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This study investigated the spatiotemporal evolution of the temperature field of paddy in quasi- low-temperature storage in flat stores using experimental research and numerical simulation. he evolution pattern of the paddy temperature field was derived from a 14-month grain temperature experiment in quasi-low-temperature storage. A numerical model of the temperature field in quasi-low-temperature storage was developed and validated against experimental results. Finally, the temperature profile of paddy over 26 months was predicted by the proposed numerical model. The conclusion can be expressed as follows: During the 14-month experimental period，the overall average temperature of paddy remained below 17 ℃, with a maximum of 15.57 ℃ and a minimum of 11.32 ℃. The 26-month quasi-low temperature storage period in the storehouse was simulated by using the above model. The simulation results showed that the overall average temperature of paddy gradually increased but remained below 17 ℃. The monthly average maximum grain temperature occurred in September each year, with values of 14.85 ℃ and 15.34 ℃ in the first and second years, respectively. Similarly, the highest surface grain temperatures, 15.3 ℃ and 15.8 ℃, were also recorded in September. The evolutionary rule of the paddy temperature field, as elucidated in this paper, offers theoretical support for the quasi-low temperature storage of paddy in storehouses.

RBOE is a new type of DNAN-based high-energy melt-cast mixed explosive, whose safety under thermal stimulation is significantly affected by heating conditions and venting area of the warhead. Based on the thermal decomposition reaction characteristics and combustion characteristics of each component of RBOE explosive, the cook-off calculation models of RBOE warhead before and after ignition were established. In addition, closed and vented warheads were designed, as well as fast and slow cook-off test devices. The cook-off characteristics and thermal safety venting area of RBOE warhead were extensively studied. The results showed that the closed RBOE warhead underwent deflagration reaction under both slow and fast cook-off conditions. The calculation result of the shell wall temperature before slow cook-off ignition response of the warhead was 454.06 K, with an error of +1.75% compared to the test result of 462.15 K, and the temperature rise rate calculated was in good agreement with the test. The calculated ignition time of RBOE warhead under fast cook-off was 161 s, with an error of +8.8% compared to the test result of 148 s, which verified the accuracy of cook-off model of RBOE warhead before ignition. According to the cook-off calculation model of the warhead after ignition and cook-off test of the vented warhead, it was determined that the thermal safety venting area was 1124.61 mm2 for fast cook-off and 530.66 mm2 for slow cook-off, effectively preventing the reaction of warhead above combustion. Therefore, this study provides a scientific basis for the thermal safety design and evaluation of insensitive warheads.

Abstract Background Case-Based Learning (CBL) and Problem-Based Learning (PBL) are popular methods in medical education. However, we do not fully understand how they affect the clinical thinking skills of Assistant General Practitioner (AGP) trainees. This randomised controlled trial aimed to assess the effectiveness of combining CBL and PBL and compare their impact on the clinical thinking skills of AGP trainees with that of traditional lecture-based learning (LBL). Methods This randomised controlled trial involved 70 second-year AGP trainees who were randomly assigned to either the CBL-PBL group or the LBL group using a simple randomisation method. The CBL-PBL group engaged in a curriculum that integrated case-based and problem-based learning, whereas the LBL group followed a traditional lecture-based format, as described in the syllabus. To evaluate clinical thinking skills, the participants were assessed using the Clinical Thinking Skills Evaluation Scale (CTSES) and an assistant general practitioner’s professional knowledge test. In addition, this study analysed various factors that influence clinical thinking skills. Results Compared with the LBL group, the CBL-PBL group showed significantly improved performance in all domains assessed by the CTSES in post-course tests (p

Abstract Objective Osteoporosis increases the risk of fragility fractures, impacting patients’ lives. This study aimed to investigate whether LINC01271 was involved in the process of fragility fractures and healing, providing a new perspective for its diagnosis and treatment. Methods This study included 94 healthy individuals, 82 patients with osteoporosis, and 85 patients with fragility fractures as subjects. RT-qPCR was used to measure the levels of LINC01271, miR-19a-3p, PIK3CA, and osteogenic differentiation markers in osteoblasts and subjects’ serum. Luciferase reporter assays, RIP experiments, and RNA pull-down assays were utilized to verify the target relationships between LINC01271 and miR-19a-3p, as well as between miR-19a-3p and PIK3CA. Cell proliferation and apoptosis were assessed using CCK-8 assays and flow cytometry. Results Compared to the healthy control group, the serum levels of LINC01271 were significantly reduced in patients with osteoporosis and fragility fractures. Furthermore, LINC01271 levels increased with time-dependent fracture healing. In vitro studies indicated that LINC01271 boosted osteoblast proliferation, inhibited apoptosis, and augmented osteogenic differences, whereas its inhibition reverses their effects. LINC01271 and PIK3CA were identified as targets of miR-19a-3p, and overexpression of miR-19a-3p could antagonize the effect of LINC01271 in promoting fracture healing. Conclusion The results indicated that LINC01271 may play a key role in osteoblast function and fracture healing through its interaction with miR-19a-3p and regulation of PIK3CA.

Abstract Background Non-isolated auditory neuropathy (AN), or syndromic AN, is marked by AN along with additional systemic manifestations. The diagnostic process is challenging due to its varied symptoms and overlap with other syndromes. This study focuses on two mitochondrial function-related genes which result in non-isolated AN, FDXR and TWNK, providing a summary and enrichment analysis of genes associated with non-isolated AN to elucidate the genotype-phenotype correlation and underlying mechanisms. Methods Seven independent Chinese Han patients with mutations in FDXR and TWNK underwent comprehensive clinical evaluations, genetic testing, and bioinformatics analyses. Diagnostic assessments included auditory brainstem response and distortion product otoacoustic emissions, supplemented by other examinations. Whole exome sequencing and Sanger sequencing validated genetic findings. Pathogenicity was assessed following American College of Medical Genetics and Genomics guidelines. Genes associated with non-isolated AN were summarized from prior reports, and functional enrichment analysis was conducted using Gene Ontology databases. Results A total of 11 variants linked to non-isolated AN were identified in this study, eight of which were novel. Patients’ age of hearing loss onset ranged from 2 to 25 years, averaging 11 years. Hearing loss varied from mild to profound, with 57.1%(4/7) of patients having risk factors and 71.4%(5/7) exhibiting additional systemic symptoms such as muscle weakness, ataxia, and high arches. Functional enrichment analysis revealed that genes associated with non-isolated AN predominantly involve mitochondrial processes, affecting the central and peripheral nervous, musculoskeletal, and visual systems. Conclusion This study identifies novel mutations in FDXR and TWNK that contribute to non-isolated AN through mitochondrial dysfunction. The findings highlight the role of mitochondrial processes in non-isolated AN, suggesting potential relevance as biomarkers for neurodegenerative diseases. Further research is required to explore these mechanisms and potential therapies. Graphical Abstract

In this paper, composite trapezoidal quadrature for numerical evaluation of hypersingular integrals was first introduced. By Taylor expansion at the singular point $ y $, error functional was obtained. We know that the divergence rate of $ O(h^{-p}), p = 1, 2 $, and there were no roots of the special function for the first part in the error functional. Meanwhile, for the second part of the error functional, the divergence rate was $ O(h^{-p+1}), p = 1, 2 $, but there were roots of the special function. We proved that the convergence rate could reach $ O(h^{2}) $ at superconvergence points far from the end of the interval. Two modified trapezoidal quadratures are presented and their convergence rate can reach $ O(h^{2}) $ at certain superconvergence points or any local coordinate point. At last, several examples were presented to test our theorem.

Abstract Growth Differentiation Factor-15 (GDF-15) is a pleiotropic cytokine that plays a significant role in metabolism and inflammation. Elevated serum levels of GDF-15 have been associated with mood disorders. We propose that GDF-15 may potentially influence cognitive impairment and metabolism in male patients with chronic schizophrenia (CS), although there is limited research on this topic. This study compared serum GDF-15 levels in 72 male patients with CS and 85 healthy controls (HC). The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), while cognitive performance was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The male CS patients performed worse than the healthy controls in both the total score and all subscales of the RBANS. Serum GDF-15 concentrations were significantly higher in the male CS patients compared to the healthy controls. Furthermore, the log-transformed serum GDF-15 concentrations in male CS patients were positively correlated with BMI and negatively correlated with Delayed Memory scores, Immediate Memory, and the total RBANS score. This preliminary study suggests that elevated serum GDF-15 levels in male patients with chronic schizophrenia may play a role in cognitive function and BMI regulation.

Abstract Background Liver metastasis from colorectal cancer (CRC) is a major clinical challenge that severely affects patient survival. myofibroblastic cancer-associated fibroblasts (myCAFs) are a major component of the CRC tumor microenvironment, where they contribute to tumor progression and metastasis through exosomes. Methods Single-cell analysis highlighted a notable increase in myCAFs in colorectal cancer liver metastases (CRLM). Exosomal sequencing identified PWAR6 as the most significantly elevated lncRNA in these metastatic tissues. In vivo and in vitro assays confirmed PWAR6's roles in CRC cell stemness, migration, and glutamine uptake. RNA pulldown, RIP, and Co-IP assays investigated the molecular mechanisms of the PWAR6/NRF2/SLC38A2 signaling axis in CRC progression, flow cytometry was used to assess NK cell activity and cytotoxicity. Results Clinically, higher PWAR6 expression levels are strongly associated with increased 68Ga FAPI-PET/CT SUVmax values, particularly in CRLM patients, where expression significantly exceeds that of non-LM cases and normal colon tissues. Regression analysis and survival data further support PWAR6 as a negative prognostic marker, with elevated levels correlating with worse patient outcomes. Mechanistically, PWAR6 promotes immune evasion by inhibiting NRF2 degradation through competitive binding with Keap1, thereby upregulating SLC38A2 expression, which enhances glutamine uptake in CRC cells and depletes glutamine availability for NK cells. Conclusion myCAFs derived exosomes PWAR6 represents a pivotal marker for CRC liver metastasis, and its targeted inhibition with ASO-PWAR6, in combination with FAPI treatment, effectively curtails metastasis in preclinical models, offering promising therapeutic potential for clinical management. Graphical abstract

Abstract Traumatic brain injury (TBI) is one of the leading public health concerns in the world. Therapeutic hypothermia is routinely used in severe TBI, and pathophysiological hyperthermia, frequently observed in TBI patients, has an unclear impact on drug transport in the injured brain due to a lack of study on its effects. We investigated the effect of post-traumatic therapeutic hypothermia at 33°C and pathophysiological hyperthermia at 39°C on brain transport and cell uptake of neuroprotectants after TBI. Recombinant high-density lipoprotein (rHDL), which possesses anti-inflammatory, antioxidant activity, and blood–brain barrier (BBB) permeability, was chosen as the model drug. First, we found that mild hypothermia and hyperthermia impaired rHDL transport to the brain and lesion targeting in controlled cortical impact mice. Second, we investigated the temperature-induced rHDL uptake shift by various brain cell types. Mild hypothermia impeded the uptake of rHDL by endothelial cells, neurons, microglia, and astrocytes. Hyperthermia impeded the uptake of rHDL by endothelial cells and neurons while promoting its uptake by microglia and astrocytes. In an attempt to understand the mechanisms behind the above phenomena, it was found that temperature induced brain-intake shift of rHDL through the regulation of low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1) stability in brain cells. We therefore reported the full view of the temperature-induced brain-intake shift of rHDL after TBI for the first time. It would be of help in coordinating pharmacotherapy with temperature management in individualization and precision medicine. Graphical Abstract

Abstract The infantile neuronal ceroid lipofuscinosis, also called CLN1 disease, is a fatal neurodegenerative disease caused by mutations in the CLN1 gene encoding palmitoyl protein thioesterase 1 (PPT1). Identifying the depalmitoylation substrates of PPT1 is crucial for understanding CLN1 disease. In this study, we found that GABAAR, the critical synaptic protein essential for inhibitory neurotransmission, is a substrate of PPT1. PPT1 depalmitoylates GABAAR α1 subunit at Cystein-260, while binding to Cystein-165 and -179. Mutations of PPT1 or its GABAAR α1 subunit binding site enhanced inhibitory synaptic transmission and strengthened oscillations powers but disrupted phase coupling in CA1 region and impaired learning and memory in 1- to 2-months-old PPT1-deficient and Gabra1 em1 mice. Our study highlights the critical role of PPT1 in maintaining GABAAR palmitoylation homeostasis and reveals a previously unknown molecular pathway in CLN1 diseases induced by PPT1 mutations.

Rice is a major crop susceptible to chilling stress. The identification of quantitative trait loci and genes for cold tolerance is crucial for the rice breeding. Of 30 quantitative-trait loci affecting seedling cold tolerance identified in a genome-wide association study of 540 rice accessions, OsbZIP72 was assigned as the causative gene for one, qCTS9.1. A single-nucleotide polymorphism in its promoter accounted for variation in expression between indica and japonica subspecies. The favorable haplotype of OsbZIP72 originated in wild rice and contributed to the expansion of japonica rice to colder habitats. OsbZIP72 positively regulates genes coding reactive oxygen species (ROS)-scavenging proteins and maintains intracellular ROS homeostasis. These findings not only enhanced our understanding of environmental adaptation but also provide novel genetic resources and potential targets for molecular design breeding for cold tolerance in rice.

Abstract This analysis revealed the alterations in the pore structure of large organic molecules in coal during the process of coal pyrolysis. Nine models of macromolecular structures in coals, representing distinct coal ranks, have been built. The research results show that along with the increasing coal rank, the average microporous volume of medium rank coal is 0.0287 cm3/g. The average microporous volume of high-grade coal is 0.0662 cm3/g. The micropore volume and specific surface area of coal samples decrease in the order of high rank, low rank, and middle coal. The experimental measurements align with the ReaxFF pyrolysis simulation calculations, indicating a decrease in the hydrogen to carbon ratio and oxygen to carbon ratio of all coal molecules. Additionally, the pore volume and specific surface area exhibit a pattern of initially decreasing and then increasing. The simulation results of gas probes indicate that a majority of the pores with a diameter larger than that of CH4 molecules are found in the macromolecular structure models of low rank coal and medium to high rank coal. The conclusions are useful for us to understand the formation and development process of pores in coal reservoir. A two-dimensional representation of coal’s macromolecular structure was constructed using ChemDraw software. The Forcite module in Materials Studio software was used to perform geometric optimization and annealing kinetics simulation of a two-dimensional macromolecular structure model. The ReaxFF-MD module in Amsterdam Modeling Suite (AMS) 2020 software to model the pyrolysis of XJ coal macromolecules.

Abstract Metasurface with natural static structure limits the development of dynamic metasurface holographic display with rapid response and broadband. Currently, liquid crystal (LC) was integrated onto the metasurface to convert the passive metasuface into an active one. But, majority of LC-assisted active metasurfaces often exhibit trade-offs among degree of freedom (DoF, typically less than 2), information capacity, response speed, and crosstalk. Herein, at first time, we experimentally demonstrate a cascaded device with polymer dispersed liquid crystal (PDLC) and broadband metasurface, enabling dynamic three-dimensional (3D) holographic display with ultra-high contrast, rapid response and continuous regulation. The PDLC droplets enable modulation of scattering state of incident light by high-speed dynamic control system for electric scanning. Based on self-addressing, rapid response and multi-channel PDLC-metasurface device, the dynamic holographic effect of monochrome holographic images switching and color-changing holographic display with broadband, low-crosstalk and high contrast, has been achieved. Our approach offers a novel perspective on dynamic metasurface.

Abstract Background Renal CD8+ tissue-resident memory T (TRM) cells display prolonged survival and activity in lupus nephritis (LN), exacerbating renal pathology. NLRP3 regulates the T cell response. This study explored the impact of NLRP3 inflammasome activity on the regulatory functions of TRM cells in LN. Methods NLRP3 inflammasome activity in renal CD8+ TRM cells from lupus-prone MRL/lpr mice and in vitro induced human CD8+CD103+ T cells was assessed by quantifying NLRP3, caspase-1, gasdermin D (GSDMD), and IL-1β levels using flow cytometry, ELISA, and western blotting analysis. The specific NLRP3 inhibitor MCC950, caspase-1 inhibitor Ac-YVAD-cmk, and NF-κB inhibitor JSH23 were utilized to delineate the role of NLRP3 in modulating the pathogenicity of CD8+ TRM cells in LN. Results Activation of the NLRP3 inflammasome was confirmed in renal CD8+CD69+CD103+ TRM cells derived from mice with LN and in vitro-induced human CD8+CD103+ TRM-like cells. MCC950 curtailed the infiltration and activity of CD8+CD69+CD103+ TRM cells and enhanced renal outcomes. MCC950 also suppressed the maturation and functional capabilities of CD8+CD103+ T cells in a manner reliant on inflammasome activity in vitro. IL-1β promoted the expression of TGF-βRII in CD8+ T cells via the NF-κB pathway. Conclusions NLRP3 inflammasome activity in renal CD8+CD69+CD103+ TRM cells contributes to LN pathogenesis by regulating cell differentiation and effector functions. Therapeutically targeting the NLRP3 inflammasome could significantly mitigate CD8+CD69+CD103+ TRM cell-mediated renal damage in LN.

Abstract Background The longitudinal vaginal septum and oblique vaginal septum are female müllerian duct anomalies that are relatively less diagnosed but severely fertility-threatening in clinical practice. Ultrasound imaging is commonly used to examine the two vaginal malformations, but in fact it’s difficult to make an accurate differential diagnosis. This study is intended to assess the performance of multiple deep learning models based on ultrasonographic images for distinguishing longitudinal vaginal septum and oblique vaginal septum. Methods The cases and ultrasound images of longitudinal vaginal septum and oblique vaginal septum were collected. Two convolutional neural network (CNN)-based models (ResNet50 and ConvNeXt-B) and one base resolution variant of vision transformer (ViT)-based neural network (ViT-B/16) were selected to construct ultrasonographic classification models. The receiver operating curve analysis and four indicators including accuracy, sensitivity, specificity and area under the curve (AUC) were used to compare the diagnostic performance of deep learning models. Results A total of 70 cases with 426 ultrasound images were included for deep learning models construction using 5-fold cross-validation. Convolutional neural network-based models (ResNet50 and ConvNeXt-B) presented significantly better case-level discriminative efficacy with accuracy of 0.842 (variance, 0.004, 95%CI, [0.639–0.997]) and 0.897 (variance, 0.004, [95%CI, 0.734-1.000]), specificity of 0.709 (variance, 0.041, [95%CI, 0.505–0.905]) and 0.811 (variance, 0.017, [95%CI, 0.622–0.979]), and AUC of 0.842 (variance, 0.004, [95%CI, 0.639–0.997]) and 0.897 (variance, 0.004, [95%CI, 0.734-1.000]) than transformer-based model (ViT-B/16) with its accuracy of 0.668 (variance, 0.014, [95%CI, 0.407–0.920]), specificity of 0.572 (variance, 0.024, [95%CI, 0.304–0.831]) and AUC of 0.681 (variance, 0.030, [95%CI, 0.434–0.908]). There was no significance of AUC between ConvNeXt-B and ResNet50 (P = 0.841). Conclusions Convolutional neural network-based model (ConvNeXt-B) shows promising capability of discriminating longitudinal and oblique vaginal septa ultrasound images and is expected to be introduced to clinical ultrasonographic diagnostic system.

Objective and MethodsThis study aims to investigate the characteristics of CO2 biomethanation and coal gasification through microbial degradation in a low-pressure environment. With low-rank bituminous coals (Rmax = 0.67%) as fermentable substrates, this study conducted a 96-day gas production experiment through microbial fermentation in a low-pressure CO2 and H2 environment. Using techniques including gas chromatography, 16S rRNA gene sequencing, and low-temperature liquid nitrogen adsorption, this study delved into the intrinsic variation patterns of biogenic gas production, microbial communities, and coal structures. Results and Conclusions The results indicate that compared to conventional fermentation, the injection of low-pressure CO2 inhibited CH4 production, leading to a reduced CH4 production efficiency. After the H2 injection, the injected H2 was consumed quickly, resulting in a rapid decrease in the H2 concentration and contributing to CH4 production. Meanwhile, the H2 injection changed the production mode of biogenic gas, exerting a profound influence on the structure of microbial communities in fermentable liquids. Specifically, the relative abundance of Firmicutes and Bacteroidota increased. Notably, the S50_wastewater_sludge_group in Bacteroidota always predominated, trending upward together with the unclassified_W27 genus. This occurred due to the late-stage H2 injection, which accelerated the growth and metabolism of both bacterial genera. Regarding the distribution of archaea at the genus level, Methanobacterium represented the highest proportion (47.66%‒83.05%), followed by Methanosarcina and Methanoculleus sequentially. Benefiting from the simultaneous consumption of H2, CO2, and substrates such as acetic acid, the relative abundance of Methanosarcina exhibited a significant upward trend. In contrast, Methanoculleus, which synthesizes methane via the hydrogenotrophic pathway, displayed a rapidly decreasing relative abundance due to a shortage of H2 in the later stage. Compared to the raw coals, coals with injected low-pressure CO2 exhibited a lower adsorption capacity, with the total pore volume and specific surface area decreasing. As more low-pressure CO2 was injected, fractal dimensions D1 and D2 trended downward and upward, respectively, suggesting an increase in the surface roughness of coal pores and a decrease in the complexity/heterogeneity of pore structures. This is inferred to be associated with the dual effects of microbial degradation and carbonate precipitation. The results of this study enrich the fundamental theories on the microbial degradation of coals and the biological transformation and utilization of CO2, especially providing a theoretical basis for the biological transformation and storage of CO2 in coal seams.

Abstract Key message This study demonstrates the potential of Pinus yunnanensis Franch. for multi-trait selection in breeding programs, highlighting positive co-variation of growth traits with fecundity, trunk straightness, and crown health in 16-year-old progenies. Integrated trait selection could enhance wood productivity and seed yield, supporting both commercial and ecological goals in reforestation efforts. Context The genetic improvement of P. yunnanensis, a species widely used for reforestation in Southwest China, is essential due to its economic importance and adaptability to harsh environments. Despite its extensive use, studies on mature trees are limited, particularly in multi-trait selection involving fecundity and trunk quality. Aims This study aimed to characterize phenotypic variation among and within provenances of P. yunnanensis, explore relationships among key traits, and evaluate the feasibility of joint selection for growth, fecundity, and trunk straightness. Methods We evaluated nine phenotypic traits in 3467 plus-tree progenies from six provenances in a common garden setting. Using structural equation modeling and “random forest” analysis, we identified key predictors of cone production and trunk straightness and assessed trait interrelationships. Results Significant phenotypic variations were observed among and within provenances of P. yunnanensis, with intra-provenance variation accounting for most of the total variation. Notably, 16.2% of trees exhibited twisted trunks, leading to a 14.9% decrease in wood volume compared to trees with straight trunks. The top 20% of individuals contributed 87.8% of total cone production, indicating substantial variation in fecundity. Growth, crown size, and crown health positively correlated with fecundity and trunk straightness, with tree height and diameter being the most important predictors. Both pairwise and multivariate analyses revealed significant and positive relationships among growth, fecundity, and crown health, suggesting high potential for multi-trait selection. Conclusion This study supports the feasibility of combined selection to optimize wood productivity, cone production, and crown health in breeding programs. These findings provide a valuable foundation for refining P. yunnanensis breeding strategies that meet the dual demands of economic utility and environmental adaptation in a changing climate.

Abstract Background Pseudomonas putida KT2440, a non-pathogenic soil bacterium, is a key platform strain in synthetic biology and industrial applications due to its robustness and metabolic versatility. Various systems have been developed for genome editing in P. putida, including transposon modules, integrative plasmids, recombineering systems, and CRISPR/Cas systems. However, rapid iterative genome editing is limited by complex and lengthy processes. Results We discovered that the pBBR1MCS2 plasmid carrying the CRISPR/Cas9 module could be easily cured in P. putida KT2440 at 30 oC. We then developed an all-in-one CRISPR/Cas9 system for yqhD and ech-vdh-fcs deletions, respectively, and further optimized the editing efficiency by varying homology arm lengths and target sites. Sequential gene deletions of vdh and vanAB were carried out rapidly using single-round processing and easy plasmid curing. This system’s user-friendliness was validated by 3 researchers from two labs for 9 deletions, 3 substitutions, and 2 insertions. Finally, iterative genome editing was used to engineer P. putida for valencene biosynthesis, achieving a 10-fold increase in yield. Conclusions We developed and applied a rapid all-in-one plasmid CRISPR/Cas9 system for genome editing in P. putida. This system requires less than 1.5 days for one edit due to simplified plasmid construction, electroporation and curing processes, thus accelerating the cycle of genome editing. To our knowledge, this is the fastest iterative genome editing system for P. putida. Using this system, we rapidly engineered P. putida for valencene biosynthesis for the first time, showcasing the system’s potential for expanding biotechnological applications.

Abstract Background Transcription factor lark has been demonstrated to play multiple functions in Drosophila, but the function of this gene in embryonic development remains to be elucidated. Results In this study, the CRISPR/Cas9 gene-editing method was used to construct a Bmlark mutant strain of Bombyx mori to investigate the roles of this gene. The results showed that the homozygous mutant Bmlark −/− was lethal. The Bmlark −/− embryos showed obvious developmental defects, such as defective sclerotization and melanization of the exoskeleton. A transcriptomic comparison of Bmlark −/− and wild-type embryos showed that the differentially expressed genes were mainly enriched in the structure and metabolic processes of chitin and cuticles. While the expression levels of chitin metabolism-related enzyme genes did not significantly change, in the mutant embryos compared to the wild-type embryos, the expression levels of 63 putative cuticle protein genes showed significant differences. Among which, 35 genes were downregulated and 28 genes were upregulated. The expression levels of the transcription factor BmPOUM2 and eight wing disc cuticle protein genes (WCP) also changed. BmPOUM2, WCP5, WCP9, WCP10, WCP11 were downregulated and WCP1, WCP2, WCP3, WCP6 were upregulated in Bmlark −/− embryos. While the expression level of TH in the tyrosine-mediated pigmentation pathway was upregulated in the mutant embryos, the expression levels of the four key pigment synthesis genes DDC, aaNAT, Laccase2A, and yellow-f2 were significantly downregulated. Conclusions The expression levels of 63 putative cuticle protein genes, eight WCP genes, and five pigment synthesis genes significantly changed in Bmlark mutant B. mori compared to those of the wildtype. These results suggest that Bmlark is essential for normal development of cuticle and tyrosine-mediated melanization in silkworm embryos.

Abstract Upon activation, naive B cells exit their quiescent state and enter germinal center (GC) responses, a transition accompanied by increased protein synthesis. How protein translation efficiency is adequately adjusted to meet the increased demand requires further investigation. Here, we identify the methyltransferase METTL1 as a translational checkpoint during GC responses. Conditional knockout of Mettl1 in mouse B cells blocks GC entry and impairs GC formation, whereas conditional knock-in of Mettl1 promotes GC responses. Mechanistically, METTL1 catalyzes m7G modification in a specific subset of tRNAs to preferentially translate BCR signaling-related proteins, ensuring mitochondrial electron transporter chain activity and sufficient bioenergetics in B cells. Pathologically, METTL1-mediated tRNA m7G modification controls B-cell autoreactivity in SLE patients or lupus-prone mice, and deletion of Mettl1 alleviates dysregulated B-cell responses during autoimmune induction. Thus, these results support the function of METTL1 in orchestrating an effective B-cell response and reveal that aberrant METTL1-mediated tRNA m7G modification promotes autoreactive B cells in systemic autoimmunity.

Abstract Background Severe acute pancreatitis (SAP) is characterized by high mortality rates and various complications, including skeletal muscle atrophy, which significantly exacerbates its outcomes. Despite its clinical relevance, the mechanistic understanding of the relationship between skeletal muscle and the pancreas in SAP remains limited. Our study aimed to elucidate this “organ crosstalk” and its potential implications. Methods We established an SAP mouse model through pancreatic duct ligation (PDL) and evaluated pancreatic necrosis, skeletal muscle atrophy, and myonectin expression levels. Recombinant myonectin protein was administered in vivo and in vitro to assess its effects on acinar cell necrosis. Mechanistic insights were gained through RNA-seq data analysis and experimental validation. Serum samples from AP patients and healthy controls were collected to investigate the correlation between serum myonectin levels and disease severity. Results The mouse model exhibited severe pancreatic necrosis, skeletal muscle atrophy, and elevated myonectin levels, with myonectin administration exacerbating model severity. We identified iron accumulation-induced ferroptosis as a key pathway contributing to myonectin-mediated acinar cell necrosis. A total of 22 healthy controls and 52 patients with varying degrees of AP were included in the serum samples and clinical data (36.5% females, age 49.79 ± 16.53). Analysis of serum samples revealed significantly higher myonectin levels in AP patients, correlating with disease severity (R = 0.28, P = 0.041). Conclusions Our findings underscore the significant role of myonectin in SAP progression and its potential as a prognostic marker for disease severity in AP patients. This study contributes to a deeper understanding of the pathophysiology of SAP and highlights potential therapeutic targets for intervention.

Abstract Background Avocado, a fruit crop renowned for its high nutritional value, has seen a steadily increasing market demand. However, breeding efforts for avocados have lagged those for other commercial fruits due to limited genomic research and germplasm resources. To address this shortfall, a genome-wide association study was conducted on 122 avocado accessions from the United States Department of Agriculture (USDA) Agricultural Research Service (ARS) Subtropical Horticultural Research Station (SHRS) germplasm collection. The study aimed to identify genetic markers and regions associated with various morphometric traits in avocado fruits, including fruit weight, length, width, diameter, seed weight, seed length, seed width, fruit seed ratio (FSR), and fruit shape index (FSI). Results Leveraging 4,226 high-quality single nucleotide polymorphism (SNP) markers obtained from genotyping arrays, fifteen markers were identified with strong associations with these traits, utilizing Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) and Fixed and random model Circulating Probability Unification (FarmCPU) models. Gene annotation analyses within a 200-kb window in the vicinity of significant SNPs revealed several genes associated with various metabolic pathways suggesting that some of them likely determine these fruit quality traits, which needs to be verified and validated. Our results, which were conducted at one location, provide directions for conducting future studies using high-resolution genotyping and long-term multi-year and multi-location trait evaluations for precisely identifying the causal SNP(s) and genes associated with these traits. Conclusions These markers reported in this manuscript provide valuable tools for applying marker-assisted selection (MAS) in avocado breeding programs aimed at enhancing fruit quality and value.

Abstract Ecosystem services (ESs), the benefits nature provides to people, are an important basis for fulfilling sustainable development goals (SDGs). Therefore, an ES-based approach will help deepen our understanding of the relationships between natural systems and human well-being and provide co-benefit pathways for sustainable development. However, monitoring progress towards achieving the SDGs based on the contributions of ESs to SDGs is lacking. Using the linkages between ESs and SDGs, this study quantified progress towards the SDGs in China from 2000 to 2020 and determined future development priorities at both the national and provincial levels. Our results indicated that (1) during the period 2000–2020, China showed decreasing trends in the 11 SDGs and SDG index scores; (2) there were significant differences in the scores for SDGs and the SDG index across 31 provinces; (3) SDG 3, SDG6, SDG11, SDG13, and SDG15 were recognized as the highest national priorities, concerning health and environment; and (4) 31 provinces faced diverse economic, social, and environmental development challenges. The ES-based approach may assist policy-makers in monitoring and comparing progress towards the SDGs in an integrated and composite way, prioritizing local action, and providing a scientific basis for formulating policies to achieve SDG implementation.

Abstract Background Long non-coding RNA (lncRNA) plays a pivotal role in bone regeneration by interaction with microRNAs (miRNAs) and constructing a lncRNA-miRNA regulatory network. Objectives This research aimed to elucidate the role of lncRNA CASC11 in the delayed healing process of tibial fractures and to explore its potential regulatory mechanisms. Materials and methods The expression levels of CASC11 and miR-150-3p in serum samples were detected and the predictive capability of CASC11 regarding delayed healing in fracture patients. Furthermore, the study confirmed the accuracy of the binding sites between CASC11 and miR-150-3p. Subsequently, overexpression/interference plasmids of CASC11, along with overexpression plasmids co-transfected with both CASC11 and miR-150-3p, were systematically introduced into MC3T3-E1 cells to investigate their effects on the expression of osteogenic marker genes, as well as their influence on cellular proliferation and apoptosis. Results The expression levels of CASC11 were significantly elevated, while miR-150-3p levels were markedly decreased in individuals exhibiting delayed fracture healing (P

Abstract Objective To examine the clinicopathological features, immunohistochemical profiles, and differential diagnosis of sclerosing angiomatiod nodular transformation (SANT). Methods Three cases of SANT of the spleen, diagnosed between 2014 and 2023 at the Affiliated Hospital of Zunyi Medical University, were analysed. Pathological features were assessed using haematoxylin and eosin staining, followed by immunohistochemistry with the EnVision system. Additionally, a review of relevant literature was conducted. Results The study included one male and two female patients aged 40–55 years, with a median age of 47.5 years. All lesions were solitary, with tumour diameters ranging from 4 to 7.4 cm (mean 5.7 cm). Gross examination demonstrated that the masses were well-demarcated from the surrounding splenic tissue, with no evident capsule. The cut surfaces of the masses exhibited irregular, porcelain-white nodules that were tough in consistency, with some areas intermingling with splenic tissue. Microscopic examination revealed round or circular nodules comprising multiple slit-like or sinusoidal capillaries, separated by concentric collagen fibres. The nodules exhibited chronic inflammatory cell infiltration, calcification, haemosiderin deposition, and fibrous connective tissue with hyaline or mucoid changes. Immunohistochemical analysis demonstrated differential expression of markers, including cluster of differentiation (CD) 34, CD31, and CD8, within the sinusoidal nodule areas. Periodic acid-Schiff staining was positive for perinodular collagen deposits, while reticulin staining highlighted nodule profiles and intranodular vessels. None of the patients experienced postoperative recurrence or metastasis, and one patient was on aspirin for thrombocytosis. Conclusion SANT of the spleen is generally considered a rare, benign lesion with angioma-like characteristics. It exhibits exhibiting distinctive histomorphological features within the red pulp. Understanding the differential diagnosis is crucial to prevent missed or incorrect diagnoses.

WE43 Mg alloy was processed by warm laser shock peening (WLSP) to tailor its surface integrity and wear resistance in this study. The influence rule of laser energy and process temperature as well as the tribological behavior of Mg alloy was revealed. The dimensions of impacted dents and surface roughness are raised with the increase of laser energy and temperature. A gradient microstructure is formed with the thickest grain refinement lay of 235 μm achieved by WLSP with 0.4 J at 150 °C. The highest surface hardness of 262.32 ± 67.32 HV is obtained with 0.4 J at room temperature (RT) with an increase of about 225% from the initial 80.82 ± 3.33 HV. All samples after WLSP exhibit enhanced wear resistance indicated by the reduced friction coefficient and even better tribological behavior examined at 200 °C than that at RT. The lowest average friction coefficient of 0.064 is achieved by WLSP with 0.4 J at RT and an acceptably low value of 0.126 is maintained with 0.4 J at 150 °C when worn at 200 °C. High-density dislocations and second-phase precipitation of Mg24Y5 and Mg41Nd5 are facilitated by dynamic strain aging (DSA) and dynamic precipitation (DP), leading to the improved grain refinement and surface modification results. The regular distribution of impacted dents, work hardening and grain refinement by surface severe plastic deformation as well as the promoted DSA and DP process during WLSP jointly contribute to the enhancement and thermal stability of the wear resistance of WE43 Mg alloy.

Abstract CD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.

Abstract In this work, we investigate short-packet communications in power beacon (PB)-assisted Internet-of-Things (IoT) networks, where an energy-constrained actuator first harvests energy from a dedicated PB, and then transmits confidential signals to a desired controller in the presence of an eavesdropper. We derive a closed-form lower bound approximation expression for the average achievable effective secrecy rate (AESR) over Nakagami-m fading channels. To gain more insights, we also present the asymptotic average AESR in the high signal-to-noise ratio (SNR) regime. Specifically, analytical results indicate that an average AESR floor appears with the increase of SNR. Moreover, a low complexity one-dimensional search method is employed to maximize the average AESR by optimizing the energy harvesting length. Monte-Carlo simulations are provided to corroborate our analysis.

Landslides are destructive natural disasters that cause catastrophic damage and loss of life worldwide. Accurately predicting landslide displacement enables effective early warning and risk management. However, the limited availability of on-site measurement data has been a substantial obstacle in developing data-driven models, such as state-of-the-art machine learning (ML) models. To address these challenges, this study proposes a data augmentation framework that uses generative adversarial networks (GANs), a recent advance in generative artificial intelligence (AI), to improve the accuracy of landslide displacement prediction. The framework provides effective data augmentation to enhance limited datasets. A recurrent GAN model, RGAN-LS, is proposed, specifically designed to generate realistic synthetic multivariate time series that mimics the characteristics of real landslide on-site measurement data. A customized moment-matching loss is incorporated in addition to the adversarial loss in GAN during the training of RGAN-LS to capture the temporal dynamics and correlations in real time series data. Then, the synthetic data generated by RGAN-LS is used to enhance the training of long short-term memory (LSTM) networks and particle swarm optimization-support vector machine (PSO-SVM) models for landslide displacement prediction tasks. Results on two landslides in the Three Gorges Reservoir (TGR) region show a significant improvement in LSTM model prediction performance when trained on augmented data. For instance, in the case of the Baishuihe landslide, the average root mean square error (RMSE) increases by 16.11%, and the mean absolute error (MAE) by 17.59%. More importantly, the model's responsiveness during mutational stages is enhanced for early warning purposes. However, the results have shown that the static PSO-SVM model only sees marginal gains compared to recurrent models such as LSTM. Further analysis indicates that an optimal synthetic-to-real data ratio (50% on the illustration cases) maximizes the improvements. This also demonstrates the robustness and effectiveness of supplementing training data for dynamic models to obtain better results. By using the powerful generative AI approach, RGAN-LS can generate high-fidelity synthetic landslide data. This is critical for improving the performance of advanced ML models in predicting landslide displacement, particularly when there are limited training data. Additionally, this approach has the potential to expand the use of generative AI in geohazard risk management and other research areas.

Accurate assessment of N staging in patients with non-small cell lung cancer (NSCLC) is critical for the development of effective treatment plans, the optimization of therapeutic strategies, and the enhancement of patient survival rates. This study proposes a hybrid model based on 3D convolutional neural networks (CNNs) and transformers for predicting the N-staging and survival rates of NSCLC patients within the NSCLC radiogenomics and Nsclc-radiomics datasets. The model achieved accuracies of 0.805, 0.828, and 0.819 for the training, validation, and testing sets, respectively. By leveraging the strengths of CNNs in local feature extraction and the superior performance of transformers in global information modeling, the model significantly enhances predictive accuracy and efficacy. A comparative analysis with traditional CNN and transformer architectures demonstrates that the CNN-transformer hybrid model outperforms N-staging predictions. Furthermore, this study extracts the one-year survival rate as a feature and employs the Lasso–Cox model for survival predictions at various time intervals (1, 3, 5, and 7 years), with all survival prediction p-values being less than 0.05, illustrating the time-dependent nature of survival analysis. The application of time-dependent ROC curves further validates the model’s accuracy and reliability for survival predictions. Overall, this research provides innovative methodologies and new insights for the early diagnosis and prognostic evaluation of NSCLC.

Abstract Objective To evaluate the effectiveness of preemptive multimodal analgesiain elderly patients undergoing laparoscopic colorectal surgery. Methods A prospective randomized controlled study was conducted in the Department of Gastrointestinal Surgery of the Second Hospital of Hebei Medical University from January 2022 to December 2022. A total of 133 patients were included according to the criteria and randomly divided into preemptive analgesia (PRA) group (test group, 67patients) and postoperative analgesia (POA) group (control group, 66patients). Results The Visual Analog Scale (VAS)scores of PRA group 24 h, 48 h, and 72 h after operation were lower than those of POA group, and the difference was statistically significant, P

Abstract Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Abstract The vertical variations and key drivers of ozone and its precursors, namely NOx and VOCs, in the atmospheric boundary layer, have vital impacts on surface ozone budgets but are poorly understood so far. Using online gradient measurements from a 356 m tower, we obtained continuous vertical profiles of ozone and its precursors, which exhibited strong gradients throughout the day. In the daytime, the vertical gradients of ozone precursors are significantly regulated by reactions with OH radicals. At night, our observations confirmed more intense VOC reactions with NO3 radicals in the residual layer than in the boundary layer. Additionally, we found that residual layer entrainment could contribute to over half of the boundary-layer ozone enhancements in the morning periods. Our results underscore the importance of considering vertical changes of ozone and its precursors in the atmospheric boundary layer when developing future ozone mitigation strategies.

Abstract With the focus on the insufficient origin-based cold storage in China, this study investigates the location and routing problem (LRP) of origin-based cold storage for fresh agricultural products. This study considers the loss of fresh agricultural products in different environments during transportation and presents a cold storage LRP model. To address this issue, a hybrid whale algorithm with heuristic rules is designed, and the effectiveness of the algorithm is verified by standard instances. Finally, taking Chenggu County as a practical case, the influence of cold storage capacity and farmers’ demand for refrigeration are analysed. Experimental results show that the proposed algorithm has a good effect in solving medium-scale LRP. As the storage capacity increases, the total cost of the system can be increased by 0.086%. As farmers’ demand for refrigeration increases, the total cost of the system can be increased by 34.034%. Farmers’ demand has a greater impact on the system’s total costs than the cold storage capacity. When optimizing the cold storage layout, changes in fresh agricultural product output in the next few years can be roughly predicted, and the most economical optimization scheme can be obtained.

Abstract Objective Endometrial cancer is stepping into the era of precision therapy. Genomic test is recommended for newly diagnostic patients. However, outpatients displayed more complex characteristics. Here, we elucidated the clinical characteristics and genomic profiling of outpatients with endometrial cancer at our institution. Methods Between 2018 and 2023, 68 endometrial cancer received genomic tests at outpatient department of Fudan University Shanghai Cancer Center. Data, including age, pathological histology, FIGO stage and treatment strategy were collected. Germline mutations, molecular subtypes and other somatic mutations were also summarized. Results Overall, 72.1% (49/68) of patients receive genomic tests at primary diagnosis, while 27.9% (19/68) of patients received tests at recurrence. Nine patients had deleterious germline mutations, including BRCA1(2), MLH1(1), MSH2(2, including one with co-mutation of RAD50), MSH6(2), FANCA(1), MUTYH(1). Molecular subtypes were recognized among 62 patients, as POLE super-mutation(4, 6.5%), MSI-H(7, 11.3%), CN-Low(36, 58.1%) and CN-High(15, 24.2%). Ten patients received anti-PD1 monotherapy or in combination with chemotherapy or anti-angiogenic therapy, with the duration of disease control of 1 to 35 months. The ORR rate was 30%, and six patients had stable disease. The median (range) follow-up time was 18(2–160) months. 23(33.8%) relapses were recorded, and CN-High subtype displayed worst PFS compared with other subtypes (P

Abstract Background Patients with hereditary multiple exostosis (HME) usually present with forearm deformity with or without radial head dislocation. Ulna lengthening has been proposed to address this condition. Exostosis resection plus ulna lengthening has been adopted in our hospital since 2008, and patients with this condition were retrospectively reviewed. Herein, we aimed to investigate the optimal timing and clinical outcomes of this surgical approach. Methods In all, thirty-five patients (40 forearms), including 22 boys and 13 girls, were enrolled in our study from July 2014 to September 2020. We divided the patients into 4 groups based on the age when they received surgery and the status of the radial head. Pronation and supination of the forearm, flexion and extension of the elbow, wrist ulnar deviation and wrist radial deviation, and radiological parameters including ulnar length (UL), ulnar variance (UV), the percentage of radial bowing (RB/RL), radio articular angle (RAA) and carpal slip (CS), were assessed and recorded. Results The mean UL was significantly improved after surgery in four Groups (P

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

As a new type of grain storage structure, the double-story squat silo (DSSS) can ensure the quality of grain storage, but also has the advantages of land saving, energy saving and carbon reduction, and high degree of mechanization. In this paper, the method of coupling discrete elements and finite elements was adopted to construct a mathematical analysis model of the dynamic response between grain particles and the silo wall during the central unloading process in a double-layer shallow round silo (DSSS). The validity of the scaling method was verified by combining experimental tests with the scaling model. Numerical analyses of the scaled-down model were compared with theoretical calculations to confirm the feasibility of the numerical methods, and the grain-silo interaction during the central unloading of the DSSS was investigated. The results showed that both the upper and lower layers exhibited a sudden increase in lateral pressure and oscillation during the unloading process, with a larger overpressure coefficient and a greater tendency for overpressure to occur in the middle of the silo wall. The stresses in both layers of the silo wall reached their maximum at 1/4 of the distance from the bottom of the silo wall when considering the grain-silo interaction. This study has provided technical support for the structural design of DSSS, facilitating its promotion and application, and had significant engineering implications.

Abstract Background To investigate the anatomic features of the root furcation of permanent mandibular first molars. Methods A total of 50 extracted mandibular first molars (25 two-rooted and 25 three-rooted) were collected and scanned using micro-computed tomography. The digital models of teeth and root canal systems were reconstructed three-dimensionally. The tooth models were displayed in parallel projection mode from buccal and distal views. Screenshots were captured and subsequently analyzed using Image-Pro Plus 6.0 software after calibration. The furcation angle, root trunk length, maximum depth and level of distal root concaves of mesial roots, and length of enamel projections were measured, and the furcation types (classified into type V, type U and type W) were detected. Statistical analysis was performed using the Shapiro-Wilk’s test, one-way analysis of variance, Student’s t-test and Chi-square test. Results The mean furcation angle between the distobuccal (DB) and distolingual (DL) roots (in distal view) was the greatest (59.2°), whereas the furcation angle between the mesial and DL roots (in buccal view) was the smallest (25.4°) among the four furcation angles (all p 0.05). The frequency of type V was the highest (54.0%), followed by type U (26.0%), and type W had the lowest occurrence rate (20.0%). The mean length of distal root trunk in the three-rooted mandibular molars was significantly greater than that of the buccal/lingual one (3.7 mm vs. 3.0 mm, p

Purpose: To study the effect of guided music management strategies on the psychological state of college students of science and technology during their graduation reply. Methods: A retrospective analysis was conducted on the relevant data of 107 college students of science and technology who underwent graduation defense in 2022. These students returned to school 1 week before their graduation reply. On the basis of whether they received guided music management strategies, the students were divided into a control group (no management strategy) and an observation group (received guided music management strategies). Among the students, 50 were included in the observation group after excluding two who did not meet the inclusion criteria. A total of 53 students were included in the control group after excluding 2 who did not meet the inclusion criteria. General demographic information and Self-Rating Anxiety Scale (SAS), Test Anxiety Scale (TAS) and Chinese Perceived Stress Scale (CPSS) scores were collected. Results: No significant differences in SAS, TAS and CPSS scores were found between the two groups before management (P > 0.05). After management, the SAS score of the observation group was lower than that of the control group (P < 0.05). The TAS and CPSS scores of the observation group after management were lower than those of the control group (P < 0.05). Conclusion: Implementing guided music management strategies can effectively alleviate anxiety and stress in college students of science and technology during their graduation reply and has a certain utility and promotion value.

To solve the problem that the controllable load management of multiple controllable load resources requires a lot of computing resources and can not achieve accurate automatic power control, a cloud-edge cooperative load resource allocation strategy for multiple controllable load regulation was proposed. Firstly, the collaborative control framework of cloud edge was designed to integrate and process the data of various controllable load resources. Secondly, considering the similarity of computing tasks of different edge nodes, the optimization goal was to minimize the time cost of all computing tasks, and the cloud computing resource allocation strategy was given to allocate computing resources reasonably. Finally, the computational resource allocation was solved by genetic algorithm based on adaptive cross-mutation probability. Finally, the calculation of resource allocation was solved using a genetic algorithm based on adaptive crossover mutation probability. The experimental results show that the algorithm proposed has significant advantages in task completion time and execution cost, and these advantages become more pronounced as the number of tasks increases and computing resources decrease. It can significantly improve computing efficiency and reduce computing time.

Abstract Background Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction. Methods A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1. Results From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8–NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8–5·6) and 5·6 months (95% CI 3·4–7·0), respectively. Conclusions This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing. Trial registration ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib).

Abstract The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification. Both known and unrecorded candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retinae indicate a largely consistent yet distinct developmental pattern. This atlas offers unparalleled resolution into the transcriptional and chromatin accessibility landscapes during development, providing an invaluable resource for deeper insights into retinal development and associated diseases.

Abstract Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving “immune cell-gut microbes-bile acid metabolites” contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD. Graphical abstract

Abstract Korla pear has a unique taste and aroma and is a breeding parent of numerous pear varieties. It is susceptible to Valsa mali var. pyri, which invades bark wounded by freezing injury. Its genetic relationships have not been fully defined and could offer insight into the mechanism for freezing tolerance and disease resistance. We generated a high-quality, chromosome-level genome assembly for Korla pear via the Illumina and PacBio circular consensus sequencing (CCS) platforms and high-throughput chromosome conformation capture (Hi-C). The Korla pear genome is ~ 496.63 Mb, and 99.18% of it is assembled to 17 chromosomes. Collinearity and phylogenetic analyses indicated that Korla might be derived from Pyrus pyrifolia and that it diverged ~ 3.9-4.6 Mya. During domestication, seven late embryogenesis abundant (LEA), two dehydrin (DHN), and 54 disease resistance genes were lost from Korla pear compared with P. betulifolia. Moreover, 21 LEA and 31 disease resistance genes were common to the Korla pear and P. betulifolia genomes but were upregulated under overwintering only in P. betulifolia because key cis elements were missing in Korla pear. Gene deletion and downregulation during domestication reduced freezing tolerance and disease resistance in Korla pear. These results could facilitate the breeding of novel pear varieties with high biotic and abiotic stress resistance.

Mobile learning allows for an interactive way of learning through devices like smartphones. However, current methods usually rely on pre-set situations and struggle to recognize new contexts when they come up during testing. To solve this, we suggest the Open-set Learning Context Recognition Model (OLCRM). This model uses data extracted from smartphone sensors to identify whether a learning context is known or unknown. It also uses a Dual Discriminator Generative Adversarial Network (DDGAN) to create high-quality fake examples, which helps improve the accuracy of recognizing contexts. Experimental results demonstrate the effectiveness of OLCRM in open-set learning context recognition problems.