High Thermal Conductivity of Sandwich-Structured Flexible Thermal Interface Materials.

Thermal interfaces are vital for effective thermal management in modern electronics, especially in the emerging fields of flexible electronics and soft robotics that impose requirements for interface materials to be soft and flexible in addition to having high thermal performance. Here, a novel sandwich-structured thermal interface material (TIM) is developed that simultaneously possesses record-low thermal resistance and high flexibility. Frequency-domain thermoreflectance (FDTR) is employed to investigate the overall thermal performance of the sandwich structure. As the core of this sandwich, a vertically aligned copper nanowire (CuNW) array preserves its high intrinsic thermal conductivity, which is further enhanced by 60% via a thick 3D graphene (3DG) coating. The thin copper layers on the top and bottom play the critical roles in protecting the nanowires during device assembly. Through the bottom-up fabrication process, excellent contacts between the graphene-coated CuNWs and the top/bottom layer are realized, leading to minimal interfacial resistance. In total, the thermal resistance of the sandwich is determined as low as ~0.23 mm2  K W-1 . This work investigates a new generation of flexible thermal interface materials with an ultralow thermal resistance, which therefore renders the great promise for advanced thermal management in a wide variety of electronics.

Systematic Review and Meta-analysis Appraising Efficacy and Safety of Vernakalant for Cardioversion of Recent-Onset Atrial Fibrillation.

Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent. Despite its good efficacy profile and rapid onset of action, there was still controversial evidence regarding vernakalant-related adverse events. We searched PubMed and Embase for studies that compared intravenous vernakalant with placebo or antiarrhythmic agents in patients with recent-onset atrial fibrillation (AF) lasting no more than 7 days. Efficacy and safety outcomes were the treatment-induced cardioversion rate within 90 minutes and adverse events after first exposure to study drug respectively. Nine randomized controlled trials enrolling 1296 patients were analyzed. Quantitative synthesis showed that vernakalant was superior to placebo for cardioversion of recent-onset AF within 90 minutes [49.7% vs. 6.2%, risk ratio (RR) 8.13, 95% confidence interval (CI) 5.35-12.36, P < 0.00001], and it did not achieve statistical significance in cardioversion when vernakalant was compared with ibutilide (62.4% vs. 47.3%, RR 1.32, 95% CI 1.00-1.73, P = 0.05). As for safety assessment, no significant differences were found in occurring serious adverse events (9.9% vs. 10.4%, RR 0.91, 95% CI 0.67-1.25, P = 0.57) and hypotension (5.3% vs. 3.3%, RR 1.53, 95% CI 0.86-2.73, P = 0.15) between vernakalant and comparator (either placebo, ibutilide, or amiodarone). There were trends that patients receiving vernakalant experienced more drug discontinuation (2.5% vs. 1.0%, RR 2.21, 95% CI 0.96-5.11, P = 0.06) and less any ventricular tachycardia (6.1% vs. 8.1%, RR 0.70, 95% CI 0.49-1.00, P = 0.05) than those receiving comparator, but the differences were not statistically significant. Furthermore, vernakalant was associated with a higher risk of bradycardia in comparison with comparator (6.3% vs. 1.1%, RR 4.04, 95% CI 1.67-9.75, P = 0.002). Vernakalant is effective in converting recent-onset AF to sinus rhythm rapidly, while significantly more bradycardia events are related to vernakalant in our meta-analysis.

DNA Encountering Terbium(III): A Smart "Chemical Nose/Tongue" for Large-Scale Time-Gated Luminescent and Lifetime-Based Sensing.

Recent years have witnessed the rapid development of pattern-based sensors due to their potential to detect and differentiate a wealth of analytes with only few probes. However, no one has found or used the combination of DNA and terbium(III) (Tb) as a pattern recognition system for large-scale mix-and-measure assays. Here we report for the first time that DNA-sensitized Tb (DNA/Tb), as a label-free and versatile "chemical nose/tongue", can be employed for wide-scale time-gated luminescent (TGL) monitoring of metal ions covering nearly the entire periodic table in a cost-effective fashion. A series of guanine/thymine (G/T)-rich DNA ligands was screened to sensitize the luminescence of Tb (referring to the antenna effect) as smart pattern responders to metal ions in solution, and metal ion-DNA interactions can differentially alter the antenna effect of DNA toward Tb as pattern signals. Our results show that as few as 3 DNA/Tb label-free sensors could successfully discriminate 49 analytes, including alkali-metal ions, alkaline-earth-metal ions, transition/post-transition metal ions, and lanthanide ions. A blind test with 49 metals further confirmed the discriminating power of DNA/Tb sensors. Moreover, the lifetime-based pattern recognition application using DNA/Tb sensors was also demonstrated. This DNA/Tb pattern recognition strategy could be extended to construct a series of "chemical noses/tongues" for monitoring various biochemical species by using different responsive DNA ligands, thus promising a versatile and powerful tool for a sensing application and investigation of DNA-involving molecular interactions.

Altered MiRNA expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND/AIMS: Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a systematic review and meta-analysis of altered miRNAs in gastric cancer in order to assess the use of miRNAs as novel biomarkers for early detection and prognosis prediction of gastric cancer. METHODS: We retrieved published articles from the PubMed online database and obtained different sets of data on miRNAs expression profiling in gastric cancer and highlighted the most frequently dysregulated miRNAs in gastric cancer. We then extracted studies that used quantitative RT-PCR and then pooled them together by using meta-disc software (version 1.4). RESULTS: We found that there were 47 aberrantly expressed miRNAs in gastric cancer (29 up-regulated and 18 down-regulated) that were most frequently reported in the literature. In publications that provided information on specific miRNA expression vs. diagnostic value, the pooled data showed good sensitivity and specificity as well as high levels of overall accuracy. However, specimen types could be a factor that introduces substantial heterogeneity. Published studies also showed association of altered miRNA expression with clinicopathological data from gastric cancer patients. CONCLUSION: Thus, various miRNAs are differentially expressed in gastric cancer and some of them could be further evaluated as biomarkers for early diagnosis of gastric cancer and prediction of prognosis or treatment response.

EUS-Guided FNA for Diagnosis of Pancreatic Cystic Lesions: a Meta-Analysis.

BACKGROUND: Preoperative diagnosis of pancreatic cystic lesions (PCLs) must be reliable as the current standard treatment, major or total pancreatectomy, dramatically affects quality of life. Additionally, early diagnosis of malignancy is essential to an improved prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been demonstrated in pancreatic solid lesions. The utility of this technique in the diagnosis of PCLs is still unknown. METHODS: A comprehensive search was performed in multiple databases. Studies differentiating benign and malignant PCLs via EUS-FNA were included in this meta-analysis. The quality of diagnostic accuracy studies (QUADAS) was adopted to evaluate the selected studies. Pooled sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curve analyses were conducted. Two main classification types of malignancy were characterized and analyzed. We also generated a subgroup analysis of available clinical factors. Publication bias was evaluated by Begg's and Egger's tests. RESULTS: Sixteen studies containing 1024 subjects have been published. The pooled sensitivity for malignant cytology according to classification 1 was 0.51 (95% CI, 0.45-0.58), and pooled specificity was 0.94 (95% CI, 0.92-0.96). When the detected PCLs were identified as classification 2, suspicious malignancy or potential malignancy, sensitivity and specificity were similar, 0.52 (95% CI, 0.46-0.57) and 0.97 (95% CI, 0.95-0.98) respectively. CONCLUSION: This meta-analysis demonstrates that EUS-FNA is a reliable clinical tool for the diagnosis of PCLs. However, a more accurate algorithm is needed to reduce various biases and to improve the sensitivity of EUS-FNA in the detection of malignant PCLs.

Combined analysis of bulk RNA and single-cell RNA sequencing to identify pyroptosis-related markers and the role of dendritic cells in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea caused by airflow limitation. Further development may lead to decreased lung function and other lung diseases. Pyroptosis is a type of programmed cell death that involves multiple pathways. For example, the pathway induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with COPD exacerbation. Therefore, in this study, various machine learning algorithms were applied to screen for diagnostically relevant pyroptosis-related genes from the GEO dataset, and the results were verified using external datasets. The results showed that deep neural networks and logistic regression algorithms had the highest AUC of 0.91 and 0.74 in the internal and external test sets, respectively. Here, we explored the immune landscape of COPD using diagnosis-related genes. We found that the infiltrating abundance of dendritic cells significantly differed between the COPD and control groups. Finally, the communication patterns of each cell type were explored based on scRNA-seq data. The critical role of significant pathways involved in communication between DCS and other cell populations in the occurrence and progression of COPD was identified.

Efficacy of GnRH Pulses in Hypogonadism Secondary to Primary Empty Sella: Case Report.

This study aims to assess the effectiveness of pulsed gonadotropin-releasing hormone (GnRH) micropump replacement therapy in the treatment of hypogonadotropic hypogonadism (HH) caused by primary empty sella (PES).The efficacy of pulsed GnRH replacement therapy using the micropump was evaluated in a middle-aged male patient with HH who had experienced the loss of his only child. Relevant literature was also consulted to compare the differences between pulse GnRH treatment and conventional treatment in terms of the development of secondary sexual characteristics, sex hormone levels, sperm production rate, and sperm activity rate in male patient with HH.In this report, a 45-year-old male diagnosed with HH and PES presented with fatigue and decreased libido. The main characteristics included decreased follicle stimulating hormone (FSH) levels of 0.03 mIU/mL, luteinizing hormone (LH) levels of 0.02 mIU/mL, and testosterone (T) levels of 0.72 nmol/L. Magnetic resonance imaging (MRI) revealed an empty sella. Semen analysis showed a small number of normal sperm with reduced motility. During treatment with the micropump pulse GnRH, the patient experienced no side effects and showed improvements in fatigue, reduced libido, sexual urge, anxiety, and feelings of inferiority. LH, FSH, and T levels returned to normal, while sperm activity rate increased to 79.9%. Ultimately, the patient's spouse achieved a natural pregnancy.Pulsed gonadotropin delivery using the micropump demonstrates good efficacy and tolerability, and aligns more closely with the physiological rhythm of GnRH secretion in the human body.

Promising roles of non-exosomal and exosomal non-coding RNAs in the regulatory mechanism and as diagnostic biomarkers in myocardial infarction. / 非外泌体/å¤–æ³Œä½“éžç¼–ç RNAsåœ¨å‚ä¸Žå¿ƒè‚Œæ¢—æ­»è°ƒèŠ‚åŠä½œä¸ºè¯Šæ–­æ€§ç”Ÿç‰©æ ‡å¿—ç‰©æ–¹é¢çš„ä½œç”¨.

Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.

Effect of dapagliflozin on liver and pancreatic fat in patients with type 2 diabetes and non-alcoholic fatty liver disease.

AIMS: To evaluate the effect of dapagliflozin on liver fat content (LFC) and pancreatic fat content (PFC). MATERIALS AND METHODS: 84 patients with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) were randomly assigned to receive either dapagliflozin (n = 42) or serve as controls (n = 42). The primary endpoint is changes in LFC and PFC using magnetic resonance imaging estimated proton density fat fraction. Secondary outcomes include liver fibrosis index, inflammatory cytokine levels, and liver enzyme levels. RESULTS: At week 24, the dapagliflozin group significantly reduced LFC (P < 0.001) and PFC (P = 0.033) compared to the control group. Differences were also observed in serum levels of tumor necrosis factor-α (TNF-α) (P = 0.004), interleukin-6 (IL-6) (P = 0.001), and alanine aminotransferase (ALT) (P < 0.001) between the two groups. CONCLUSIONS: Dapagliflozin can significantly decrease LFC and PFC in patients with T2D and NAFLD. It also improves serum ALT, TNF-α, and IL-6 levels, making it a promising treatment option for NAFLD. The trial is registered on Chinese Clinical Trial Registry (Registration No. ChiCTR2100054612).

Modular Assembly of MXene Frameworks for Noninvasive Disease Diagnosis via Urinary Volatiles.

Volatile organic compounds (VOCs) in urine are valuable biomarkers for noninvasive disease diagnosis. Herein, a facile coordination-driven modular assembly strategy is used for developing a library of gas-sensing materials based on porous MXene frameworks (MFs). Taking advantage of modules with diverse composition and tunable structure, our MFs-based library can provide more choices to satisfy gas-sensing demands. Meanwhile, the laser-induced graphene interdigital electrodes array and microchamber are laser-engraved for the assembly of a microchamber-hosted MF (MHMF) e-nose. Our MHMF e-nose possesses high-discriminative pattern recognition for simultaneous sensing and distinguishing of complex VOCs. Furthermore, with the MHMF e-nose being a plug-and-play module, a point-of-care testing (POCT) platform is modularly assembled for wireless and real-time monitoring of urinary volatiles from clinical samples. By virtue of machine learning, our POCT platform achieves noninvasive diagnosis of multiple diseases with a high accuracy of 91.7%, providing a favorable opportunity for early disease diagnosis, disease course monitoring, and relevant research.

DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: Several clinical studies have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic effects of DPP-4 inhibitors on T1DM. METHODS: We thoroughly searched the Medline, Embase, PubMed, and Cochrane Library databases and ClinicalTrials.gov for studies concerning the use of DPP-4 inhibitors in patients with T1DM. RESULTS: In preclinical trials, DPP-4 inhibitors improved the pathogenesis of T1DM. However, only a portion of the studies showed potential efficacy regarding clinical glycemic control and other clinical parameters. From this meta-analysis, pooled data from 5 randomized controlled trials revealed that the additional use of DPP-4 inhibitors resulted in a greater decrease in glycated hemoglobin A1c (HbA1c) levels (0.07%, 95% CI (-0.37%-0.23%)) than insulin monotherapy, although the decrease was not significant. A small decrease in postprandial glucose or insulin consumption was confirmed. CONCLUSION: Although DPP-4 inhibitors may be beneficial for T1DM, existing studies do not strongly support these positive effects in clinical practice. Further optimized clinical trials are needed.

Dual lanthanide-doped complexes: the development of a time-resolved ratiometric fluorescent probe for anthrax biomarker and a paper-based visual sensor.

In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO2-Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO2-Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties.

Nanomolar sensitive colorimetric assay for Mn2+ using cysteic acid-capped silver nanoparticles and theoretical investigation of its sensing mechanism.

A new facile, rapid, sensitive and selective colorimetric assay is proposed for the determination of manganese ions (Mn2+) utilizing cysteic acid (CA)-capped silver nanoparticles (CA-AgNPs) as colorimetric probes. The CA-AgNPs were prepared by reducing AgNO3 with NaBH4 in the presence of CA as the capping ligand. The presence of Mn2+ induces the quick aggregation of CA-AgNPs, associated with notable color changes of the CA-AgNPs solution from yellow to dark green. The Mn2+ can form a coordinated structure with CA capping on the AgNPs and leads to formation of large particles aggregation. We also used density functional theory (DFT) to calculate the change of the Gibbs free energy (ΔG) of the interactions between the CA-AgNPs and various metal ions, which shows that CA-AgNPs have high specificity for Mn2+. The high sensitivity and selectivity for Mn2+ were achieved and the detection limit is as low as 5 nM. Furthermore, the proposed method was successfully applied in detecting Mn2+ in a rat model of focal ischemia and the results indicate that our proposed method has great potential for practical applications.

An integrated logic system for time-resolved fluorescent "turn-on" detection of cysteine and histidine base on terbium (III) coordination polymer-copper (II) ensemble.

Cysteine (Cys) and histidine (His) both play indispensable roles in many important biological activities. An enhanced Cys level can result in Alzheimer's and cardiovascular diseases. Likewise, His plays a significant role in the growth and repair of tissues as well as in controlling the transmission of metal elements in biological bases. Therefore, it is meaningful to detect Cys and His simultaneously. In this work, a novel terbium (III) coordination polymer-Cu (II) ensemble (Tb(3+)/GMP-Cu(2+)) was proposed. Guanosine monophosphate (GMP) can self-assemble with Tb(3+) to form a supramolecular Tb(3+) coordination polymer (Tb(3+)/GMP), which can be suited as a time-resolved probe. The fluorescence of Tb(3+)/GMP would be quenched upon the addition of Cu(2+), and then the fluorescence of the as-prepared Tb(3+)/GMP-Cu(2+) ensemble would be restored again in the presence of Cys or His. By incorporating N-Ethylmaleimide and Ni(2+) as masking agents, Tb(3+)/GMP-Cu(2+) was further exploited as an integrated logic system and a specific time-resolved fluorescent "turn-on" assay for simultaneously sensing His and Cys was designed. Meanwhile it can also be used in plasma samples, showing great potential to meet the need of practical application.

Altered expression profile of micrornas in gastric stromal tumor.

MicroRNAs (miRNAs) play important roles in carcinogenesis, but the global miRNA expression profile in gastric stromal tumor tissues remains unclear. This study was to examine the miRNA expression profile in gastric stromal tumor tissues and explore the function of dysregulated miRNAs by performing gene ontology (GO) and pathway enrichment analysis. Total RNA was extracted and purified from 3 pairs of frozen gastric stromal tumor tissues and the adjacent non-tumor tissues by using mirVana™ miRNA isolation kit. The miRNA expression was analyzed with Affymetrix microarrays (version 4.0) containing 2578 human mature microRNA probes. The dysregulated microRNAs were validated by quantitative RT-PCR in 30 pairs of gastric stromal tumor tissues. The target gene of the dysregulated microRNAs was predicted by miRanda, TargetScan and PicTar. GO and pathway enrichment analysis was conducted to examine the potential function of miR-3178 and miR-193a-5p. The results showed that there were 12 differently expressed microRNAs in gastric stromal tumor tissues, among which 10 miRNAs were down-regulated, and 2 were up-regulated (P<0.05). The validation results by RT-PCR were in accordance with those by microRNA microarry. GO analysis found that the target genes of miR-3178 were involved in 5 GO terms and those of miR-193a-5p in 7 GO terms in level 2. Pathway enrichment analysis suggested that miR-3178 and miR-193a-5p were related to 57 and 122 signaling pathways, respectively. It was concluded that gastric stromal tumor displays a unique miRNA signature. This specific expression may become a new diagnostic and prognostic biomarker for gastric stromal tumor. miR-3178 and miR-193a-5p function as suppressive microRNAs, and they may also become diagnosis and treatment targets for gastric stromal tumor.

Accuracy of early detection of colorectal tumours by stool methylation markers: a meta-analysis.

AIM: To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours. METHODS: Electronic databases including PubMed, Web of Science, Chinese Journals Full-Text Database and Wanfang Journals Full-Text Database were searched to find relevant original articles about methylated genes to be used in diagnosing colorectal tumours. A quality assessment of diagnostic accuracy studies tool (QADAS) was used to evaluate the quality of the included articles, and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis. RESULTS: Thirty-seven articles met the inclusion criteria, and 4484 patients were included. The sensitivity and specificity for the detection of colorectal cancer (CRC) were 73% (95%CI: 71%-75%) and 92% (95%CI: 90%-93%), respectively. For adenoma, the sensitivity and specificity were 51% (95%CI: 47%-54%) and 92% (95%CI: 90%-93%), respectively. Pooled diagnostic performance of SFRP2 methylation for CRC provided the following results: the sensitivity was 79% (95%CI: 75%-82%), the specificity was 93% (95%CI: 90%-96%), the diagnostic OR was 47.57 (95%CI: 20.08-112.72), the area under the curve was 0.9565. Additionally, the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows: sensitivity was 43% (95%CI: 38%-49%), specificity was 94% (95%CI: 91%-97%), the diagnostic OR was 11.06 (95%CI: 5.77-21.18), and the area under the curve was 0.9563. CONCLUSION: Stool-based DNA testing may be useful for noninvasively diagnosing colorectal tumours and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis.