Crebanine, an aporphine alkaloid, induces cancer cell apoptosis through PI3K-Akt pathway in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most prevalent and lethal primary central nervous system malignancies. GBM is notorious for its high rates of recurrence and therapy resistance and the PI3K/Akt pathway plays a pivotal role in its malignant behavior. Crebanine (CB), an alkaloid capable of penetrating the blood-brain barrier (BBB), has been shown to have inhibitory effects on proinflammatory molecules and multiple cancer cell lines via pathways such as PI3K/Akt. This study aims to investigate the efficacy and mechanisms of CB treatment on GBM. It is the first study to elucidate the anti-tumor role of CB in GBM, providing new possibilities for GBM therapy. Through a series of experiments, we demonstrate the significant anti-survival, anti-clonogenicity, and proapoptotic effects of CB treatment on GBM cell lines. Next-generation sequencing (NGS) is also conducted and provides a complete list of significant changes in gene expression after treatment, including genes related to apoptosis, the cell cycle, FoxO, and autophagy. The subsequent protein expressions of the upregulation of apoptosis and downregulation of PI3K/Akt are further proved. The clinical applicability of CB to GBM treatment could be high for its BBB-penetrating feature, significant induction of apoptosis, and blockage of the PI3K/Akt pathway. Future research is needed using in vivo experiments and other therapeutic pathways shown in NGS for further clinical or in vivo studies.

Multiplication-free and hardware-efficient baud-rate timing error detector for Nyquist and faster than Nyquist optical IM/DD systems.

Clock recovery (CR) algorithms that support higher baud rates and advanced modulation formats are crucial for short-distance optical interconnections, and it is desirable to push CR to operate at baud rate with minimal computing resources and power. In this Letter, we proposed a hardware-efficient and multiplication operation-free baud-rate timing error detector (TED) as a solution to meet these demands. Our approach involves employing both the absolute value of samples and the nonlinear sign operation to emphasize the clock tone, which is deteriorated by severe bandwidth limitation in Nyquist and faster than Nyquist (FTN) systems. Through experimental investigations based on a transceiver system with a 3 dB bandwidth of 30 GHz, the proposed baud-rate TED exhibits excellent performance. The proposed scheme successfully achieves clock synchronization of the received signals with the transmitted signals, including 50 GBaud PAM4/8, 80 GBaud PAM4, and up to 120 GBaud PAM4 FTN signals. To the best of our knowledge, the CR based on the proposed baud-rate TED is the most optimal solution for ultrahigh-speed short-reach IM/DD transmission, comprehensively considering the timing jitter, bit error rate (BER), and implementation complexity.

Effects of various functional monomers' reaction on the surface characteristics and bonding performance of polyetheretherketone.

PURPOSE: Polyetheretherketone (PEEK) is a new polymeric material that has received significant attention in dentistry because of its mechanical properties, biocompatibility, and aesthetics. However, the bonding performance of PEEK to other materials is not preferable. This study aimed to analyze the variations in the surface characteristics of PEEK under the chemical action of primers containing different functional monomers or polymers and to evaluate the bonding performance of PEEK and dental cement. METHODS: Disk-shaped PEEK samples were prepared by dental milling, blasting with alumina oxide, and covering with primers containing functional monomers or polymers. The surface characteristics of the samples were analyzed by microscopy and spectroscopy. The shear bond strength (SBS) between PEEK and dental cement, with and without thermocycling, was tested using a universal testing machine. Finally, the data were statistically analyzed and compared. RESULTS: Functional monomers or polymers were successfully bonded to the surface of PEEK. This treatment significantly improved its hydrophilicity and surface free energy (P < 0.05). The primer containing pentaerythritol triacrylate had the highest SBS without thermocycling (13.89 MPa). Meanwhile, the primers containing urethane dimethacrylate (UDMA) and methyl methacrylate (MMA) (abbreviated as the HC group) showed the highest SBS and lowest reduction (25.51%) after thermocycling. Notably, all the testing groups achieved the ISO10477 standard of 5 MPa. After thermocycling, adhesive failure accounted for the largest proportion of failures in all the groups except the HC group. CONCLUSIONS: The chemical priming treatment can significantly improve the SBS of PEEK and dental cement. Moreover, a primer containing both UDMA and MMA can provide improved bonding for PEEK materials.

The effects of different surgical approaches on the psychological status, medical coping mode and quality of life of patients with lung cancer.

Objective: This study aimed to compare the effects of robot-assisted thoracic surgery (RATS), video-assisted thoracic surgery (VATS), and thoracotomy on the psychological status, medical coping mode, and quality of life of patients with lung cancer. Methods: A total of 158 patients with lung cancer were selected from the thoracic surgery center of a third-grade hospital in Hunan Province, China, from September to November 2020. The Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Medical Coping Modes Questionnaire (MCMQ), and Medical Outcomes Study (MOS) 36-item Short Form Health Survey (SF-36) were used to assess the effects of the surgical approaches on the study parameters before and 48-96 h after surgery. The t-test and analysis of variance were used to analyze the data. Results: The results revealed that the patients' depression increased, their short-term quality of life decreased, and they tended to adopt a positive coping mode after surgery (p < 0.05). The RATS and VATS groups differed in avoidance dimension of medical coping modes (p < 0.05). The VATS and thoracotomy groups differed in the body pain dimension of quality of life (p < 0.05). Different surgical approaches had no effect on the psychological status, medical coping modes except the avoidance dimension, and quality of life except the body pain dimension. Conclusion: Surgical approaches have little effect on the psychological status, medical coping modes, and quality of life of patients with lung cancer; however, their depression increased and quality of life decreased after the surgery.

Effectiveness and Safety of Immunosuppressive Drug Therapy for Neuromyelitis Optica Spectrum Disorders: An Overview of Meta-Analyses and Systematic Reviews.

OBJECTIVE: This study aims to provide an overview of meta-analyses and systematic reviews on the effectiveness and safety of immunosuppressive drug therapy for neuromyelitis optica spectrum disorders (NMOSD) by evaluating the methodological quality and reporting quality of reviews. METHODS: The Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database, Web of Science, the Cochrane Library, PubMed, and Embase databases were searched to collect systematic reviews or meta-analyses on the effectiveness and safety of immunosuppressive therapy for NMOSD from inception to December 2, 2021. Two researchers independently screened reviews and extracted data. Any differences in the procession of review assessment between the two researchers were re-evaluated, and the disagreement was resolved by discussion with other researchers. The following data were extracted: author, year of publication, the country where the study was conducted, study type, the number of included studies, sample size, risk bias tools, medication of immunosuppressive therapy, and main outcomes. Then, the AMSTAR-2, which is a critical appraisal tool for systematic reviews (2nd edition), and Grades of Recommendation, Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality and reporting quality of evidence. A comprehensive analysis was conducted on the outcomes for all included reviews. RESULTS: A total of 15 reviews were included. Of the included reviews, 3 were systematic reviews, 7 were meta-analyses, and 5 were systematic reviews and meta-analyses. According to the AMSTAR-2 criteria, 6 studies had high quality, 1 study had moderate quality, 4 studies had low quality, and 4 studies had critically low quality. Based on the GRADE, neither evidence quality for effectiveness nor safety was high. CONCLUSION: Immunosuppressive drug therapy is effective for patients with NMOSD, but its safety is controversial. Due to the poor quality of evidence, reliability needs to be considered. Thus, large sample, multi-center, double-blind, randomized controlled studies are still needed in the future.

Cytokine-induced killer cell infusion combined with conventional treatments produced better prognosis for hepatocellular carcinoma patients with barcelona clinic liver cancer B or earlier stage: A systematic review and meta-analysis.

BACKGROUND AIMS: To investigate the clinical benefits of cytokine-induced killer (CIK) cell infusions on hepatocellular carcinoma (HCC) patients, combined with other conventional treatments. METHODS: This was a systematic review and meta-analysis conducted among phase II and III randomized control trials worldwide. Review manager 5.2 version was used to pool the effect size across studies. Sensitivity analyses and risk of bias were estimated among included studies. Egger's test was used to characterize the publication bias. RESULTS: Eight randomized controlled trials and 945 patients with HCC were included in the study. CIK infusion reduced cancer recurrence risk to 0.74 (95% confidence interval [CI] 0.5-0.92), I2 75% (P <0.001), and reduced cancer death risk to 0.76 (95% CI 0.65-0.88), I2 50% (P = 0.09). Among studies blinded for outcome assessment and Barcelona Clinic Liver Cancer stages of 0, A and B, CIK infusion reduced recurrence risk by 18% (relative risk [RR] = 0.82, 95% CI 0.70-0.96) and death risk by 37% (RR = 0.63, 95% CI 0.47-0.85); heterogeneity was 0% and 39%, respectively (P > 0.05). The intercepts of linear regressions for recurrence and death were -2.17 and -2.07, respectively, but the P value was 0.17 and 0.38; no significant publication bias was observed with Egger's test. DISCUSSION: Among hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer score of B or less, CIK cell infusions combined with conventional treatments significantly prolonged recurrence-free and overall survival. This adoptive immunotherapy could be recommended to HCC patients.

Acetylcholine modulates the immune response in Zhikong scallop Chlamys farreri.

Acetylcholine (ACh) is an indispensable neurotransmitter and neuromodulator in the cholinergic nervous system and it is implicated in the dynamic modulation of immune response in vertebrates. Although ACh has also been identified in most invertebrates, the knowledge about its immunomodulation is still limited. In the present study, the immunoreactivities of ACh and acetylcholinesterase (AChE) were observed in all the tested tissues of scallop Chlamys farreri, including adductor muscle, mantle, gill, hepatopancreas, kidney and gonad. The ACh concentration in the supernate of scallop hemolymph increased from 11.59 ± 0.27 to 14.36 ± 0.17 µM L(-1) at 6 h after LPS (0.5 mg ml(-1)) stimulation, and increased to 15.51 ± 1.20 µM L(-1) at 3 h after the stimulation of tumor necrosis factor alpha (TNF-α) (50 ng ml(-1)). After LPS stimulation, the mRNA expression levels of superoxide dismutase (CfSOD), catalase (CfCAT) and lysozyme (CfLYZ) in hemocytes increased significantly at 3 h (P < 0.05), 6 h (P < 0.05) and 12 h (P < 0.05), respectively. Compared with the LPS treatment, the induction of CfSOD, CfCAT and CfLYZ expression in hemocytes was repressed effectively (P < 0.05) by the co-stimulation of LPS and ACh (5 × 10(-7) M) at 3 h (P < 0.05), 6 h (P < 0.05) and 12 h (P < 0.05), respectively. Furthermore, the expression level of CfCAT in hemocytes increased significantly after 12 h by the co-stimulation with LPS and ACh (P < 0.05). These results indicated collectively that the scallop cholinergic nervous system could be activated by immune stimulations, and it might play an essential role in immunomodulation of scallops.