Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

Screening of mRNA markers in early bovine tuberculosis blood samples.

Bovine tuberculosis (bTB) is a chronic zoonotic disease caused by Mycobacterium bovis. A large number of cattle are infected with bTB every year, resulting in huge economic losses. How to control bTB is an important issue in the current global livestock economy. In this study, the original transcriptome sequences related to this study were obtained from the dataset GSE192537 by searching the Gene Expression Omnibus (GEO) database. Our differential gene analysis showed that there were obvious biological activities related to immune activation and immune regulation in the early stage of bTB. Immune-related biological processes were more active in the early stage of bTB than in the late. There were obvious immune activation and immune cell recruitment in the early stage of bTB. Regulations in immune receptors are associated with pathophysiological processes of the early stage of bTB. A gene module consisting of 236 genes significantly related to the early stage of bTB was obtained by weighted gene co-expression network analysis, and 18 hub genes were further identified as potential biomarkers or therapeutic targets. Finally, by random forest algorithm and logistic regression modeling, FCRL1 was identified as a representative mRNA marker in early bTB blood. FCRL1 has the potential to be a diagnostic biomarker in early bTB.

Rhizosphere Ventilation Effects on Root Development and Bacterial Diversity of Peanut in Compacted Soil.

Soil compaction is one of the crucial factors that restrains the root respiration, energy metabolism and growth of peanut (Arachis hypogaea L.) due to hypoxia, which can be alleviated by ventilation. We therefore carried out a pot experiment with three treatments: no ventilation control (CK), (2) ventilation volumes at 1.2 (T1), and 1.5 (T2) times of the standard ventilation volume (2.02 L/pot). Compared to no-ventilation in compacted soil, ventilation T1 significantly increased total root length, root surface area, root volume and tips at the peanut anthesis stage (62 days after sowing), while T2 showed a negative impact on the above-mentioned root morphological characteristics. At the podding stage (S2, 95 days after sowing), both ventilation treatments improved root morphology, especially under T1. Compared to CK, both ventilation T1 and T2 decreased the activities of enzymes involving the anaerobic respiration, including root lactate dehydrogenase, pyruvate decarboxylase and alcohol dehydrogenase. The activities of antioxidant enzymes of root superoxide dismutase, peroxidase and catalase also decreased at S1, while superoxide dismutase and peroxidase significantly increased under T1 at S2. The ventilation of compacted soil changed soil nitrogen-fixing bacterial communities, with highest bacterial alpha diversity indices under T1. The Pearson correlation analyses indicated a positive relationship between the relative abundance of Bradyrhizobiaceae and root activity, and between unclassified_family of Rhizobiales and the root surface area, while Enterobacteriaceae had a negative impact on the root nodule number. The Pearson correlation test showed that the root surface, tips and activity positively correlated with root superoxide dismutase and peroxidase activities. These results demonstrate that soil ventilation could enhance plant root growth, the diversity and function of soil nitrogen-fixing bacterial communities. The generated results from this present study could serve as important evidence in alleviating soil hypoxia caused by compaction.

Cost-effectiveness of immune checkpoint inhibitors in treating metastatic urothelial cancer.

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients. Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab). The patients were divided into three different groups: receiving chemotherapy alone, receiving a combination of first-line ICI and chemotherapy (ICI combination therapy), and receiving chemotherapy as the first-line treatment followed by second-line ICI therapy (Subsequent ICI therapy). The primary endpoint was cost per life day, while lifetime medical costs and overall survival were also evaluated. Results: The 74 enrolled patients had a median age of 67.0 years, with 62.2% being male. Of these patients, 23 had received chemotherapy only, while the remaining patients had received combined therapy with ICI in either first-line or as subsequent agents (37 patients had ever received atezolizumab, 18 pembrolizumab, 1 Durvalumab, 1 Nivolumab, and 1 Avelumab separately.). Fifty-five patients (74.3%, 55/74) received cisplatin amongst all the patients who underwent chemotherapy. Median overall survival was 27.5 months (95% CI, 5.2-49.9) in the first-line ICI combination therapy group, and 8.9 months (95% CI, 7.1-10.8) in the chemotherapy only. Median overall survival for the subsequent ICI therapy group was not reached. The median lifetime cost after metastatic UC diagnosis was USD 31,221. The subsequent ICI therapy group had significantly higher costs when compared with the ICI combination therapy group (155.8 USD per day, [IQR 99.0 to 220.5] v 97.8 USD per day, [IQR 60.8 to 159.19], p = 0.026). Higher insurance reimbursement expenses for the subsequent ICI therapy group were observed when compared with the ICI combination therapy group. Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy.

Effects of Hericium erinaceus polysaccharide in porcine IPEC-J2 intestinal epithelial cells against apoptosis induced by oxidative stress.

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.

Malfunction endostapler trapped on renal vein - Nightmare scenario for surgeon.

The utilization of endostapler devices has become standard practice for renal vein ligation during laparoscopic nephroureterectomy. While exceptionally rare, malfunctions can occur in these devices. In the video, we present a malfunctioning endostapler that became trapped on the renal vein. Fortunately, this catastrophic event was successfully managed without conversion to open surgery or massive blood loss and was recorded on video. We propose a structured management flow chart for addressing GIA malfunction, aiming to assist surgeons in navigating through this potentially life-threatening situation.

Ankle-brachial index associates with arteriovenous fistula stenosis.

BACKGROUND: Arteriovenous fistula (AVF) stenosis is associated with pre-existing arterial atherosclerosis of AVF and results in significant morbidity and hospitalization for hemodialysis patients. The ankle brachial index (ABI) is a noninvasive method of assessing atherosclerosis. This study was to examine whether ABI is a significant predictor for AVF stenosis. METHODS: This was a retrospective, longitudinal cohort study. Patients with hemodialysis between 1 January 2016 and 31 December 2022 were reviewed. ABI was assessed in January 2016. AVF stenosis was diagnosed by fistulography. RESULTS: A total of 82 patients were included. Forty-two patients experienced AVF stenosis. The univariate logistic regression analysis showed that AVF stenosis was associated with age (OR: 1.045, p = 0.033), DM status (OR: 5.529, p = 0.013), 7-year averaged cholesterol level (OR: 1.018, p = 0.034), 7-year averaged triglyceride level (OR: 1.007, p = 0.017), and ABI (OR: 0.011, p < 0.001). In multivariate logistic regression analysis, ABI was a strong predictor for AVF stenosis (OR: 0.036, p = 0.023). Then, a cut-off point of ABI with optimal sensitivity and specificity for AVF stenosis was 1.01. An analysis of time to events with adjustment for other variables showed that patients with ABI < 1.01 were significantly associated with AVF stenosis (HR: 3.859, p < 0.001). CONCLUSIONS: ABI below 1.01 was associated with AVF stenosis. This finding may be useful in tailoring surveillance programs for monitoring AVF function.

Effectiveness of Chewing Gum on Nausea and Vomiting Following Postprocedure: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to evaluate the effectiveness of chewing gum in reducing postprocedure nausea and vomiting. DESIGN: A systematic review and meta-analysis. METHODS: A systematic literature search was performed on MEDLINE Complete, EMBASE, CINAHL, PubMed, Web of Science, Academic Search Complete, and Cochrane Library databases from their inception to October 2, 2022. Methodological quality was assessed using the revised Cochrane Risk of Bias 2.0 tool for randomized trials. A meta-analysis was performed using a fixed-effects model to calculate pooled effects with Review Manager 5.4.1. FINDINGS: Twelve randomized trials encompassing 1,458 participants were pooled. The chewing gum intervention was effective in reducing vomiting (P = .007; risk ratio = 0.55; 95% Cl = 0.35-0.85), but not nausea (P = .14; risk ratio = 0.84; 95% Cl = 0.66-1.06). Thirty-minute sessions of gum chewing were significantly more effective in reducing vomiting than 15-minute sessions (P = .04; risk ratio = 0.31; 95% Cl = 0.1-0.93). CONCLUSIONS: The results indicate that repeated gum chewing sessions of at least 30 minutes may act as a nonpharmacological intervention for reducing vomiting. However, further studies are necessary to determine the outcomes of chewing gum interventions.

Biochar relieves the toxic effects of microplastics on the root-rhizosphere soil system by altering root expression profiles and microbial diversity and functions.

The accumulation of microplastics in agricultural soil brings unexpected adverse effects on crop growth and soil quality, which is threatening the sustainability of agriculture. Biochar is an emerging soil amendment material of interest as it can remediate soil pollutants. However, the mechanisms underlying biochar alleviated the toxic effects of microplastics in crops and soil were largely unknown. Using a common economic crop, peanut as targeted species, the present study evaluated the plant physiologica and molecular response and rhizosphere microbiome when facing microplastic contamination and biochar amendment. Transcriptome and microbiome analyses were conducted on peanut root and rhizosphere soil treated with CK (no microplastic and no biochar addition), MP (1.5% polystyrene microplastic addition) and MB (1.5% polystyrene microplastic+2% peanut shell biochar addition). The results indicated that microplastics had inhibitory effects on plant root development and rhizosphere bacterial diversity and function. However, biochar application could significantly promote the expressions of key genes associated with antioxidant activities, lignin synthesis, nitrogen transport and energy metabolism to alleviate the reactive oxygen species stress, root structure damage, nutrient transport limitation, and energy metabolism inhibition induced by microplastic contamination on the root. In addition, the peanut rhizosphere microbiome results showed that biochar application could restore the diversity and richness of microbial communities inhibited by microplastic contamination and promote nutrient availability of rhizosphere soil by regulating the abundance of nitrogen cycling-related and organic matter decomposition-related microbial communities. Consequently, the application of biochar could enhance root development by promoting oxidative stress resistance, nitrogen transport and energy metabolism and benefit the rhizosphere microecological environment for root development, thereby improved the plant-soil system health of microplastic-contaminated agroecosystem.

Biochar alleviated the toxic effects of microplastics-contaminated geocarposphere soil on peanut (Arachis hypogaea L.) pod development: roles of pod nutrient metabolism and geocarposphere microbial modulation.

BACKGROUND: The accumulation of microplastics in agricultural soil poses a threat to the sustainability of agriculture, impacting crop growth and soil health. Due to the geocarpy feature of peanut, geocarposphere soil environment is critical to pod development and its nutritional quality. While the effects of microplastics in the rhizosphere have been studied, their impact on peanut pod in the geocarposphere remains unknown. Biochar has emerged as a potential soil agent with the ability to remediate soil contamination. However, the mechanisms of biochar in mitigating the toxic effects of microplastics-contaminated geocarposphere soil on peanut pod development remain largely unexplored. RESULTS: We evaluated the peanut pod performance and microbiome when facing microplastics contamination and biochar amendment in geocarposphere soil. The results showed that microplastics present in geocarposphere soil could directly enter the peanut pod, cause pod developmental disorder and exert adverse effects on nutritional quality. Aberrant expression of key genes associated with amino acid metabolism, lipid synthesis, and auxin and ethylene signaling pathways were the underlying molecular mechanisms of microplastics-induced peanut pod developmental inhibition. However, these expression abnormalities could be reversed by biochar application. In addition, peanut geocarposphere microbiome results showed that biochar application could restore the diversity of microbial communities inhibited by microplastics contamination and promote the relative abundance of bacteria correlated with pathogen resistance and nitrogen cycle of geocarposphere soil, further promoting peanut pod development. CONCLUSION: This study demonstrated that biochar application is an effective strategy to mitigate the toxic effects of microplastics-contaminated geocarposphere soil on pod development and nutritional quality. © 2023 Society of Chemical Industry.

Characteristics of Transcriptome and Metabolome Concerning Intramuscular Fat Content in Beijing Black Pigs.

To study the characteristics of genes and metabolites related to intramuscular fat (IMF) content with less influence by breed background and individual differences, the skeletal muscle samples from 40 Beijing black pigs with either high or low IMF content were used to perform transcriptome and metabolome analyses. About 99 genes (twofold-change) were differentially expressed. Up-regulated genes in the high IMF pigs were mainly related to fat metabolism. The key genes in charge of IMF deposition are ADIPOQ, CIDEC, CYP4B1, DGAT2, LEP, OPRL1, PLIN1, SCD, and THRSP. KLHL40, TRAFD1, and HSPA6 were novel candidate genes for the IMF trait due to their high abundances. In the low IMF pigs, the differentially expressed genes involved in virus resistance were up-regulated. About 16 and 18 differential metabolites (1.5 fold-change) were obtained in the positive and negative modes, respectively. Pigs with low IMF had weaker fatty acid oxidation due to the down-regulation of various carnitines. Differentially expressed genes were more important in determining IMF deposition than differential metabolites because relatively few differential metabolites were obtained, and they were merely the products under the physiological status of diverged IMF content. This study provided valuable information for further studies on IMF deposition.

LncHLEF promotes hepatic lipid synthesis through miR-2188-3p/GATA6 axis and encoding peptides and enhances intramuscular fat deposition via exosome.

Long noncoding RNAs (lncRNAs) have emergingly been implicated in mammalian lipid metabolism. However, their biological functions and regulatory mechanisms underlying adipogenesis remain largely elusive in chicken. Here, we systematically characterized the genome-wide full-length lncRNAs in the livers of pre- and peak-laying hens, and identified a novel intergenic lncRNA, lncHLEF, an RNA macromolecule with a calculated molecular weight of 433 kDa. lncHLEF was primarily distributed in cytoplasm of chicken hepatocyte and significantly up-regulated in livers of peak-laying hens. Functionally, lncHLEF could promote hepatocyte lipid droplet formation, triglycerides and total cholesterol contents. Mechanistically, lncHLEF could not only serve as a competitive endogenous RNA to modulate miR-2188-3p/GATA6 axis, but also encode three small functional polypeptides that directly interact with ACLY protein to enable its stabilization. Importantly, adeno-associated virus-mediated liver-specific lncHLEF overexpression resulted in increased hepatic lipid synthesis and intramuscular fat (IMF) deposition, but did not alter abdominal fat (AbF) deposition. Furthermore, hepatocyte lncHLEF could be delivered into intramuscular and abdominal preadipocytes via hepatocyte-secreted exosome to enhance intramuscular preadipocytes differentiation without altering abdominal preadipocytes differentiation. In conclusion, this study revealed that the lncHLEF could promote hepatic lipid synthesis through two independent regulatory mechanisms, and could enhance IMF deposition via hepatocyte-adipocyte communications mediated by exosome.

Context-aware augmentation for liver lesion segmentation: shape uniformity, expansion limit and fusion strategy.

Background: Data augmentation with context has been an effective way to increase the robustness and generalizability of deep learning models. However, to our knowledge, shape uniformity, expansion limit, and fusion strategy of context have yet to be comprehensively studied, particularly in lesion segmentation of medical images. Methods: To examine the impact of these factors, we take liver lesion segmentation based on the well-known deep learning architecture U-Net as an example and thoroughly vary the context shape, the expansion bandwidth as well as three representative fusion methods. In particular, the context shape includes rectangular, circular and polygonal, the expansion bandwidth is scaled by a maximum value of 2 compared to the lesion size, and the context fusion weighting strategy is composed of average, Gaussian and inverse Gaussian. Results: Studies conducted on a newly constructed high-quality and large-volume dataset show that (I) uniform context improves lesion segmentation, (II) expanding the context with either 5 or 7 pixels yields the highest performance for liver lesion segmentation, depending on the lesion size, and (III) an unevenly distributed weighting strategy for context fusion is appreciated but in the opposite direction, depending on lesion size as well. Conclusions: Our findings and newly constructed dataset are expected to be useful for liver lesion segmentation, especially for small lesions.

Unilateral Bi/Multi-Portal Endoscopy for the Treatment of Complicated Lumbar Degenerative Diseases with Utilization of Uniaxial Spinal Endoscope, Instead of Arthroscope: Technique Note and Clinical Results.

Objective: This article aims to discuss a novel surgical strategy, referred to as unilateral bi/multi-portal endoscopy (UME), which used a uniaxial spinal endoscope instead of an arthroscope in the traditional unilateral biportal endoscopy (UBE) surgical procedure in our study of the treatment of complicated lumbar degenerative diseases. Methods: This retrospective study included 42 patients diagnosed with high-migrated lumbar disc herniation and bilateral spinal stenosis who underwent UME surgery from January 2021 to December 2021. Patients included 20 men and 22 women, with an average age of 55.97±14.92 years. The average follow-up period was 13.19 months. The demographic data, operation time (min), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry Disability Index (ODI) scores were used to evaluate the surgical outcomes. Three-dimensional CT scans and MRI were conducted to evaluate the radiographic improvement. Results: A total of 26 patients were diagnosed with lumbar disc herniation and 16 with lumbar spinal stenosis. All 42 patients underwent UME surgery and achieved satisfactory outcomes. The operation time was 154.46±46.09 min. The average follow-up time was 13.19±1.33 months. The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 3.84±1.00 and 0.70±0.46, respectively (P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 6.46±1.08 and 1.03±0.64, respectively (P <0.05). Significant differences existed between preoperative ODI scores (58.70±11.22%) and the last follow-up ODI scores (9.24±3.04%; P<0.05). All patients achieved significant pain relief and functional improvement after the surgery. No severe complications occurred, except for two cases of postoperative dysesthesia and one case suffered from vertebral compression fractures induced by a postoperative accidental injury. Symptoms of numbness disappeared within one week with treatment using dexamethasone and neurotrophic drugs. The vertebral fracture case recovered with percutaneous kyphoplasty treatment. Conclusion: This study suggests that UME is a promising treatment strategy for high-migrated disc herniation and bilateral spinal stenosis.

Successful rescue pneumovesicoscopic surgery for post-Deflux® vesicoureteral junction obstruction.

BACKGROUND: Vesicoureteral junction (VUJ) obstruction after Deflux® subureteral injection for vesicoureteral reflux (VUR) is rare and minimally invasive management has not been reported. This work investigated the patients who underwent Deflux® injection for VUR and identified those with subsequent VUJ obstruction. METHODS: Medical records of matched patients from October 2003 to March 2022 were reviewed, and parameters were retrospectively studied. All patients underwent Deflux® injection. The injection was performed under general anesthesia using the same manner. For patients complicated with VUJ obstruction, the symptoms, signs, management, images, renal ultrasounds, Tc-99m dimercaptosuccinic acid renal scintigraphy, histology of VUJ region, and outcomes were documented and reported. VUJ stenosis was diagnosed by performing renal ultrasound and magnetic resonance imaging. RESULTS: Totally 407 patients (554 ureterorenal units) received Dx/HA injections for VUR. VUJ obstruction was found in three patients (four ureterorenal units). Originally, three were grade V VUR, and one was grade IV. The repeated injection was not a risk factor for VUJ obstruction. The overall incidence of VUJ obstruction post-Dx/HA injection was 0.7% by ureter. The incidences were 0%, 0.75%, and 2.25% for grade I-III, IV, and V VUR, respectively. After the initial conversion case of pneumovesicoscopic ureteral reimplantation, the procedure was performed smoothly and successfully in the two following cases. CONCLUSIONS: Pneumovesicoscopic ureteral reimplantation offers an alternative for VUJ obstruction following Dx/HA injection for VUR. Fibrosis and foreign-body reaction may influence the feasibility. High-grade VUR and young age of injection were related to VUJ obstruction.

Exploring the mechanism of Cd uptake and translocation in rice: Future perspectives of rice safety.

Cadmium (Cd) contamination in rice fields has been recognized as a severe global agro-environmental issue. To reach the goal of controlling Cd risk, we must pay more attention and obtain an in-depth understanding of the environmental behavior, uptake and translocation of Cd in soil-rice systems. However, to date, these aspects still lack sufficient exploration and summary. Here, we critically reviewed (i) the processes and transfer proteins of Cd uptake/transport in the soil-rice system, (ii) a series of soil and other environmental factors affecting the bioavailability of Cd in paddies, and (iii) the latest advances in regard to remediation strategies while producing rice. We propose that the correlation between the bioavailability of Cd and environmental factors must be further explored to develop low Cd accumulation and efficient remediation strategies in the future. Second, the mechanism of Cd uptake in rice mediated by elevated CO2 also needs to be given more attention. Meanwhile, more scientific planting methods (direct seeding and intercropping) and suitable rice with low Cd accumulation are important measures to ensure the safety of rice consumption. In addition, the relevant Cd efflux transporters in rice have yet to be revealed, which will promote molecular breeding techniques to address the current Cd-contaminated soil-rice system. The potential for efficient, durable, and low-cost soil remediation technologies and foliar amendments to limit Cd uptake by rice needs to be examined in the future. Conventional breeding procedures combined with molecular marker techniques for screening rice varieties with low Cd accumulation could be a more practical approach to select for desirable agronomic traits with low risk.

HIF-1α/MMP-9 promotes spinal cord central sensitization in rats with bone cancer pain.

Bone cancer pain (BCP) is one of the most prevalent and serious symptoms of patients with cancer. Currently, the medical interventions used for the treatment of BCP do not act with optimal safety and efficacy. In this study, we appraised whether the hypoxia-inducible factor 1α (HIF-1α)/metalloproteinase-9 (MMP9) axis activates the PI3K/AKT pathway, resulting in elevated spinal cord central sensitization and aggravated BCP. BCP rats were established by tibial injection of Walker 256 cells, followed by different interventions in rats using HIF-1ɑ inhibitor LW6 or antibody treatments. After treatment with LW6 or antibody against HIF-1α, central sensitization in the spinal cord tissues of rats was inhibited, and pain perception in rats was reduced. Moreover, the activation of glial cells in the spinal cord tissues was ameliorated. The expression of MMP9 was remarkably suppressed in spinal cord tissues after inhibition of HIF-1ɑ activity, and the activity of the PI3K/AKT signaling pathway was inhibited. Further activation of MMP9 expression suppressed the alleviating effect of HIF-1ɑ inhibitor LW6 or antibody on pain perception in rats inoculated with tumors. Taken together, our studies suggest a HIF-1α/MMP9-mediated activation of PI3K/AKT in the spinal cord tissues, resulting in increased pain perception in a rat model with BCP.

Metabolite and Proteomic Profiling of Serum Reveals the Differences in Molecular Immunity between Min and Large White Pig Breeds.

Pig diseases seriously threaten the health of pigs and the benefits of pig production. Previous research has indicated that Chinese native pigs, such as the Min (M) pig, has a better disease resistance ability than Large White (LW) pigs. However, the molecular mechanism of this resistance is still unclear. In our study, we used serum untargeted metabolomics and proteomics, interrogated to characterize differences in the molecular immunities between six resistant and six susceptible pigs raised in the same environment. A total of 62 metabolites were identified as being significantly exhibited in M and LW pigs. Ensemble feature selection (EFS) machine learning methods were used to predict biomarkers of metabolites and proteins, and the top 30 were selected and retained. Weighted gene co-expression network analysis (WGCNA) confirmed that four key metabolites, PC (18:1 (11 Z)/20:0), PC (14:0/P-18: 0), PC (18:3 (6 Z, 9 Z, 12 Z)/16:0), and PC (16:1 (9 Z)/22:2 (13 Z, 16 Z)), were significantly associated with phenotypes, such as cytokines, and different pig breeds. Correlation network analysis showed that 15 proteins were significantly correlated with the expression of both cytokines and unsaturated fatty acid metabolites. Quantitative trait locus (QTL) co-location analysis results showed that 13 of 15 proteins co-localized with immune or polyunsaturated fatty acid (PUFA)-related QTL. Moreover, seven of them co-localized with both immune and PUFA QTLs, including proteasome 20S subunit beta 8 (PSMB8), mannose binding lectin 1 (MBL1), and interleukin-1 receptor accessory protein (IL1RAP). These proteins may play important roles in regulating the production or metabolism of unsaturated fatty acids and immune factors. Most of the proteins could be validated with parallel reaction monitoring, which suggests that these proteins may play an essential role in producing or regulating unsaturated fatty acids and immune factors to cope with the adaptive immunity of different pig breeds. Our study provides a basis for further clarifying the disease resistance mechanism of pigs.