CircTMEM165 facilitates endothelial repair by modulating mitochondrial fission via miR-192/SCP2 in vitro and in vivo.

Constitutive explorations indicate a correlation between circular RNAs (circRNAs) and cardiovascular diseases. However, the involvement of circRNAs in endothelial recuperation and in-stent restenosis (ISR) remains underexplored. CircTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs). Here, we identified that circTMEM165 was downregulated in ISR patients, inversely correlating with ISR severity. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation, and adhesion. Particularly, we first observed that circTMEM165 could alleviate HUVECs apoptosis and mitochondrial fission induced by lipopolysaccharide (LPS). Mechanistically, circTMEM165, as a miR-192-3p sponge, enhancing SCP2 expression, which serves as a critical regulator of HUVECs biological functions. Moreover, in vivo, circTMEM165 attenuated intimal hyperplasia and facilitated repair following classic rat carotid artery balloon injury model. These findings investigated the circTMEM165-miR-192-3p-SCP2 axis as a critical determinant of endothelial health and a potential biomarker and therapeutic target for vascular disorders.

Sialylated glycoproteins and sialyltransferases in digestive cancers: Mechanisms, diagnostic biomarkers, and therapeutic targets.

Sialic acid (SA), as the ultimate epitope of polysaccharides, can act as a cap at the end of polysaccharide chains to prevent their overextension. Sialylation is the enzymatic process of transferring SA residues onto polysaccharides and is catalyzed by a group of enzymes known as sialyltransferases (SiaTs). It is noteworthy that the sialylation level of glycoproteins is significantly altered when digestive cancer occurs. And this alteration exhibits a close correlation with the progression of these cancers. In this review, from the perspective of altered SiaTs expression levels and changed glycoprotein sialylation patterns, we summarize the pathogenesis of gastric cancer (GC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Furthermore, we propose potential early diagnostic biomarkers and prognostic indicators for different digestive cancers. Finally, we summarize the therapeutic value of sialylation in digestive system cancers.

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression.

Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

Distribution and influencing factors of atmospheric nitrogen oxides (NOx) over the east coast of China in spring: Indication of the sea as a sink of the atmospheric NOx.

An integrated observation of NOx that included coastal cities and oceanic cruises covering the Qingdao coastal waters sites (QDCW) and the Yellow Sea and East China Sea sites (YECS) was conducted in spring. The average concentrations of the coastal cities, the QDCW, and the YECS were 5.4 ± 4.1, 4.2 ± 3.5, and 2.9 ± 6.8 ppb for NO while 18.5 ± 7.2, 9.4 ± 5.2, and 4.9 ± 6.4 ppb for NO2, depicting lowest levels in the open seas. Atmospheric NO and NO2 showed similar spatial variations over the seas, the stations where the air masses originated from land or nearshore regions showed higher levels, but the decisive influencing factors were not the same in the different study areas. The calculated NOx flux value in the YECS (-8.7 × 10-17 mol N cm-2) indicated that the sea surface was a net sink of atmospheric NOx.

Circular RNA expression profile identifies potential circulating biomarkers for keratoconus.

Early diagnosis is important for improving the outcomes of keratoconus (KC). Stable expression and a closed-loop structure of circular RNAs (circRNAs) make them ideal for the diagnosis and treatment of diseases. However, the expression pattern and potential function of circRNAs in KC is not studied yet. Hence, this study explored the circRNA expression profile of KC corneas through transcriptome sequencing and circRNA expression profile analysis. The diagnostic potential of blood circRNAs for KC was explored by analysing the circRNAs' expression levels of fifty paired blood samples from patients with KC and normal controls. The results showed that 107 significantly upregulated and 145 significantly downregulated circRNAs (|fold change| ≥ 2.0, p-value <0.05) were identified in KC tissues. Eight top differently expressed circRNAs were further validated in more cornea samples. Among them, five circRNAs expressed in peripheral blood, and four circRNAs (circ_0006156, circ_0006117, circ_0000284 and circ_0001801) showed significant downregulation in KC patients' peripheral blood too. The blood circ_0000284 expression levels of early, moderate, and advanced KC patients both were significantly lower than the controls. The blood circ_0006117 expression levels present a positive correlation with corrected distance visual acuity values, and a negative correlation with back elevation values of KC eyes. Notably, the expression levels of these circRNAs distinguished KC patients from their healthy counterparts, with the area under the curve (AUC) of circ_0000284, circ_0001801, and circ_0006117 being 0.7306, 0.6871 and 0.6701, respectively. Further, the AUC value for five circRNAs under the logistic regression model was 0.8203, indicating that they can function as effective biomarkers for the KC diagnostics. In conclusion, the expression of circRNAs showed a relationship with KC, with four significantly differentially expressed circRNAs demonstrating potential as biomarkers for the disease.

Driving force of tidal pulses on denitrifiers-dominated nitrogen oxide emissions from intertidal wetland sediments.

Intertidal wetland sediments are an important source of atmospheric nitrogen oxides (NOx), but their contribution to the global NOx budget remains unclear. In this work, we conducted year-round and diurnal observations in the intertidal wetland of Jiaozhou Bay to explore their regional source-sink patterns and influence factors on NOx emissions (initially in the form of nitric oxide) and used a dynamic soil reactor to further extend the mechanisms underlying the tidal pulse of nitric oxide (NO) observed in our investigations. The annual fluxes of NOx in the vegetated wetland were significantly higher than those in the wetland without vegetation. Their annual variations could be attributed to changes in temperature and the amount of organic carbon in the sediment, which was derived from vegetated plants and promoted the carbon-nitrogen cycle. Anaerobic denitrifiers had advantages in the intertidal wetland sediment and accounted for the major NO production (63.8 %) but were still limited by nitrite and nitrate concentrations in the sediment. Moreover, the tidal pulse was likely a primary driver of NOx emissions from intertidal wetlands over short periods, which was not considered in previous investigations. The annual NO exchange flux considering the tide pulse contribution (8.93 ± 1.72 × 10-2 kg N ha-1 yr-1) was significantly higher than that of the non-pulse period (4.14 ± 1.13 × 10-2 kg N ha-1 yr-1) in our modeling result for the fluxes over the last decade. Therefore, the current measurement of NOx fluxes underestimated the actual gas emission without considering the tidal pulse.

The sulfate assimilation and reduction of marine microalgae and the regulation of illumination.

To examine the sulfate assimilation and reduction process and the regulation of illumination, diatom Phaeodactylum tricornutum and dinoflagellate Amphidinium carterae were selected for continuous simulation incubation under different photon flux densities (PFDs) (54, 108 and 162 µmol photons m-2 s-1), and concentration variations of related sulfur compounds sulfate, dimethylsulfoniopropionate (DMSP), dimethylsulfide (DMS) and acrylic acid (AA) in the culture system were observed. The optimal PFD for the growth of two microalgae was 108 µmol photons m-2 s-1. However, the maximum sulfate absorption occurred at 162 µmol photons m-2 s-1 for P. tricornutum and at 54 µmol photons m-2 s-1 for A. carterae. With the increase of PFD, the release of DMSP by P. tricornutum decreased while A. carterae increased. The largest release amount of DMS was 0.59 ± 0.05 fmol cells-1 for P. tricornutum and 2.61 ± 0.89 fmol cells-1 for A. carterae under their optimum growth light condition. The sulfate uptake of P. tricornutum was inhibited by the addition of amino acids, cysteine had a greater inhibitory effect than methionine, and the absorption process was controlled by light. The intermediate products of sulfur metabolism had an up-control effect on the sulfate uptake process of P. tricornutum. However, the addition of amino acids had no obvious effect on the sulfate absorption of A. carterae.

Integrative analysis of DNA methylome and transcriptome reveals epigenetic regulation of bisphenols-induced cardiomyocyte hypertrophy.

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans.

Advances in Point-of-Care Testing of microRNAs Based on Portable Instruments and Visual Detection.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that are approximately 22 nt in length and regulate gene expression post-transcriptionally. miRNAs play a vital role in both physiological and pathological processes and are regarded as promising biomarkers for cancer, cardiovascular diseases, neurodegenerative diseases, and so on. Accurate detection of miRNA expression level in clinical samples is important for miRNA-guided diagnostics. However, the common miRNA detection approaches like RNA sequencing, qRT-PCR, and miRNA microarray are performed in a professional laboratory with complex intermediate steps and are time-consuming and costly, challenging the miRNA-guided diagnostics. Hence, sensitive, highly specific, rapid, and easy-to-use detection of miRNAs is crucial for clinical diagnosis based on miRNAs. With the advantages of being specific, sensitive, efficient, cost-saving, and easy to operate, point-of-care testing (POCT) has been widely used in the detection of miRNAs. For the first time, we mainly focus on summarizing the research progress in POCT of miRNAs based on portable instruments and visual readout methods. As widely available pocket-size portable instruments and visual detection play important roles in POCT, we provide an all-sided discussion of the principles of these methods and their main limitations and challenges, in order to provide a guide for the development of more accurate, specific, and sensitive POCT methods for miRNA detection.

TMEM11 regulates cardiomyocyte proliferation and cardiac repair via METTL1-mediated m7G methylation of ATF5 mRNA.

The mitochondrial transmembrane (TMEM) protein family has several essential physiological functions. However, its roles in cardiomyocyte proliferation and cardiac regeneration remain unclear. Here, we detected that TMEM11 inhibits cardiomyocyte proliferation and cardiac regeneration in vitro. TMEM11 deletion enhanced cardiomyocyte proliferation and restored heart function after myocardial injury. In contrast, TMEM11-overexpression inhibited neonatal cardiomyocyte proliferation and regeneration in mouse hearts. TMEM11 directly interacted with METTL1 and enhanced m7G methylation of Atf5 mRNA, thereby increasing ATF5 expression. A TMEM11-dependent increase in ATF5 promoted the transcription of Inca1, an inhibitor of cyclin-dependent kinase interacting with cyclin A1, which suppressed cardiomyocyte proliferation. Hence, our findings revealed that TMEM11-mediated m7G methylation is involved in the regulation of cardiomyocyte proliferation, and targeting the TMEM11-METTL1-ATF5-INCA1 axis may serve as a novel therapeutic strategy for promoting cardiac repair and regeneration.

Circular RNAs in ferroptosis: regulation mechanism and potential clinical application in disease.

Ferroptosis, an iron-dependent non-apoptotic form of cell death, is reportedly involved in the pathogenesis of various diseases, particularly tumors, organ injury, and degenerative pathologies. Several signaling molecules and pathways have been found to be involved in the regulation of ferroptosis, including polyunsaturated fatty acid peroxidation, glutathione/glutathione peroxidase 4, the cysteine/glutamate antiporter system Xc-, ferroptosis suppressor protein 1/ubiquinone, and iron metabolism. An increasing amount of evidence suggests that circular RNAs (circRNAs), which have a stable circular structure, play important regulatory roles in the ferroptosis pathways that contribute to disease progression. Hence, ferroptosis-inhibiting and ferroptosis-stimulating circRNAs have potential as novel diagnostic markers or therapeutic targets for cancers, infarctions, organ injuries, and diabetes complications linked to ferroptosis. In this review, we summarize the roles that circRNAs play in the molecular mechanisms and regulatory networks of ferroptosis and their potential clinical applications in ferroptosis-related diseases. This review furthers our understanding of the roles of ferroptosis-related circRNAs and provides new perspectives on ferroptosis regulation and new directions for the diagnosis, treatment, and prognosis of ferroptosis-related diseases.

Emissions of Nitric Oxide from Photochemical and Microbial Processes in Coastal Waters of the Yellow and East China Seas.

Nitric oxide (NO) is an atmospheric pollutant and climate forcer as well as a key intermediary in the marine nitrogen cycle, but the ocean's NO contribution and production mechanisms remain unclear. Here, high-resolution NO observations were conducted simultaneously in the surface ocean and the lower atmosphere of the Yellow Sea and the East China Sea; moreover, NO production from photolysis and microbial processes was analyzed. The NO sea-air exchange showed uneven distributions (RSD = 349.1%) with an average flux of 5.3 ± 18.5 × 10-17 mol cm-2 s-1. In coastal waters where nitrite photolysis was the predominant source (89.0%), NO concentrations were remarkably higher (84.7%) than the overall average of the study area. The NO from archaeal nitrification accounted for 52.8% of all microbial production (11.0%). We also examined the relationship between gaseous NO and ozone which helped identify sources of atmospheric NO. The sea-to-air flux of NO in coastal waters was narrowed by contaminated air with elevated NO concentrations. These findings indicate that the emissions of NO from coastal waters, mainly controlled by reactive nitrogen inputs, will increase with the reduced terrestrial NO discharge.

Construction of rolling circle amplification products-based pure nucleic acid nanostructures for biomedical applications.

Nucleic acid nanomaterials with good biocompatibility, biodegradability, and programmability have important applications in biomedical field. Nucleic acid nanomaterials are usually combined with some inorganic nanomaterials to improve their biological stability. However, undefined toxic side effects of composite nanocarriers hamper their application in vivo. As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. RCA products with different functional parts can be customized by changing the sequence of the circular template, thereby generating complex multifunctional DNA nanostructures, such as DNA nanowire, nanoflower, origami, nanotube, nanoribbon, etc. More importantly, RCA products as nonnicked building blocks can enhance the biostability of DNA nanostructures, especially in vivo. These RCA products-based nucleic acid nanostructures can be used as scaffolds or nanocarriers to interact or load with metal nanoparticles, proteins, lipids, cationic polymers, therapeutic nucleic acids or drugs, etc. This paper reviews the assembly strategies of RCA based DNA nanostructures with different shape and their applications in biosensing, bioimaging and biomedicine. Finally, the development prospects of the nucleic acid nanomaterials in clinical diagnosis and treatment of diseases are described. STATEMENT OF SIGNIFICANCE: As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. This paper reviews the construction of various shapes of pure nucleic acid nanomaterials based on RCA products and their applications in biosensing, bioimaging and biomedicine. This will promote the development of biocompatible DNA nanovehicles and their further application in living systems, including bioimaging, molecular detection, disease diagnosis and drug delivery, finally producing a significant impact in the field of nanotechnology and nanomedicine.

CRISPR/Cas9 therapeutics: progress and prospects.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing. Diseases are both varied and complex, and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics. Additionally, this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.

7,8-Dihydroxyflavone alleviates cardiac fibrosis by restoring circadian signals via downregulating Bmal1/Akt pathway.

Brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway is a therapeutic target in cardiac diseases. A BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is emerging as a protective agent in cardiomyocytes; however, its potential role in cardiac fibroblasts (CFs) and fibrosis remains unknown. Thus, we aimed to explore the effects of 7,8-DHF on cardiac fibrosis and the possible mechanisms. Myocardial ischemia (MI) and transforming growth factor-ß1 (TGF-ß1) were used to establish models of cardiac fibrosis. Hematoxylin & eosin and Masson's trichrome stains were used for histological analysis and determination of collagen content in mouse myocardium. Cell viability kit, EdU (5-ethynyl-2'-deoxyuridine) assay and immunofluorescent stain were employed to examine the effects of 7,8-DHF on the proliferation and collagen production of CFs. The levels of collagen I, α-smooth muscle actin (α-SMA), TGF-ß1, Smad2/3, and Akt as well as circadian rhythm-related signals including brain and muscle Arnt-like protein 1 (Bmal1), period 2 (Per2), and cryptochrome 2 (Cry2) were analyzed. Treatment with 7,8-DHF markedly alleviated cardiac fibrosis in MI mice. It inhibited the activity of CFs accompanied by decreasing number of EdU-positive cells and downregulation of collagen I, α-SMA, TGF-ß1, and phosphorylation of Smad2/3. 7,8-DHF significantly restored the dysregulation of Bmal1, Per2, and Cry2, but inhibited the overactive Akt. Further, inhibition of Bmal1 by SR9009 effectively attenuated CFs proliferation and collagen production of CFs. In summary, these findings indicate that 7,8-DHF attenuates cardiac fibrosis and regulates circadian rhythmic signals, at least partly, by inhibiting Bmal1/Akt pathway, which may provide new insights into therapeutic cardiac remodeling.

Small-molecule 7,8-dihydroxyflavone counteracts compensated and decompensated cardiac hypertrophy via AMPK activation.

BACKGROUND: Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic. The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy. METHODS: Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol (ISO) with or without 7,8-DHF, respectively. F-actin staining was performed to calculate the cell area. Transcriptional levels of hypertrophic markers, including ANP, BNP, and ß-MHC, were detected. Echocardiography, hematoxylin-eosin staining, and transmission electron microscopy were used to examine the cardiac function, histology, and ultrastructure of ventricles. Protein levels of mitochondria-related factors, such as adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), were detected. RESULTS: 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy, diminished the cross-sectional area, and alleviated the mitochondrial disorders of cardiomyocytes. Meanwhile, 7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes. In addition, 7,8-DHF activated AMPK and PGC-1α signals without affecting the protein levels of mitochondrial dynamics-related molecules. The effects of 7,8-DHF were eliminanted by Compound C, an AMPK inhibitor. CONCLUSIONS: These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling, providing a potential agent for the treatment of pathological cardiac hypertrophy.

Mutual regulation of lactate dehydrogenase and redox robustness.

The nature of redox is electron transfer; in this way, energy metabolism brings redox stress. Lactate production is associated with NAD regeneration, which is now recognized to play a role in maintaining redox homeostasis. The cellular lactate/pyruvate ratio could be described as a proxy for the cytosolic NADH/NAD ratio, meaning lactate metabolism is the key to redox regulation. Here, we review the role of lactate dehydrogenases in cellular redox regulation, which play the role of the direct regulator of lactate-pyruvate transforming. Lactate dehydrogenases (LDHs) are found in almost all animal tissues; while LDHA catalyzed pyruvate to lactate, LDHB catalyzed the reverse reaction . LDH enzyme activity affects cell oxidative stress with NAD/NADH regulation, especially LDHA recently is also thought as an ROS sensor. We focus on the mutual regulation of LDHA and redox robustness. ROS accumulation regulates the transcription of LDHA. Conversely, diverse post-translational modifications of LDHA, such as phosphorylation and ubiquitination, play important roles in enzyme activity on ROS elimination, emphasizing the potential role of the ROS sensor and regulator of LDHA.

Sensitive naked-eye detection of telomerase activity based on exponential amplification reaction and lateral flow assay.

Telomerase is a promising diagnostic and prognostic biomarker for cancers. Sensitive, simple, and reliable telomerase activity detection is vital for cancer diagnosis. Herein, we developed an ultrasensitive visualized assay for telomerase activity that combined the exponential amplification reaction (EXPAR) and lateral flow assay for easy and quick signal readout, which we termed as a lateral flow readout-EXPAR (LFR-EXPAR) assay. In the LFR-EXPAR assay, telomerase elongation products initiate the exponential amplification reaction, the generated trigger hybridizes with the reporter to form the recognition site of the nicking enzyme, and the nicking enzyme cuts the reporter strand. The degradation of the reporter can be detected with a universal lateral flow dipstick and read out with the naked eye. After conducting a series of proof-of-concept investigations, the LFR-EXPAR assay was found to achieve a sensitivity comparable to that of a TRAP (telomere repeat amplification protocol) assay. The LFR-EXPAR assay can be used to realize ultrasensitive and point-of-care detection of telomerase without requiring specialized instruments, holding great promise for early cancer diagnosis.

Changes in dissolved organic pool and regulation of associated nutrients during green tides: A case study of Ulva prolifera bloom in the southern Yellow Sea.

To explore the spatial and temporal distributions of dissolved organic matter (DOM) affected by Ulva prolifera bloom and the regulation of DOM released by the addition of nitrate (NO3-N) nutrients, the variation in DOM was analyzed by three cruises in the coastal waters of the southern Yellow Sea (SYS) off Qingdao during a 2018 U. prolifera bloom. A mesocosm experiment was conducted during the decay of U. prolifera. The U. prolifera bloom resulted in higher concentrations of the bulk DOM except for total dissolved amino acids (TDAA), compared with levels recorded during non-bloom periods. Three different fluorescent substances of chromophoric dissolved organic matter (CDOM) were identified, which were also affected by the bloom. Concentrations of total dissolved carbohydrates (TCHO), monosaccharides (MCHO), and polysaccharides (PCHO) peaked during the late bloom, with average levels of 49.78 ± 9.73, 14.23 ± 3.32, and 35.55 ± 9.19 µmol C L-1, respectively, accompanied by an increase of DOC, indicating release of DOM with U. prolifera decay. In contrast, the concentrations of CDOM and TDAA declined during the late bloom, with averages of 0.10 ± 0.10 m-1 and 1.16 ± 0.82 µmol L-1, suggesting that the yields of CDOM and TDAA were regulated by the U. prolifera bloom and other mechanism. These findings were confirmed by the mesocosm experiment. DOM production was obviously improved by NO3-N addition except for TDAA and CDOM. The release of protein-like CDOM was primarily regulated by NO3-N nutrients, however, it was not obvious with humic-like CDOM. Our findings provide evidence supporting the role of U. prolifera blooms in the coastal DOM pool and its significant effect on the marine carbon cycle.