ABSTRACT
Brown adipose tissue (BAT) is rich in mitochondria and plays important roles in energy expenditure, thermogenesis, and glucose homeostasis. We find that levels of mitochondrial protein succinylation and malonylation are high in BAT and subject to physiological and genetic regulation. BAT-specific deletion of Sirt5, a mitochondrial desuccinylase and demalonylase, results in dramatic increases in global protein succinylation and malonylation. Mass spectrometry-based quantification of succinylation reveals that Sirt5 regulates the key thermogenic protein in BAT, UCP1. Mutation of the two succinylated lysines in UCP1 to acyl-mimetic glutamine and glutamic acid significantly decreases its stability and activity. The reduced function of UCP1 and other proteins in Sirt5KO BAT results in impaired mitochondria respiration, defective mitophagy, and metabolic inflexibility. Thus, succinylation of UCP1 and other mitochondrial proteins plays an important role in BAT and in regulation of energy homeostasis.
Subject(s)
Energy Metabolism/genetics , Mitochondria/metabolism , Obesity/genetics , Sirtuins/genetics , Uncoupling Protein 1/genetics , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/pathology , Animals , Gene Expression Regulation , Glucose/metabolism , Mice , Mice, Knockout , Mitochondria/genetics , Mitochondrial Proteins/genetics , Obesity/metabolism , Obesity/pathology , Proteomics/methods , Succinic Acid/metabolism , Thermogenesis/genetics , Uncoupling Protein 1/metabolismABSTRACT
The high-order three-dimensional (3D) organization of regulatory genomic elements provides a topological basis for gene regulation, but it remains unclear how multiple regulatory elements across the mammalian genome interact within an individual cell. To address this, herein, we developed scNanoHi-C, which applies Nanopore long-read sequencing to explore genome-wide proximal high-order chromatin contacts within individual cells. We show that scNanoHi-C can reliably and effectively profile 3D chromatin structures and distinguish structure subtypes among individual cells. This method could also be used to detect genomic variations, including copy-number variations and structural variations, as well as to scaffold the de novo assembly of single-cell genomes. Notably, our results suggest that extensive high-order chromatin structures exist in active chromatin regions across the genome, and multiway interactions between enhancers and their target promoters were systematically identified within individual cells. Altogether, scNanoHi-C offers new opportunities to investigate high-order 3D genome structures at the single-cell level.
ABSTRACT
The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.
ABSTRACT
Histamine is a conserved neuromodulator in mammalian brains and critically involved in many physiological functions. Understanding the precise structure of the histaminergic network is the cornerstone in elucidating its function. Herein, using histidine decarboxylase (HDC)-CreERT2 mice and genetic labeling strategies, we reconstructed a whole-brain three dimensional (3D) structure of histaminergic neurons and their outputs at 0.32 × 0.32 × 2 µm3 pixel resolution with a cutting-edge fluorescence microoptical sectioning tomography system. We quantified the fluorescence density of all brain areas and found that histaminergic fiber density varied significantly among brain regions. The density of histaminergic fiber was positively correlated with the amount of histamine release induced by optogenetic stimulation or physiological aversive stimulation. Lastly, we reconstructed a fine morphological structure of 60 histaminergic neurons via sparse labeling and uncovered the largely heterogeneous projection pattern of individual histaminergic neurons. Collectively, this study reveals an unprecedented whole-brain quantitative analysis of histaminergic projections at the mesoscopic level, providing a foundation for future functional histaminergic study.
Subject(s)
Brain , Histamine , Mice , Animals , Brain/metabolism , Neurons/metabolism , Brain Mapping , Histidine Decarboxylase/genetics , Histidine Decarboxylase/metabolism , Mammals/metabolismABSTRACT
While lead sulfide shows notable thermoelectric properties, its production costs remain high, and its mechanical hardness is low, which constrains its commercial viability. Herein, we demonstrate a straightforward and cost-effective method to produce PbS nanocrystals at ambient temperature. By introducing controlled amounts of silver, we achieve p-type conductivity and fine-tune the energy band structure and lattice configuration. Computational results show that silver shifts the Fermi level into the valence band, facilitating band convergence and thereby enhancing the power factor. Besides, excess silver is present as silver sulfide, which effectively diminishes the interface barrier and enhances the Seebeck coefficient. Defects caused by doping, along with dislocations and interfaces, reduce thermal conductivity to 0.49 W m-1 K-1 at 690 K. Moreover, the alterations in crystal structure and chemical composition enhance the PbS mechanical properties. Overall, optimized materials show thermoelectric figures of merit approximately 10-fold higher than that of pristine PbS, alongside an average hardness of 1.08 GPa.
ABSTRACT
BACKGROUND: Late embryogenesis abundant (LEA) proteins play important roles in plant growth and development, as well as stresses responsiveness. Nowadays, it has been found that LEAs also have function in fruit ripening. However, the comprehensive analysis on a genome-wide basis of LEA family remains limited, and the role of LEA in fruit ripening has not been fully explored yet, especially in strawberry, an economic important plant and ideal material for studying fruit ripening. RESULTS: In this study, a total of 266 putative LEA proteins were identified and characterized in strawberry genome. Subcellular localization prediction indicated that they were mostly localized in chloroplast, cytoplasm and nucleus. Duplication events detection revealed that whole genome duplication or segmental was the main driver for the expansion of LEA family in strawberry. The phylogenetic analysis suggested that FaLEAs were classified into eight groups, among which, LEA2 was the largest subgroup with 179 members, followed by LEA3, dehydrin (DHN), LEA4 and SMP (seed maturation protein). The LEA1 and DHN groups were speculated to play dominant roles in strawberry fruit development and ripening, according to their larger proportion of members detected as differentially expressed genes during such process. Notably, the expression of FaLEA167 belonging to LEA1 group was altered by strawberry maturation, and inhibited by overexpression of negative regulators of ripening (a cytosolic/plastid glyceraldehyde-3-phosphate dehydrogenase, FaGAPC2 and a cytosolic pyruvate kinase, FaPKc2.2). Subsequently, overexpression of FaLEA167 significantly increased the percentage of fruit at green stage, while reduced the full red fruit proportion. In consistent, the anthocyanins content and the fruit skin color variable reflecting a range from greenness to redness (a* value) were significantly reduced. Whereas, FaLEA167 overexpression apparently up-regulated citric acid, soluble protein and malondialdehyde content, but had no obvious effects on total soluble solids, sugar, flavonoids, phenolics content and antioxidant capacity. CONCLUSIONS: These findings not only provided basic information of FaLEA family for further functional research, but also revealed the involvement of FaLEA167 in negatively regulating strawberry fruit ripening, giving new insights into understanding of FaLEA functions.
Subject(s)
Fragaria , Anthocyanins/metabolism , Fruit , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, PlantABSTRACT
BACKGROUND: Chinese cherry [Cerasus pseudocerasus (Lindl.) G.Don] (syn. Prunus pseudocerasus Lindl.) is an economically important fruiting cherry species with a diverse range of attractive colors, spanning from the lightest yellow to the darkest black purple. However, the MYB transcription factors involved in anthocyanin biosynthesis underlying fruit color variation in Chinese cherry remain unknown. RESULTS: In this study, we characterized the R2R3-MYB gene family of Chinese cherry by genome-wide identification and compared it with those of 10 Rosaceae relatives and Arabidopsis thaliana. A total of 1490 R2R3-MYBs were classified into 43 subfamilies, which included 29 subfamilies containing both Rosaceae MYBs and AtMYBs. One subfamily (S45) contained only Rosaceae MYBs, while three subfamilies (S12, S75, and S77) contained only AtMYBs. The variation in gene numbers within identical subfamilies among different species and the absence of certain subfamilies in some species indicated the species-specific expansion within MYB gene family in Chinese cherry and its relatives. Segmental and tandem duplication events primarily contributed to the expansion of Chinese cherry R2R3-CpMYBs. The duplicated gene pairs underwent purifying selection during evolution after duplication events. Phylogenetic relationships and transcript profiling revealed that CpMYB10 and CpMYB4 are involved in the regulation of anthocyanin biosynthesis in Chinese cherry fruits. Expression patterns, transient overexpression and VIGS results confirmed that CpMYB10 promotes anthocyanin accumulation in the fruit skin, while CpMYB4 acts as a repressor, inhibiting anthocyanin biosynthesis of Chinese cherry. CONCLUSIONS: This study provides a comprehensive and systematic analysis of R2R3-MYB gene family in Chinese cherry and Rosaceae relatives, and identifies two regulators, CpMYB10 and CpMYB4, involved in anthocyanin biosynthesis in Chinese cherry. These results help to develop and utilize the potential functions of anthocyanins in Chinese cherry.
Subject(s)
Anthocyanins , Multigene Family , Phylogeny , Transcription Factors , Anthocyanins/biosynthesis , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Prunus avium/genetics , Prunus avium/metabolism , Genome, Plant , Arabidopsis/genetics , Arabidopsis/metabolism , Fruit/genetics , Fruit/metabolismABSTRACT
Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.
Subject(s)
Asparagus Plant , Gene Expression Profiling , Plant Growth Regulators , Plant Stems , Asparagus Plant/genetics , Asparagus Plant/metabolism , Asparagus Plant/growth & development , Plant Stems/genetics , Plant Stems/metabolism , Plant Stems/growth & development , Plant Growth Regulators/metabolism , Gene Expression Regulation, Plant , Transcriptome , Sugars/metabolism , Gibberellins/metabolismABSTRACT
Charge separation driven by the internal electric field is a research hotspot in photocatalysis. However, it remains challenging to accurately control the electric field to continuously accelerate the charge transfer. Herein, a strategy of constructing a tandem electric field to continuously accelerate charge transfer in photocatalysts is proposed. The plasma electric field, interface electric field, and intramolecular electric field are integrated into the Ag/g-C3N4/urea perylene imide (Ag/PCN/UPDI) ternary heterojunction to achieve faster charge separation and longer carrier lifetime. The triple electric fields function as three accelerators on the charge transport path, promoting the separation of electron-hole pairs, accelerating charge transfer, enhancing light absorption, and increasing the concentration of energetic electrons on the catalyst. The H2 evolution rate of Ag/PCN/UPDI is 16.8 times higher than that of pristine PDI, while the degradation rate of oxytetracycline is increased by 4.5 times. This new strategy will provide a groundbreaking idea for the development of high-efficiency photocatalysts.
ABSTRACT
Increasing crop yield depends on selecting and utilizing pleiotropic genes/alleles to improve multiple yield-related traits (YRTs) during crop breeding. However, synergistic improvement of YRTs is challenging due to the trade-offs between YRTs in breeding practices. Here, the favourable haplotypes of the TaCYP78A family are identified by analysing allelic variations in 1571 wheat accessions worldwide, demonstrating the selection and utilization of pleiotropic genes to improve yield and related traits during wheat breeding. The TaCYP78A family members, including TaCYP78A3, TaCYP78A5, TaCYP78A16, and TaCYP78A17, are organ size regulators expressed in multiple organs, and their allelic variations associated with various YRTs. However, due to the trade-offs between YRTs, knockdown or overexpression of TaCYP78A family members does not directly increase yield. Favourable haplotypes of the TaCYP78A family, namely A3/5/16/17Ap-Hap II, optimize the expression levels of TaCYP78A3/5/16/17-A across different wheat organs to overcome trade-offs and improve multiple YRTs. Different favourable haplotypes have both complementary and specific functions in improving YRTs, and their aggregation in cultivars under strong artificial selection greatly increase yield, even under various planting environments and densities. These findings provide new support and valuable genetic resources for molecular breeding of wheat and other crops in the era of Breeding 4.0.
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Immune checkpoint inhibitors (ICIs) have completely changed the approach pertaining to tumor diagnostics and treatment. Similarly, immunotherapy has also provided much needed data about mutation, expression and prognosis, affording an unprecedented opportunity for discovering candidate drug targets and screening for immunotherapy-relevant biomarkers. Although existing web tools enable biologists to analyze the expression, mutation and prognostic data of tumors, they are currently unable to facilitate data mining and mechanism analyses specifically related to immunotherapy. Thus, we effectively developed our own web-based tool, called Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer (CAMOIP), in which we are able to successfully screen various prognostic markers and analyze the mechanisms involved in biomarker expression and function, as well as immunotherapy. The analyses include information relevant to survival analysis, expression analysis, mutational landscape analysis, immune infiltration analysis, immunogenicity analysis and pathway enrichment analysis. This comprehensive analysis of biomarkers for immunotherapy can be carried out by a click of CAMOIP, and the software should greatly encourage the further development of immunotherapy. CAMOIP provides invaluable evidence that bridges the information between the data of cancer genomics based on immunotherapy, providing comprehensive information to users and assisting in making the value of current ICI-treated data available to all users. CAMOIP is available at https://www.camoip.net.
Subject(s)
Biomarkers, Tumor , Neoplasms , Biomarkers, Tumor/genetics , Humans , Immune Checkpoint Inhibitors , Immunotherapy , Mutation , Neoplasms/drug therapy , Neoplasms/geneticsABSTRACT
MOTIVATION: The confusion of acute inflammation infected by virus and bacteria or noninfectious inflammation will lead to missing the best therapy occasion resulting in poor prognoses. The diagnostic model based on host gene expression has been widely used to diagnose acute infections, but the clinical usage was hindered by the capability across different samples and cohorts due to the small sample size for signature training and discovery. RESULTS: Here, we construct a large-scale dataset integrating multiple host transcriptomic data and analyze it using a sophisticated strategy which removes batch effect and extracts the common information from different cohorts based on the relative expression alteration of gene pairs. We assemble 2680 samples across 16 cohorts and separately build gene pair signature (GPS) for bacterial, viral, and noninfected patients. The three GPSs are further assembled into an antibiotic decision model (bacterial-viral-noninfected GPS, bvnGPS) using multiclass neural networks, which is able to determine whether a patient is bacterial infected, viral infected, or noninfected. bvnGPS can distinguish bacterial infection with area under the receiver operating characteristic curve (AUC) of 0.953 (95% confidence interval, 0.948-0.958) and viral infection with AUC of 0.956 (0.951-0.961) in the test set (N = 760). In the validation set (N = 147), bvnGPS also shows strong performance by attaining an AUC of 0.988 (0.978-0.998) on bacterial-versus-other and an AUC of 0.994 (0.984-1.000) on viral-versus-other. bvnGPS has the potential to be used in clinical practice and the proposed procedure provides insight into data integration, feature selection and multiclass classification for host transcriptomics data. AVAILABILITY AND IMPLEMENTATION: The codes implementing bvnGPS are available at https://github.com/Ritchiegit/bvnGPS. The construction of iPAGE algorithm and the training of neural network was conducted on Python 3.7 with Scikit-learn 0.24.1 and PyTorch 1.7. The visualization of the results was implemented on R 4.2, Python 3.7, and Matplotlib 3.3.4.
Subject(s)
Transcriptome , Virus Diseases , Humans , Neural Networks, Computer , Bacteria , Virus Diseases/diagnosis , Virus Diseases/genetics , InflammationABSTRACT
Sirtuins (SRTs) are a group of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that target both histone and nonhistone proteins. The biological function of SRT in horticultural plants has been rarely studied. In this study, FaSRT1-2 was identified as a key member of the 8 FaSRTs encoded in cultivated strawberry genome. Transient overexpression of FaSRT1-2 in strawberry fruit accelerated ripening, increased the content of anthocyanins and sugars, enhanced ripening-related gene expression. Moreover, stable transformation of FaSRT1-2 in strawberry plants resulted in enhanced vegetative growth, increased sensitivity to heat stress and increased susceptibility to Botrytis cinerea infection. Interestingly, knocking out the homologous gene in woodland strawberry had the opposite effects. Additionally, we found the content of stress-related hormone abscisic acid (ABA) was decreased, while the growth-related gibberellin (GA) concentration was increased in FaSRT1-2 overexpression lines. Gene expression analysis revealed induction of heat shock proteins, transcription factors, stress-related and antioxidant genes in the FaSRT1-2-overexpressed plants while knocked-out of the gene had the opposite impact. In conclusion, our findings demonstrated that FaSRT1-2 could positively promote strawberry plant vegetative growth and fruit ripening by affecting ABA and GA pathways. However, it negatively regulates the resistance to heat stress and B. cinerea infection by influencing the related gene expression.
Subject(s)
Botrytis , Fragaria , Fruit , Gene Expression Regulation, Plant , Plant Proteins , Fragaria/genetics , Fragaria/growth & development , Fragaria/physiology , Fragaria/metabolism , Fruit/genetics , Fruit/growth & development , Plant Proteins/genetics , Plant Proteins/metabolism , Botrytis/physiology , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Plant Diseases/microbiology , Plant Diseases/genetics , Abscisic Acid/metabolism , Stress, Physiological/genetics , Plant Growth Regulators/metabolism , Gibberellins/metabolism , Plants, Genetically Modified , Disease Resistance/geneticsABSTRACT
Background: The SYNTAX score (SS) is useful for predicting clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). The clinical SYNTAX score (CSS), developed by combining clinical parameters with the SS, enhances the risk model's ability to predict clinical outcomes. However, prior research has not yet evaluated the prognostic capacity of CSS in patients with complex coronary artery disease (CAD) and chronic renal insufficiency (CRI) who are undergoing PCI. We aimed to demonstrate the prognostic potential of CSS in assessing long-term adverse events in this high-risk patient cohort. Methods: A total of 962 patients with left main and/or three-vessel CAD and CRI were enrolled in the study spanning from January 2014 to September 2017. The CSS was calculated by multiplying the SS by the modified age, creatinine, and left ventricular ejection fraction (ACEF) score (age/ejection fraction + 1 for each 10 mL of creatinine clearance < 60 mL/min per 1.73 m 2 ). The patients were categorized into three groups based on their CSS values: low-CSS group (CSS < 18.0, n = 321), mid-CSS group (18.0 ≤ CSS < 28.3, n = 317), and high-CSS group (CSS ≥ 28.3, n = 324) as per the tertiles of CSS. The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints included myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE). Results: At the median 3-year follow-up, the high-CSS group exhibited higher rates of ACM (19.4% vs. 6.6% vs. 3.6%, p < 0.001), CM (15.6% vs. 5.1% vs. 3.2%, p = 0.003), and MACCE (33.8% vs. 29.0% vs. 20.0%, p = 0.005) in comparison to the low and mid-CSS groups. Multivariable Cox regression analysis revealed that CSS was an independent predictor for all primary and secondary endpoints (p < 0 .05). Moreover, the C-statistics of CSS for ACM (0.666 vs. 0.597, p = 0.021) and CM (0.668 vs. 0.592, p = 0.039) were significantly higher than those of SS. Conclusions: The clinical SYNTAX score substantially enhanced the prediction of median 3-year ACM and CM in comparison with SS in complex CAD and CRI patients following PCI.
ABSTRACT
Improving bioprocess efficiency is important to reduce the current costs of biologics on the market, bring them faster to the market, and to improve the environmental footprint. The process intensification efforts were historically focused on the main stage, while intensification of pre-stages has started to gain attention only in the past decade. Performing bioprocess pre-stages in the perfusion mode is one of the most efficient options to achieve higher viable cell densities over traditional batch methods. While the perfusion-mode operation allows to reach higher viable cell densities, it also consumes large amount of medium, making it cost-intensive. The change of perfusion rate during a process (perfusion profile) determines how much medium is consumed, thereby running a process in optimal conditions is key to reduce medium consumption. However, the selection of the perfusion profile is often made empirically, without full understanding of bioprocess dynamics. This fact is hindering potential process improvements and means for cost reduction. In this study, we propose a process modeling approach to identify the optimal perfusion profile during bioprocess pre-stages. The developed process model was used internally during process development. We could reduce perfused medium volume by 25%-45% (project-dependent), while keeping the difference in the final cell within 5%-10% compared to the original settings. Additionally, the model helps to reduce the experimental workload by 30%-70% and to predict an optimal perfusion profile when process conditions need to be changed (e.g., higher seeding density, change of operating mode from batch to perfusion, etc.). This study demonstrates the potential of process modeling as a powerful tool for optimizing bioprocess pre-stages and thereby guiding process development, improving overall bioprocess efficiency, and reducing operational costs, while strongly reducing the need for wet-lab experiments.
Subject(s)
Bioreactors , Perfusion , Cell CountABSTRACT
BACKGROUND: The SYNTAX score â ¡ 2020 (SSâ ¡-2020) was created as a customized decision-making tool for individuals diagnosed with complex coronary artery disease (CAD). Nevertheless, there has been a scarcity of research investigating the long-term predictive significance of SSâ ¡-2020 for patients with both CAD and chronic renal insufficiency (CRI) who undergo percutaneous coronary intervention (PCI). AIMS: We sought to showcase the prognostic capacity of SSII-2020 in evaluating long-term all-cause mortality (ACM) within this high-risk patient cohort. METHODS: A retrospective cohort comprising 1156 individuals diagnosed with CRI and exhibiting left main CAD, three-vessel CAD or both was included in this investigation. We categorized participants into three groups based on the optimal SSII-2020 threshold for predicting long-term ACM, determined using the X-tile software. RESULTS: At the median follow-up duration of 6.3 years, the ACM rates were determined to be 10% in the low, 17% in the moderate, and 28% in the high SSII-2020 groups (p < 0.001). Employing multivariate Cox regression analysis, it was observed that the high SSII-2020 group exhibited a 3.289-fold increased risk of ACM (95% confidence interval [CI]: 2.229-4.856, p < 0.001) compared with the low SSII-2020 group, whereas the high SSII-2020 group displayed a 1.757-fold (95% CI: 1.190-2.597, p = 0.005) in comparison to the median SSII-2020 groups. Compared with SSII, the SSII-2020 had an incremental value for predicting 7-year ACM (C-index: 0.662 vs. 0.534, p = 0.007; IDI: 0.016, p < 0.001). CONCLUSIONS: SSII-2020 enhances long-term ACM prediction, facilitates improved risk stratification, and improves clinical utility for PCI patients with complex CAD and CRI.
Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Renal Insufficiency, Chronic , Humans , Percutaneous Coronary Intervention/adverse effects , Retrospective Studies , Treatment Outcome , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Risk Factors , Risk AssessmentABSTRACT
AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.
Subject(s)
Life Style , Stroke , Humans , China/epidemiology , Female , Male , Middle Aged , Prospective Studies , Stroke/epidemiology , Stroke/prevention & control , Stroke/etiology , Aged , Risk Factors , Healthy Lifestyle , Diabetes Mellitus/epidemiology , Exercise , Adult , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Proportional Hazards Models , Cerebral Hemorrhage/epidemiology , Cohort StudiesABSTRACT
High-sensitivity and fast-response photodetectors (PDs) are vital part of optical wireless communication (OWC) system. In this work, we develop an organic-inorganic hybrid perovskite material (MAPbI3) based p-i-n structured PD. By optimizing the precursor solution concertation, the PD showed a high responsivity of 0.98 A W-1, a fast response timetrise/tfallof 12/12.5 µs, a specific detectivity of 2.62 × 1013Jones, and the f-3dBof 24 kHz under the 532 nm laser and -0.2 V bias voltage. Furthermore, we designed an OWC system based on the prepared PD. With the baud rate of 19200 bps, the system exhibits a bit error rate less than 10-6, and it can realize 9.63 m long-distance communication and quick transmission applications such as strings, texts, photos, and audios. Our work demonstrates the great application potential of perovskite PDs in the field of optical communication.
ABSTRACT
BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.
Subject(s)
Communicable Diseases, Emerging , Mpox (monkeypox) , Vaccines , Humans , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/epidemiology , Mpox (monkeypox)/drug therapy , Mpox (monkeypox)/epidemiology , TechnologyABSTRACT
BACKGROUND: Effective management of cancer pain critically depends on timely medication administration and adherence to precise medication guidelines. In the context of limited time and a busy healthcare environment, tailoring the optimal medication schedule for each patient with cancer pain presents a significant challenge for physicians and clinical pharmacists. METHODS: To address this challenge, we conducted a comprehensive analysis of healthcare professionals' needs in guiding cancer pain medication. By developing core features based on key user needs and continuously updating them, we have created the Universal Medication Schedule System (UMSS). We invited 20 physicians and pharmacists specializing in oncology or cancer pain to trial the system and assessed UMSS usage through distributed questionnaires. RESULTS: We identified five key needs of healthcare professionals in cancer pain medication guidance. Based on these needs, we (1) constructed a comprehensive drug information database, including basic information for 1135 drugs, 130,590 drug interaction data entries, and 1409 individual medication timing constraints, and (2) developed a web-based system that provides essential reference information such as drug interactions and dietary restrictions. It can create medication schedules and provide medication education tailored to the patient's daily routine. Participating evaluators unanimously agreed (100%) that the system aids in accurately assessing the risks of polypharmacy and quickly scheduling medication regimens. CONCLUSION: UMSS, by offering personalized medication schedule support, assists healthcare professionals in better managing patients' medication treatment plans. However, further improvements are needed in the automation of database updates and maintenance, as well as in integrating it with electronic health records.