A bio-orthogonal linear ubiquitin probe identifies STAT3 as a direct substrate of OTULIN in glioblastoma.

While linear ubiquitin plays critical roles in multiple cell signaling pathways, few substrates have been identified. Global profiling of linear ubiquitin substrates represents a significant challenge because of the low endogenous level of linear ubiquitination and the background interference arising from highly abundant ubiquitin linkages (e.g. K48- and K63-) and from the non-specific attachment of interfering proteins to the linear polyubiquitin chain. We developed a bio-orthogonal linear ubiquitin probe by site-specific encoding of a norbornene amino acid on ubiquitin (NAEK-Ub). This probe facilitates covalent labeling of linear ubiquitin substrates in live cells and enables selective enrichment and identification of linear ubiquitin-modified proteins. Given the fact that the frequent overexpression of the linear linkage-specific deubiquitinase OTULIN correlates with poor prognosis in glioblastoma, we demonstrated the feasibility of the NAEK-Ub strategy by identifying and validating substrates of linear ubiquitination in patient-derived glioblastoma stem-like cells (GSCs). We identified STAT3 as a bona fide substrate of linear ubiquitin, and showed that linear ubiquitination negatively regulates STAT3 activity by recruitment of the phosphatase TC-PTP to STAT3. Furthermore, we demonstrated that preferential expression of OTULIN in GSCs restricts linear ubiquitination on STAT3 and drives persistent STAT3 signaling, and thereby maintains the stemness and self-renewal of GSCs.

Rapid discrimination of four Salmonella enterica serovars: A performance comparison between benchtop and handheld Raman spectrometers.

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.

Efficient generation of endogenous protein reporters for mouse development.

Fluorescent proteins and epitope tags can reveal protein localization in cells and animals, yet the large size of many tags hinders efficient genome targeting. Accordingly, many studies have relied on characterizing overexpressed proteins, which might not recapitulate endogenous protein activities. Here, we present two strategies for higher throughput production of endogenous protein reporters in mice, focusing on the blastocyst model of development. Our first strategy makes use of a split fluorescent protein, mNeonGreen2 (mNG2). Knock-in of a small portion of the mNG2 gene, in frame with gene coding regions of interest, was highly efficient in embryos, potentially obviating the need to establish mouse lines. When complemented by the larger portion of the mNG2 gene, fluorescence was reconstituted and endogenous protein localization faithfully reported in living embryos. Our second strategy achieves in-frame knock-in of a relatively small protein tag, which provides high efficiency and higher sensitivity protein reporting. Together, these two approaches provide complementary advantages and enable broad downstream applications.

Shape Anisotropy-Governed High-Performance Nanomagnetosol for In Vivo Magnetic Particle Imaging of Lungs.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has shown extensive lung manifestations in vulnerable individuals, putting lung imaging and monitoring at the forefront of early detection and treatment. Magnetic particle imaging (MPI) is an imaging modality, which can bring excellent contrast, sensitivity, and signal-to-noise ratios to lung imaging for the development of new theranostic approaches for respiratory diseases. Advances in MPI tracers would offer additional improvements and increase the potential for clinical translation of MPI. Here, a high-performance nanotracer based on shape anisotropy of magnetic nanoparticles is developed and its use in MPI imaging of the lung is demonstrated. Shape anisotropy proves to be a critical parameter for increasing signal intensity and resolution and exceeding those properties of conventional spherical nanoparticles. The 0D nanoparticles exhibit a 2-fold increase, while the 1D nanorods have a > 5-fold increase in signal intensity when compared to VivoTrax. Newly designed 1D nanorods displayed high signal intensities and excellent resolution in lung images. A spatiotemporal lung imaging study in mice revealed that this tracer offers new opportunities for monitoring disease and guiding intervention.

Obtaining Lower Query Complexities Through Lightweight Zeroth-Order Proximal Gradient Algorithms.

Zeroth-order (ZO) optimization is one key technique for machine learning problems where gradient calculation is expensive or impossible. Several variance, reduced ZO proximal algorithms have been proposed to speed up ZO optimization for nonsmooth problems, and all of them opted for the coordinated ZO estimator against the random ZO estimator when approximating the true gradient, since the former is more accurate. While the random ZO estimator introduces a larger error and makes convergence analysis more challenging compared to coordinated ZO estimator, it requires only O(1) computation, which is significantly less than O(d) computation of the coordinated ZO estimator, with d being dimension of the problem space. To take advantage of the computationally efficient nature of the random ZO estimator, we first propose a ZO objective decrease (ZOOD) property that can incorporate two different types of errors in the upper bound of convergence rate. Next, we propose two generic reduction frameworks for ZO optimization, which can automatically derive the convergence results for convex and nonconvex problems, respectively, as long as the convergence rate for the inner solver satisfies the ZOOD property. With the application of two reduction frameworks on our proposed ZOR-ProxSVRG and ZOR-ProxSAGA, two variance-reduced ZO proximal algorithms with fully random ZO estimators, we improve the state-of-the-art function query complexities from Omindn1/2ε2,dε3 to O˜n+dε2 under d>n12 for nonconvex problems, and from Odε2 to O˜nlog1ε+dε for convex problems. Finally, we conduct experiments to verify the superiority of our proposed methods.

Direct visualization and 3D reconstruction of conductive filaments in aSiO2 material-based memristive device.

Observation of conductive filaments has greatly aided the development of theoretical models of memristive devices. In this work, we visualized and reconstructed the conductive filaments in a Cu/Cu-doped SiO2/W device employing a focused ion beam (FIB) as a milling technique. The SEM images taken from the device after 150 DC sweep cycles showed that Joule heat played a vital role in determining the morphology of a conductive filament, where the vaporization of the conductive filament resulted in the creation of defects, including particles, voids, and cavities. The competition between the formation and vaporization of conductive filaments generally induces a remarkable current fluctuation. Since Cu-doped SiO2 was utilized as the electrolyte, the vapors exfoliated adjacent single layers. FIB milling proceeded in top-down and front-back modes; thus, a 3D model of conductive filaments and defects was constructed according to a series of FIB-SEM images. This methodology is promising for a future failure analysis of memristive devices.

Differential Analysis of Blood Routine Examination Parameters in Patients with Upper Gastrointestinal Bleeding and Lower Gastrointestinal Bleeding.

Background: This study addresses the critical need for differentiating between upper and lower gastrointestinal bleeding by focusing on blood routine parameters to enhance diagnostic precision. Objective: This study aims to identify and compare specific blood routine parameters to determine their efficacy in distinguishing between upper and lower gastrointestinal bleeding for improved clinical decision-making. Methods: This retrospective study analyzed 119 patients with gastrointestinal bleeding (GIB) admitted to our hospital between January 2017 and June 2020. Among them, 86 were diagnosed with upper GIB (UGIB) and 33 with lower GIB (LGIB). After admission, peripheral blood samples were collected for a comprehensive blood routine examination, including white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), blood urea nitrogen (BUN), creatinine (Cr), and BUN to Cr ratio (BUN/Cr ratio). Differences in blood routine parameters were compared between the UGIB and LGIB groups. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the efficacy of blood routine examinations in differentiating between UGIB and LGIB. Results: The study revealed no significant differences in WBC and Cr levels between LGIB and UGIB patients (P > .05). However, UGIB patients exhibited statistically lower levels of RBC, Hb, and PLT, along with higher BUN and BUN/Cr ratio levels compared to LGIB patients (P < .05). Pearson correlation coefficient analysis indicated an inverse correlation of BUN/Cr with RBC, Hb, and PLT in GIB patients and a positive association between BUN/Cr and BUN (P < .05). ROC analysis demonstrated that RBC, Hb, PLT, BUN, and BUN/Cr ratios were effective in distinguishing UGIB from LGIB (P < .05). Conclusions: Blood routine parameters, including RBC, Hb, PLT, BUN, and BUN/Cr ratio, are valuable in differentiating between UGIB and LGIB. These parameters can serve as early evaluation indexes for GIB, facilitating timely intervention and treatment to enhance therapeutic outcomes.

Clinical practice of sepsis-induced immunosuppression: Current immunotherapy and future options.

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

ARL9 is upregulated and serves as a biomarker for a poor prognosis in colon adenocarcinoma.

BACKGROUND: ARL9 is a newly identified member of the ARF family, and the clinical significance of ARL9 in colon adenocarcinoma is unknown. In this study, we aimed to explore the expression of ARL9 mRNA in colon adenocarcinoma, and its effect on the prognosis of patients with colon adenocarcinoma. METHODS: We investigated the differential expression of ARL9 between colon adenocarcinoma tissue and adjacent tissues through a bioinformatics analysis using The Cancer Genome Atlas (TCGA) database. The correlation between clinical characteristics and the mRNA expression level of ARL9 were analyzed. A survival analysis and a Cox regression analysis were used to determine the prognostic significance of ARL9. Finally, we conducted a gene set enrichment analysis (GSEA) to explore the ARL9 signaling pathways involved in the development of colon adenocarcinoma. The effect of the expression of ARL9 on the proliferation and migration of colon adenocarcinoma was analyzed by the CCK8 method and a cell scratch test, respectively. RESULTS: The mRNA expression of ARL9 in colon adenocarcinoma tissues was higher in comparison to the level in normal adjacent tissues (P < 0.05). The mRNA expression of ARL9 was not related to sex, tumor stage, T stage, N stage, M stage, but to age. The 5-year survival rate of colon adenocarcinoma patients with high ARL9 mRNA expression levels was significantly lower than that of patients with low ARL9 mRNA expression levels (P < 0.05). Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. The GSEA suggested that ARL9 may be able to upregulate cell adhesion, extracellular matrix receptor interactions, tumor-associated pathways, and downregulate the citrate cycle and tricarboxylic acid cycle pathway, which are involved in the development of colon adenocarcinoma. After knocking down ARL9, the proliferation and migration abilities of colon adenocarcinoma cells were decreased (P < 0.01). CONCLUSION: The mRNA expression of ARL9 is upregulated in colon adenocarcinoma, and higher mRNA expression levels are associated with a poor prognosis. Knocking down ARL9 can reduce the proliferation and migration of colon adenocarcinoma cells. ARL9 mRNA can be used as a prognostic biomarker in patients with colon adenocarcinoma.

A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients.

There is an urgent need for effective treatment and preventive vaccine to contain this devastating global pandemic, which requires a comprehensive understanding of humoral responses specific to SARS-CoV-2 during the disease progression and convalescent phase of COVID-19 patients. We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. Most patients generated humoral responses against NP and spike protein-related antigens but with their distinct kinetics profiles. Combined detection of NP and ECD antigens as detecting antigen synergistically improved the sensitivity of the serological assay, compared to that of using NP or RBD as detection antigen. 80.7% of convalescent sera from COVID-19 patients revealed that the varying extents of neutralization activities against SARS-CoV-2. S1-specific and ECD-specific IgA responses were strongly correlated with the neutralization activities in non-severe patients, but not in severe patients. Moreover, the neutralizing activities of the convalescent sera were shown to significantly decline during the period between 21 days to 28 days after hospital discharge, accompanied by a substantial drop in RBD-specific IgA response. Our data provide evidence that are crucial for serological testing, antibody-based intervention, and vaccine design of COVID-19.

Distribution and clinical significance of circulating CD8+CD28- regulatory T cells in the peripheral blood of patients with pulmonary tuberculosis.

BACKGROUND: Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8+CD28- Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8+CD28- Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis. METHODS: Flow cytometry, sputum smears and computed tomography imaging were used to analyze the distribution characteristics of CD8+CD28- Treg cells in the peripheral blood of patients with PTB and the correlation between CD8+CD28-Treg cells and clinical and immune indices. RESULTS: The percentages of CD4+CD25high and CD8+CD28- Treg cells in the peripheral blood of patients with PTB were significantly higher than those in the healthy control (HC) group. Further analysis showed that the percentage of CD4+CD25highTreg cells in the Stage II group was significantly higher than that in the HC group. The percentages of CD4+CD25high and CD8+CD28- Treg cells increased significantly in patients in the Stage II group. The proportion of CD8+CD28- Treg cells was directly proportional to the degree of positivity in sputum smears, while CD4+CD25highTreg cells did not exhibit this trend. The correlations between the percentage of CD4+CD25high and CD8+CD28- Treg cells and the percentage of lymphocyte subsets were examined. The percentage of CD8+CD28- Treg cells was negatively correlated with the percentage of CD4+T cells and positively correlated with the CD8+T cell percentage in the HC and PTB groups. The percentage of CD4 + CD25highTreg cells was positively correlated with the percentage of CD4+T cells only in the PTB group. CONCLUSIONS: This study was the first to show that the proportion of CD8+CD28- Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8+CD28- Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.

Comparative efficacy of traditional conservative treatment and CT-guided local chemotherapy for mild spinal tuberculosis.

BACKGROUND: There are considerable differences in the treatment strategy for spinal tuberculosis, including conservative or surgical procedures. Conservative treatment is always suitable for most patients. This study aimed to compare the clinical efficacy of traditional conservative treatment with CT-guided local chemotherapy strategy of mild spinal tuberculosis. METHODS: This research retrospectively analysed 120 patients with spinal tuberculosis between January 2005 and January 2016 according to the diagnostic criteria of mild spinal tuberculosis. In total, 89 patients underwent traditional conservative treatment, 31 underwent CT-guided local chemotherapy. Clinical outcome, laboratory indexes, and radiological results were analysed to provide a clinical basis for the choice of mild spinal tuberculosis treatment. RESULTS: All cases achieved a clinical cure with 24 to 50 months followed up. Cobb angle of the two groups spinal tuberculosis segments was 6.25 ± 3.1100B0, 5.69 ± 2.5800B0 before treatment and 12.36 ± 6.3100B0, 14.87 ± 7.2600B0 after treatment, respectively. The VAS scores were significantly decreased post-treatment. At the 1 month follow-up, the VAS scores and erythrocyte sedimentation rate (ESR) were significantly differences between the two groups. The efficacy in the CT-guided local chemotherapy (Group B) was better than the traditional conservative treatment (Group A). But from the 3 months follow-up to the last follow-up, the VAS scores and ESR was no significant differences between the two groups and the average ESR decreased to normal. There was no evident kyphosis, symptoms or neurological deficits at the final follow-up. The paravertebral abscesses had disappeared, with no significant progression of local kyphosis, significant absorption and clear lesion edges, pain relief and normal ESR in the two groups. CONCLUSIONS: For mild spinal tuberculosis, traditional conservative treatment can achieve satisfactory results. The strategy combined with CT-guided local chemotherapy treatment is minimally invasive, beneficial for the drainage of paravertebral abscesses and pain relief.

Reconstruction of Large Cervicofacial Defects With Expanded Island Superficial Temporal Artery Flaps and an 810-nm Diode Laser Hair Removal Technique.

BACKGROUND: Extensive cervicofacial reconstruction is challenging for plastic surgeons. Because of the location of the adjacent scalp flap nourished by the superficial temporal artery (STA), it can be a candidate for cervicofacial reconstruction. OBJECTIVES: This article aims to report a combined treatment of an expanded island STA flap and an 810-nm diode laser hair removal technique for extensive cervicofacial defects. METHODS: Between January 2015 and December 2018, 10 patients with lower face and neck scar contraction were reconstructed with a bilateral or unilateral expanded STA island flap and an 810-nm diode laser for hair removal in this retrospective study. Hair removal via the 810-nm laser was started when the injected volume reached the volume of the expander, with a fluence of 35 to 40 J/cm2 and a 1 to 2 Hz repetition rate. Before second-stage surgery, the hair reduction rate was assessed. Twelve months after surgery, the degree of epilation efficacy according to the satisfaction scale and Global Aesthetic Improvement Scale was evaluated. RESULTS: This study included 2 single-pedicle flaps and 8 double-pedicle flaps. The average size of the implanted expanders was 600 mL. The average injected volume was 1405 mL. Before second surgery, there was a 67.4% hair reduction rate. Twelve months after surgery, the results of Global Aesthetic Improvement Scale were very good (3), good (6), average (1), and poor (0). CONCLUSIONS: The expanded island STA flap and 810-nm diode laser technique may be a novel treatment option for severe face and neck aesthetic reconstruction.

Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma.

CONTEXT: Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). OBJECTIVE: To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. MATERIALS AND METHODS: We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. RESULTS: SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (-72%), PIK3R1 (-40%), and COL3A1 (-65%) compared with OVA + LPS. CONCLUSIONS: Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA.

Effect of Deep Versus Moderate Neuromuscular Block on Pain After Laparoscopic Colorectal Surgery: A Randomized Clinical Trial.

BACKGROUND: Anesthesia with deep neuromuscular block for laparoscopic surgery may result in less postoperative pain with lower intra-abdominal pressure. However, results in the existing literature are controversial. OBJECTIVE: The study aimed to evaluate the effect of deep neuromuscular block on postoperative pain at rest and during coughing after laparoscopic colorectal surgery. DESIGN: The design is a parallel-group, randomized clinical trial. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: Patients undergoing laparoscopic resection of colorectal tumors were included. INTERVENTIONS: Patients were randomly assigned to either a deep (posttetanic count 1 to 2) or moderate (train-of-four 1 to 2) neuromuscular group. MAIN OUTCOME MEASURES: The coprimary efficacy outcomes were numeric rating scale scores of the postoperative pain at rest and during coughing after surgery. RESULTS: Pain was lower in the deep neuromuscular block group at rest and during coughing at 1, 6, 24, and 48 hours after surgery (median difference of 2 points and 1 point at 1 h; p < 0.001 at each time point). The deep neuromuscular block group displayed a significantly lower number of bolus attempts by the patient (4 in the deep group vs 9 in the moderate group; p < 0.001) and boluses delivered (4 in the deep group vs 9 in the moderate group; p < 0.001) on postoperative day 1. The number of rescue analgesics was lower in the deep group on postoperative day 2 (p < 0.001). The deep neuromuscular block group showed a lower frequency of postoperative nausea and vomiting (p = 0.02) and lower intraoperative intra-abdominal pressure (p < 0.001). LIMITATIONS: This was a single-center study. CONCLUSIONS: Deep neuromuscular block resulted in better pain relief and lower opioid consumption and use of rescue analgesics after laparoscopic colorectal surgery. Deep neuromuscular block was associated with less postoperative nausea and vomiting and facilitated the use of lower intra-abdominal pressure in laparoscopic surgery. See Video Abstract at http://links.lww.com/DCR/B458. EFECTO DEL BLOQUEO NEUROMUSCULAR PROFUNDO VERSUS MODERADO EN EL DOLOR, DESPUS DE LA CIRUGA COLORRECTAL LAPAROSCPICA UN ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La anestesia con bloqueo neuromuscular profunda para cirugía laparoscópica, puede resultar con menor dolor postoperatorio y con menos presión intraabdominal. Sin embargo, los resultados en la literatura existente son controvertidos.OBJETIVO:El objetivo del estudio, fue evaluar el efecto del bloqueo neuromuscular profundo en dolor postoperatorio de reposo y con la tos, después de cirugía colorrectal laparoscópica.DISEÑO:Ensayo clínico aleatorizado de grupos paralelos.AJUSTE:El estudio se realizó en un centro de atención terciaria.PACIENTES:Se incluyeron pacientes sometidos a resección laparoscópica de tumores colorrectales.INTERVENCIONES:Los pacientes fueron aleatorizados a un grupo neuromuscular profundo (recuento posttetánico 1 a 2) o moderado (tren de cuatro 1 a 2).PRINCIPALES MEDIDAS DE RESULTADO:Los resultados coprimarios de eficacia, fueron las puntuaciones numéricas en la escala de calificación del dolor postoperatorio en reposo y durante la tos, después de la cirugía.RESULTADOS:El dolor fue menor en el grupo de bloqueo neuromuscular profundo en reposo y durante la tos, en 1, 6, 24, 48 horas después de la cirugía, (diferencia de mediana de 2 puntos y 1 punto respectivamente en 1 hora; p <0,001 en cada punto de tiempo). El grupo de bloqueo neuromuscular profundo, mostró un número significativamente menor de intentos de bolo por parte del paciente, (4 en el grupo profundo versus 9 del grupo moderado, p <0,001) y de bolos administrados (4 en el grupo profundo versus 9 en el grupo moderado, p <0,001) en el primer día postoperatorio. El número de analgésicos de rescate, fue menor en el grupo profundo en el segundo día postoperatorio (p <0,001). El grupo de bloqueo neuromuscular profundo, mostró una menor frecuencia de náuseas y vómitos postoperatorios (p = 0,02) y una menor presión intraoperatoria e intraabdominal (p <0,001).LIMITACIONES:Este estudio fue un estudio de un solo centro.CONCLUSIONES:El bloqueo neuromuscular profundo, resultó en mayor alivio del dolor y menor consumo de opioides y uso de analgésicos de rescate, después de la cirugía colorrectal laparoscópica. El bloqueo neuromuscular profundo, se asoció con menos náuseas y vómitos posoperatorios y facilitó el uso de una presión intraabdominal más baja, en la cirugía laparoscópica. Consulte Video Resumen en http://links.lww.com/DCR/B458.

Asperfloketals A and B, the First Two Ergostanes with Rearranged A and D Rings: From the Sponge-Associated Aspergillus flocculosus 16D-1.

Asperfloketals A (1) and B (2), two 1(10 → 6)-abeo-14,15-secosteroids featuring a novel trioxahexaheterocyclic ring system, were isolated from the sponge-associated fungus Aspergillus flocculosus 16D-1. Their structures were elucidated by extensive spectroscopic analysis and NMR chemical shifts calculations, supported by DP4+ probability analysis, and their absolute configurations were determined by ECD calculations and the modified Mosher's method. Asperfloketals A and B showed strong anti-inflammatory activity in the CuSO4-induced transgenic fluorescent zebrafish but displayed no cytotoxicity against HeLa, HepG2, and SW480 cell lines.

B cell lymphoma with IRF4 rearrangement: A clinicopathological study of 13 cases.

Interferon regulatory factor 4 (IRF4) rearrangement is commonly detected in patients with a range of lymphoproliferative malignancies, including myelomas, large B cell lymphomas and low-grade B cell neoplasms. However, IRF4 rearrangement is generally a relatively rare finding in these latter two cancer types. In the present article, we describe and summarize the clinicopathological and genetic features of 13 cases of B cell lymphoma with IRF4 rearrangement, including 12 cases of large B cell lymphoma and one case of low-grade lymphoma exhibiting such rearrangement. These cases were detected in six females and seven males between 14 and 71 years of age. From a morphological perspective, large B cell lymphoma tumors included in this analysis exhibited large neoplastic cells in diffuse or follicular patterns, while the case of low-grade lymphoma mainly composed of small lymphocytes. All analyzed cases exhibited a split in the IRF4 gene consistent with IRF4 translocation. Three of six analyzed large B cell lymphoma cases harbored IGLL5 mutations. Mutations in SAMHD1 were detected in the low-grade lymphoma with IRF4 rearrangement case. In summary, our results offer further insight into the morphological and molecular heterogeneity of cases of B cell lymphoma exhibiting IRF4 rearrangements.

[Research progress and prospect of collaborative brain-computer interface for group brain collaboration].

As the most common active brain-computer interaction paradigm, motor imagery brain-computer interface (MI-BCI) suffers from the bottleneck problems of small instruction set and low accuracy, and its information transmission rate (ITR) and practical application are severely limited. In this study, we designed 6-class imagination actions, collected electroencephalogram (EEG) signals from 19 subjects, and studied the effect of collaborative brain-computer interface (cBCI) collaboration strategy on MI-BCI classification performance, the effects of changes in different group sizes and fusion strategies on group multi-classification performance are compared. The results showed that the most suitable group size was 4 people, and the best fusion strategy was decision fusion. In this condition, the classification accuracy of the group reached 77%, which was higher than that of the feature fusion strategy under the same group size (77.31% vs. 56.34%), and was significantly higher than that of the average single user (77.31% vs. 44.90%). The research in this paper proves that the cBCI collaboration strategy can effectively improve the MI-BCI classification performance, which lays the foundation for MI-cBCI research and its future application.

MiR-27b-3p suppresses glioma development via targeting YAP1.

Previous studies have reported that miRNAs are involved in the progression of glioma, and that miR-27b-3p is involved in a variety of cancers. However, whether miR-27b-3p has a role in glioma is still unknown. Here, we demonstrated that miR-27b-3p is downregulated in glioma, and this is associated with the development of glioma. Overexpression of miR-27b-3p in glioma cells inhibits cell proliferation and migration, and induces cell apoptosis, which suppresses the progression of glioma. Furthermore, in our study, overexpression of miR-27b-3p also inhibited the growth of xenografted glioma tumors in-vivo. Finally, we verified that Yes Associated Protein 1 (YAP1) is the downstream target of miR-27b-3p, and that miR-27b-3p controls the proliferation, migration, and apoptosis of glioma cells via regulating YAP1. Our study reveals a novel mechanism through which miR-27b-3p functions in the development of glioma, and thus provides a potential therapeutic target for the treatment of glioma.

Collaborative Cross mice reveal extreme epilepsy phenotypes and genetic loci for seizure susceptibility.

OBJECTIVE: Animal studies remain essential for understanding mechanisms of epilepsy and identifying new therapeutic targets. However, existing animal models of epilepsy do not reflect the high level of genetic diversity found in the human population. The Collaborative Cross (CC) population is a genetically diverse recombinant inbred panel of mice. The CC offers large genotypic and phenotypic diversity, inbred strains with stable genomes that allow for repeated phenotypic measurements, and genomic tools including whole genome sequence to identify candidate genes and candidate variants. METHODS: We evaluated multiple complex epileptic traits in a sampling of 35 CC inbred strains using the flurothyl-induced seizure and kindling paradigm. We created an F2 population of 297 mice with extreme seizure susceptibility and performed quantitative trait loci (QTL) mapping to identify genomic regions associated with seizure sensitivity. We used quantitative RNA sequencing from CC hippocampal tissue to identify candidate genes and whole genome sequence to identify genetic variants likely affecting gene expression. RESULTS: We identified new mouse models with extreme seizure susceptibility, seizure propagation, epileptogenesis, and SUDEP (sudden unexpected death in epilepsy). We performed QTL mapping and identified one known and seven novel loci associated with seizure sensitivity. We combined whole genome sequencing and hippocampal gene expression to pinpoint biologically plausible candidate genes (eg, Gabra2) and variants associated with seizure sensitivity. SIGNIFICANCE: New mouse models of epilepsy are needed to better understand the complex genetic architecture of seizures and to identify therapeutics. We performed a phenotypic screen utilizing a novel genetic reference population of CC mice. The data we provide enable the identification of protective/risk genes and novel molecular mechanisms linked to complex seizure traits that are currently challenging to study and treat.