Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.

Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.

Retraction of "Effect of Fluoride Layer Growth on the Deposition Rate under Different Microchannel Structures".

[This retracts the article DOI: 10.1021/acsomega.3c06182.].

Effect of Fluoride Layer Growth on the Deposition Rate under Different Microchannel Structures.

In the plasma-enhanced chemical vapor deposition (PECVD) process, a showerhead is used to enhance fluid uniformity in the chamber. The uniformity of the flow field will be affected by changing the microchannel on the showerhead, which in turn directly affects the uniformity of deposition. The showerhead will be etched during the cleaning process due to the presence of HF, which will form a fluoride layer. This layer will cause a decrease in the diameter of the microchannels, resulting in changes in the deposition uniformity. The impact of diameter changes can be reduced by making modifications to the microchannel structure. By adopting a coupling of the Navier-Stokes and Direct Simulation Monte Carlo (NS-DSMC) methods, we obtained the velocity variation of two typical microchannels (equal-diameter type and expansion type) under the same diameter change. The results indicate that compared to the equal-diameter type, the expansion type exhibits a smaller change in velocity for the same change in diameter. For the surface reaction limited regime, a stable velocity leads to a consistent residence time, which is advantageous for maintaining the uniformity of the film thickness. Therefore, compared to the equal-diameter type microchannel, the expansion type can reduce the impact of changes in diameter.

Functional conservation and divergence of SEPALLATA-like genes in floral development in Cymbidium sinense.

Cymbidium sinense is one of the most important traditional Chinese Orchids due to its unique and highly ornamental floral organs. Although the ABCDE model for flower development is well-established in model plant species, the precise roles of these genes in C. sinense are not yet fully understood. In this study, four SEPALLATA-like genes were isolated and identified from C. sinense. CsSEP1 and CsSEP3 were grouped into the AGL9 clade, while CsSEP2 and CsSEP4 were included in the AGL2/3/4 clade. The expression pattern of CsSEP genes showed that they were significantly accumulated in reproductive tissues and expressed during flower bud development but only mildly detected or even undetected in vegetative organs. Subcellular localization revealed that CsSEP1 and CsSEP4 were localized to the nucleus, while CsSEP2 and CsSEP3 were located at the nuclear membrane. Promoter sequence analysis predicted that CsSEP genes contained a number of hormone response elements (HREs) and MADS-box binding sites. The early flowering phenotype observed in transgenic Arabidopsis plants expressing four CsSEP genes, along with the expression profiles of endogenous genes, such as SOC1, LFY, AG, FT, SEP3 and TCPs, in both transgenic Arabidopsis and C. sinense protoplasts, suggested that the CsSEP genes played a regulatory role in the flowering transition by influencing downstream genes related to flowering. However, only transgenic plants overexpressing CsSEP3 and CsSEP4 caused abnormal phenotypes of floral organs, while CsSEP1 and CsSEP2 had no effect on floral organs. Protein-protein interaction assays indicated that CsSEPs formed a protein complex with B-class CsAP3-2 and CsSOC1 proteins, affecting downstream genes to regulate floral organs and flowering time. Our findings highlighted both the functional conservation and divergence of SEPALLATA-like genes in C. sinense floral development. These results provided a valuable foundation for future studies of the molecular network underlying floral development in C. sinense.

Development of a protoplast isolation system for functional gene expression and characterization using petals of Camellia Oleifera.

Protoplasts preparation and purification have been frequently used in plant genetics and breeding studies, whereas application of protoplasts in woody plants is still in its infancy. Although transient gene expression using purified protoplasts is well-documented and widely used in model plants and agriculture crops, no instance of either stable transformation or transient gene expression in the woody plant Camellia Oleifera has as of yet been reported. Here, we developed a protoplast preparation and purification method using C. oleifera petals by optimizing osmotic condition with D-mannitol and polysaccharide-degrading enzyme concentrations for petal cell wall digestion, to reach a high efficiency of protoplast productivity and viability. The achieved protoplasts yield was approximately 1.42 × 107 cells per gram of petal material and the viability of protoplasts was up to 89%. In addition, we explored influencing factors of protoplast transformation, including concentrations of PEG4000 and plasmid DNA. The transformation efficiency of 81% could be reached under the optimized condition. This protoplast isolation and transient expression system were deployed to further identify the functional regulation of C. oleifera related genes and the subcellular distribution of their encoded products. In summary, the protoplast isolation and transient expression system we established using oil-tea tree petals is an efficient, versatile and time-saving system, being suitable for gene function characterization and molecular mechanism analysis.

The multifarious role of callose and callose synthase in plant development and environment interactions.

Callose is an important linear form of polysaccharide synthesized in plant cell walls. It is mainly composed of ß-1,3-linked glucose residues with rare amount of ß-1,6-linked branches. Callose can be detected in almost all plant tissues and are widely involved in various stages of plant growth and development. Callose is accumulated on plant cell plates, microspores, sieve plates, and plasmodesmata in cell walls and is inducible upon heavy metal treatment, pathogen invasion, and mechanical wounding. Callose in plant cells is synthesized by callose synthases located on the cell membrane. The chemical composition of callose and the components of callose synthases were once controversial until the application of molecular biology and genetics in the model plant Arabidopsis thaliana that led to the cloning of genes encoding synthases responsible for callose biosynthesis. This minireview summarizes the research progress of plant callose and its synthetizing enzymes in recent years to illustrate the important and versatile role of callose in plant life activities.

[Effect of Eltrombopag on Response to Immunosuppressive Therapy in Patients with Transfusion-Dependent Non-Severe Aplastic Anemia].

OBJECTIVE: To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA). METHODS: The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed. RESULTS: There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated. CONCLUSION: Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.

Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes.

Background: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identification and clinical significance of efferocytosis-related genes (EFRGs) in EM is sparse. Methods: The EFRDEGs (differentially expressed efferocytosis-related genes) linked to datasets associated with endometriosis were thoroughly examined utilizing the Gene Expression Omnibus (GEO) and GeneCards databases. The construction of the protein-protein interaction (PPI) and transcription factor (TF) regulatory network of EFRDEGs ensued. Subsequently, machine learning techniques including Univariate logistic regression, LASSO, and SVM classification were applied to filter and pinpoint diagnostic biomarkers. To establish and assess the diagnostic model, ROC analysis, multivariate regression analysis, nomogram, and calibration curve were employed. The CIBERSORT algorithm and single-cell RNA sequencing (scRNA-seq) were employed to explore immune cell infiltration, while the Comparative Toxicogenomics Database (CTD) was utilized for the identification of potential therapeutic drugs for endometriosis. Finally, immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to quantify the expression levels of biomarkers in clinical samples of endometriosis. Results: Our findings revealed 13 EFRDEGs associated with EM, and the LASSO and SVM regression model identified six hub genes (ARG2, GAS6, C3, PROS1, CLU, and FGL2). Among these, ARG2, GAS6, and C3 were confirmed as diagnostic biomarkers through multivariate logistic regression analysis. The ROC curve analysis of GSE37837 (AUC = 0.627) and GSE6374 (AUC = 0.635), along with calibration and DCA curve assessments, demonstrated that the nomogram built on these three biomarkers exhibited a commendable predictive capacity for the disease. Notably, the ratio of nine immune cell types exhibited significant differences between eutopic and ectopic endometrial samples, with scRNA-seq highlighting M0 Macrophages, Fibroblasts, and CD8 Tex cells as the cell populations undergoing the most substantial changes in the three biomarkers. Additionally, our study predicted seven potential medications for EM. Finally, the expression levels of the three biomarkers in clinical samples were validated through RT-qPCR and IHC, consistently aligning with the results obtained from the public database. Conclusion: we identified three biomarkers and constructed a diagnostic model for EM in this study, these findings provide valuable insights for subsequent mechanistic research and clinical applications in the field of endometriosis.

The AP2/ERF transcription factor ORA59 regulates ethylene-induced phytoalexin synthesis through modulation of an acyltransferase gene expression.

The gaseous ethylene (ET) and the oxylipin-derived jasmonic acid (JA) in plants jointly regulate an arsenal of pathogen responsive genes involved in defending against necrotrophic pathogens. The APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) transcription factor ORA59 is a major positive regulator of the ET/JA-mediated defense pathway in Arabidopsis thaliana. The Arabidopsis agmatine coumaroyltransferase (AtACT) catalyzes the formation of hydroxycinnamic acid amides (HCAAs) which are effective toxic antimicrobial substances known as phytoalexins and play an important role in plant defense response. However, induction and regulation of AtACT gene expression and HCAAs synthesis in plants remain less understood. Through gene coexpression network analysis, we identified a list of GCC-box cis-element containing genes that were coexpressed with ORA59 under diverse biotic stress conditions and might be potential downstream targets of this AP2/ERF-domain transcription factor. Particularly, ORA59 directly binds to AtACT gene promoter via the GCC-boxes and activates AtACT gene expression. The ET precursor 1-aminocyclopropane-1-carboxylic acid (ACC)-treatment significantly induces AtACT gene expression. Both ORA59 and members of the class II TGA transcription factors are indispensable for ACC-induced AtACT expression. Interestingly, the expression of AtACT is also subject to the signaling crosstalk of the salicylic acid- and ET/JA-mediated defense response pathways. In addition, we found that genes of the phenylpropanoid metabolism pathway were specifically induced by Botrytis cinerea. Taking together, these evidence suggest that the ET/JA signaling pathway activate the expression of AtACT to increase antimicrobial HCAAs production through the transcription factor ORA59 in response to the infection of necrotrophic plant pathogens.

Deuteration of Arylthianthren-5-ium Salts in CD3OD.

Deuteration of arylthianthren-5-ium triflates with CD3OD or CD3OD/CD3COCD3 in the presence of Cs2CO3 by palladium catalysis or photoirradiation allowed the convenient synthesis of deuterated arenes in good yields. The Pd-catalyzed reaction generally gave better yields than the photoinduced deuteration, but exceptions also exist. They could complement each other in some cases. These reactions featured eco-friendly conditions, simplicity, inexpensive deuterium sources, good functional group tolerance, and a range of substrates. Since arylthianthren-5-ium salts could be readily synthesized from arenes and thianthrene 5-oxide, this protocol provided a formal aromatic C-H deuteration with high selectivity, enabling efficient deuterium labeling of multifunctionalized arenes and drug molecules.

The Protective Effect of Evodiamine in Osteoarthritis: An In Vitro and In Vivo Study in Mice Model.

Osteoarthritis (OA) is a chronic disease with high economic burden characterized by cartilage degradation and joint inflammation. Evodiamine (EV), which can be extracted from Evodia rutaecarpa (Rutaceae), is a traditional Chinese medicine to treat inflammation, cardiovascular disorders, infection, and obesity. Studies have shown that EV can suppress the activation of immune cells and restrain the secretion of pro-inflammatory cytokines. However, it is still not well known about its role in the treatment of OA. In this study, we utilized interleukin-1ß (IL-1ß)-stimulated mouse chondrocytes in vitro and the destabilization of the medial meniscus (DMM) model in vivo to demonstrate the anti-inflammatory properties of EV in OA. The results suggested that EV decreased the generation of NO, IL-6, TNF-α, and PGE2. Meanwhile, the increased expression of iNOS, COX-2, and MMP-13 and the degradation of aggrecan and Col-II were significantly alleviated by EV in IL-1ß-activated mouse chondrocytes. Moreover, EV can inhibit the considerable IL-1ß-stimulated phosphorylation of the NF-κB signaling pathway and nuclear translocation of p65, compared with the control group. Furthermore, EV alleviated cartilage degeneration and reversed the increased Osteoarthritis Research Society International (OARSI) scores in the OA model in vivo. Our study demonstrates that EV can suppress inflammation in vitro and cartilage degeneration in vivo in OA, which implies that EV may be a potential candidate for the treatment of OA.

High-resolution cerebral blood flow simulation with a domain decomposition method and verified by the TCD measurement.

BACKGROUND: An efficient and accurate blood flow simulation can be useful for understanding many vascular diseases. Accurately resolving the blood flow velocity based on patient-specific geometries and model parameters is still a major challenge because of complex geomerty and turbulence issues. In addition, obtaining results in a short amount of computing time is important so that the simulation can be used in the clinical environment. In this work, we present a parallel scalable method for the patient-specific blood flow simulation with focuses on its parallel performance study and clinical verification. METHODS: We adopt a fully implicit unstructured finite element method for a patient-specific simulation of blood flow in a full precerebral artery. The 3D artery is constructed from MRI images, and a parallel Newton-Krylov method preconditioned with a two-level domain decomposition method is adopted to solve the large nonlinear system discretized from the time-dependent 3D Navier-Stokes equations in the artery with an integral outlet boundary condition. The simulated results are verified using the clinical data measured by transcranial Doppler ultrasound, and the parallel performance of the algorithm is studied on a supercomputer. RESULTS: The simulated velocity matches the clinical measured data well. Other simulated blood flow parameters, such as pressure and wall shear stress, are within reasonable ranges. The results show that the parallel algorithm scales up to 2160 processors with a 49% parallel efficiency for solving a problem with over 20 million unstructured elements on a supercomputer. For a standard cerebral blood flow simulation case with approximately 4 million finite elements, the calculation of one cardiac cycle can be finished within one hour with 1000 processors. CONCLUSION: The proposed method is able to perform high-resolution 3D blood flow simulations in a patient-specific full precerebral artery within an acceptable time, and the simulated results are comparable with the clinical measured data, which demonstrates its high potential for clinical applications.

One-step synthesis of site-specific antibody-drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates.

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Evaluation the loosening of abutment screws in fluid contamination: an in vitro study.

Screw loosening is one of the most common clinical problems of dental implants. Research on the influencing factors of screw loosening is very important to prevent screw loosening. The purpose of this in vitro study was to evaluate the influence of liquid contamination on the screw loosening. According to the contamination condition, forty-five abutment screws were divided into three groups (n = 15): no contamination, artificial saliva contamination, and mouthwash contamination. The preload and friction coefficient of the abutment screws were recorded. Then, the reverse torque values (RTVs) and settlement were measured after 3.0 × 105 and 6.0 × 105 cycles. The surface wear of the screws was analyzed. Finally, the stress distribution of the abutment screws was calculated by finite element analysis (FEA). The results showed that fluid contamination reduced the friction coefficient, increased the preload, decrease the settlement, improved resistance to screw loosening, and reduced wear on the thread surface. Appropriate antimicrobial lubrication may improve the anti-loosening performance of abutment screws and prevent excessive wear on the threaded surface.

Ti3C2Tx MXene-Coated Electrospun PCL Conduits for Enhancing Neurite Regeneration and Angiogenesis.

An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo. The results show that the NGCs have good biocompatibility in vitro. Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.

[Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology].

OBJECTIVE: To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbß3 on the surface of platelet membrane. METHODS: The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbß3 on the surface of platelet. RESULTS: The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbß3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05). CONCLUSION: A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Effect of central screw taper angles on the loosening performance and fatigue characteristics of dental implants.

Biomechanical performance plays an important role in the long-term service of dental implants. Loosening and fatigue damage of the central screw are the most common problems. This research investigated the effect of the central screw taper angle on the loosening performance and fatigue characteristics of dental implants. Central screws with four taper angles, 30°, 60°, 90° and 180°, were processed and tested. The loosening performance of the screws under initial and postload conditions was compared. Then, the fatigue characteristics of dental implants was measured. Finally, the wear and fracture modes of the screws were observed. The damage locations were verified by finite element analysis (FEA). The results showed that the central screws with 30° taper had substantially better anti-loosening performance and less fretting wear. The central screws with 180° taper had a higher preload, resulting in a longer fatigue life. Furthermore, the fatigue fracture of the central screw occurred at the level of the first thread position, consistent with the FEA results. In the future clinical applications, central screws with a 30° taper angle may improve anti-loosening performance and prolong fatigue life by increasing the tightening torque.

Fatigue properties of plasma nitriding for dental implant application.

STATEMENT OF PROBLEM: Fatigue failure of implant components is a common clinical problem. Plasma nitriding, an in situ surface-strengthening method, may improve fatigue properties of dental implants. PURPOSE: The purpose of this in vitro study was to evaluate the effect of plasma nitriding on the fatigue behavior of implant systems. MATERIAL AND METHODS: The preload and friction coefficient of plasma nitrided abutment screws, as well as settlement of the implant-abutment interface, were measured. Then, the reverse torque values and pullout force were evaluated after cyclic loading. Finally, the fatigue properties of the implant system were investigated with static fracture and dynamic fatigue life tests, and the morphology of the fracture on the surface of the implant system was observed. RESULTS: The plasma nitriding treatment reduced the friction coefficient; increased the preload, settlement value, reverse torque values, pullout force, and static fracture load; and prolonged fatigue life. Furthermore, abutment screws with plasma nitriding treatment showed a different fatigue fracture mode. CONCLUSIONS: Plasma nitriding improved mechanical performance and may be a suitable way to optimize the fatigue behavior of dental implants.

Impact of intraoperative intravenous magnesium on spine surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effectiveness and safety of intraoperative intravenous magnesium (IIM) on spine surgery remain uncertain, as recent randomized controlled trials (RCTs) yielded conflicting results. The purpose of this study was to determine the impact of IIM on spine surgery. METHODS: A literature search was performed on multiple electronic databases, ClinicalTrial.gov and Google Scholar on July 12th 2021, and reference lists were examined. We selected RCTs comparing the effects of IIM with placebo treatment on spine surgery. We calculated pooled standard mean difference (SMD) or risk ratio (RR) with 95% confident interval (CI) under a random-effect model. We assessed risk of bias using Cochrane risk-of-bias tool and Jadad score was applied to assess the quality of each included trial. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to determine the confidence in effect estimates. Sensitivity analysis was conducted by omitting each included study one by one from the pooled analysis. PROSPERO Registration: CRD42021266170. FINDINGS: Fourteen trials of 781 participants were included. Low- to moderate-quality evidence suggested that IIM reduces postoperative morphine consumption at 24 h (SMD: -1·61 mg, 95% CI: -2·63 to -0·58) and intraoperative remifentanil requirement (SMD: -2·09 ug/h, 95% CI: -3·38 to -0·81). High-quality evidence suggested that IIM reduces the risk of postoperative nausea and vomiting compared with placebo (RR: 0·43, 95% CI: 0·26 to 0·71). Besides, moderate-quality evidence suggested that recovery orientation time in the IIM group is longer than control group (SMD: 1·13 min, 95% CI: 0·83 to 1·43). INTERPRETATION: IIM as adjuvant analgesics showed overall benefits on spine surgery in terms of reducing analgesic requirement and postoperative nausea and vomiting; however, potential risks of IIM, such as delayed anesthetic awakening, should not be ignored. Future evidence will inform the optimal strategy of IIM administration for patients undergoing spine surgery. FUNDING: This study was funded by Beijing Municipal Natural Science Foundation (Grant No :7212117).

Long non-coding RNA HAGLROS promotes the development of diffuse large B-cell lymphoma via suppressing miR-100.

BACKGROUND: Long non-coding RNAs (lncRNAs), a vital component of functional regulators, are involved in various human cancers development, including diffuse large B-cell lymphoma (DLBCL). In particular, lncRNA HAGLROS has been reported to be associated with several types of cancer in humans. Nevertheless, the role of HAGLROS in DLBCL has yet to be described. METHODS: The HAGLROS expression patterns and its relationship with clinicopathological features and survival were investigated in DLBCL patients. CCK-8 and transwell assays were used to analyze the cell proliferation, migration, and invasion capacities. AGO2-RIP, dual-luciferase assay, RT-qPCR, and rescue experiments were fulfilled to measure the physical interaction between HAGLROS and miR-100. Xenograft assay was conducted to test tumor growth ability. RESULTS: HAGLROS was upregulated in DLBCL tissues and cells, and closely associated with advanced clinicopathological features. Upregulation of HAGLROS resulted in poor survival outcomes in DLBCL patients. In addition, HAGLROS knockdown inhibited the proliferation, migration, and invasion of DLBCL cells in vitro. Further experiments revealed that HAGLROS negatively regulated the expression of miR-100 in DLBCL, and the expression of miR-100 and HAGLROS showed an inverse correlation in DLBCL tissues. HAGLROS functioned as a competing endogenous RNA for miR-100 in DLBCL cells, and miR-100 overexpression abolished the oncogenic effects of HAGLROS upregulation on DLBCL progression. Besides, in-vivo assays revealed that HAGLROS knockdown suppressed tumor growth in nude mice. CONCLUSION: HAGLROS overexpression contributes to DLBCL development and poor prognosis via targeting miR-100, which could be a potential prognostic biomarker and therapeutic target for DLBCL patients.