Antibody inhibition of influenza A virus assembly and release.

Antibodies are frontline defenders against influenza virus infection, providing protection through multiple complementary mechanisms. Although a subset of monoclonal antibodies (mAbs) has been shown to restrict replication at the level of virus assembly and release, it remains unclear how potent and pervasive this mechanism of protection is, due in part to the challenge of separating this effect from other aspects of antibody function. To address this question, we developed imaging-based assays to determine how effectively a broad range of mAbs against the IAV surface proteins can specifically restrict viral egress. We find that classically neutralizing antibodies against hemagglutinin are broadly multifunctional, inhibiting virus assembly and release at concentrations 1-20-fold higher than the concentrations at which they inhibit viral entry. These antibodies are also capable of altering the morphological features of shed virions, reducing the proportion of filamentous particles. We find that antibodies against neuraminidase and M2 also restrict viral egress and that inhibition by anti-neuraminidase mAbs is only partly attributable to a loss in enzymatic activity. In all cases, antigen crosslinking-either on the surface of the infected cell, between the viral and cell membrane, or both-plays a critical role in inhibition, and we are able to distinguish between these modes experimentally and through a structure-based computational model. Together, these results provide a framework for dissecting antibody multifunctionality that could help guide the development of improved therapeutic antibodies or vaccines and that can be extended to other viral families and antibody isotypes.IMPORTANCEAntibodies against influenza A virus provide multifaceted protection against infection. Although sensitive and quantitative assays are widely used to measure inhibition of viral attachment and entry, the ability of diverse antibodies to inhibit viral egress is less clear. We address this challenge by developing an imaging-based approach to measure antibody inhibition of virus release across a panel of monoclonal antibodies targeting the influenza A virus surface proteins. Using this approach, we find that inhibition of viral egress is common and can have similar potency to the ability of an antibody to inhibit viral entry. Insights into this understudied aspect of antibody function may help guide the development of improved countermeasures.

Mitochondria-targeted BODIPY dyes for small molecule recognition, bio-imaging and photodynamic therapy.

Mitochondria are essential for a diverse array of biological functions. There is increasing research focus on developing efficient tools for mitochondria-targeted detection and treatment. BODIPY dyes, known for their structural versatility and excellent spectroscopic properties, are being actively explored in this context. Numerous studies have focused on developing innovative BODIPYs that utilize optical signals for imaging mitochondria. This review presents a comprehensive overview of the progress made in this field, aiming to investigate mitochondria-related biological events. It covers key factors such as design strategies, spectroscopic properties, and cytotoxicity, as well as mechanism to facilitate their future application in organelle imaging and targeted therapy. This work is anticipated to provide valuable insights for guiding future development and facilitating further investigation into mitochondria-related biological sensing and phototherapy.

Click Chemistry-Based Force Spectroscopy Revealed Enhanced Binding Dynamics of Phosphorylated HMGB1 to Cisplatin-DNA.

Cisplatin, a cornerstone in cancer chemotherapy, is known for its DNA-binding capacity and forms lesions that lead to cancer cell death. However, the repair of these lesions compromises cisplatin's effectiveness. This study investigates how phosphorylation of HMGB1, a nuclear protein, modifies its binding to cisplatin-modified DNA (CP-DNA) and thus protects it from repair. Despite numerous methods for detecting protein-DNA interactions, quantitative approaches for understanding their molecular mechanism remain limited. Here, we applied click chemistry-based single-molecule force spectroscopy, achieving high-precision quantification of the interaction between phosphorylated HMGB1 and CP-DNA. This method utilizes a synergy of click chemistry and enzymatic ligation for precise DNA-protein immobilization and interaction in the system. Our results revealed that HMGB1 binds to CP-DNA with a significantly high rupture force of ∼130 pN, stronger than most natural DNA-protein interactions and varying across different DNA sequences. Moreover, Ser14 is identified as the key phosphorylation site, enhancing the interaction's kinetic stability by 35-fold. This increase in stability is attributed to additional hydrogen bonding suggested by molecular dynamics (MD) simulations. Our findings not only reveal the important role of phosphorylated HMGB1 in potentially improving cisplatin's therapeutic efficacy but also provide a precise method for quantifying protein-DNA interactions.

Reconfiguration, Welding, Reprogramming, and Complex Shape Transformation of An Optical Shape Memory Polymer Network Enabled by Patterned Secondary Crosslinking.

Stimuli-triggered generation of complicated 3D shapes from 2D strips or plates without using sophisticated molds is desirable and achieving such 2D-to-3D shape transformation in combination with shape reconfiguration, welding, and reprogramming on a single material is very challenging. Here, a convenient and facile strategy using the solution of a disulfide-containing diamine for patterned secondary crosslinking of an optical shape-memory polymer network is developed to integrate the above performances. The dangling thiolectones attached to the backbones react with the diamine in the solution-deposited region so that the secondary crosslinking may not only weld individual strips into assembled 3D shapes but also suppress the relaxation of the deformed polymer chains to different extents for shape reconfiguration or heating-induced complex 3D deformations. In addition, as the dynamic disulfide bonds can be thermally activated to erase the initial programming information and the excessive thiolectones are available for subsequent patterned crosslinking, the material also allows shape reprogramming. Combining welding with patterning treatment, it is further demonstrated that a gripper can be assembled and photothermally controlled to readily grasp an object.

Fluorescent Probes for Biological Species and Microenvironments: from Rational Design to Bioimaging Applications.

Some important biological species and microenvironments maintain a complex and delicate dynamic balance in life systems, participating in the regulation of various physiological processes and playing indispensable roles in maintaining the healthy development of living bodies. Disruption of their homeostasis in living organisms can cause various diseases and even death. Therefore, real time monitoring of these biological species and microenvironments during different physiological and pathological processes is of great significance. Fluorescent-probe-based techniques have been recognized as one of the most powerful tools for real time imaging in biological samples. In this Account, we introduce the representative works from our group in the field of fluorescent probes for biological imaging capable of detecting metal ions, small bioactive molecules, and the microenvironment. The design strategies of small molecule fluorescent probes and their applications in biological imaging will be discussed. By regulating the design strategy and mechanism (e.g., ICT, PeT, and FRET) of the electronic and spectral characteristics of the fluorescent platforms, these chemical probes show high selectivity and diverse functions, which can be used for imaging of various physiological and pathological processes. Through the exploration of the rational response mechanism and design strategy, combined with a variety of imaging techniques, such as super-resolution imaging, photoacoustic (PA) imaging, etc., we have realized multimode imaging of the important biological analytes from the subcellular level to the in vivo level, which provides powerful means to study the physiological and pathological functions of these species and microenvironments. This Account aims to offer insights and inspiration for the development of novel fluorescent probes for biological imaging, which could provide powerful tools for the study of chemical biology. Overall, we represent a series of turn-on/turn-off/ratiometric fluorescent/PA probes to visually and dynamically trace biological species and microenvironments in cells and even in vivo that seek higher resolution and depth molecular imaging to improve diagnostic methods and clarify new discoveries related to chemical biology. Our future efforts will be devoted to developing multiorganelle targeted fluorescent probes to study the mechanism of subcellular organelle interaction and employing various dual-mode probes of NIR II and PA imaging to investigate the development of related diseases and treat the related diseases at subcellular and in vivo levels.

Fluorescence and Lifetime Imaging of Endoplasmic Reticulum Polarity Change During Ferroptosis.

As a new form of regulated cell death, ferroptosis is closely related to various diseases. Tracing ferroptosis related biological behavior is helpful to better understand this process and its related biology. Considering that ferroptosis is featured with remarkable lipid peroxidation which can easily change the membranes' compositions and structures, it is potential to detect intracellular environmental changes for direct assessment of ferroptosis. In view of the close relationship between endoplasmic reticulum (ER) and ferroptosis, we designed an ER-targeted and polarity-sensitive fluorescent probe SBD-CH, which has superior photostability and can respond to polarity with high selectivity without the affection of viscosity. SBD-CH can monitor the trend of ER polarity during ferroptosis by confocal laser scanning microscopy (CLSM), and analyze the distribution of polarity in ferroptosis by fluorescence lifetime imaging microscopy (FLIM). During Erastin induced ferroptosis, the polarity of ER in HT-1080 cells increased and the polarity distribution in ER was more dispersed. Our work provides an effective strategy for evaluating the process of ferroptosis by monitoring the changes of ER polarity.

Establishment and validation of a nomogram predicting the risk of deep vein thrombosis before total knee arthroplasty.

PURPOSE: This study aimed to analyze the independent risk factors contributing to preoperative DVT in TKA and constructed a predictive nomogram to accurately evaluate its occurrence based on these factors. METHODS: The study encompassed 496 patients who underwent total knee arthroplasty at our hospital between June 2022 and June 2023. The dataset was randomly divided into a training set (n = 348) and a validation set (n = 148) in a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were used to screen the predictors of preoperative DVT occurrence in TKA and construct a nomogram. The performance of the predictive models was evaluated using the concordance index (C-index), calibration curves, and the receiver operating characteristic (ROC) curves. Decision curve analysis was used to analyze the clinical applicability of nomogram. RESULTS: A total of 496 patients who underwent TKA were included in this study, of which 28 patients were examined for lower extremity DVT preoperatively. Platelet crit, Platelet distribution width, Procalcitonin, prothrombin time, and D-dimer were predictors of preoperative occurrence of lower extremity DVT in the nomograms of the TKA patients. In addition, the areas under the curve of the ROC of the training and validation sets were 0.935 (95%CI: 0.880-0.990) and 0.854 (95%CI: 0.697-1.000), and the C-indices of the two sets were 0.919 (95%CI: 0.860-0.978) and 0.900 (95%CI: 0.791-1.009). The nomogram demonstrated precise risk prediction of preoperative DVT occurrence in TKA as confirmed by the calibration curve and decision curve analysis. CONCLUSIONS: This Nomogram demonstrates great differentiation, calibration and clinical validity. By assessing individual risk, clinicians can promptly detect the onset of DVT, facilitating additional life monitoring and necessary medical interventions to prevent the progression of DVT effectively.

Correlation between environmental nickel exposure and the development of arthritis: A large-sample cross-sectional investigation.

BACKGROUND: Nickel is a common metallic element in orthopedic implanted devices and living environment exposures. It is associated with varieties of diseases. The purpose of this investigation was to explore the correlation between nickel exposure and the prevalence of arthritis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2018. Multivariate logistic regression was utilized to analyze the relationship between urinary nickel levels and arthritis. In addition, hierarchical modeling further explored the interactions and trends between urinary nickel levels and arthritis. Propensity score matching (PSM) method was used to reduce the effect of confounders. Additionally, restricted cubic spline curve (RCS) was used to assess the possible nonlinear association between urinary nickel and arthritis. RESULTS: The investigation was comprised of 139 arthritis patients and 547 healthy participants. After correction by PSM, there was a positive correlation between arthritis and Nickel exposure levels. The risk of developing arthritis was significantly increased when nickel exposure levels were in the Q4 interval (OR=2.25, 95 % CI=1.03-5.02). When stratified by age and sex, nickel exposure was significantly and positively associated with arthritis in the subgroup aged over 65 years. (OR=2.78,95 %CI=1.20-6.46). Also, the difference between nickel exposure and arthritis was significant in the different gender subgroups (interaction P<0.05). Restricted cubic spline (RCS) results showed a significant linear association between nickel exposure levels and arthritis. In addition, there was a non-linear association between nickel exposure and arthritis across gender and age subgroups. CONCLUSION: A significant positive association between nickel exposure levels and arthritis was showed by the experimental data. Controlling the use of nickel-containing medical prostheses and reducing exposure to nickel-containing daily necessity could help to slow the onset of arthritis.

A Small-Molecule Ratiometric Photoacoustic Probe for the High-Spatiotemporal-Resolution Imaging of Copper(II) Dynamics in the Mouse Brain.

Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood-brain barrier (BBB) and providing high-spatial-resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu2+ dynamics in the mouse brain with high-spatiotemporal-resolution. The probe demonstrates selective ratiometric and reversible responses to Cu2+ , while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron-level resolution. The imaging results revealed a significant increase in Cu2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu2+ distribution in the PD model mouse brain during L-dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu2+ dynamics in the mouse brain offers valuable insights into the copper-related molecular mechanisms underlying neurodegenerative diseases.

Activation of RIG-I/MDA5 Signaling and Inhibition of CD47-SIRPα Checkpoint with a Dual siRNA-Assembled Nanoadjuvant for Robust Cancer Immunotherapy.

Antigen-presenting cells (APCs) play a crucial role in the anti-tumor immunity as they are responsible for capturing, processing, and presenting tumor antigens to T cells. However, their activation is often limited by the absence of adjuvants and the suppressive effects of immune checkpoints, such as CD47-SIRPα. Herein, we present a nanoadjuvant that is self-assembled from long RNA building blocks generated through rolling circle transcription (RCT) reaction and further modified with cationic liposomes. Owing to the high load of densely packed RNA, this nanoadjuvant could robustly activate RIG-I/MDA5 signaling in APCs, leading to the maturation of dendritic cells (DCs) and the polarization of tumor-associated macrophages (TAMs) toward an anti-tumor M1-like phenotype. In addition, with a well-designed template, the generated long RNA from RCT reaction includes two kinds of siRNA targeting both CD47 in tumor cells and SIRPα in APCs. This dual gene silencing results in efficient inhibition of the CD47-SIRPα checkpoint. Collectively, the robust activation of RIG-I/MDA5 signaling and efficient inhibition of CD47-SIRPα checkpoint enhance the phagocytic activity of APCs, which in turn promotes the cross-priming of effector T cells and the activation of anti-tumor immune responses. This study therefore provides a simple and robust RNA nanoadjuvant for cancer immunotherapy.

A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo.

Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.

A Ferroptosis-Inducing Arsenene-Iridium Nanoplatform for Synergistic Immunotherapy in Pancreatic Cancer.

Due to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two-dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis-inducing effects with high drug loading capacity and, importantly, excellent anti-cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin-loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis-induced chemotherapy with immunotherapy via an all-in-one strategy, providing new insights for future pancreatic cancer therapy.

Patient-derived Immunocompetent Tumor Organoids: A Platform for Chemotherapy Evaluation in the Context of T-cell Recognition.

Most of the anticancer compounds synthesized by chemists are primarily evaluated for their direct cytotoxic effects at the cellular level, often overlooking the critical role of the immune system. In this study, we developed a patient-derived, T-cell-retaining tumor organoid model that allows us to evaluate the anticancer efficacy of chemical drugs under the synergistic paradigm of antigen-specific T-cell-dependent killing, which may reveal the missed drug hits in the simple cytotoxic assay. We evaluated clinically approved platinum (Pt) drugs and a custom library of twenty-eight PtIV compounds. We observed low direct cytotoxicity of Pt drugs, but variable synergistic effects in combination with immune checkpoint inhibitors (ICIs). In contrast, the majority of PtIV compounds exhibited potent tumor-killing capabilities. Interestingly, several PtIV compounds went beyond direct tumor killing and showed significant immunosynergistic effects with ICIs, outstanding at sub-micromolar concentrations. Among these, Pt-19, PtIV compounds with cinnamate axial ligands, emerged as the most therapeutically potent, demonstrating pronounced immunosynergistic effects by promoting the release of cytotoxic cytokines, activating immune-related pathways and enhancing T cell receptor (TCR) clonal expansion. Overall, this initiative marks the first use of patient-derived immunocompetent tumor organoids to explore and study chemotherapy, advancing their path toward more effective small molecule drug discovery.

Blood-Brain Barrier Permeable Photoacoustic Probe for High-Resolution Imaging of Nitric Oxide in the Living Mouse Brain.

Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging of NO in the brain is essential for understanding pathophysiological processes. However, currently available NO probes are unsuitable for this purpose due to their poor ability to cross the blood-brain barrier (BBB) or to image in deep tissues with spatial resolution. Herein, we developed a photoacoustic (PA) probe with BBB crossing ability to overcome this obstacle. The probe shows a highly selective ratiometric response toward NO, which enables the probe to image NO with micron resolution in the whole brain of living mice. Using three-dimensional PA imaging, we demonstrated that the probe could be used to visualize the detailed NO distribution in varying depth cross-sections (0-8 mm) of the living Parkinson's disease (PD) mouse brain. We also investigated the therapeutic properties of natural polyphenols in the PD mouse brain using the probe as an imaging agent and suggested the potential of the probe for screening therapeutic agents. This study provides a promising imaging agent for imaging of NO in the mouse brain with high resolution. We anticipate that these findings may open up new possibilities for understanding the biological functions of NO in the brain and the development of new imaging agents for the diagnosis and treatment of brain diseases.

Chemoenzymatic Measurement of LacNAc in Single-Cell Multiomics Reveals It as a Cell-Surface Indicator of Glycolytic Activity of CD8+ T Cells.

Despite the rich information about the physiological state of a cell encoded in the dynamic changes of cell-surface glycans, chemical methods to capture specific glycan epitopes at the single-cell level are quite limited. Here, we report a chemoenzymatic method for the single-cell detection of N-acetyllactosamine (LacNAc) by labeling LacNAc with a specific DNA barcode. The chemoenzymatic labeling does not alter the transcriptional status of immune cells and is compatible with multiple scRNA-seq platforms. Integrated analysis of LacNAc and the transcriptome of T cells at the single-cell level reveals that the amount of cell-surface LacNAc is significantly upregulated in activated CD8+ T cells but maintained at basal levels in resting CD8+ T cells (i.e., naive and central memory T cells). Further analysis confirms that LacNAc levels are positively correlated with the glycolytic activity of CD8+ T cells during differentiation. Taken together, our study demonstrates the feasibility of the chemoenzymatic detection of cell-surface glycan in single-cell RNA sequencing-based multiomics with TCR sequence and cell-surface epitope information (i.e., scTCR and CITE-seq), and provides a new way to characterize the biological role of glycan in diverse physiological states.

Optically Pure Double-Stranded Dinuclear Ir(III) Metallohelices Enabled Chirality-Induced Photodynamic Responses.

Investigation on the interactions between enantiomers of chiral drugs and biomolecules can help precisely understand their biological behaviors in vivo and provide insights into the design of new drugs. Herein, we designed and synthesized a pair of optically pure, cationic, double-stranded dinuclear Ir(III)-metallohelices (Λ2R4-H and Δ2S4-H), and their dramatic enantiomer-dependent photodynamic therapy (PDT) responses were thoroughly studied in vitro and in vivo. Compared to the mononuclear enantiomeric or racemic [Ir(ppy)2(dppz)][PF6] (Λ-/Δ-Ir, rac-Ir) that with high dark toxicity and low photocytotoxicity index (PI) values, both of the optically pure metallohelices displayed negligible toxicity in the dark while exhibiting very distinctive light toxicity upon light irradiation. The PI value of Λ2R4-H was approximately 428, however, Δ2S4-H significantly reached 63,966. Interestingly, only Δ2S4-H was found to migrate from mitochondria to nucleus after light irradiation. Further proteomic analysis verified that Δ2S4-H activated the ATP-dependent migration process after light irradiation, and subsequently inhibited the activities of the nuclear proteins such as superoxide dismutase 1 (SOD1) and eukaryotic translation initiation factor 5A (EIF5A) to trigger the accumulation of superoxide anions and downregulate mRNA splicing processes. Molecular docking simulations suggested that the interactions between metallohelices and nuclear pore complex NDC1 dominated the migration process. This work presents a new kind of Ir(III) metallohelices-based agent with the highest PDT efficacy, highlights the importance of metallohelices' chirality, and provides inspirations for the future design of chiral helical metallodrugs.

The status and trends of mitochondrial dynamics research: A global bibliometric and visualized analysis.

BACKGROUND: Mitochondria are remarkably dynamic organelles encapsulated by bilayer membranes. The dynamic properties of mitochondria are critical for energy production. AIMS: The aim of our study is to investigate the global status and trends of mitochondrial dynamics research and predict popular topics and directions in the field. METHODS: Publications related to the studies of mitochondrial dynamics from 2002 to 2021 were retrieved from Web of Science database. A total of 4,576 publications were included. Bibliometric analysis was conducted by visualization of similarities viewer and GraphPadPrism 5 software. RESULTS: There is an increasing trend of mitochondrial dynamics research during the last 20 years. The cumulative number of publications about mitochondrial dynamics research followed the logistic growth model [Formula: see text]. The USA made the highest contributions to the global research. The journal Biochimica et Biophysica Acta (BBA)-Molecular Cell Research had the largest publication numbers. Case Western Reserve University is the most contributive institution. The main research orientation and funding agency were cell biology and HHS. All keywords related studies could be divided into three clusters: "Related disease research", "Mechanism research" and "Cell metabolism research". CONCLUSIONS: Attention should be drawn to the latest popular research and more efforts will be put into mechanistic research, which may inspire new clinical treatments for the associated diseases.

CXCL11 negatively regulated by MED19 favours antitumour immune infiltration in breast cancer.

BACKGROUND: Through microarray results, we found that the C-X-C motif chemokine ligand 11 (CXCL11) was negatively regulated by mediator complex subunit 19 (MED19), a protumour factor. However, the biological role and potential mechanism of CXCL11 need to be explored in breast cancer (BRCA). METHODS: The BRCA dataset was obtained from the Cancer Genome Atlas (TCGA) dataset. Our microarray data and the BRCA dataset of TCGA were analysed and visualized using the R software package. The mRNA and protein levels were measured by qRT-PCR and western blotting. RESULTS: Inhibition of MED19 in MDA-MB-231 cells caused CXCL11 upregulation. The relative positive regulation of cytokine pathways was enriched after MED19 knockdown. High CXCL11 was determined to be positively correlated with immune response activation, increased antitumour immune cell infiltration, immune checkpoint molecule expression, and enhanced sensitivity to immunotherapy and chemotherapy. Collectively, CXCL11 promoted antitumour immunity and was regulated by MED19 in BRCA. Clarifying the prognostic value and underlying mechanism of CXCL11 in BRCA could provide a theoretical basis to find new diagnostic and therapeutic targets.

Can Remimazolam Be a New Sedative Option for Outpatients Undergoing Ambulatory Oral and Maxillofacial Surgery?

PURPOSE: Midazolam is a classic sedative drug. The sedative effect of remimazolam has not been demonstrated in ambulatory oral and maxillofacial surgery (OMS). This study aimed to measure whether remimazolam can achieve the same sedation effects compared with midazolam, but with a faster recovery and fewer adverse reactions in outpatients undergoing ambulatory OMS. MATERIALS AND METHODS: This was a prospective, randomized, controlled, single-center study of 40 patients who underwent ambulatory OMS at Peking University Hospital of Stomatology, Beijing, China, between April 2021 and June 2021. The patients were randomly divided into a midazolam group (Group M) and a remimazolam group (Group R). The success rate of sedation, which was defined as completion of the operation with no rescue sedative medication, was the primary outcome. In this study, bispectral index and modified observer's assessment of alertness/sedation value, intraoperative adverse events, time to discharge, and the number of additional doses of sedative were compared. Descriptive, comparative analyses were conducted. RESULTS: Forty patients were eligible for this study, and the final sample size was 40 (including 25 males, average age was 29). The success rate of sedation in Group R was statistically significantly higher than that in Group M (Group R vs Group M: 95% [19/20] vs 70% [14/20], P = .037, 95% confidence interval [CI]: 0.681 to 0.913). The median number of additional doses of the medications per 5 minutes in Group R was lower than that in Group M (0.51 [0.19, 0.71] vs 0.82 [0.51, 1.25], P = .006, 95% CI: 0.013 to 0.583). Group R showed a higher bispectral index number (93.9 ± 4.6 vs 86.6 ± 7.2, P = .001, 95% CI: 3.451 to 11.149) at the end of the surgery and a higher modified observer's assessment of alertness/sedation score (4.70 ± 0.47 vs 4.05 ± 0.68, P = .001, 95% CI: 0.273 to 1.027) after 5 minutes at the recovery room compared with Group M. CONCLUSIONS: The success rate of remimazolam is higher than that of midazolam. The use of remimazolam is effective for sedation of patients undergoing ambulatory OMS.

LINC00536 Promotes Breast Cancer Progression by Regulating ROCK1 via Sponging of miR-214-5p.

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play a significant role in regulating gene expression and participating in the progression of various malignancies. In our study, by analyzing data from The Cancer Genome Atlas (TCGA), LINC00536 was found to be highly expressed in breast cancer (BC) tissues, but its function and clinical significance in BC are still unknown. Therefore, we aimed to explore the role and molecular mechanism of LINC00536 in BC. We collected human BC tissue specimens and validated that LINC00536 was overexpressed in BC tissues. Increased LINC00536 expression was associated with advanced TNM stage, larger tumor diameter, lymph node metastasis and poor prognosis in patients with BC. Univariate and multivariate Cox regression analyses showed that high LINC00536 expression was an independent prognostic risk factor for overall survival in BC patients. Furthermore, quantitative reverse transcription PCR (qRT-PCR) showed that LINC00536 was upregulated in BC cell lines. Then, we confirmed that LINC00536 silencing-inhibited BC cell proliferation, migration, and invasion and led to cell cycle arrest in vitro. Animal experiments showed that knockdown of LINC00536 expression suppressed tumorigenesis in vivo. Mechanistically, LINC00536 serves as a ceRNA for miR-214-5p, increasing the expression of ROCK1, which acts as a tumor promoter in BC. Rescue assays revealed that miR-214-5p inhibition or ROCK1 overexpression could neutralize the suppressive effects of LINC00536 knockdown on cell proliferation, migration and invasion. Our data indicated that LINC00536 accelerates BC progression by regulating the miR-214-5p/ROCK1 pathway, which might provide a new perspective to investigate the development process of BC.