effective fashion.

Abstract This paper presents the investigation of the dynamic mechanical properties of coal rock under complex stress conditions at depth, based on the improved Separate Hopkinson Pressure Bar Test System. A total of 15 groups of coal samples were used to perform dynamic impact tests under different conditions. The changing rules of dynamic strength, crushing, fractal dimension and damage modes of coal under different stress conditions were analyzed. A total of nine groups of coal samples were selected for numerical simulation using ANSYS/LS-DYNA. The results show that: (1) The stress–strain curves of coal specimens under different strain rates, different confining pressures and axial pressures have basically the same trend and the curves show a certain jump forward. (2) The peak dynamic stress of the coal specimens increased linearly with the increase of strain rate and confining pressure, and the ambient pressure limited the expansion of internal cracks of the coal specimens under impact loading. Based on the experimental and simulated data, the maximum relative errors between the experimental and simulated data were determined to be 2.9578% for Group A, 6.177% for Group B, and 6.382% for Group C, respectively. (3) The damage modes of the coal samples under the three-dimensional dynamic-static combined loading were mainly “X” type and “conical” shear damage. The fractal dimension increases with the increase of strain rate, decreases with the increase of confining pressure, and first decreases and then increases with the increase of axial pressure. This research achievement can provide theoretical support for the prevention of dynamic disasters in deep coal mine engineering.

Summary: Cell functions are based on the integrity of actin filaments. The actin cytoskeleton is typically the target but also the source of signals. Arabidopsis PRL1 (Pleiotropic Regulatory Locus 1), regulates multiple cellular processes and physiological responses. However, the precise mechanisms underlying PRL1`s multiple functions are unclear. Here, we show that PRL1 maintains actin integrity and concomitant cellular homeostasis. The cortical actin cytoskeleton was de-polymerized in the prl1 mutant, causing the developmental root defect. Actin depolymerization, rather than reactive oxygen species (ROS) imbalance, constituted the fundamental cause of retarded root growth in prl1. ANAC085 upregulation by, and cooperation with, actin depolymerization triggered stele cell death in prl1 roots. Differential gene expression and alternative splicing defects resulting from actin depolymerization occurred independently in prl1. Our work establishes the cause-effect relationships between actin depolymerization and downstream stress-related signals, revealing a novel function of PRL1 and enhancing the understanding of PRL`s functional mechanisms.

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

Abstract With the rapid development of 5G networks, the influence of the radiofrequency field (RF) generated from 5G communication equipment on human health is drawing increasing attention in public. The study aimed at assessing the effects of long-term exposure to 4.9 GHz (one of the working frequencies of 5G communication) RF field on fecal microbiome and metabolome profiles in adult male C57BL/6 mice. The animals were divided into Sham group and radiofrequency group (RF group). For RF group, the mice were whole body exposed to 4.9 GHz RF field for three weeks, 1 h/d, at average power density (PD) of 50 W/m2. After RF exposure, the mice fecal samples were collected to detect gut microorganisms and metabolites by 16S rRNA gene sequencing and LC–MS method, respectively. The results showed that intestinal microbial compositions were altered in RF group, as evidenced by reduced microbial diversity and changed microbial community distribution. Metabolomics profiling identified 258 significantly differentially abundant metabolites in RF group, 57 of which can be classified to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Besides, functional correlation analysis showed that changes in gut microbiota genera were significantly correlated with changes in fecal metabolites. In summary, the results suggested that altered gut microbiota and metabolic profile are associated with 4.9 GHz radiofrequency exposure.

Abstract Although chromatin organizations in plants have been dissected at the scales of compartments and topologically associating domain (TAD)-like domains, there remains a gap in resolving fine-scale structures. Here, we use Micro-C-XL, a high-throughput chromosome conformation capture (Hi-C)-based technology that involves micrococcal nuclease (instead of restriction enzymes) and long cross-linkers, to dissect single nucleosome-resolution chromatin organization in Arabidopsis. Insulation analysis reveals more than 14,000 boundaries, which mostly include chromatin accessibility, epigenetic modifications, and transcription factors. Micro-C-XL reveals associations between RNA Pols and local chromatin organizations, suggesting that gene transcription substantially contributes to the establishment of local chromatin domains. By perturbing Pol II both genetically and chemically at the gene level, we confirm its function in regulating chromatin organization. Visible loops and stripes are assigned to super-enhancers and their targeted genes, thus providing direct insights for the identification and mechanistic analysis of distal CREs and their working modes in plants. We further investigate possible factors regulating these chromatin loops. Subsequently, we expand Micro-C-XL to soybean and rice. In summary, we use Micro-C-XL for analyses of plants, which reveal fine-scale chromatin organization and enhancer-promoter loops and provide insights regarding three-dimensional genomes in plants.

Abstract Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA–miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.

Abstract Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13 H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.

Abstract Intrahepatic cholangiocarcinoma (ICC) is a rare but highly aggressive malignant tumor arising within the liver, with a 5-year survival rate of only 20–40% after surgery. The role of interleukin-8 (IL-8) in ICC progression remains elusive. A transcriptomic approach based on IL-8 stimulation first revealed significant upregulation of the prometastatic gene CD97 and key epithelial–mesenchymal transition (EMT) factors E-cadherin and vimentin. Immunohistochemistry of 125 ICC tissues confirmed the positive correlation between IL-8 and CD97. Multivariable Cox regression indicated that they are both independent predictors of ICC prognosis. Mechanistically, IL-8 treatment induced CD97 expression at 50 and 100 ng/ml in QBC-939 and QBE cells, respectively. Moreover, the induction of cell migration and invasion upon IL-8 treatment was attenuated by CD97 RNA interference, and the expression of EMT-associated genes was dramatically inhibited. To determine whether CXCR1 or CXCR2 are downstream effectors of IL-8, siCXCR2 was applied and shown to significantly attenuate the oncogenic effects of IL-8 by inhibiting the phosphorylation of PI3K/AKT. Finally, the induction of CD97 expression by the PI3K pathway was verified by treatment with the inhibitor LY294002. In vivo, the significant tumor growth and lung metastasis effects induced by intraperitoneal injection of IL-8 were greatly inhibited by silencing CD97 in nude mice. Collectively, the study presents a novel mechanism of the IL-8-CXCR2-PI3K/AKT axis in regulating CD97 expression, which leads to ICC metastasis mainly through EMT. The study may provide alternatives for targeting the tumor microenvironment in metastatic ICC.

Abstract To clarify the pathways and effects of the behavioral inhibition and activation systems in the relationship between exercise participation and depressive symptoms among college students. A cross-sectional research design was employed to survey 2606 college students using physical activity questionnaires, the Behavioral Inhibition/Activation Systems Scale, and the Beck Depression Inventory. Data were analyzed using methods including one-way ANOVA, independent sample t-tests, non-parametric tests, chi-square tests, correlation analysis, and structural equation modeling. Depressive symptoms were significantly negatively correlated with exercise participation (r = − 0.107, P

Abstract Leaf rust, caused by Puccinia triticina Eriksson (Pt), is one of the most severe foliar diseases of wheat. Breeding for leaf rust resistance is a practical and sustainable method to control this devastating disease. Here, we report the identification of Lr47, a broadly effective leaf rust resistance gene introgressed into wheat from Aegilops speltoides. Lr47 encodes a coiled-coil nucleotide-binding leucine-rich repeat protein that is both necessary and sufficient to confer Pt resistance, as demonstrated by loss-of-function mutations and transgenic complementation. Lr47 introgression lines with no or reduced linkage drag are generated using the Pairing homoeologous1 mutation, and a diagnostic molecular marker for Lr47 is developed. The coiled-coil domain of the Lr47 protein is unable to induce cell death, nor does it have self-protein interaction. The cloning of Lr47 expands the number of leaf rust resistance genes that can be incorporated into multigene transgenic cassettes to control this devastating disease.

Abstract The combined effect of obesity and metabolic abnormalities on liver injury is unclear. Aiming to address this knowledge gap, this cross-sectional study was conducted among 16,201 US adults. Multiple linear regression and logistic regression analyses were conducted to assess the associations of obesity profiles, metabolic health status, and weight change with the levels of liver enzymes. The analysis revealed that general obesity and abdominal obesity were positively associated with the levels of liver enzymes and the prevalence of abnormal liver enzymes (P and P trend

Abstract Inflammation‐responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)‐responsive injectable hydrogel is constructed by integrating an MMP‐cleavable peptide (pp) into a covalent tetra‐armed poly‐(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro‐regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG‐pp‐PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG‐pp‐PS to transform macrophages into the anti‐inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell‐free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.

Abstract The formation of helium bubbles and subsequent property degradation poses a significant challenge to tungsten as a plasma-facing material in future long-pulse plasma-burning fusion reactors. In this study, we investigated helium bubble formation in dispersion-strengthened tungsten doped with transition metal carbides, including TaC, ZrC, and TiC. Of the three dispersoids, TaC exhibited the highest resistance to helium bubble formation, possibly due to the low vacancy mobility in the Group VB metal carbide and oxide phases. Under identical irradiation conditions, large helium bubbles formed at grain boundaries in tungsten, while no bubbles were observed at the interfaces between the carbide dispersoid and tungsten matrix. Moreover, our results showed the interfaces could suppress helium bubble formation in the nearby tungsten matrix, suggesting that the interfaces are more effective in trapping helium as tiny clusters. Our research provided new insights into optimizing the microstructure of dispersion-strengthened tungsten alloys to enhance their performance.

Abstract To explore the association between depression and anxiety symptoms among college students and the relationship between the two and physical activity. A cross-sectional study design was used to survey 1790 enrolled university students using the Depression Self-Rating Scale, Anxiety Self-Rating Scale and Physical Activity Rating Scale. 37.75% of male students and 39.73% of female students detected depressive symptoms, 17.65% of male students and 17.86% of female students detected anxiety symptoms, 11.89% of male students and 11.75% of female students detected both depressive and anxiety symptoms. Canonical correlation between depression and anxiety symptoms of college students were significant. The depression and anxiety score of college students in the high level group was significantly lower than that in the low and medium level groups, and no significant difference was found between the low and medium level groups. Affective disorder and anxious mood of male students correlated most closely with intensity, while somatic disorder, psychomotor disorder and depressive psychological disorder correlated most closely with duration. Affective disorder of female students correlated most closely with frequency, depressive psychological disorder and anxious mood correlated most closely with intensity, while premonition of misfortune and frequent urination correlated most closely with duration. Depression and anxiety symptoms of college students were closely related and co-occurrence was common. Students with high level of physical activity had milder symptoms. Different exercise interventions are recommended for different symptoms.

Abstract We will use micro-computed tomography to scan 31 sets of the adult lower cervical vertebrae (155 vertebrae) to observe the morphological characteristics and direction of trabeculae in the lower cervical vertebrae by outlining and reconstructing the regions of interest and to calculate the variation laws of the microstructure in the regions of interest to reveal their structural characteristics and weak areas. As a result, the images showed that the trabeculae in the lower cervical pedicle near the medial and lateral cortices were relatively dense, and their bone plates were lamellar. There were cavities between the superior and inferior articular processes where the ossification centers had not been absorbed after ossified. The lamellar trabeculae in the vertebral plates near the cortical bones were only 1–2 layers, extended and transformed into rod-shaped trabeculae in a radial shape toward the medullary space. The lamellar trabeculae of the vertebral plate extend over the spinous process near the cortical bone. The statistical results of the trabeculae's morphological parameters showed significant differences in bone volume fraction values among the four parts (P

Real-time remote sensing segmentation technology is crucial for unmanned aerial vehicles (UAVs) in battlefield surveillance, land characterization observation, earthquake disaster assessment, etc., and can significantly enhance the application value of UAVs in military and civilian fields. To realize this potential, it is essential to develop real-time semantic segmentation methods that can be applied to resource-limited platforms, such as edge devices. The majority of mainstream real-time semantic segmentation methods rely on convolutional neural networks (CNNs) and transformers. However, CNNs cannot effectively capture long-range dependencies, while transformers have high computational complexity. This paper proposes a novel remote sensing Mamba architecture for real-time segmentation tasks in remote sensing, named RTMamba. Specifically, the backbone utilizes a Visual State-Space (VSS) block to extract deep features and maintains linear computational complexity, thereby capturing long-range contextual information. Additionally, a novel Inverted Triangle Pyramid Pooling (ITP) module is incorporated into the decoder. The ITP module can effectively filter redundant feature information and enhance the perception of objects and their boundaries in remote sensing images. Extensive experiments were conducted on three challenging aerial remote sensing segmentation benchmarks, including Vaihingen, Potsdam, and LoveDA. The results show that RTMamba achieves competitive performance advantages in terms of segmentation accuracy and inference speed compared to state-of-the-art CNN and transformer methods. To further validate the deployment potential of the model on embedded devices with limited resources, such as UAVs, we conducted tests on the Jetson AGX Orin edge device. The experimental results demonstrate that RTMamba achieves impressive real-time segmentation performance.

BackgroundGastric cancer (GC) is a highly malignant gastrointestinal tumor characterized by difficult early diagnosis and poor prognosis. Therefore, it is imperative to explore potential therapeutic targets for gastric cancer. PARP9 is abnormally expressed in a variety of tumors and is associated with tumor cell apoptosis and DNA damage. However, its relationship with GC has not been fully studied.MethodsThe expression and prognostic significance of PARP9 in gastric cancer (GC) were examined using bioinformatics approaches. Cell lines with either knockdown or overexpression of PARP9 were established through lentiviral transduction, and the role of PARP9 in the malignant phenotypes of GC cells was validated via CCK8 assays, wound healing assays, clonogenic assays, and Transwell migration experiments. Finally, alterations in downstream targets and signaling pathways following changes in PARP9 expression were analyzed through RNA sequencing.ResultsPARP9 is highly expressed in GC tissues and is associated with poor prognosis. PARP9 knockdown can significantly inhibit the proliferation, invasion and migration of GC cells, and increase the apoptosis and DNA damage of GC cells. The therapeutic process of PARP9 in GC may be realized by synergistic interaction with SOX6 through MAPK signaling pathway.ConclusionsOur study reveals a potential link between PARP9 and GC, providing a new target for the treatment of GC.

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

China’s first Mars exploration mission, Tianwen-1, successfully landed in southern Utopia Planitia on Mars on May 15, 2021. This work presents a detailed investigation of the geologic context of the landing area surface for this mission based on orbital remote-sensing data. We constructed a geomorphologic map for the Tianwen-1 landing area. Results of our detailed geomorphologic map show several major landforms within the landing area, including rampart craters, mesas, troughs, cones, and ridges. Analysis of materials on the landing area surface indicates that most of the landing area is covered by Martian dust. Transverse aeolian ridges are widely distributed within the landing area, indicating the surface contexts were (and still are) modified by regional winds. In addition, a crater counting analysis indicates the landing area has an absolute model age of ~3.3 Ga and that a later resurfacing event occurred at ~1.6 Ga. Finally, we outline four formational scenarios to test the formation mechanisms for the geomorphologic features on the landing area surface. The most likely interpretation to explain the existence of the observed surface features can be summarized as follows: A thermal influence may have played an important role in the formation of the surface geomorphologic features; thus, igneous-related processes may have occurred in the landing area. Water ice may also have been involved in the construction of the primordial surface configuration. Subsequent resurfacing events and aeolian processes buried and modified the primordial surface.

The small, relict-like moth family Endromidae is well-established within the superfamily Bombycoidea, but relationships within the family have remained vague for the last decade, primarily due to very limited taxon sampling. This resulted in the explicit removal of all internal suprageneric classification by Zwick et al. (2011) when they synonymized Mirinidae and the bombycid subfamilies Oberthueriinae and Prismostictinae with Endromidae. Nucleotide and amino acid data sets of the 13 mitochondrial, protein-coding genes from representatives of 13 of the 16 accepted endromid genera were used to estimate phylogenetic relationships based on maximum likelihood and Bayesian inference methods. The results strongly support Endromidae as a monophyletic group and enable the establishment and diagnosis of four subfamilies (Endrominae, Mirininae stat. rev., Oberthueriinae stat. rev. and Prismostictinae stat. rev.). Within subfamily Oberthueriinae, we establish three tribes: Oberthueriini stat. rev., Andracini tribe nov. and Mustiliini tribe nov. We provide morphological diagnoses and a genus-level checklist for the three tribes. Promustilia yajiangensis Wang, X. & Zolotuhin, 2015 is transferred to Mustilizans as M. yajiangensis comb. nov. to establish reciprocal monophyly of the two genera, and Andraca gongshanensis is transferred to Pseudandraca as P. gongshanensis comb. nov. We also synonymize Andraca (Chrypathemola) syn. nov. with Andraca (Andraca), as the latter is deeply nested within the former.

The South Atlantic Anomaly (SAA) is a region where the geomagnetic field is significantly lower than that of the surrounding area. On the basis of the models of CHAOS-7.8, Mass Spectrometer Incoherent Scatter Model (NRLMSISE-00), and International Reference Ionosphere 2016 (IRI-2016), we theoretically investigated the lower and upper boundaries of the ionospheric dynamo region inside the SAA. In the ionospheric dynamo region, electrons are coupled with magnetic field lines, whereas ions are decoupled from magnetic field lines. Our results showed that the ionospheric dynamo region inside the SAA is higher and larger than that outside the SAA. We also studied the boundary variations of the dynamo region inside the SAA depending on the seasons and solar activities. We found that the dynamo region inside the SAA is the highest and largest in the summer of the southern hemisphere at solar maximum. The larger and higher altitude range of the ionospheric dynamo region in the SAA can contribute to the stronger ionospheric currents in this region.

Dehazing individual remote sensing (RS) images is an effective approach to enhance the quality of hazy remote sensing imagery. However, current dehazing methods exhibit substantial systemic and computational complexity. Such complexity not only hampers the straightforward analysis and comparison of these methods but also undermines their practical effectiveness on actual data, attributed to the overtraining and overfitting of model parameters. To mitigate these issues, we introduce a novel dehazing network for non-uniformly hazy RS images: GLUENet, designed for both lightweightness and computational efficiency. Our approach commences with the implementation of the classical U-Net, integrated with both local and global residuals, establishing a robust base for the extraction of multi-scale information. Subsequently, we construct basic convolutional blocks using gated linear units and efficient channel attention, incorporating depth-separable convolutional layers to efficiently aggregate spatial information and transform features. Additionally, we introduce a fusion block based on efficient channel attention, facilitating the fusion of information from different stages in both encoding and decoding to enhance the recovery of texture details. GLUENet’s efficacy was evaluated using both synthetic and real remote sensing dehazing datasets, providing a comprehensive assessment of its performance. The experimental results demonstrate that GLUENet’s performance is on par with state-of-the-art (SOTA) methods and surpasses the SOTA methods on our proposed real remote sensing dataset. Our method on the real remote sensing dehazing dataset has an improvement of 0.31 dB for the PSNR metric and 0.13 for the SSIM metric, and the number of parameters and computations of the model are much lower than the optimal method.

Abstract Despite many studies have revealed that developing honey bee (Apis mellifera) larvae are posting a high risk on exposure to insecticides, the toxicology information on bee larvae remain limited. The present study demonstrated the first assessment of the effects of no observed adverse effect concentration (NOAEC) of carbaryl (CR) and acetamiprid (ACE) on transcriptome and metabolome in honeybee larvae reared in vitro. Chronic exposure to carbaryl caused transcriptional disorders associated with oxidative stress. In addition, a series of metabolic homeostasis were disrupted by carbaryl stress, such amino acid metabolism, purine and pyrimidine metabolism and flavone and flavonol biosynthesis. The activities of enzymic biomarkers including GST, P450, CAT, AChE and SOD were not influenced by ACE stress, while the CR exposure slightly decreased the activity of CAT and SOD. Our results clearly show that ACE and CR display different potential to modulate transcriptome and metabolome associated with their different toxicity against bee larvae.

Laboratory spectroscopic and X-ray diffraction analyses on the Chang’E-5 lunar soil samples have demonstrated that the spectral features of lunar late-stage mare basalts are representative of iron-rich high-Ca pyroxene rather than olivine.

Summary: Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells in vitro. Furthermore, I1-MMAE and I1-DXd mediated a potent tumor regression in ATC and PTC xenograft models. To develop a precision medicine, we also explored magnetic resonance imaging (MRI) as a non-invasive biomarker detection method to quantitatively map ICAM1 antigen expression in heterogeneous thyroid tumors. Taken together, this study provides a strong rationale for the further development of I1-MMAE and I1-DXd as promising therapeutic candidates to treat advanced PTC and ATC.

Summary: Heterosis is an important genetic phenomenon that has been observed and widely utilized in agriculture. However, the genetic and molecular bases of heterosis are unclear. Through transcriptome-wide association studies (TWAS) and expression quantitative trait locus (eQTL) analysis to integrate genome, transcriptome, and heterotic phenotype of a half-sibling Arabidopsis hybrid population, we report that the genetic and molecular bases of variations in leaf growth heterosis can be explained by the varied expression levels of growth-regulating genes resulting from distinct sets of heterozygous eQTLs carried by the half-sibling hybrids. In F1 versus parent, the degree of up-regulated gene expression in the cell cycle pathway in the shoot apex and the photosynthesis pathway in true leaf positively correlates with true leaf area heterosis level, and this is affected by the accumulation of superior heterozygous eQTLs. This was further corroborated by the major contribution of increased photosynthetic cell number to leaf area heterosis.

Abstract Catalytically inactive CRISPR‐Cas13 (dCas13)‐based base editors can achieve the conversion of adenine‐to‐inosine (A‐to‐I) or cytidine‐to‐uridine (C‐to‐U) at the RNA level, however, the large size of dCas13 protein limits its in vivo applications. Here, a compact and efficient RNA base editor (ceRBE) is reported with high in vivo editing efficiency. The larger dCas13 protein is replaced with a 199‐amino acid EcCas6e protein, derived from the Class 1 CRISPR family involved in pre‐crRNA processing, and conducted optimization for toxicity and editing efficiency. The ceRBE efficiently achieves both A‐to‐I and C‐to‐U base editing with low transcriptome off‐target in HEK293T cells. The efficient repair of the DMD Q1392X mutation (68.3±10.1%) is also demonstrated in a humanized mouse model of Duchenne muscular dystrophy (DMD) after AAV delivery, achieving restoration of expression for gene products. The study supports that the compact and efficient ceRBE has great potential for treating genetic diseases.

Nanoscale emitters are useful for measuring biomolecular interactions, but are limited by weak signals. Here, the authors use a photonic crystal surface for 3000-fold signal enhancement, achieving single emitter sensitivity with extended on-time, and demonstrate its application in miRNA biomarker sensing.

The development of non-invasive, rapid responsive phosphorescence is highly desirable but has rarely been described. Herein, the authors designed and prepare a series of molecular rotors containing a room temperature phosphorescence active triazine core and three bromobiphenyl units acting as rotors and demonstrate light stimulus triggered phosphorescence.

Model systems to study SARS-CoV-2 infection are required to better understand the immune response. Here the authors use a lung and macrophage co-culture system by differentiation of human pluripotent stem cells to better understand the phenotype and gene expression changes in host lung cells and macrophages after SARS-CoV-2 infection in vitro.

Abstract The doubly labelled water (DLW) method is widely used to determine energy expenditure. In this work, we demonstrate the addition of the third stable isotope, 17O, to turn it into triply labelled water (TLW), using the three isotopes measurement of optical spectrometry. We performed TLW (2H, 18O and17O) measurements for the analysis of the CO2 production (rCO2) of mice on different diets for the first time. Triply highly enriched water was injected into mice, and the isotope enrichments of the distilled blood samples of one initial and two finals were measured by an off-axis integrated cavity output spectroscopy instrument. We evaluated the impact of different calculation protocols and the values of evaporative water loss fraction. We found that the dilution space and turnover rates of 17O and 18O were equal for the same mice group, and that values of rCO2 calculated based on 18O–2H, or on 17O–2H agreed very well. This increases the reliability and redundancy of the measurements and it lowers the uncertainty in the calculated rCO2 to 3% when taking the average of two DLW methods. However, the TLW method overestimated the rCO2 compared to the indirect calorimetry measurements that we also performed, much more for the mice on a high-fat diet than for low-fat. We hypothesize an extra loss or exchange mechanism with a high fractionation for 2H to explain this difference.