The glutamate (Glu)-glutamine (Gln) cycle between astrocytes and neurons plays a crucial role in maintaining extracellular Glu levels during excitatory neurotoxicity, with glutamine synthetase (GS) and glutaminase (GLS) serving as the key enzymes. Ampelopsin (Amp) exhibits diverse biological and pharmacological activities, including antioxidant, anti-inflammatory, and antitumor effects. Notably, Amp regulates GLS, which is also the established target of CB-839, a potent and specific inhibitor known to suppress tumorigenesis. However, the influence of this effect on neuroprotective effects and Glu homeostasis remains unclear. This study aimed to construct a middle cerebral artery occlusion/reperfusion (MCAO/R) model to assess the effects of Amp and CB-839 on Glu-induced ischemic injury in vivo. Herein, Glu and Gln levels within the Glu-Gln metabolic cycle, and protein levels of GLS, GS, glutamate transporter-1 (GLT-1), and N-methyl-D-aspartate receptor (NMDAR) were analyzed. Immunofluorescence staining was performed to determine the distribution of GLS and GS in brain astrocytes and neurons. Notably, both Amp and CB-839 exerted neuroprotective effects in MCAO/R mice by reducing cerebral infarction area, alleviating brain edema, and improving neurological function. Furthermore, they attenuated neuronal necrosis and mitigated the ischemia-induced damage to neurons and Nissl bodies. In addition, both Amp and CB-839 enhanced GS-mediated Glu-to-Gln conversion in astrocytes by increasing GS activity in the ischemic brain and reducing Glu accumulation through GLT-1 upregulation, which facilitated Glu uptake. In neurons, both Amp and CB-839 inhibited GLS-mediated Gln hydrolysis to Glu by downregulating GLS expression, leading to elevated Gln and decreased Glu levels during cerebral ischemia. Simultaneously, NMDAR expression was reduced, preventing excitatory neurotoxicity driven by excessive glutamatergic signaling. Overall, this study highlights the potential of Amp in providing neuroprotection in mice subjected to transient focal cerebral ischemia by promoting the dynamic Glu homeostasis.

Ampullary carcinoma is an uncommon malignant neoplasm located in Vater’s ampulla, necessitating comprehensive exploration of its pathogenesis and therapeutic alternatives. Currently, the available models of ampullary carcinoma are severely restricted, impeding the advancement of fundamental research. Consequently, further models of ampullary carcinoma are required to enhance pertinent fundamental research. This study reports the development of a novel Chinese-origin human ampullary carcinoma cell line, named DPC-X2, utilizing fresh primary tumor tissue from ampullary carcinoma. DPC-X2 has been consistently passaged for more than 60 generations, exhibiting a population doubling time of around 95 h. The cells display atypical shape and distinct heterogeneity. STR profiling verifies that DPC-X2 is a unique human ampullary carcinoma cell line. Karyotype analysis indicates that all DPC-X2 cells have hyper-triploid karyotypes, characterized by a typical karyotype of 100, XXXX der(4), der(6), der(7), inv(9), der(12), der(13), der(19). The xenograft tumor development rate in NXG mice was 66.67

Ferric chloride (FeCl3) is a common agent for inducing thrombosis in laboratory animals. However, there is no sufficient data regarding the conditions of model preparation in dogs. We aimed to identify the optimal concentration and solvent of FeCl3 for inducing canine superficial femoral artery thrombosis. We applied 30, 40, or 50% FeCl3 in 1 M hydrochloric acid or water topically on the superficial femoral artery for 30 min to induce thrombosis, respectively, with the distal end of the exposed artery clipped for 15 min. Then the thrombus size and blood flow were assessed by the High-Resolution Ultrasonic Photoacoustic Multimode Imaging System, and pathological changes were evaluated with HE staining. Regardless of the concentration or solvent, FeCl3 solutions successfully induced stable and dense thrombi. At day 28, 30% FeCl3 in 1 M HCl demonstrated greater peak systolic velocity (PSV) ratios of normal and recanalization rates than 40% FeCl3 in 1 M HCl. Except for day 14, 40% FeCl3 in H2O had lower PSV ratios and recanalization rates compared to 50% FeCl3 in H2O. The 40% FeCl3 in H2O demonstrated greater blood flow recovery than the 40% FeCl3 in 1 M HCl. Compared to the water solution, the acidic solution caused more pronounced endothelial cell damage, with no differences between varying concentrations in the same solvent. FeCl3 application combined with blood flow blockage effectively induced stable thrombi in the superficial femoral arteries of dogs. Hydrochloric acid solutions demonstrated better thrombus formation efficacy than water.

Cholangiocarcinoma (CCA) is a highly heterogeneous primary malignant tumor of the biliary tract. Intrahepatic and extrahepatic cholangiocytes originate from different sources, resulting in significant clinical, epidemiological, molecular, and genetic heterogeneity. Globally, the incidence and mortality rates of CCA are generally increasing, highlighting the need for more foundational research to support advances in clinical diagnosis and treatment. Tumor cell lines remain a crucial tool for unraveling the molecular mechanisms underlying tumor development and for the development of novel therapeutic strategies. The existing CCA cell lines are insufficient to meet research demands, underscoring the urgent need to establish new CCA cell lines. In this study, we successfully established a novel human CCA cell line, designated EBC-X1, derived from a Chinese patient. It exhibits robust proliferative capacity and was successfully passaged for more than 40 generations. STR analysis confirmed that EBC-X1 is a distinct human-derived CCA cell line. The population doubling time was 64.5 h. Karyotypic analysis revealed that EBC-X1 cells exhibit complex karyotypes, with 91

AbstractAmpullary carcinoma (AC) of the intestinal type represents a distinct variant within the broader category of ampullary neoplasms. The scarcity of pertinent cellular models has constrained investigations centered on this particular malignancy. This research effectively generated a cell line (CL) of intestinal-type AC (DPC-X3). This newly developed CL has been continuously cultured for 1 year and has demonstrated stable passaging exceeding 60 generations. Morphologically, DPC-X3 exhibited characteristic attributes of an epithelial tumor. The cell proliferation rate of DPC-X3 exhibited a doubling interval of 79 h. Short tandem repeat (STR) analysis validated the high consistency between DPC-X3 and the patient’s primary tumor. Characteristically, DPC-X3 displayed sub diploid karyotypes, primarily featuring 44, XY inv (9), -18, -20, -22, and + mar. Under suspension culture conditions, DPC-X3 could efficiently form organoids, and DPC-X3 cells inoculated subcutaneously into NXG mice could form transplanted tumors. Drug susceptibility assays demonstrated that DPC-X3 resisted paclitaxel, oxaliplatin, 5-fluorouracil(5-FU), and gemcitabine. Immunohistochemical (IHC) evaluation revealed affirmative reactivity for CK7 and CK20 within DPC-X3 cells, while CDX2 exhibited no detectable expression. E-cadherin and Vimentin demonstrated positive immunoreactivity, whereas CEA and CA19-9 displayed faint positivity. The Ki-67 proliferation index was determined to be approximately 40%. DPC-X3 presents a valuable experimental platform for elucidating the pathogenesis of intestinal-type AC and can serve as a driver for drug development efforts.

Chemotherapy resistance poses clinical challenges in pancreatic cancer treatment. Developing cell lines resistant to chemotherapy is crucial for investigating drug resistance mechanisms and identifying alternative treatment pathways. The genetic and biological attributes of pancreatic cancer depend on its aetiology, racial demographics and anatomical origin, underscoring the need for models that comprehensively represent these characteristics. Here, we introduce PDAC-X2, a pancreatic cancer cell line derived from Chinese patients. We conducted a comprehensive analysis encompassing the immune phenotype, biology, genetics, molecular characteristics and tumorigenicity of the cell line. PDAC-X2 cells displayed epithelial morphology and expressed cell markers (CK7 and CK19) alongside other markers (E-cadherin, Vimentin, Ki-67, CEA and CA19-9). The population doubling time averaged around 69 h. In vivo, PDAC-X2 cells consistently maintained their tumorigenicity, achieving a 100% tumour formation rate. Characterised by a predominantly tetraploid karyotype, this cell line exhibited a complex genetic markup. Notably, PDAC-X2 cells demonstrated resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil and oxaliplatin. In conclusion, PDAC-X2 presents an invaluable preclinical model. Its utility lies in facilitating the study of drug resistance mechanisms and the exploration of alternative therapeutic approaches aimed at enhancing the prognosis of this tumour type.

Mixed-type ampullary cancer is a distinct subtype of ampullary cancer that manifests a merging of the biological characteristics of both intestinal and pancreaticobiliary subtypes. The absence of established cell lines specific to this subtype has resulted in a concomitant scarcity of research on its tumorigenic mechanisms and the development of novel therapeutic modalities. The present study achieved the successful establishment of a novel mixed-type ampullary cancer cell line, designated DPC-X4 through primary culture techniques. Subsequent analyses pertaining to phenotypic characteristics, molecular profiling, biomarker identification, and histological features validated the DPC-X4 cell line as a potent model for delineating the pathogenesis of mixed-type ampullary cancer and facilitating the development of new pharmacological agents. This newly established cell line was subjected to continuous cultivation for 1 year, with stable passaging for over 50 generations. Notably, the DPC-X4 cell line manifested typical morphological features associated with epithelial tumors. Furthermore, the population doubling time for the DPC-X4 cell line was determined at 70 h. Short tandem repeat (STR) analysis confirmed that the DPC-X4 cell line exhibited a high genetic concordance with the primary tumor from the patient. Karyotypic profiling indicated an abnormal sub-triploid karyotype, with representative karyotypes of 57, XXY inv (9), 14p + , 15p + , der (17), + mar. The DPC-X4 cell line demonstrated a high capacity for efficient organoid formation under suspension culture conditions. In addition, the subcutaneous inoculation of DPC-X4 cells into NXG mice led to the formation of xenografted tumors. The results of drug sensitivity testing indicated that DPC-X4 cells were sensitive to paclitaxel and resistant to oxaliplatin, 5-fluorouracil, and gemcitabine. Immunohistochemistry revealed positive expression of CK7, CK19, and CK20 in DPC-X4 cells, while CDX2 demonstrated negative expression. In addition, positive expression of E-cadherin and vimentin was identified in DPC-X4 cells, with a proliferation index indicated by Ki-67 at 70%. The findings of our study establish DPC-X4 as a novel mixed-type ampullary cancer cell line, which can serve as a potential experimental model for exploring the pathogenesis of ampullary cancer and the development of therapeutic drugs.

PURPOSE:Initial treatment for Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC) often involves Gemcitabine plus cisplatin with or without PD-1 inhibitors. However, PD-1 inhibitors' effectiveness varies, prompting for better treatments. This study explores effect and safety of combining PD-1 inhibitors with chemoradiotherapy for oligometastatic NPC patients. METHODS:Oligometastatic NPC patients underwent radical treatment with PD-1 inhibitors and chemotherapy, followed by concurrent PD-1 inhibitors and chemoradiotherapy, and then maintenance PD-1 inhibitors. Objective response rate (ORR) and disease control rate (DCR) were calculated by irRECIST-1.1, and CTCAE-4.0 was used to evaluate the toxicity. RESULTS:The study enrolled 47 patients with a median age of 46. The median follow-up lasted 16.5 months, with metastatic lesions receiving a median radiation dose of 45 Gy. The median courses of PD-1 inhibitors and chemotherapy were 9.5 and 5 respectively. The metastasis sites included lung (40.8 %), liver (21.1 %), mediastinal lymph node (7.9 %), abdominal lymph nodes (3.9 %), bone (21.1 %), adrenal gland (3.9 %), and brain (1.3 %). ORR and DCR were 85.1 % and 100 % at 3 months after radiotherapy. The median survival was not reached yet, and 1 and 2-year OS rates were 93.1 % and 78.4 %. The median PFS was 18 months, with 1 and 2-year PFS rates of 70.2 % and 47.7 % respectively. PD-L1 expression showed a positive correlation for PFS. Twenty-five patients experienced grade 3 or 4 adverse events (AE) that were possibly related to chemotherapy. No grade 5 AE was observed. CONCLUSIONS:The synergy of concurrent PD-1 inhibitors and chemoradiotherapy shows promising efficacy and an acceptable toxicity for oligometastasis NPC patients.

Abstract The glutamate-glutamine(Glu-Gln) cycle between astrocytes and neurons is an essential component in balancing extracellular Glu levels during excitatory neurotoxicity. Glutamine synthetase (GS) and glutaminase (GLS) are the key mediators in keeping Glu balance. Ampelopsin (AMP) has an inhibitory effect on peripheral GLS. It is uncertain whether this effect of AMP could produce neuroprotective effects and affect glutamate balance. The middle cerebral artery occlusion/ reperfusion (MCAO/R) model was constructed to investigate the effect of AMP and CB-839 on glutamate-induced ischemic injury in vivo. The protein expression of GLS, GS, glutamate transporter-1 (GLT-1), and N-methyl-D-aspartate receptor (NMDAR) was detected, and the distribution of GLS and GS in brain astrocytes and neurons was analyzed by immunofluorescence staining. Glu is the active molecule that mediates the upstream and downstream excitotoxic responses. The levels of Glu and Gln in the Glu-Gln metabolic cycle were also assayed. Our studies demonstrated that either AMP or CB-839 showed neuroprotective effects on MCAO/R mice through alleviating cerebral infarction area, relieving brain edema and neurological deficit function. They also reduced the necrosis of nerve tissue, rescued the damage of neurons and Nissl bodies undergoing ischemia. In addition, both AMP and CB-839 enhanced GS-mediated conversion of Glu to Gln on astrocytes by increasing ischemic brain GS activity and reducing Glu accumulation via facilitating GLT-1 expression and promoting Glu uptake. On neurons, the GLS-mediated hydrolysis of Gln to Glu is hindered by AMP and CB-839 through reducing the expression of GLS, which results in elevated Gln content and downregulated Glu levels in cerebral ischemia. At the same time, the expression of NMDAR was decreased to prevent the excitatory neurotoxicity caused by Glu's excessive activation. AMP exhibited neuroprotection in mice subjected transient focal cerebral ischemia via its ability to promote the dynamic balance of the glutamate concentration.

In this study, a novel pancreatic cancer cell line, termed pancreatic ductal adenocarcinoma (PDAC)-X3 cell line, was successfully derived from the primary tumor. Comprehensive analyses of its malignant phenotype, molecular properties, specific biomarkers, and histological features confirmed that PDAC-X3 cells serve as a valuable model for investigating the underlying mechanisms driving pancreatic carcinogenesis and advancing potential therapeutic strategies. The newly established cell line was continuously cultured for over 12 months and was stably passaged through more than 50 generations. Morphologically, PDAC-X3 cells displayed characteristics typical of epithelial tumors. The population doubling time for PDAC-X3 cells was determined to be 50 h. Karyotype analysis revealed that 75

In this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line’s phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents. GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient’s primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10). Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel. Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development.

Drug resistance remains a significant challenge in the treatment of pancreatic cancer. The development of drug-resistant cell lines is crucial to understanding the underlying mechanisms of resistance and developing novel drugs to improve clinical outcomes. Here, a novel pancreatic cancer cell line, PDAC-X1, derived from Chinese patients has been established. PDAC-X1 was characterized by the immune phenotype, biology, genetics, molecular characteristics, and tumorigenicity. In vitro analysis revealed that PDAC-X1 cells exhibited epithelial morphology and cell markers (CK7 and CK19), expressed cancer-associated markers (E-cadherin, Vimentin, Ki-67, CEA, CA19-9), and produced pancreatic cancer-like organs in suspension culture. In vivo analysis showed that PDAC-X1 cells maintained tumorigenicity with a 100% tumor formation rate. This cell line exhibited a complex karyotype, dominated by subtriploid karyotypes. In addition, PDAC-X1 cells exhibited intrinsic multidrug resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil, and oxaliplatin. In conclusion, the PDAC-X1 cell line has been established and characterized, representing a useful and valuable preclinical model to study the underlying mechanisms of drug resistance and develop novel drug therapeutics to improve patient outcomes.

Astrocytes are key targets for treating cerebral ischemia in the central nervous system. Non-coding RNAs (ncRNAs) participate in the pathological processes of astrocytes in cerebral ischemia. Recent reports suggest that ncRNAs ameliorate the outcome of cerebral ischemia by mediating astrocytes' inflammatory reaction, oxidative stress, excitotoxicity, autophagy, and apoptosis. Reconstructing cellular systems might offer a promising strategy for treating cerebral ischemia. This review briefly discusses the potential of ncRNAs as drug targets and explores the molecular regulatory mechanisms through which ncRNAs target astrocytes in cerebral ischemia. It provides an overview of the current research, discusses ncRNAs' implications as clinical markers for cerebral ischemia, and anticipates that ongoing research on ncRNAs may contribute to novel therapeutic approaches for treating this condition.

To explore the effects of a single dose of uridine adenosine tetraphosphate (Up4A) administered through the tail vein, on the blood pressure of mice. The mice were separated into three groups: the Up4A group, the norepinephrine (NA) group, and the α, β-methylene adenosine triphosphate (α, β-meATP) group. Each group of mice were injected drugs through the tail vein at 1, 3, 10, and 30 nmol/kg doses in an ascending order. Additionally, six mice were injected Up4A through the tail vein at 20, 40, 60, and 80 nmol/kg doses in an ascending order. The administration intervals for each dose were 20 min. Mice in these groups experienced a rapid increase in blood pressure, reaching its peak within 10 s after drug administration. It took approximately 120 s for the blood pressure to return to baseline levels after the administration of the drugs in both the NA and α, β-meATP groups. After higher doses of Up4A were administered to the mice, their blood pressure exhibited biphasic changes. Initially, blood pressure of the mice rapidly dropped to a minimum within 10 s, then rose rapidly to a peak within 30 s. Subsequently, it gradually declined, taking around 10 min to return to the levels before the drug administration. Compared to NA and α, β-meATP, Up4A, which contains purine and pyrimidine components, displayed a weaker blood pressure-elevating potency. Through its corresponding structure, Up4A exerted vasodilatory and vasoconstrictive effects throughout the entire experiment resulting in biphasic changes in blood pressure.

Objective Non-small cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. Whole-brain radiotherapy (WBRT) is one of the standard treatment strategies for NSCLC. It is interesting to combine angiogenesis inhibitors such as bevacizumab with radiation therapy. This study aimed to explore the efficacy and safety of stereotactic radiosurgery (SRS) with WBRT combined with bevacizumab in the treatment of brain metastases. Methods A total of 21 patients with brain metastases from NSCLC were treated with bevacizumab and WBRT-SRS, while 28 patients were treated with WBRT-SRS only. The bevacizumab average dose was 5-7.5 mg/kg, approximately 2 cycles during radiotherapy. Tumor responses were evaluated every 3 months based on Response Evaluation Criteria in Solid Tumors version 1.1. Results The median follow-up time was 13.5 months (range 2.7-88.4 months). The ORR and DCR of patients who received WBRT-SRS with or without bevacizumab were similar (p = 0.458, p = 0.382). OS(42.63 years VS 25.23 years, p = 0.02)and LPFS (39.53 years VS 23 years, p = 0.047)were better in WBRT-SRS with bevacizumab groups. After radiotherapy and 3 months after radiotherapy, the volume of peritumoral edema was significantly reduced in WBRT-SRS with bevacizumab groups(45.62 +/- 24.03 cm(3) vs 63.03 +/- 25.44 cm(3), p = 0.036;8.63 +/- 6.87 cm(3) vs 15.62 +/- 10.58 cm(3), p = 0.021). The main adverse reactions were similar in the two groups except for Venous thrombosis with bevacizumab (0 patients vs 5 patients, p = 0.006). Conclusion Bevacizumab with radiotherapy improved the overall efficacy and reduced the peritumoral edema of BM from NSCLC.

Adipose-derived stem cells (ADSCs) could be ideal seed cells for repairing nerve injury as they have the potential for multidirectional dif-ferentiation. However, it is still unclear whether the undifferentiated or the differentiated ADSCs have priorities in promoting axonal regeneration and my-elin formation. In this study, the primary ADSCs from rats were cultured and differentiated. The morphology, differentiation potential, and secretion of neu-rotrophic factors of ADSCs were compared before and after induction. Undiffer-entiated ADSCs (uADSCs) were aggregated into bundles containing reticular, star, and polygonal structures. They contained a large number of lipid droplets and were positive for Oil red O staining. After differentiation, differentiation ADSCs (dADSCs) become long and spindle-shaped with decreasing protrusions around the cells, spiraling growth, and were negative for Oil red O staining. When comparing the groups the flow cytometer analysis showed: similar CD29 and CD45 surface markers in both groups; and CD44 and CD90 markers were very low in the undifferentiated groups. The levels of neurotrophin 3 (NT-3) and neuregulin 1 (NRG-1), and their receptors tropomyosin receptor kinase C (TrkC) and receptor protein-tyrosine kinase erbB-4 (ErbB-4) in dADSCs were higher than those in uADSCs. While the expressions of myelin protein zero (P0), myelin-associated glycoprotein (MAG), and purine receptor P2X7 (P2X7) were not significantly different before and after differentiation. It may be specu-lated that the dADSCs have enhanced abilities in nerve repairment which is associated with increased expression of neurotrophic factors

Programmed cell death-1 (PD-1) inhibitor was proven to be useful for the recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients. Though both PD-1 inhibitor alone and combination with chemotherapy showed some benefit for PFS and OS, the survival outcome was still not satisfactory. Some studies showed the possible benefit for PD-1 inhibitors combination with radiation for head and neck squamous carcinoma, however there was few studies concerned about synergy of concurrent PD-1 inhibitor combination with chemoradiotherapy for R/M HNSCC. So, we aimed to explore the potential effect and toxicity of the concurrent PD-1 inhibitor and chemoradiotherapy for R/M HNSCC. We consecutively enrolled the R/M HNSCC patients treated with concurrent PD-1 inhibitor and chemoradiotherapy from August 2018 to April 2022 in Sichuan Cancer hospital. All the patients received the combination of PD-1 inhibitor and chemotherapy, and followed with synergy of concurrent PD-1 inhibitor and chemoradiotherapy, then maintenance PD-1 inhibitor. ORR and DCR was calculated by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST-1.1), and Common terminology criteria for adverse events (CTCAE-4.0) was used to evaluate the toxicity.The Kaplan–Meier method was used to analyze OS and PFS. 40 R/M HNSCC patients were enrolled in our stuty. The median follow up time was 14 months. 22 patients had recurrent disease only, 16 patients had metastatic disease only, and 2 patients had both recurrence and metastasis disease. For the recurrent lesions, 23 patients received a median radiation dose of 64 Gy (range 50–70 Gy). 18 patients received a median dose of 45 Gy (range 30–66 Gy) for metastatic lesions. The median courses of PD-1 inhibitors and chemotherapy were 8 and 5 respectively. After the treatment, the ORR and DCR were 70.0

Circular RNAs (circRNAs) are a class of non-coding RNA that play crucial roles in the growth and development of skeletal muscle. However, little is known about the role of circRNAs in caprine skeletal muscle. In this study, the size of muscle fiber and the expression profiles of circRNAs were compared in Longissimus dorsi muscle of Liaoning cashmere (LC) goats and Ziwuling black (ZB) goats with significant phenotypic differences in meat production performance, using hematoxylin and eosin staining and RNA-Seq, respectively. The size of muscle fiber in LC goats was larger than those in ZB goats ( P < 0.05). A total of 10,875 circRNAs were identified and 214 of these were differentially expressed between the two caprine breeds. The parent genes of differentially expressed circRNAs were mainly enriched in connective tissue development, Rap1, cGMP-PKG, cAMP and Ras signaling pathway. In conclusion, circRNAs may play important roles in skeletal mass, meat production performance and meat quality traits in goats. The results provide an improved understanding of the functions of circRNAs in skeletal muscle development of goats.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive dysfunction. The glutamate (Glu) metabolic pathway may be a major contributor to the memory dysfunction associated with AD. The TWIK-related potassium channel-1 (TREK-1) protects against brain ischemia, but any specific role for the channel in AD remains unknown. In this study, we used SAMP8 mice as an AD model and age-matched SAMR1 mice as controls. We explored the trends of changes in TREK-1 channel activity and the levels of AD-related molecules in the brains of SAMP8 mice. We found that the expression level of TREK-1 increased before 3 months of age and then began to decline. The levels of Tau and Glu increased with age whereas the acetylcholine level decreased with age. α-Linolenic acid (ALA), an activator of the TREK-1 channel, significantly increased the TREK-1 level, and improved the learning and memory deficits of SAMP8 mice aged 6 months. The mechanism in play may involve the Glu metabolic pathway. After activation of the TREK-1 channel, damaged neurons and astrocytes were rescued, the levels of Glu and the N-methyl-D-aspartate receptor were downregulated, and the level of glutamate transporter-1 was upregulated. These findings suggest that TREK-1 plays a crucial role in the pathological progression of AD; activation of the TREK-1 channel improved cognitive deficits in SAMP8 mice via a mechanism that involved Glu metabolism. The TREK-1 potassium channel may thus be a valuable therapeutic target in AD patients.