Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer.

Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

Transition Layer Assisted Synthesis of Defect Free Amine-Phosphine Based InP QDs.

Environmentally friendly InP-based quantum dots (QDs) are promising for light-emitting diodes (LEDs) and display applications. So far, the synthesis of highly emitting InP-based QDs via safe and economically viable amine-phosphine remains a challenge. Herein, we report the synthesis of amine-phosphine based InP/ZnSe/ZnS QDs by introducing an alloyed oxidation-free In-ZnSe transition layer (TL) at the core-shell interface. The TL not only has the essential function of preventing oxidation of the core and relieving interfacial strain but also results in oriented epitaxial growth of shell. The alloyed TL significantly mitigates the nonradiative recombination at core-shell interfacial trap states, thereby boosting the photoluminescence (PL) efficiency of the QDs up to 98%. Also, the Auger recombination is suppressed, extending the biexciton lifetime from 60 to 100 ps. The electroluminescence device based on the InP-based QDs shows a high external quantum efficiency over 10%, further demonstrating high quality QDs synthesized by this process.

Biological aging mediates the associations of metabolic score for insulin resistance with all-cause and cardiovascular disease mortality among US adults: A nationwide cohort study.

AIM: To investigate the associations of metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular disease (CVD)-specific mortality and the potential mediating role of biological ageing. METHODS: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan-Meier survival curves were used to determine the relationships of METS-IR with all-cause and CVD-specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). RESULTS: During a median follow-up of 9.17 years, we observed 2818 deaths, of which 875 were CVD-specific. Multivariable Cox regression showed that the highest METS-IR level (Q4) was associated with increased all-cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14-1.67) and CVD mortality (HR 1.52, 95% CI 1.10-2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS-IR and all-cause mortality. Only METS-IR above the threshold (41.02 µg/L) was positively correlated with all-cause death. METS-IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS-IR and all-cause and CVD-specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. CONCLUSIONS: This study highlights the detrimental effects of insulin resistance, as measured by METS-IR, on all-cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders.

Extraction, purification and anticancer activity studies on triterpenes from pomegranate peel.

Pomegranate peel is the by-product of pomegranate processing, which contains a lot of triterpene compounds. In this study, the total triterpenes of pomegranate peel (TPP) were extracted using an ultrasonic-assisted ethanol extraction method under optimal conditions, purified using D-101 macroporous resin to obtain a purity of 75.28%. The triterpenes in TPP were mainly pentacyclic triterpenes determined by LC-MS/MS. Network pharmacological analysis predicted that the anticancer targets were closely related to the MAPK pathway. The in vitro results showed that TPP could inhibit cell proliferation, promote apoptosis, reduce mitochondrial membrane potential and increase ROS levels. The western blot results indicated that the expression levels of the apoptotic proteins Bax, Bcl-2, cytochrome C, cleaved caspase-3 and cleaved caspase-9 were increased. In addition, the protein expression of the MAPK pathway predicted by network pharmacology also changed significantly. These results provided that TPP has potential for adjuvant therapy of tumors.

Small RNA signatures of acute ischemic stroke in L1CAM positive extracellular vesicles.

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA transcript modules correlated to diagnosis, initial NIH stroke scale, and age. L1EV RNA signatures associated with the diagnosis of AIS were derived from WGCNA and RF classification. These small RNA signatures demonstrated a high degree of accuracy in the diagnosis of AIS with an area under the curve (AUC) of the signatures ranging from 0.833 to 0.932. Further work is necessary to understand the role of small RNA L1EV cargoes in the response to brain injury, however, this study supports the utility of L1EV small RNA signatures as a biomarker of stroke.

Transparent grating-based metamaterials for dynamic infrared radiative regulation smart windows.

Dynamic infrared radiation regulation has been widely explored for smart windows because of its vital importance for comfortable and energy-efficient buildings. However, it remains a great challenge to synchronously achieve high visible transmittance and pronounced infrared tunability. Here, we propose a dynamic infrared tunable metamaterial composed of indium tin oxide (ITO) gratings, an air insulator, and an ITO reflector. The ITO grating-based infrared radiation regulator exhibits a high emissivity tunability of 0.73 at 8-13 µm while maintaining a high visible transmittance of 0.65 and 0.72 before and after actuation, respectively. By adjusting the geometric parameters, the tunable bandwidth can be further extended to 3-30 µm and the ultra-broadband tunability reaches 0.62. The excellent infrared tunable performance arises from the insulator thickness-dependent effect of Fabry-Pérot and propagating surface plasmon resonance coupling and decoupling, which lead to perfect and low absorption, respectively. This work provides potential for the advancement of smart window technology and makes a significant contribution to sustainable buildings.

The phenotypic changes of Schwann cells promote the functional repair of nerve injury.

Functional recovery after nerve injury is a significant challenge due to the complex nature of nerve injury repair and the non-regeneration of neurons. Schwann cells (SCs), play a crucial role in the nerve injury repair process because of their high plasticity, secretion, and migration abilities. Upon nerve injury, SCs undergo a phenotypic change and redifferentiate into a repair phenotype, which helps in healing by recruiting phagocytes, removing myelin fragments, promoting axon regeneration, and facilitating myelin formation. However, the repair phenotype can be unstable, limiting the effectiveness of the repair. Recent research has found that transplantation of SCs can be an effective treatment option, therefore, it is essential to comprehend the phenotypic changes of SCs and clarify the related mechanisms to develop the transplantation therapy further.

Association between dietary supplement use and mortality in cancer survivors with different body mass index and frailty status: a cohort study.

Background: The association between Body Mass Index (BMI), frailty index (FI), and dietary supplement in cancer survivors has been a subject of growing interest. This study investigates the relationship of BMI and FI with mortality in American cancer survivors and explores the impact of dietary supplement usage on different BMI and FI groups. Methods: Three thousand nine hundred and thirty-two cancer patients from the National Health and Nutrition Examination Survey (NHANES) database were included in the analyses. BMI, FI, and supplement usage were obtained through the NHANES structured survey and the 49-item FI tool. Weighted logistic and Cox proportional hazards models, Kaplan-Meier survival analyses, and propensity score matching (PSM) were used to elucidate the relationships between BMI, FI, dietary supplement, and mortality outcomes. Results: The study found significant associations between higher BMI and increased frailty (Odds ratio [OR] = 1.04, 95% confidence interval [95% CI], 1.02-1.06). BMI < 25 kg/m2 and FI > 0.2 are associated with an increased mortality rate. Dietary supplement use can reduce all-cause and cancer mortality in cancer patients with BMI < 25 kg/m2 (Hazard ratio [HR] = 0.63, 95% CI, 0.47-0.84; HR = 0.48, 95% CI, 0.29-0.80) or FI ≤ 0.2 (HR = 0.77, 95% CI, 0.60-0.99; HR = 0.59, 95% CI, 0.39-0.89). In cancer patients with BMI < 25 kg/m2 and FI ≤ 0.2, dietary supplement users had lower all-cause and cancer mortality (HR = 0.49, 95% CI, 0.30-0.79; HR = 0.25, 95% CI, 0.10-0.60). Conclusion: The study revealed a negative correlation between BMI and the FI among the cancer patient cohort as well as their complex impact on mortality and highlighted the role of dietary supplement in cancer prognosis, indicating benefits for non-frail patients with BMI < 25 kg/m2.

Human Papilloma Virus Infection and Gene Subtypes Analysis in Women Undergoing Physical Examinations: A 2015-2020 Study in Wenzhou, China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is closely related to cervical cancer. The epidemiologic characteristics of cervical HPV have regional differences. Therefore, it is necessary to develop the most favorable policies according to the actual situation of each region to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes, and temporal trends of HPV in women undergoing physical examination in Wenzhou, to provide a decision-making basis for further prevention and control of HPV. METHODS: A total of 31 131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China, from 2015 to 2020 were collected. The age distribution was analyzed using the chi-squared test, and the time change trend was analyzed using the Mann-Kendall trend test. On this basis, the distribution characteristics of the HPV subtypes were analyzed. RESULTS: The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group 25 years old, followed by the group >61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16, and HPV39, whereas the low-risk subtypes were HPV61, HPV81, HPV44, HPV43, and HPV55. Of all the positive samples, 76.03% were infected with a high-risk subtype. CONCLUSION: Most female HPV patients in Wenzhou are infected with high-risk gene subtypes. Therefore, physical examination and screening for HPV should be further strengthened, and the corresponding vaccination policy should focus on high-risk gene subtypes.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. The epidemic characteristics of cervical HPV have regional differences, Therefore, it is necessary to formulate the most favorable policies according to the actual situation of each region, so as to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes and temporal trends of HPV in women undergoing physical examination in Wenzhou. To provide decision-making basis for further prevention and control of HPV. METHODS: A total of 31,131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China from 2015 to 2020, were collected. The age distribution was analyzed by the chi-squared test, and the time change trend was analyzed by the Mann­Kendall trend test. On this basis, the distribution characteristics of HPV subtypes were analyzed. RESULTS: The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group less than or equal to 25 years old, followed by the group greater than 61 years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16 and HPV39, while for low-risk were HPV61, HPV81, HPV44, HPV43 and HPV55, respectively. Of all the positive samples, 76.03% were infected with a high-risk subtype.

Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer.

Background: Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors. Methods: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments. Results: GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells. Conclusion: This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.

The attentional guidance and facilitating effects of group behavioral cues on individual college pedestrians' jaywalking decisions.

OBJECTIVE: Jaywalking is an important cause of pedestrian-related automobile accidents. Exploring the factors that influence jaywalking behavior and suggesting appropriate improvement measures are critical for reducing automobile accidents involving pedestrians. METHODS: This study divided traffic situations into high-risk and low-risk situations. Each situation contained three visual attention cues: vehicle, traffic light, and group behavior. Based on this, the role of visual cues in guiding pedestrians' attention and influencing their decisions during jaywalking was examined. Sixty participants, with an average age of 19, were recruited. They were shown 84 crosswalk videos randomly while their crossing decisions and eye movement data were recorded. RESULTS: In low-risk situations, pedestrians spent more attention on group behavioral cues when making jaywalking decisions. The rate of jaywalking increased with the number of other jaywalking pedestrians. In high-risk situations, the pedestrians' total fixation duration at vehicle hazard cues was longer when making jaywalking decisions, and the jaywalking rate decreased. CONCLUSIONS: The results indicate that pedestrians' jaywalking decisions were based on other pedestrians' illegal crossing cues and automatic associative processes in low-risk situations. The higher the number of people crossing the street, the higher the number of pedestrians illegally crossing the road. In high-risk situations, pedestrians paid more attention to vehicle hazard cues before making jaywalking decisions, and fewer illegal crossings. The jaywalking decisions were based on a risk assessment, a controlled analytical process. The results verify the effect of visual cues on pedestrians' attentional guidance and decision-making in different traffic situations, as well as the effectiveness of visual attention in predicting decision intention. The findings provide a theoretical basis and data reference for pedestrian safety education and constructing an intelligent driving pedestrian trajectory prediction model.

RNAi of yellow-y, required for normal cuticle pigmentation, impairs courtship behavior and oviposition in the German cockroach (Blattella germanica).

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.

Wireless Sensing System Based on Biodegradable Triboelectric Nanogenerator for Evaluating Sports and Sleep Respiratory.

The rapid growth of the Internet of Things and wearable sensors has led to advancements in monitoring technology in the field of health. One such advancement is the development of wearable respiratory sensors, which offer a new approach to real-time respiratory monitoring compared to traditional methods. However, the energy consumption of these sensors raises concerns about environmental pollution. To address the issue, this study proposes the use of a triboelectric nanogenerator (TENG) as a sustainable energy source. The electrical conductivity of the TENG is improved by incorporating chitosan and carbon nanotubes, with the added benefit of chitosan's biodegradability reducing negative environmental impact. A wireless intelligent respiratory monitoring system (WIRMS) is then introduced, which utilizes a degradable triboelectric nanogenerator for real-time respiratory monitoring, diagnosis, and prevention of obstructive respiratory diseases. WIRMS offers stable and highly accurate respiratory information monitoring, while enabling real-time and nondestructive transmission of information. In addition, machine learning technology is used for sleep respiration state analysis. The potential applications of WIRMS extend to wearables, medical monitoring and sports monitoring, thereby presenting innovative ideas for modern medical and sports monitoring.

Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification.

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.

Machine learning-assisted novel recyclable flexible triboelectric nanogenerators for intelligent motion.

In the smart era, big data analysis based on sensor units is important in intelligent motion. In this study, a dance sports and injury monitoring system (DIMS) based on a recyclable flexible triboelectric nanogenerator (RF-TENG) sensor module, a data processing hardware module, and an upper computer intelligent analysis module are developed to promote intelligent motion. The resultant RF-TENG exhibits an ultra-fast response time of 17 ms, coupled with robust stability demonstrated over 4200 operational cycles, with 6% variation in output voltage. The DIMS enables immersive training by providing visual feedback on sports status and interacting with virtual games. Combined with machine learning (K-nearest neighbor), good classification results are achieved for ground-jumping techniques. In addition, it shows some potential in sports injury prediction (i.e., ankle sprains, knee hyperextension). Overall, the sensing system designed in this study has broad prospects for future applications in intelligent motion and healthcare.

Investigation of the Effect of Stress on Oxygen Diffusion in Pure Titanium Using a Phase-Field Model.

Diffusion plays a vital role during the fabrication of many materials. It is a well-known fact that stress can influence diffusion behavior. In order to optimize material processing techniques, a quantitative evaluation of the effect of stress on diffusion is essentially required. By analyzing the free energy change in a Ti-O system during diffusion, a phase-field model was developed to address this issue. Using this model, the diffusion of oxygen atoms in pure titanium under different stress states was investigated. It was observed that the true equilibrium concentration of oxygen was proportional to its hydrostatic pressure. Tensile stress can increase the oxygen concentration. This raise in concentration decreased with temperature. However, the promotion of diffusion can be attained in deeper regions at a higher temperature. On the contrary, compressive stress inhibited the diffusion of oxygen in pure titanium. Under a certain compressive stress, the decrease in the oxygen concentration at the surface layer was more significant at a lower temperature, while a decrease could be observed at a deeper distance from the surface at a higher temperature. A thermodynamic explanation of the effect of stress on diffusion was given based on the proposed phase-field model.

DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability.

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish.

Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Emericellopsis maritima Y39-2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT-PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to exert antithrombotic effects.