Research output of artificial intelligence in arrhythmia from 2004 to 2021: a bibliometric analysis.

Background: With the advancement in machine learning (ML) and artificial neural networks as well as the development of portable electrocardiogram devices, artificial intelligence (AI) has been increasing in popularity over the years. In this study, we aimed to provide an overview of the research regarding the utilization of AI techniques to improve the diagnosis of arrhythmia. Methods: We extracted data published 2004 to 2021 from Web of Science database. The online analytic platform, Literature Metrology (http://bibliometric.com), was used to analyze publication trends, including information about journals, authors, institutions, collaborations between countries, citations, and keywords. Results: Keywords, such as deep learning, electrocardiogram (ECG), and convolutional neural network, have been increasing in frequency over the years. The analysis outcomes demonstrated that topics associated with AI, robotic prosthesis, and big data analysis for arrhythmia have become increasingly popular since 2016. Our study also found that atrial fibrillation (AF) and ventricular arrhythmia were the two ECG signal sharing the most interest. Conclusions: The utility of deep learning in diagnostics and the prognostication of arrhythmia has been gaining traction over the years, covering areas from electrocardiogram detection to atrial arrhythmogenesis model construction. Our study revealed the trend of topics from 2004 to 2021, which may help researchers to monitor future trends.

Steady-State Based Model of Airborne Particle/Gas and Settled Dust/Gas Partitioning for Semivolatile Organic Compounds in the Indoor Environment.

Indoor semivolatile organic compounds (SVOCs), present in the air, airborne particles, settled dust, and other indoor surfaces, can enter the human body through several pathways. Knowing the partitioning between gaseous and particulate phases is important in identifying specific pathway contributions and thereby accurately assessing human exposure. Numerous studies have developed equilibrium equations to predict airborne particle/gas (P/G) partitioning in air (KP) and dust/gas (D/G) partitioning in settled dust (KD). The assumption that P/G and D/G equilibria are instantaneous for airborne and settled dust phases, commonly adopted by current indoor fate models, is not likely valid for compounds with high octanol-air partition coefficients (KOA). Here, we develop steady-state based equations to predict KP and KD in the indoor environment. Results show that these equations perform well and are verified by worldwide monitoring data. It is suggested that instantaneous steady state could work for P/G and D/G partitioning of SVOCs in indoor environments, and the equilibrium is just a special case of the steady state when log KOA < 11.38 for P/G partitioning and log KOA < 10.38 for D/G partitioning. These newly developed equations and methods provide a tool for more accurate assessment for human exposure to SVOCs in the indoor environment.

Mycobacterium vaccae Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.

TCR-Induced Tyrosine Phosphorylation at Tyr270 of SUMO Protease SENP1 by Lck Modulates SENP1 Enzyme Activity and Specificity.

Small ubiquitin-like modifier (SUMO) modification plays an important regulatory role in T cell receptor (TCR) signaling transduction. SUMO-specific proteases (SENPs) have dual-enzyme activities; they can both process SUMO precursors as endopeptidases and participate in SUMO deconjugation as isopeptidases. It remains unclear how the SUMO system, especially SENP1, is regulated by TCR signaling. Here, we show that Lck phosphorylates tyrosine 270 (Y270) of SENP1 upon TCR stimulation, indicating that SENP1 is a substrate of Lck. In vitro endopeptidase activity analysis showed that mutating SENP1 Y270 to either phenylalanine (F) to mimic the phosphorylation-defective state or to glutamate (E) to mimic the negative charge of tyrosine phosphorylation in the enzyme microenvironment did not change its endopeptidase activity towards pre-SUMO1. However, SENP1 Y270E but not Y270F mutation exhibited decreased endopeptidase activity towards pre-SUMO3. Through in vivo isopeptidase activity analysis by rescue expression of SENP1 and its Y270 mutants in a SENP1 CRISPR knockout T cell line, we found that SENP1 Y270F downregulated its isopeptidase activity towards both SUMO1 and SUMO2/3 conjugation by reducing SENP1 binding with sumoylated targets. While overexpression of SENP1 inhibited TCR-induced IL-2 production, overexpression of SENP1 Y270F enhanced it instead. In summary, TCR-induced Y270 phosphorylation of SENP1 may promote its isopeptidase activity and specifically decrease its endopeptidase activity against pre-SUMO3, which finely tunes activation of T cells.

An Intelligent Data Uploading Selection Mechanism for Offloading Uplink Traffic of Cellular Networks.

Wi-Fi uploading is considered an effective method for offloading the traffic of cellular networks generated by the data uploading process of mobile crowd sensing applications. However, previously proposed Wi-Fi uploading schemes mainly focus on optimizing one performance objective: the offloaded cellular traffic or the reduced uploading cost. In this paper, we propose an Intelligent Data Uploading Selection Mechanism (IDUSM) to realize a trade-off between the offloaded traffic of cellular networks and participants' uploading cost considering the differences among participants' data plans and direct and indirect opportunistic transmissions. The mechanism first helps the source participant choose an appropriate data uploading manner based on the proposed probability prediction model, and then optimizes its performance objective for the chosen data uploading manner. In IDUSM, our proposed probability prediction model precisely predicts a participant's mobility from spatial and temporal aspects, and we decrease data redundancy produced in the Wi-Fi offloading process to reduce waste of participants' limited resources (e.g., storage, battery). Simulation results show that the offloading efficiency of our proposed IDUSM is (56.54×10-7), and the value is the highest among the other three Wi-Fi offloading mechanisms. Meanwhile, the offloading ratio and uploading cost of IDUSM are respectively 52.1% and (6.79×103). Compared with other three Wi-Fi offloading mechanisms, it realized a trade-off between the offloading ratio and the uploading cost.

The expression of apolipoproteina1 and its correlation with infiltration of urologic neoplasm.

BACKGROUND: To explore the differential expression of apolipoproteinA1 (APOA1) in urologic neoplasm patient compared with controls, as well as investigates whether APOA1 correlated with infiltration of urologic neoplasm. METHODS: A total of 59 tissue sections of surgically-resected urologic neoplasm and 6 cases of normal tissue sections were collected. Fourteen cases of urine samples from transitional cell carcinoma patients and 6 cases urine samples from controls were also applied in this experiment. We also selected 6 cases of fresh bladder transitional cell carcinoma tissues. The urologic neoplasm tissue sections were classified into infiltration and non-infiltration urologic neoplasm groups. The expressions of APOA1 between urologic neoplasm and normal control were detected by Western blot, Immunohistochemistry and qRT-PCR. The method of Immunohistochemistry was applied to examine the differences of APOA1 expression between infiltration and non-infiltration urologic neoplasm tissue section groups. RESULTS: Compared with none expression in normal controls, APOA1 was exhibited higher level in urologic neoplasm patient's urine and fresh bladder transitional cell carcinoma tissues (P<0.05). There were statistical differences of APOA1 between infiltration and non-infiltration urologic neoplasm tissue section groups. APOA1 expressions were found to be up-regulated in the infiltration neoplasm tissue sections compared to non-infiltration group (P<0.001). CONCLUSIONS: APOA1 could act as a valuable biomarker for predicting the occurrence and development of urologic neoplasm.

T Cell Receptor (TCR)-Induced PLC-γ1 Sumoylation via PIASxß and PIAS3 SUMO E3 Ligases Regulates the Microcluster Assembly and Physiological Function of PLC-γ1.

The SUMO modification system plays an important role in T cell activation, yet how sumoylation regulates TCR-proximal signaling remains largely unknown. We show here that Phospholipase C-γ1 (PLC-γ1) is conjugated by SUMO1 at K54 and K987 upon TCR stimulation and that K54 sumoylation is pivotal for PLC-γ1-mediated T cell activation. We further demonstrate that TCR-induced K54 sumoylation of PLC-γ1 significantly promotes the formation of PLC-γ1 microclusters and the association of PLC-γ1 with the adaptor proteins SLP76 and Gads, but only slightly affects the phosphorylation of PLC-γ1 on Y783, which determines the enzyme catalytic activity. Moreover, upon TCR stimulation, the SUMO E3 ligases PIASxß and PIAS3 both interact with PLC-γ1 and cooperate to sumoylate PLC-γ1, facilitating the assembly of PLC-γ1 microclusters. Together, our findings reveal a critical role of PLC-γ1 K54 sumoylation in PLC-γ1 microcluster assembly that controls PLC-γ1-mediated T cell activation, suggesting that sumoylation may have an important role in the microcluster assembly of TCR-proximal signaling proteins.

Characterisation of amphioxus protein kinase C-δ/θ reveals a unique proto-V3 domain suggesting an evolutionary mechanism for PKC-θ unique V3.

A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species. Phylogenetic analysis showed BbPKC-δ/θ to be the common ancestor of vertebrate PKC-δ and PKC-θ, with a V3 domain containing two PxxP motifs. One motif is conserved in both zebrafish and mammalian PKC-θ but is absent in PKC-δ V3 domain of these species, and has already emerged in drosophila PKC-δ. The other non-conserved motif emerged in BbPKC-δ/θ, and only retained in Danio rerio PKC-δ (DrPKC-δ) but lost in mammalian PKC-δ and -θ. Comparative analyses of the sequence and function of BbPKC-δ/θ, DrPKC-δ, DrPKC-θ and Homo sapiens PKC-θ (HsPKC-θ) in IS translocation and T-cell receptor (TCR)-induced NF-κB activation revealed that retention of the conserved PxxP motif and loss of the non-conserved PxxP motif in mammalian PKC-θ and loss of both PxxP motifs in mammalian PKC-δ accomplish the unique function of PKC-θ in T cells. Together, this study suggests an evolutionary mechanism for PKC-θ unique V3 and reveals BbPKC-δ/θ is the common ancestor of PKC-δ and -θ with a functional proto-V3 domain, supplying new evidence for the existence of primitive adaptive immune system in amphioxus.

Stabilizing alkenyl succinic anhydride (ASA) emulsions with starch nanocrystals and fluorescent carbon dots.

Stabilizing alkenyl succinic anhydride (ASA) emulsions using fine particles instead of cationic starch have attracted much attention in recent years. Herein, starch nanocrystals (SNCs) made from maize starch by H2SO4 hydrolysis were used to co-stabilize ASA emulsions with fluorescent carbon dots (CDs) made hydrothermally from gelatin. The introduction of CDs can significantly enhance the stability and reduce the droplet size of SNC-stabilized ASA-in-water emulsions. Consequently, the sizing performance of the SNC-stabilized ASA emulsion is significantly improved by increasing the CD-to-SNC mass ratio. SNC and CD co-stabilized ASA emulsions show much better sizing performance than starch and CD co-stabilized ASA emulsions, achieving their best sizing performance at a CD-to-SNC mass ratio of 80%. Meanwhile, the morphology of SNC/starch and CD co-stabilized ASA emulsions can be traced under UV excitation.

Understanding shape and morphology of unusual tubular starch nanocrystals.

Starch nanocrystals (SNC) are aptly described as the insoluble degradation byproducts of starch granules that purportedly display morphologies that are platelet-like, round, square, and oval-like. In this work, we reported the preparation of SNC with unprecedented tubular structures through sulfuric acid hydrolysis of normal maize starch, subsequent exposure to ammonia and relaxation at 4°C. High-resolution transmission electron microscopy observation clearly proved that the SNCs possess tubular nanostructures with polygonal cross-section. After further reviewing the transformations of SNC by acid hydrolysis, ammonia treatment, and curing time at 4°C, a mechanism for T-SNC formation is suggested. It is conjectured that T-SNC gradually self-assembles by combination of smaller platelet-like/square nanocrystals likely loosely aggregated by starch molecular chains from residual amorphous regions. This work paves the way for the pursuit of new approaches for the preparation of starch-based nanomaterials possessing unique morphologies.

DNA Methylation mediated down-regulating of MicroRNA-33b and its role in gastric cancer.

The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, down-regulation of tumor suppressive miRNAs by CpG island hypermethylation is emerging as a common hallmark of cancer. Here, we reported that the down-regulation of miR-33b was associated with pM stage of gastric cancer (GC) patients. Ectopic expression of miR-33b in HGC-27 and MGC-803 cells inhibited cell proliferation, migration and invasion, which might be due to miR-33b targeting oncogene c-Myc. Moreover, enhanced methylation level of the CpG island upstream of miR-33b in GC patients with down-regulated miR-33b was confirmed by methylation-specific PCR (MSP) amplification. Furthermore, re-introduction of miR-33b significantly suppressed tumorigenesis of GC cells in the nude mice. In conclusion, miR-33b acts as a tumor suppressor and hypermethylation of the CpG island upstream of miR-33b is responsible for its down-regulation in gastric cancer.

TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation.

Sumoylation regulates many cellular processes, but its role in signaling via the T cell antigen receptor (TCR) remains unknown. We found that the kinase PKC-θ was sumoylated upon costimulation with antigen or via the TCR plus the coreceptor CD28, with Lys325 and Lys506 being the main sumoylation sites. We identified the SUMO E3 ligase PIASxß as a ligase for PKC-θ. Analysis of primary mouse and human T cells revealed that sumoylation of PKC-θ was essential for T cell activation. Desumoylation did not affect the catalytic activity of PKC-θ but inhibited the association of CD28 with PKC-θ and filamin A and impaired the assembly of a mature immunological synapse and central co-accumulation of PKC-θ and CD28. Our findings demonstrate that sumoylation controls TCR-proximal signaling and that sumoylation of PKC-θ is essential for the formation of a mature immunological synapse and T cell activation.

Unique Dual Functions for Carbon Dots in Emulsion Preparations: Costabilization and Fluorescence Probing.

Recently, carbon dots (CDs) have drawn much attention as evidenced by their incorporation into many branches of science and engineering. Herein, a further unique application is elucidated: CDs that are synthesized by the hydrothermal treatment of gelatin for a dual functionality as expressed in costabilization of particle-based emulsions and their concomitant role as fluorescent probes. CDs either with or without gelatin matrixes induce the aggregation of Laponite particles. The introduction of CDs thus enhanced the stability of Laponite-stabilized emulsions and promoted the formation of multiple emulsions and emulsions with fine and uniform droplets when the CD-to-Laponite mass ratio was less than 45% and exceeded 60%, respectively. However, CDs without gelatin matrixes show slightly higher efficiency than CDs within gelatin matrixes for the costabilization of emulsions. CDs also costabilized emulsions with Laponite to allow the distribution of Laponite particles to be traced and the emulsion profiled under UV.

[Expression of apolipoprotein A-I in eight histological types of renal neoplasms].

OBJECTIVE: To investigate the expression of apolipoprotein A-I(ApoA-I) in eight histological types of renal neoplasms and to explore a new biomarker for differential diagnosis. METHODS: The immunochemistry was used to detect the expression of ApoA-I in 23 cases of renal tumors, including clear cell carcinoma,papillary cell carcinoma, chromophobe cell carcinoma, oncocytoma,multilocular cystic carcinoma, renal pelvis invasive urothelial carcinoma,metanephric adenoma and collecting ducts carcinoma. Five cases of cancer-adjacent normal tissues were obtained from another five renal tumor patients and were chosen as control group. RESULTS: In the 23 cases of renal tumors, ApoA-I was expressed in 21 cases (positive rate was 91.3%). There were only two in five cases of normal tissues which expressed this protein (positive rate was 40.0%). A significant differentiation was observed between the two groups(Z=-2.829,P=0.003). In renal clear cell carcinoma (RCC), ApoA-I expression level was correlated with the grade and stage of tumor tissues. ApoA-I was stained much more stronger in RCC II-III than in RCC I (Z=-2.070,P=0.038).In various histological types of renal cancer, ApoA-I was all expressed to some degrees. CONCLUSION: ApoA-I can be chosen as a tumor biomarker to differentiate various histological types of renal neoplasms.

Molecular insights into DNA interference by CRISPR-associated nuclease-helicase Cas3.

Mobile genetic elements in bacteria are neutralized by a system based on clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins. Type I CRISPR-Cas systems use a "Cascade" ribonucleoprotein complex to guide RNA specifically to complementary sequence in invader double-stranded DNA (dsDNA), a process called "interference." After target recognition by Cascade, formation of an R-loop triggers recruitment of a Cas3 nuclease-helicase, completing the interference process by destroying the invader dsDNA. To elucidate the molecular mechanism of CRISPR interference, we analyzed crystal structures of Cas3 from the bacterium Thermobaculum terrenum, with and without a bound ATP analog. The structures reveal a histidine-aspartate (HD)-type nuclease domain fused to superfamily-2 (SF2) helicase domains and a distinct C-terminal domain. Binding of ATP analog at the interface of the SF2 helicase RecA-like domains rearranges a motif V with implications for the enzyme mechanism. The HD-nucleolytic site contains two metal ions that are positioned at the end of a proposed nucleic acid-binding tunnel running through the SF2 helicase structure. This structural alignment suggests a mechanism for 3' to 5' nucleolytic processing of the displaced strand of invader DNA that is coordinated with ATP-dependent 3' to 5' translocation of Cas3 along DNA. In agreement with biochemical studies, the presented Cas3 structures reveal important mechanistic details on the neutralization of genetic invaders by type I CRISPR-Cas systems.

MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells.

BACKGROUND: MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Total RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1. CONCLUSIONS/SIGNIFICANCE: Our data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.

[MiR-24 improves beta-like globin gene expression through targeting Sp1].

We studied the function and mechanism of miR-24 in regulating beta-like globin gene expression. We first detected the expression of miR-24 during erythroid differentiation and also detected the globin gene expression in miR-24 overexpressing K562 cells through q-PCR. Dual-luciferase reporter assay and Western blotting were used to identify target genes of miR-24. "Rescue experiment" was further used to investigate the regulation of miR-24 on globin gene expression whether depending on targeting Sp1 or not. We found that miR-24 increased during hemin-induced K562 cells and EPO-induced HPCs (hematopoietic progenitor cells) erythroid differentiation. Overexpression of miR-24 in K562 cells promoted the epsilon- and gamma-globin gene expression during hemin-induced erythroid differentiation through targeting the negative globin regulator Sp1. These results suggested that miR-24 can improve the expression of beta-like globin gene through targeting Sp1.

A feedback loop consisting of microRNA 23a/27a and the ß-like globin suppressors KLF3 and SP1 regulates globin gene expression.

The developmental stage-specific expression of the human ß-like globin genes has been studied for decades, and many transcriptional factors as well as other important cis elements have been identified. However, little is known about the microRNAs that potentially regulate ß-like globin gene expression directly or indirectly during erythropoiesis. In this study, we show that microRNA 23a (miR-23a) and miR-27a promote ß-like globin gene expression in K562 cells and primary erythroid cells through targeting of the transcription factors KLF3 and SP1. Intriguingly, miR-23a and miR-27a further enhance the transcription of ß-like globin genes through repression of KLF3 and SP1 binding to the ß-like globin gene locus during erythroid differentiation. Moreover, KLF3 can bind to the promoter of the miR-23a∼27a∼24-2 cluster and suppress this microRNA cluster expression. Hence, a positive feedback loop comprised of KLF3 and miR-23a promotes the expression of ß-like globin genes and the miR-23a∼27a∼24-2 cluster during erythropoiesis.

Expression of survivin and patients survival in non-small cell lung cancer: a meta-analysis of the published studies.

Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant (HR = 1.71, 95 % CI: 1.44-2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC.