The efficacy and safety of ciprofol and propofol in patients undergoing colonoscopy: A double-blind, randomized, controlled trial.

STUDY OBJECTIVE: Propofol is a commonly utilized anesthetic for painless colonoscopy, but its usage is occasionally limited due to its potential side effects, including cardiopulmonary suppression and injection pain. To address this limitation, the novel compound ciprofol has been proposed as a possible alternative for propofol. This study sought to determine whether there are any differences in the safety and efficacy of propofol and ciprofol for painless colonoscopy. DESIGN: Randomized clinical trial. SETTING: Single-centre, class A tertiary hospital, November 2021 to November 2022. PATIENTS: Adult, American Society of Anesthesiologists Physical Status I to II and body mass index of 18 to 30 kg m-2 patients scheduled to undergo colonoscopy. INTERVENTIONS: Consecutive patients were randomly allocated in a 1:1 ratio to receive sedation for colonoscopy with ciprofol (group C) or propofol (group P). MEASUREMENTS: The primary outcome was the success rate of colonoscopy. The secondary outcomes were onset time of sedation, operation time, recovery time and discharge time, patients and endoscopists satisfaction, side effects (e.g. injection pain, myoclonus, drowsiness, dizziness, procedure recall, nausea and vomiting) and incidence rate of cardiopulmonary adverse events. MAIN RESULTS: No significant difference was found in the success rate of colonoscopy between the two groups (ciprofol 96.3% vs. propofol 97.6%; mean difference - 1.2%, 95% CI: -6.5% to 4.0%, P = 0.650). However, group C showed prolonged sedation (63.4 vs. 54.8 s, P < 0.001) and fully alert times (9 vs 8 min, P = 0.013), as well as reduced incidences of injection pain (0 vs. 40.2%, P < 0.001), respiratory depression (2.4% vs. 13.4%, P = 0.021) and hypotension (65.9% vs. 80.5%, P = 0.034). Patients satisfaction was also higher in Group C (10 vs 9, P < 0.001). CONCLUSIONS: Ciprofol can be used independently for colonoscopy. When comparing the sedation efficacy of ciprofol and propofol, a 0.4 mg kg-1 dose of ciprofol proved to be equal to a 2.0 mg kg-1 dose of propofol, with fewer side effects and greater patient satisfaction during the procedure.

Specializing Carbon Nanozyme Active Sites for Sensitive Alkaline Phosphatase Activity Metal-Free Detection.

As biological enzymes regulate metabolic processes, alkaline phosphatase (ALP) is a critical diagnostic indicator associated with many diseases. To accurately measure the enzyme activity, nanozymactic materials can offer sensitive strategies for ALP detection. However, nanozymes often lack specific target binding sites, and the presence of common co-components, e. g., metal ions, may cause false-positive or false-negative results in enzyme activity determination. Herein, we developed a colorimetric assay for ALP detection using metal-free nanozymatic carbon dots (CDs). The ALP hydrolysis of pyrophosphate ions (PPi) to phosphate ions (Pi) induces a "turn-on" response based on the nanozyme activity. This PPi-induced inhibition mechanism is extensively studied via the Michaelis-Menten model, revealing that PPi acts as a noncompetitive inhibitor for CDs at a binding site distinct from the common nanozyme active site. With superior responses to ALP substrates, a highly sensitive and selective method is established for sensing ALP activity with a linear range of 0.010-0.200 U/L and a detection limit of 0.009 U/L. This finding explores the recognition and binding behavior of nanozymes, allowing for precise and reliable measurements even in complex samples, and represents a significant breakthrough for nanozyme-based assays in biological analysis.

Intra-Sac Injection of Thrombin During Endovascular Aneurysm Repair to Remedy Type II Endoleak and Promote Sac Shrinkage.

PURPOSE: To evaluate the safety and effectiveness of intra-sac thrombin injection to remedy type II endoleaks (T2ELs) during endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: 224 cases abdominal aortic aneurysm (AAA) were treated with EVAR. For the 52 cases of intra-operative type II endoleaks and 8 cases of ruptured AAAs, after the grafts were deployed, thrombin was injected into the aneurysm sac through a preset catheter. The occurrence of endoleaks post-EVAR were followed up with by Computed Tomography (CT) angiogram. The diameter and the volume of the aneurysm sac were also measured. Endpoints included incidence of T2ELs, AAA sac shrinkage and re-intervention rate and all-cause mortality. RESULTS: The overall technical success rate was 100%. Fifty-two patients were followed up with for 9-56 (median 24) months. No serious complications were observed during follow-up. The incidence of endoleak was 5.8% (3/52) during follow-up. The maximum diameter of the aneurysm decreased from 61.1 ± 14.2 mm to 53.7 ± 10.6 mm, 47.9 ± 8.3 mm and 43.7 ± 7.2 mm (87.9%, 78.4% and 71.5% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively (P < .05). The volume of the aneurysm sac shrank from 236.2 ± 136.2 cm3 to 202.6 ± 114.1 cm3, 155.6 ± 68.4 cm3 and 129.7 ± 52.4 cm3 (85.8%, 65.9%, and 54.9% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively (P < .05). The rate of various endoleaks was 5.8% (3/52) and the re-intervention rate was 1.9% (1/52) in this research. CONCLUSIONS: Clinical outcomes show that intra-sac injection of thrombin during EVAR is safe and may be effective in remedying small amount and low-velocity endoleaks and promoting shrinkage of the aneurysm sac.

Higenamine inhibits acute and chronic inflammatory pain through modulation of TRPV4 channels.

Pain is the cardinal symptom of many debilitating diseases and results in heavy health and economic burdens worldwide. Asarum (Asarum sieboldii Miq.) is a commonly used analgesic in Chinese medicine. However, the analgesic components and mechanisms of asarum in acute and chronic pain mice model remain unknown. In this study, we first generated asarum water extract and confirmed strong analgesic properties in mice in both the acute thermal and mechanical pain models, as well as in the complete Freund's adjuvant (CFA) induced chronic inflammatory pain model. Second, we identified higenamine as a major component of asarum and found that higenamine significantly inhibited thermal and mechanical induced acute pain and CFA induced chronic inflammatory pain. Then, using Trpv4-/- mice, we found that TRPV4 is necessary for CFA induced thermal and mechanical allodynia, and demonstrated that higenamine analgesia in the CFA model is partly through TRPV4 channel inhibition. Finally, we found that GSK1016790A, a TRPV4 agonist, induced calcium response was significantly inhibited by higenamine in both cultured DRG neurons and TRPV4 transfected HEK293 cells. Consistent with calcium imaging results, higenamine pretreatment also dose-dependently inhibited GSK1016790A induced acute pain. Taken together, our behavior and calcium imaging results demonstrate that the asarum component higenamine inhibits acute and chronic inflammatory pain by modulation of TRPV4 channels.

Stent fracture after transjugular intrahepatic portosystemic shunt placement using the bare metal stent/stent-graft combination technique.

BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is widely placed to treat portal hypertension. Because the Viatorr® stent (W. L. Gore and Associates, Flagstaff, AZ, United States) is not available in all hospitals in China, the bare metal stent (BMS)/stent-graft combination technique is still popular for TIPS construction. Stent fracture is a complication after TIPS placement using this technique, with limited available literature focusing on it. AIM: To assess the incidence of stent fracture after TIPS placement using the BMS/ stent-graft combination technique and to identify the risk factors for stent fracture. We proposed technique modifications to improve the clinical results of TIPS placement with the BMS/stent-graft combination technique. METHODS: We retrospectively analyzed the computed tomography (CT) data of all patients with portal hypertension who underwent the TIPS procedure between June 2011 and December 2021 in a single center. Patients implanted with the BMS/stent graft and had follow-up imaging data available were included. We identified patients with stent fracture and analyzed their characteristics. Multivariable logistic regression was applied to identify the potential predictors of stent fracture. RESULTS: Of the 68 included patients, stent fracture occurred in seven (10.3%) patients. Based on CT images, the stent fractures were categorized into three types. Our study consisted of four (57.1%) type I fractures, one (14.3%) type II fracture, one (14.3%) type IIIa fracture, and one (14.3%) type IIIb fracture. After adjusting for covariates, multivariable logistic regression revealed that the risk factors for stent fracture were the implantation of a greater number of stents [adjusted odds ratio (aOR) = 22.2, 95% confidence interval (CI): 1.2-415.4, P = 0.038] and a larger proximal sagittal stent bending angle (aOR = 1.1, 95%CI: 1.0-1.3, P = 0.020). CONCLUSION: Stent fracture occurred in approximately 10% of patients with portal hypertension who underwent TIPS with the BMS/stent-graft combination technique. The number of implanted stents and stent bending angle at the inferior vena cava end were predictors of stent fracture, which suggests that the incidence of stent fracture could potentially be reduced by procedural modifications.

Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data.

ABSTRACT: The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.

The effect of music intervention on sedation in elderly patients undergoing transurethral resection of prostate under spinal anesthesia: a prospective randomized controlled clinical trial.

PURPOSE: Music intervention is commonly used as a non-pharmacologic therapeutic modality to alleviate anxiety in perioperative patients. This study aimed to assess the sedative and anxiolytic effects of music on elderly patients receiving transurethral resection of prostate (TURP) under spinal anesthesia. METHODS: This was a prospective randomized controlled trial on patients who aged over 60 and received TURP under spinal anesthesia. Participants were randomized to the music group or the control group (no music). The primary outcome was perioperative BIS values, and the secondary outcomes were patient's perioperative anxiety levels, heart rate (HR), blood pressure, and patient satisfaction score. RESULTS: A total of 82 patients were analyzed. The perioperative BIS values in the music group were significantly lower than those of the control group at almost all time points (P < 0.001), as well as showed a significant reduction compared with baseline (P < 0.001), whereas the control group did not. In comparison with the control group, systolic blood pressure (SBP) significantly decreased in the music group at the beginning (mean difference, - 8.0 mmHg; 95% CI - 15.70 to 0.35; P = 0.041) and the 60th minute (mean difference, - 7.9 mmHg; 95% CI - 15.30 to 0.51; P = 0.037) of TURP. Furthermore, compared with baseline within the music group, diastolic blood pressure (DBP) and HR significant reduced at whole time points (P < 0.05), yet the control group not. CONCLUSION: Music intervention effectively provided slight sedation for elderly patients when undergoing TURP under spinal anesthesia without sedatives.

Comparison of complete multi-level vs. iliac-only revascularization for concomitant iliac and superficial femoral artery occlusive disease.

Objective: The aim of this study is to compare the efficacy and safety of complete multi-level vs. iliac-only revascularization for the treatment of concomitant iliac and superficial femoral artery (SFA) occlusive disease. Methods: A total of 139 consecutive adult patients with severe stenosis and occlusive iliac and SFA disease with Rutherford categories 2-5 underwent multi-level (n = 71) and iliac-only (n = 68) revascularization at the Department of Intervention Vascular Surgery, Peking University Third Hospital, and Aerospace Center Hospital, between March 2015 and June 2017. Improvement in Rutherford class, perioperative major adverse events, the length of stay, survival rate, and limb salvage rate were assessed. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were compared between the two groups. Results: At 48 months, improvement in the Rutherford category was observed in the two groups with no significant difference (P = 0.809). Additionally, the two groups were similar concerning the primary patency (84.0% vs. 79.1%, P = 0.717) and limb salvage rate (93.1% vs. 91.3%, P = 0.781). A higher proportion of the perioperative major adverse events (33.8% vs. 27.9%, P = 0.455), the all-cause mortality (11.3% vs. 8.8%, P = 0.632), and the average length of hospital stay [7.0 (6.0, 11.0) vs. 7.0 (5.0, 8.0), P = 0.037] were seen in the multi-level group compared with the iliac-only group. Conclusion: For concomitant iliac and superficial femoral artery occlusive disease, iliac-only revascularization has favorable efficacy and safety outcomes compared with complete multi-level revascularization in selected patients with patent profunda femoris artery and at least one healthy outflow tract of the infrapopliteal artery.

Guiding Metal Organic Framework Morphology via Monolayer Artificial Defect-Induced Preferential Facet Selection.

Guiding metal organic framework (MOF) morphology, especially without the need for chemical additives, still remains a challenge. For the first time, we report a unique surface guiding approach in controlling the crystal morphology formation of zeolitic imidazole framework-8 (ZIF-8) and HKUST-1 MOFs on disrupted alkanethiol self-assembled monolayer (SAM)-covered Au substrates. Selective molecule removal is applied to generate diverse SAM matrices rich in artificial molecular defects in a monolayer to direct the dynamic crystal growth process. When a 11-mercaptoundecanol alkanethiol monolayer is ruptured, the hydroxyl tail groups of surface residue molecules act as nucleating sites by coordination with precursor metal ions. Meanwhile, the exposed alkane chain backbones stabilize a particular facet of MOF nuclei in the dynamic growth by slowing down their crystal growth rates along a specific direction. The competitive formation between the [110] and [100] planes of ZIF-8 ultimately regulates the crystal shapes from rhombic dodecahedron, truncated rhombic dodecahedron, and truncated cube to cube. Similarly, changeable morphologies of HKUST-1 crystals are also achieved from cube and tetrakaidekahedron to octahedron, originating from the competitive selection between the [100] and [111] planes. In addition to the artificial matrix preferred orientation of initial nucleation, parameters such as temperature also play a crucial role in the resulting crystal morphology. Standing on the additive-free MOF crystal morphology growth control, porous architectures prepared in this approach can act as templates for ligand-free metal (Au, Ag, and Cu) nanocluster synthesis. The nanocluster-embedded MOF structures represent distinct crystal morphology-dependent optical properties, and interestingly, their fluorescence emission can be highly enhanced by facet-induced nanocluster packing alignments. These findings not only provide a unique thought on MOF crystal morphology guidance but also pave a new route for the accompanied property investigation and further application.

Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

Management of male erectile dysfunction: From the past to the future.

Erectile dysfunction is a common disease of the male reproductive system, which seriously affects the life quality of patients and their partners. At present, erectile dysfunction is considered as a social-psychological-physiological disease with complex etiology and various treatment methods. Oral PDE5I is the first-line treatment for erectile dysfunction with the advantages of high safety, good effect and non-invasiveness. But intracavernosal injection, hormonal replacement therapy, vacuum erection device, penile prosthesis implantation can also be alternative treatments for patients have organic erectile dysfunction or tolerance to PDE5I. With the rapid development of technologies, some new methods, such as low-intensity extracorporeal shock wave and stem cell injection therapy can even repair the organic damage of the corpora cavernosa. These are important directions for the treatment of male erectile dysfunction in the future. In this mini-review, we will introduce these therapies in detail.

Gap-directed chemical lift-off lithographic nanoarchitectonics for arbitrary sub-micrometer patterning.

We introduce a unique soft lithographic operation that exploits stamp roof collapse-induced gaps to selectively remove an alkanethiol self-assembled monolayer (SAM) on Au to generate surface patterns that are orders of magnitude smaller than structures on the original elastomer stamp. The smallest achieved feature dimension is 5 nm using a micrometer-scale structured stamp in a chemical lift-off lithography (CLL) process. Molecular patterns retained in the gaps between stamp features and their circumscribed or inscribed circles follow mathematical predictions, and their sizes can be tuned by altering the stamp structure dimensions, including height, pitch, and shape. These generated surface molecular patterns can function as biorecognition arrays or be transferred to the underneath Au layer for metallic structure creation. By combining CLL process with this gap phenomenon, soft material properties that are previously thought as demerits can be used to achieve sub-10 nm features in a straightforward sketch.

A comparative study on the efficacy and safety of propofol combined with different doses of alfentanil in gastroscopy: a randomized controlled trial.

PURPOSE: Propofol can be used alone or in combination with opioids during gastroscopy. This study aimed to assess the efficacy and safety of intravenous propofol and different doses of alfentanil in patients undergoing gastroscopy. METHODS: A total of 300 patients undergoing sedative gastroscopy were randomly divided into four groups, and 0.9% saline (group A), 2 µg/kg alfentanil (group B), 3 µg/kg alfentanil (group C) or 4 µg/kg alfentanil (group D) were injected intravenously 1 min before the intravenous injection of 1.5 mg/kg propofol. If body movement and coughing occurred during the procedure, 0.5 mg/kg propofol would be administered intravenously. The primary outcome (awakening time) and secondary outcomes were recorded and analyzed, including hemodynamic changes, the incidences of body movement, coughing, hypoxemia, hypotension, hypertension, bradycardia, tachycardia, nausea and vomiting, drowsiness and dizziness. RESULTS: Patients in group C (7.0 [5.0 to 8.0] min) and group D (6.0 [5.0 to 7.0] min) woke up significantly earlier than those in group A (8.0 [6.0 to 10.0] min) (P < 0.001). Patients in group A experienced more body movement (P = 0.001) and coughing (P < 0.001) than the other groups. With the increasing dose of alfentanil, the morbidity of hypotension and bradycardia increased significantly (P = 0.001), while the incidence of dizziness decreased significantly (P = 0.037). The incidences of hypoxemia, tachycardia, drowsiness, nausea and vomiting were similar among the four groups (P > 0.05). CONCLUSIONS: Intravenous 1.5 mg/kg propofol combined with 3 µg/kg alfentanil is more suitable for patients undergoing gastroscopy, and the dose of alfentanil can be reduced according to the patient's actual physical condition.

An Experimental Investigation of the Mechanical Behavior and Particle Crushing Characteristic of Volcanic Soil.

Volcanic soil is a special soil that is well-known for its distinctive texture, vesicular nature, and particle fragility. The fragility characteristic of volcanic soil is the main factor affecting the foundation stability in road engineering. This study focuses on the mechanical properties and particle crushing characteristics of volcanic soil retrieved from Northeast China. A series of triaxial consolidation and drainage shear tests are performed on volcanic coarse-grained soil (5 mm > d > 0.075 mm) under different initial relative densities and effective confining pressures. Results show the peak friction angle of volcanic soil significantly decreases with the increase of confining pressure. The particle crushing degree of volcanic soil increases with the increase of confining pressure, particle size, and relative density. The relative breakage rate of the same particle size group has a good linear relationship with a fractal dimension. Moreover, for the same particle size, the relationship between plastic work and relative breakage rate can be fitted by a power function, which is not significantly affected by relative density or effective confining pressure. From an engineering view, in addition to increasing the compaction degree of volcanic soil, volcanic soil with fine particles used as a roadbed filler can significantly reduce the deformation of the roadbed and improve the bearing capacity of the foundation.

[Effects of GSK3ß/eEF2K signaling pathway on pulmonary fibrosis in mice].

Objective: To investigate the effects of glycogen synthase kinase-3ß (GSK3ß)/eukaryotic extension factor kinase 2 (eEF2K) signaling pathway on the process of pulmonary fibrosis through in vivo experiments, and find new ideas for clinical treatment of pulmonary fibrosis. Methods: The pulmonary fibrosis model of C57BL/6 male mice was induced by bleomycin with intratracheal injection at the dose of 2 mg/kg. After 14 days of modeling, animals were divided into model group, negative inhibition group and inhibition group (n=5 for each group), and control group was not processed. The inhibition group was treated with TDZD-8 (4 mg/kg) after modeling, the negative inhibition group was given DMSO solution after modeling, and the samples were collected after 28 days. Hematoxylin-eosin staining method was used to detect lung fibrosis in mice and scored according to Ashcroft scale. Expression levels of GSK3ß, p-GSK3ß, eEF2K, p-eEF2K (Ser70, Ser392, Ser470), precursor protein of matrix metalloproteinase-2 (pro-MMP-2), matrix metalloproteinase-2 (MMP-2), collagen I (Col I), collagen Ⅲ (Col Ⅲ) and α-smooth muscle actin (α-SMA) were detected by Western blot. Results: Compared with control group, the fibrosis score was up-regulated, the expression levels of GSK3ß, p-GSK3ß, p-eEF2K (Ser70, Ser392, Ser470), pro-MMP-2, MMP-2, Col I, Col Ⅲ and α-SMA were increased, while that of eEF2K was decreased in model group (P＜0.05). Compared with model group, the fibrosis score, expression levels of GSK3ß, p-GSK3ß, p-eEF2K (Ser70, Ser392, Ser470), pro-MMP-2, MMP-2, Col I, Col Ⅲ and α-SMA were decreased, but the expression level of eEF2K was increased in inhibition group (P＜0.05). Conclusion: GSK3ß can activate eEF2K by phosphorylation at the sites of Ser70, Ser392 and Ser470, increase the contents of fibrosis indicators, promote the formation of pulmonary fibrosis, and aggravate lung tissue lesions.

LncRNA NEAT1-associated aerobic glycolysis blunts tumor immunosurveillance by T cells in prostate cancer.

Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is nuclear-located and transcribed from chromatin 11. To date, little is known about the cellular functions and regulatory mechanisms of NEAT1 in prostate cancer (PCa). In this study, whole-genome RNA sequencing data were downloaded from TCGA and GEO databases. Biological information was used to analyze the different expressions of NEAT1. In situ hybridization (ISH) was performed to detect the expression of NEAT1 in PCa and paracarcinoma clinical samples. Then, NEAT1 was knocked down in PC3 cells through lentiviral infection with a plasmid construct. Bioinformatics and integrative analytical approaches were utilized to identify the relationships of NEAT1 with specific cancer-related gene sets. Cell proliferation assay and colony formation assay were performed to evaluate the cell proliferative ability. Glycolysis stress test, metabolism assay, and infiltrating T-cell function analysis were implemented to assess the changes in metabolism and immune microenvironment of PCa. We found that the expression of NEAT1 was higher in PCa than in non-neoplastic tissues. The cell proliferative capability of PCa cells was significantly reduced in the NEAT1 knockdown group. PCR array and bioinformatics analysis revealed that the enrichment of acidic substance-related gene sets was associated with NEAT1 expression. NEAT1 depletion inhibited PCa cell aerobic glycolysis accompanied by the reduction of lactate levels in the medium. Further, we found that lactate dehydrogenase A (LDHA) expression was positively regulated by NEAT1. At last, co-culture systems indicated that NEAT1 or LDHA knockdown promoted the secretion of CD8+ T-lymphocyte factors, including TNF-α, IFN-γ, and Granzyme B, and enhanced the antitumor effects.

Metal-Free Transparent Three-Dimensional Flexible Electronics by Selective Molecular Bridges.

Flexible and transparent electronics is a new generation of device enabling modern interactive designs, which facilitates the recent development of low-cost, lightweight, and flexible materials. Although conventional indium tin oxide material still dominates the major market, its brittleness and steadily increasing price drive scientists to search for other alternatives. To meet the high demand, numerous metallic or organic conductive materials have been developed, but their poor adhesion toward supporting substrates and the subsequent circuit patterning approach remains problematic. In this study, a robust metal-free flexible conductive film fabrication strategy is introduced. The flexible polyethylene terephthalate (PET) film is utilized as the base, where a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive layer is tightly linked onto this supporting substrate. An interface activation process, i.e., oxygen plasma treatment, generates PET surface active spots to react with the subsequently introduced poly(vinyl alcohol) (PVA) molecule functional groups. This spatially selective PVA molecular bridge therefore acts as a dual-function intermediate layer through covalent bonding toward PET and hydrogen bonding toward PEDOT:PSS to conjugate two distinct materials. This PEDOT:PSS/PVA/PET film delivers superior physical properties, such as a high conductivity of 38.2 Ω/sq and great optical transmittance of 84.1%, which are well tunable under conductive polymer thickness controls. The film is also durable and can maintain original electrical properties even under serious bending for hundreds of cycles. Relying on these outstanding performances, arbitrary conductive circuits are built on this flexible substrate and can function as normal electronics when integrated with multiple electronic parts, e.g., light-emitting diodes (LEDs). Superior electrical signal outputs are achieved when complicated stereo structures including folding, splicing, interlacing, and braiding are incorporated, enabling the use of these films for flexible three-dimensional electronics assembling. Space identifying smart key and lock pair, origami rabbit-carrot touch response, pressure-stimulated jumping frog, and moving dinosaur recognition designs realize these PEDOT:PSS/PVA/PET film-based human-machine interactive devices. This flexible, transparent, and conductive film generation approach by molecular bridge creation should facilitate future development of flexible or foldable devices with complex circuits.

The Effect of Atropine on Trigeminocardiac Reflex-induced Hemodynamic Changes During Therapeutic Compression of the Trigeminal Ganglion.

BACKGROUND: Percutaneous compression of the trigeminal ganglion (PCTG) can induce significant hemodynamic perturbations secondary to the trigeminocardiac reflex (TCR). The aim of this study was to investigate the effect of atropine pretreatment on hemodynamic responses during PCTG for trigeminal neuralgia. MATERIALS AND METHODS: A total of 120 patients who received PCTG were randomly assigned to control and atropine groups that were pretreated with saline (n=60) and atropine 0.004 mg/kg intravenously (n=60), respectively. Heart rate (HR) and mean arterial pressure (MAP) were measured at 9 timepoints from before induction of anesthesia until the end of the PCTG procedure; the incidence of TCR was also observed. RESULTS: HR was higher in the atropine compared with control group from the time of skin puncture with the PCTG needle until after the procedure was completed (P<0.05). MAP was also higher in the atropine compared with control group, but only at entry of the needle into the foramen ovale until 1 minute after trigeminal ganglion compression (P<0.05). HR was reduced in both groups during entry of the needle into the foramen ovale and during ganglion compression, but less so in the atropine compared with the control group (P<0.05). MAP increased during PCTG compared with baseline in both groups, but with a larger increase in the atropine group (P<0.05). Two and 52 cases in the control group, and 6 and 1 cases in the atropine group, exhibited a TCR during entry of the needle into the foramen ovale and at ganglion compression, respectively (P<0.05). CONCLUSION: Pretreatment with atropine was effective in most patients at minimizing abrupt reduction in HR during PCTG.

Manipulating Chemical Processes by Pseudosolid Spatial Limitation.

It is always preferred to perform chemical processes in liquid or gas phases because of the merits of operation convenience, reaction efficiency, and component homogeneity. However, tremendous efforts have to be made to purify the final product and minimize procedure losses unless a well-defined chemical mechanism is found. Herein, an unconventional chemical functioning system accommodating molecule-in-pseudosolid manipulation is reported. It entails the properties of enhanced molecular effective collision and directional guidance for delicate chemical reaction spatial controls. This design achieves facilitated rates on multicomponent chemical reactions with pros of unique simultaneous final product separation through intrapseudosolid spatial limitation. Localized homogeneous component mixing, pronounced molecular collision, and pure product separation happening in this action surmount the obstacles of conventional chemical operation with a straightforward sketch. A path toward fine chemistry is therefore paved, where traditional thoughts on beneficial reaction environments may be reconsidered.