Building a stable and robust anti-interference DNA dissipation system by eliminating the accumulation of systemic specified errors.

BACKGROUND: The emergence of DNA nanotechnology has enabled the systematic design of diverse bionic dissipative behaviors under the precise control of nucleic acid nanodevices. Nevertheless, when compared to the dissipation observed in robust living systems, it is highly desirable to enhance the anti-interference for artificial DNA dissipation to withstand perturbations and facilitate repairs within the complex biological environments. RESULTS: In this study, we introduce strategically designed "trash cans" to facilitate kinetic control over interferences, transforming the stochastic binding of individual components within a homogeneous solution into a competitive binding process. This approach effectively eliminates incorrect binding and the accumulation of systemic interferences while ensuring a consistent pattern of energy fluctuation from response to silence. Remarkably, even in the presence of numerous interferences differing by only one base, we successfully achieve complete system reset through multiple cycles, effectively restoring the energy level to a minimum. SIGNIFICANCE: The system was able to operate stably without any adverse effect under conditions of irregular interference, high-abundance interference, and even multiplex interferences including DNA and RNA crosstalk. This work not only provides an effective paradigm for constructing robust DNA dissipation systems but also greatly broadens the potential of DNA dissipation for applications in high-precision molecular recognition and complex biological reaction networks.

The Active Ingredient Catalpol in Rehmannia glutinosa Reduces Blood Glucose in Diabetic Rats via the AMPK Pathway.

Background: Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic. Methods: The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed. Results: Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL. Conclusion: As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.

Epidemiology, pathogenesis, immune evasion mechanism and vaccine development of porcine Deltacoronavirus.

Coronaviruses have been identified as pathogens of gastrointestinal and respiratory diseases in humans and various animal species. In recent years, the global spread of new coronaviruses has had profound influences for global public health and economies worldwide. As highly pathogenic zoonotic viruses, coronaviruses have become the focus of current research. Porcine Deltacoronavirus (PDCoV), an enterovirus belonging to the family of coronaviruses, has emerged on a global scale in the past decade and significantly influenced the swine industry. Moreover, PDCoV infects not only pigs but also other species, including humans, chickens and cattles, exhibiting a broad host tropism. This emphasizes the need for in-depth studies on coronaviruses to mitigate their potential threats. In this review, we provided a comprehensive summary of the current studies on PDCoV. We first reviewed the epidemiological investigations on the global prevalence and distribution of PDCoV. Then, we delved into the studies on the pathogenesis of PDCoV to understand the mechanisms how the virus impacts its hosts. Furthermore, we also presented some exploration studies on the immune evasion mechanisms of the virus to enhance the understanding of host-virus interactions. Despite current limitations in vaccine development for PDCoV, we highlighted the inhibitory effects observed with certain substances, which offers a potential direction for future research endeavors. In conclusion, this review summarized the scientific findings in epidemiology, pathogenesis, immune evasion mechanisms and vaccine development of PDCoV. The ongoing exploration of potential vaccine candidates and the insights gained from inhibitory substances have provided a solid foundation for future vaccine development to prevent and control diseases associated with PDCoV.

Better Life's Essential 8 contributes to slowing the biological aging process: a cross-sectional study based on NHANES 2007-2010 data.

Objective: To investigate the relationship between Life's Essential 8 (LE8) and Phenotypic Age Acceleration (PhenoAgeAccel) in United States adults and to explore the impact of LE8 on phenotypic biological aging, thereby providing references for public health policies and health education. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2010, this cross-sectional study analyzed 7,339 adults aged 20 and above. Comprehensive assessments of LE8, PhenoAgeAccel, and research covariates were achieved through the integration of Demographics Data, Dietary Data, Laboratory Data, and Questionnaire Data derived from NHANES. Weighted generalized linear regression models and restricted cubic spline plots were employed to analyze the linear and non-linear associations between LE8 and PhenoAgeAccel, along with gender subgroup analysis and interaction effect testing. Results: (1) Dividing the 2007-2010 NHANES cohort into quartiles based on LE8 unveiled significant disparities in age, gender, race, body mass index, education level, marital status, poverty-income ratio, smoking and drinking statuses, diabetes, hypertension, hyperlipidemia, phenotypic age, PhenoAgeAccel, and various biological markers (p < 0.05). Mean cell volume demonstrated no intergroup differences (p > 0.05). (2) The generalized linear regression weighted models revealed a more pronounced negative correlation between higher quartiles of LE8 (Q2, Q3, and Q4) and PhenoAgeAccel compared to the lowest LE8 quartile in both crude and fully adjusted models (p < 0.05). This trend was statistically significant (p < 0.001) in the full adjustment model. Gender subgroup analysis within the fully adjusted models exhibited a significant negative relationship between LE8 and PhenoAgeAccel in both male and female participants, with trend tests demonstrating significant results (p < 0.001 for males and p = 0.001 for females). (3) Restricted cubic spline (RCS) plots elucidated no significant non-linear trends between LE8 and PhenoAgeAccel overall and in gender subgroups (p for non-linear > 0.05). (4) Interaction effect tests denoted no interaction effects between the studied stratified variables such as age, gender, race, education level, and marital status on the relationship between LE8 and PhenoAgeAccel (p for interaction > 0.05). However, body mass index and diabetes manifested interaction effects (p for interaction < 0.05), suggesting that the influence of LE8 on PhenoAgeAccel might vary depending on an individual's BMI and diabetes status. Conclusion: This study, based on NHANES data from 2007-2010, has revealed a significant negative correlation between LE8 and PhenoAgeAccel, emphasizing the importance of maintaining a healthy lifestyle in slowing down the biological aging process. Despite the limitations posed by the study's design and geographical constraints, these findings provide a scientific basis for the development of public health policies focused on healthy lifestyle practices. Future research should further investigate the causal mechanisms underlying the relationship between LE8 and PhenoAgeAccel and consider cross-cultural comparisons to enhance our understanding of healthy aging.

Identification of key genes increasing susceptibility to atrial fibrillation in nonalcoholic fatty liver disease and the potential mechanisms: mitochondrial dysfunction and systemic inflammation.

Background: Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are major health burdens, with emerging evidence suggesting NAFLD as a significant risk factor for AF, but the mechanism is remain unclear. Methods: In this study, we analyzed gene expression data from NAFLD (GSE89632) and AF (GSE75092) datasets from the Gene Expression Omnibus. We identified co-upregulated and co-downregulated genes between NAFLD and AF, assessed diagnostic potential of specific genes, conducted immune infiltration analysis, and performed molecular docking studies with sodium glucose co-transporter 2 inhibitors (SGLT2i). Results: We identified eight co-upregulated and 31 co-downregulated genes between NAFLD and AF. Genes such as AMOT, PDE11A, TYMS, TMEM98, and PTGS2 demonstrated substantial diagnostic potential for identifying NAFLD patients at risk of AF. Immune infiltration analysis discovered an elevated presence of CD8 T cells, γδ T cells, and M2 macrophages in NAFLD livers, linking systemic inflammation to NAFLD and AF. Additionally, studies have shown that a connection between mitochondrial dysfunction and several hub genes like DGAT1, TYMS, and PTGS2, suggesting that mitochondrial disturbances may underpin the systemic inflammation in NAFLD, which possibly exacerbating AF. Molecular docking studies indicated that empagliflozin's binding affinity with key genes such as DGAT1, TYMS, and PTGS2 presents a novel therapeutic avenue for NAFLD-associated AF. Conclusion: Our study firstly discovered that AMOT, PDE11A, TYMS, TMEM98, and PTGS2 are associated with NAFLD-related AF and hold strong diagnostic values. Our study also indicates that mitochondrial dysfunction and systemic inflammation may be potential mechanisms bridging NAFLD and AF. Additionally, we identified empagliflozin as a potentially effective therapeutic agent for NAFLD-related AF at the molecular structure level. These novel insights contribute to the further understanding, diagnosis, and intervention of NAFLD-related AF.

Water conservation pattern of Fangcheng River Basin in Beibu Gulf and its response to precipitation.

Assessing the spatiotemporal patterns of watershed water conservation under the influence of the South Asian monsoon climate and its response to precipitation is essential for revealing the evolving patterns of water conservation under different temporal scales. Following the principles of water balance and using the Soil and Water Assessment Tool (SWAT) model, we investigated the spatiotemporal patterns of water conservation and its response to precipitation in the Fangcheng River Basin of Beibu Gulf. The results showed that water conservation in Fangcheng River Basin calculated by SWAT model were 1637.4 mm·a-1, accounting for 50.7% of the mean annual precipitation. The variation of water conservation in different sub-basins was obviously different. Sub-basins with high forest coverage and steep slopes exhibited higher water conservation, while sub-basins with other land use types (such as cropland and grassland), gentle slopes, and intense human activities showed lower water conservation. At the monthly scale, both water conservation and its variation showed similar response characteristics to precipitation in the basin. The response of water conservation variation to sub-precipitation events could be classified into two types. For the short-term rainfall events (duration≤2 days), water conservation variation showed a linear relationship. For the medium to long-term rainfall events (2 days

Bioinspired cytomembrane coating besieges tumor for blocking metabolite transportation.

The metabolite transport inhibition of tumor cells holds promise to achieve anti-tumor efficacy. Herein, we presented an innovative strategy to hinder the delivery of metabolites through the in-situ besieging tumor cells with polyphenolic polymers that strongly adhere to the cytomembrane of tumor cells. Simultaneously, these polymers underwent self-crosslinking under the induction of tumor oxidative stress microenvironment to form an adhesive coating on the surface of the tumor cells. This polyphenol coating effectively obstructed glucose uptake, reducing metabolic products such as lactic acid, glutathione, and adenosine triphosphate, while also causing reactive oxygen species to accumulate in the tumor cells. The investigation of various tumor models, including 2D cells, 3D multicellular tumor spheroids, and xenograft tumors, demonstrated that the polyphenolic polymers effectively inhibited the growth of tumor cells by blocking key metabolite transport processes. Moreover, this highly adhesive coating could bind tumor cells to suppress their metastasis and invasion. This work identified polyphenolic polymers as a promising anticancer candidate with a mechanism by impeding the mass transport of tumor cells.

Strategies on biosynthesis and production of bioactive compounds in medicinal plants.

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

The crucial role of lateral root angle in enhancing drought resilience in cotton.

Introduction: Plant responses to drought stress are influenced by various factors, including the lateral root angle (LRA), stomatal regulation, canopy temperature, transpiration rate and yield. However, there is a lack of research that quantifies their interactions, especially among different cotton varieties. Methods: This experiment included two water treatments: well-watered (75 ± 5% soil relative water content) and drought stress (50 ± 5% soil relative water content) starting from the three-leaf growth stage. Results: The results revealed that different LRA varieties show genetic variation under drought stress. Among them, varieties with smaller root angles show greater drought tolerance. Varieties with smaller LRAs had significantly increased stomatal opening by 15% to 43%, transpiration rate by 61.24% and 62.00%, aboveground biomass by 54% to 64%, and increased seed cotton yield by 76% to 79%, and decreased canopy temperature by 9% to 12% under drought stress compared to the larger LRAs. Varieties with smaller LRAs had less yield loss under drought stress, which may be due to enhanced access to deeper soil water, compensating for heightened stomatal opening and elevated transpiration rates. The increase in transpiration rate promotes heat dissipation from leaves, thereby reducing leaf temperature and protecting leaves from damage. Discussion: Demonstrating the advantages conferred by the development of a smaller LRA under drought stress conditions holds value in enhancing cotton's resilience and promoting its sustainable adaptation to abiotic stressors.

Aspartyl proteases identified as candidate genes of a fiber length QTL, qFLD05, that regulates fiber length in cotton (Gossypium hirsutum L.).

KEY MESSAGE: GhAP genes were identified as the candidates involved in cotton fiber length under the scope of fine mapping a stable fiber length QTL, qFLD05. Moreover, the transcription factor GhWRKY40 positively regulated GhAP3 to decrease fiber length. Fiber length (FL) is an economically important fiber quality trait. Although several genes controlling cotton fiber development have been identified, our understanding of this process remains limited. In this study, an FL QTL (qFLD05) was fine-mapped to a 216.9-kb interval using a secondary F2:3 population derived from the upland hybrid cultivar Ji1518. This mapped genomic segment included 15 coding genes, four of which were annotated as aspartyl proteases (GhAP1-GhAP4). GhAPs were identified as candidates for qFLD05 as the sequence variations in GhAPs were associated with FL deviations in the mapping population, and functional validation of GhAP3 and GhAP4 indicated a longer FL following decreases in their expression levels through virus-induced gene silencing (VIGS). Subsequently, the potential involvement of GhWRKY40 in the regulatory network was revealed: GhWRKY40 positively regulated GhAP3's expression according to transcriptional profiling, VIGS, yeast one-hybrid assays and dual-luciferase experiments. Furthermore, alterations in the expression of the eight previously reported cotton FL-responsive genes from the above three VIGS lines (GhAP3, GhAP4 and GhWRKY40) implied that MYB5_A12 was involved in the GhWRKY40-GhAP network. In short, we unveiled the unprecedented FL regulation roles of GhAPs in cotton, which was possibly further regulated by GhWRKY40. These findings will reveal the genetic basis of FL development associated with qFLD05 and be beneficial for the marker-assisted selection of long-staple cotton.

Association between apolipoprotein B/A1 ratio and quantities of tissue prolapse on optical coherence tomography examination in patients with atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) continues to be a major health concern globally. Apolipoprotein (Apo) B/A1 ratio is a reliable predictor of ASCVD and an important factor in assessing the risk of myocardial infarction. Tissue prolapse (TP) is defined as the tissue extrusion into the lumen through the stent struts after implantation, which is a significant factor for poor short-term outcomes such as acute and subacute thrombosis, severe myocardial necrosis, and vulnerable plaque. Therefore, the aim of this study was to investigate the relationship between Apo B/A1, plaque vulnerability, and tissue prolapse on optical coherence tomography (OCT). This study enrolled 199 patients with atherosclerotic cardiovascular disease (ASCVD) who underwent percutaneous coronary intervention (PCI). Both pre- and post-procedural optical coherence tomography (OCT) examinations were conducted to assess TP volume and plaque morphology. Logistic regression analyses were performed to identify potential risk factors for tissue prolapse volume. Receiver operator characteristic (ROC) curve analysis was carried out to evaluate the value of the Apo B/A1 ratio for tissue prolapse volume. The high Apo B/A1 ratio group showed a larger TP volume (P = 0.001) and a higher percentage of plaque rupture and erosion in comparison to the low Apo B/A1 ratio group (P = 0.022 and P = 0.008). The high Apo B/A1 ratio group and the high TP volume group also had a higher proportion of thin-cap fibroatheroma (TCFA) (P = 0.046, P = 0.021). Multivariate logistic regression analysis revealed that both Apo B/A1 ratio (odds ratio [OR]: 1.041, 95% confidence interval [CI] 1.007-1.076; P = 0.019) and TCFA (OR: 3.199, 95%CI 1.133-9.031; 0.028) were significantly related to high TP volume. Furthermore, the area under the curve (AUC) for predictive value of TP volume was 0.635 for Apo B/A1 (95% CI 0.554-0.717, P = 0.002) compared to 0.615 for low density lipoprotein cholesterol (LDL-C) (95% CI 0.533-0.697, P = 0.008). The Apo B/A1 ratio is an independent predictor of TP volume on OCT and is related to plaque vulnerability.

The relationship between life satisfaction and nostalgia: Perceived social support and meaning in life chain mediation.

Much of the previous research has used experimental studies to explore the positive predictive effect of nostalgia on life satisfaction. However, the possible mediating effects involved remain unclear. To analyze the chain mediating mechanism between perceived social support and meaning in life in the relationship between nostalgia and life satisfaction and to improve the positive application of nostalgia to life satisfaction to ensure the physical and mental health of individuals, this study adopted the method of questionnaire survey, applied the Southampton Nostalgia scale, Perceived Social Support scale, Meaning in Life Scale and Life Satisfaction Scale. This study conducted a horizontal survey on 452 subjects recruited online from Gansu Province, Guangdong Province, Qinghai Province, and other places in China. The results showed that (1) there was a significant positive correlation between nostalgia and perceived social support, presence of meaning in life, searching for meaning in life, and life satisfaction. (2) Perceived social support and meaning in life play a chain mediating role in the relationship between nostalgia and life satisfaction. (3) Perceived social support and different dimensions of meaning in life are different in the relationship between nostalgia and life satisfaction. The findings contribute to understanding the chain-mediated mechanism between life satisfaction and nostalgia and provide recommendations for psychological service providers to apply nostalgia to enhance individual life satisfaction.

Association between dietary and behavioral-based oxidative balance score and phenotypic age acceleration: a cross-sectional study.

Objectives: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2010, including 13,142 U.S. adults (48.75% female and 51.25% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. Results: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific results the negative association between OBS and PhenoAgeAccel was more pronounced in men than in women. An analysis using restricted cubic splines revealed no significant nonlinear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. Conclusion: A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Levels of neuronal pentraxin 2 in plasma is associated with cognitive function in patients with schizophrenia.

RATIONALE: The precise diagnosis and treatment of cognitive impairment remains a major challenge in the field of schizophrenia (SCZ) research. Synaptic dysfunction and loss are thought to be closely related to the occurrence and development of SCZ and may be involved in cognitive dysfunction. OBJECTIVES: The purpose of this study was to investigate whether neuronal pentraxins (NPTXs) plays a role in the etiology of SCZ and provide evidence of its possible therapeutic value a new target for drug development. METHODS: We recruited 275 participants, of whom 148 were SCZ from psychiatric hospital and 127 healthy control (HC) subjects from communities. Plasma concentrations of NPTXs were measured in HC and SCZ at baseline and after 8 weeks of antipsychotic treatment. The MATRICS Cognitive Consensus Battery was used to evaluate cognitive function. Furthermore, the brain is parcellated into 246 subregions using the Brainnetome atlas, and we extracted regional white matter volumes from magnetic resonance images of the SCZ groups. RESULTS: Plasma NPTX2 levels were significantly lower in SCZ compared with HC subjects, but were significantly raised in SCZ after 8 weeks of antipsychotic treatment compared to baseline. In addition, baseline plasma NPTX2 levels were positively correlated with cognitive performance. CONCLUSIONS: These findings indicate that NPTX2 may reveal novel aspects of disease etiology and act as a promising target for new drug development.

Association between diurnal temperature range and outpatient visits for urticaria disease in Lanzhou, China: a distributed lag nonlinear analysis.

BACKGROUND: A growing number of epidemiological studies have shown that daily temperatures are associated with urticaria. However, the relationship between daily changes in temperature and urticaria is unclear. OBJECTIVES: To assess the diurnal temperature difference (DTR) effects on urticaria outpatient visits in Lanzhou, China. METHODS: Urticaria outpatient visits data during 2011-2019 were collected from three major tertiary hospitals in Lanzhou. Daily temperature data from the official website of China Meteorological Administration. Assessment of the relationship between urticaria outpatient volume and DTR in Lanzhou City using a distributed lag nonlinear model. RESULTS: A total of 83,022 urticaria visits were enrolled. There was a nonlinear relationship between DTR and urticaria outpatient visits and a lagged effect of DTR impact. The effects of high DTR on urticaria visits were not seen in all populations but in the male population and in the 15-59 age group. High DTR (P95: 18.2 °C) was associated with a 27% (95% CI: 0.01, 60.53%) and 31% (95% CI: 1.60, 68.99%) increase in the number of urticaria visits in the 21-day lag effect for the male cohort and the 15-59 year old cohort, respectively, compared with 11.5 °C, respectively. CONCLUSIONS: Our study suggests that DTR is a potential risk factor for urticaria. The results of this study may provide a scientific basis for local governments to improve preventive measures in the health care system.

Enhancement of nitrogen cycling and functional microbial flora by artificial inoculation of biological soil crusts in sandy soils of highway slopes.

Biological soil crusts (BSCs) are common in arid and semi-arid ecosystems and enhance soil stability and fertility. Highway slopes severely deplete the soil ecological structure and soil nutrients, hindering plant survival. The construction of highway slope BSCs under human intervention is critical to ensure the long-term stable operation of the slope ecosystem. This study investigated the variation rules and interaction mechanisms between soil nutrients and microbial communities in the subsoil BSCs on highway slopes. Bacterial 16S rRNA high-throughput sequencing was employed to investigate the dynamic compositional changes in the microbial community and perform critical metabolic predictive analyses of functional bacteria. This study revealed that the total soil nitrogen increased significantly from 0.557 to 0.864 g/kg after artificial inoculation with desert Phormidium tenue and Scytonema javanicum. Actinobacteria (44-48%) and Proteobacteria (28-31%) were the dominant phyla in all samples. The abundance of Cyanobacteria, Cytophagaceae, and Chitinophagaceae increased significantly after inoculation. PICRUST analysis showed that the main metabolic pathways of soil microorganisms on highway slopes included cofactor and vitamin, nucleotide, and amino acid metabolisms. These findings suggest that the artificial inoculation with Phormidium tenue and Scytonema javanicum could alter soil microbial distribution to promote soil development on highway slopes toward nutrient accumulation.

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction.

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma.

Chemotherapy resistance is the leading cause for hepatocellular carcinoma (HCC)-induced death. Exploring resistance generation mechanism is an urgent need for HCC therapy. Here, we found STEAP4 was significantly downregulated in HCC patients with recurrence. Patients with low STEAP4 had poor outcome, suggesting STEAP4 might inhibit chemotherapy resistance. Cell viability assay, colony formation assay, apoptosis assay, soft agar growth assay, and tumor animal model showed STEAP4 inhibited cisplatin resistance. Mechanism analysis showed STEAP4 inhibited PI3K/AKT pathway through directly interacting with AKT. Double knockdown of STEP4 and AKT significantly inhibited cisplatin resistance. We also found STEAP4 expression was negatively correlated with PI3K/AKT pathway activity in clinic specimens. In summary, our findings suggested STEAP4 inhibited cisplatin resistance through suppressing PI3K/AKT pathway activity, providing a target for HCC therapy.

Water Intake and Handgrip Strength in US Adults: A Cross-Sectional Study Based on NHANES 2011-2014 Data.

This study aimed to examine the relationship between daily total intake of water (DTIW) and handgrip strength (HGS) among US adults and to explore the impact of water intake on muscle function and health, providing a reference for public health policies and health education. Using the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, a cross-sectional survey design was adopted to analyze 5427 adults (48.37% female and 51.63% male) aged 20 years and above. DTIW was assessed using two non-consecutive 24 h dietary recall interviews, and the HGS level was measured using a Takei Dynamometer. Weighted generalized linear regression models and restricted cubic spline plots were used to analyze the linear and nonlinear associations between DTIW and HGS level and to conduct a gender subgroup analysis and an interaction effect test. The results showed that there were significant differences in HGS and other characteristics among different quartile groups of DTIW (p < 0.05). There was a significant nonlinear trend (exhibiting an inverted U-curve) between DTIW and HGS (p for nonlinear = 0.0044), with a cut-off point of 2663 g/day. Gender subgroup analysis showed that the nonlinear trend (exhibiting an inverted U-curve) was significant only in males (p for nonlinear = 0.0016), with a cut-off point of 2595 g/day. None of the stratified variables had an interaction effect on the association between DTIW and HGS (p for interaction > 0.05). In conclusion, this study found a nonlinear association between DTIW and HGS levels, as well as a gender difference. This finding provides new clues and directions for exploring the mechanism of the impact of DTIW on muscle function and health and also provides new evidence and suggestions for adults to adjust their water intake reasonably.

Dynamic atlas of immune cells reveals multiple functional features of macrophages associated with progression of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality rate and unclarified aetiology. Immune response is elaborately regulated during the progression of IPF, but immune cells subsets are complicated which has not been detailed described during IPF progression. Therefore, in the current study, we sought to investigate the role of immune regulation by elaborately characterize the heterogeneous of immune cells during the progression of IPF. To this end, we performed single-cell profiling of lung immune cells isolated from four stages of bleomycin-induced pulmonary fibrosis-a classical mouse model that mimics human IPF. The results revealed distinct components of immune cells in different phases of pulmonary fibrosis and close communication between macrophages and other immune cells along with pulmonary fibrosis progression. Enriched signals of SPP1, CCL5 and CXCL2 were found between macrophages and other immune cells. The more detailed definition of the subpopulations of macrophages defined alveolar macrophages (AMs) and monocyte-derived macrophages (mo-Macs)-the two major types of primary lung macrophages-exhibited the highest heterogeneity and dynamic changes in expression of profibrotic genes during disease progression. Our analysis suggested that Gpnmb and Trem2 were both upregulated in macrophages and may play important roles in pulmonary fibrosis progression. Additionally, the metabolic status of AMs and mo-Macs varied with disease progression. In line with the published data on human IPF, macrophages in the mouse model shared some features regarding gene expression and metabolic status with that of macrophages in IPF patients. Our study provides new insights into the pathological features of profibrotic macrophages in the lung that will facilitate the identification of new targets for disease intervention and treatment of IPF.