Deficiency of geranylgeranyl biphosphate synthase in kidney tubules causes cystic kidney disease.

Polycystic kidney disease (PKD) is a common hereditary kidney disease. Although PKD occurrence is associated with certain gene mutations, its onset regulatory mechanisms are still not well understood. Here, we first report that the key enzyme geranylgeranyl diphosphate synthase (GGPPS) is specifically expressed in renal tubular epithelial cells of mouse kidneys. We aimed to explore the role of GGPPS in PKD. In this study, we established a Ggppsfl/fl:Cdh16cre mouse model and compared its phenotype with that of wild-type mice. A Ggpps-downregulation HK2 cell model was also used to further determine the role of GGPPS. We found that GGPPS was specifically expressed in renal tubular epithelial cells of mouse kidneys. Its expression also increased with age. Low GGPPS expression was observed in human ADPKD tissues. In the Ggppsfl/fl:Cdh16cre mouse model, Ggpps deletion in renal tubular epithelial cells induced the occurrence and development of renal tubule cystic dilation and caused the death of mice after birth due to abnormal renal function. Enhanced proliferation of cyst-lining epithelial cells was also observed after the knockout of Ggpps. These processes were related to the increased rate of Rheb on membrane/cytoplasm and hyperactivation of mTORC1 signaling. In conclusion, the deficiency of GGPPS in kidney tubules induced the formation of renal cysts. It may play a critical role in PKD pathophysiology. A novel therapeutic strategy could be designed according to this work.

Effect of modified opioid sparing anaesthesia on postoperative quality of recovery in patients undergoing laparoscopic bariatric surgery: protocol for a monocentre, double-blind randomised controlled trial - the MOSA study.

INTRODUCTION: Obesity patients undergoing laparoscopic bariatric surgery (LBS) are frequently encountered perioperative adverse events related to opioids-based anaesthesia (OBA) or opioids-free anaesthesia (OFA). While modified opioid-sparing anaesthesia (MOSA) has been shown to lower the occurrence of adverse events related to OBA and OFA. This study is to assess the efficacy of MOSA in enhancing the recovery quality among individuals undergoing LBS. METHODS AND ANALYSIS: A single-centre, prospective, double-blind, randomised controlled trial is conducted at a tertiary hospital. A total of 74 eligible participants undergoing elective LBS will be recruited and randomly allocated. Patients in the MOSA group will receive a combination of low-dose opioids, minimal dexmedetomidine, esketamine and lidocaine, while in the OBA group will receive standard general anaesthesia with opioids. Patients in both groups will receive standard perioperative care. The primary outcome is the quality of recovery-15 score assessed at 24 hours after surgery. Secondary outcomes include pain levels, anxiety and depression assessments, gastrointestinal function recovery, perioperative complication rates, opioid consumption and length of hospital stay. ETHICS AND DISSEMINATION: Ethical approval has been provided by the Ethical Committee of Yan'an Hospital of Kunming City (approval No. 2023-240-01). Eligible patients will provide written informed consent to the investigator. The outcomes of this trial will be disseminated in a peer-reviewed scholarly journal. TRIAL REGISTRATION NUMBER: The study protocol is registered at https://www.chictr.org.cn/ on 19 December 2023. (identifier: ChiCTR2300078806). The trial was conducted using V.1.0.

Structural optimization of Moracin M as novel selective phosphodiesterase 4 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

Structural Evolution of Bacterial Polyphosphate Degradation Enzyme for Phosphorus Cycling.

Living organisms ranging from bacteria to animals have developed their own ways to accumulate and store phosphate during evolution, in particular as the polyphosphate (polyP) granules in bacteria. Degradation of polyP into phosphate is involved in phosphorus cycling, and exopolyphosphatase (PPX) is the key enzyme for polyP degradation in bacteria. Thus, understanding the structure basis of PPX is crucial to reveal the polyP degradation mechanism. Here, it is found that PPX structure varies in the length of ɑ-helical interdomain linker (ɑ-linker) across various bacteria, which is negatively correlated with their enzymatic activity and thermostability - those with shorter ɑ-linkers demonstrate higher polyP degradation ability. Moreover, the artificial DrPPX mutants with shorter ɑ-linker tend to have more compact pockets for polyP binding and stronger subunit interactions, as well as higher enzymatic efficiency (kcat/Km) than that of DrPPX wild type. In Deinococcus-Thermus, the PPXs from thermophilic species possess a shorter ɑ-linker and retain their catalytic ability at high temperatures (70 °C), which may facilitate the thermophilic species to utilize polyP in high-temperature environments. These findings provide insights into the interdomain linker length-dependent evolution of PPXs, which shed light on enzymatic adaption for phosphorus cycling during natural evolution and rational design of enzyme.

Metabolic impairments associated with type 2 diabetes mellitus and the potential effects of exercise therapy: An exploratory randomized trial based on untargeted metabolomics.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles. METHODS: This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy. RESULTS: Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline. CONCLUSION: T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.

An inorganic mineral-based protocell with prebiotic radiation fitness.

Protocell fitness under extreme prebiotic conditions is critical in understanding the origin of life. However, little is known about protocell's survival and fitness under prebiotic radiations. Here we present a radioresistant protocell model based on assembly of two types of coacervate droplets, which are formed through interactions of inorganic polyphosphate (polyP) with divalent metal cation and cationic tripeptide, respectively. Among the coacervate droplets, only the polyP-Mn droplet is radiotolerant and provides strong protection for recruited proteins. The radiosensitive polyP-tripeptide droplet sequestered with both proteins and DNA could be encapsulated inside the polyP-Mn droplet, and form into a compartmentalized protocell. The protocell protects the inner nucleoid-like condensate through efficient reactive oxygen species' scavenging capacity of intracellular nonenzymic antioxidants including Mn-phosphate and Mn-peptide. Our results demonstrate a radioresistant protocell model with redox reaction system in response to ionizing radiation, which might enable the protocell fitness to prebiotic radiation on the primitive Earth preceding the emergence of enzyme-based fitness. This protocell might also provide applications in synthetic biology as bioreactor or drug delivery system.

ß-sitosterol alleviates dextran sulfate sodium-induced experimental colitis via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis.

Background: Inflammation-related NLRP3/Caspase-1/GSDMD-mediated pyroptosis is involved in the progression of ulcerative colitis (UC). ß-sitosterol (SIT) was reported to have anti-inflammatory effects on experimental colitis, while the regulation of SIT on pyroptosis is unclear. Therefore, the present study aimed to define the protective and healing effects of SIT on dextran sulfate sodium (DSS)-induced experimental UC rats and human epithelial colorectal adenocarcinoma cells (Caco-2) and explore the underlying mechanisms that are responsible for its effects on NLRP3/Caspase-1/GSDMD-mediated pyroptosis in UC. Methods: UC model rats were established by oral 4% DSS. Following colitis injury, the animals received SIT (doses of 50, 100, and 200 mg/kg) treatment for 2 weeks. For in vitro study, we exposed Caco-2-50 mg/mL DSS with or without SIT (concentrations of 8 and 16 µg/mL). Disease activity index (DAI) and histopathological injury were assessed in vivo. Activation proteins of nuclear factor kappa B (NF-κB) signaling axis, and tight junction-related proteins of zonula occludens-1 (ZO-1) and occludin were detected in colon tissues. TNF-α, IL-1ß, and IL-18 in serum and cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Changes in NLRP3/Caspase-1/GSDMD-mediated pyroptosis signaling pathway activation were analyzed both in tissues and cells. Results: Our findings suggested that SIT treatment attenuated the severity of 4% DSS-induced UC by protecting rats from weight and colon length loss, and macroscopic damage. SIT also reduced proinflammatory factors production (TNF-α, IL-1ß, and IL-18) in serum and cell supernatant. Mechanistically, SIT downregulated the expression levels of pyroptosis-related proteins including Caspase-1, cleaved-Caspase-1, NLRP3, GSDMD, and GSDMD-N in colon tissues and Caco-2 cells. Further analysis indicated that SIT maintained the colonic barrier integrity by enhancing the protein expression of ZO-1 and occludin. Conclusion: We confirmed that SIT exerts protective and therapeutic effects on DSS-induced colitis injury by suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and inflammation response. These findings demonstrated that SIT could be a potential medication for UC treatment.

Phthalate acid ester release from microplastics in water environment and their comparison between single and competitive adsorption.

The ability of microplastics (MPs) to adsorb environmental pollutants has been extensively studied. However, little is known about the ability of MPs to release inherent additives and the interaction between them. This paper explored the effects of environmental factors on the release of phthalic acid esters (PAEs) from three different types of microplastics (polyethylene microplastics (PE-MPs), polypropylene microplastics (PP-MPs), and polystyrene microplastics (PS-MPs)) by simulating water environments, as well as the differences in the adsorption of one or more PAEs by MPs. The results showed that the types of MPs, single environmental factors, and combined environmental factors had a great influence on the release of di(2-ethylhexyl) phthalate (DEHP). In the influence of a single environmental factor, the releasing amount of DEHP increased significantly. When the pH value increased from 5 to 9, the release of three PAEs from all MPs decreased. Moreover, under the combined influence of three environmental factors, the DEHP release from PP-MPs was most affected by environmental factors, and the order of influence of the three environmental factors was ionic strength > organic matter > pH. The DEHP release of PS-MPs was the highest (0.058 ± 0.023 µg/L), followed by PP-MPs (0.038 ± 0.010 µg/L) and PE-MPs (0.035 ± 0.008 µg/L). Adsorption kinetics and isotherm fitting showed that the adsorption process of the three MPs was suitable for the pseudo-second-order kinetic model, and the Freundlich adsorption isotherm had a higher fitting degree. Compared with single adsorption, the competitive adsorption of three PAEs increased the adsorption capacity of DEHP and decreased the adsorption capacity of dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP). These findings help predict the potential of MPs to release toxic additives under different environmental conditions.

Radioactive iodine therapy strategies for distinct types of differentiated thyroid cancer: a propensity score-matched analysis.

Background: The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated. Methods: DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching. Results: 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC. Conclusion: RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.

Bevacizumab-induced arrhythmia in a patient with lung adenocarcinoma: A case report.

RATIONALE: Cardiotoxicity is an important side effect of vascular endothelial growth factor inhibitors therapy in the treatment of cancer. Massive studies have shown bevacizumab-related hypertension, venous, and arterial thrombosis. PATIENT CONCERNS: A 56-year-old female patient was treated with bevacizumab monotherapy for lung adenocarcinoma. The patient was detected a poor R-wave increase with slight ST segment elevation in V1-V3 leads, and ventricular arrhythmia. DIAGNOSIS: The incidental arrhythmia caused by bevacizumab was considered. INTERVENTIONS: The patients received aspirin and amiodarone (0.2 g tid) to treat arrhythmia. After consultation with the cardiology department, the patient received a diagnostic coronary angiography. Coronary angiography showed 30% of the right coronary artery stenoses and no obvious organic stenosis in the left main artery, left anterior ascending, or left circumflex. OUTCOMES: The patient exhibited disappearance of chest tightness and rapid heartbeat after the treatment of amiodarone. Electrocardiogram monitoring results returning to normal. LESSONS: This is the first reported case of bevacizumab-associated arrhythmia. It is advisable to consider the risk of arrhythmia in bevacizumab monotherapy or combines treatment.

Efficacy of endoscopic mucosal resection versus endoscopic submucosal dissection for rectal neuroendocrine tumors ≤10mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are surgical methods used for rectal neuroendocrine tumors (NETs) with diameters of ≤ 10 mm. However, which method has a higher performance remains uncertain. OBJECTIVES: Evaluate which of the two methods shows a higher performance. DESIGN: Systematic review and meta-analysis METHODS: Data from PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to 12 April 2022. Outcomes, including complete resection, en bloc resection, recurrence, perforation, bleeding, and procedure time, were pooled by 95% confidence intervals (95% CI) using a fixed- or random-effects model. MAIN OUTCOME MEASURES: Complete resection, en bloc resection, and recurrence. SAMPLE SIZE: 18 studies, including 1168 patients were included in the study. RESULTS: Eighteen retrospective cohort studies were included in this meta-analysis. There were no statistical differences in the rates of complete resection, en bloc resection, recurrence, perforation, and bleeding rates between EMR and ESD. However, a statistical difference was detected in the procedure time; EMR had a significantly shorter time (MD=-17.47, 95% CI=-22.31 - -12.62, P<.00001). CONCLUSIONS: EMR and ESD had similar efficacies and safety profiles in resectioning rectal NETs ≤ 10 mm. Even so, the advantages of EMR included a shorter operation time and expenditure. Thus, with respect to health economics, EMR outperformed ESD. LIMITATION: Most of these studies are retrospective cohort studies instead of RCTs. CONFLICT OF INTEREST: None.

Characterization and heterologous expression of plasmalogen synthase MeHAD from Megasphaera elsdenii.

Plasmalogens (Pls) are vinyl-ether bond-containing glycerophospholipids or glycosyl diradyl glycerols, and are of great importance in the physiological functions and stability of cell membrane. Here, we identified and characterized that the plasmalogen synthase MeHAD from anaerobic Megasphaera elsdenii was responsible for vinyl-ether bond formation. Different from the 2-hydroxyacyl-CoA dehydratase (HAD) family plasmalogen synthase PlsA-PlsR which are encoded by two genes in Clostridium perfringens, the HAD homolog (MeHAD) encoded by a single gene MELS_0169 was found in M. elsdenii. By heterologous expression of the MeHAD gene into a nonplasmalogen-producing Escherichia coli strain, the expressed MeHAD was found to be located in the cell membrane region. Plasmalogens were detected in the recombinant strain using GC-MS and LC-MS, demonstrating that MeHAD was the key enzyme for plasmalogen synthesis. Moreover, the synthesized plasmalogens could enhance the oxidative stress-resistance and osmotic pressure-resistance of the recombinant strain, probably due to the ROS scavenging and decreased membrane permeability by the plasmalogens, respectively. The four-cysteine (Cys125, Cys164, Cys445 and Cys484) site-mutant of MeHAD, which were predicted binding to the [4Fe-4S] cluster, was unable to synthesize plasmalogens, indicating that the cysteines are important for the catalytic activity of MeHAD. Our results revealed the single gene encoded plasmalogen synthase in M. elsdenii and established a recombinant E. coli strain with plasmalogen production potential.

The Herbal Medicine Suanzaoren (Ziziphi Spinosae Semen) for Sleep Quality Improvements: A Systematic Review and Meta-analysis.

BACKGROUND: Sleep disturbances are common and bothersome among cancer and noncancer populations. Suanzaoren (Ziziphi Spinosae Semen) is commonly used to improve sleep, yet its efficacy and safety are unclear. METHODS: We systematically searched PubMed, Cochrane Library, and EMBASE from inception through October 5, 2021, to identify randomized trials of Suanzaoren. We included randomized trials comparing Suanzaoren to placebo, medications, cognitive behavioral therapy (CBT), or usual care for improving sleep outcomes in cancer and noncancer patients with insomnia or sleep disturbance. We performed a risk of bias analysis following Cochrane guidelines. Depending on heterogeneity, we pooled studies with similar comparators using fixed- and random-effects models. RESULTS: We included participants with insomnia disorder (N = 785) or sleep disturbance (N = 120) from 9 trials. Compared with placebo, Suanzaoren led to significant subjective sleep quality improvements in participants with insomnia and patients with sleep disturbance combined (standard mean difference -0.58, 95% CI -1.04, -0.11; P < .01); Compared with benzodiazepines or CBT, Suanzaoren was associated with a significant decrease in insomnia severity (mean difference -2.68 points, 95% CI -5.50, -0.22; P = .03) at 4 weeks in the general population and cancer patients. The long-term effects of Suanzaoren were mixed among trials. Suanzaoren did not increase the incidence of major adverse events. The placebo-controlled studies had a low risk of bias. CONCLUSION: Suanzaoren is associated with short-term patient-reported sleep quality improvements among individuals with insomnia or sleep disturbance. Due to the small sample size and variable study quality, the clinical benefits and harms of Suanzaoren, particularly in the long term, should be further assessed in a sufficiently powered randomized trial. REGISTRATION: PROSPERO CRD42021281943.

Raman microspectroscopy based TNM staging and grading of breast cancer.

The tumor-node-metastasis (TNM) system is the most common way that doctors determine the anatomical extent of cancer on the basis of clinical and pathological criteria. In this study, a spectral histopathological study has been carried out to bridge Raman micro spectroscopy with the breast cancer TNM system. A total of seventy breast tissue samples, including healthy tissue, early, middle, and advanced cancer, were investigated to provide detailed insights into compositional and structural variations that accompany breast malignant evolution. After evaluating the main spectral variations in all tissue types, the generalized discriminant analysis (GDA) pathological diagnostic model was established to discriminate the TNM staging and grading information. Moreover, micro-Raman images were reconstructed by K-means clustering analysis (KCA) for visualizing the lobular acinar in healthy tissue and ductal structures in all early, middle and advanced breast cancer tissue groups. While, univariate imaging techniques were adapted to describe the distribution differences of biochemical components such as tryptophan, ß-carotene, proteins, and lipids in the scanned regions. The achieved spectral histopathological results not only established a spectra-structure correlations via tissue biochemical profiles but also provided important data and discriminative model references for in vivo Raman-based breast cancer diagnosis.

Correlations between serum levels of microRNA-148a-3p and microRNA-485-5p and the progression and recurrence of prostate cancer.

BACKGROUND: Unpredicted postoperative recurrence of prostate cancer, one of the most common malignancies among males worldwide, has become a prominent issue affecting patients after treatment. Here, we investigated the correlation between the serum miR-148a-3p and miR-485-5p expression levels and cancer recurrence in PCa patients, aiming to identify new biomarkers for diagnosis and predicting postoperative recurrence of prostate cancer. METHODS: A total of 198 male PCa cases treated with surgery, postoperative radiotherapy, and chemotherapy were involved in the presented study. Serum levels of miR-148a-3p and miR-485-5p were measured before the initial operation for the involved cases, which were then followed up for two years to monitor the recurrence of cancer and to split the cases into recurrence and non-recurrence groups. Comparison of the relative expressions of serum miR-148a-3p and miR-485-5p were made and related to other clinic pathological features. RESULTS: Pre-surgery serum levels of miR-148a-3p in patients with TNM stage cT1-2a prostate cancer (Gleason score < 7) were significantly lower (P < 0.05) than levels in patients with TNM Classification of Malignant Tumors (TNM) stage cT2b and higher prostate cancer (Gleason score ≥ 7). pre-surgery serum levels of miR-485-5p in patients with TNM stage cT1-2a prostate cancer (Gleason score < 7) were significantly higher (P < 0.05) than in patients with TNM stage cT2b and higher cancer (Gleason score ≥ 7). Serum miR-148a-3p level in recurrence group is higher than the non-recurrence group (P < 0.05) while serum miR-485-5p level in recurrence group is lower than non-recurrence group (P < 0.05). ROC curve analysis showed the AUCs of using miR-148a-3p, miR-485-5p, and combined detection for predicting recurrence of prostate cancer were 0.825 (95% CI 0.765-0.875, P < 0.0001), 0.790 (95% CI 0.726-0.844, P < 0.0001), and 0.913 (95% CI 0.865-0.948, P < 0.0001). CONCLUSION: Pre-surgery serum miR-148a-3p level positively correlates while miR-485-5p level negatively correlates with prostate cancer's progressing and postoperative recurrence. Both molecules show potential to be used for predicting postoperative recurrence individually or combined.

FGF5 alleviated acute lung injury via AKT signal pathway in endothelial cells.

Acute lung injury (ALI), with high morbidity and mortality, is mainly resulted by infectious or non-infectious inflammatory stimulators, and it will further evolve into acute respiratory distress syndrome if not controlled. Fibroblast growth factors (FGFs) consist of more than 23 kinds of members, which are involved in various pathophysiological processes of body. However, the effect of FGF5, one member of FGFs, is still not certain in lipopolysaccharide (LPS)-induced ALI. In this study, we explored the possible impacts of FGF5 in LPS-induced ALI and primarily focused on endothelial cell, which was one of the most vulnerable cells in septic ALI. In the mouse group of FGF5 overexpression, LPS-induced lung injuries were mitigated, as well as the pyroptosis levels of pulmonary vascular endothelial cells. Additionally, in vitro human umbilical vein endothelial cells (HUVECs), our results showed that the level of cell pyroptosis was ameliorated with FGF5 overexpression, and AKT signal was activated with the overexpression of FGF5, whereas after administration of MK2206, an inhibitor of AKT signal, the protection of FGF5 was inhibited. Therefore, these results suggested that FGF5 exerted protective effects in endothelial cells exposed to LPS, and this protection of FGF5 could be attributed to activated AKT signal.

Dual role of pseudogene TMEM198B in promoting lipid metabolism and immune escape of glioma cells.

Dysregulation of pseudogenes, enhancement of fatty acid synthesis and formation of immunosuppressive microenvironment are important factors that promote the malignant progression of glioma. It is of great significance to search for the molecular mechanism of interaction between the three and then perform targeted interference for improving the treatment of glioma. In this study, we found that pseudogene transmembrane protein 198B (TMEM198B) was highly expressed in glioma tissues and cell lines, and it could promote malignant progression of glioma by regulating lipid metabolism reprogramming and remodeling immune microenvironment. Applying the experimental methods of gene interference, lipidomics and immunology, we further confirmed that TMEM198B promoted PLAG1 like zinc finger 2 (PLAGL2) expression by mediating tri-methylation of histone H3 on lysine 4 (H3K4me3) of PLAGL2 through binding to SET domain containing 1B (SETD1B). Increased PLAGL2 could transcriptional activate ATP citrate lyase (ACLY) and ELOVL fatty acid elongase 6 (ELOVL6) expression, and then influenced the biological behaviors of glioma cells via enhancing the de novo lipogenesis and fatty acid acyl chain elongation. At the same time, TMEM198B promoted macrophages lipid accumulation and intensification of fatty acid oxidation (FAO) through glioma-derived exosomes (GDEs), further induced macrophages to M2 polarization, which subsequently facilitated immune escape of glioma cells. In conclusion, our present study clarifies that the TMEM198B/PLAGL2/ACLY/ELOVL6 pathway conducts crucial regulatory effects on the malignant progression of glioma, which provides novel targets and new ideas for molecular targeted therapy and immunotherapy of glioma.

Case Report: A Case of Infant Bronchial Dieulafoy's Disease and Article Review.

Background: Bronchial Dieulafoy's disease (BDD), characterized by constant diameter arterial malformation, is rare, especially among infants. The pathogenesis and clinical features of pediatric patients are unknown. Misdiagnosis and biopsy operations may lead to potential massive hemorrhage, which endangers the patient's life. Case Presentation: Here, we present a case of a 9-month-old boy who was diagnosed with BDD with massive hemoptysis. The boy was cured by embolization of the bronchial artery and was in good health at the 1-year follow-up. In addition, we searched PubMed, Google Scholar, and Web of Science databases using keyword "Bronchial Dieulafoy's Disease (BDD)" and found six additional cases of pediatric BDD. Conclusion: It is still insufficient to draw a conclusion about the origin of the disease. Bronchial angiography and endobronchial ultrasonography are considered promising methods to diagnose Dieulafoy's disease of the bronchus. Bronchoscopy with transbronchial biopsy should not be deployed due to the high risk of fatal hemorrhage. Explicit clinical case reports of BDD are needed to enhance the understanding of this rare disease.

Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study.

BACKGROUND: Ulcerative colitis (UC), a chronic and nonspecific inflammatory bowel disease, seriously affects the quality of patients' life. Han Re Bing Yong Fa (treating diseases with both cool- and warm-natured herbs) is a classical therapeutic principle of traditional Chinese medicine (TCM), which is often used to treat chronic diseases, including UC. The Gan Jiang-Huang Qin-Huang Lian-Ren Shen decoction (GJHQHLRSD), a representative of Han Re Bing Yong Fa, is effective in alleviating inflammatory symptoms in UC. However, the pharmacological mechanism underlying its anti-inflammatory effect remains unclear. METHODS: A network pharmacology strategy, including the construction and analysis of the drug-disease network, was used to explore the complex mechanism of GJHQHLRSD treatment of UC. In addition, molecular docking technology was used to preliminarily examine the binding ability of the potential active components and core therapeutic targets of GJHQHLRSD. RESULTS: The network pharmacology results revealed 140 targets of GJHQHLRSD which are involved in UC. The PPI network analysis identified seven target genes: BCL2L1, NR3C1, ALOX5, S1PR5, NR1I2, CYP2D6, and LPAR6. The molecular docking results revealed that the following displayed strongest combined effects: EGFR with kaempferol, ERK1 with worenine, STAT3 with Palmidin A, BCL2L1 with diop and VEGFA with ginsenoside Rg3. The KEGG and gene ontology enrichment analyses results indicated that GJHQHLRSD functions by regulating the EGFR signaling pathway in UC treatment. Other effective biological processes involved in UC treatment included cancer-related as well as inflammation and viral infection signaling pathways, such as the "MicroRNAs in cancer," "TNF signaling pathway," and "JAK-STAT signaling pathway." CONCLUSIONS: This study reflects the multicomponent, multitarget, and multipathway characteristics of the action mechanism of GJHQHLRSD in treating UC. Furthermore, it helps better understand the TCM therapeutic principle of Han Re Bing Yong Fa and explore novel candidate drug targets for UC treatment.

KLF11 Expression Predicts Poor Prognosis in Glioma Patients.

PURPOSE: Glioma is a primary intracranial malignant tumor with high recurrence and mortality rates. It is very important to study the prognostic factors. KLF11 can function as an oncogene or a tumor suppressor, depending on the tumor and tissue types and the cancer stage. In this study, we aimed to determine whether KLF11 expression is related to the overall survival of glioma patients. PATIENTS AND METHODS: We investigated KLF11 expression in 116 glioma patients with different grades using Western blot and immunohistochemistry assay. We analyzed the patients with different glioma grades and KLF11 expression levels by Kaplan-Meier survival curves. Independent prognostic factors for poor overall survival were identified by univariate and multivariate analyses. RESULTS: There were 37 patients in KLF11 low expression group and 79 patients in high expression group. There was no difference in gender, age, tumor diameter or tumor location between two groups. The patients in KLF11 high expression group had higher ECOG score (P =0.025) and higher WHO grades (P =0.029). Western blot and immunohistochemistry assay showed KLF11 expression was significantly upregulated in glioma groups compared with normal brain tissues group (P < 0.05), and the expression in grades III-IV was significantly higher than those in grades I-II (P < 0.05). Kaplan-Meier survival curve analysis showed high KLF11 expression tended to reduce the overall survival (P < 0.05). After univariate and multivariate analyses, KLF11 expression (P =0.003) and age (P =0.007) were independent prognostic factors for poor survival in glioma patients. CONCLUSION: KLF11 expression was increased in glioma tissues, and high KLF11 expression was associated with poor prognosis. KLF11 expression was an independent prognostic factor for poor survival in glioma patients. KLF11 may serve as a novel prognostic marker for gliomas and as a novel treatment target.