Single-cell transcriptome analysis of epithelial, immune, and stromal signatures and interactions in human ovarian cancer.

A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of NECTIN2 using CRISPR/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC.

Online Monitoring for Human Sit-to-Stand Movement Based on Karush-Kuhn-Tucker Optimized Zonotope Set-Membership Filter.

As the global aging population continues to grow, there has been a significant increase in the number of fall-related injuries among the elderly, primarily due to reduced muscle strength and balance control, especially during sit-to-stand (STS) movements. Intelligent wearable robots have the potential to provide fall prevention assistance to individuals at risk, but an accurate and timely assessment of human movement stability is essential. This article presents a fall prediction algorithm for STS movements based on the Karush-Kuhn-Tucker (KKT) optimized zonotope set-membership filter (KKT-ZSMF), enabling real-time assessment of human stability. To quantify the feasible stability region of human STS movement, a mathematical model is proposed based on dynamic stability theory. Additionally, an online fall-prediction approach is developed, utilizing the zonotope set-membership filter to iteratively update the set that represents the instantaneous stability region. The approach incorporates a KKT optimization algorithm to compute the optimal convex hull, thereby enhancing the accuracy and efficiency of the set-membership filter. Experimental validation is conducted with the participation of 13 subjects including 5 elderly subjects, comparing the performance of the proposed KKT-ZSMF algorithm with other relevant methods. The results confirm the accuracy and real-time performance of the KKT-ZSMF algorithm for predicting human STS movement stability, achieving an overall prediction accuracy of 93.49% and a runtime of no more than 7.91 ms. These findings demonstrate the suitability of the algorithm for fall prevention assistance in daily activities.

The changes of neuroactivity of Tui Na (Chinese massage) at Hegu acupoint on sensorimotor cortex in stroke patients with upper limb motor dysfunction: a fNIRS study.

BACKGROUND: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. METHODS: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. RESULT: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). CONCLUSION: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

Comparative analysis of single cell lung atlas of bat, cat, tiger, and pangolin.

Horseshoe bats (Rhinolophus sinicus) might help maintain coronaviruses severely affecting human health, such as severe acute respiratory syndrome coronavirus (SARS-CoV). Bats may be more tolerant of viral infection than other mammals due to their unique immune system, but the exact mechanism remains to be fully explored. During the coronavirus disease 2019 (COVID-19) pandemic, multiple animal species were diseased by coronavirus infection, especially in the respiratory system. Herein, a comparative analysis with single nucleus transcriptomic data of the lungs across four species, including horseshoe bat, cat, tiger, and pangolin, were conducted. The distribution of entry factors for twenty-eight respiratory viruses was characterized for the four species. Our findings might increase our understanding of the immune background of horseshoe bats.

Double-target neural circuit-magnetic stimulation improves motor function in spinal cord injury by attenuating astrocyte activation.

Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1ß, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury: a resting-state functional MRI study.

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Screening of cell-virus, cell-cell, gene-gene crosstalk among animal kingdom at single cell resolution.

BACKGROUND: The exact animal origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains obscure and understanding its host range is vital for preventing interspecies transmission. METHODS: Herein, we applied single-cell sequencing to multiple tissues of 20 species (30 data sets) and integrated them with public resources (45 data sets covering 26 species) to expand the virus receptor distribution investigation. While the binding affinity between virus and receptor is essential for viral infectivity, understanding the receptor distribution could predict the permissive organs and tissues when infection occurs. RESULTS: Based on the transcriptomic data, the expression profiles of receptor or associated entry factors for viruses capable of causing respiratory, blood, and brain diseases were described in detail. Conserved cellular connectomes and regulomes were also identified, revealing fundamental cell-cell and gene-gene cross-talks from reptiles to humans. CONCLUSIONS: Overall, our study provides a resource of the single-cell atlas of the animal kingdom which could help to identify the potential host range and tissue tropism of viruses and reveal the host-virus co-evolution.

Electrooxidative Dearomatization of Inactive Biphenyls to Cyclohexadienones.

An efficient electrooxidative dearomatization of inactive biphenyls has been developed under mild and easy-to-operate conditions. The protocol provides a powerful tool for the rapid synthesis of cyclohexadienones in moderate to high yields with wide substrate scope and good functional group compatibility even to oxidation-sensitive motifs. This method provides an environment-friendly and direct approach for the construction of C-O bonds with high regioselectivity.

Expression and Predictive Value of Serum NLR, PLR Combined with SAA in Patients with Different Stages of Colorectal Cancer.

Colorectal cancer (CRC) is one of the major causes of death in the world, and has become a serious threat to human life. The prognosis of CRC patients in different pathological stages is quite different, so it is necessary to evaluate the clinical stages of CRC patients before surgery. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), serum amyloid A (SAA) and other indicators have been widely proved to play the role of early diagnosis and prognosis monitoring in chronic inflammatory diseases and cancers. In this study, we collected clinical data of 103 patients with CRC confirmed by pathology in Yiwu Central Hospital from January 2019 to December 2021. In addition, it aims to explore the expression and predictive value of NLR, PLR combined with SAA in patients with different stages of CRC, so as to provide reference for patients to choose a reasonable treatment plan. The results show that serum NLR, PLR combined with SAA can predict CRC staging effectively, which has certain auxiliary value for clinical decision-making.

A Weighted Symmetric Graph Embedding Approach for Link Prediction in Undirected Graphs.

Link prediction is an important task in social network analysis and mining because of its various applications. A large number of link prediction methods have been proposed. Among them, the deep learning-based embedding methods exhibit excellent performance, which encodes each node and edge as an embedding vector, enabling easy integration with traditional machine learning algorithms. However, there still remain some unsolved problems for this kind of methods, especially in the steps of node embedding and edge embedding. First, they either share exactly the same weight among all neighbors or assign a completely different weight to each node to obtain the node embedding. Second, they can hardly keep the symmetry of edge embeddings obtained from node representations by direct concatenation or other binary operations such as averaging and Hadamard product. In order to solve these problems, we propose a weighted symmetric graph embedding approach for link prediction. In node embedding, the proposed approach aggregates neighbors in different orders with different aggregating weights. In edge embedding, the proposed approach bidirectionally concatenates node pairs both forwardly and backwardly to guarantee the symmetry of edge representations while preserving local structural information. The experimental results show that our proposed approach can better predict network links, outperforming the state-of-the-art methods. The appropriate aggregating weight assignment and the bidirectional concatenation enable us to learn more accurate and symmetric edge representations for link prediction.

Single-cell atlas of peripheral blood mononuclear cells from pregnant women.

BACKGROUND: During pregnancy, mother-child interactions trigger a variety of subtle changes in the maternal body, which may be reflected in the status of peripheral blood mononuclear cells (PBMCs). Although these cells are easy to access and monitor, a PBMC atlas for pregnant women has not yet been constructed. METHODS: We applied single-cell RNA sequencing (scRNA-seq) to profile 198,356 PBMCs derived from 136 pregnant women (gestation weeks 6 to 40) and a control cohort. We also used scRNA-seq data to establish a transcriptomic clock and thereby predicted the gestational age of normal pregnancy. RESULTS: We identified reconfiguration of the peripheral immune cell phenotype during pregnancy, including interferon-stimulated gene upregulation, activation of RNA splicing-related pathways and immune activity of cell subpopulations. We also developed a cell-type-specific model to predict gestational age of normal pregnancy. CONCLUSIONS: We constructed a single-cell atlas of PBMCs in pregnant women spanning the entire gestation period, which should help improve our understanding of PBMC composition turnover in pregnant women.

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single-cell sequencing.

BACKGROUND: Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. METHODS: In this study, we compared the single-cell transcriptomes of immune cells from 12 species. Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. RESULTS: Our data revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular crosstalks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells. CONCLUSIONS: This study is the first to provide a comprehensive analysis of the cross-species single-cell transcriptome atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders.

VThunter: a database for single-cell screening of virus target cells in the animal kingdom.

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.

Fine mapping and candidate gene analysis of proportion of four-seed pods by soybean CSSLs.

Soybean yield, as one of the most important and consistent breeding goals, can be greatly affected by the proportion of four-seed pods (PoFSP). In this study, QTL mapping was performed by PoFSP data and BLUE (Best Linear Unbiased Estimator) value of the chromosome segment substitution line population (CSSLs) constructed previously by the laboratory from 2016 to 2018, and phenotype-based bulked segregant analysis (BSA) was performed using the plant lines with PoFSP extreme phenotype. Totally, 5 ICIM QTLs were repeatedly detected, and 6 BSA QTLs were identified in CSSLs. For QTL (qPoFSP13-1) repeated in ICIM and BSA results, the secondary segregation populations were constructed for fine mapping and the interval was reduced to 100Kb. The mapping results showed that the QTL had an additive effect of gain from wild parents. A total of 14 genes were annotated in the delimited interval by fine mapping. Sequence analysis showed that all 14 genes had genetic variation in promoter region or CDS region. The qRT-PCR results showed that a total of 5 candidate genes were differentially expressed between the plant lines having antagonistic extreme phenotype (High PoFSP > 35.92%, low PoFSP< 17.56%). The results of haplotype analysis showed that all five genes had two or more major haplotypes in the resource population. Significant analysis of phenotypic differences between major haplotypes showed all five candidate genes had haplotype differences. And the genotypes of the major haplotypes with relatively high PoFSP of each gene were similar to those of wild soybean. The results of this study were of great significance to the study of candidate genes affecting soybean PoFSP, and provided a basis for the study of molecular marker-assisted selection (MAS) breeding and four-seed pods domestication.

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.

Efficacy of Different Preemptive Analgesia on Postoperative Analgesia, Oxidative Stress, and Inflammatory Response after Gynecological Laparoscopic Surgery.

OBJECTIVE: To observe and compare the analgesic effects of oxycodone, pentazocine, and ketorolac tromethamine pre-emptive analgesia on gynecological laparoscopic patients after operation and the effects on oxidative stress and inflammatory reaction. METHODS: A total of 64 patients who underwent elective gynecological laparoscopic surgery in Yiwu Central Hospital from June 2019 to December 2020 were randomly divided into four groups (n = 16). Before anesthesia induction, oxycodone (group A), pentazocine (group B), ketorolac tromethamine (group C), and normal saline (group D) were, respectively, administered. Patients' mean arterial pressure (MAP) and heart rate (HR) changes, visual analogue scale (VAS), Bruggemann comfort scale (BCS), serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), blood glucose (CLU), serum cortisol level, postoperative adverse reactions, and additional analgesia were recorded at each time point. RESULTS: The MAP levels of T2 (immediate intubation), T3 (immediate catheter removal), and T4 (5 min after catheter removal) in the four groups were higher than those of T1 (quiescent state), and the HR levels T2, T3, and T4 were lower than those of T1 (P < 0.05). The MAP and HR levels of T2, T3, and T4 in patients of groups A, B, and C were lower than those of group D in the same period (P < 0.05). The VAS and BCS scores of groups A, B, and C at 1, 6, 12, and 24 h after operation were better than those of group D at the same time, and the scores of group A at 1 h and 6 h after operation were better than those of groups B and C at the same time (P < 0.05). The levels of serum TNF-α, IL-6, and CRP in the four groups of patients at 6, 12, and 24 h after operation were higher than those before operation, but those in groups A, B, and C were lower than those in group D, and those in group A were higher than those in groups B and C at 12 h and 24 h after operation (P < 0.05). The CLU and serum cortisol levels in the four groups were significantly higher at 6, 12, and 24 h after operation, but those in groups A, B, and C were lower than those in group D, and those in group A were lower than those in groups B and C at 6 and 12 h after operation (P < 0.05). There was no significant difference in the incidence of adverse reactions within 24 h between the four groups (P > 0.05). The incidence of additional analgesia in groups A, B, and C was lower than that in group D (P < 0.05). CONCLUSION: Oxycodone, pentazocine, and ketorolac tromethamine are effective and safe in inhibiting postoperative pain and the generation of inflammatory factors and relieving inflammatory state in gynecological laparoscopic pre-emptive analgesia. Oxycodone has better postoperative analgesic effect because it can effectively alleviate stress reaction.

Enhancing Flavan-3-ol Biosynthesis in Saccharomyces cerevisiae.

Flavan-3-ols are a group of flavonoids that exert beneficial effects. This study aimed to enhance key metabolic processes related to flavan-3-ols biosynthesis. The engineered Saccharomyces cerevisiae strain E32 that produces naringenin from glucose was further engineered for de novo production of two basic flavan-3-ols, afzelechin (AFZ) and catechin (CAT). Through introduction of flavonoid 3-hydroxylase, flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase (DFR), and leucoanthocyanidin reductase (LAR), de novo production of AFZ and CAT can be achieved. The combination of FaDFR from Fragaria × ananassa and VvLAR from Vitis vinifera was optimal. (GGGGS)2 and (EAAAK)2 linkers between DFR and LAR proved optimal for the production of AFZ and CAT, respectively. Optimization of promoters and the enhanced supply of NADPH further increased the production. By combining the best engineering strategies, the optimum strains produced 500.5 mg/L AFZ and 321.3 mg/L CAT, respectively, after fermentation for 90 h in a 5 L bioreactor. The strategies presented could be applied for a more efficient production of flavan-3-ols by various microorganisms.

ShenmaYizhi Decoction Improves the Mitochondrial Structure in the Brain and Ameliorates Cognitive Impairment in VCI Rats via the AMPK/UCP2 Signaling Pathway.

BACKGROUND: ShenmaYizhi decoction (SMYZD) is an effective prescription of traditional Chinese medicine used to treat vascular dementia (VD). Modern research methods have identified its active ingredients clearly as gastrodin, ferulic acid, ginsenosides, and ß-sitosterol. Chronic cerebral hypoperfusion is a driving factor or risk factor for VD, which leads to the disturbance of mitochondrial structure and function. PURPOSE: To observe whether SMYZD improves cognitive impairment by improving mitochondrial structure and function. METHODS: Forty adult rats with vascular cognitive impairment (VCI) caused by the bilateral ligation of common carotid arteries were divided into four groups randomly, including the model group, donepezil group, and low-dose and high-dose SMYZD groups, with 10 rats in each group. Additionally, a sham group was established with 10 rats as the control group. The treatment groups were administered donepezil and two different dosages of SMYZD. The donepezil group was administered 0.45 mg/kg/d donepezil, and the SMYZ-L group was administered 2.97 g/kg/d SMYZ, which were equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats were treated by gavage for 8 consecutive weeks. Morris water maze (MWM) test was performed to evaluate the learning and memory ability. The mitochondria of brain tissue were extracted from brain for further test. Mitochondrial morphology and the signal path of AMPK/PPARα/PGC-1α/UCP2 in mitochondria were detected. RESULTS: With the SMYZD intervention, behavioral performance of rats and pathological changes of mitochondria of brain tissue were significantly improved. In the serum, SOD, GSH-Px, and GSH activities were increased, and the MDA content was decreased. Moreover, the AMPK, PPARα, PGC-1α, UCP2, and ATP5A mRNA and protein expression levels were also reversed by SMYZD. CONCLUSION: SMYZD may provide a potential therapeutic strategy via activating the AMPK/PPARα/PGC-1α/UCP2 signal pathway to improve mitochondrial structure and energy metabolism thereby alleviate vascular cognitive impairment.

A high-resolution cell atlas of the domestic pig lung and an online platform for exploring lung single-cell data.

The genetically engineered pig is regarded as an optimal source of organ transplantation for humans and an excellent model for human disease research, given its comparable physiology to human beings. A myriad of single-cell RNA sequencing (scRNA-seq) data on humans has been reported, but such data on pigs are scarce. Here, we apply scRNA-seq technology to study the cellular heterogeneity of 3-month-old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types. Based on these data, we systematically characterize the similarities and differences in the cellular cross-talk and expression patterns of respiratory virus receptors in each cell type of pig lungs compared with human lungs. Furthermore, we analyze pig lung xenotransplantation barriers and reported the cell-type expression patterns of 10 genes associated with pig-to-human immunobiological incompatibility and coagulation dysregulation. We also investigate the conserved transcription factors (TFs) and their candidate target genes and constructed five conserved TF regulatory networks in the main cell types shared by pig and human lungs. Finally, we present a comprehensive and openly accessible online platform, ScdbLung. Our scRNA-seq atlas of the domestic pig lung and ScdbLung database can guide pig lung research and clinical applicability.

The Wnt/ß-Catenin Pathway Regulated Cytokines for Pathological Neuropathic Pain in Chronic Compression of Dorsal Root Ganglion Model.

Neuropathic pain is one of the important challenges in the clinic. Although a lot of research has been done on neuropathic pain (NP), the molecular mechanism is still elusive. We aimed to investigate whether the Wnt/ß-catenin pathway was involved in NP caused by sustaining dorsal root ganglion (DRG) compression with the chronic compression of dorsal root ganglion model (CCD). Our RNA sequencing results showed that several genes related to the Wnt pathway have changed in DRG and spinal cord dorsal horn (SCDH) after CCD surgery. Therefore, we detected the activation of the Wnt/ß-catenin pathway in DRG and SCDH and found active ß-catenin significantly upregulated in DRG and SCDH 1 day after CCD surgery and peaked on days 7-14. Immunofluorescence results also confirmed nuclear translocalization of active ß-catenin in DRG and SCDH. Additionally, rats had obvious mechanical induced pain after CCD surgery and the pain was significantly alleviated after the application of the Wnt/ß-catenin pathway inhibitor XAV939. Furthermore, we found that the levels of proinflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were significantly elevated in CCD rat serum, while the levels of them were correspondingly decreased after the Wnt/ß-catenin pathway being inhibited. The results of Spearman correlation coefficient analysis showed that the levels of TNF-α and IL-18 were negatively correlated with the mechanical withdrawal thresholds (MWT) after CCD surgery. Collectively, our findings suggest that the Wnt/ß-catenin pathway plays a critical role in the pathogenesis of NP and may be an effective target for the treatment of NP.