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Long-lived species Homo sapiens have evolved robust protection mechanisms against cancer by repressing telomerase and maintaining short telomeres, thereby delaying the onset of the majority of cancer types until post-reproductive age. Indeed, telomerase is silent in most differentiated human cells, predominantly due to the transcriptional repression of its catalytic component telomerase reverse transcriptase (TERT) gene. The lack of telomerase/TERT expression leads to progressive telomere erosion in dividing human cells, whereas critically shortened telomere length induces a permanent growth arrest stage named replicative senescence. TERT/telomerase activation has been experimentally shown to be essential to cellular immortalization and malignant transformation by stabilizing telomere length and erasing the senescence barrier. Consistently, TERT expression/telomerase activity is detectable in up to 90% of human primary cancers. Compelling evidence has also accumulated that TERT contributes to cancer development and progression via multiple activities beyond its canonical telomere-lengthening function. Given these key roles of telomerase and TERT in oncogenesis, great efforts have been made to decipher mechanisms underlying telomerase activation and TERT induction. In the last two decades since the TERT gene and promoter were cloned, the derepression of the TERT gene has been shown to be achieved typically at a transcriptional level through dysregulation of oncogenic factors or signaling, post-transcriptional/translational regulation and genomic amplification. However, advances in high-throughput next-generation sequencing technologies have prompted a revolution in cancer genomics, which leads to the recent discovery that genomic alterations take center stage in activating the TERT gene. In this review article, we summarize critical mechanisms activating TERT transcription, with special emphases on the contribution of TERT promoter mutations and structural alterations at the TERT locus, and briefly discuss the underlying implications of these genomic events-driven TERT hyperactivity in cancer initiation/progression and potential clinical applications as well.

Continuous and long-term therapeutic monitoring of medicine molecules in biological systems will revolutionize healthcare by offering personalized pharmacokinetic reports. However, the extremely complex biological environment brings great challenges for in vivo molecule detection in living organisms. Here we introduce an in vivo photoelectrochemical biosensor following a reverse design strategy with single atoms as molecular recognition units. Atomic dispersion of Cu single atoms on TiO 2- x substrate create synergistic anchoring triple-site for efficiently and selectively capturing of dual-carbonyl group and neighboring dual-hydroxyl group of tetracycline molecules. The photoelectrode is encapsulated with antibiofouling layer and implanted into the vein of living mouse to enable long-term in vivo monitoring of tetracycline in real biological environments. It is important to note that our approach was exclusively tested in male mice, and therefore, the findings may not be generalizable to female mice or other species without further research. The rationally designed biological-components-free in vivo biosensor with excellent selectivity, robustness, and stability endows possibility for enabling personalized medicine guidance through real-time feedbacking information and providing direct and authentic medicine molecular analysis. Continuous and long-term monitoring of medicines in biological systems could offer personalized pharmacokinetic reports but is challenging due to the complexity of the biological environment in living organisms. Here, the authors present a photoelectrochemical biosensor with single atom Cu on TiO2-x as recognition unit for selective, precise, long-term tetracycline monitoring in living organisms.

The recent global pandemic of coronavirus disease 2019 (COVID-19) has enormously promoted the development of diagnostic technology. To control the spread of pandemic diseases and achieve rapid screening of the population, ensuring that patients receive timely treatment, rapid diagnosis has become the top priority in the development of clinical technology. This review article aims to summarize the current rapid nucleic acid diagnostic technologies applied to pandemic disease diagnosis, from rapid extraction and rapid amplification to rapid detection. We also discuss future prospects in the development of rapid nucleic acid diagnostic technologies.

The need for precise modulation of blood concentrations of pharmaceutical molecule, especially for high-risk drugs like Methotrexate (MTX), is underscored by the significant impact of individual variations on treatment efficacy. Achieving selective recognition of pharmaceutical molecules within the complex biological environment is a substantial challenge. To tackle this, we propose a synergistic atomic-molecular docking strategy that utilizes a hybrid-dual single-atom Fe1-Zn1 on a TiO2 photoelectrode to selectively bind to the carboxyl and aminopyrimidine groups of MTX respectively. By integrating this Fe 1 -Zn 1 -TiO 2 photoelectrode with a microcomputer system, an implantable photoelectrochemical-therapeutic drug monitoring (PEC-TDM) system is developed for real-time, continuous in vivo MTX monitoring. This system facilitates personalized therapeutic decision-making and intelligent drug delivery for individualized cancer therapy, potentially revolutionizing oncological care and enhancing patient outcomes. Concentration of methotrexate (MTX) in the blood needs precise monitoring, Here, the authors propose an atomic-molecular docking strategy that utilizes a hybrid-dual single-atom Fe 1 -Zn 1 on TiO 2 photoelectrode to bind to the carboxyl and aminopyrimidine groups of MTX.

Norepinephrine (NE), a pivotal neurotransmitter in the central and sympathetic nervous systems, is crucial for numerous physiological and pathophysiological processes. Distinguishing NE from structurally similar dopamine and epinephrine in complex in vivo environments is a significant challenge. Herein, we propose a molecular docking strategy for selective, sensitive, and ultrafast detection of NE in vivo. Leveraging the molecular structure of NE, we design a Zn single-atom-modified TiO 2 substrate (Zn 1 /TiO 2 ) as a photoelectrochemical (PEC) biosensor, providing synergistic atomic anchoring sites to “lock” NE molecules and enabling real-time NE detection in the brain of living male mice with a response time of 60 ms. The high specificity and rapid detection capabilities of this biosensor have unveiled a regulatory mechanism of the noradrenergic system across multiple brain regions, including the locus coeruleus, cortex, and hippocampus, highlighting a synergistic effect during epilepsy. This rationally designed single-atomic PEC biosensor for in situ monitoring of neurotransmitter dynamics holds promise for future brain science research. Distinguishing norepinephrine (NE) from structurally similar neurotransmitters in complex in vivo environments is a significant challenge. Here authors report a photoelectrochemical biosensor which uses Zn single atoms on TiO 2 to allow selective in vivo NE quantification in various brain regions.

Road target detection is a crucial aspect of current research in automotive advanced driver assistance systems and intelligent transportation systems, where accuracy, speed, and lightweight design are key considerations. Compared to various sensors employed in driving assistance systems, millimeter-wave radar offers advantages such as all-weather operation, low hardware cost, strong penetration capability, and the ability to extract rich spatial information about targets. This paper tackles the challenges posed by the characteristics of Range-Angle map data from 77 GHz Frequency-Modulated Continuous Wave radar—namely, non-visible light imagery, abstract representation, rich fine details, and overlapping features. To this end, this paper proposes MMPFNet, a lightweight model based on the hypergraph mechanism with attention enhancement, as an extension of YOLOv13. First, an M-DSC3k2 module is proposed based on the hypergraph mechanism to enhance attention toward small targets. Second, a detection head with a double-bottleneck inverted MBConv-block structure is designed to improve the model’s accuracy and generalization capability. Third, a lightweight PPLConv module is customized to transform the backbone network, enhancing the model’s lightweight design while slightly reducing its accuracy. Considering the differences from traditional visible light datasets, the Focus Expansion-IoU loss function is introduced into the model to focus attention on different regression samples. The MMPFNet model achieves significant improvements in detecting common road targets such as pedestrians, bicycles, cars, and trucks on the Frequency-Modulated Continuous Wave radar Range-Angle dataset compared to the baseline YOLOv13n model: mAP50-95 increases by 16%, precision improves by 6%, and recall rises by 8.7%. MMPFNet is also evaluated on other non-visible light datasets such as CRUW-ONRD and soundprint datasets. Compared to commonly used detection models like FCOS and RetinaNet, MMPFNet achieves significant performance gains, attaining state-of-the-art results.

Landscape ecological health (LEH) assessment of blue–green space is vital for the management and restoration of the urban environment. At present, existing LEH assessment research has mainly focused on the single measurement of landscape pattern or external ecological service function, ignoring the effect mechanism. Moreover, there is a lack of targeted assessment of urban blue–green space LEH. In this study, we constructed an urban blue–green space LEH assessment framework based on the integration of pattern, process, function and sustainability, and conducted an empirical analysis in Harbin, a megacity in Northeastern China. The results showed that the spatial changes in the four assessment units of landscape ecological pattern, process, function and sustainability were not coordinated in the study area. From 2011 to 2020, the overall condition of blue–green space LEH in the study area improved but still at an unhealthy level, and the spatial difference increased. Grassland, water and wetland suffered from the widespread degradation of LEH in the study area, and the LEH level improvement type had the largest area proportion, and the stabilization type had the smallest. Moreover, based on the spatial autocorrelation analysis, we clarified the LEH spatial correlation characteristics of the study area and proposed targeted optimization suggestions. Our assessment framework will extend the LEH assessment scope and methodology, and the research results can provide significant references for urban blue–green space protection and management.

Delayed fruit softening in tomato ( Solanum lycopersicum ) is highly desirable for extending shelf life, facilitating long-distance transportation, and reducing post-harvest losses caused by mechanical damage. Fruit softening is a natural ripening process characterized by the increased expression of genes involved in cell wall modification, leading to the breakdown of cell wall polysaccharides and the gradual disintegration of cellular structure. The yft1 mutant ( yellow-fruited tomato 1 , originally designated n3122 ) exhibits inhibited ethylene production, preventing normal ripening and resulting in firmer fruit. Concurrently, yft1 shows significant downregulation of several genes associated with cell wall degradation, including endoglucanase SlCEL2 and EXPANSIN SlEXP1 . Both genes exhibit similar expression patterns, peaking during ripening, suggesting their importance in fruit softening. To investigate this further, RNAi silencing lines targeting SlCEL2 and SlEXP1 were generated. The double mutant, slcel2 slexp1 , displayed increased firmness at the red ripe stage (54 days post-anthesis, dpa), whereas the single mutants showed similar softening to the wild-type M82. Anatomical analysis at 54 dpa revealed enhanced cell wall structure, slightly increased cuticle thickness, and significantly higher pericarp cellulose content in slcel2 slexp1 compared to M82, slcel2 , and slexp1 . Furthermore, this study found that SlEXP1 expression was significantly upregulated in slcel2 fruit, compared to M82 (wild type), at 54 dpa. This suggests a compensatory transcriptional regulation between these two genes in tomato fruit, potentially aimed at maintaining normal softening during ripening. These findings demonstrate that SlCEL2 and SlEXP1 act synergistically in cellulose degradation during tomato ripening, and promoting fruit softening.

Background Red (R) and far-red (FR) light distinctly influence phytochrome-mediated initial tomato growth and development, and more recent evidence indicates that these spectra also modulate responses to a multitude of abiotic and biotic stresses. This research investigated whether different R: FR values affect tomato growth response and salinity tolerance. Tomato seedlings were exposed to different R: FR conditions (7.4, 1.2 and 0.8) under salinity stress (100 mM NaCl), and evaluated for their growth, biochemical changes, active reactive oxygen species (ROS) and ROS scavenging enzymes, pigments, rate of photosynthesis, and chlorophyll fluorescence. Results The results showed that under conditions of salinity, tomato seedlings subjected to a lower R: FR value (0.8) significantly increased both their growth, proline content, chlorophyll content and net photosynthesis rate (Pn), while they decreased malondialdehyde (MDA) compared to the higher R: FR value (7.4). Under conditions of salinity, the lower R: FR value caused a decrease in both the superoxide anion (O 2 •− ) and in hydrogen peroxide (H 2 O 2 ) generation, an increase in the activities of superoxidase dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.7). Tomato seedlings grown under the lower R: FR value and conditions of salinity showed a higher actual quantum yield of photosynthesis (ΦPSII), electron transport rate (ETR), and photochemical quenching (qP) than those exposed to a higher R: FR, indicating overall healthier growth. However, the salinity tolerance induced at the lower R: FR condition disappeared in the tomato phyB1 mutant. Conlusion These results suggest that growing tomato with a lower R: FR value could improve seedlings’ salinity tolerance, and phytochrome B1 play an very important role in this process. Therefore, different qualities of light can be used to efficiently develop abiotic stress tolerance in tomato cultivation.

Delayed neurologic sequelae (DNS) is a common complication in patients with carbon monoxide poisoning (COP). We aimed to investigate the association of the neutrophil-to-lymphocyte ratio (NLR) with the frequency of DNS in COP patients. A total of 371 COP patients were investigated in retrospective and prospective studies. A receiver operator curve (ROC) test was performed to evaluate the ability of the NLR to predict DNS in COP patients. The retrospective study included 288 COP patients, of whom 84 (29.2%) were confirmed to have DNS, and 1 (0.3%) died within 28 days. The NLR in the DNS group was significantly higher than that in the non-DNS group (6.84 [4.22–12.43] vs. 3.23 [1.91–5.60] × 10 9 /L). NLR was a significant predictor of the frequency of DNS [odds ratio (OR): 1.130, 95% confidence interval (CI): 1.030, 1.240] in COP patients. The area under the ROC curve of NLR for predicting DNS was 0.766 (95% CI 0.701, 0.832), and the cut-off value was 3.745 (sensitivity, 83.3%; specificity, 58.8%). The prospective study included 83 COP patients, of whom 19 (22.9%) were confirmed to have DNS, and all patients survived. Moreover, the frequency of DNS in the patients with an NLR ≥ 3.745 was notably higher than that in the patients with an NLR < 3.745 [41.4% (12/29) vs. 13.0 (7/54)]. In conclusion, the NLR was a significant, independent predictor of the frequency of DNS in COP patients.