Advances in Functionalized Biocomposites of Living Cells Combined with Metal-Organic Frameworks.

Motivated by the remarkable innate characteristics of cells in living organisms, we have found that hybrid materials that combine bioorganisms with nanomaterials have significantly propelled advancements in industrial applications. However, the practical deployment of unmodified living entities is inherently limited due to their sensitivity to environmental fluctuations. To surmount these challenges, an efficacious strategy for the biomimetic mineralization of living organisms with nanomaterials has emerged, demonstrating extraordinary potential in biotechnology. Among them, innovative composites have been engineered by enveloping bioorganisms with a metal-organic framework (MOF) coating. This review systematically summarizes the latest developments in living cells/MOF-based composites, detailing the methodologies employed in structure fabrication and their diverse applications, such as bioentity preservation, sensing, catalysis, photoluminescence, and drug delivery. Moreover, the synergistic benefits arising from the individual compounds are elucidated. This review aspires to illuminate new prospects for fabricating living cells/MOF composites and concludes with a perspective on the prevailing challenges and impending opportunities for future research in this field.

Prognosis of concurrent endoscopic dacryocystorhinostomy and nasal septoplasty for chronic dacryocystitis with moderate nasal septum deviation.

CONTEXT: The prognosis of combined septoplasty and endoscopic dacryocystorhinostomy (En-DCR) for moderate nasal septum deviation (NSD) has not yet been fully investigated. PURPOSE: To evaluate whether septoplasty improves the prognosis of En-DCR for moderate NSD. SETTINGS AND DESIGN: A retrospective cohort study in a real-world clinical setting. METHODS: The postoperative FICI DCR ostium grading scores and functional and anatomical information at 1, 2, 3, and 6 months were determined for consecutive patients with chronic dacryocystitis (CD) and moderate NSD who underwent En-DCR. STATISTICAL ANALYSIS USED: Univariate and generalized estimating equation multivariate analyses were used to compare the outcomes of the septoplasty and non-septoplasty groups. RESULTS: En-DCR and septoplasty were concurrently performed for 32 (20.1%, 32/158) cases. The total FICI DCR ostial scores for the septoplasty and non-septoplasty groups were highest at the first (4.97 ± 0.177 vs. 4.97 ± 0.176, P > 0.05) and lowest at the sixth (4.41 ± 1.341 vs. 4.50 ± 1.355, P > 0.05) postoperative months. At the end of follow-up, the two groups showed comparable proportions of patients requiring definitive intervention for the ostium (6.3% vs. 7.1%, P > 0.05), comparabe functional success rates (87.5% vs. 90.5%, P > 0.05) and anatomical success rates (93.8% vs. 92.9%, P > 0.05). Only the non-septoplasty group experienced nasal mucosal adhesions (3.2%, 4/126). CONCLUSIONS: In patients with CD and moderate NSD, nasal septoplasty did not impact En-DCR prognosis, but reduced the complications. Skilled surgeons should reconsider septoplasty in the absence of otolaryngological indications.

Electrically Evoked Auditory Brainstem Responses in Children Fitted with Hearing Aids Prior to Cochlear Implantation.

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.

Identification of DTL as Related Biomarker and Immune Infiltration Characteristics of Nasopharyngeal Carcinoma via Comprehensive Strategies.

Purpose: Although considerable progress has been made in basic and clinical research on nasopharyngeal carcinoma (NPC), the biomarkers of the progression of NPC have not been fully studied and described. This study was designed to identify potential novel biomarkers for NPC using integrated analyses and explore the immune cell infiltration in this pathological process. Methods: Five GEO data sets were downloaded from gene expression omnibus database (GEO) and analysed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The four algorithms were adopted for screening of novel and key biomarkers for NPC, including random forest (RF) machine learning algorithm, least absolute shrinkage and selection operator (LASSO) logistic regression, support vector machine-recursive feature elimination (SVM-RFE), and weighted gene co-expression network analysis (WGCNA). Lastly, CIBERSORT was used to assess the infiltration of immune cells in NPC, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Results: Herein, we identified 46 DEGs, and enrichment analysis results showed that DEGs and several kinds of signaling pathways might be closely associated with the occurrence and progression of NPC. DTL was recognized as NPC-related biomarker. DTL, also known as retinoic acid-regulated nuclear matrix-associated protein (RAMP), or DNA replication factor 2 (CDT2), is reported to be correlated with the cell proliferation, cell cycle arrest and cell invasion in hepatocellular carcinoma, breast cancer and gastric cancer. Immune infiltration analysis demonstrated that macrophages M0, macrophages M1 and T cells CD4 memory activated were linked to pathogenesis of NPC. Conclusion: In summary, we adopted a comprehensive strategy to screen DTL as biomarkers related to NPC and explore the critical role of immune cell infiltration in NPC.

Electrically evoked auditory brainstem responses to electrical stimulation at round window membrane in congenitally deaf children at different ages.

OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem responses (eABRs) to electrical stimulation at the round window niche (RWN) and round window membrane (RWM) and the effect of deafness duration on functions of the auditory pathway to the level of the brainstem. METHODS: According to the age at cochlear implantation (CI), 99 children with profound sensorineural hearing loss were divided into four groups: ≤12 months (group A), 13-36 months (group B), 37-60 months (group C) and >60 months (group D). The eABRs were evoked by electrical stimulation at RWN and RWM during the operation of CI. RESULTS: The higher eABR extraction rate and lower threshold for RWM stimulation was found than those for RWN stimulation. The eⅢ latencies and eⅢ-eⅤ latency intervals for RWM stimulation were similar among four groups. However, children with earlier CI (group A) showed a significantly shorter eⅤ latency than others. CONCLUSION: The eABR evoked by the electrical stimulation at RWM is more stable and sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway. Development in the upper brainstem pathway may be more vulnerable to long-term deafness as revealed by the eⅤ latency.

Learning Macromanagement in Starcraft by Deep Reinforcement Learning.

StarCraft is a real-time strategy game that provides a complex environment for AI research. Macromanagement, i.e., selecting appropriate units to build depending on the current state, is one of the most important problems in this game. To reduce the requirements for expert knowledge and enhance the coordination of the systematic bot, we select reinforcement learning (RL) to tackle the problem of macromanagement. We propose a novel deep RL method, Mean Asynchronous Advantage Actor-Critic (MA3C), which computes the approximate expected policy gradient instead of the gradient of sampled action to reduce the variance of the gradient, and encode the history queue with recurrent neural network to tackle the problem of imperfect information. The experimental results show that MA3C achieves a very high rate of winning, approximately 90%, against the weaker opponents and it improves the win rate about 30% against the stronger opponents. We also propose a novel method to visualize and interpret the policy learned by MA3C. Combined with the visualized results and the snapshots of games, we find that the learned macromanagement not only adapts to the game rules and the policy of the opponent bot, but also cooperates well with the other modules of MA3C-Bot.

Epac1 Signaling Pathway Mediates the Damage and Apoptosis of Inner Ear Hair Cells after Noise Exposure in a Rat Model.

To investigate the role of the exchange protein directly activated by cAMP (Epac) signaling pathway in inner ear hair cell damage and apoptosis after noise exposure, we analyzed the expression level of Epac1 in a rat model of noise-induced hearing loss (NIHL), based on rat exposure to a 4-kHz and 106-dB sound pressure level (SPL) for 8 h. Loss of outer hair cells (OHCs), mitochondrial lesions, and hearing loss were examined after treatment with the Epac agonist, 8-CPT, or the Epac inhibitor, ESI-09. The effects of 8-CPT and ESI-09 on cell proliferation and apoptosis were examined by CCK-8 assays, holographic microscopy imaging, and Annexin-V FITC/PI staining in HEI-OC1 cells. The effects of 8-CPT and ESI-09 on Ca2+ entry were evaluated by confocal Ca2+ fluorescence measurement. We found that the expression level of Epac1 was significantly increased in the cochlear tissue after noise exposure. In NIHL rats, 8-CPT increased the loss of OHCs, mitochondrial lesions, and hearing loss compared to control rats, while ESI-09 produced the opposite effects. Oligomycin was used to induce HEI-OC1 cell damage in vitro. In HEI-OC1 cells treated with oligomycin, 8-CPT and ESI-09 increased and reduced cell apoptosis, respectively. Moreover, 8-CPT promoted Ca2+ uptake in HEI-OC1 cells, while ESI-09 inhibited this process. In conclusion, our data provide strong evidence that the Epac1 signaling pathway mediates early pathological damage in NIHL, and that Epac1 inhibition protects from NIHL, identifying Epac1 as a new potential therapeutic target for NIHL.

Effect of unilateral cochlear implant use on contralateral electrically evoked auditory brainstem responses to round window membrane electrical stimulation.

BACKGROUND: Long-term use of a unilateral cochlear implant (CI) may lead to abnormal development of contralateral auditory pathway. OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem response (eABR) with the electrical stimulation at the round window membrane and the effect of unilateral CI use on the contralateral auditory pathway functions. MATERIALS AND METHODS: According to duration of unilateral CI use, 45 children with severe or profound sensorineural hearing loss were divided into sCI (≤12 months), lCI (≥24 months) and nCI (no CI use) groups. Intra-operative eABRs evoked by electrical stimulation at the round window membrane were recorded. RESULTS: The latencies of eIII and eV were significantly longer in lCI group than in sCI group and in nCI group, respectively, but not significantly different between sCI group and nCI group. The eABR thresholds and eIII-eV latency intervals were not significantly different among three groups. CONCLUSIONS AND SIGNIFICANCE: The eABR evoked by the electrical stimulation at the round window membrane is a reliable and effective way of evaluating functions of the auditory pathway in deaf children. Long-term use of a unilateral CI may promote the degenerative process of the contralateral auditory pathway to the level of the brainstem.

CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis.

BACKGROUND: Aberrant expression of circular RNA (circRNA) is involved in the occurrence and development of multifarious cancers, including oral squamous cell carcinoma (OSCC). However, the biological role of circGDI2 and the action mechanism in OSCC remain largely unclear. METHODS: The expression levels of circGDI2, miR-454-3p and forkhead box F2 (FOXF2) were examined by quantitative real-time PCR (qRT-PCR) or Western blot. The stability of circGDI2 was confirmed by Ribonuclease R (RNase R) assay. Cell Counting Kit 8 (CCK8) assay, colony formation and transwell assay were used to detect cell proliferation, migration or invasion. Cell apoptosis was tested by flow cytometry. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the interaction between miR-454-3p and circGDI2 or FOXF2. Moreover, xenograft mouse models were constructed to assess tumor growth in vivo. RESULTS: CircGDI2 was a stable circRNA and was low expressed in OSCC tissues and cells. CircGDI2 overexpression could effectively inhibit the proliferation, migration, invasion and promote apoptosis in OSCC cells, and suppress OSCC tumor growth in nude mice in vivo. MiR-454-3p could be sponged by circGDI2, and its overexpression could mitigate the suppressive effects of circGDI2 overexpression on OSCC progression. In addition, FOXF2 was a target of miR-454-3p, and miR-454-3p silence could impede the cell growth of OSCC cells by enhancing FOXF2 expression. Meanwhile, circGDI2 positively regulated FOXF2 expression by targeting miR-454-3p. CONCLUSION: CircGDI2 served as a repressor to restrain OSCC malignancy via miR-454-3p/FOXF2 axis, which might be a novel biomarker for targeted OSCC therapy.

Microbial spectrum and antibiotic sensitivity in infantile dacryocystitis.

PURPOSE: To identify the characteristics and the spectrum of microbial agents of infantile dacryocystitis and to assess the trends in both antibiotic sensitivities and pathogens over the past 10 years. METHODS: The microbial and medical records of 546 culture-proven patients (546 eyes) of infantile dacryocystitis diagnosed at Henan Eye Hospital between January 2009 and December 2018 were retrospectively reviewed. Patient demographics, microbial analysis, and susceptibility rates to various antibiotics were done. A chi-squared test for trends was applied to evaluate changes in antibiotic susceptibility and microbial spectrum over time. RESULTS: A total of 546 patients with infantile dacryocystitis were documented. The average age was 2.97 ± 4.15 months, and 42.7% were female. The proportion of gram-positive microbes, gram-negative microbes, and fungi was 80.2, 19.4, and 0.4%, respectively. Minocycline was sensitive to gram-positive bacteria (98.0%). Imipenem was sensitive to gram-negative bacteria (89.2%). Increasing susceptibility was observed in two bacterial isolates: Staphylococcus aureus (P = 0.005) and Streptococcus mitis (P = 0.001). Decreasing susceptibility was observed in one bacterial isolate: Staphylococcus epidermidis (P < 0.0001). Increasing microbial susceptibility over time was detected for 12 antibiotics. Decreasing microbial sensitivity was observed for one antibiotic. CONCLUSIONS: The most common cause of infantile dacryocystitis is Staphylococcus epidermidis. Though a significant trend towards increasing microbial sensitivity to some antibiotics was observed, including glycopeptides, cephalosporins, fluoroquinolones, tetracyclines, and lincosamides, a significant trend towards decreasing microbial sensitivity to amikacin was also detected.

Fast A3RL: Aesthetics-Aware Adversarial Reinforcement Learning for Image Cropping.

Image cropping aims at improving the quality of images by removing unwanted outer areas, which is widely used in the photography and printing industry. Most previous cropping methods that don't need bounding box supervision rely on the sliding window mechanism. The sliding window method results in fixed aspect ratios and limits the shape of the cropping region. Moreover, the sliding window method usually produces lots of candidates on the input image, which is very time-consuming. Motivated by these challenges, we formulate image cropping as a sequential decision-making process and propose a reinforcement learning based framework to address this problem, namely Fast Aesthetics-Aware Adversarial Reinforcement Learning (Fast A3RL). Particularly, the proposed method develops an aesthetics-aware reward function, which is dedicated for image cropping. Similar to human's decisionmaking process, we use a comprehensive state representation including both the current observation and historical experience. We train the agent using the actor-critic architecture in an end-to-end manner. The adversarial learning process is also applied during the training stage. The proposed method is evaluated on several popular cropping datasets, in which the images are unseen during training. Experiment results show that our method achieves state-of-the-art performance with much fewer candidate windows and much less time compared with related methods.

Mixed Supervised Object Detection with Robust Objectness Transfer.

In this paper, we consider the problem of leveraging existing fully labeled categories to improve the weakly supervised detection (WSD) of new object categories, which we refer to as mixed supervised detection (MSD). Different from previous MSD methods that directly transfer the pre-trained object detectors from existing categories to new categories, we propose a more reasonable and robust objectness transfer approach for MSD. In our framework, we first learn domain-invariant objectness knowledge from the existing fully labeled categories. The knowledge is modeled based on invariant features that are robust to the distribution discrepancy between the existing categories and new categories; therefore the resulting knowledge would generalize well to new categories and could assist detection models to reject distractors (e.g., object parts) in weakly labeled images of new categories. Under the guidance of learned objectness knowledge, we utilize multiple instance learning (MIL) to model the concepts of both objects and distractors and to further improve the ability of rejecting distractors in weakly labeled images. Our robust objectness transfer approach outperforms the existing MSD methods, and achieves state-of-the-art results on the challenging ILSVRC2013 detection dataset and the PASCAL VOC datasets.

Optimal design of the absolute positioning sensor for a high-speed maglev train and research on its fault diagnosis.

This paper studies an absolute positioning sensor for a high-speed maglev train and its fault diagnosis method. The absolute positioning sensor is an important sensor for the high-speed maglev train to accomplish its synchronous traction. It is used to calibrate the error of the relative positioning sensor which is used to provide the magnetic phase signal. On the basis of the analysis for the principle of the absolute positioning sensor, the paper describes the design of the sending and receiving coils and realizes the hardware and the software for the sensor. In order to enhance the reliability of the sensor, a support vector machine is used to recognize the fault characters, and the signal flow method is used to locate the faulty parts. The diagnosis information not only can be sent to an upper center control computer to evaluate the reliability of the sensors, but also can realize on-line diagnosis for debugging and the quick detection when the maglev train is off-line. The absolute positioning sensor we study has been used in the actual project.

Method development and validation of capillary sodium dodecyl sulfate gel electrophoresis for the characterization of a monoclonal antibody.

A capillary sodium dodecyl sulfate gel electrophoresis (cSDS) method has been developed and qualified for purity and impurity analysis of monoclonal antibodies. This method was optimized and qualified for the analysis of monoclonal antibody (mAb1) under reduced and non-reduced conditions. Some of the sample preparation parameters including sample buffer pH, incubation temperature and duration, alkylation conditions with iodoacetamide (IAM), and reduction conditions with 2-mercaptoethanol (2-ME) were optimized. It was observed that under slightly acidic conditions (pH 5.5-6.5) the thermally induced fragmentation of non-reduced mAb1 was greatly decreased. As such, a citrate-phosphate buffer at pH 6.5 was used for sample preparation to replace the original Beckman sample buffer (pH 9.0). The optimal sample preparation conditions were found to be as follows: (1) incubation temperature and duration (reduced and non-reduced), 65 degrees C for 5 min; (2) alkylation condition, 10 microL of 0.25 M IAM; (3) reduction condition, 10 microL of 5-fold diluted 2-ME. The method was qualified by evaluating specificity, accuracy, precision, limit of quantitation (LOQ), and linearity. The method exhibited no interference from sample buffer matrix. The method was found to be linear, accurate, and precise in the range of 0.25-3.0mg/mL protein concentration. The LOQ of the method was determined to be 0.02 mg/mL for reduced and non-reduced mAb1. In addition, some aspects of sample stability were examined during qualification.

Determination of residual cell culture media components by MEKC.

Folic acid, hypoxanthine, mycophenolic acid, nicotinic acid, riboflavin, and xanthine are widely used as cell culture media components in monoclonal antibody manufacturing. These components are subsequently removed during the downstream purification processes. This article describes a single MEKC method that can simultaneously determine all the listed compounds with acceptable LOD and LOQ. All the analytes were successfully separated by MEKC using running buffer containing 40 mM SDS, 20 mM sodium phosphate, and 20 mM sodium borate at pH 9.0. The MEKC method was compared to the corresponding CZE method using the same running buffer containing no SDS. The effect of SDS concentration on separation, the pH of the running buffer, and the detection wavelength were studied and optimal MEKC conditions were established. Good linearity was obtained with correlation coefficients of more than 0.99 for all analytes. Specificity, accuracy, and precision were also evaluated. The recovery was in the range of 89-112%. The precision results were in the range of 1.7-4.8%. The experimentally determined data demonstrated that the MEKC method is applicable to the determination of the six analytes in in-process samples from monoclonal antibody manufacturing processes.

Optimization and qualification of capillary zone electrophoresis method for glycoprotein isoform distribution of erythropoietin for quality control laboratory.

The European Pharmacopoeia (Ph. Eur.) monograph for Erythropoietin Concentrated Solution describes a capillary zone electrophoresis method for identification of recombinant human erythropoietin. However, this method has shown poor reproducibility due to inadequate capillary conditioning. We have modified the Ph. Eur. method to make it more robust and suitable for the quality control laboratory for the analysis of epoetin alfa and epoetin alfa after formulation with polysorbate 80. This study qualified the modified method by showing improved robustness and reproducibility. The study also characterized and qualified a secondary standard of epoetin alfa as a substitute for the primary standard, Ph. Eur. erythropoietin Biological Reference Preparation, which is available in limited supply. Four sets of analyses were performed to assess repeatability, intermediate precision, and the secondary standard. The results showed that the modified method is suitable for its intended purpose to test epoetin alfa and formulated epoetin alfa samples. The epoetin alfa secondary standard is a suitable substitute for the primary standard. Further, we developed a procedure for the removal of polysorbate 80 from formulated epoetin alfa, allowing the material to be analyzed by the modified Ph. Eur. method.