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Abstract Pyrene-based metal-organic frameworks (MOFs) have tremendous potential for various applications. With infinite structural possibilities, the MOF community often relies on simulations to identify the most promising candidates for given applications. Among thousands of reported structures, many exhibit limited reproducibility — in either synthesis, performance, or both — owing to the sensitivity of synthetic conditions. Geometric distortions that may arise in the functional groups of pyrene-based ligands during synthesis and/or activation cannot easily be predicted. This sometimes leads to discrepancies between in silico and experimental results. Here, we investigate a series of pyrene-based MOFs for carbon capture. These structures share the same ligand (1,3,6,8–tetrakis(p–benzoic acid)pyrene (TBAPy)) but have different metals (M-TBAPy, M = Al, Ga, In, and Sc). The ligands stack parallel in their orthorhombic crystal structure, creating a promising binding site for CO2. As predicted, the metal is shown to affect the pyrene stacking distance and, therefore, the CO2 uptake. Here, we investigate the metal’s intrinsic effects on the MOFs’ crystal structure. Crystallographic analysis shows the emergence of additional phases, which thus impacts the overall adsorption characteristics of the MOFs. Considering these additional phases improves the prediction of adsorption isotherms, enhancing our understanding of pyrene-based MOFs for carbon capture.

Abstract We systematically examine the application of different phasing strategies to decrypt strawberry genome organization and produce a fully phased and accurate reference genome for Fragaria x ananassa cv. “EA78” (2n = 8x = 56). We identify 147 bp canonical centromeric repeats across 50 strawberry chromosomes and uncover the formation of six neocentromeres through centromere turnover. Our findings indicate strawberry genomes have diverged centromeric satellite arrays among chromosomes, particularly across homoeologs, while maintaining high sequence similarity between homologs. We trace the evolutionary dynamics of centromeric repeats and find substantial centromere size expansion in wild and cultivated octoploids compared to the diploid ancestor, F. vesca.

In order to solve the problem of heat flux identification of temperature-sensitive paints under the interference condition of high-temperature gas radiation luminescence, based on the gradient change of radiation light intensity of the coating, a heat flux identification method using the Levenberg-Marquardt optimization algorithm had been established, and experiments were carried out using the flat plate-wedge model in the high-enthalpy shock tunnel, with the total temperature of 2 816 K and 4 620 K, respectively. The results show that the high-temperature gas radiation has an important influence on the optical measurement method, and the gas radiation luminescence is further enhanced with the increase of the total temperature of the incoming flows. The amplitude of the light intensity gradient on the coating surface gradually decreases with time and tends to be stable. Under different total temperature conditions, in the flat area with a small temperature rise, the maximum value of the gas radiation light intensity gradient amplitude in the total gradient amplitude is 16.9%, accounting for less than 4.8% in areas with large temperature rise. The global optimal heat flux identification method based on gradient change can effectively eliminate the influence of high-temperature gas radiation, and the difference between the measurement results of temperature-sensitive paint and the thermocouple measurement results is less than 20% in the non-disturbing area of the plate and the peak heat flux area of the wedge.

Abstract A new type of nonapoptotic, iron-dependent cell death induced by lipid peroxidation is known as ferroptosis. Numerous pathological processes, including inflammation and cancer, have been demonstrated to be influenced by changes in the ferroptosis-regulating network. Long non-coding RNAs (LncRNAs) are a group of functional RNA molecules that are not translated into proteins, which can regulate gene expression in various manners. An increasing number of studies have shown that lncRNAs can interfere with the progression of ferroptosis by modulating ferroptosis-related genes directly or indirectly. Despite evidence implicating lncRNAs in cancer and inflammation, studies on their mechanisms and therapeutic potential remain scarce. We investigate the mechanisms of lncRNA-mediated regulation of inflammation and cancer immunity, assessing the feasibility and challenges of lncRNAs as therapeutic targets in these conditions.

Abstract To develop an atrophic Meibomian Gland Dysfunction (MGD) animal model via liquid nitrogen cryotherapy, the eyelid edges of C57 mice exposure to liquid nitrogen for 30 s. Morphology of MG and ocular surface were assessed using stereomicroscopy and a slit lamp microscope at multiple time points post-injury. Acinar loss and atrophy were observed from day 7, with increased inflammation and apoptosis, and decreased proliferation in acinar cells. Corneal epithelial defects appeared after day 14. Liquid nitrogen induced selective damage to meibomian acinar cells, simulating MGD pathology effectively, with peak effects at day 21, providing a relevant model for atrophic MGD research.

Abstract Drums are the core working mechanism of the coal mining machine for coal mining. The structural design level of the drum is crucial for mining efficiency and safety production. Traditional design methods not only have long design cycles and high costs, but also limited design capabilities. This study used computer numerical simulation methods to establish coupled models for drum cutting complex coal seams, which was used to obtain the working performance of drums with different structures. By fitting the comprehensive performance evaluation function of the drum, the optimal structural parameters are obtained through the improved Non-Dominated Sorting Genetic Algorithms (NSGA-II). Taking into account both technical and economic factors, the optimal helix angle is ultimately determined to be 18°, the optimal installation angle is 45°, and the optimal cutting distance is 71 mm. Through experiments, it has been proven that the performance of the optimized drum has significantly improved. Specifically, the average cutting resistance has been reduced by 12.72%, the load fluctuation coefficient has been reduced by 9.81%, the cutting specific energy consumption has been reduced by 2.85%, and the coal loading rate has been increased by 9.59%, providing a reference for the optimization design of the shearer drum structure.

The depositional facies types of the fourth member of the Middle Triassic Leokoupo Formation (Lei-4 Member) in western Sichuan Basin are examined through the methods of sedimentology, lithology and analysis of well-logging data, as well as the special lithofacies indicators such as microbialite, gypsum-salt rock and tempestites, using the data of about 400 wells and 11 outcrop sections. The distribution and evolution and its hydrocarbon geological significances of the bay facies have been discussed. The Lei-4 Member in western Sichuan Basin has an ocean–bay–flat depositional model, with the presence of evaporated tidal flat, restricted tidal flat and paleo-bay facies from east to west. The subfacies such as bay margin, subtidal bay and bay slope are recognized within the paleo-bay, with microbial reef and grain bank microfacies in the bay margin, microbial flat, deep-water spongy reef and hydrostatic mudstone microfacies in the subtidal bay, and tempestites and collapsed deposits in the upper bay slope. The bay boundary covered the Guangyuan-Zitong-Dujiangyan area in the period of the first submember of the Lei-4 Member (Lei-4-1) with falling sea level, regressed westward into the Shangsi-Jiangyou-Dujiangyan area in the period of Lei-4-2, and expanded to the Shangsi-Zitong-Langzhong- Wusheng-Yanting-Chengdu area in the northern part of central Sichuan Basin in the period of Lei-4-3 along with a small-scale transgression. The topographic pattern of “one high and two lows” is confirmed in the Lei-4 Member, corresponding to a configuration of source rocks and reservoir rocks alternated horizontally and superimposed vertically. Two efficient source-reservoir configuration models, i.e. side source & side reservoir, and self-generating & self-storing, are available with the microbial reef and grain bank reservoirs at the bay margin and the high-quality source rocks within the sags on both sides of the bay. The research findings will inevitably open up a new situation for the hydrocarbon exploration in the Leikoupo Formation.

Abstract The episymbiotic Candidatus Saccharibacteria is the most studied lineage of candidate phyla radiation. Living an epiparasitic lifestyle, Saccharibacteria might be associated with human mucosal diseases by modulating the structure of the oral microbiome through interactions with host bacteria. However, the knowledge of Saccharibacterial genomic diversity and the potential underlying their adaptation to a wide range of habitats remains limited. Here, we construct a high-quality genome collection of Saccharibacteria from multiple sources, providing 2041 high-quality genomes and previously unidentified taxa. The comparative genomic analysis shows the widespread metabolic defects of Saccharibacteria. Specific metabolic modules are commonly found in Saccharibacteria of different habitats, suggesting Saccharibacteria might have undergone habitat adaptation during the transition from different environments. We additionally show that Saccharibacteria account for ~1% of the Chinese oral microbiome. A preliminary analysis of rheumatoid arthritis individuals and healthy controls implies that Saccharibacteria might be associated with human systemic disease.

Abstract L-Homoserine, serves as a non-essential precursor for the essential amino acids derived from L-aspartate in both animals and humans. It finds widespread applications across the food, cosmetics, pharmaceutical, and animal feed industries. Microbial fermentation, primarily utilizing Escherichia coli, is the dominant approach for L-Homoserine production. However, despite recent advancements in fermentative processes employing E. coli strains, low production efficiency remains a significant barrier to its commercial viability. This review explores the biosynthesis, secretion, and regulatory mechanisms of L-Homoserine in E. coli while assessing various metabolic engineering strategies aimed at improving production efficiency.

Abstract Potential evaluation to assist demand response decisions has garnered significant attention with the development of new power systems. However, existing data‐driven methods are challenging to properly exploit multivariate features and the process of response potential evaluation is unclear. Therefore, the authors propose an evaluation method that fuses expert features with multi‐image inputs and analyses the model evaluation process based on gradient. First, typical load profiles are extracted by the proposed procedure. Next, features derived from expert knowledge are calculated from the perspectives of adjustability, regularity, and sensitivity of electricity usage. Additionally, the typical load profile's recurrence plot, Markov leapfrog field, and Gramian angle field are created and incorporated into the colourful image as inputs. Then, the evaluation results are obtained by a two‐stream neural network fusing multivariate features. In the experiments, the proposed method is validated and discussed by comparing with many existing methods using London household users' data under the time‐of‐use price, providing new insights for demand response potential evaluation.

Abstract Prostate cancer, a common malignancy in older men, often requires laparoscopic radical prostatectomy, considered the gold standard treatment. However, postoperative complications can significantly impact quality of life and psychological well-being. The emergence of mobile internet health management offers a promising approach for accessible and effective post-discharge care. This study evaluates the effectiveness of mobile internet management in postoperative care for prostate cancer patients, focusing on disease knowledge, psychological well-being, self-care capabilities, and quality of life. From September 2020 to September 2021, prostate cancer patients who underwent radical surgery at our Department of Urology were divided into a control group receiving standard care and an intervention group receiving mobile internet-based care. Patients were followed over six months, with assessments conducted at both 3 and 6 months post-intervention. We evaluated changes in disease knowledge, psychological status (using SAS/SDS scales), self-care ability (via the ESCA scale), and quality of life (measured by SF-36). A total of 112 patients were divided into two groups of 56 each. Repeated measures ANOVA indicated significant improvements in disease knowledge over time, between groups, and in their interaction (P

Abstract Endosomes are crucial sites for intracellular material sorting and transportation. Endosomal transport is a critical process involved in the selective uptake, processing, and intracellular transport of substances. The equilibrium between endocytosis and circulation mediated by the endosome-centered transport pathway plays a significant role in cell homeostasis, signal transduction, and immune response. In recent years, there have been hints linking endosomal transport abnormalities to neurodegenerative diseases, including Alzheimer's disease. Nonetheless, the related mechanisms remain unclear. Here, we provide an overview of endosomal-centered transport pathways and highlight potential physiological processes regulated by these pathways, with a particular focus on the correlation of endosomal trafficking disorders with common pathological features of neurodegenerative diseases. Additionally, we summarize potential therapeutic agents targeting endosomal trafficking for the treatment of neurodegenerative diseases. Graphical abstract

Abstract O-GlcNAcylation catalyzed by O-GlcNAc transferase (OGT) plays an important role in the regulation of tumor glycolysis. However, the mechanism underlying OGT regulation remains largely unknown. Here, we showed that coactivator associated arginine methyltransferase 1 (CARM1) sensed changes of extracellular glucose levels in non-small cell lung cancer (NSCLC) cells. Increased glucose upregulated CARM1 and OGT. CARM1 methylated OGT at arginine 348, promoting its stability through binding of the deubiquitinase USP9X. The arginine methylation of OGT increased global O-GlcNAcylation levels, thereby promoting glycolysis in NSCLC cells. OGT arginine methylation also upregulated c-Myc expression and promoted the proliferation of NSCLC cells in vitro and in vivo. Consistently, OGT expression was positively correlated with CARM1 in human NSCLC samples. The present findings shed light on the mechanism underlying the stabilization of OGT by arginine methylation in response to changes of glucose concentration. The study also clarified the role of the CARM1-USP9X-OGT axis in glycolysis in NSCLC, providing a potential new target or therapeutic strategy in NSCLC.

Abstract Semantic segmentation in the context of 3D point clouds for the railway environment holds a significant economic value, but its development is severely hindered by the lack of suitable and specific datasets. Additionally, the models trained on existing urban road point cloud datasets demonstrate poor generalisation on railway data due to a large domain gap caused by non‐overlapping special/rare categories, for example, rail track, track bed etc. To harness the potential of supervised learning methods in the domain of 3D railway semantic segmentation, we introduce RailPC, a new point cloud benchmark. RailPC provides a large‐scale dataset with rich annotations for semantic segmentation in the railway environment. Notably, RailPC contains twice the number of annotated points compared to the largest available mobile laser scanning (MLS) point cloud dataset and is the first railway‐specific 3D dataset for semantic segmentation. It covers a total of nearly 25 km railway in two different scenes (urban and mountain), with 3 billion points that are finely labelled as 16 most typical classes with respect to railway, and the data acquisition process is completed in China by MLS systems. Through extensive experimentation, we evaluate the performance of advanced scene understanding methods on the annotated dataset and present a synthetic analysis of semantic segmentation results. Based on our findings, we establish some critical challenges towards railway‐scale point cloud semantic segmentation. The dataset is available at https://github.com/NNU‐GISA/GISA‐RailPC, and we will continuously update it based on community feedback.

Hydrogen sulfide (H2S) is a gas signaling molecule with versatile bioactivities; however, its exploitation for disease treatment appears challenging. This study describes the design and characterization of a novel type of H2S donor–drug conjugate (DDC) based on the thio-ProTide scaffold, an evolution of the ProTide strategy successfully used in drug discovery. The new H2S DDCs achieved hepatic co-delivery of H2S and an anti-fibrotic drug candidate named hydronidone, which synergistically attenuated liver injury and resulted in more sufficient intracellular drug exposure. The potent hepatoprotective effects were also attributed to the H2S-mediated multipronged intervention in lipid peroxidation both at the whole cellular and lysosomal levels. Lysosomal H2S accumulation and H2S DDC activation were facilitated by the hydrolysis through the specific lysosomal hydrolase, representing a distinct mechanism for lysosomal targeting independent of the classical basic moieties. These findings provided a novel pattern for the design of optimally therapeutic H2S DDC and organelle-targeting functional molecules.

Objective: This study was formulated with the objective of elucidating the correlation between 25-hydroxyvitamin D (25(OH)D) and the occurrence of severe headache or migraine, employing a cross-sectional analytical approach. Methods: A cross-sectional survey was conducted over two cycles involving 7,661 participants, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. A weighted logistic regression method was employed to construct a relationship model between the two variables. Subgroup analysis, adjusting for confounding factors, was performed through stratified analysis to explore the association between 25(OH)D and severe headaches or migraines. Finally, a restricted cubic spline regression (RCS) was utilized to investigate the non-linear relationship between the variables. Results: A total of 7,661 participants were included in this study, with an overall prevalence of severe headaches or migraines of 1,576/7,661 (22.3%). The results from all models consistently indicated a significant negative correlation between serum 25(OH)D levels and the risk of severe headaches or migraines (P < 0.05). Stratified analysis revealed that in the female population (odds ratios [OR]: 0.995, 95% CI: 0.991–0.998, P = 0.001), never smokers (OR: 0.991, 95% CI: 0.985–0.997, P = 0.003), and non-drinkers (OR: 0.993, 95% CI: 0.987–0.999, P = 0.022), the risk of severe headaches or migraines decreased with increasing serum 25(OH)D concentrations. RCS results demonstrated a linear relationship between serum 25(OH)D levels and the risk of severe headaches or migraines. Conclusion: We discovered a negative correlation between serum 25(OH)D levels and the prevalence of severe headaches or migraines, particularly in females, non-smokers, and non-hypertensive individuals. Further clinical research is necessary to confirm these findings, establish causality, and explore potential preventive and therapeutic mechanisms for migraines.

Objective: To explore the ameliorative effects and mechanisms of Pogostemon cablin aqueous extract (PCAE) on mice with ulcerative colitis (UC) based on gut barrier research. Methods: Mice were randomly divided into five groups: Control, model, mesalazine, low-dose of PCAE and high-dose of PCAE groups. A UC model was induced in mice by freely drinking 2.5% dextran sodium sulfate (DSS) for 10 d, with simultaneous oral administration of interventions. The study measured levels of serum interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α). Pathological alterations in the colon were observed using hematoxylin-eosin and periodic acid-schiff staining. The expression of the colonic tight junction proteins zonula occludens-1 (ZO-1), occludin-1, and mucin 2 (MUC2) were assessed via immunohistochemistry. High-throughput sequencing technology was utilized to analyze changes in the gut microbiota of colonic contents. Results: Following intervention with PCAE, DSS-induced mice exhibited a significant reduction in serum levels of IL-6, IL-1β, and TNF-α (P

The role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.

Primary malignant melanoma of the esophagus (PMME) is an extremely rare esophageal malignancy that is often misdiagnosed or overlooked due to its atypical symptoms. We report a case of a 75-year-old male patient who presented with progressive dysphagia. Endoscopic examination revealed a black mass located 25 cm from the incisors. Further imaging studies, including computed tomography (CT) and emission computed tomography (ECT), showed significant thickening of the mid-esophageal wall with localized soft tissue mass formation and heterogeneous enhancement on contrast scans. Multiple lymph nodes around the lesion were visible, leading to an initial misdiagnosis of esophageal cancer. Additionally, metabolic abnormalities in the left scapula suggested possible bone metastasis of the tumor. The final pathological diagnosis was esophageal melanoma. After thorough evaluation of the patient's medical history and additional relevant tests, the primary origin was considered. Diagnosing primary malignant melanoma of the esophagus is a challenging task. This case, through the combination of endoscopic examination, imaging, and pathology, illustrates the characteristics of PMME, providing important insights for clinicians and emphasizing the necessity of comprehensive early evaluation to improve diagnostic accuracy and treatment outcomes.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

Rejuvenation presents a promising way to improve the plasticity of metallic glasses. How modulating the degree of rejuvenation of metallic glasses remains a challenging issue. Here, based on the molecular dynamics simulation, we investigate the evolution of the structural and mechanical properties of a binary Al75Mg25 metallic glass and successfully realized the rejuvenation modulation through the multiple recovery annealing treatment. A range of samples with different degrees of rejuvenation were obtained by successive multiple recovery annealing process. According to our calculations, we found that the degree of rejuvenation is highly correlated with the Al-centered clusters. Microstructural analyses show that a higher degree of rejuvenation is concomitant with less 1551 index of Honeycutt-Andersen indices and a lower content of in terms of Voronoi Tessellation analysis. Moreover, our calculated results demonstrate that the samples with the aging initial state show a higher degree of rejuvenation as compared to the samples with the rejuvenated initial state. This can be attributed to that there are more icosahedral clusters, which are more likely to change to other types of clusters with low local fivefold symmetry in the aged samples during the subsequent high-temperature annealing process. Our work confirms that proper multiple (no more than three times) recovery annealing treatment can increase the degree of rejuvenation of metallic glasses and can offer a better understanding of the effect of rejuvenation on the microstructures and mechanical properties of metallic glasses.

Abstract Microvascular obstruction (MVO) is linked with adverse clinical outcome in acute coronary syndrome (ACS) patients, therefore, early prediction of MVO with non-invasive peripheral microcirculation is crucial in facilitating optimal treatment. Current study aims to analyze the significance of opisthenar microvessel area (OMA, measured using optical coherence tomography, OCT) in predicting coronary stenosis (Gensini score, GS) and short-term cardiac recovery of ACS patients and the results were compared to those of arterial stiffness parameters (Pulse Wave Velocity, PWV; Ankle-Brachial Index; ABI). Results showed that cardiac functional parameters (e.g. ejection fraction, EF; fractional shortening, FS) and OMA were higher in normal/low risk (GS 0–≤ 20, n = 69) compared to medium/high risk patients (GS > 20, n = 44, P

Abstract Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic strategies. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the cellular heterogeneity and transcriptional dynamics of OSA tumors. Our study identified eleven distinct tumor cell subpopulations, including osteoblastic, chondroblastic, and myeloid lineages, each exhibiting unique transcriptional profiles associated with disease progression and metastasis. Epithelial-mesenchymal transition (EMT) emerged as a critical process driving aggressive phenotypes, supported by gene set enrichment analyses (GSVA) and transcription factor regulatory network analyses. Integration of copy number variation (CNV) data highlighted genomic alterations in osteoblastic and chondroblastic cells, implicating potential therapeutic targets. Furthermore, immune cell infiltration analyses revealed distinct immune profiles across OSA subtypes, correlating with tumor mutational burden (TMB) and clinical outcomes. Our findings underscore the complexity of OSA biology and provide a foundation for developing personalized treatment strategies targeting tumor heterogeneity and immune interactions.

Abstract Pathway analysis is a crucial analytical phase in disease research on single-cell RNA sequencing (scRNA-seq) data, offering biological interpretations based on prior knowledge. However, currently available tools for generating cell-level pathway activity scores (PAS) exhibit computational inefficacy in large-scale scRNA-seq datasets. Additionally, disease-related pathways are often identified through cross-condition comparisons within specific cell types, overlooking potential patterns that involve multiple cell types. Here, we present single-cell pathway activity factor analysis (scPAFA), a Python library designed for large-scale single-cell datasets allowing rapid PAS computation and uncovering biologically interpretable disease-related multicellular pathway modules, which are low-dimensional representations of disease-related PAS alterations in multiple cell types. Application on colorectal cancer (CRC) datasets and large-scale lupus atlas over 1.2 million cells demonstrated that scPAFA can achieve over 40-fold reductions in the runtime of PAS computation and further identified reliable and interpretable multicellular pathway modules that capture the heterogeneity of CRC and transcriptional abnormalities in lupus patients, respectively. Overall, scPAFA presents a valuable addition to existing research tools in disease research, with the potential to reveal complex disease mechanisms and support biomarker discovery at the pathway level.

Background: Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar (in yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules or organelles for degradation, a process termed selective autophagy. Recently, accumulating studies have demonstrated that the abnormality of selective autophagy is closely associated with the occurrence and progression of many human diseases, including neurodegenerative diseases, cancers, metabolic diseases, and cardiovascular diseases. Aim of Review: This review aims at systematically and comprehensively introducing selective autophagy and its role in various diseases, while unravelling the molecular mechanisms of selective autophagy. By providing a theoretical basis for the development of related small-molecule drugs as well as treating related human diseases, this review seeks to contribute to the understanding of selective autophagy and its therapeutic potential. Key Scientific Concepts of Review: In this review, we systematically introduce and dissect the major categories of selective autophagy that have been discovered. We also focus on recent advances in understanding the molecular mechanisms underlying both classical and non-classical selective autophagy. Moreover, the current situation of small-molecule drugs targeting different types of selective autophagy is further summarized, providing valuable insights into the discovery of more candidate small-molecule drugs targeting selective autophagy in the future. On the other hand, we also reveal clinically relevant implementations that are potentially related to selective autophagy, such as predictive approaches and treatments tailored to individual patients.

Abstract In this paper, an electro-hydraulic exciter controlled by an alternating current distribution valve is proposed, and a systematic analysis of the influence of pipe effect on the vibration characteristics of the electro-hydraulic exciter is investigated by simulation and experiments. The vibration characteristics curves for different pipe parameters are obtained, and the relative errors between simulation and experiment are evaluated. Moreover, a significant regression model of pipe parameters and vibration characteristics of the electro-hydraulic exciter is established by using the quadratic regression analysis method and the Box-Behnken experiment design method. Significant differences in the influence of pipe parameters on vibration characteristics are obtained by ANOVA (Analysis of Variance), and the influence of pipe parameter interaction on vibration characteristics is discussed. The results show that the relative importance of pipe parameters on the vibration characteristics of electro-hydraulic exciter, from high to low, is as follows: pipe diameter, elastic modulus, and pipe length. Notably, there is also an interaction between the pipe parameters, and the significance of these interactions is ranked from high to low as the interaction between the layers of steel wire and diameter, the interaction between diameter and length, and the interaction between the layers of steel wire and length.

Abstract Image hiding is a task that embeds secret images in digital images without being detected. The performance of image hiding has been greatly improved by using the invertible neural network. However, current image hiding methods are less robust in the face of Joint Photographic Experts Group (JPEG) compression. The secret image cannot be extracted from the stego image after JPEG compression of the stego image. Some methods show good robustness for some certain JPEG compression quality factors but poor robustness for other common JPEG compression quality factors. An image‐hiding network (RIHINNet) that is robust to all common JPEG compression quality factors is proposed. First of all, the loss function is redesigned; thus, the secret image is hidden as much as possible in the area that is less likely to be changed after JPEG compression. Second, the classifier is designed, which can help the model to select the extractor according to the range of JPEG compression degree. Finally, the interval robustness of the secret image extraction is improved through the design of a denoising module. Experimental results show that this RIHINNet outperforms other state‐of‐the‐art image‐hiding methods in the face of JPEG compressed noise with random compression quality factors, with more than 10 dB peak signal‐to‐noise ratio improvement in secret image recovery on ImageNet, COCO and DIV2K datasets.

Abstract Due to the increasing sophistication of face forgery techniques, the images generated are becoming more and more realistic and difficult for human eyes to distinguish. These face forgery techniques can cause problems such as fraud and social engineering attacks in facial recognition and identity verification areas. Therefore, researchers have worked on face forgery detection studies and have made significant progress. Current face forgery detection algorithms achieve high detection accuracy within-dataset. However, it is difficult to achieve satisfactory generalization performance in cross-dataset scenarios. In order to improve the cross-dataset detection performance of the model, this paper proposes a multi-feature fusion network based on two-stream extraction and multi-scale enhancement. First, we design a two-stream feature extraction module to obtain richer feature information. Secondly, the multi-scale feature enhancement module is proposed to focus the model more on information related to the current sub-region from different scales. Finally, the forgery detection module calculates the overlap between the features of the input image and real images during the training phase to determine the forgery regions. The method encourages the model to mine forgery features and learns generic and robust features not limited to a particular feature. Thus, the model achieves high detection accuracy and performance. We achieve the AUC of 99.70% and 90.71% on FaceForensics++ and WildDeepfake datasets. The generalization experiments on Celeb-DF-v2 and WildDeepfake datasets achieve the AUC of 80.16% and 65.15%. Comparison experiments with multiple methods on other benchmark datasets confirm the superior generalization performance of our proposed method while ensuring model detection accuracy. Our code can be found at: https://github.com/1241128239/MFNet .

Abstract Background The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk. Methods We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups. Results Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for “CC” started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort. Conclusion The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice.

Abstract Background Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities. Results Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male’s. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences. Conclusions In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.

Understanding the thermal conductivity of granite is critical for many geological and deep engineering applications. The heated granite was subjected to air-, water-, and liquid nitrogen (LN2-) coolings in this context. The transient hot-wire technique was used to determine the equivalent thermal conductivity (ETC) of the granite before and after treatment. The deterioration mechanism of ETC is analyzed from the meso-perspective. Finally, the numerical model is used to quantitatively study the impact of cooling rate on the microcrack propagation and heat conduction characteristics of granite. The results show that the ETC of granite is not only related to the heating temperature, but also affected by the cooling rate. The ETC of granite decreases nonlinearly with increasing heating temperature. A faster cooling rate causes a greater decrease in ETC at the same heating temperature. The higher the heating temperature, the stronger the influence of cooling rate on ETC. The main explanation for the decrease in ETC of granite is the increase in porosity and microcrack density produced by the formation and propagation of pore structure and microcracks during heating and cooling. Further analysis displays that the damage of granite at the heating stage is induced by the difference in thermal expansion and elastic properties of mineral particles. At the cooling stage, the faster cooling rate causes a higher temperature gradient, which in turn produces greater thermal stress. As a result, it not only causes new cracks in the granite, but also aggravates the damage at the heating stage, which induces a further decrease in the heat conduction performance of granite, and this scenario is more obvious at higher temperatures.

Abstract In low mountain and hilly regions, vegetation cover is higher and plant growth has an accumulative effect, sequestering carbon more strongly. The traditional remote sensing based ecological index (RSEI) lacks the consideration of vegetation productivity, and using it to evaluate ecological environment in low mountain and hilly regions will be biased. In this study, the vegetation productivity was introduced to construct a natural remote sensing based ecological index (NRSEI) that responds to the low mountain and hilly regions, as an example of Gaizhou City, China. Additionally, this study explored the spatiotemporal evolution of ecological environment quality from 2014 to 2020 and quantified the influences of factors. The results show that the first principal component (PC1) increased from 56 to 67% to 65–87% and considered the accumulation process in the ecosystem. NRSEI was more valid. From 2014 to 2020, the quality of the ecological environment generally declined and then increased. The area with “Excellent” increased from 23 to 38%. The quality of ecosystems in the west, northwest, and south deteriorated significantly, a distribution pattern of “high in the center, low in the north and south”. Landuse and topographic conditions dominate the impacts on the ecosystem in the context of social, economic and policy influences. The interactions of the factors were two-factor enhancement that together affect the ecological environment. The results contribute to the development of urban conservation policies in low mountain and hilly regions.

Abstract Ferroptosis is a cell death modality in which iron-dependent lipid peroxides accumulate on cell membranes. Cysteine, a limiting substrate for the glutathione system that neutralizes lipid peroxidation and prevents ferroptosis, can be converted by cystine reduction or synthesized from methionine. However, accumulating evidence shows methionine-based cysteine synthesis fails to effectively rescue intracellular cysteine levels upon cystine deprivation and is unable to inhibit ferroptosis. Here, we report that methionine-based cysteine synthesis is tissue-specific. Unexpectedly, we find that rather than inhibiting ferroptosis, methionine in fact plays an essential role during cystine deprivation-induced ferroptosis. Methionine-derived S-adenosylmethionine (SAM) contributes to methylation-dependent ubiquinone synthesis, which leads to lipid peroxides accumulation and subsequent ferroptosis. Moreover, SAM supplementation synergizes with Imidazole Ketone Erastin in a tumor growth suppression mouse model. Inhibiting the enzyme that converts methionine to SAM protects heart tissue from Doxorubicin-induced and ferroptosis-driven cardiomyopathy. This study broadens our understanding about the intersection of amino acid metabolism and ferroptosis regulation, providing insight into the underlying mechanisms and suggesting the methionine-SAM axis is a promising therapeutic strategy to treat ferroptosis-related diseases.

Abstract Objective To analyze the influencing factors and treatment options of cervical spondylotic myelopathy (CSM) complicated with traumatic central cord syndrome (TCCS). Methods A total of 243 patients with CSM admitted to our hospital from January 2021 to September 2022 were retrospectively analyzed, and then divided into the control group (n = 152) and the observation group (n = 91) according to the presence or absence of concurrent TCCS. The clinical data and imaging data of the two groups were compared, and multivariate logistic regression was used to analyze the influencing factors of CSM complicated with TCCS. Patients in the observation group were further divided into the zero notch anterior cervical interbody fusion device (Zero-P) group (n = 45) and the cervical spine locking plate (CSLP) group (n = 46) according to the treatment mode, and the perioperative indexes of the two groups were compared. The treatment effects were evaluated by the American Spinal Injury Association (ASIA) and the Japanese Orthopedic Association (JOA) before surgery, 1 week after surgery and 6 months after surgery. The height of intervertebral space and the cervical lordosis angle were measured. Results Multivariate logistic regression analysis showed that the injury mechanism (hyperextension injury), hand muscle weakness, cervical instability, age, degree of cervical spinal stenosis, degree of cervical spinal cord compression, and changes in intramedullary high signal were the risk factors, while the type of compression (soft), ASIA score and JOA score were the protective factor for CSM complicated with TCCS (P

Abstract The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand–receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, Stat6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology.

Abstract Glaucoma poses a significant threat to vision, capable of causing irreversible damage and, in severe instances, leading to permanent blindness. Accurate optic cup (OC) and optic disc (OD) segmentation are essential in glaucoma screening. In this study, a novel OC and OD segmentation approach is proposed. Based on U‐Net, it is optimized by introducing cardinality dimensions. Moreover, attention gates are implemented to reinforce salient features while suppressing irrelevant information. Additionally, a convolutional block attention module (CBAM) is integrated into the decoder segment. This fusion hones in on effective information in both channel and spatial dimensions. Meanwhile, an image processing procedure is proposed for image normalization and enhancement. All of these increase the accuracy of the model. This model is evaluated on the ORIGA and REFUGE datasets, demonstrating the model's superiority in OC and OD segmentation compared to the state‐of‐the‐art methods. Additionally, after the proposed image processing, cup‐to‐disc ratio (CDR) prediction on a batch of 155 in‐house fundus images yields an absolute CDR error of 0.099, which is reduced by 0.04 compared to the case where only conventional processing was performed.

Sorafenib and lenvatinib are frontline treatments for advanced hepatocellular carcinoma (HCC). While lenvatinib surpasses sorafenib in efficacy and tolerability, resistance remains a significant clinical challenge. Recent research highlights the potential of TRIM family proteins in modulating lenvatinib resistance in HCC, necessitating a deeper understanding of their specific mechanisms. In this study, we screened TRIM family genes differentially expressed in lenvatinib-resistant cells using the GEO database, verifying their expression through qRT-PCR and identifying TRIM29 as a key target. Clinical samples were analyzed to assess TRIM29 expression, clinical significance, and its correlation with lenvatinib treatment efficacy. Stable TRIM29 overexpression in SK-Hep1 and LM3 cells was confirmed by Western blotting. The impact of TRIM29 on lenvatinib sensitivity in liver cancer cells was evaluated using colony formation assays, CCK8, flow cytometry, and in vivo experiments. Transcriptome sequencing, mass spectrometry, and co-immunoprecipitation (CO-IP) were employed to elucidate TRIM29′s regulatory mechanisms. Results from the GEO database indicated significant upregulation of TRIM29, TRIM50, TRIM31, and TRIM9 in HUH7-resistant cells, with qRT-PCR confirming TRIM29 as markedly upregulated. In 112 liver cancer patients clinical samples, TRIM29 expression was significantly higher in patients with stable disease or partial response to lenvatinib compared to those with disease progression. High TRIM29 expression was associated with longer overall survival and recurrence-free periods in HCC patients. Mechanistic studies revealed that TRIM29 enhances lenvatinib sensitivity by degrading YBX1 through ubiquitination, thereby inhibiting the PI3K/AKT signaling pathway and reversing resistance. These findings suggest that TRIM29 is a promising therapeutic target for overcoming lenvatinib resistance in HCC. Conclusion: TRIM29 degrades YBX1 through ubiquitination, thereby inhibiting the PI3K/AKT signaling pathway and reversing lenvatinib resistance in HCC. TRIM29 can serve as an independent prognostic indicator of survival and recurrence in HCC patients, and it may provide new avenues for developing innovative treatment strategies for HCC.

Summary: Non-invasive prenatal testing (NIPT) not only enables the detection of chromosomal anomalies in fetuses but also generates vast amounts of ultra-low-depth sequencing data, which can be leveraged for population genomic studies. Here, we present a protocol designed for massive ultra-low-depth sequencing datasets. We detail the steps for data processing, quality control, and genotype imputation, followed by genome-wide association study (GWAS) and post-GWAS analyses. This protocol applies to a wide range of ultra-low-depth sequencing studies, extending beyond data from NIPT.For complete details on the use and execution of this profile, please refer to Xiao et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and disrupt intracellular Cu homeostasis. Extra intracellular Cu induces cuproptosis and chemodynamic therapy (CDT), which further cascades immunogenic cell death (ICD) and activates antitumor immune responses. However, the tumor immunosuppressive microenvironment (TIM) attenuates the efficiency of the immune response. Herein, a biomimic nanodrug (ECNM) is fabricated, of which ES, Cu2+ and NLG919 (an IDO1 inhibitor) are integrated via a self‐assembly process and subsequently coated with 4T1 cell membrane. ECNM can overcome the typical drawbacks of ES, ameliorating the stability and half‐life of ES by membrane‐coating and enhancing its tumor accumulation and internalization via homotypic targeting. It is worth mentioning that, the addition of NLG919 is also beneficial to the system circulation stability of ES and reduces the non‐specific ES release. After internalization, ECNM dissociates via the glutathione‐responsive process and exhibits comprehensive antitumor capabilities, including cuproptosis, CDT and TIM reversing, thereby eliciting ICD and optimizing the antitumor immune response. Furthermore, ECNM not only accelerates tumor regression but also gains a strong abscopal effect and displays the potential of tumor vaccination. Overall, ECNM can activate antitumor immunity via cuproptosis and CDT, together with TIM reversing, for cancer treatment.

Lake health assessment is the basis for lake ecosystem management and protection. A comprehensive index system is essential for diagnosing these problems. However, previous assessments may have neglected the integrity of lake ecosystems and assessed lake health from a partial perspective. Selecting the optimum indicators and constructing the index system in a rational and scientific way are key to lake health. Here, ecosystem integrity and services were incorporated into the lake assessment framework to guide the selection and arrangement of indices. Under this framework, a multilevel and multi-index system was constructed, which can provide a comprehensive diagnosis of lake ecosystems. The index system consists of five dimensions: organism structural integrity, habitat structural integrity, matter process integrity, hydrological process integrity, and social services function. Each dimension contained several basic indices, and a total of 16 indicators were selected for the basic index layer. Furthermore, the reference state was carefully selected and used to set the health level and health scores. In addition, a fuzzy binary comparison method was used to assign the optimum weights for each index. The framework was applied to Lake Baiyangdian to provide a comprehensive diagnosis. The overall status of the lake was sub-healthy. Structural and process integrity were impaired to some extent and assessed as unhealthy and sub-healthy, whereas services were assessed as healthy. The framework proposed a rational and balanced way to construct a comprehensive index system and incorporated social services, which is more accurate and reliable to provide a diagnosis result. It can also be widely applied, benefiting lake ecosystem management and protection and increasing public awareness of lake health.

The expansion of sharing accommodation has raised concerns about consumer distrust. Scholars have increasingly focused on studying the negative effects of distrust spillover in this field. This study aimed to analyze the factors influencing distrust spillover, understand its mechanism, and propose effective methods to prevent it. Based on triadic reciprocal determinism and trust transfer theory, the study developed a model of distrust origins, transmission, and spillover. Beijing Airbnb listings data were collected and analyzed using sentiment analysis, machine learning, and econometric statistics in English and Chinese languages. The findings revealed that guests’ distrust results in two types of spillover: affecting individual repurchase decisions and influencing potential consumers consumption intentions. And the study identified a window period threshold for the spillover of guests’ distrust, where experiencing more than three failure experiences lead to a spillover effect on consumer decision-making. By monitoring consumer failure experiences, controlling the window period, and addressing negative impressions of hosts, the impact of distrust spillover could be mitigated. This study served as a clue for hosts and platforms in the sharing accommodation industry, highlighting the dual spillover effects of guests’ distrust. It also provided strategic support for the development of sharing accommodations and contributed to optimizing service.

Abstract As functional derivatives of mesenchymal stem cells (MSCs), small extracellular vesicles (sEVs) have garnered significant attention and application in regenerative medicine. However, the technical limitations for large‐scale isolation of sEVs and their heterogeneous nature have added complexity to their applications. It remains unclear if the heterogeneous sEVs represent different aspects of MSCs functions. Here, we provide a method for the large‐scale production of sEVs subpopulations derived from human umbilical cord mesenchymal stem cells (HucMSCs), utilizing tangential flow filtration combined with size exclusion chromatography. The resulting subpopulations, S1‐sEVs and S2‐sEVs, exhibited stable variations in size, membrane‐marked proteins, and carrying cargos, thereby displaying distinct functions both in vitro and in animal disease models. S1‐sEVs, that highly expressed CD9, HRS and GPC1, demonstrated a greater immunomodulatory impact, while S2‐sEVs with enriched expression of CD63 and FLOT1/2 possessed enhanced capacities in promoting cell proliferation and angiogenesis. These discrepancies are attributed to the specific proteins and miRNAs they contain. Further investigation revealed that the two distinct sEVs subpopulations corresponded to different biological processes: the ESCRT pathway (S1‐sEVs) and the ESCRT‐independent pathway represented by lipid rafts (S2‐sEVs). Therefore, we propose the potential for large‐scale isolation and purification of sEVs subpopulations from HucMSCs with distinct functions. This approach may provide advantages for targeted therapeutic interventions in various MSC indications.

Summary: The physiological perturbations induced by high-altitude exposure in mountain climbers, manifesting as immunological and metabolic deviations, have been previously reported but are not fully understood. In this study, we obtain multi-omic profiles of climbers’ blood samples, including single-cell transcriptomic analysis of 375,722 immune cells, and plasma metabolomics and lipidomics. Longitudinal analysis reveals dynamic immune response profiles, during the acclimatization period, characterized by the downregulation of inflammatory responses in myeloid cell subsets and by the enhancement of immune effector processes in cytotoxic CD8+ T, γδT, and CD16+ natural killer cells. In contrast, during extreme-altitude mountaineering, the activation of inflammatory responses and impairment of immune effector function are observed, concomitant with an increased cellular response to hypoxia and oxidative stress pathways. Furthermore, glycolysis and antioxidant gene expression are upregulated during extreme-altitude mountaineering. Plasma metabolic analysis reveals significant alterations, involving enhanced glutamine and fatty acid metabolism.

PurposeThis study aimed to report the ocular manifestations in individuals with coronavirus disease 2019 (COVID-19) and investigate any correlation between the occurrence of ocular symptoms and systemic symptoms.MethodsA retrospective electronic survey was conducted among the general public in northern China from December 2022 through February 2023. Inclusion criteria for COVID-19 was confirmed testing positive via a polymerase chain reaction (PCR) test or testing positive for COVID-19 via an antigen kit. The anonymous survey collected information on demographics, systemic COVID-19 symptoms, ocular diagnosis and symptoms, comorbidities and disease history.ResultsA total of 2,405 survey responses were collected and the final analysis included individuals in the 335 COVID-19 positive group and 434 individuals in the COVID-19 negative group. Among COVID-19 positive patients 66.3% (n = 222) reported experiencing ocular symptoms. Dryness (n = 106, 31.6%), blurred vision (n = 81, 24.2%), eye pain (n = 72, 21.5%), and itching (n = 71, 21.2%) were the main features. COVID-19 was found to be associated with a higher prevalence of conjunctivitis, iritis, uveitis, retinal vein occlusion and optic neuritis. The majority of individuals (51.0%) developed eye symptoms after the onset of COVID-19 systemic symptoms. There was no significant association between the severity of systemic symptoms and ocular symptoms.ConclusionIndividuals with COVID-19 were significantly more likely to experience ocular symptoms. COVID-19 was found to be associated with a higher prevalence of retinal diseases. The majority of individuals developed ocular symptoms right after the onset of systemic symptoms.

Summary: Learned action sequences are suggested to be organized hierarchically, but how the various hierarchical levels are processed by different cortical regions remains largely unknown. By training monkeys to perform heterogeneous saccade sequences, we investigated the role of the dorsolateral prefrontal cortex (DLPFC) and the lateral intraparietal cortex (LIP) in sequence planning and execution. The electrophysiological recording revealed that sequence-level initiation information was mostly signaled by DLPFC neurons, whereas subsequence-level transition was largely encoded by LIP neurons. Although electrical microstimulation on DLPFC weakly affected sequence performance, inactivating DLPFC significantly increased the initiation latency of the entire sequences, indicating that DLPFC was involved in the sequence initiation. In contrast, either microstimulation or inactivation of area LIP caused improper switches between subsequences, suggesting that LIP played a role in subsequence switch. Overall, these results demonstrated that frontal and parietal cortices play distinct yet complementary roles in controlling learned saccade sequences.

Chimeric Antigen Receptor (CAR) T cell therapy has gained success in adoptive cell therapy for hematological malignancies. Although most CAR cell therapies in clinical trials or markets remain autologous, their acceptance has been limited due to issues like lengthy manufacturing, poor cell quality, and demanding cost. Consequently, “Off-the-shelf”, universal CAR (UCAR) cell therapy has emerged. Current concerns with UCAR therapies revolve around side effects such as graft versus host disease (GVHD) and host versus graft response (HVGR). Preclinical research on UCAR cell therapies aims to enhance efficacy and minimize these side effects. Common approaches involve gene editing techniques to knock out T cell receptor (TCR), human leukocyte antigen (HLA), and CD52 expression to mitigate GVHD and HVGR risks. However, these methods carry drawbacks including potential genotoxicity of the edited cells. Most recently, novel editing techniques, such as epigenetic editing and RNA writer systems, have been developed to reduce the risk of GVHD and HVGR, allowing for multiplex editing at different sites. Additionally, incorporating more cell types into UCAR cell therapies, like T-cell subtypes (DNT, γδT, virus-specific T cells) and NK cells, can efficiently target tumors without triggering side effects. In addition, the limited efficacy of T cells and NK cells against solid tumors is being addressed through CAR-Macrophages. In summary, CAR cell therapy has evolved to accommodate multiple cell types while expanding applications to various diseases, including hematologic malignancies and solid tumors, which holds tremendous growth potential and is promised to improve the lives of more patients in the future.

Objective: The relationship between serum lipids and prognosis of pancreatic cancer has not been confirmed. Our purpose in the study was to investigate the associations between serum lipids level and prognosis in patients with pancreatic cancer. Methods: A retrospective study was performed on 286 pancreatic cancer patients who admitted to our hospital from January 1, 2017 to December 31, 2021. Serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, progression free survival (PFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model. Results: Regarding serum lipids level, compared to normal apolipoprotein B/ apolipoprotein A (ApoB/ApoA1), high ApoB/ApoA1 level indicated a shorter OS (HR:2.028, 95% CI: 1.174–2.504, P = 0.011) and a shorter PFS (HR:1.800, 95% CI: 1.076–3.009, P = 0.025). Other serum lipid molecules were not associated with PFS and OS. Conclusion: ApoB/ApoA1 might be an independent prognostic factor of pancreatic cancer.