The Advancing Role of Nanocomposites in Cancer Diagnosis and Treatment.

The relentless pursuit of effective cancer diagnosis and treatment strategies has led to the rapidly expanding field of nanotechnology, with a specific focus on nanocomposites. Nanocomposites, a combination of nanomaterials with diverse properties, have emerged as versatile tools in oncology, offering multifunctional platforms for targeted delivery, imaging, and therapeutic interventions. Nanocomposites exhibit great potential for early detection and accurate imaging in cancer diagnosis. Integrating various imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging, into nanocomposites enables the development of contrast agents with enhanced sensitivity and specificity. Moreover, functionalizing nanocomposites with targeting ligands ensures selective accumulation in tumor tissues, facilitating precise imaging and diagnostic accuracy. On the therapeutic front, nanocomposites have revolutionized cancer treatment by overcoming traditional challenges associated with drug delivery. The controlled release of therapeutic agents from nanocomposite carriers enhances drug bioavailability, reduces systemic toxicity, and improves overall treatment efficacy. Additionally, the integration of stimuli-responsive components within nanocomposites enables site-specific drug release triggered by the unique microenvironment of the tumor. Despite the remarkable progress in the field, challenges such as biocompatibility, scalability, and long-term safety profiles remain. This article provides a comprehensive overview of recent developments, challenges, and prospects, emphasizing the transformative potential of nanocomposites in revolutionizing the landscape of cancer diagnostics and therapeutics. In Conclusion, integrating nanocomposites in cancer diagnosis and treatment heralds a new era for precision medicine.

Corrigendum: Optimization of tomato (Solanum lycopersicum L.) juice fermentation process and analysis of its metabolites during fermentation.

[This corrects the article DOI: 10.3389/fnut.2024.1344117.].

Rotenone-induced PINK1/Parkin-mediated mitophagy: establishing a silkworm model for Parkinson's disease potential.

Parkinson's disease (PD), ranking as the second most prevalent neurodegenerative disorder globally, presents a pressing need for innovative animal models to deepen our understanding of its pathophysiology and explore potential therapeutic interventions. The development of such animal models plays a pivotal role in unraveling the complexities of PD and investigating promising treatment avenues. In this study, we employed transcriptome sequencing on BmN cells treated with 1 µg/ml rotenone, aiming to elucidate the underlying toxicological mechanisms. The investigation brought to light a significant reduction in mitochondrial membrane potential induced by rotenone, subsequently triggering mitophagy. Notably, the PTEN induced putative kinase 1 (PINK1)/Parkin pathway emerged as a key player in the cascade leading to rotenone-induced mitophagy. Furthermore, our exploration extended to silkworms exposed to 50 µg/ml rotenone, revealing distinctive motor dysfunction as well as inhibition of Tyrosine hydroxylase (TH) gene expression. These observed effects not only contribute valuable insights into the impact and intricate mechanisms of rotenone exposure on mitophagy but also provide robust scientific evidence supporting the utilization of rotenone in establishing a PD model in the silkworm. This comprehensive investigation not only enriches our understanding of the toxicological pathways triggered by rotenone but also highlights the potential of silkworms as a valuable model organism for PD research.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. OBJECTIVES: This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. METHODS: We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER, ≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. RESULTS: There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0 to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (odds ratio: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7% to 65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8 to 42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. CONCLUSIONS: Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Bombyx mori RPL13 participates in UV-induced DNA damage repair of B. mori nucleopolyhedrovirus through interaction with Bm65.

Ribosomal protein L13 (RPL13) is highly conserved in evolution. At present, the properties and functions of RPL13 have not been characterised in insects. In this study, Bombyx mori RPL13 (BmRPL13) was first found to be specifically recruited to the sites of ultraviolet (UV)-induced DNA damage and contributed to UV damage repair. Escherichia coli expressing BmRPL13 showed better resistance to UV radiation. After knocking down the expression of BmRPL13 in BmN cells, the repair speed of UV-damaged DNA slowed down. The further results showed that BmRPL13 interacted with B. mori nucleopolyhedrovirus (BmNPV) ORF65 (Bm65) protein to locate at the UV-induced DNA damage sites of BmNPV and helped repair UV-damaged viral DNA.

Genetically predicted systemic inflammation and the risk of atrial fibrillation: A bidirectional two-sample Mendelian randomization study.

Background: Systemic inflammation has been proposed to be associated with the incidence of atrial fibrillation (AF), but whether it is a cause or a consequence of AF remains uncertain. We sought to explore the causal associations between systemic inflammation and AF using bidirectional Mendelian randomization (MR) analysis. Methods: Independent genetic variants strongly associated with AF were selected as instrumental variables from the largest genome-wide association study (GWAS) with up to 1,030,836 individuals. Regarding inflammation traits, genetic associations with 41 inflammatory cytokines and 5 inflammatory biomarkers were obtained from their corresponding GWASs databases. Effect estimates were primarily evaluated using the inverse-variance weighted (IVW) method, supplemented by sensitivity analyses using MR-Egger, weighted median, and MR-PRESSO methods. Results: In our initial MR analyses, we observed suggestive associations of genetically predicted interleukin-17 (IL-17), interleukin-2 receptor subunit alpha (IL-2rα), and procalcitonin (PCT) with AF. One standard deviation (SD) increase in IL-17, IL-2rα, and PCT caused an increase in AF risk by 6.3 % (OR 1.063, 95 %CI 1.011---1.118, p = 0.018), 4.9 % (OR 1.049, 95 %CI 1.007---1.094, p = 0.023) and 3.4 % (OR 1.034, 95 %CI 1.005---1.064, p = 0.022), respectively. Furthermore, our reverse MR analyses indicated that genetically predicted AF contributed to a suggestive increase in the levels of macrophage inflammatory protein-1ß (MIP1ß) (ß 0.055, 95 %CI 0.006 to 0.103, p = 0.028), while a decrease in the levels of fibrinogen (Fbg) (ß -0.091, 95 %CI -0.140 to -0.041, p < 0.001), which remained significant after multiple test correction. Conclusions: Our MR study identified several inflammatory biomarkers with suggestive causal associations regarding the upstream and downstream regulation of AF occurrence, offering new insights for therapeutic exploitation of AF. Further research is required to validate the underlying link between systemic inflammation and AF in larger cohorts.

The zona pellucida protein piopio regulates the metamorphosis and reproduction in Tribolium castaneum.

The zona pellucida domain protein piopio (Pio) was only reported to mediate the adhesion of the apical epithelial surface and the overlying apical extracellular matrix in Drosophila melanogaster, but the developmental roles of Pio were poorly understood in insects. To address this issue, we comprehensively analyzed the function of Pio in Tribolium castaneum. Phylogenetic analysis indicated that pio exhibited one-to-one orthologous relationship among insects. T. castaneum pio had a 1236-bp ORF and contained eight exons. During development pio was abundantly expressed from larva to adult and lowly expressed at the late stage of embryo and adult, while it had more transcripts in the head, epidermis, and gut but fewer in the fat body of late-stage larvae. Knockdown of pio inhibited the pupation, eclosion, and reproduction of T. castaneum. The expression of vitellogenin 1 (Vg1), Vg2, and Vg receptor (VgR) largely decreased in pio-silenced female adults. Silencing pio increased the 20-hydroxyecdysone titer by upregulating phm and spo expression but decreased the juvenile hormone (JH) titer through downregulating JHAMT3 and promoting JHE, JHEH-r4, and JHDK transcription. These results suggested that Pio might regulate the metamorphosis and reproduction via modulating the ecdysone and JH metabolism in T. castaneum. This study found the novel roles of pio in insect metamorphosis and reproduction, and provided the new insights for analyzing other zona pellucida proteins functions in insects.

A Novel Strategy for Mixed Jam Evaluation: Apparent Indicator, Sensory, Metabolomic, and GC-IMS Analysis.

Jam is a popular traditional and modern food product for daily consumption. However, the benefits of mixed jams over single-fruit jams have not been thoroughly explored, with analyses limited to superficial indices. In this study, Xinjiang special Morus nigra L. and Prunus domestica L. were used as raw materials to prepare single-fruit and mixed jams, and their differences in antioxidants, organoleptic qualities, pH, texture, and color were analyzed. The dynamics of metabolites before and after thermal processing were assessed using untargeted metabolomics. The results indicate that the main metabolites were flavonoids, terpenoids, amino acids, phenolic acids, and carbohydrates. Flavonoid metabolites changed significantly after thermal processing, with 40 up-regulated and 13 down-regulated. During storage, polyphenols were the prominent differential metabolites, with fifty-four down-regulated and one up-regulated. Volatile aroma components were analyzed using gas chromatography-ion mobility spectrometry (GC-IMS); the aroma components E-2-hexenal, E-2-pentenal, 3-methylbutanal, 1-penten-3-ol, tetrahydro-linalool, 1-penten-3-one, hexyl propionate, isoamyl acetate, α-pinene, and propionic acid in mixed jam were significantly higher than in single-fruit jam. In this study, untargeted metabolomics and GC-IMS were used to provide a more comprehensive and in-depth evaluation system for jam analysis.

Metabolomics captures the differential metabolites in the replication pathway of snakehead vesiculovirus regulated by glutamine.

Snakehead vesiculovirus (SHVV) is a negative-sense single-stranded RNA virus that infects snakehead fish. This virus leads to illness and mortality, causing significant economic losses in the snakehead aquaculture industry. The replication and spread of SHVV in cells, which requires glutamine as a nitrogen source, is accompanied by alterations in intracellular metabolites. However, the metabolic mechanisms underlying the inhibition of viral replication by glutamine deficiency are poorly understood. This study utilized liquid chromatography-mass spectrometry to measure the differential metabolites between the channel catfish Parasilurus asotus ovary cell line infected with SHVV under glutamine-containing and glutamine-deprived conditions. Results showed that the absence of glutamine regulated 4 distinct metabolic pathways and influenced 9 differential metabolites. The differential metabolites PS(16:0/16:0), 5,10-methylene-THF, and PS(18:0/18:1(9Z)) were involved in amino acid metabolism. In the nuclear metabolism functional pathway, differential metabolites of guanosine were observed. In the carbohydrate metabolism pathway, differential metabolites of UDP-d-galacturonate were detected. In the signal transduction pathway, differential metabolites of SM(d18:1/20:0), SM(d18:1/22:1(13Z)), SM(d18:1/24:1(15 Z)), and sphinganine were found. Among them, PS(18:0/18:1(9Z)), PS(16:0/16:0), and UDP-d-galacturonate were involved in the synthesis of phosphatidylserine and glycoprotein. The compound 5,10-methylene-THF provided raw materials for virus replication, and guanosine and sphingosine are related to virus virulence. The differential metabolites may collectively participate in the replication, packaging, and proliferation of SHVV under glutamine deficiency. This study provides new insights and potential metabolic targets for combating SHVV infection in aquaculture through metabolomics approaches.

Study on anti-BmNPV mechanism of branched-chain amino acid aminotransferases in silkworm.

Bombyx mori nucleopolyhedrovirus (BmNPV) is the most important virus that threatens sericulture industry. At present, there is no effective treatment for BmNPV infection in silkworms, and lncRNA plays an important role in biological immune response and host-virus interaction, but there are relatively few studies in silkworms. In this study, the four midgut tissue samples of the resistance strain NB (NB) and susceptible strain 306 (306) and the NB and 306 continuously infected with BmNPV for 96 h are used for whole transcriptome sequencing to analyze the differences in the genetic background of NB and 306 and the differences after inoculation of BmNPV, and the significantly different mRNA, miRNA and lnRNA between NB and 306 after BmNPV inoculation were screened. By comparing NB and 306, 2651 significantly different mRNAs, 57 significantly different miRNAs and 198 significantly different lncRNAs were screened. By comparing NB and 306 after BmNPV inoculation, 2684 significantly different mRNAs, 39 significantly different miRNAs and 125 significantly different lncRNAs were screened. According to the significantly different mRNA, miRNA and lncRNA screened from NB and 306 and NB and 306 after virus inoculation, the mRNA-miRNA-lncRNA regulatory network was constructed before and after virus inoculation, and the BmBCAT-Bomo_chr7_8305-MSTRG.3236.2 regulatory axis was screened from them, and it was found that BmBCAT was not Bomo_chr7_8305 regulated in the genetic background, after viral infection, MSTRG.3236.2 competes for binding Bomo_chr7_8305 regulates BmBCAT. The whole transcriptome sequencing results were verified by qPCR and the time-series expression analysis was performed to prove the reliability of the regulatory network. The BmBCAT-Bomo_chr7_8305-MSTRG.3236.2 regulatory axis may play a potential role in the interaction between silkworms and BmNPV. These results provide new insights into the interaction mechanism between silkworms and BmNPV.

Focal atrial tachycardias originating from the aorta-mitral continuity: Anatomical and electrophysiological characteristics.

BACKGROUND: The aorta-mitral annulus conjunction (AMC) is an uncommon site of origin of focal atrial tachycardias (ATs). Hence, the electrophysiological and ablation target characteristics are poorly described. OBJECTIVE: The purpose of this study was to describe the characteristics of AMC AT in detail. METHODS: The study enrolled 650 patients with AT, 21 (3.2%) of whom had AT originating from the AMC. A comprehensive evaluation, including electrocardiography, electrophysiology study, computed tomography scan, and intracardiac echocardiography, was performed. RESULTS: The majority (90.5%) of ATs occurred spontaneously. The mean age of this group was 48.9 ± 21.6 years, with 12 being female (57.1%). Seventeen patients had a typical biphasic P wave with a prominent positive component. The earliest activation site in the right atrium was near the His bundle, with average activation -10.3 ± 6.0 ms preceding the P wave. The successful ablation targets were distributed as follows: 1 case at 9 o'clock, 6 cases at 10 o'clock, 7 cases at 11 o'clock, 6 cases at 12 o'clock, and 1 case in the left coronary cusp. The local AMC potential differed from the commonly perceived annular potential and was characterized by a large A and a small V (atrial-to-ventricular ratio > 1). The angle of encroachment on the left atrial anterior wall, compressed by the left coronary cusp, was significantly smaller in the AMC AT group than in the control group, which may have contributed to the arrhythmia substrate (141.7° ± 11.5° vs 155.2° ± 13.9°; P = .026). CONCLUSION: A new strategy for mapping AMC ATs has been introduced. The ablation target should have an atrial-to-ventricular ratio of >1.

Transcriptome analysis indicates the mechanisms of BmNPV resistance in Bombyx mori midgut.

Bombyx mori nucleopolyhedrovirus (BmNPV) caused serious economic losses in sericulture. Analyzing the molecular mechanism of silkworms (B. mori) resistance to BmNPV is of great significance for the prevention and control of silkworm virus diseases and the biological control of agricultural lepidopteran pests. In order to clarify the defense mechanisms of silkworms against BmNPV, we constructed a near isogenic line BC8 with high resistance to BmNPV through the highly BmNPV-resistant strain NB and the highly BmNPV-susceptible strain 306. In this study, RNA-Seq technique was used to analyze the transcriptome level differences in the midgut of BC8 and 306 following BmNPV infection. A total of 1350 DEGs were identified. Clustering analysis showed that these genes could be divided into 8 clusters with different expression patterns. Functional annotations based on GO and KEGG analysis indicated that they were involved in various metabolism pathways. Finally, 32 BmNPV defense responsive genes were screened. They were involved in metabolism, reactive oxygen species (ROS), signal transduction and immune response, and insect hormones. The further verification shows that HSP70 should participate in resistance responses of anti-BmNPV. These findings have paved the way in further functional characterization of candidate genes and subsequently can be used in breeding of BmNPV resistance dominant silkworms.

Comprehensive transcriptome sequencing of silkworm Midguts: Uncovering extensive isoform diversity and alternative splicing in BmNPV-Sensitive and BmNPV-resistant strains.

The silkworm, Bombyx mori, stands out as one of the few economically valuable insects within the realm of model organisms. However, Bombyx mori nucleopolyhedrovirus (BmNPV) poses a significant threat, decreasing the quality and quantity of silkworm cocoons. Over the past few decades, a multitude of researchers has delved into the mechanisms that underlie silkworm resistance to BmNPV, employing diverse methodologies and approaching the problem from various angles. Despite this extensive research, the role of alternative splicing (AS) in the silkworm's response to BmNPV infection has been largely unexplored. This study leveraged both third-generation (Oxford Nanopore Technologies) and second-generation (Illumina) high-throughput sequencing technologies to meticulously identify and analyze AS patterns in the context of BmNPV response, utilizing two distinct silkworm strains-the susceptible strain 306 and the resistant strain NB. Consequently, we identified five crucial genes (Dsclp, LOC692903, LOC101743583, LOC101742498, LOC101743809) that are linked to the response to BmNPV infection through AS and differential expression. Additionally, a thorough comparative analysis was conducted on their diverse transcriptomic expression profiles, including alternative polyadenylation, simple sequence repeats, and transcription factors.

Development and Validation of a Novel Predictive Model for the Early Differentiation of Cardiac and Non-Cardiac Syncope.

Background: The diagnosis of cardiac syncope remains a challenge. This study sought to develop and validate a diagnostic model for the early identification of individuals likely to have a cardiac cause. Methods: 877 syncope patients with a determined cause were retrospectively enrolled at a tertiary heart center. They were randomly divided into the training set and validation set at a 7:3 ratio. We analyzed the demographic information, medical history, laboratory tests, electrocardiogram, and echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. Then a multivariable logistic regression analysis was performed to identify independent predictors and construct a diagnostic model. The receiver operating characteristic curves, area under the curve (AUC), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy and clinical value of this nomogram. Results: Five independent predictors for cardiac syncope were selected: BMI (OR 1.088; 95% CI 1.022-1.158; P =0.008), chest symptoms preceding syncope (OR 5.251; 95% CI 3.326-8.288; P <0.001), logarithmic NT-proBNP (OR 1.463; 95% CI 1.240-1.727; P <0.001), left ventricular ejection fraction (OR 0.940; 95% CI 0.908-0.973; P <0.001), and abnormal electrocardiogram (OR 6.171; 95% CI 3.966-9.600; P <0.001). Subsequently, a nomogram based on a multivariate logistic regression model was developed and validated, yielding AUC of 0.873 (95% CI 0.845-0.902) and 0.856 (95% CI 0.809-0.903), respectively. The calibration curves showcased the nomogram's reasonable calibration, and the decision curve analysis demonstrated good clinical utility. Conclusion: A diagnostic tool providing individualized probability predictions for cardiac syncope was developed and validated, which may potentially serve as an effective tool to facilitate early identification of such patients.

Kinetic properties of glucose 6-phosphate dehydrogenase and inhibition effects of several metal ions on enzymatic activity in vitro and cells.

Due to the non-degradable and persistent nature of metal ions in the environment, they are released into water bodies, where they accumulate in fish. In order to assess pollution in fish, the enzyme, glucose 6-phosphate dehydrogenase (G6PD), has been employed as a biomarker due to sensitivity to various ions. This study investigates the kinetic properties of the G6PD enzyme in yellow catfish (Pelteobagrus fulvidraco), and analyzes the effects of these metal ions on the G6PD enzyme activity in the ovarian cell line (CCO) of channel catfish (Ictalurus punctatus). IC50 values and inhibition types of G6PD were determined in the metal ions Cu2+, Al3+, Zn2+, and Cd2+. While, the inhibition types of Cu2+ and Al3+ were the competitive inhibition, Zn2+ and Cd2+ were the linear mixed noncompetitive and linear mixed competitive, respectively. In vitro experiments revealed an inverse correlation between G6PD activity and metal ion concentration, mRNA levels and enzyme activity of G6PD increased at the lower metal ion concentration and decreased at the higher concentration. Our findings suggest that metal ions pose a significant threat to G6PD activity even at low concentrations, potentially playing a crucial role in the toxicity mechanism of metal ion pollution. This information contributes to the development of a biomonitoring tool for assessing metal ion contamination in aquatic species.

Arpc2 integrates ecdysone and juvenile hormone metabolism to influence metamorphosis and reproduction in Tribolium castaneum.

BACKGROUND: Actin-related protein 2/3 complex regulates actin polymerization and the formation of branched actin networks. However, the function and evolutionary relationship of this complex subunit 2 (Arpc2) has been poorly understood in insects. RESULTS: To address these issues, we performed comprehensive analysis of Arpc2 in Tribolium castaneum. Phylogenetic analysis revealed that Arpc2 was originated from one ancestral gene in animals but evolved independently between vertebrates and insects after species differentiation. T. castaneum Arpc2 has a 906-bp coding sequence and consists of 4 exons. Arpc2 transcripts were abundantly detected in embryos and pupae but less so in larvae and adults, while it had high expression in the gut, fat body and head but low expression in the epidermis of late-stage larvae. Knockdown of it at the late larval stage inhibited the pupation and resulted in arrested larvae. Silencing it in 1-day pupae impaired eclosion, which caused adult wings to fail to close. Injection of Arpc2 dsRNAs into 5-day pupae made adults have smaller testis and ovary and could not lay eggs. The expression of vitellogenin 1 (Vg1), Vg2 and Vg receptor (VgR) was downregulated after knocking down Arpc2 5 days post-adult emergence. Arpc2 silencing reduced 20-hydroxyecdysone titer by affecting the enzymes of its biosynthesis and catabolism but increased juvenile biosynthesis via upregulating JHAMT3 expression. CONCLUSION: Our results indicate that Arpc2 is associated with the metamorphosis and reproduction by integrating ecdysone and juvenile hormone metabolism in T. castaneum. This study provides theoretical basis for developing Arpc2 as a potential RNA interference target for pest control. © 2024 Society of Chemical Industry.

Prognostic implications of premature ventricular contractions and non-sustained ventricular tachycardia in light-chain cardiac amyloidosis.

AIMS: Premature ventricular contractions (PVC) and non-sustained ventricular tachycardia (NSVT) are commonly observed in light chain cardiac amyloidosis (AL-CA), but their association with prognosis is still unclear. We aimed to evaluate the prognostic value of PVCs and NSVT in patients with moderate-to-advanced AL-CA. METHODS AND RESULTS: We retrospectively included patients with AL-CA at modified 2004 Mayo stages II-IIIb between February 2014 and December 2020. Twenty-four-hour Holter recordings were assessed on admission. The outcomes included (i) new onset of adverse ventricular arrhythmia (VA) or sudden cardiac death (SCD) and (ii) cardiac death during follow-up. Of the 143 patients studied (60.41 ± 11.06 years, male 64.34%), 132 (92.31%) had presence of PVC, and 50 (34.97%) had NSVT on Holter. Twelve (8.4%) patients died in hospital and 131 patients were followed up (median 24.4 months), among whom 71 patients had cardiac death, and 15 underwent adverse VA/SCD. NSVT [hazard ratio (HR): 13.57, 95% confidence interval (CI): 3.06-60.18, P < 0.001], log-transformed PVC counts (HR: 1.46, 95%CI: 1.15-1.86, P = 0.002) and PVC burden (HR: 1.43 95%CI:1.14-1.80, P = 0.002) were predictive of new onset of adverse VA/SCD. The highest tertile of PVC counts (HR: 2.33, 95%CI: 1.27-4.28, P = 0.006) and PVC burden (HR: 2.58, 95%CI: 1.42-4.69, P = 0.002), rather than NSVT (HR: 1.16, 95%CI: 0.67-1.98, P = 0.603), was associated with cardiac death. Higher PVC counts/burden provided incremental value on modified 2004 Mayo stage in predicting cardiac death, with C index increasing from 0.681 to 0.712 and 0.717, respectively (P values <0.05). CONCLUSION: PVC count, burden, and NSVT significantly correlated with adverse VA/SCD during follow-up in patients with AL-CA. Higher PVC counts/burdens added incremental value for predicting cardiac death.

C and G are frequently mutated into T and A in coding regions of human genes.

Nucleotide mutations in human genes have long been a hot subject for study because some of them may lead to severe human diseases. Understanding the general mutational process and evolutionary trend of human genes could help answer such questions as why certain diseases occur and what challenges we face in protecting human health. In this study, we conducted statistics on 89,895 single-nucleotide variations identified in coding regions of 18,339 human genes. The results show that C and G are frequently mutated into T and A in human genes. C/G (C or G)-to-T/A mutations lead to reduction of hydrogen bonds in double-stranded DNA because C-G and T-A base pairs are maintained by three and two hydrogen bonds respectively. C-to-T and G-to-A mutations occur predominantly in human genes because they not only reduce hydrogen bonds but also belong to transition mutation. Reduction of hydrogen bonds could reduce energy consumption not only in separating double strands of mutated DNA for transcription and replication but also in disrupting stem-loop structure of mutated mRNA for translation. It is thus considered that to reduce hydrogen bonds (and thus to reduce energy consumption in gene expression) is one of the driving forces for nucleotide mutation. Moreover, codon mutation is positively correlated to its content, suggesting that most mutations are not targeted on changing any specific codons (amino acids) but are merely for reducing hydrogen bonds. Our study provides an example of utilizing single-nucleotide variation data to infer evolutionary trend of human genes, which can be referenced to conduct similar studies in other organisms.

CMR feature tracking-based left atrial mechanics predicts response to cardiac resynchronization therapy and adverse outcomes.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for advanced heart failure (HF) with prolonged QRS duration. However, 30% of patients have shown no benefit from the treatment. OBJECTIVE: This study aimed to examine the value of left atrial (LA) mechanics by cardiac magnetic resonance (CMR) to predict response to CRT and clinical outcomes. METHODS: A total of 163 CRT recipients with preimplantation CMR examination were retrospectively recruited. CMR feature tracking was used to evaluate LA size and function. The end points include (1) improvement of at least 5% in left ventricular ejection fraction combined with a reduction of at least 1 New York Heart Association functional class at 6-month follow-up and (2) any all-cause death or HF hospitalization during follow-up. RESULTS: Overall, 82 (50.3%) were CRT responders. CRT nonresponders had larger LA and worse LA reservoir and booster pump function than did responders (P < .001 for all). LA structural (maximum volume index < 47 mL/m2) and functional (booster pump strain > 8.5%) criteria were incremental to traditional indicators in detecting CRT response (χ2, 40.83 vs 9.98; P < .001). During follow-up (median 41 months), survival free from death or HF hospitalization increased with the number of positive LA criteria (log-rank, P < .001). After adjustment for clinical confounders, the absence of the 2 criteria remained associated with a considerably increased risk of death or HF hospitalization (adjusted hazard ratio 6.2; 95% confidence interval 2.15-17.88; P = .001). CONCLUSION: The preprocedure LA mechanics evaluated using CMR may be useful to predict response to CRT and improve risk stratification in CRT recipients.

Comparison of Three Detection Methods for Seoul Virus Causing Hemorrhagic Fever with Renal Syndrome.

BACKGROUND: Seoul virus (SEOV) is a significant causative pathogen of hemorrhagic fever with renal syndrome (HFRS). Accurate discrimination of SEOV infection from other viral or bacterial infections holds vital clinical importance. METHODS: Our study utilized quantitative real-time PCR (qRT-PCR), metagenomic next-generation sequencing (mNGS), and immunological assays to identify the pathogen causing HFRS. RESULTS: For the case, mNGS identified SEOV and suspected host or environmental microorganisms at 5 days from symptom onset. qRT-PCR detected SEOV between 5 to 8 days from symptom onset. Anti-hantavirus IgM antibodies reached positive criteria at 7 days and IgG antibodies at 9 days from symptom onset. CONCLUSIONS: qRT-PCR, mNGS, and immunological assays each have merits and drawbacks. Optimal selection depends on laboratory conditions and clinical requirements.