A case report of Stevens-Johnson syndrome caused by omeprazole.

RATIONALE: Stevens-Johnson syndrome (SJS) is a rare but severe skin-mucosal reaction with a high mortality rate. It is characterized by sudden, painful blistering lesions on the skin, often accompanied by high fever and systemic toxicity. Lesions typically appear on the dorsal surfaces of the hands, feet, forearms, legs, and soles of the feet. They can also affect the conjunctiva, oral mucosa, labial mucosa, and vaginal mucosa. Patients may experience complications such as pneumonia, severe comorbidities, and liver and renal failure. PATIENT CONCERNS: A 51-year-old female patient was admitted to the hospital due to "abdominal distention and skin yellowing for 20 days." After using omeprazole, she developed a rash all over her body, and her liver function further deteriorated, ultimately leading to chronic acute liver failure. DIAGNOSES: The diagnosis included fever, rash suspected to be drug-induced, chronic and acute liver failure, and decompensation of post-Hepatitis B cirrhosis. INTERVENTIONS: During hospitalization, suspected adverse drug reactions were discontinued, and symptomatic supportive treatment with methylprednisolone and fluid replacement was promptly provided. OUTCOMES: The patient's symptoms and follow-up showed that the rash disappeared and liver and kidney function improved significantly after treatment. LESSONS: We explored how chronic acute liver failure can cause immune system abnormalities and immune paralysis in patients, manifested as susceptibility to infection. This case report describes a drug-induced allergic reaction - SJS - in patients with chronic acute liver failure, as well as subsequent treatment, including hormone dosage and treatment duration. I hope this report will help enrich the relevant literature on drug-induced SJS combined with chronic and acute liver failure, laying the foundation for improving the survival rate of patients with the disease.

Analysis of the frequency-response stability and reliability of a tower-column unstable rock mass on a high and steep slope.

The first-order second-moment checking point method was introduced to judge the instability probability and evaluate the stability of the TCURM. The frequency-response stability calculation and the reliability results were compared, and a frequency-response stability and reliability analysis method was proposed. Taking the Zengziyan W12# unstable rock mass in Nanchuan, Chongqing, China, as an example, the calculation shows that the dynamic indexes and geological indexes decrease as the stiffness of the deterioration area decreases. According to the statistical data of the laboratory test and the field investigation, reliability theory is used to evaluate the stability of the TCURM, and the failure probabilities are 80.3% and 96.27% under natural and saturated conditions, which correspond to states of poor stability and instability, respectively. The reliability evaluation results are consistent with the conclusion of the frequency-response stability analysis. The new method can provide a theoretical basis for developing the dynamic monitoring and early warning indicators of the TCURM and disaster prevention and mitigation in mountainous areas.

Perinatal complications and neonatal outcomes in in vitro fertilization/intracytoplasmic sperm injection: a propensity score matching cohort study.

Background: The utilization of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) has witnessed a significant increase in recent years. However, the comparative perinatal and neonatal outcomes compared to natural pregnancies are unclear. This study aims to compare the outcomes of pregnancies from IVF and ICSI with natural pregnancies. Methods: This retrospective, propensity score-matched cohort study was conducted at the First People's Hospital of Shangqiu and The First Affiliated Hospital of Xinjiang Medical University, involving 5,628 patients from February 2019 to December 2022. It compared pregnancies achieved through IVF/ICSI with those conceived naturally. The primary outcomes assessed were perinatal complications and neonatal health parameters. Propensity score matching and multivariate logistic regression analysis were employed to adjust for potential confounders and identify independent associations. Results: After propensity score matching, the IVF/ICSI group demonstrated significantly higher rates of placental adherence (12.1% vs. 7.4%, p < 0.001) and postpartum hemorrhage (11.1% vs. 7.6%, p = 0.002) compared to the NP group. Neonates in the IVF/ICSI group had a lower gestational age (38.21 ± 2.12 weeks vs. 38.63 ± 2.29 weeks, p < 0.001), reduced birth weight (3159.42 ± 722.75 g vs. 3211.31 ± 624.42 g, p = 0.032), and an increased preterm delivery rate (11.2% vs. 8.9%, p = 0.017). Multivariate analysis further confirmed these findings, highlighting the independent associations between IVF/ICSI and these adverse outcomes. Conclusion: This study suggests a potential correlation between the use of IVF/ICSI and unfavorable perinatal and neonatal outcomes. These findings underscore the critical need for ongoing monitoring and research efforts to enhance the safety and effectiveness of these reproductive technologies.

Rapid Determination of 12 Classes of Per- and Polyfluoroalkyl Substances in Water Samples from Environmental Forensic Cases.

The widespread use of per- and polyfluoroalkyl substances (PFASs) with different physico-chemical properties poses a great threat to the environment and human health. Simultaneous detection of different classes of PFASs is a difficult task, especially for rapid analysis of polluted water samples in environmental forensic cases. In this study, a simple sample preparation ultrahigh-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was established for the detection of PFASs in a wide range of water matrices. By optimizing the conditions of pretreatment and the parameters of the instrument, the developed method provided good linearity of calibration standards (R2 > 0.99), and demonstrated excellent MLOQ (0.008-1.2 µg/L), with spiked recoveries ranging from 57.7% to 151% for 47 targets in surface water samples, and from 45.7 to 165% for 46 targets in ground and waste water samples, respectively. This method required an injection volume of 3 µL and an analysis time of only 18 min per sample. The validation method was successfully applied to the analysis of 20 environmental water samples, in which 15 target substances with different concentrations were detected, with total concentrations of 0.082 to 262.455 µg/L. The method is simple and exclusive, and can rapidly confirm the occurrence of PFASs in different water samples, providing a convenient and fast high-throughput analysis, which is especially suitable for the application in the environmental forensic investigation of PFASs pollution.

Endogenous Plasma Peptides Modulated by Protease in a Time-Dependent Manner as Effective Biomarkers for Preanalytical Quality Control.

Non-cryopreservation temperature exposure (NCE) is a vital preanalytical factor for assessing plasma quality. NCE can introduce undesirable errors in clinical diagnosis or when developing biomarkers of diseases. Biomarkers that can effectively indicate the changes in sample quality caused by long-term NCE (0-several days) are limited. Low-molecular-weight (LMW) peptides in the plasma are modulated by endogenous proteases. These protease activities are significantly correlated with NCE temperatures and duration, indicating a potential link of these protease reactions with the preanalytical quality of plasma samples. In this study, two groups of plasma samples were aged at room temperature (RT, 57 samples) and 4 °C (69 samples) for different durations (0, 1, 2, 5, and 10 days), and LMW peptidomics were analyzed through nanopore-assisted matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The analysis revealed 10 peptides that consistently exhibited time-dependent changes, which were used to develop multiple-variable models for predicting the changes in sample quality resulting from extended NCE. These biomarker models exhibited outstanding performance in distinguishing poor-quality samples aged at both RT and 4 °C. To validate the findings, tests on samples from validation sets were conducted by analysts who were blinded to the detailed conditions, which revealed a high specificity (94.3-96.9%) and sensitivity (90.5-99.3%). These results indicate the potential of these peptides as novel biomarkers of quality control.

Very-early symptomatic recurrence is associated with late recurrence after radiofrequency ablation of atrial fibrillation.

AIMS: After radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), the effect of very-early (within 48 h) symptomatic recurrence (VESR) on late (after 3 months of RFCA) recurrence (LR) has been seldomly reported. We aimed to explore the relationship between VESR and LR among post-RFCA patients. METHODS AND RESULTS: This was a single-centre prospective cohort study that enrolled 6887 AF patients who received the first RFCA procedure from June 2018 to December 2021 at Beijing Anzhen Hospital. Patients were divided into four groups based on VESR and early (from 48 h to 3 months after RFCA) recurrence (ER): Group A (no VESR, no ER); Group B (VESR but no ER); Group C (ER but no VESR); and Group D (both VESR and ER). Three hundred and thirty (4.79%) patients experienced VESR (Groups B and D). With an average follow-up of 14.7 months after grouping, the Kaplan-Meier curve showed that LR risk in VESR patients was higher than in other patients (log-rank, P < 0.001), and the difference was significant in both paroxysmal (log-rank, P < 0.001) and persistent (log-rank, P < 0.001) AF patients (P for interaction = 0.118). In multivariate analysis, Groups B, C, and D were associated with a 2.161-, 5.409-, and 7.401-fold increase in the risk of LR, respectively. What is more, compared with Group A, VESR-atrial tachycardia and VESR-AF were related to a 3.467- and 5.564-fold LR risk, respectively. In VESR patients, classification based on ER and VESR modes improved the prediction potential of LR risk. CONCLUSION: Very-early symptomatic recurrence is associated with an increased risk of LR.

ETV1 inhibition depressed M2 polarization of tumor-associated macrophage and cell process in gastrointestinal stromal tumor via down-regulating PDE3A.

M2-type polarization of tumor associated-macrophage (TAM) is involved in the malignancy of gastrointestinal stromal tumor (GIST) progression. ETS variant 1 (ETV1) has been previously validated to regulate GIST pathogenesis. Our study intended to explore the role and mechanism of ETV1 in mediating the M2-polarization of TAM in GIST progression. First, we analyzed the correlation between ETV1 expression and M2-polarization in GIST tissues. IL-4 was used to treat THP-1-derived TAM cells and IL-4-stimulated TAM were co-cultured with GIST-T1 cells to mimic the GIST microenvironment. A loss-of-function assay was performed to explore the role of ETV1. Results showed that ETV1 elevation was positively correlated with M2-polarization. IL-4-induced TAM promoted ETV1 expression, silencing ETV1 inhibited proliferation, invasion and KIT activation in IL-4-treated GIST cells, while cell apoptosis was enhanced. Besides, co-culture of ETV1-silenced GIST cells significantly depressed M2-polarization in TAM, presented as decreased levels of CD206, Agr-1 and cytokines, as well as the proportion of CD206-positive TAM. PDE3A was positively correlated with ETV1 and M2-polarization. Overexpressing PDE3A reversed the inhibitory effects of ETV1 silencing. Generally, ETV1 inhibition depressed M2-polarization of TAM in GIST and its promotion on pathological aggravation via down-regulating PDE3A. This evidence may provide a new target for GIST regulation.

Hsa_circ_0072765 knockdown inhibits proliferation, activation and migration in transforming growth factor-beta (TGF-ß)-induced hepatic stellate cells (HSCs) by the miR-197-3p/TRPV3 axis.

BACKGROUND: Circular RNAs (circRNAs) participate in the progression of diverse human diseases. However, the effects of circRNAs on liver fibrosis are limited. In this study, we aimed to investigate the functions of hsa_circ_0072765 in liver fibrosis. METHODS: Transforming growth factor-beta (TGF-ß)-treated hepatic stellate cells (HSCs) were used as the cell model of liver fibrosis. Quantitative real-time polymerase chain reaction (qRT-PCR) or western blot was performed to determine the expression of hsa_circ_0072765, microRNA-197-3p (miR-197-3p) and transient receptor potential cation channel subfamily V member 3 (TRPV3). 5'-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis and wound-healing assay were conducted to evaluate cell proliferation, cell cycle and migration. HSC activation was assessed by determining the expression of alpha-smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1A1). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were manipulated to analyze the relationship of hsa_circ_0072765, miR-197-3p and TRPV3. The exosome morphology was observed under transmission electron microscopy (TEM). RESULTS: Hsa_circ_0072765 level was increased in TGF-ß-induced HSCs. Hsa_circ_0072765 knockdown inhibited cell proliferation, cell cycle, activation and migration in TGF-ß-induced HSCs. Hsa_circ_0072765 sponged miR-197-3p and negatively regulated miR-197-3p expression. MiR-197-3p inhibition reversed the effects of hsa_circ_0072765 knockdown on TGF-ß-induced HSC proliferation, cell cycle, activation and migration. In addition, TRPV3 was the target gene of miR-197-3p and miR-197-3p overexpression inhibited TGF-ß-treated HSC proliferation, cell cycle, activation and migration by targeting TRPV3. Besides, we found that exosomal hsa_circ_0072765 was increased in TGF-ß-treated HSCs. CONCLUSION: Hsa_circ_0072765 promoted the progression of TGF-ß-treated HSCs by decoying miR-197-3p and upregulating TRPV3.

Estimation of the Frequency and Time of Human Exposure to Arsenic by Single Hair Analysis.

Arsenic (As) and its compounds are widely used in many applications. Long-term exposure to As can cause acute and chronic poisoning. In severe cases, it can lead to adverse effects, such as gene mutation, cell cancer and fetal malformation. The objective of this study was to accurately estimate As exposure frequency and time. Quantitative analysis of As in single hairs obtained from APL (acute promyelocytic leukemia) patients treated with As2O3 was performed by LA-ICP-MS. An informative As concentration distribution profile of single hair was applied to estimate the As exposure frequency and time. As exposure frequency was estimated according to the number of As concentration peaks. As exposure time was estimated according to the hair growth length in combination with the hair growth rate. The validation results demonstrate that this method was more efficient than the traditional method; compared with the traditional method, which provides estimates in months, our model shortened the As exposure time estimate to the range of a few days, which considerably improved the inference accuracy. Therefore, these results can be used for forensic toxicology studies, environmental exposure monitoring, etc.

KAT7 promoted gastric cancer progression through promoting YAP1 activation.

Lysine acetyltransferase 7 (KAT7) was upregulated in gastric cancer (GC) patient tissues, and associated with poor prognosis and metastasis. However, its specific role in GC remains unclear. This study aimed to annotate the role of KAT7 in GC cells. The results showed that the overexpression of KAT7 promoted cell growth, migration, and invasion, while KAT7 inhibition has the opposite effect. Besides, KAT7 participated in cell cycle phase distribution and epithelial-mesenchymal transition (EMT) process of GC cells. In addition, KAT7 promoted the transcription and nuclear translocation of Yes-associated protein 1 (YAP1) in MKN45 cells. Silence of YAP1 partly reversed the promoting effect of KAT7 on GC cells progression. In summary, this study indicates that KAT7 promoted GC cells progression through promoting YAP1 activation, contributes to understand the specific role of KAT7 in GC.

An In Vitro Study of Fluid Contaminations Influences on Reverse Torque Values of Implant-Abutment Connections.

Purpose: To examine the effects of fluid contamination on the reverse torque value (RTV) of abutment screws. 484 titanium fixtures were mounted into the stainless-steel holders. Methods: 11 groups (44 specimens in each group) of implants were mounted in acrylic resin. Ten groups of fixture screw holes were contaminated with chlorhexidine, saliva, blood, fluoride, or combination groups, and one group served as a control without contamination. To simulate the oral environment, samples were subjected to thermal cycling and cyclic loading. Results: The RTV means were less than the initial torque in both control and contamination groups. The maximum RTV mean was observed in the fluoride group (26.00 ± 1.02 Ncm). In other groups, this rate for control, blood, saliva, and chlorhexidine groups were 18.00 ± 1.78 Ncm, 22.12 ± 1.56 Ncm, 21.56 ± 1.43 Ncm, and 21.89 ± 1.02 Ncm, respectively. In combination groups, the maximum RTV mean was observed in the saliva+CHX group (23.89 ± 1.92 Ncm). In other combination groups, this rate for the blood+CHX, blood+saliva, saliva+fluoride, fluoride+CHX, and fluoride+blood groups were 22.56 ± 1.73 Ncm, 22.00 ± 1.54 Ncm, 20.11 ± 1.58 Ncm, 23.51 ± 1.19 Ncm, 21.02 ± 1.38 Ncm, and 20.11 ± 1.58 Ncm, respectively. The RTV was statistically significant (p < 0.05) for the contamination groups (except saliva) and combination groups compared to the control group. There is no statistically significant difference (p > 0.05) between the reverse torque value mean of the blood and saliva groups and between that of the fluoride and chlorhexidine groups. Conclusion: Implant-abutment specimens are suggested to be placed in a saliva environment and should be subjected to cyclic loading.

Excessive hydrogen sulfide causes lung and brain tissue damage by promoting PARP1/Bax and C9 and inhibiting LAMB1.

Excessive hydrogen sulfide (H2S) causes serious damage to human organs and tissues. In this study, we aimed to explore the role and underlying mechanism of excessive H2S in brain and lung tissues. A H2S concentration of 100-800 pm promotes apoptosis and inflammation of brain and lung cells in ICR mice. Mechanistically, a H2S concentration of 100-800 pm upregulates PARP1 and Bax expression in a dose-dependent manner in vivo and in vitro, and functional gain-and-loss experiments verified that an excessive amount of H2S plays a pro-apoptotic role in HT22 and MML1 cells via regulation of PARP1 and Bax in vitro. By combining animal and cell experiments, we clarified that excess H2S promotes the inflammatory response of mouse brain and lung cells by promoting the expression of C9. In addition, the downregulation of LAMB1 by an excessive H2S concentration was confirmed using mass spectrometry and western blotting in vivo and in vitro. Combined with in vitro experiments, we found that an excessive H2S concentration promotes the expression of STAT1 and EGFR in HT22 and MML1 cells by inhibiting the expression of LAMB1. In summary, 100-800 pm H2S causes the brain and lung tissue damage in ICR mice, the underlying mechanisms include H2S induced apoptosis and inflammation of mouse brain and lung cells by upregulation of PARP1/Bax and C9, respectively, and H2S might induce fibrosis of mouse brain and lung cells by downregulation of LAMB1.

Spatio-temporal variation in potential habitats for rare and endangered plants and habitat conservation based on the maximum entropy model.

Rare and endangered plants (REPs) act as key indicators for species habitat priorities, and can thus be critical in global biodiversity protection work. Human activities and climate change pose great threats to REPs, so protection should be a top priority. In this study, we used the maximum entropy model (Maxent) to identify current and future (2050) potential habitats of REPs in the Xishuangbanna tropical area of China. We compared potential habitats with existing protected areas (PAs) in gap analysis, and used a transfer matrix to quantify changes in potential habitats. By comparing the potential distribution obtained with existing land use and land cover, we analyzed the impact of human-dominated land use changes on potential habitats of REPs and identified the main habitat patch types of REPs. The results showed that the current potential habitat area of hotspots is 2989.85 km2, which will be reduced to 247.93 km2 by 2050, accounting for 15.60% and 1.29% of the total research area, respectively. Analysis of land use and land cover showed that rubber plantation was the human-dominated land use posing the greatest threat to potential habitats of REPs, occupying 23.40% and 21.62% of current and future potential habitats, respectively. Monsoon evergreen broad-leaved forest was identified as the main habitat patch type for REPs in Xishuangbanna and occupied the highest proportion of potential habitat area. Gap analysis showed that only 35.85% of habitat hotspots are currently included in existing PAs and that this will decrease to 32.26% by 2050. This emphasizes the importance of protecting current and future potential habitats of REPs in a dynamic conservation approach that can adapt to changes in future climate and human activities.

Epithelial Cell Biomarkers Are Predictive of Response to Biologic Agents in Crohn's Disease.

BACKGROUND: Therapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn's disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ) and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis, with respect to response to VDZ. METHOD: Ileal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of 2 biomarkers to VDZ was examined. RESULTS: Clinical response in UST was significantly higher than placebo (65% vs 39%; P = 0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs 20% (P = 0.02). For VDZ, clinical response with MVL of 1.35 to 1.55 µm was 82% vs 44% (<1.35 µm) and 40% (>1.55 µm; P = 0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis <14 positive cells/1000 IECs or MVL of 1.35 to 1.55 µm could identify 84% of responders and 67% of nonresponders (P = 0.001). CONCLUSION: Ileal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, and combination of the 2 biomarkers enhanced the discriminate ability of responders from nonresponders to VDZ.

Evidence of Duodenal Epithelial Barrier Impairment and Increased Pyroptosis in Patients With Functional Dyspepsia on Confocal Laser Endomicroscopy and "Ex Vivo" Mucosa Analysis.

INTRODUCTION: Duodenal epithelial barrier impairment and immune activation may play a role in the pathogenesis of functional dyspepsia (FD). This study was aimed to evaluate the duodenal epithelium of patients with FD and healthy individuals for detectable microscopic structural abnormalities. METHODS: This is a prospective study using esophagogastroduodenoscopy enhanced with duodenal confocal laser endomicroscopy (CLE) and mucosal biopsies in patients with FD (n = 16) and healthy controls (n = 18). Blinded CLE images analysis evaluated the density of epithelial gaps (cell extrusion zones), a validated endoscopic measure of the intestinal barrier status. Analyses of the biopsied duodenal mucosa included standard histology, quantification of mucosal immune cells/cytokines, and immunohistochemistry for inflammatory epithelial cell death called pyroptosis. Transepithelial electrical resistance (TEER) was measured using Ussing chambers. Epithelial cell-to-cell adhesion proteins expression was assessed by real-time polymerase chain reaction. RESULTS: Patients with FD had significantly higher epithelial gap density on CLE in the distal duodenum than that of controls (P = 0.002). These mucosal abnormalities corresponded to significant changes in the duodenal biopsy samples of patients with FD, compared with controls, including impaired mucosal integrity by TEER (P = 0.009) and increased number of epithelial cells undergoing pyroptosis (P = 0.04). Reduced TEER inversely correlated with the severity of certain dyspeptic symptoms. Furthermore, patients with FD demonstrated altered duodenal expression of claudin-1 and interleukin-6. No differences in standard histology were found between the groups. DISCUSSION: This is the first report of duodenal CLE abnormalities in patients with FD, corroborated by biopsy findings of epithelial barrier impairment and increased cell death, implicating that duodenal barrier disruption is a pathogenesis factor in FD and introducing CLE a potential diagnostic biomarker in FD.

Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn's Disease.

OBJECTIVE: Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn's disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. DESIGN: Crohn's disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI <5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). RESULTS: One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis <14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3-48.6; P < 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03-7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change. CONCLUSIONS: Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

Transcriptome profile of rat genes in bone marrow-derived macrophages at different activation statuses by RNA-sequencing.

The underlying mechanisms of macrophage polarization have been detected by genome-wide transcriptome analysis in a variety of mammals. However, the transcriptome profile of rat genes in bone marrow-derived macrophages (BMM) at different activation statuses has not been reported. Therefore, we performed RNA-Sequencing to identify gene expression signatures of rat BMM polarized in vitro with different stimuli. The differentially expressed genes (DEGs) among unactivated (M0), classically activated pro-inflammatory (M1), and alternatively activated anti-inflammatory macrophages (M2) were analyzed by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In this study, not only we have identified the changes of global gene expression in rat M0, M1 and M2, but we have also made clear systematically the key genes and signaling pathways in the differentiation process of M0 to M1 and M2. These will provide a foundation for future researches of macrophage polarization.

Correction to: Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain.

In the original publication, Figure 4G was incorrectly published. The correct version of Figure 4G is presented in this correction. This correction does not affect the conclusions of the paper.

Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain.

The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naïve and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression.