Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published. AIM: To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time. METHODS: DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out. RESULTS: LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro. CONCLUSION: LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

Prediction of additional hospital days in patients undergoing cervical spine surgery with machine learning methods.

BACKGROUND: Machine learning (ML), a subset of artificial intelligence (AI), uses algorithms to analyze data and predict outcomes without extensive human intervention. In healthcare, ML is gaining attention for enhancing patient outcomes. This study focuses on predicting additional hospital days (AHD) for patients with cervical spondylosis (CS), a condition affecting the cervical spine. The research aims to develop an ML-based nomogram model analyzing clinical and demographic factors to estimate hospital length of stay (LOS). Accurate AHD predictions enable efficient resource allocation, improved patient care, and potential cost reduction in healthcare. METHODS: The study selected CS patients undergoing cervical spine surgery and investigated their medical data. A total of 945 patients were recruited, with 570 males and 375 females. The mean number of LOS calculated for the total sample was 8.64 ± 3.7 days. A LOS equal to or <8.64 days was categorized as the AHD-negative group (n = 539), and a LOS > 8.64 days comprised the AHD-positive group (n = 406). The collected data was randomly divided into training and validation cohorts using a 7:3 ratio. The parameters included their general conditions, chronic diseases, preoperative clinical scores, and preoperative radiographic data including ossification of the anterior longitudinal ligament (OALL), ossification of the posterior longitudinal ligament (OPLL), cervical instability and magnetic resonance imaging T2-weighted imaging high signal (MRI T2WIHS), operative indicators and complications. ML-based models like Lasso regression, random forest (RF), and support vector machine (SVM) recursive feature elimination (SVM-RFE) were developed for predicting AHD-related risk factors. The intersections of the variables screened by the aforementioned algorithms were utilized to construct a nomogram model for predicting AHD in patients. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and C-index were used to evaluate the performance of the nomogram. Calibration curve and decision curve analysis (DCA) were performed to test the calibration performance and clinical utility. RESULTS: For these participants, 25 statistically significant parameters were identified as risk factors for AHD. Among these, nine factors were obtained as the intersection factors of these three ML algorithms and were used to develop a nomogram model. These factors were gender, age, body mass index (BMI), American Spinal Injury Association (ASIA) scores, magnetic resonance imaging T2-weighted imaging high signal (MRI T2WIHS), operated segment, intraoperative bleeding volume, the volume of drainage, and diabetes. After model validation, the AUC was 0.753 in the training cohort and 0.777 in the validation cohort. The calibration curve exhibited a satisfactory agreement between the nomogram predictions and actual probabilities. The C-index was 0.788 (95% confidence interval: 0.73214-0.84386). On the decision curve analysis (DCA), the threshold probability of the nomogram ranged from 1 to 99% (training cohort) and 1 to 75% (validation cohort). CONCLUSION: We successfully developed an ML model for predicting AHD in patients undergoing cervical spine surgery, showcasing its potential to support clinicians in AHD identification and enhance perioperative treatment strategies.

Identifying critical features of iron phosphate particle for lithium preference.

One-dimensional (1D) olivine iron phosphate (FePO4) is widely proposed for electrochemical lithium (Li) extraction from dilute water sources, however, significant variations in Li selectivity were observed for particles with different physical attributes. Understanding how particle features influence Li and sodium (Na) co-intercalation is crucial for system design and enhancing Li selectivity. Here, we investigate a series of FePO4 particles with various features and revealed the importance of harnessing kinetic and chemo-mechanical barrier difference between lithiation and sodiation to promote selectivity. The thermodynamic preference of FePO4 provides baseline of selectivity while the particle features are critical to induce different kinetic pathways and barriers, resulting in different Li to Na selectivity from 6.2 × 102 to 2.3 × 104. Importantly, we categorize the FePO4 particles into two groups based on their distinctly paired phase evolutions upon lithiation and sodiation, and generate quantitative correlation maps among Li preference, morphological features, and electrochemical properties. By selecting FePO4 particles with specific features, we demonstrate fast (636 mA/g) Li extraction from a high Li source (1: 100 Li to Na) with (96.6 ± 0.2)% purity, and high selectivity (2.3 × 104) from a low Li source (1: 1000 Li to Na) with (95.8 ± 0.3)% purity in a single step.

CircSCNN1A inhibits the proliferation, migration and invasion of renal cell carcinoma cells by decreasing CLDN8 expression through miR-590-5p.

BACKGROUND: Increasing evidence suggests that circular RNA (circRNA) plays a regulatory role in the progression of renal cell carcinoma (RCC). However, the precise function and underlying mechanism of circSCNN1A in RCC progression still remain unclear. METHODS: The expression levels of circSCNN1A, microRNA-590-5p (miR-590-5p), claudin 8 (CLDN8), cyclin D1, matrix metalloprotein 2 (MMP2), MMP9, E-cadherin, N-cadherin and vimentin were detected by a quantitative real-time polymerase chain reaction and Western blotting analysis. Immunohistochemistry assay was performed to analyze the positive expression rate of CLDN8. Cell proliferation was investigated by cell colony formation, 5-Ethynyl-2'-deoxyuridine and DNA content quantitation assays. Cell migration and invasion were assessed by wound-healing and transwell invasion assays. Interactions among circSCNN1A, miR-590-5p and CLDN8 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft mouse model assay was conducted to verify the effect of circSCNN1A on tumor formation in vivo. RESULTS: CircSCNN1A and CLDN8 expression were significantly downregulated, while miR-590-5p was upregulated in both RCC tissues and cells. CircSCNN1A overexpression inhibited RCC cell proliferation, migration and invasion, accompanied by decreases of cyclin D1, MMP2, MMP9, N-cadherin and vimentin expression and an increase of E-cadherin expression. CircSCNN1A acted as a miR-590-5p sponge and regulated RCC cell processes by binding to miR-590-5p. CLDN8, a target gene of miR-590-5p, was involved in the regulation of the biological behaviors of RCC cells by miR-590-5p. In addition, circSCNN1A induced CLDN8 production by interacting with miR-590-5p. Further, circSCNN1A suppressed tumor formation in vivo. CONCLUSION: CircSCNN1A inhibited RCC cell proliferation, migration and invasion by regulating the miR-590-5p/CLDN8 pathway.

Preparation of Rehmanniae Radix Praeparata Polysaccharide Iron(III) Complex and Evaluation of Its Biological Activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Overexpression of phosphatidylserine synthase IbPSS1 enhances salt tolerance by stimulating ethylene signaling-dependent lignin synthesis in sweetpotato roots.

Phosphatidylserine (PS) is an important lipid signaling required for plant growth regulation and salt stress adaptation. However, how PS positively regulate plant salt tolerance is still largely unknown. In this study, IbPSS1-overexpressed sweetpotato plants that exhibited overproduction of PS was employed to explore the mechanisms underlying the PS stimulation of plant salt tolerance. The results revealed that the IbPSS1-overexpressed sweetpotato accumulated less Na+ in the stem and leaf tissues compared with the wild type plants. Proteomic profile of roots showed that lignin synthesis-related proteins over-accumulated in IbPSS1-overexpressed sweetpotato. Correspondingly, the lignin content was enhanced but the influx of Na + into the stele was significantly blocked in IbPSS1-overexpressed sweetpotato. The results further revealed that ethylene synthesis and signaling related genes were upregulated in IbPSS1-overexpressed sweetpotato. Ethylene imaging experiment revealed the enhancement of ethylene mainly localized in the root stele. Inhibition of ethylene synthesis completely reversed the PS-overproduction induced lignin synthesis and Na+ influx pattern in stele tissues. Taken together, our findings demonstrate a mechanism by which PS regulates ethylene signaling and lignin synthesis in the root stele, thus helping sweetpotato plants to block the loading of Na+ into the xylem and to minimize the accumulation of Na+ in the shoots.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies.

OBJECTIVE: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. RESULTS: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). CONCLUSIONS: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.

IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. IL1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. In this study, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAM) to inhibit BTIC self-renewal and CD8+ T-cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models. IL1R2 activation by TAM-derived IL1ß increased PD-L1 expression by interacting with the transcription factor Yin Yang 1 (YY1) and inducing YY1 ubiquitination and proteasomal degradation in both TAMs and TNBC cells. Loss of YY1 alleviated the transcriptional repression of c-Fos, which is a transcriptional activator of PDL-1. Combined treatment with an IL1R2-neutralizing antibodies and anti-PD-1 led to enhanced antitumor efficacy and reduced TAMs, BTICs, and exhausted CD8+ T cells. These results suggest that IL1R2 blockade might be a strategy to potentiate immune checkpoint blockade efficacy in TNBC to improve patient outcomes. Significance: IL1R2 in both macrophages and breast cancer cells orchestrates an immunosuppressive tumor microenvironment by upregulating PD-L1 expression and can be targeted to enhance the efficacy of anti-PD-1 in triple-negative breast cancer.

UFObow: A single-wavelength excitable Brainbow for simultaneous multicolor ex-vivo and in-vivo imaging of mammalian cells.

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

Enhancing Neuroprotection in Mouse Model of Parkinson's Disease through Protein Nanosystem Conjugation with ApoE Peptide for miR-124 Delivery.

Parkinson's disease (PD) affects millions of people's lives worldwide. The main pathogenesis of PD is dopaminergic neuron necrosis and neuroinflammation mediated by activated microglia cells. In recent years, the anti-inflammatory ability and neuroprotective effects of miR-124 in PD models were well proved, but the in vivo delivery of miR-124 remains challenging. Herein, we report a protein nanosystem modified with a brain-targeting peptide ApoE that could efficiently deliver miR-124 across the blood-brain barrier (BBB). This nanosystem showed good cell viability on brain endothelial cells and microglia cells, and administration of this nanosystem significantly decreased the neuroinflammation and dopaminergic neuron loss, as well as recovered parts of neurobehavioral deficits. This ApoE peptide-based protein nanosystem holds great promise for the delivery of RNA therapeutics to the brain and for realizing neuron protection in PD treatment.

The Effect of Scalp Nerve Block on Postoperative Analgesia and Stress Response in Patients Undergoing Craniotomy: A Meta-Analysis.

Objective: To evaluate the effect of scalp nerve block (SNB) on postoperative analgesia and stress response in patients undergoing craniotomy by meta-analysis. Methods: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials involving SNB for elective craniotomy under general anesthesia from inception to August 1, 2022. Meta-analysis was performed using RevMan 5.4 and Stata MP17.0. Based on scalp block operation time (preoperative block, postoperative block), different control groups (no block, normal saline), local anesthetic types (bupivacaine, levobupivacaine, ropivacaine), the postoperative pain score at different time points was analyzed by subgroup analysis. Results: 23 studies involving 1515 patients were included. The combined results showed that SNB could significantly reduce the pain scores at all time points compared with the control group (P < .05). Subgroup analysis showed that the analgesic effect of preoperative scalp nerve block was better than that of postoperative block, and the effect of ropivacaine and levobupivacaine was better than bupivacaine. SNB could reduce morphine consumption within 48 hours after surgery (SMD = -1.51, 95% CI -2.80 -0.21, P = .02, I2 = 89%). The first rescue analgesia time was significantly longer in the SNB group than the control group (SMD = 0.57, 95% CI 0.16-0.99, P = .01, I2 = 68.76%). Compared with the control group, the levels of postoperative angiotensin, intraoperative blood glucose, and both intraoperative and postoperative cortisol levels were significantly decreased (P < .05). SNB can inhibit hemodynamic changes caused by surgical stimulation and effectively reduce the incidence of postoperative nausea and vomiting (RR = 0.71, 95% CI 0.51~0.97, P = .03). Conclusion: Scalp nerve block is an effective analgesic that reduces pain within 48 hours after craniotomy. It effectively inhibit the stress response caused by surgical stimulation, stabilize hemodynamics, and reduce the incidence of postoperative nausea and vomiting.

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation.

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2'3'-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA demands tight regulatory mechanisms that are necessary to maintain cell and tissue homeostasis under normal conditions. Inside the cell nucleus, anchoring to nucleosomes and competition with chromatin architectural proteins jointly prohibit cGAS activation by genomic DNA8-15. However, the fate of nuclear cGAS and its role in cell physiology remains unclear. Here we show that the ubiquitin proteasomal system (UPS) degrades nuclear cGAS in cycling cells. We identify SPSB3 as the cGAS-targeting substrate receptor that associates with the cullin-RING ubiquitin ligase 5 (CRL5) complex to ligate ubiquitin onto nuclear cGAS. A cryo-electron microscopy structure of nucleosome-bound cGAS in a complex with SPSB3 reveals a highly conserved Asn-Asn (NN) minimal degron motif at the C terminus of cGAS that directs SPSB3 recruitment, ubiquitylation and cGAS protein stability. Interference with SPSB3-regulated nuclear cGAS degradation primes cells for type I interferon signalling, conferring heightened protection against infection by DNA viruses. Our research defines protein degradation as a determinant of cGAS regulation in the nucleus and provides structural insights into an element of cGAS that is amenable to therapeutic exploitation.

Developing CAR-immune cell therapy against SARS-CoV-2: Current status, challenges and prospects.

Chimeric antigen receptor (CAR)-immune cell therapy has revolutionized the anti-tumor field, achieving efficient and precise tumor clearance by directly guiding immune cell activity to target tumors. In addition, the use of CAR-immune cells to influence the composition and function of the immune system and ultimately achieve virus clearance and immune system homeostasis has attracted the interest of researchers. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered a global pandemic of coronavirus disease 2019 (COVID-19). To date, the rapidly mutating SARS-CoV-2 continues to challenge existing therapies and has raised public concerns regarding reinfection. In patients with COVID-19, the interaction of SARS-CoV-2 with the immune system influences the course of the disease, and the coexistence of over-activated immune system components, such as macrophages, and severely compromised immune system components, such as natural killer cells, reveals a dysregulated immune system. Dysregulated immune-induced inflammation may impair viral clearance and T-cell responses, causing cytokine storms and ultimately leading to patient death. Here, we summarize the research progress on the use of CAR-immune cells against SARS-CoV-2 infection. Furthermore, we discuss the feasibility, challenges and prospect of CAR-immune cells as a new immune candidate therapy against SARS-CoV-2.

Macrophage ß-arrestin-1 deteriorates DSS-induced colitis through interaction with NF-κB signaling.

ß-arrestin-1 has been demonstrated to participate in the regulation of inflammatory reactions in several diseases. Thus, this study aimed to investigate the role of macrophage ß-arrestin-1 in the pathogenesis and progression of ulcerative colitis (UC). A myeloid ß-arrestin-1 conditional knockout mouse model was generated to explore the role of macrophage ß-arrestin-1. DSS was employed for the establishment of an ulcerative colitis mouse model, using TNF-α as an inflammatory stressor in vitro. The expression level of ß-arrestin-1 was detected via western blot and immunofluorescence assays, whilst disease severity was evaluated by clinical score and H&E staining in the DSS-induced colitis model. In the in vitro experiments, the levels of inflammatory cytokines were examined using real-time PCR. NF-κB activation was detected through the double luciferase reporter system, western blot, and electrophoretic mobility shift assay (EMSA). BAY11-7082 was used to inhibit NF-κB activation. Our results exposed that the level of ß-arrestin-1 was increased in monocytes/macrophages derived from DSS-induced colitis mice or under the TNF-α challenge. Moreover, conditionally knocking out the expression of myeloid ß-arrestin-1 alleviated disease severity, while knocking out the expression of ß-arrestin-1 decreased the levels of inflammatory cytokines. Additionally, NF-κB was identified as a central regulatory element of ß-arrestin-1 promoter, and using BAY11-7082 to inhibit NF-κB activation lowered the level of ß-arrestin-1 under TNF-α challenge. ß-arrestin-1 led to the activation of the NF-κB signaling pathway by enhancing binding to IκBα and IKK under the TNF-α challenge. Taken together, our findings demonstrated macrophage ß-arrestin-1 contributes to the deterioration of DSS-induced colitis through the interaction with NF-κB signaling, thus highlighting a novel target for the treatment of UC.

Combined administration of anisodamine and neostigmine alleviated colitis by inducing autophagy and inhibiting inflammation.

Our previous work demonstrated that the anisodamine (ANI) and neostigmine (NEO) combination produced an antiseptic shock effect and rescued acute lethal crush syndrome by activating the α7 nicotinic acetylcholine receptor (α7nAChR). This study documents the therapeutic effect and underlying mechanisms of the ANI/NEO combination in dextran sulfate sodium (DSS)-induced colitis. Treating mice with ANI and NEO at a ratio of 500:1 alleviated the DSS-induced colitis symptoms, reduced body weight loss, improved the disease activity index, enhanced colon length, and alleviated colon inflammation. The combination treatment also enhanced autophagy in the colon of mice with DSS-induced colitis and lipopolysaccharide/DSS-stimulated Caco-2 cells. Besides, the ANI/NEO treatment significantly reduced INF-γ, TNF-α, IL-6, and IL-22 expression in colon tissues and decreased TNF-α, IL-1ß, and IL-6 mRNA levels in Caco-2 cells. Meanwhile, the autophagy inhibitor 3-methyladenine and ATG5 siRNA attenuated these effects. Furthermore, 3-methyladenine (3-MA) and the α7nAChR antagonist methyllycaconitine (MLA) weakened the ANI/NEO-induced protection on DSS-induced colitis in mice. Overall, these results indicate that the ANI/NEO combination exerts therapeutic effects through autophagy and α7nAChR in a DSS-induced colitis mouse model.

'Skip' osteoporosis vertebral compression fractures caused by electrical injury: a case report and review of the literature.

INTRODUCTION: Electrical injuries rarely result in fractures, such as long bone fractures and spinal fractures. A few articles have reported osteoporosis vertebral compression fractures (OVCFs) caused by electrical injuries. Here, we present a rare case of 37-year-old male suffering from the 9th thoracic (T9) and 5th lumbar (L5) OVCFs after receiving a electric shock. CASE PRESENTATION: A 37-year-old Han male experienced an electric shock (480 V direct current) at the working time and felt immediately serious back pain. He did not fall and lose consciousness. X-ray and magnetic resonance imaging showed acute OVCFs, as well as dual-energy X-ray absorptiometry indicated osteoporosis. Normal laboratory tests can avoid secondary osteoporosis resulting from metabolic diseases and tumors. Finally, he was diagnosed with acute discontinuous OVCFs (T9 and L5). The patient denied having a history of back pain, whereas, he had a history of smoking, alcohol abuse, and congenital heart disease (tetralogy of Fallot) were associated with osteoporosis. Considering no local kyphosis and < 50% anterior body compression, we selected conservative treatment for this patient. At a 1-year and 3-year follow-up, the lateral thoracic and lumbar radiography demonstrated no instability of the spine, and the back pain has been relieved. CONCLUSIONS: This rare case reminds us the importance of consulting a detailed medical history when we encounter young patients receiving electrical injuries. Discontinuously OVCFs must not be overlooked, even though we encounter a young man.