Endothelial progenitor cells control remodeling of uterine spiral arteries for the establishment of utero-placental circulation.

Placental ischemia, resulting from inadequate remodeling of uterine spiral arteries, is a factor in the development of preeclampsia. However, the effect of endothelial progenitor cells that play a role in the vascular injury-repair program is largely unexplored during remodeling. Here, we observe that preeclampsia-afflicted uterine spiral arteries transition to a synthetic phenotype in vascular smooth muscle cells and characterize the regulatory axis in endothelial progenitor cells during remodeling in human decidua basalis. Excessive sEng, secreted by AMP-activated protein kinase (AMPK)-deficient endothelial progenitor cells through the inhibition of HO-1, damages residual endothelium and leads to the accumulation of extracellular matrix produced by vascular smooth muscle cells during remodeling, which is further confirmed by animal models. Collectively, our findings suggest that the impaired functionality of endothelial progenitor cells contributes to the narrowing of remodeled uterine spiral arteries, leading to reduced utero-placental perfusion. This mechanism holds promise in elucidating the pathogenesis of preeclampsia.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor.

BACKGROUND: The neuroendoscopic approach has the advantages of a clear operative field, convenient tumor removal, and less damage, and is the development direction of modern neurosurgery. At present, transnasal surgery for sphenoidal pituitary tumor is widely used. But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts. AIM: To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors. METHODS: A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups, with 30 in each group. Experimental group: After anesthesia, a gastric tube was placed through the mouth under direct vision using a visual laryngoscope, and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection, during the operation, and when the patient recovered from anesthesia. Control group: Given the routine intraoperative care, no gastric tube was left. The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups; the scores of pharyngalgia after waking up, 6 h post-operation, and 24 h post-operation. The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared. The hospitalization days of the two groups were statistically compared. RESULTS: The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group, and the difference in the incidence of nausea was statistically significant (P < 0.05). After the patient woke up, the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group, and the difference was statistically significant (P < 0.05). The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group, but there was no statistically significant difference from the control group (P > 0.05). The hospitalization days of the experimental group was lower than that of the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors, combined with intraoperative and postoperative gastrointestinal decompression, can effectively reduce the incidence of nausea, reduce the number of vomiting and aspiration in patients, and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

High-performance fibre battery with polymer gel electrolyte.

Replacement of liquid electrolytes with polymer gel electrolytes is recognized as a general and effective way of solving safety problems and achieving high flexibility in wearable batteries1-6. However, the poor interface between polymer gel electrolyte and electrode, caused by insufficient wetting, produces much poorer electrochemical properties, especially during the deformation of the battery7-9. Here we report a strategy for designing channel structures in electrodes to incorporate polymer gel electrolytes and to form intimate and stable interfaces for high-performance wearable batteries. As a demonstration, multiple electrode fibres were rotated together to form aligned channels, while the surface of each electrode fibre was designed with networked channels. The monomer solution was effectively infiltrated first along the aligned channels and then into the networked channels. The monomers were then polymerized to produce a gel electrolyte and form intimate and stable interfaces with the electrodes. The resulting fibre lithium-ion battery (FLB) showed high electrochemical performances (for example, an energy density of about 128 Wh kg-1). This strategy also enabled the production of FLBs with a high rate of 3,600 m h-1 per winding unit. The continuous FLBs were woven into a 50 cm × 30 cm textile to provide an output capacity of 2,975 mAh. The FLB textiles worked safely under extreme conditions, such as temperatures of -40 °C and 80 °C and a vacuum of -0.08 MPa. The FLBs show promise for applications in firefighting and space exploration.

Age-related pharmacokinetics differences were observed between young and elderly populations of a novel PDE5 inhibitor, youkenafil, and its metabolite M459.

PURPOSE: Youkenafil is a novel oral selective PDE5 inhibitor for treating Erectile Dysfunction. This investigation assessed pharmacokinetics (PK), safety, and tolerability of youkenafil and its main metabolite (M459) after taking 100 mg youkenafil hydrochloride tablets in elderly and young subjects. METHODS: This Phase I, single-center, open-label, parallel-group, single-dose study was conducted on 24 individuals (12 elders and 12 youngsters). Each subject received a single oral 100 mg youkenafil hydrochloride tablets. Blood samples were collected before medication and up to 48 h after medication for PK analysis. Safety and tolerability were also assessed, including treatment-emergent adverse events (TEAEs), laboratory tests, 12-lead ECG, vital sign inspections, color vision examinations, and physical examinations. RESULTS: Plasma concentrations of youkenafil and M459 were quantified. PK parameters were determined by non-compartmental analysis. Median Tmax of elderly and young groups were both 0.733 h. However, Cmax, AUC0-t, and AUC0-∞ of youkenafil were separately 16.8 %, 37.2 %, and 37.5 % higher in elders and t1/2 of youkenafil was 2.1 h longer in elders. More great differences were observed for M459. T1/2 values were 4.05 h longer in elders, with Cmax, AUC0-t and AUC0-∞ 73.7 %, 81.1 %, and 81.4 % higher in elders. Two (8.3 %) elderly subjects reported TEAEs (all grade Ⅰ in severity) and both recovered without any treatment. No serious adverse reactions (SAEs) or serious unexpected suspected adverse reactions (SUSARs) occurred in this study. CONCLUSIONS: This was the first PK research of youkenafil and M459 in elderly men. PK parameters differences between youkenafil and M459 were comparable between elderly and young groups. Moreover, safety and tolerability of youkenafil were favorable in both groups.

FRP-XGBoost: Identification of ferroptosis-related proteins based on multi-view features.

Ferroptosis represents a novel form of programmed cell death. Pan-cancer bioinformatics analysis indicates that identifying and modulating ferroptosis offer innovative approaches for preventing and treating diverse tumor pathologies. However, the precise detection of ferroptosis-related proteins via conventional wet-laboratory techniques remains a formidable challenge, largely due to the constraints of existing methodologies. These traditional approaches are not only labor-intensive but also financially burdensome. Consequently, there is an imperative need for the development of more sophisticated and efficient computational tools to facilitate the detection of these proteins. In this paper, we presented a XGBoost and multi-view features-based machine learning prediction method for predicting ferroptosis-related proteins, which was referred to as FRP-XGBoost. In this study, we explored four types of protein feature extraction methods and evaluated their effectiveness in predicting ferroptosis-related proteins using six of the most commonly used traditional classifiers. To enhance the representational power of the hybrid features, we employed a two-step feature selection technique to identify the optimal subset of features. Subsequently, we constructed a prediction model using the XGBoost algorithm. The FRP-XGBoost achieved an accuracy of 96.74 % in 10-fold cross-validation and a further accuracy of 91.52 % in an independent test. The implementation source code of FRP-XGBoost is available at https://github.com/linli5417/FRP-XGBoost.

Insight into the high-temperature oxidation kinetics of acetylene: A first-principles molecular dynamics study.

The study on high-temperature oxidation kinetics and kinetic modeling of acetylene (C2H2) has significant importance for its engineering applications. In this paper, the first-principles molecular dynamics method is used to simulate the C2H2 oxidation under high temperatures for the first time. Our results show that there are 38 intermediates and 225 elementary reactions in the process of C2H2 oxidation. The formation mechanisms of "prompt" CO2, as well as gas pollutants CHOCHO and HCOOH are revealed in depth. Four intermediates, CHCHO, CHOCO, CHOCHO and HCOOH, which have significant controversy in current kinetic models, are verified. And a new intermediate, CHOCO2, is discovered. Meanwhile, our simulation also shows that radicals, such as HO2, OH, O, etc. play a key role in promoting the oxidation of intermediates in the early stage of C2H2 oxidation. Combined with quantum chemical calculations, a detailed chemical kinetic model of C2H2/air (FP-C2H2) is built and verified by simulating ignition delay time, species concentration in the flow reactor and premixed laminar flame speed. Our studies provide novel insight for understanding the complex chemical reaction kinetics, and environmental and human health threats from air pollutant formation during C2H2 combustion.

BRCC36 Deubiquitinates HMGCR to Regulate the Interplay Between Ferroptosis and Pyroptosis.

Various forms of programmed cell death (PCD) exhibit distinct characteristics depending on their specific molecular mechanisms, and there are interactions among these different forms. Ferroptosis, which is related to autophagy and apoptosis, has an unknown potential interaction with pyroptosis. This study revealed a mutually antagonistic relationship between ferroptosis and pyroptosis, with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) playing a key role in their interaction. It is found that HMGCR predominantly localized to mitochondria during ferroptosis but shifted to the endoplasmic reticulum following treatment with a pyroptosis inducer. Furthermore, this study demonstrated that BRCC36 (BRCA1/BRCA2-containing complex subunit 36) deubiquitinated HMGCR in a manner dependent on deubiquitinating enzyme (DUB) activity, and inhibited ferroptosis and promoted pyroptosis. Moreover, as an oncogene in hepatocellular carcinoma (HCC), BRCC36 promoted cancer cell proliferation, migration, invasion, and tumor growth. Thiolutin, an inhibitor of BRCC36, effectively suppressed the interaction between BRCC36 and HMGCR, leading to the inhibition of HCC growth. Therefore, targeting BRCC36 can offer a novel and promising therapeutic strategy for HCC treatment. In conclusion, these findings provide new theoretical evidence for further characterizing tumor heterogeneity and offer new molecular targets for the diagnosis and treatment of HCC.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.

Synthesis mechanism of four metallic Cyclo-N5- energetic materials: A theoretical Perspective.

In the past five years, over 20 types of cyclo-N5- energetic materials (EMs) have been successfully synthesized. Metallic cyclo-N5- EMs exhibit higher density and performance compared to non-metallic cyclo-N5- EMs. However, the mechanisms for such metallic cyclo-N5- EMs remain unexplored. Herein, we performed a thorough quantum chemistry study on the mechanistic pathway for the cyclo-N5- trapped by metal cations in four cyclo-N5- EMs: [Na(H2O) (N5)] · 2H2O, [M(H2O)4(N5)2] · 4H2O (M = Mn, Fe, and Co), by density functional theory methods and transition state theory. During the synthesis process, the cyclo-N5- in the precursor hybrid aromatic compound is susceptible to electrophilic attack by metal cations. This attack disrupts the hydrogen bond interaction surrounding the cyclo-N5-, ultimately leading to the formation of either an ionic bond or a coordination bond between the metal cation and the cyclo-N5-, resulting in an electrophilic substitution reaction. In addition, solvent effects reduce the energy of the ionic bond, thereby promoting the reaction. Our findings will provide valuable insights for future route design and contribute to enhancing the synthesis yield of cyclo-N5- EMs in both theoretical and experimental aspects.

"In situ bone flap" combined with vascular pedicled mucous flap to reconstruction of skull base defect.

BACKGROUND: At present, neuroendoscopy technology has made rapid development, and great progress has been made in the operation of lesions in the saddle area of the skull base. However, the complications of cerebrospinal fluid and intracranial infection after the operation are still important and life-threatening complications, which may lead to poor prognosis. AIM: To investigate the method of in situ bone flap combined with nasal septum mucosal flap for reconstruction of enlarged skull base defect by endonasal sphenoidal approach and to discuss its application effect. METHODS: Clinical data of 24 patients undergoing transnasal sphenoidal endoscopic approach in the Department of Neurosurgery, Affiliated 2 Hospital of Nantong University from January 2019 to December 2022 were retrospectively analyzed. All patients underwent multi-layer reconstruction of skull base using in situ bone flap combined with nasal septum mucosa flap. The incidence of intraoperative and postoperative cerebrospinal fluid leakage and intracranial infection were analyzed, and the application effect and technical key points of in situ bone flap combined with nasal septum mucosa flap for skull base bone reconstruction were analyzed. RESULTS: There were 5 cases of high flow cerebrospinal fluid (CSF) leakage and 7 cases of low flow CSF leakage. Postoperative cerebrospinal fluid leakage occurred in 2 patients (8.3%) and intracranial infection in 2 patients (8.3%), which were cured after strict bed rest, continuous drainage of lumbar cistern combined with antibiotic treatment, and no secondary surgical repair was required. The patients were followed up for 8 to 36 months after the operation, and no delayed cerebrospinal fluid leakage or intracranial infection occurred during the follow-up. Computed tomography reconstruction of skull base showed satisfactory reconstruction after surgery. CONCLUSION: The use of in situ bone flap combined with vascular pedicled mucous flap to reconstruction of skull base defect after endonasal sphenoidal approach under neuroendoscopy has a lower incidence of cerebrospinal fluid leakage and lower complications, which has certain advantages and is worthy of clinical promotion.

Positioning and design by computed tomography imaging in neuroendoscopic surgery of patients with chronic subdural hematoma.

BACKGROUND: Neuroendoscopy is a very useful technique to Chronic Subdural Hematoma (CSH). But how to achieve the goal of treatment more minimally invasive? AIM: To develop a simple, fast and accurate preoperative planning method in our way for endoscopic surgery of patients with CSH. METHODS: From June 2018 to May 2020, forty-two patients with CSH, admitted to our hospital, were performed endoscopic minimally invasive surgery; computed tomography (CT) imaging was employed to locate the intracerebral hematoma and select the appropriate endoscopic approach before the endoscopic surgery. The clinical data and treatment efficacy were analyzed. RESULTS: According to the learning of CT scanning images, the surgeon can accurately design the best minimally invasive neuroendoscopic surgical approach and realize the precise positioning and design of the drilling site of the skull and the size of the bone window, so as to provide the most effective operation space with the smallest bone window. In this group, the average operation time was only about 1 h, and the clearance rate of hematoma was about 95%. CONCLUSION: Patients with CSH can achieve good therapeutic effect by using our way to positioning and design to assist the operation of CSH according to CT scan and image, and our way is very useful and necessary.

The effect of scrotal versus inguinal orchiopexy on the testicular function of children with clinically palpable, inguinal undescended testis: a randomized controlled trial.

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism, a randomized controlled trial was conducted involving boys who were 6-12 months old at surgery and were diagnosed with clinically palpable, inguinal undescended testis. Between June 2021 and December 2021, these boys at Fujian Maternity and Child Health Hospital (Fuzhou, China) and Fujian Children's Hospital (Fuzhou, China) were enrolled. Block randomization with a 1:1 allocation ratio was employed. The primary outcome was testicular function assessed by testicular volume, serum testosterone, anti-Müllerian hormone (AMH), and inhibin B (InhB) levels. Secondary outcomes included operative time, amount of intraoperative bleeding, and postoperative complications. Among 577 screened patients, 100 (17.3%) were considered eligible and enrolled in the study. Of the 100 children who completed the 1-year follow-up, 50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy. The testicular volume, serum testosterone, AMH, and InhB levels in both groups increased markedly after surgery (all P < 0.05), but there were no apparent differences between groups at 6 months and 12 months after operation (all P > 0.05). No differences between the scrotal and inguinal groups were noted regarding the operative time ( P = 0.987) and amount of intraoperative bleeding ( P = 0.746). The overall complication rate (2.0%) of the scrotal group was slightly lower than that of the inguinal group (8.0%), although this difference was not statistically significant ( P > 0.05). Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism, with similar operative status and postoperative complications. Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.

Braided Fiber Current Collectors for High-Energy-Density Fiber Lithium-Ion Batteries.

Fiber lithium-ion batteries represent a promising power strategy for the rising wearable electronics. However, most fiber current collectors are solid with vastly increased weights of inactive materials and sluggish charge transport, thus resulting in low energy densities which have hindered the development of fiber lithium-ion batteries in the past decade. Here, a braided fiber current collector with multiple channels was prepared by multi-axial winding method to not only increase the mass fraction of active materials, but also to promote ion transport along fiber electrodes. In comparison to typical solid copper wires, the braided fiber current collector hosted 139 % graphite with only 1/3 mass. The fiber graphite anode with braided current collector delivered high specific capacity of 170 mAh g-1 based on the overall electrode weight, which was 2 times higher than that of its counterpart solid copper wire. The resulting fiber battery showed high energy density of 62 Wh kg-1 .

GPR162 activates STING dependent DNA damage pathway as a novel tumor suppressor and radiation sensitizer.

In the treatment of most malignancies, radiotherapy plays a significant role. However, the resistance of cancer cells to ionizing radiation (IR) is the main reason for the failure of radiotherapy, which causes tumor recurrence and metastasis. In this study, we confirmed that GPR162, an orphan receptor in the G-protein-coupled receptor family, acted as a novel radiotherapy sensitizer by interacting with the stimulator of interferon genes (STING), which targeted DNA damage responses, activated IRF3, accelerated the activation of type I interferon system, promoted the expression of chemokines including CXCL10 and CXCL4, and inhibited the occurrence and development of tumors. Interestingly, the activation of STING by overexpression of GPR162 was independent of the classical pathway of cGAS. STING inhibitors could resist the antitumor effect of overexpression of GPR162 in IR-induced mouse models. In addition, most solid tumors showed low expression of GPR162. And the higher expression of GPR162 indicated a better prognosis in patients with lung adenocarcinoma, liver cancer, breast cancer, etc. In summary, these results suggested that GPR162 may serve as a potential sensitizer of radiotherapy by promoting radiotherapy-induced STING-IFN production and increasing the expression of chemokines including CXCL10 and CXCL4 in DNA damage response, providing an alternative strategy for improving cancer radiotherapy.

Morroniside ameliorates glucocorticoid-induced osteoporosis and promotes osteoblastogenesis by interacting with sodium-glucose cotransporter 2.

CONTEXT: Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown. OBJECTIVE: We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms. MATERIALS AND METHODS: The effects of MOR (10-100 µM) on the proliferation and differentiation of MC3T3-E1 cells were studied in vitro. The glucocorticoid-induced zebrafish OP model was treated with 10, 20 and 40 µM MOR for five days to evaluate its effects on vertebral bone density and related osteogenic markers. In addition, molecular targets prediction and molecular docking analysis were carried out to explore the binding interactions of MOR with the target proteins. RESULTS: In cultured MC3T3-E1 cells, 20 µM MOR significantly increased cell viability (1.64 ± 0.12 vs. 0.95 ± 0.16; p < 0.01) and cell differentiation (1.57 ± 0.01 vs. 1.00 ± 0.04; p < 0.01) compared to the control group. MOR treatment significantly ameliorated vertebral bone loss in the glucocorticoid-induced OP zebrafish model (0.86 ± 0.02 vs. 0.40 ± 0.03; p < 0.01) and restored the expression of osteoblast-specific markers, including ALP, Runx2 and Col-І. Ligand-based target prediction and molecular docking revealed the binding interaction between MOR and the glucose pockets in sodium-glucose cotransporter 2 (SGLT2). DISCUSSION AND CONCLUSIONS: These findings demonstrated that MOR treatment promoted osteoblastogenesis and ameliorated glucocorticoid-induced OP by targeting SGLT2, which may provide therapeutic potential in managing glucocorticoid-induced OP.

HOXC11 drives lung adenocarcinoma progression through transcriptional regulation of SPHK1.

Lung adenocarcinoma (LUAD) is a fatal threat to human health, while the mechanism remains unclear, and the therapy brings limited therapeutic effects. Transcription factor Homeobox C11 (HOXC11) was previously proved to be related to hind limbs and metanephric development during the embryonic phase, and its role in tumors has been gradually recognized. Our study found that HOXC11 overexpressed in LUAD and was associated with worse overall survival. Moreover, its expression in lung cancer was regulated by IκB kinase α (IKKα), a pivotal kinase in NF-κB signaling, which was related to the ubiquitination of HOXC11. We further proved that HOXC11 could enhance the ability of proliferation, migration, invasion, colony formation, and the progression of the cell cycle in LUAD cells. Meanwhile, it also accelerated the formation of subcutaneous and lung metastases tumors. In contrast, loss of HOXC11 in LUAD cells significantly inhibited these malignant phenotypes. At the same time, HOXC11 regulated the expression of sphingosine kinase 1 (SPHK1) by directly binding to its promoter region. Therefore, we conclude that HOXC11 impacts the development of LUAD and facilitates lung cancer progression by promoting the expression of SPHK1.

circNFXL1 Modulates the Kv2.1 Channel Function in Hypoxic Human Pulmonary Artery Smooth Muscle Cells via Sponging miR-29b-2-5p as a Competitive Endogenous RNA.

ABSTRACT: Pulmonary arterial hypertension is characterized by abnormal pulmonary vasoconstriction and vascular remodeling caused by the dysregulation of K + channels in PA smooth muscle cells (PASMCs). However, how the K + channels are dysregulated is still unclear. Circular RNAs (circRNAs) are noncoding RNAs with a closed-loop structure capable of sponging microRNAs (miRs), thus regulating gene expression at the post-transcriptional level. Our previous studies have demonstrated the importance of one novel circRNA (hsa_circNFXL1_009, circNFXL1) in pulmonary arterial hypertension patients, playing as a critical regulator for K + channel activation in hypoxic human PASMCs (hPASMCs). Here, we explore the mechanisms underlying circNFXL1-regulated K + channel expression and functions in hypoxic hPASMCs. In cultured hPASMCs, the reduction of Kv current induced by hypoxia was significantly recovered by delivering exogenous circNFXL1. Moreover, luciferase, quantitative reverse transcription-quantitative polymerase chain reaction, western blot, and mutagenesis studies confirmed that circNFXL1 reversed hypoxia-induced inhibitory effects on the Kv2.1 channel via sponging hsa-miR-29b-2-5p (miR-29b-2). Furthermore, we found that circNFXL1 reversed the miR-29b-induced Kv2.1 channel dysfunction at the whole-cell and single-channel level in HEK cells using a patch-clamp. Finally, calcium imaging revealed that hypoxia also triggered a substantial rise in the cytosolic calcium concentration ([Ca2 + ]cyt) in hPASMCs, and this hypoxia-induced elevation of [Ca2 + ]cyt was reduced by circNFXL1 through miR-29b-2. These data suggested that circNFXL1-mediated regulation of the Kv2.1 channel activation and the related intracellular calcium concentration may contribute to the effects of hypoxic pulmonary vasoconstriction.

Adverse events after different forms of botulinum neurotoxin A injections in children with cerebral palsy: An 8-year retrospective study.

AIM: To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations. METHOD: A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database. RESULTS: The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}] = 3.65 [1.56, 5.40], p < 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI] = 2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p < 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p > 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r = 0.36 and r = 0.27 respectively, p < 0.01). INTERPRETATION: Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors. WHAT THIS PAPER ADDS: The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.

RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-κB Pathway.

In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.