The impact of the time factors on the exercise-based cardiac rehabilitation outcomes of the patients with acute myocardial infarction after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Cardiac rehabilitation (CR) has been demonstrated to improve outcomes in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, the optimal CR initiation time and duration remain to be determined. This study aimed to explore the impact of the time factors on the CR outcomes in AMI patients who received PCI by the method of meta-regression analysis. METHODS: We searched five databases (PubMed, Embase, Cochrane Library, Web of Science and Google scholar) up to October 31, 2023. Meta-regression analysis was utilized to explore the impact of the time factors on the effect sizes. Subgroups with more than 3 studies were used for meta-regression analysis. RESULTS: Our analysis included 16 studies and a total of 1810 patients. The meta-regression analysis revealed that the initiation time and duration of CR had no significant impact on the occurrence of arrhythmia, coronary artery restenosis and angina pectoris. The initiation time and duration of CR also had no significant impact on the changes in left ventricular ejection fraction (LVEF, starting time: estimate = 0.160, p = 0.130; intervention time: estimate = 0.017, p = 0.149), left ventricular end-diastolic volume (LVEDV, starting time: estimate = - 0.191, p = 0.732; intervention time: estimate = - 0.033, p = 0.160), left ventricular end-systolic volume (LVESV, starting time: estimate = - 0.301, p = 0.464; intervention time: estimate = 0.015, p = 0.368) and 6-minute walk test (6MWT, starting time: estimate = - 0.108, p = 0.467; intervention time: estimate = 0.019, p = 0.116). CONCLUSION: Implementation of CR following PCI in patients with AMI is beneficial. However, in AMI patients, there is no significant difference in the improvement of CR outcomes based on different CR starting times within 1 month after PCI or different durations of the CR programs. It indicates that it is feasible for patients with AMI to commence CR within 1 month after PCI and continue long-term CR, but the time factors which impact CR are intricate and further clinical research is still needed to determine the optimal initiation time and duration of CR.

Two stripe rust effectors impair wheat resistance by suppressing import of host Fe-S protein into chloroplasts.

Several effectors from phytopathogens usually target various cell organelles to interfere with plant defenses, and they generally contain sequences that direct their translocation into organelles, such as chloroplasts. In this study, we characterized a different mechanism for effectors to attack chloroplasts in wheat (Triticum aestivum). Two effectors from Puccinia striiformis f. sp. tritici (Pst), Pst_4, and Pst_5, inhibit Bax-mediated cell death and plant immune responses, such as callose deposition and reactive oxygen species (ROS) accumulation. Gene silencing of the two effectors induced significant resistance to Pst, demonstrating that both effectors function as virulence factors of Pst. Although these two effectors have low sequence similarities and lack chloroplast transit peptides, they both interact with TaISP (wheat cytochrome b6-f complex iron-sulfur subunit, a chloroplast protein encoded by nuclear gene) in the cytoplasm. Silencing of TaISP impaired wheat resistance to avirulent Pst and resulted in less accumulation of ROS. Heterogeneous expression of TaISP enhanced chloroplast-derived ROS accumulation in Nicotiana benthamiana. Co-localization in N. benthamiana and western blot assay of TaISP content in wheat chloroplasts show that both effectors suppressed TaISP from entering chloroplasts. We conclude that these biotrophic fungal effectors suppress plant defenses by disrupting the sorting of chloroplast protein, thereby limiting host ROS accumulation and promoting fungal pathogenicity.

Relationships Between Obstructive Sleep Apnea and Cardiovascular Disease: A Bibliometric Analysis (2010-2021).

BACKGROUND Obstructive sleep apnea (OSA) is a common disease that can lead to intermittent hypoxia, increased sympathetic overdrive, and excessive oxidative stress, and eventually lead to cardiovascular/cerebrovascular diseases and metabolic disorders. The prevalence of OSA is reported to be higher in people with certain cardiovascular diseases (CVD). Therefore, the relationship between OSA and CVD has been gradually favored by researchers. MATERIAL AND METHODS Data were downloaded from the Web of Science Core Collection database. Citespace was used to remove duplicated data and construct knowledge visual maps. RESULTS A total of 7047 publications were obtained. The USA was the largest contributor as well as an important player in the cooperation network between nations. The leading institution was the Mayo Clinic. Our study ultimately identified the top 5 hotspots and 4 research frontiers in this field. Top 5 hotspots were: the specific types of obstructive sleep apnea-related cardiovascular and metabolic co-morbidities, the curative effects of CPAP on these co-morbidities, the specific mechanisms of co-morbidities, the importance of polysomnography on OSA and its co-morbidities with CVD, and the prevalence of OSA and its co-morbidities with CVD in particular populations. The top 4 frontiers were: the relationship between OSA and resistant hypertension, the molecular mechanisms of OSA and its co-morbidities with CVD, specific medications and treatment guidelines for the co-morbidities, and the mainstream research methods in this field. CONCLUSIONS This study provides insight and valuable information for researchers and helps to identify new perspectives concerning potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.

Expression regulation of cold-inducible protein RBM3 by FAK/Src signaling for neuroprotection against rotenone under mild hypothermia.

Mild hypothermia is a well-established technique for alleviating neurological injuries in clinical surgery. RNA-binding protein motif 3 (RBM3) has been identified as a crucial factor in mediating hypothermic neuroprotection, providing its induction as a promising strategy for mimicking therapeutic hypothermia. However, little is known about molecular control of RBM3 and signaling pathways affected by hypothermia. In the present study, human SH-SY5Y neuroblastoma cells were used as a neural cell model. Screening of signaling pathways showed that cold exposure led to inactivation of ERK and AMPK pathways, and activation of FAK and PLCγ pathways, with activities of p38, JNK and AKT pathways moderately changed. Next, various small molecule inhibitors specific to these signaling pathways were applied. Interestingly, only FAK-specific inhibitor exhibited a significant inhibitory effect on hypothermia-induced RBM3 gene transcription and protein expression. Likewise, FAK silencing using siRNA technique significantly abrogated the induction of RBM3 by hypothermia. Moreover, FAK inhibition accounted for an inactivation of Src, a known kinase downstream of FAK. Next, either the silencing of Src by siRNA or its inactivation by a chemical inhibitor, strongly blocked the induction of RBM3 by cooling. Notably, in HEK293 and PC12 cells, FAK/Src activation was also shown to be indispensable for hypothermia-stimulated RBM3 expression. Lastly, the CCK8 and Western blot assays showed that both FAK/Src inacitivation and their knockdown substantially abrogate the neuroprotective effects of mild hypothermia against rotenone in SH-SY5Y cells. These data suggest that FAK/Src signaling axis regulates the transcription of Rbm3 gene and mediates neuroprotective effects of mild hypothermia.

On-chip generation of the reconfigurable orbital angular momentum with high order.

In this manuscript, the generation of an optical vortex beam with high order and reconfigurable orbital angular momentum (OAM) is studied. Multi-waveguide holographic gratings (MWHG) are deployed to generate OAM beams with high order. The generation of the OAM beam with an order l from +4 to +8 is demonstrated by numerical simulations, and the generated OAM order is manipulable and configurable by incident phase. The working bandwidths of the MWHG for different OAM orders are at the level of 40 nm. This work could provide valuable references for practical implementation of OAM in integrated optics.

Cold-inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling.

Mild hypothermia and its key product, cold-inducible protein RBM3, possess robust neuroprotective effects against various neurotoxins. However, we previously showed that mild hypothermia fails to attenuate the neurotoxicity from MPP+ , one of typical neurotoxins related to the increasing risk of Parkinson disease (PD). To better understand the role of mild hypothermia and RBM3 in PD progression, another known PD-related neurotoxin, rotenone (ROT) was utilized in this study. Using immunoblotting, cell viability assays and TUNEL staining, we revealed that mild hypothermia (32°C) significantly reduced the apoptosis induced by ROT in human neuroblastoma SH-SY5Y cells, when compared to normothermia (37°C). Meanwhile, the overexpression of RBM3 in SH-SY5Y cells mimicked the neuroprotective effects of mild hypothermia on ROT-induced cytotoxicity. Upon ROT stimulation, MAPK signalling like p38, JNK and ERK, and AMPK and GSK-3ß signalling were activated. When RBM3 was overexpressed, only the activation of p38, JNK and ERK signalling was inhibited, leaving AMPK and GSK-3ß signalling unaffected. Similarly, mild hypothermia also inhibited the activation of MAPKs induced by ROT. Lastly, it was demonstrated that the MAPK (especially p38 and ERK) inhibition by their individual inhibitors significantly decreased the neurotoxicity of ROT in SH-SY5Y cells. In conclusion, these data demonstrate that RBM3 mediates mild hypothermia-related neuroprotection against ROT by inhibiting the MAPK signalling of p38, JNK and ERK.

Overexpression of the peanut CLAVATA1-like leucine-rich repeat receptor-like kinase AhRLK1 confers increased resistance to bacterial wilt in tobacco.

Bacterial wilt caused by Ralstonia solanacearum is a devastating disease affecting hundreds of plant species, yet the host factors remain poorly characterized. The leucine-rich repeat receptor-like kinase gene AhRLK1, characterized as CLAVATA1, was found to be up-regulated in peanut upon inoculation with R. solanacearum. The AhRLK1 protein was localized in the plasma membrane and cell wall. qPCR results showed AhRLK1 was induced in a susceptible variety but little changed in a resistant cultivar after inoculated with R. solanacearum. Hormones such as salicylic acid, abscisic acid, methyl jasmonate, and ethephon induced AhRLK1 expression. In contrast, AhRLK1 expression was down-regulated under cold and drought treatments. Transient overexpression of AhRLK1 led to a hypersensitive response (HR) in Nicotiana benthamiana. Furthermore, AhRLK1 overexpression in tobacco significantly increased the resistance to R. solanacearum. Besides, the transcripts of most representative defense responsive genes in HR and hormone signal pathways were significantly increased in the transgenic lines. EDS1 and PAD4 in the R gene signaling pathway were also up-regulated, but NDR1 was down-regulated. Accordingly, AhRLK1 may increase the defense response to R. solanacearum via HR and hormone defense signaling, in particular through the EDS1 pathway of R gene signaling. These results provide a new understanding of the CLAVATA1 function and will contribute to genetic enhancement of peanut.

Implant-Supported Hybrid Prosthesis for Severe Mandibular Defects: A Sequence of Treatments From Alveolar Distraction Osteogenesis to Implant Restoration.

PURPOSE: Although a variety of treatment methodologies for the physiological reconstruction of mandibular defects exist, the use of these methods has often been fragmented and has focused on partial effects of therapy. This article describes a sequence of treatments for a severe mandibular defect. PATIENTS AND METHODS: Two patients with severe hard and soft tissue defects had physiological function restored in 4 steps, including alveolar distraction osteogenesis, implant insertion based on a prosthesis, application of dermal matrix membrane in reconstruction of attachment gingiva, and the use of a hybrid prosthesis designed via computer-aided design and computer-aided manufacturing, to produce an adequate bone tissue volume, an adequate amount of attached gingiva, and a reliable prosthesis. RESULTS: The sequence of treatments successfully achieved physiological reconstruction. Biological complications around the implants and mechanical complications in the implants or prostheses did not occur within a 4-year follow-up period. CONCLUSIONS: On the basis of the current 4-year follow-up, this study shows that a treatment sequence can be predictable and effective for severe mandibular defects, which suggests that it could be considered a potential protocol for patients with severe mandibular defects.

[Techniques and methods evaluation on pharmaceutical stability of liposomes].

Liposomes as a drug carrier is easy to form aggregation and cause drug leakage in vitro. In addition, the degradation and elimination in vivo happens frequently to reduce its delivery activity. Development and application of liposomes are restricted by the instability. The appropriate techniques and methods are great important in the study of pharmaceutical stability of liposomes. In this paper, the techniques and methods are reviewed on pharmaceutical stability evaluation of liposomes, which was done from physical, chemical and biological stability for the difference in stability of liposomes. The research strategies for establishing the stability evaluation system and improving the value of liposomes have been discussed to make full therapeutic advantage of it.

[Timing of nasojejunal feeding tube placement and enteral nutrition in children with acute pancreatitis].

OBJECTIVE: To investigate the impact of timing of nasojejunal feeding tube placement and enteral nutrition on clinical outcomes in children with acute pancreatitis. METHODS: A retrospective analysis was performed on the clinical data of 31 children with acute pancreatitis, who received nasojejunal feeding between January 2008 and July 2013, to investigate the relationship of abdominal symptoms/signs and serum amylase level with the tolerability of catheterization and success rate of enteral nutrition. The treatment outcome and incidence of adverse reactions and complications were compared between the early enteral nutrition group ( ≤7 days from the onset of the disease) and late enteral nutrition group (>7 days from the onset of the disease). RESULTS: Abdominal symptoms/signs and serum amylase level were independent of the tolerable rate of catheterization and success rate of enteral nutrition. Compared with the late enteral nutrition group, the early enteral nutrition group had a shortened time to normal serum amylase level, significantly reduced incidence of systemic complications, length of hospital stay, and hospitalization expenses, and less weight gain. The tolerable rate of catheterization and success rate of enteral nutrition showed no significant difference between the two groups. Similarly, no significant differences were found in the increase in albumin level after enteral nutrition, duration of enteral nutrition, incidence of adverse reactions, and incidence of local complications. CONCLUSIONS: Abdominal symptoms/signs and serum amylase level cannot be used as a measure of whether nasojejunal feeding tube placement and enteral nutrition can be performed. Early enteral nutrition can better improve clinical outcomes in children with acute pancreatitis, and it is feasible.

Association of hyperuricemia with coronary heart disease: Protocol for an updated systematic review and dose-response meta-analysis.

INTRODUCTION: Hyperuricemia, characterized by elevated serum uric acid levels, has garnered significant attention in cardiovascular research due to its potential association with coronary heart disease (CHD). While some studies suggest hyperuricemia as a risk factor of CHD, others present conflicting findings. A systematic review and dose-response meta-analysis is warranted to comprehensively summarize the previous studies and determine the association between hyperuricemia and CHD, thereby supporting clinical practice and future studies in this field. METHODS: In this study, we will comprehensively search Medline, EMBase, Cochrane Central, ICTRP, and ClinicalTrials.gov, from inception to December 31, 2024. Prospective or retrospective cohort studies and case-control studies investigating the association between hyperuricemia and CHD will be included. Two independent reviewers will conduct study selection, data extraction, and risk of bias assessment. The primary outcome will be the pooled relative risk of CHD associated with hyperuricemia by using random-effect model. Dose-response meta-analysis will be performed with linear and non-linear model to explore the the magnitude and direction of the association between serum uric acid levels and CHD risk. Subgroup analyses will be conducted based on uric acid test approaches and corresponding cut-off values and human races. Sensitivity analyses will assess the robustness of the results with leave-one-out method, while publication bias will be evaluated using funnel plots, Egger's test, and Begg's test. We will further use GRADE to evaluate the quality of the evidences provided by our systematic review. EXPECTED RESULTS: From this systematic review and dose-response meta-analysis, we hope out findings will provide reliable conclusion and data support on the association between hyperuricemia and CHD. The transparent and replicable methodologies outlined in this protocol contribute to advancing understanding of hyperuricemia as a potentially modifiable risk factor for CHD, thus supporting evidence-based strategies for cardiovascular disease management. CONCLUSIONS: This protocol describes a rigorous plan to systematically review and analyze the quantitative association between hyperuricemia and CHD risk. In a word, we will help further clinical practice and scientific studies in this field. TRIAL REGISTRATION: This protocol was registered in PROSPERO CRD42024538553.

Anemia in Heart Failure: A Perspective from 20-Year Bibliometric Analysis.

Background & Objective: Anemia in patients with heart failure (HF) is a growing concern. However, there has no bibliometric analysis in this area up to now. The aim of this study is to explore the status and trends in the field of anemia in HF through the bibliometric analysis, and to provide an outlook on future research. Methods: We retrieved publications from the Web of Science Core Collection database, and the following data analysis and visualization tools were utilized to perform data processing, statistical computing and graphics generation: VOSviewer (v.1.6.18), CiteSpace (v.6.2 R5), Scimago Graphica (v.1.0.36), Biblimatrix and Microsoft Excel. Results: We identified a total of 3490 publications from 2004 to 2023. The publications in the field of anemia in HF are growing steadily. The United States, the United Kingdom, and Italy were the leading countries in this area. Stefan D Anker, as the most influential author, held the most total citations and publications. Harvard University was the most productive institution in this area. The European Journal of Heart Failure had published the most papers. Through the analysis of co-citations, 14 major clusters based on cluster labels were identified. Keyword analysis showed that mortality, outcome, prevalence, and risk were the most frequent keywords, and the potential research hotspots in the future will be intravenous iron and iron deficiency. Conclusion: This study provides a comprehensive analysis of countries, authors, institutions, journals, co-cited references, and keywords in the field of anemia in HF through bibliometric analysis and data visualization. The status, hotspots and future trends in this field offer a reference for in-depth research. Further studies are necessary in the future to broaden the spectrum of research in this field, to evaluate comprehensive approaches to treating anemia in patients with HF, and to find rational targets for the management of anemia.

The role of coffee and potential mediators in subclinical atherosclerosis: insights from Mendelian randomization study.

Background and aims: Coffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators. Methods: We first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses. Results: Coffee, filtered coffee, and instant coffee were associated with the risk of CAC (ß = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; ß = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; ß = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (ß = -1.32, 95% CI: -2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (ß = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030). Conclusion: Our study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.

Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis.

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.

A high-affinity fluorescent probe for human uridine-disphosphate glucuronosyltransferase 1A9 function monitoring under environmental pollutant exposure.

Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.

Molecular targets and mechanisms of Guanxinning tablet in treating atherosclerosis: Network pharmacology and molecular docking analysis.

BACKGROUND: Guanxinning tablet (GXNT), a Chinese patent medicine, is composed of salvia miltiorrhiza bunge and ligusticum striatum DC, which may play the role of endothelial protection through many pathways. We aimed to explore the molecular mechanisms of GXNT against atherosclerosis (AS) through network pharmacology and molecular docking verification. METHODS: The active ingredients and their potential targets of GXNT were obtained in traditional Chinese medicine systems pharmacology database and analysis platform and bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. DrugBank, TTD, DisGeNET, OMIM, and GeneCards databases were used to screen the targets of AS. The intersection targets gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were performed in DAVID database. GXNT-AS protein-protein interaction network, ingredient-target network and herb-target-pathway network were constructed by Cytoscape. Finally, we used AutoDock for molecular docking. RESULTS: We screened 65 active ingredients of GXNT and 70 GXNT-AS intersection targets. The key targets of protein-protein interaction network were AKT1, JUN, STAT3, TNF, TP53, IL6, EGFR, MAPK14, RELA, and CASP3. The Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling pathway were the main pathways. The ingredient-target network showed that the key ingredients were luteolin, tanshinone IIA, myricanone, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone. The results of molecular docking showed that tanshinone IIA, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone all had good binding interactions with AKT1, EGFR and MAPK14. CONCLUSION: The results of network pharmacology and molecular docking showed that the multiple ingredients within GXNT may confer protective effects on the vascular endothelium against AS through multitarget and multichannel mechanisms. AKT1, EGFR and MAPK14 were the core potential targets of GXNT against AS.

Emerging trends and hotspots evolution in cardiotoxicity: A bibliometric and knowledge-Map analysis From 2010 to 2022.

Background: There is growing emphasis on the cardiotoxicity research over the past 12 years. To look for the hotspots evolution and to explore the emerging trends in the field of cardiotoxicity, publications related to cardiotoxicity were acquired from the Web of Science Core Collection on August 2, 2022. Methods: We used the CiteSpace 5.8 R3 and VOSviewer 1.6.18 to perform bibliometric and knowledge-map analysis. Results: A total of 8,074 studies by 39,071 authors from 6,530 institutions in 124 countries or regions were published in different academic journals. The most productive country was absolutely the United States, and the University of Texas MD Anderson Cancer Center was the institution with the largest output. Zhang, Yun published the most articles, and the author who had the most frequent co-citations was Moslehi, Javid. New England Journal of Medicine was the most frequently cited journals in this field. Mechanisms of cardiotoxicity have received the most attention and was the main research directions in the field. The disease of cardiotoxicity together with the related risk factors are potential research hotspots. Immune checkpoint inhibitor and myocarditis are two recently discussed and rapidly expanding research topic in the areas of cardiotoxicity. Conclusions: This bibliometric analysis provided a thorough analysis of the cardiotoxicity, which would provide crucial sources of information and concepts for academics studying this area. As a rapidly expanding field in cardiology, the related field of cardiotoxicity will continue to be a focus of research.

Insight into the role of crystallinity in oxide electrolytes enabling high-performance all-solid-state lithium-sulfur batteries.

All-solid-state lithium-sulfur batteries (ASSLSBs) would be a promising candidate for the next-generation batteries due to the utilization of energy-dense electrodes and the non-flammable oxide solid-state electrolytes (SSEs), but still face great challenges such as low ionic conductivity of SSEs, poor interfacial contact and lithium (Li) dendrite propagation. Herein, we regulated the crystallinity degrees of the large-scale-fabricated Li1.5Al0.5Ge1.5(PO4)3 (LAGP) SSEs and explored the critical role of crystallinity optimization in reinforcing the basic properties of LAGP, developing a fundamental explanation for the inherent relation between the crystallinity and the performance of ASSLSBs. Benefiting from the optimized crystallinity (∼99.9 %), the large-scale-fabricated LAGP not only realizes the low surface roughness and high ionic conductivity (2.11 × 10-4 S cm-1) to improve interfacial contact and reduce resistance in ASSLSBs, but also possesses the dense internal structure with low porosity (1.49 %) to physically resist dendritic propagation and penetration. Consequently, the ASSLSB with the optimized LAGP delivers a high reversible capacity of 647.9 mAh/g even after 150 cycles at 0.1 C. This work confirms the significance of crystallinity in understanding the working mechanisms of oxide SSEs and developing future high-performance ASSLSBs.

Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis.

The detection of nonsmall cell lung cancer (NSCLC) at an early stage presents a daunting challenge due to the lack of a specific noninvasive marker. The discovery of microRNAs (miRNAs), particularly those found in serum, has opened a new avenue for tumor diagnosis. To determine whether the expression profile of serum miRNAs can serve as a NSCLC fingerprint, we performed Taqman probe-based quantitative RT-PCR assay to selected differentially expressed serum miRNAs from a sample set including 400 NSCLC cases and 220 controls, and risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. After a two-phase selection and validation process, 10 miRNAs were found to have significantly different expression levels in NSCLC serum samples compared with the control serum samples. Risk score analysis showed that this panel of miRNAs was able to distinguish NSCLC cases from controls with high sensitivity and specificity. Under ROC curves, the AUC for tumor identification in training set and validation set were 0.966 and 0.972, respectively. Furthermore, the expression profile of the 10-serum miRNAs was correlated with the stage of NSCLC patients, especially in younger patients and patients with current smoking habits. More importantly, the serum miRNA-based biomarker for early NSCLC detection was supported by a retrospective analysis in which the 10-serum miRNA profile could accurately classify serum samples collected up to 33 months ahead of the clinical NSCLC diagnosis. Taken together, we demonstrate that the profiling of 10-serum miRNAs provides a novel noninvasive biomarker for NSCLC diagnosis.

Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer.

BACKGROUND: Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS: We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA-based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS: After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA-based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS: These data demonstrate that the 7 miRNA-based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.