The influence of erosion on the dynamic process of landslide in Xinmo Village, Maoxian.

A large-scale, high-speed, long-runout landslide occurred in Xinmo Village, Maoxian, Sichuan Province, China, on June 24, 2017. It was characterized by fast sliding speed, rapid volume growth, and large impact area. The dynamic process of such landslides and the influence of erosion on the dynamic process are studied by field investigation, numerical inversion and simulation. The results showed that entrainment erosion was a major factor of landslide volumetric change and a salient feature of the landslide process. An exponential equation relating the erosion rate and the deposition volume was established. Moreover, the study found that a slight change of the erosion rate (1e-4) also had a significant impact on the lateral spreading, longitudinal runout, and vertical erosion. As the erosion rate increased, the lateral spreading, longitudinal runout, and vertical erosion of this type of landslide became more obvious. By using the coefficient of variation method, it was obtained that the erosion rate had a greater influence on the vertical erosion than on the lateral spreading and longitudinal runout. In the study of the velocity of the rock avalanche under different erosion conditions, it was found that the erosion amount and the landslide velocity were not strictly linearly related. This study has important significance for understanding the dynamic process and erosion effect of rock avalanche, and provides useful references and insights for future research in related fields.

mhealth-based interventions to improving liver cancer screening among high-risk populations: a study protocol for a randomized controlled trial.

BACKGROUND: Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people's main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg's Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. METHODS: We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. DISCUSSION: The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

ß-hydroxybutyrate and ischemic stroke: roles and mechanisms.

Stroke is a significant global burden, causing extensive morbidity and mortality. In metabolic states where glucose is limited, ketone bodies, predominantly ß-hydroxybutyrate (BHB), act as alternative fuel sources. Elevated levels of BHB have been found in the ischemic hemispheres of animal models of stroke, supporting its role in the pathophysiology of cerebral ischemia. Clinically, higher serum and urinary BHB concentrations have been associated with adverse outcomes in ischemic stroke, highlighting its potential utility as a prognostic biomarker. In both animal and cellular models, exogenous BHB administration has exhibited neuroprotective effects, reduction of infarct size, and improvement of neurological outcomes. In this review, we focus on the role of BHB before and after ischemic stroke, with an emphasis on the therapeutic potential and mechanisms of ketone administration after ischemic stroke.

Semaglutide mitigates testicular damage in diabetes by inhibiting ferroptosis.

Diabetes is linked to male infertility, but the mechanisms and therapeutic options remain unclear. This study investigates the effects of semaglutide on testicular function in a diabetes mouse model. Clinical data shows that diabetes affects blood glucose, lipid levels, and sperm quality. Single-cell and transcriptome analyses reveal changes in testicular tissue cell proportions and activation of ferroptosis pathways in diabetic patients/rats. In the diabetes mouse model, sperm quality decreases significantly. Treatment with semaglutide (Sem) and the ferroptosis inhibitor ferrostatin-1 (Fer-1) alleviates testicular damage, as evidenced by improved lipid peroxidation and ferroptosis markers. Moreover, the diabetes-induced decrease in the TM-3 cell line's vitality, increased lipid peroxidation, ROS, ferrous ions, and mitochondrial membrane potential damage are all improved by semaglutide and ferrostatin-1 intervention. Overall, these findings highlight semaglutide's potential as a therapeutic approach for mitigating diabetes-induced testicular damage through modulation of the ferroptosis pathway.

Factors affecting the compliance of hepatocellular carcinoma screening among high-risk populations: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.

Influence of soil composition and environmental factors on the adsorption of per- and polyfluoroalkyl substances: A review.

Per- and polyfluoroalkyl substances (PFASs) have garnered considerable scientific and regulatory scrutiny due to their widespread distribution across environments and their potential toxicological impacts on human health. The pedosphere serves as a vital reservoir for these chemicals, significantly determining their environmental trajectory and chemical transformations. This study offers a comprehensive synthesis of the current understanding regarding the adsorption mechanics of PFASs in soil matrices. Due to their unique molecular structure, PFASs predominantly engage in hydrophobic and electrostatic interactions during soil adsorption. This work thoroughly evaluates the influence of various factors on adsorption efficiency, including soil properties, molecular characteristics of PFASs, and the prevailing environmental conditions. The complex nature of soil environments complicates isolating individual impacts on PFAS behavior, necessitating an integrated approach to understanding their environmental destinies better. Through this exploration, we seek to clarify the complex interplay of factors that modulate the adsorption of PFASs in soils, highlighting the urgent need for future research to disentangle the intricate and combined effects that control the environmental behavior of PFAS compounds.

Interventions to Improve Endoscopic Screening Adherence of Cancer in High-Risk Populations: A Scoping Review.

Background: Colorectal, and gastric cancers have the second, and fourth mortality rates worldwide, respectively. Endoscopic screening is a crucial diagnostic tool for colorectal, and gastric cancers. Effective interventions can improve adherence to endoscopic screening in high-risk populations, which is important for cancer prevention and mortality reduction. This study aimed to identify interventions that could improve adherence to endoscopic screening for cancer in high-risk populations. Methods: Combination keywords including colorectal cancer, gastric cancer, screening adherence, and interventions were used to search for articles in PubMed, Web of Science, Cochrane Library, and MEDLINE Complete. The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR). Results: A total of 12 articles were included in this review: 9 randomized controlled trials(RCT) and 3 quasi-experimental studies(QEDs). Among the extracted studies, 11 were about colorectal cancer, and 1 was about gastric cancer. Most studies used lecture-based or Information Technology-based health education interventions. Narrative interventions have proven to be novel and effective approaches for promoting adherence to endoscopic screening. Health education interventions included cancer epidemiology, cancer risk factors, warning symptoms, and screening methods. Conclusion: All interventions involved were effective in increasing individual knowledge of cancer-related endoscopic screening, willingness to undergo screening, and screening behaviors. These findings provide a reference for designing endoscopy-related cancer screening interventions.

FeNi (oxy)hydroxides embedded with high-valence Mo atoms: A efficient and robust water oxidation electrocatalyst.

The incorporation of high-valence transition metal atoms into FeNi (oxy)hydroxides may be a promising strategy to regulate the intrinsic electronic states, thereby reducing the thermodynamic barrier and accelerating oxygen evolution reaction (OER). Here, a high-valence Mo atoms doping route is proposed by an efficient self-reconstruction strategy to prepare MoFeNi (oxy)hydroxides for efficient alkaline OER. By using borides (MoNiB) as sacrificial template and Mo source, FeNi (oxy)hydroxides nanoflakes embedded with high-valence Mo atoms (MoFeNi) is successfully synthesized, which can modulate the electron coordination to improve the intrinsic catalytic activity. Remarkably, the obtained MoFeNi exhibits extremely low overpotential (η100 = 252 mV and η500 = 288 mV) and small Tafel slope (18.35 mV dec-1). The robust catalyst can run stably for hours at 500 mA cm-2. Characterization results and theoretical calculations confirmed that the addition of high-valence Mo effectively modulated the intrinsic electronic structure of metal sites and optimized the adsorption/desorption energy of the intermediates, accelerating OER reactions kinetics. By coupling MoFeNi anode with Pt/C cathode, anion exchange membrane (AEM) electrolyser can operate stably at 500 mA cm-2 with about less than 2.2 V. This research introduces a novel approach to develop ideal electrocatalysts through the incorporation of high-valence molybdenum species.

Comparative assessment of orthodontic clear aligner versus fixed appliance for anterior retraction: a finite element study.

BACKGROUND: The aim of this study is to conduct a comparative evaluation of different designs of clear aligners and examine the disparities between clear aligners and fixed appliances. METHODS: 3D digital models were created, consisting of a maxillary dentition without first premolars, maxilla, periodontal ligaments, attachments, micro-implant, 3D printed lingual retractor, brackets, archwire and clear aligner. The study involved the creation of five design models for clear aligner maxillary anterior internal retraction and one design model for fixed appliance maxillary anterior internal retraction, which were subsequently subjected to finite element analysis. These design models included: (1) Model C0 Control, (2) Model C1 Posterior Micro-implant, (3) Model C2 Anterior Micro-implant, (4) Model C3 Palatal Plate, (5) Model C4 Lingual Retractor, and (6) Model F0 Fixed Appliance. RESULTS: In the clear aligner models, a consistent pattern of tooth movement was observed. Notably, among all tested models, the modified clear aligner Model C3 exhibited the smallest differences in sagittal displacement of the crown-root of the central incisor, vertical displacement of the central incisor, sagittal displacement of the second premolar and second molar, as well as vertical displacement of posterior teeth. However, distinct variations in tooth movement trends were observed between the clear aligner models and the fixed appliance model. Furthermore, compared to the fixed appliance model, significant increases in tooth displacement were achieved with the use of clear aligner models. CONCLUSIONS: In the clear aligner models, the movement trend of the teeth remained consistent, but there were variations in the amount of tooth displacement. Overall, the Model C3 exhibited better torque control and provided greater protection for posterior anchorage teeth compared to the other four clear aligner models. On the other hand, the fixed appliance model provides superior anterior torque control and better protection of the posterior anchorage teeth compared to clear aligner models. The clear aligner approach and the fixed appliance approach still exhibit a disparity; nevertheless, this study offers a developmental direction and establishes a theoretical foundation for future non-invasive, aesthetically pleasing, comfortable, and efficient modalities of clear aligner treatment.

Resuscitation effect of sodium bicarbonate Ringer's solution on traumatic hemorrhagic shock in patients / 中国基层医药

Objective:To investigate the resuscitation effect of sodium bicarbonate Ringer's solution on traumatic hemorrhagic shock in patients.Methods:A randomized controlled trial was conducted on 70 patients with traumatic hemorrhagic shock who were admitted to Yiwu Central Hospital between February 2021 and February 2022. The patients were randomly assigned to a control group ( n = 35) and an observation group ( n = 35) using the random number table method. Both groups received routine treatment. The control group was given adequate resuscitation by intravenous injection of a compound sodium chloride injection, while the observation group received restricted resuscitation with sodium bicarbonate Ringer's solution. Related clinical indicators, coagulation function, lactate levels, hemorheological indicators, and incidence of complications were compared between the two groups. Results:The blood oxygen saturation, shock index, pulse pressure difference, and urine output in the observation group were (76.53 ± 2.56)%, (0.43 ± 0.07), (38.56 ± 6.52) mmHg (1 mmHg = 0.133 kPa), and (35.62 ± 4.21) mL/h, respectively. These values were all superior to those in the control group [(65.32 ± 3.21)%, (1.21 ± 0.13), (23.56 ± 4.23) mmHg, (23.65 ± 5.68) mL/h, t = 16.15, 31.25, 11.42, 10.06, all P < 0.001]. The prothrombin time, fibrinogen, activated partial thromboplastin time, and thrombin time in the observation group were (17.65 ± 0.83) seconds, (1.69 ± 0.89) g/L, (39.68 ± 0.52) seconds, and (17.86 ± 0.74) seconds, respectively. These values were significantly superior to those in the control group [(14.56 ± 0.86) seconds, (1.32 ± 0.23) g/L, (35.26 ± 0.16) seconds, and (16.02 ± 0.05) seconds, t = 15.30, 2.38, 48.06, 14.68, all P < 0.05]. The lactate level in the observation group was significantly lower than that in the control group [(2.24 ± 0.53) mmol/L vs. (2.94 ± 0.78) mmol/L, t = 4.39, P < 0.05]. The platelet cohesion, red blood cell deformability, and blood viscosity in each group were significantly reduced, and these indices in the observation group were superior to those in the control group ( t = 13.71, 5.64, 5.67, all P < 0.001). The incidence of complications in the observation group was significantly lower than that in the control group (8.6% (3/35) vs. 60.0% (21/35), χ2 = 10.08, P < 0.05). Conclusion:Restricted resuscitation with sodium bicarbonate Ringer's solution can improve clinical indicators, coagulation function, and lactate levels in patients with traumatic hemorrhagic shock. It can effectively improve hemodynamic indicators and reduce the incidence of complications. It is worthy of clinical promotion.

Multicenter phase I dose escalation and expansion study of pyrotinib in combination with camrelizumab and chemotherapy as first-line treatment for HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma.

Background: Pembrolizumab plus trastuzumab and chemotherapy showed remarkable efficacy as first-line therapy for advanced HER2-positive gastric cancer. Pyrotinib is an irreversible pan-HER inhibitor. This single-arm, open-label phase 1 dose-escalation (1a) and expansion (1b) study investigated camrelizumab, an anti-PD-1 antibody, plus pyrotinib and chemotherapy as first-line treatment for advanced HER2-positive gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. Methods: Between June 2020 and June 2022, 41 patients with previously untreated HER2-positive locally advanced unresectable or metastatic G/GEJ adenocarcinoma were enrolled. In phase 1a, patients underwent a 3 + 3 escalating dose design, receiving oral pyrotinib (240 mg, 320 mg, or 400 mg daily), intravenous camrelizumab (200 mg), and CapeOX (oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily for two weeks) every 3 weeks until progression, intolerable toxicity or consent withdrawal. The recommended phase 2 dose (RP2D) of pyrotinib was determined and used in the phase 1b. The primary endpoints were the safety, maximum tolerated dose (MTD), RP2D, and confirmed objective response rate (ORR). This trial was registered with chictr.org, number ChiCTR2000029717. Findings: Among 41 patients, 10 were in phase 1a (3 at 240 mg, 3 at 400 mg, and 4 at 320 mg due to one patient withdrawing consent), and 31 were in phase 1b. In phase 1a, the MTD of pyrotinib was 320 mg daily due to dose-limiting toxicities (diarrhea [n = 3] and vomiting [n = 1]) observed at 400 mg. Based on all available data, the RP2D of pyrotinib was set at 320 mg. Among 41 patients, 20 patients (48.8%) developed grade ≥3 treatment-emergent adverse events (TEAEs), and four patients (9.8%) had any grade serious adverse events. No deaths occurred due to TEAEs. Among 27 patients who received the RP2D of pyrotinib and had a post-baseline tumor assessment, two patients (7.4%) achieved a confirmed complete response, and 19 patients (70.4%) achieved a confirmed partial response, resulting in a confirmed ORR of 77.8% (95% CI: 57.7-91.4). Interpretation: Pyrotinib plus camrelizumab and chemotherapy showed promising efficacy in the first-line treatment of advanced HER2-positive G/GEJ cancer. The safety profile was consistent with known toxicities of the agents, and no new or unexpected safety signals were identified. Funding: This study was funded by the Beijing Xisike Clinical Oncology Research Foundation (Y-HR2019-0377).

Complete lumbarization with calcified disc herniations at L5S1 and S1-2 levels treated with percutaneous endoscopic interlaminar discectomy: a case report and technique note.

Objective: This study aims to report a case of a patient with complete lumbarization (Castellvi-IB) who developed symptomatic calcified disc herniations at L5S1 and lumbarized S1-2 levels and achieved excellent neurological recovery following percutaneous endoscopic interlaminar discectomy (PEID). Summary of Background Data: In 1984, Castellvi et al. classified lumbosacral transitional vertebra (LSTV) into four types. They incorrectly classified I LSTV anomalies as only type I sacralization, not realizing type I lumbarization also belonged to type I LSTV, with the latter exhibiting a well-developed S1-2 disc (lumbosacral transitional disc, LSTD). Patients with type I lumbarization rarely develop calcified disc herniations concomitantly at L5S1 and LSTD levels. PEID has been developed to perform discectomy for neurological decompression at the lumbar region, especially at the lowest level where the higher iliac crest and/or widened transverse process exists. Methods: A 47-year-old male presented to our hospital complaining of an intractable left leg radiating pain for 3 weeks after suffering from chronic radiating pain for 4 years. His physical examination found hyperalgesia at the lateral side of the left calf, decreased dorsal flexion strength of the ankle (grade 4/5), and a positive sign of straight leg raising test at the left side (30°). The preoperational Lumbar JOA (Japanese Orthopaedic Association) score was 12. Image examinations including whole spinal radiograph, MRI, and CT confirmed complete lumbarization (Castellvi-IB) with calcified disc herniations at L5S1 and LSTD levels at the left side. PEID was carried out at two index levels to accomplish decompression via the left approach. Results: The patient's neurological function recovered quickly. One day postoperatively, he began to walk without discomfort. After 3 months, his muscle strength recovered to normal, and after 6 months, the residual dysesthesia at his posterolateral calf disappeared. The follow-up Lumbar JOA score was 26. Conclusion: Calcified lumbar disc herniation could develop at two distal levels concomitantly in the case of type I complete lumbarization. This anomaly might be misinterpreted as a normal lumbar sequence by only lumbar MRI. PEID may be an effective procedure to treat such calcified disc herniations in a single visit.

An Amphiphilic Star-Shaped Polymer (Star-PEG-PCL2) used as a Stationary Phase for GC.

A star-shaped polymer (Star-PEG-PCL2) was synthesized with PCL and PEG and used as a stationary phase for gas chromatography. The statically coated Star-PEG-PCL2 column exhibited an efficiency of 2260 plates/m determined by naphthalene at 120 °C and moderate polarity. The Star-PEG-PCL2 column showed high resolution performance for isomers of a wide ranging polarity, including methylnaphthalenes, halogenated benzenes, nitrobenzene, phenols, and anilines, and displayed dual-nature selectivity for a mixture of 17 analytes. Also, the Star-PEG-PCL2 column exhibited good separation performance and column inertness for Grob test mixture and a series of cis-/trans-isomers. In addition, it exhibited advantageous separation performance over the commercial HP-35 and PEG-20M columns for chloroaniline and bromoaniline isomers through its unique three-dimensional framework. In conclusion, it has good potential as a new stationary phase for separating a variety of analytes because of its special structure and excellent separation performance.

Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway.

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the "MYC_TARGETS_V2" gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the "MYC_TARGETS_V2" gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

A Two-Center, Prospective, Randomized Controlled Trial to Evaluate the Efficacy and Safety of and Satisfaction with Different Methods of ART FILLER® UNIVERSAL Injection for Correcting Moderate to Severe Nasolabial Folds in Chinese Individuals.

BACKGROUND: Hyaluronic acid is the most popular dermal filler in the treatment of nasolabial folds. Injection methods vary among physicians. METHODS: A randomized, two-center, double-blind, intraindividual trial was designed to compare a new method of injecting ART FILLER® UNIVERSAL using the retaining ligament with the traditional method (linear threading and bolus injection) in moderate to severe nasolabial folds. Forty patients with moderate to severe nasolabial folds were randomized into groups A and B. Group A received injections via the traditional method on the left side and the ligament method on the right side, while group B received the reverse. Clinical efficacy and patient safety were independently assessed by a blinded evaluator, the injector, using the Wrinkle Severity Rating Scale (WSRS), the Global Aesthetic Improvement Scale (GAIS), and the Medicis Midface Volume Scale (MMVS) at 4 weeks (before and after the touch-up injection), 8 weeks, 12 weeks, and 24 weeks after the baseline injection. RESULTS: From the perspective of the blinded evaluator, the improvements in WSRS scores from baseline did not differ significantly between the ligament method (0.73 ± 0.61) and the traditional method (0.89 ± 0.61) at week 24 (p > 0.05). The mean GAIS score at week 24 was 1.41 ± 0.49 for the traditional method and 1.32 ± 0.47 for the ligament method (p > 0.05). CONCLUSIONS: The efficacy and safety of the ligament method for the management of nasolabial folds are comparable to those of the traditional method in terms of WSRS and GAIS score improvement in the long run. The ligament method is superior to the traditional method in that it improves midface deficits with fewer adverse events. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . CLINICAL TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry under the registration number ChiCTR2100041702.

Roles of the Notch signaling pathway and microglia in autism.

The Notch signaling pathway is mainly involved in the regulation of neural stem cell proliferation, survival and differentiation during the development of the central nervous system. As a neurodevelopmental disorder, autism is associated with an abnormal increase in the number of microglia in several brain regions. These findings suggest that the pathogenesis of autism may be related to the Notch signaling pathway and microglia. In this review, we discuss how Notch pathway activity leads to behavioral abnormalities such as learning and memory impairment by influencing neuronal biological activities. An increase in microglial protein synthesis and abnormal autophagy can affect synaptic development and lead to behavioral abnormalities, and all of these changes can lead to autism. Furthermore, the Notch signaling pathway regulates the activation and differentiation of microglia and promotes inflammatory responses, leading to the occurrence of autism. When excessive reactive oxygen species (ROS) secreted by microglia cannot be cleared by autophagy in a timely manner, Notch signaling pathway activity is affected, possibly further increasing susceptibility to autism. This review reveals the mechanism underlying the role of the Notch signaling pathway, microglia and their interaction in the pathogenesis of autism and provides a theoretical reference for targeted clinical therapies for autism.

Efficacy and safety evaluation of a novel domestic extracorporeal membrane oxygenation mainframe / 中华急诊医学杂志

Objective:To evaluate the safety and efficacy of a novel domestic extracorporeal membrane oxygenation (ECMO) mainframe in a porcine model, and to provide the basis for further clinical application.Methods:Five domestic healthy male white pigs, weighing (51±4) kg, were selected. The ECMO system was established by using a novel ECMO mainframe with imported membrane oxygenator and pipeline, and continued to run for 72 hours. ECMO parameters are as follows: veno-arterial ECMO, centrifugal pump speed 3 000-3 500 r/min, continuous infusion of heparin anticoagulation to maintain the activate clotting time (ACT) of 140-200 s. Real-time monitoring of speed, flow, pressure before pump, pressure after pump, pressure after membrane and other equipment parameters, and the equipment performance was scored. The changes of hemodynamics, blood lactic acid and blood routine were monitored dynamically. Repeated measures analysis of variance was used to compare different time points within the group. At the end of the experiment, the thrombosis in the pump head and oxygenator was observed. The animals were sacrificed to obtain the tissue samples of the main organs for gross observation and pathological injury evaluation.Results:All animals successfully ran the ECMO system for 72 hours. (1) The centrifugal pump speed should be maintained at 3 029-3 483 r/min, the flow rate was maintained at 2.24-2.60 L/min, The pressure before the pump between minus 107.57 and minus 31.86 mmHg, the pressure after the pump was 197.50-282.43 mmHg, and the pressure after the membrane was 178.71-261.5 mmHg, all were in the normal range, and there was no significant difference between different time points (all P>0.05). The performance scores of the mainframe were all 4 points or above, indicating that the use requirements were met. (2) The heart rate of the animals was 50-80 beats /min, the mean arterial pressure was 85-115 mmHg, and the lactic acid was 0.996-2.25 mmol/L, all within the normal range, and there was no significant difference between different time points (all P>0.05). The free hemoglobin was 8.98-16.39 mg/L, and the hemoglobin was 6.58-7.52 g/L, both within a reasonable range, and there was no significant difference between different time points (all P>0.05). The platelet count was 69.6-231.6×10 9/L, and showed a continuous downward trend ( P<0.05). ACT was maintained at 135-169 s, which was within the target range, and there was no significant difference between different time points ( P<0.05). (3) At the end of the experiment, there was no obvious thrombosis in the pump head and oxygenator, no obvious thrombosis or infarction in the heart, brain, liver, lung and kidney, and no obvious hemorrhage or necrosis under the microscope. Conclusions:The ECMO established by the novel domestic ECMO mainframe combined with imported membrane oxygenator and pipeline ran smoothly for 72 hours, achieving the target of effect and safety.

Loss of Mature Lamin A/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPKα Activation.

The roles of lamin A/C in adipocyte differentiation and skeletal muscle lipid metabolism are associated with familial partial lipodystrophy of Dunnigan (FPLD). We confirmed that LMNA knockdown (KD) in mouse adipose-derived mesenchymal stem cells (AD-MSCs) prevented adipocyte maturation. Importantly, in in vitro experiments, we discovered a significant increase in phosphorylated lamin A/C levels at serine 22 or 392 sites (pLamin A/C-S22/392) accompanying increased lipid synthesis in a liver cell line (7701 cells) and two hepatocellular carcinoma (HCC) cell lines (HepG2 and MHCC97-H cells). Moreover, HCC cells did not survive after LMNA knockout (KO) or even KD. Evidently, the functions of lamin A/C differ between the liver and adipose tissue. To date, the mechanism of hepatocyte lipid metabolism mediated by nuclear lamin A/C remains unclear. Our in-depth study aimed to identify the molecular connection between lamin A/C and pLamin A/C, hepatic lipid metabolism and liver cancer. Gain- and loss-of-function experiments were performed to investigate functional changes and the related molecular pathways in 7701 cells. Adenosine 5' monophosphate-activated protein kinase α (AMPKα) was activated when abnormalities in functional lamin A/C were observed following lamin A/C depletion or farnesyltransferase inhibitor (FTI) treatment. Active AMPKα directly phosphorylated acetyl-CoA-carboxylase 1 (ACC1) and subsequently inhibited lipid synthesis but induced glycolysis in both HCC cells and normal cells. According to the mass spectrometry analysis, lamin A/C potentially regulated AMPKα activation through its chaperone proteins, ATPase or ADP/ATP transporter 2. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of the two HCC cell lines more efficiently than lonafarnib alone by inhibiting glycolysis or the maturation of prelamin A.

Potential dependence of OER/EOP performance on heteroatom-doped carbon materials by grand canonical density functional theory.

Revealing the effect of external applied potential on the reaction mechanism and product selectivity is of great significance in electrochemical studies. In this work, the grand canonical density functional theory method was applied to simulate the explicit electrocatalytic process of oxygen evolution reaction and electrochemical ozone production due to the O3 product sensitivity toward the applied potential. Over the Pt/Pd single atom embedded on B/N co-doped graphene (Pt/Pd-BNC) surface, crossover points of O2/O3 selectivity inversion were predicted to be 1.33 and 0.89 V vs standard hydrogen electrode, which were also consistent with the previous experimental results. An in-depth analysis of the energetic terms in the reaction free energies also found the considerable impact of the applied potential on the Helmholtz free energy term, with optimal potential predicted for the key elementary steps, and linear correlations between electrode potential (U) and reaction free energy were found for each elementary step. This study offers extensive knowledge on the potential effect on the O2/O3 selective formation on two-dimensional anode surfaces and provides new insights for investigating the reactivity/selectivity on electrode surfaces in real reaction conditions.