Explore the vast range of titles available.

Background Painless gastrointestinal endoscopy is widely used for the diagnosis and treatment of digestive diseases. At present, propofol is commonly used to perform painless gastrointestinal endoscopy, but the high dose of propofol often leads to a higher incidence of cardiovascular and respiratory complications. Studies have shown that the application of propofol combined with ketamine in painless gastrointestinal endoscopy is beneficial to reduce the dosage of propofol and the incidence of related complications. Esketamine is dextrorotatory structure of ketamine with a twice as great anesthetic effect as normal ketamine but fewer side effects. We hypothesized that esketamine may reduce the consumption of propofol and to investigate the safety of coadministration during gastrointestinal endoscopy. Methods A total of 260 patients undergoing painless gastrointestinal endoscopy (gastroscope and colonoscopy) were randomly divided into P group (propofol + saline), PK1 group (propofol + esketamine 0.05 mg/kg), PK2 group (propofol + esketamine 0.1 mg/kg), and PK3 group (propofol + esketamine 0.2 mg/kg). Anesthesia was achieved by 1.5 mg/kg propofol with different doses of esketamine. Propofol consumption per minute was recorded. Hemodynamic index, pulse oxygen saturation, operative time, induction time, awakening status, orientation recovery time, adverse events, and Mini-Mental State Examination (MMSE) were also recorded during gastrointestinal endoscopy. Results Propofol consumption per minute was 11.78, 10.56, 10.14, and 9.57 (mg/min) in groups P, PK1, PK2, and PK3, respectively; compared with group P, groups PK2 and PK3 showed a decrease of 13.92% ( P  = 0.021) and 18.76% ( P  = 0.000), respectively. In all four groups, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), but not pulse oxygen saturation (SpO 2 ) significantly decreased ( P  = 0.000) immediately after administration of induction, but there were no significant differences between the groups. The induction time of groups P, PK1, PK2, and PK3 was 68.52 ± 18.394, 64.83 ± 13.543, 62.23 ± 15.197, and 61.35 ± 14.470 s, respectively ( P  = 0.041). Adverse events and psychotomimetic effects were observed but without significant differences between the groups. Conclusions The combination of 0.2 mg/kg esketamine and propofol was effective and safe in painless gastrointestinal endoscopy as evidenced by less propofol consumption per minute, shorter induction time, and lower incidence of cough and body movement relative to propofol alone. The lack of significant differences in hemodynamic results, anesthesia-related indices, adverse events, and MMSE results showed the safety to apply this combination for painless gastrointestinal endoscopy. Trial registration This study was registered with China Clinical Trial Registration on 07/11/2020 (registration website: chictr.org.cn; registration numbers: ChiCTR https://clinicaltrials.gov/ct2/show/2000039750 ).

Many patients remain unresponsive to intensive PD-1/PD-L1 blockade therapy despite the presence of tumor-infiltrating lymphocytes. We propose that impaired innate sensing might limit the complete activation of tumor-specific T cells after PD-1/PD-L1 blockade. Local delivery of type I interferons (IFNs) restores antigen presentation, but upregulates PD-L1, dampening subsequent T-cell activation. Therefore, we armed anti-PD-L1 antibody with IFNα (IFNα-anti-PD-L1) to create feedforward responses. Here, we find that a synergistic effect is achieved to overcome both type I IFN and checkpoint blockade therapy resistance with the least side effects in advanced tumors. Intriguingly, PD-L1 expressed in either tumor cells or tumor-associated host cells is sufficient for fusion protein targeting. IFNα-anti-PD-L1 activates IFNAR signaling in host cells, but not in tumor cells to initiate T-cell reactivation. Our data suggest that a next-generation PD-L1 antibody armed with IFNα improves tumor targeting and antigen presentation, while countering innate or T-cell-driven PD-L1 upregulation within tumor. Despite the presence of tumor-infiltrating lymphocytes, many patients do not respond to PD-L1/PD-1 blockade therapy. Here they show that PD-L1 antibody armed with interferon-α (IFNα) improves tumor targeting and antigen presentation while countering innate or T-cell-drive PD-L1 upregulation, and overcomes resistance to checkpoint blockade therapy.

Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.

By modeling the brain as a network, the challenge of abating seizure can be recast as a problem of network control. In the premise of bringing network under control, the minimum number of nodes prerequisite for controlling seizures are thus a natural aim of interest, which is still an outstanding issue. Here, we use the network structural control theory to guide the selection for the optimal control nodes with the aim of fully abating seizures. Firstly, we construct the dynamical complex network of pathological seizure by estimating the synchronicity and directionality of information flows over time between EEG signals from 10 patients with focal epilepsy. Then, based on the controllability and observability principles of complex systems, the minimum key nodes which are effective to fully control the network seizure behaviors are obtained. Results show that the calculated control nodes are distinct with the focus zones from clinic report. This suggests that the full control of epileptic network may not only related to the focus zone, the other non-focus nodes could also play important roles. This finding is validated by using the spatiotemporal neural network model connected with our modeled dynamical adjacent matrix. It successfully reproduces the original EEG signals which can be effectively abated by applying pulse stimulation on the identified key nodes or resecting them, while the partial effects can be obtained when functioning onto the clinically identified focus zones of 60% patients. Interestingly, for another 30% patients lesser nodes than clinic reports are need to fully control seizures. In addition, our work facilitates to identify the evolution paths of information flows, so the non-clinic focus zones identified through controllability principle can be supposed to be the potential seizure foci. In sum, our work propose a general methodology or strategy for seizures focus localizations that could comprehensively consider the time-evolving information flow and the analysis of controllability mechanisms driven by the real seizures data, as well as the computational validation. This may promote to develop the canonical computational framework with the core intent of providing support for clinical treatment decisions.

The dynamic reconfiguration of network oscillations is connected with cognitive processes. Changes in how neural networks and signaling pathways work are crucial to how epilepsy and related conditions develop. Specifically, there is evidence that prolonged or recurrent seizures may induce or exacerbate cognitive impairment. However, it still needs to be determined how the seizure brain configures its functional structure to shape the battle of strong local oscillations vs. slow global oscillations in the network to impair cognitive function. In this paper, we aim to deduce the network mechanisms underlying seizure-induced cognitive impairment by comparing the evolution of strong local oscillations with slow global oscillations and their link to the resting state of healthy controls. Here, we construct a dynamically efficient network of pathological seizures by calculating the synchrony and directionality of information flow between nine patients' SEEG signals. Then, using a pattern-based method, we found hierarchical modules in the brain's functional network and measured the functional balance between the network's local strong and slow global oscillations. According to the findings, a tremendous rise in strong local oscillations during seizures and an increase in slow global oscillations after seizures corresponded to the initiation and recovery of cognitive impairment. Specifically, during the interictal period, local strong and slow global oscillations are in metastable balance, which is the same as a normal cognitive process and can be switched easily. During the pre-ictal period, the two show a bimodal pattern of separate peaks that cannot be easily switched, and some flexibility is lost. During the seizure period, a single-peak pattern with negative peaks is showcased, and the network eventually transitions to a very intense strong local oscillation state. These results shed light on the mechanism behind network oscillations in epilepsy-induced cognitive impairment. On the other hand, the differential (similarity) of oscillatory reorganization between the local (non) epileptogenic network and the global network may be an emergency protective mechanism of the brain, preventing the spread of pathological information flow to more healthy brain regions.

Sphingosine-1-phosphate (S1P), a pleiotropic lipid mediator, participates in various cellular processes during tumorigenesis, including cell proliferation, survival, drug resistance, metastasis, and angiogenesis. S1P is formed by two sphingosine kinases (SphKs), SphK1 and SphK2. The intracellularly produced S1P is delivered to the extracellular space by ATP-binding cassette (ABC) transporters and spinster homolog 2 (SPNS2), where it binds to five transmembrane G protein-coupled receptors to mediate its oncogenic functions (S1PR1-S1PR5). MicroRNAs (miRNAs) are small non-coding RNAs, 21–25 nucleotides in length, that play numerous crucial roles in cancer, such as tumor initiation, progression, apoptosis, metastasis, and angiogenesis via binding to the 3′‐untranslated region (3′‐UTR) of the target mRNA. There is growing evidence that various miRNAs modulate tumorigenesis by regulating the expression of SphKs, and S1P receptors. We have reviewed various roles of miRNAs, SphKs, S1P, and S1P receptors (S1PRs) in malignancies and how notable miRNAs like miR-101, miR-125b, miR-128, and miR-506, miR-1246, miR-21, miR-126, miR499a, miR20a-5p, miR-140-5p, miR-224, miR-137, miR-183-5p, miR-194, miR181b, miR136, and miR-675-3p, modulate S1P signaling. These tumorigenesis modulating miRNAs are involved in different cancers including breast, gastric, hepatocellular carcinoma, prostate, colorectal, cervical, ovarian, and lung cancer via cell proliferation, invasion, angiogenesis, apoptosis, metastasis, immune evasion, chemoresistance, and chemosensitivity. Therefore, understanding the interaction of SphKs, S1P, and S1P receptors with miRNAs in human malignancies will lead to better insights for miRNA-based cancer therapy.

PurposeAutophagy and EMT (epithelial–mesenchymal transition) are the two principal biological processes and ideal therapeutic targets during cancer development. Autophagy, a highly conserved process for degrading dysfunctional cellular components, plays a dual role in tumors depending on the tumor stage and tissue types. The EMT process is the transition differentiation from an epithelial cell to a mesenchymal-like cell and acquiring metastatic potential. There is evidence that the crosstalk between autophagy and EMT is complex in cancer. In recent years, more studies have shown that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in autophagy, EMT, and their crosstalk. Therefore, accurate understanding of the regulatory mechanisms of lncRNAs and miRNAs in autophagy, EMT and their interactions is crucial for the clinical management of cancers.MethodsAn extensive literature search was conducted on the Google Scholar and PubMed databases. The keywords used for the search included: autophagy, EMT, crosstalk, lncRNAs, miRNAs, cancers, diagnostic biomarkers, and therapeutic targets. This search provided relevant articles published in peer-reviewed journals until 2021. Data from these various studies were extracted and used in this review.ResultsThe results showed that lncRNAs/miRNAs as tumor inhibitors or tumor inducers could regulate autophagy, EMT, and their interaction by regulating several molecular signaling pathways. The lncRNAs/miRNAs involved in autophagy and EMT processes could have potential uses in cancer diagnosis, prognosis, and therapy.ConclusionSuch information could help find and develop lncRNAs/miRNAs based new tools for diagnosing, prognosis, and creating anti-cancer therapies.

Enantioselective esterification of ibuprofen has been successfully carried out in an organic solvent catalyzed by recombinant APE 1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1). Here we used microwave irradiation (MW) as the mode of heating to improve the enzyme performance. Under the optimum conditions, the enzyme activity of APE 1547 was 4.16 μmol/mg/h and the enantioselectivity (E value) was 52.9. Compared with conventional heating, the enzyme activity and the enantioselectivity were increased about 21.9-fold and 1.4-fold, respectively. The results also indicated that APE 1547 can maintain 95% of its activity even after being used five times, suggesting that the enzyme is stable under low power MW conditions.

In this paper, phase space reconstruction from stereo-electroencephalography data of ten patients with focal epilepsy forms a series of graphs. Those obtained graphs reflect the transition characteristics of brain dynamical system from pre-seizure to seizure of epilepsy. Interestingly, it is found that the rank of Laplacian matrix of these graphs has a sharp decrease when a seizure is close to happen, which thus might be viewed as a new potential biomarker in epilepsy. In addition, the reliability of this method is numerically verified with a coupled mass neural model. In particular, our simulation suggests that this potential biomarker can play the roles of predictive effect or delayed awareness, depending on the bias current of the Gaussian noise. These results may give new insights into the seizure detection.

In recent years, the field of 3D printing technology has experienced rapid advancements, notably expanding its application within the medical sector. This study focuses on the custom design of 3D-printed spinal implants, specifically examining porous interbody fusion products. It integrates considerations of mechanical strength and bone ingrowth to establish a finite element model of porous interbody fusion, subsequently conducting topology optimization to design three distinct types of spinal interbody fusion implants. Analytical investigations were carried out on the stress and displacement responses of these three implant types under compressive loading. Furthermore, a detailed stress analysis was conducted on implants varying in porosity, length, and screw angle of the bone graft to assess the performance characteristics of the porous interbody fusion devices. Results indicated that the Type C implant exhibited superior performance, demonstrating a stress reduction to 89.21 MPa and a displacement change of 0.006 mm, optimally at a 60% porosity level. Adjustments in the lengths and screw clamp angles of the splint ensured that the maximal stress experienced by each vertebra remained below the yield limits of both cortical and cancellous bone, thus preventing vertebral damage. This paper presents a comparative analysis of three types of porous interbody fusion devices, providing substantial data support and a theoretical framework that can inform the future development of fusion products.