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Surface-enhanced Raman spectroscopy (SERS) is a vibrational spectroscopic technique in which the Raman scattering signal strength of molecules, absorbed by rough metals or the surface of nanoparticles, experiences an exponential growth (103–106 times and even 1014–1015 times) because of electromagnetic or chemical enhancements. Nowadays, SERS has attracted tremendous attention in the field of analytical chemistry due to its specific advantages, including high selectivity, rich informative spectral properties, nondestructive testing, and the prominent multiplexing capabilities of Raman spectroscopy. In this review, we present the applications of state-of-the-art SERS for the detection of DNA, proteins and drugs. Moreover, we focus on highlighting the merits and mechanisms of achieving enhanced SERS signals for food safety and clinical treatment. The machine learning techniques, combined with SERS detection, are also indicated herein. This review concludes with recommendations for future studies on the development of SERS.

Marine climate significantly influences the spatial morphology of coastal village’s streets. However, research on coastal villages lacks spatial parameterization analysis that can cope with the complex climatic environment. Focusing on the coastal village’s street in Fuzhou City, China, this paper studies the relationship between street space morphology and the impact of extreme heat and wind conditions. Thermal comfort degree and the average wind speed are main optimization objectives. By using parameterization techniques to establish a dynamic model and conducting multi-objective optimization driven by genetic algorithms, the degree of influence of morphological indicators and climate indicators is revealed. The conclusions of the study indicate that the morphological indicators of the main space have a more significant impact on the climatic environment than the morphological indicators of the interfaces on either side of the street. The influence of thermal comfort indicators on the street space within the climate environment is greater than that of wind speed indicators. This study concludes by proposing a ranking of key morphological indicators along with their optimal intervals for coastal villages adapted to the marine climate. The key morphological indicators, listed in order of importance, include appropriate street widths (2.3–4.3 m), eave height for single-storey buildings (2.0–4.6 m), eave height for double-storey buildings (5.4–7.7 m), eave depth (0.8–1.1 m for brick-timber dwellings and 0.3–0.6 m for masonry dwellings), roof slope (20–28°), entrance space depth (0.8–1.3 m), balcony overhang depth (0.6–0.7 m), colonnade depth (1.5–2.4 m), street orientation (NE-SW) and building depth (3.2–5.0 m). This study provides an empirical reference for climate-adapted village design and renewal.

Ethnopharmacological relevance: Curcumin is a bright yellow chemical produced by plants of the Curcuma longa species. Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids. The therapeutic potential of curcumin has been widely investigated, including its utilization in various of cardiovascular diseases. However, its effect in cardiac remodeling post myocardial infarction and underlying mechanism remains to be uncover. Aim: To evaluate the therapeutic effect and underlying mechanism of curcumin on cardiac fibrosis after myocardial infarction via macrophage-fibroblast crosstalk. Methods: Male C57BL/6 (C57) mice were subjected to left anterior descending coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle or curcumin (50 mg/kg or 100 mg/kg) for 4 weeks. In parallel, neonatal rat cardiac fibroblasts were isolated and co-cultured with liposaccharide (LPS − or LPS + ) curcumin-treated macrophages, followed by TGF-β stimulation for 24 h. Cardiac function was determined by 2-dimensional echocardiography, and cardiac fibrosis was measured by picrosirius red staining. Apoptosis of macrophages was investigated by flow cytometry; all pro-fibrotic protein expression (EDA-Fibronectin, Periostin, Vimentin, and α-SMA) as well as TGF-βR1 downstream signaling activation reflected by phosphorylated SMAD2/3 ( p -SMAD2 and p -SMAD3) were demonstrated by western blotting. Results: Curcumin significantly ameliorated the inflammation process subsequent to myocardial infarction, reflected by decreased expression of CD68 + and CD3 + cells, accompanied by dramatically improved cardiac function compared with the placebo group. In addition, cardiac fibrosis is inhibited by curcumin administration. Interestingly, no significant reduction in fibrotic gene expression was observed when isolated cardiac fibroblasts were directly treated with curcumin in vitro; however, pro-fibrotic protein expression was significantly attenuated in CF, which was co-cultured with LPS-stimulated macrophages under curcumin treatment compared with the placebo group. Mechanistically, we discovered that curcumin significantly downregulated pro-inflammatory cytokines in macrophages, which in turn inhibited IL18 expression in co-cultured cardiac fibroblasts using bulk RNA sequencing, and the TGF-β1- p -SMAD2/3 signaling network was also discovered as the eventual target downstream of IL18 in curcumin-mediated anti-fibrosis signaling. Conclusion: Curcumin improves cardiac function and reduces cardiac fibrosis after myocardial infarction. This effect is mediated by the inhibition of macrophage-fibroblast crosstalk in the acute phase post-MI and retrained activation of IL18-TGFβ1- p -SMAD2/3 signaling in cardiac fibroblasts.

Tet-mediated DNA demethylation plays an important role in shaping the epigenetic landscape and chromatin accessibility to control gene expression. While several studies demonstrated pivotal roles of Tet in regulating embryonic development, little is known about their functions in heart development. Here we analyze DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice. We find that cardiac-specific deletion of Tet2 and Tet3 in mice (Tet2/3-DKO) leads to ventricular non-compaction cardiomyopathy (NCC) with embryonic lethality. Single-cell RNA-seq analyses reveal a reduction in cardiomyocyte numbers and transcriptional reprogramming in cardiac tissues upon Tet2/3 depletion. Impaired DNA demethylation and reduced chromatin accessibility in Tet2/3-DKO mice further compromised Ying-yang1 (YY1) binding to its genomic targets, and perturbed high-order chromatin organization at key genes involved in heart development. Our studies provide evidence of the physiological role of Tet in regulating DNA methylation dynamics and chromatin organization during early heart development. Tet-mediated DNA demethylation is intimately involved in reguatling embryonic development. Here the authors characterise DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice and provide evidence that Tet-mediated DNA demethylation plays a role in regulating chromatin organization during early heart development.

The regulation of the informational flow from the mitochondria to the nucleus (mitonuclear communication) is not fully characterized in the heart. We have determined that mitochondrial ribosomal protein S5 (MRPS5/uS5m) can regulate cardiac function and key pathways to coordinate this process during cardiac stress. We demonstrate that loss of Mrps5 in the developing heart leads to cardiac defects and embryonic lethality while postnatal loss induces cardiac hypertrophy and heart failure. The structure and function of mitochondria is disrupted in Mrps5 mutant cardiomyocytes, impairing mitochondrial protein translation and OXPHOS. We identify Klf15 as a Mrps5 downstream target and demonstrate that exogenous Klf15 is able to rescue the overt defects and re-balance the cardiac metabolome. We further show that Mrps5 represses Klf15 expression through c-myc, together with the metabolite L-phenylalanine. This critical role for Mrps5 in cardiac metabolism and mitonuclear communication highlights its potential as a target for heart failure therapies. The heart requires high levels of mitochondria to sustain function, and mitochondrial stressors can be transmitted to the nucleus and reprogram metabolism. Here, the authors show that a mitochondrial ribosomal protein is important for heart development in mice by increasing nuclear Klf15 expression.

Breast cancer encompasses a group of heterogeneous diseases, each associated with distinct clinical implications. Dozens of molecular biomarkers capable of categorizing tumors into clinically relevant subgroups have been proposed which, though considerably contribute in precision medicine, complicate our understandings toward breast cancer subtyping and its clinical translation. To decipher the networking of markers with diagnostic roles on breast carcinomas, we constructed the diagnostic networks by incorporating 6 publically available gene expression datasets with protein interaction data retrieved from BioGRID on previously identified 1015 genes with breast cancer subtyping roles. The Greedy algorithm and mutual information were used to construct the integrated diagnostic network, resulting in 37 genes enclosing 43 interactions. Four genes, FAM134B , KIF2C , ALCAM , KIF1A , were identified having comparable subtyping efficacies with the initial 1015 genes evaluated by hierarchical clustering and cross validations that deploy support vector machine and k nearest neighbor algorithms. Pathway, Gene Ontology, and proliferation marker enrichment analyses collectively suggest 5 primary cancer hallmarks driving breast cancer differentiation, with those contributing to uncontrolled proliferation being the most prominent. Our results propose a 37-gene integrated diagnostic network implicating 5 cancer hallmarks that drives breast cancer heterogeneity and, in particular, a 4-gene panel with clinical diagnostic translation potential.

Connexin-43 (Cx43) gap junctions provide intercellular coupling, which ensures rapid action potential propagation and synchronized heart contraction. Alterations in Cx43 localization and reductions in gap junction coupling occur in failing hearts, contributing to ventricular arrhythmias and sudden cardiac death. Recent reports have found that an internally translated Cx43 isoform, GJA1-20k, is an auxiliary subunit for the trafficking of Cx43 in heterologous expression systems. Here, we have created a mouse model by using CRISPR technology to mutate a single internal translation initiation site in Cx43 (M213L mutation), which generates full-length Cx43, but not GJA1-20k. We found that GJA1M213L/M213L mice had severely abnormal electrocardiograms despite preserved contractile function, reduced total Cx43, and reduced gap junctions, and they died suddenly at 2 to 4 weeks of age. Heterozygous GJA1M213L/WT mice survived to adulthood with increased ventricular ectopy. Biochemical experiments indicated that cytoplasmic Cx43 had a half-life that was 50% shorter than membrane-associated Cx43. Without GJA1-20k, poorly trafficked Cx43 was degraded. The data support that GJA1-20k, an endogenous entity translated independently of Cx43, is critical for Cx43 gap junction trafficking, maintenance of Cx43 protein, and normal electrical function of the mammalian heart.

Urban landscape patterns significantly impact land surface temperature (LST) and the urban heat island (UHI) effect. This study employs the boosted regression tree (BRT) model and variance partitioning analysis to examine the contributions and relationships of two-dimensional and three-dimensional building and vegetation patterns to LST, and their marginal effects at different heights. The results show that the dominant indicators affecting LST differ between buildings and vegetation, with three-dimensional building features being slightly more important than two-dimensional features (percentage of landscape of buildings) and two-dimensional vegetation features (three-dimensional green index) having a greater impact than three-dimensional features. When both buildings and vegetation are considered, building patterns still have significant explanatory power. Building height differences influence each indicator’s contribution and marginal effects on LST, with lower-height areas seeing a joint dominance of buildings and vegetation on LST changes, and higher-height areas showing greater impact from vegetation indicators. Increasing the percentage of landscape of vegetation (PLAND_V) provides the best cooling effect in lower-building-height areas, but in higher-building-height areas, the cooling effect weakens, requiring additional vegetation indicators to assist in cooling.

Myocardial energy metabolism disorders are essential pathophysiology in sepsis-associated myocardial injury. Yet, the underlying mechanisms involving impaired mitochondrial respiratory function upon myocardial injury remain poorly understood. Here we identify an unannotated and cardiomyocyte-enriched long non-coding RNA, Cpat (cardiac-protector-associated transcript), that plays an important role in regulating the dynamics of cardiomyocyte mitochondrial tricarboxylic acid (TCA) cycle. Cpat is essential to the mitochondrial respiratory function by targeting key metabolic enzymes and modulating TCA cycle flux. Specifically, Cpat enhances the association of TCA cycle core components malate dehydrogenase (MDH2), citrate synthase (CS), and aconitase (ACO2). Acetyltransferase general control non-repressed protein-5 (GCN5) acetylates CS and destabilizes the MDH2-CS-ACO2 complex formation. Cpat inhibits this GCN5 activity and facilitates MDH2-CS-ACO2 complex formation and TCA cycle flux. We reveal that Cpat-mediated mitochondrial metabolic homeostasis is vital in mitigating myocardial injury in sepsis-induced cardiomyopathy, positioning Cpat as a promising therapeutic target for preserving myocardial cellular metabolism and function. Mitochondrial dysfunction contributes to septic cardiomyopathy and poor outcomes. Here, the authors identify a cardiomyocyte-enriched non-coding RNA that preserves mitochondrial function and reduces mortality in septic mice by preventing citrate synthase acetylation.

Alzheimer’s disease (AD) is the most common cause of dementia and cannot be cured. The etiology and pathogenesis of AD is still not fully understood, the genetics is considered to be one of the most important factors for AD onset, and the identified susceptible genes could provide clues to the AD mechanism and also be the potential targets. MicroRNA-146a-5p (miR-146a) is well known in the regulation of the inflammatory response, and the functional SNP of miR-146a was associated with AD risk. In this study, using a noninvasive nasal administration, we discovered that a miR-146a agomir (M146AG) rescued cognitive impairment in the APP/PS1 transgenic mouse and alleviated the overall pathological process in the AD mouse model, including neuroinflammation, glia activation, Aβ deposit, and tau phosphorylation in hippocampi. Furthermore, the transcriptional analysis revealed that besides the effect of neuroinflammation, M146AG may serve as a multi-potency target for intervention in AD. In addition, Srsf6 was identified as a target of miR-146a, which may play a role in AD progression. In conclusion, our study supports that the nasal-to-brain pathway is efficient and operable for the brain administration of microRNAs (miRNAs), and that miR-146a may be a new potential target for AD treatment.