Combined effects of microplastics and pharmaceutical and personal care products on algae: A critical review.

Microplastics (MPs) and pharmaceuticals and personal care products (PPCPs) are ubiquitous in aquatic environments. Algae play an important role in aquatic environments. Thus, it is important to study the response of algae to combined exposure of MPs and PPCPs. Here, we review the effects of MPs and PPCPs on algae. First, the individual effects of MPs and PPCPs on algae were summarized. Second, the combined effects of MPs and PPCPs on algae were systematically analyzed. (1) Antagonism: ① when the MPs are too large to enter the algal cells, the adsorption of PPCPs onto MPs results in decreased the contact of MPs and PPCPs with algae; ② PPCPs and MPs have opposing actions on the same biological target; ③ MPs increase the activity of metabolic enzymes in algae, thus promoting the PPCP degradation. (2) Synergy: ① when the MPs are small enough to enter algal cells, the adsorption of PPCPs on MPs promotes the entry of PPCPs; ② when MPs are negatively charged, the adsorption of positively charged PPCPs by MPs decreases the electrostatic repulsion, increasing the interaction between algae and MPs; ③ complementary modes of action between MPs and PPCPs show combined effects on the same biological target. Third, the relative importance of the factors that impact the combined effects are evaluated using the random forest model decreased in the following order: PPCP types > algal species > MP size > MP concentration > MP types > exposure time. Finally, future directions for the combined effects of MPs and PPCPs are proposed, which will facilitate a better understanding of the environmental fate and risks of both MPs and PPCPs.

Force Field X: A computational microscope to study genetic variation and organic crystals using theory and experiment.

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.

Research Progress of Central Serous Chorioretinopathy in Recent 20 Years Based on Visual Bibliometric Analysis.

OBJECTIVE: To dynamically track the publications on central serous chorioretinopathy (CSC) and depict the research status and hot spots to guide future research. METHODS: Gather all papers published in this area between 2004 and 2024 in the WOSCC databases comprehensively, assess their trends, and characterize the contributions of various nations, authors, institutions, and journals. In addition, VOSviewer, CiteSpace, and R software are used to obtain the most popular keywords for the topic. RESULTS: A total of 2,203 papers were published across 1,863 institutions in 59 countries. Among these, 6,907 authors contributed to publications in 300 journals and generated a total of 35,638 citations. The number of publications continues to grow steadily. Notably, Jay Chhablani's team/Lab stands out as the leading contributor with ownership of 84 publications. Through keyword network analysis and clustering techniques, risk factor-related clustering, imaging-related clustering, pathogenesis-related clustering, and treatment-related clustering were identified. Furthermore, keyword analysis has unveiled emerging frontier areas including pachychoroid disease, choroidal vasculature abnormalities, PDT therapy, and optical coherence tomography that have garnered increasing interest. CONCLUSION: This study presents a comprehensive review of central serous retinopathy research conducted in the past two decades, highlighting key trends and exploring emerging research frontiers within this field. As such, it provides valuable references and suggestions for researchers engaged in studying this topic.

Correlated Charge Density Wave Insulators in Chirally Twisted Triple Bilayer Graphene.

Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.

The application effect of the optimized scheduling model of virtual power plant participation in the new electric power system.

To build a comprehensive framework for virtual power plant (VPP) development aligned with market dynamics and to devise effective strategies to foster its growth, this study undertakes several key steps. Firstly, it constructs a VPP development framework based on market conditions, to drive the evolution of new power systems and facilitating energy transformation. Secondly, through a blend of theoretical analysis and model construction, the fundamental principles of VPP are systematically elucidated, and a decision model for the VPP development framework, focusing on price demand response, is formulated. Lastly, an optimal scheduling model for the new power system is developed, with its efficacy validated across three distinct scenarios. The findings underscore the critical importance of integrating energy storage technologies, particularly pumped storage hydropower systems, for achieving balance and optimization within new power systems. Model verification reveals that the incorporation of energy storage power stations significantly enhances system stability and efficiency, particularly in addressing the volatility associated with renewable energy sources. Additionally, the analysis indicates that while the adoption of energy storage technologies may marginally increase overall power generation costs, the total power generation cost declines with the integration of battery storage and pumped storage hydropower stations. This suggests that leveraging energy storage technologies not only enhances system operational reliability but also contributes to reducing the overall cost of power production to a certain extent. In summary, this study presents an economic and environmentally sustainable scheduling model for new power systems within the context of market trading environments. By offering both theoretical insights and practical guidance, it aims to support sustainable development and energy transformation initiatives. Ultimately, the study is poised to foster the adoption of clean energy, facilitate the establishment of smart grids, and bolster the sustainable utilization of energy resources, thereby advancing environmental conservation efforts.

Arrays of Bowl-Shaped Janus Particle Film with Structured Colors.

Structural colors generated via total internal reflection (TIR) using nanostructure-free micro-concave shapes have garnered increasing attention. However, the application of large micro-concave structures for structural coloration remains limited. Herein, a flexibly tunable structural color film fabricated by casting polydimethylsiloxane (PDMS) on an array of large poly(glycidyl methacrylate) (PGMA) bowl-shaped particles is reported. The resultant film exhibits tunable red to green structural colors with changing observation angles. Moreover, the color can be further tailored by altering the shape of the film itself. The incorporation of the PDMS layer not only facilitates a shift in the locus of TIR from the bottom surface to the top concave surface of the particles, thereby enabling the generation of structural color, but also confers enhanced flexibility to the film. Further decoration with silver nanoparticles imparts antimicrobial properties, yielding a novel antimicrobial coating material with structural colors. The simple and cost-effective strategy for the production of structural color films provides potential applications in antimicrobial coatings, enabling accessible and customizable structural coloration using big-size micro-concave particles.

Multiparametric MRI-based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

Emergency rescue of a patient with hemorrhagic shock caused by superior mesenteric artery rupture: A case report.

BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Evaluating artificial intelligence-enhanced digital urine cytology for bladder cancer diagnosis.

BACKGROUND: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time. METHODS: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers. RESULTS: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers. CONCLUSIONS: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes.

Obesity, abdominal obesity, metabolic obesity phenotypes, and Helicobacter pylori infection: results from NHANES 1999-2000.

BACKGROUND: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection. METHODS: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association. RESULTS: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI. CONCLUSIONS: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years.

Triflate anion chemistry for enhanced four-electron zinc-iodine aqueous batteries.

I+ hydrolysis, sluggish iodine redox kinetics and the instability of Zn anodes are the primary challenges for aqueous four-electron zinc-iodine batteries (4eZIBs). Herein, the OTf- anion chemistry in aqueous electrolyte is essential for developing advanced 4eZIBs. It is elucidated that OTf- anions establish weak hydrogen bonds (H bonds) with water to stabilize I+ species while optimizing a water-lean Zn2+ coordination structure to mitigate Zn dendrites and corrosion. Moreover, the interaction of the OTf- anions with the iodine species results in an increased equilibrium average intermolecular bond length of the iodine species, facilitating the 4e redox kinetics of iodine with improved reversibility.

High-Intensity Focused Ultrasound Ablation Combined With Pharmacogenomic-Guided Chemotherapy for Advanced Pancreatic Cancer: Initial Experience.

OBJECTIVE: To investigate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation combined with pharmacogenomic-guided chemotherapy in treating patients with advanced pancreatic cancer (PC). METHODS: Thirty-one patients with unresectable PC (stage III 17, stage IV 14) were enrolled in this study. The patients were divided into group A (pharmacogenomic-guided chemotherapy following HIFU treatment, n = 13) and group B (traditional chemotherapy following HIFU treatment, n = 18). Contrast-enhanced computed tomography and magnetic resonance imaging were used to evaluate tumor response. Pain intensity was assessed using the numerical rating scale. The Kaplan-Meier method and log-rank test were used to analyze survival. RESULTS: The mean pain intensity score in 18 patients decreased from 6.6 ± 2.2 before HIFU to 3.3 ± 1.0 after HIFU (p = 0.000). The mean duration of pain relief was 5.2 ± 3.2 mo in group A and 2.4 ± 1.3 mo in group B (p = 0.026). There was no significant difference of the non-perfused volume ratio (83.5% ± 22.3% in group A and 85.3% ± 16.8% in group B) between the two groups. The median survival time was 14 mo in group A and 5 mo in group B. The 6 and 12-mo survival rates were 74.1% and 59.3% in group A, and 32.4% and 19.4% in group B, respectively. The difference in survival between the two groups was significant (p = 0.04). No severe complications (≥grade 3) related to HIFU were observed. Bone marrow depression was the main adverse reaction related to chemotherapy, with grade 3 bone marrow depression observed 2 (15.4%) patients in group A and 7 (38.9%) patients in group B. CONCLUSION: HIFU combined with pharmacogenomic-guided chemotherapy is safe and effective in treating patients with advanced PC. It provides better clinical outcomes in pain relief, quality of life and survival benefits for patients with advanced PC compared to HIFU combined with traditional chemotherapy. This combined approach may have the potential to become an important supplement to the treatment of advanced PC.

Clinical efficacy of thalidomide for various genotypes of beta thalassemia.

OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of ß-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. METHODS: From our initial sample of 52 patients, we observed 48 patients with ß-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with ßCD41-42/ßCD17 and 6 cases with ßCD41-42/ß-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001). CONCLUSION: In this study, we identified 10 ß-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.

Association between outdoor jogging behavior and PM2.5 exposure: Evidence from massive GPS trajectory data in Beijing.

Outdoor jogging is one of the most popular practised exercises worldwide, providing various benefits for health and wellbeing. However, PM2.5 exposure risks of jogging behaviors were rarely explored. This study aims to investigate the association between jogging behavior and PM2.5 exposure with big data. PM2.5 exposure concentration and dose inhalation of individuals were calculated by integrating hourly PM2.5 concentration data and jogging GPS trajectory recorded by a sports app during 2015 in Beijing, after which relationships between jogging behaviors and PM2.5 exposure were unpacked using statistics analysis and structural equation modelling. Experimental results on massive jogging trajectories show that: (1) the average jogging PM2.5 exposure concentration is 60.43 µg/m3, and female joggers inhaled significantly less air pollution dose (19.70 µg) than men (24.91 µg). (2) There exist significant spatiotemporal disparities in jogging exposure to PM2.5. Joggings in the city center, in the morning, on weekdays and in autumn and winter seasons were exposed to higher pollution concentrations. (3) Jogging behavior characteristics, especially distance, activity space size, duration and rotation, were systematically associated with PM2.5 exposure across space and time. (4) The role of gender directly shaped joggers' dose inhalation of PM2.5 pollution and indirectly via duration, timing choice and distance. (5) The effects of weather conditions on joggers' exposure to PM2.5 are mainly via direct effects, whereas the direct impacts of precipitation and wind speed are mitigated by indirect effects stemming from jogging behavior patterns. Our findings provide insights for personal guidance and policy intervention for the sake of promoting physical activity and reducing PM2.5 exposure.

Improved assembly DC circuit breaker based on resonant current injection.

DC circuit breakers (DCCBs) with high breaking capacity and low cost are necessary for quick fault clearance in DC networks. The assembly DC circuit breakers (ADCCBs) have a main breaking section (MBS) and a sub-breaking sections (SBS) for each line, which greatly reduce the cost. But in conventional operation, it bears high voltage for a long time when there is a main switch grounding process in any line fault action. To address this problem, a multiport assembly circuit breaker based on current injection (CI-MPACB) is proposed, which is able to generate a resonant current with increasing amplitude by controlling the duty cycle of Integrated Gate-Commutated Thyristors (IGCTs). Then the resonant current is injected into the SBS to generate current zero crossing and arc extinction. A complex frequency domain circuit analysis is performed on the MBS to describe the action logic as well as the commutation characteristics. In addition, the parameters of each component of the MBS are subject to multiple constraints and reasonable design to ensure the fault current could be cut off quickly and reliably. The cost of existing design is greatly reduced due to the design idea of resonant current injection device parameter selection. Finally, a PSCAD/EMTDC simulation confirms the opening viability of CI-MPACB and the accuracy of the parameter design. The test results show that the designed CI-MPACB can cut off DC fault lines.

Zinc gluconate improves atopic dermatitis by modulating CXCL10 release of keratinocytes via PPARα activation.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex causes involving immune factors. The presence of essential trace elements that support immune system function can influence the development of this condition. This study investigated how serum trace elements impact the pathogenesis of atopic dermatitis. Upon analyzing serum microelements in AD patients and control subjects, it was observed that patients with AD had notably lower zinc levels. Genomic analysis of AD skin revealed distinct gene expression patterns, specifically the increased expression of CXCL10 in the epidermis. The heightened levels of CXCL10 in AD skin lesions were found to correlate with reduced serum zinc levels. Treatment with zinc gluconate showed reduced chemotactic response and CXCL10 release, suggesting its potential to regulate CXCL10 expression of keratinocytes in AD. The mechanism behind this involved the downregulation of STAT phosphorylation through activating PPARα. In the AD-like dermatitis mouse model, zinc gluconate therapy decreased serum IgE levels, alleviated skin lesion severity, reduced skin thickness, and lowered CXCL10 expression, demonstrating its efficacy in managing AD-like skin conditions. These findings indicate that zinc gluconate can reduce inflammation in keratinocytes by activating PPARα, inhibiting STAT signaling, and decreasing CXCL10 release, thus highlighting its potential as a therapeutic target for AD.

Symbolic recording of signalling and cis-regulatory element activity to DNA.

Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit. We show how this strategy can be used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging signal transduction pathway-responsive cis-regulatory elements, we also demonstrate time- and concentration-dependent genomic recording of WNT, NF-κB and Tet-On activities. By coupling ENGRAM to sequential genome editing via DNA Typewriter1, we stably record information about the temporal dynamics of two orthogonal signalling pathways to genomic DNA. Finally we apply ENGRAM to integratively record the transient activity of nearly 100 transcription factor consensus motifs across daily windows spanning the differentiation of mouse embryonic stem cells into gastruloids, an in vitro model of early mammalian development. Although these are proof-of-concept experiments and much work remains to fully realize the possibilities, the symbolic recording of biological signals or states within cells, to the genome and over time, has broad potential to complement contemporary paradigms for how we make measurements in biological systems.

The impacts of percutaneous coronary intervention to treat chronic total occlusion of right coronary artery on the 5-year prognosis: A single-centered retrospective study.

BACKGROUND: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study. METHODS: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR). RESULTS: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003). CONCLUSION: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up.