Photoluminescence Enhancement of 0D Organic-Inorganic Metal Halides via Aggregation-Induced Emission and Halide Substitution.

0D organic-inorganic metal halides (OIMHs) provide unprecedented versatility in structures and photoluminescence properties. Here, a series of bluish-white emissive 0D OIMHs, (TPE-TPP)2Sb2BrxCl8-x (x = 1.16 to 8), are prepared by assembling the 1-triphenylphosphonium-4-(1,2,2-triphenylethenyl)benzene cation (TPE-TPP)+ with antimony halides anions. Based on experimental characterizations and theoretical calculations, the emission of the 0D OIMHs are attributed to the fluorescence of the organic cations with aggregation-induced emission (AIE) properties. The 0D structure minimized the molecular motion and intermolecular interactions between (TPE-TPP)+ cations, effectively suppressing the non-radiative recombination processes. Consequently, the photoluminescence quantum efficiency (PLQE) of (TPE-TPP)2Sb2Br1.16Cl6.84 is significantly enhanced to 55.4% as compared to the organic salt (TPE-TPP)Br (20.5%). The PLQE of (TPE-TPP)2Sb2BrxCl8-x can also be readily manipulated by halide substitution, due to the competitive processes between non-radiative recombination on the inorganic moiety and the energy transfer from inorganic to organic. In addition, electrically driven light-emitting diodes (LEDs) are fabricated based on (TPE-TPP)2Sb2Br1.16Cl6.84 emitter, which exhibited bluish-white emission with a maximum external quantum efficiency (EQE) of 1.1% and luminance of 335 cd m-2. This is the first report of electrically driven LED based on 0D OIMH with bluish-white emission.

Baicalin protects against hepatocyte injury caused by aflatoxin B1 via the TP53-related ferroptosis Pathway.

OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.

A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice.

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.

Phosphonium Iodide Featuring Blue Thermally Activated Delayed Fluorescence for Highly Efficient X-ray Scintillator.

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100%. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy·s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

Microplastics weaken the digestion and absorption functions in the golden pompano (Trachinotus blochii) by affecting the intestinal structure, bacteria and metabolites.

Microplastics are difficult to degrade and widespread environmental pollutants. Coastal areas are hardest hit of microplastic pollution as they receive significant amounts of microplastics discharged from inland sources. Golden pompano (Trachinotus blochii) is a high commercial valuable marine aquaculture fish species, most of the golden pompano are raised in coastal areas, which means they are at significant risk of exposure to microplastics. Therefore, we exposed golden pompano to 10 µg/L, 100 µg/L and 1000 µg/L of 5 µm spherical polystyrene microplastics and conducted a 14-day stress experiment. Histopathology results showed the intestinal villi shrank. The 16s sequencing analysis revealed that microplastics significantly impacted the abundance and community structure of intestinal microorganisms, which may affect the metabolic function of the gastrointestinal tract. Metabolomics sequencing of the intestinal contents showed that microplastics caused disruptions in lipid, glucose, and amino acid metabolism, thus compromising the normal digestion and absorption functions in the intestinal system. In addition, the activation of various pathways, including the intestinal endocrine system, proline metabolism, and signal transduction, which can lead to the occurrence of several diseases. This study combined various methods to investigate the adverse effects of microplastics on intestinal digestion and absorption, and provided new insights into the toxic mechanisms of microplastics.

Efficient purging of deleterious mutations contributes to the survival of a rare conifer.

Cupressaceae is a conifer family rich in plants of horticultural importance, including Cupressus, Chamaecyparis, Juniperus, and Thuja, yet genomic surveys are lacking for this family. Cupressus gigantea, one of the many rare conifers that are threatened by climate change and anthropogenic habitat fragmentation, plays an ever-increasing role in ecotourism in Tibet. To infer how past climate change has shaped the population evolution of this species, we generated a de novo chromosome-scale genome (10.92 Gb) and compared the species' population history and genetic load with that of a widespread close relative, C. duclouxiana. Our demographic analyses, based on 83 re-sequenced individuals from multiple populations of the two species, revealed a sharp decline of population sizes during the first part of the Quaternary. However, populations of C. duclouxiana then started to recover, while C. gigantea populations continued to decrease until recently. The total genomic diversity of C. gigantea is smaller than that of C. duclouxiana, but contrary to expectations, C. gigantea has fewer highly and mildly deleterious mutations than C. duclouxiana, and simulations and statistical tests support purifying selection during prolonged inbreeding as the explanation. Our results highlight the evolutionary consequences of decreased population size on the genetic burden of a long-lived endangered conifer with large genome size and suggest that genetic purging deserves more attention in conservation management.

Discovery of piperine derivatives as inhibitors of human dihydroorotate dehydrogenase to induce ferroptosis in cancer cells.

Inhibition of human dihydroorotate dehydrogenase (hDHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent hDHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and hDHODH inhibitory activities were also evaluated. Among them, compound H19, exhibited the strongest inhibitory activities (NCI-H226 IC50 = 0.95 µM, hDHODH IC50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising hDHODH inhibitor with potential anticancer properties warranting development.

AST/ALT ratio is an independent risk factor for diabetic retinopathy: A cross-sectional study.

The aspartate to alanine transaminase (AST/ALT) ratio indicates oxidative stress and inflammatory reactions related to the occurrence of diabetic retinopathy (DR). Currently, there are no reports on the correlation between AST/ALT ratio and DR. Hence, this study aimed to explore the relationship between AST/ALT ratio and DR. This cross-sectional study utilized data from the Metabolic Management Center of the First People's Hospital in City. In total, 1365 patients with type 2 diabetes mellitus (T2DM) participated in the study, including 244 patients with DR and 1121 patients without DR. We collected the results of fundus photography, liver function, and other research data and grouped them according to tertiles of AST/ALT ratios. DR prevalence was the highest in the group with the highest AST/ALT ratio (22.12%, P = .004). Both univariate (OR = 2.25, 95% CI: 1.51-3.34, P < .001) and multivariable logistic regression analyses (adjusted for confounding factors) showed that the risk of DR increased by 36% when the AST/ALT ratio increased by 1 standard deviation (SD) (OR = 1.36, 95% CI: 1.16-1.59, P < .001), and 29.3% was mediated by the duration of diabetes. A sensitivity analysis confirmed the stability of the results. This study showed that an increase in AST/ALT ratio is an independent risk factor for DR.

Multi-optimization for thermal deformation of gravitational wave telescope based on CFRP characteristics.

Gravitational wave telescope place extremely high demands on structural thermal deformation, making material selection a critical issue. Carbon fiber reinforced polymer (CFRP) is an ideal choice for the support structure of telescope due to its low coefficient of thermal expansion (CTE) and designable properties. However, current research on the optimization of the CTE of CFRP is scarce, and conventional methods struggle to find layups that meet the requirements. In this paper, an unconventional layup optimization method is proposed to solve this problem. Initially defining the characteristics of the telescope structure and using different layup material for the main and side support rods to minimize thermal deformation. Subsequently, the NSGA-II algorithm is used to optimize the layups which are divided into conventional and unconventional layups. Specimens are then produced from these results and tested to assess the impact of processing errors on practical applications. The results demonstrate that the optimized CFRP meet the CTE requirements and, when applied to the structure, significantly reduces the thermal deformation in the eccentric direction compared to conventional designs. Additionally, a numerical analysis evaluates the effect of ply orientation errors on the performance of unconventional layups, discussing the method's limitations within these contexts.

Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy.

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.

Risk factors for deep vein thrombosis after traumatic lower extremity fracture: A systematic review and meta-analysis.

BACKGROUND: The study aimed to predict the risk factors of deep vein thrombosis of lower extremity after traumatic fracture of lower extremity, so as to apply effective strategies to prevent deep vein thrombosis of lower extremity, improve survival rate, and reduce medical cost. METHODS: The English and Chinese literatures published from January 2005 to November 2023 were extracted from PubMed, Embase, Willey Library, Scopus, CNKI, Wanfang, and VIP databases. Statistical analysis was performed using Stata/SE 16.0 software. RESULTS: A total of 13 articles were included in this paper, including 2699 venous thromboembolism (VTE) patients and 130,507 normal controls. According to the meta-results, 5 independent risk factors can be identified: history of VTE was the most significant risk factor for deep vein thrombosis after traumatic lower extremity fracture (risk ratio [RR] = 6.45, 95% confidence interval [CI]: 1.64-11.26); age (≥60) was the risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.60, 95% CI: 1.02-2.18); long-term braking was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.52, 95% CI: 1.11-1.93); heart failure was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.92, 95% CI: 1.51-2.33); obesity was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.59, 95% CI: 1.35-1.83). CONCLUSION: The study confirmed that the history of deep vein thrombosis, age (60 + years), previous history of VTE, obesity, prolonged bed rest, and heart failure are all associated with an increased risk of VTE. By identifying these significant risk factors, we can more intensively treat patients at relatively high risk of VTE, thereby reducing the incidence of VTE. However, the limitation of the study is that the sample may not be diversified enough, and it fails to cover all potential risk factors, which may affect the universal applicability of the results. Future research should include a wider population and consider more variables in order to obtain a more comprehensive risk assessment.

The impact of CYP3A4 genetic polymorphism on crizotinib metabolism and drug-drug interactions.

To elucidate the impact of CYP3A4 activity inhibition and genetic polymorphism on the metabolism of crizotinib. Enzymatic incubation systems for crizotinib were established, and Sprague-Dawley rats were utilized for in vivo experiments. Analytes were quantified using LC-MS/MS. Upon screening 122 drugs and natural compounds, proanthocyanidins emerged as inhibitor of crizotinib metabolism, exhibiting a relative inhibition rate of 93.7%. The IC50 values were 24.53 ± 0.32 µM in rat liver microsomes and 18.24 ± 0.12 µM in human liver microsomes. In vivo studies revealed that proanthocyanidins markedly affected the pharmacokinetic parameters of crizotinib. Co-administration led to a significant reduction in the AUC(0-t), Cmax of PF-06260182 (the primary metabolite of crizotinib), and the urinary metabolic ratio. This interaction is attributed to the mixed-type inhibition of liver microsome activity by proanthocyanidins. CYP3A4, being the principal metabolic enzyme for crizotinib, has its genetic polymorphisms significantly influencing crizotinib's pharmacokinetics. Kinetic data showed that the relative metabolic rates of crizotinib across 26 CYP3A4 variants ranged from 13.14% (CYP3A4.12, 13) to 188.57% (CYP3A4.33) when compared to the wild-type CYP3A4.1. Additionally, the inhibitory effects of proanthocyanidins varied between CYP3A4.12 and CYP3A4.33, when compared to the wild type. Our findings indicate that proanthocyanidins coadministration and CYP3A4 genetic polymorphism can significantly influence crizotinib metabolism.

Nickel-Catalyzed Electrochemical Cross-Electrophile C(sp2)-C(sp3) Coupling via a NiII Aryl Amido Intermediate.

Cross-electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp2)-C(sp3) bond construction, which is highly valuable in medicinal chemistry. Based on a key NiII aryl amido intermediate, we developed a highly selective and scalable Ni-catalyzed electrochemical XEC reaction between (hetero)aryl halides and primary and secondary alkyl halides. Experimental and computational mechanistic studies indicate that an amine secondary ligand slows down the oxidative addition process of the Ni-polypyridine catalyst to the aryl bromide and a NiII aryl amido intermediate is formed in-situ during the reaction process. The relatively slow oxidative addition is beneficial for enhancing the selectivity of the XEC reaction. The NiII aryl amido intermediate stabilizes the NiII-aryl species to prevent the aryl-aryl homo-coupling side reactions and acts as a catalyst to activate the alkyl bromide substrates. This electrosynthesis system provides a facile, practical, and scalable platform for the formation of (hetero)aryl-alkyl bonds using standard Ni catalysts under mild conditions. The mechanistic insights from this work could serve as a great foundation for future studies on Ni-catalyzed cross-couplings.

Local Ordering, Distortion, and Redox Activity in (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 Investigated by a Computational Workflow for Compositionally Complex Perovskite Oxides.

Mixing multiple cations can result in a significant configurational entropy, offer a new compositional space with vast tunability, and introduce new computational challenges. For applications such as the two-step solar thermochemical hydrogen (STCH) generation techniques, we demonstrate that using density functional theory (DFT) combined with Metropolis Monte Carlo method (DFT-MC) can efficiently sample the possible cation configurations in compositionally complex perovskite oxide (CCPO) materials, with (La0.75Sr0.25)(Mn0.25Fe0.25Co0.25Al0.25)O3 as an example. In the presence of oxygen vacancies (VO), DFT-MC simulations reveal a significant increase of the local site preference of the cations (short-range ordering), compared to a more random mixing without VO. Co is found to be the redox-active element and the VO is the preferentially generated next to Co due to the stretched Co-O bonds. A clear definition of the vacancy formation energy (Evf) is proposed for CCPO in an ensemble of structures evolved in parallel from independent DFT-MC paths. By combining the distribution of Evf with VO interactions into a statistical model, the oxygen nonstoichiometry (δ), under the STCH thermal reduction and oxidation conditions, is predicted and compared with the experiments. Similar to the experiments, the predicted δ can be used to extract the enthalpy and entropy of reduction using the van't Hoff method, providing direct comparisons with the experimental results. This procedure provides a full predictive workflow for using DFT-MC to obtain possible local ordering or fully random structures, understand the redox activity of each element, and predict the thermodynamic properties of CCPOs, for computational screening and design of these CCPO materials at STCH conditions.

LncRNA Peg13 Alleviates Myocardial Infarction/Reperfusion Injury through Regulating MiR-34a/Sirt1-Mediated Endoplasmic Reticulum Stress.

Myocardial infarction/reperfusion (I/R) injury significantly impacts the health of older individuals. We confirmed that the level of lncRNA Peg13 was downregulated in I/R injury. However, the detailed function of Peg13 in myocardial I/R injury has not yet been explored.To detect the function of Peg13, in vivo model of I/R injury was constructed. RT-qPCR was employed to investigate RNA levels, and Western blotting was performed to assess levels of endoplasmic reticulum stress and apoptosis-associated proteins. EdU staining was confirmed to assess the cell proliferation.I/R therapy dramatically produced myocardial injury, increased the infarct area, and decreased the amount of Peg13 in myocardial tissues of mice. In addition, hypoxia/reoxygenation (H/R) notably induced the apoptosis and promoted the endoplasmic reticulum (ER) stress of HL-1 cells, while overexpression of Peg13 reversed these phenomena. Additionally, Peg13 may increase the level of Sirt1 through binding to miR-34a. Upregulation of Peg13 reversed H/R-induced ER stress via regulation of miR-34a/Sirt1 axis.LncRNA Peg13 reduces ER stress in myocardial infarction/reperfusion injury through mediation of miR-34a/Sirt1 axis. Hence, our research might shed new lights on developing new strategies for the treatment of myocardial I/R injury.

Human tNeurons reveal aging-linked proteostasis deficits driving Alzheimer's phenotypes.

Aging is a prominent risk factor for Alzheimer's disease (AD), but the cellular mechanisms underlying neuronal phenotypes remain elusive. Both accumulation of amyloid plaques and neurofibrillary tangles in the brain1 and age-linked organelle deficits2-7 are proposed as causes of AD phenotypes but the relationship between these events is unclear. Here, we address this question using a transdifferentiated neuron (tNeuron) model directly from human dermal fibroblasts. Patient-derived tNeurons retain aging hallmarks and exhibit AD-linked deficits. Quantitative tNeuron proteomic analyses identify aging and AD-linked deficits in proteostasis and organelle homeostasis, particularly affecting endosome-lysosomal components. The proteostasis and lysosomal homeostasis deficits in aged tNeurons are exacerbated in sporadic and familial AD tNeurons, promoting constitutive lysosomal damage and defects in ESCRT-mediated repair. We find deficits in neuronal lysosomal homeostasis lead to inflammatory cytokine secretion, cell death and spontaneous development of Aß and phospho-Tau deposits. These proteotoxic inclusions co-localize with lysosomes and damage markers and resemble inclusions in brain tissue from AD patients and APP-transgenic mice. Supporting the centrality of lysosomal deficits driving AD phenotypes, lysosome-function enhancing compounds reduce AD-associated cytokine secretion and Aß deposits. We conclude that proteostasis and organelle deficits are upstream initiating factors leading to neuronal aging and AD phenotypes.

Prophylactic Antibiotics Delivered Via the Respiratory Tract to Reduce Ventilator-Associated Pneumonia: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the effects of antibiotics delivered via the respiratory tract in preventing ventilator-associated pneumonia (VAP). DATA SOURCES: We searched PubMed, Scopus, the Cochrane Library, and ClinicalTrials.gov for studies published in English up to October 25, 2023. STUDY SELECTION: Adult patients with mechanical ventilation of over 48 h and receiving inhaled or instilled antibiotics (with control group) to prevent VAP were included. DATA EXTRACTION: Two independent groups screened studies, extracted the data, and assessed the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty/quality of the evidence. Results of a random-effects model were reported for overall and predefined subgroup meta-analyses. The analysis was primarily conducted on randomized controlled trials, and observational studies were used for sensitivity analyses. DATA SYNTHESIS: Seven RCTs with 1445 patients were included, of which six involving 1283 patients used nebulizers to deliver antibiotics. No obvious risk of bias was found among the included RCTs for the primary outcome. Compared with control group, prophylactic antibiotics delivery via the respiratory tract significantly reduced the risk of VAP (risk ratio [RR], 0.69 [95% CI, 0.53-0.89]), particularly in subgroups where aminoglycosides (RR, 0.67 [0.47-0.97]) or nebulization (RR, 0.64 [0.49-0.83]) were used as opposed to other antibiotics (ceftazidime and colistin) or intratracheal instillation. No significant differences were observed in mortality, mechanical ventilation duration, ICU and hospital length of stay, duration of systemic antibiotics, need for tracheostomy, and adverse events between the two groups. Results were confirmed in sensitivity analyses. CONCLUSIONS: In adult patients with mechanical ventilation for over 48 h, prophylactic antibiotics delivered via the respiratory tract reduced the risk of VAP, particularly for those treated with nebulized aminoglycosides.

Research on High-Stability Composite Control Methods for Telescope Pointing Systems under Multiple Disturbances.

During the operation of space gravitational wave detectors, the constellation configuration formed by three satellites gradually deviates from the ideal 60° angle due to the periodic variations in orbits. To ensure the stability of inter-satellite laser links, active compensation of the breathing angle variation within the constellation plane is achieved by rotating the optical subassembly through the telescope pointing mechanism. This paper proposes a high-performance robust composite control method designed to enhance the robust stability, disturbance rejection, and tracking performance of the telescope pointing system. Specifically, based on the dynamic model of the telescope pointing mechanism and the disturbance noise model, an H∞ controller has been designed to ensure system stability and disturbance rejection capabilities. Meanwhile, employing the method of an H∞ norm optimized disturbance observer (HODOB) enhances the nonlinear friction rejection ability of the telescope pointing system. The simulation results indicate that, compared to the traditional disturbance observer (DOB) design, utilizing the HODOB method can enhance the tracking accuracy and pointing stability of the telescope pointing system by an order of magnitude. Furthermore, the proposed composite control method improves the overall system performance, ensuring that the stability of the telescope pointing system meets the 10 nrad/Hz1/2 @0.1 mHz~1 Hz requirement specified for the TianQin mission.

IFDlong: an isoform and fusion detector for accurate annotation and quantification of long-read RNA-seq data.

Advancements in long-read transcriptome sequencing (long-RNA-seq) technology have revolutionized the study of isoform diversity. These full-length transcripts enhance the detection of various transcriptome structural variations, including novel isoforms, alternative splicing events, and fusion transcripts. By shifting the open reading frame or altering gene expressions, studies have proved that these transcript alterations can serve as crucial biomarkers for disease diagnosis and therapeutic targets. In this project, we proposed IFDlong, a bioinformatics and biostatistics tool to detect isoform and fusion transcripts using bulk or single-cell long-RNA-seq data. Specifically, the software performed gene and isoform annotation for each long-read, defined novel isoforms, quantified isoform expression by a novel expectation-maximization algorithm, and profiled the fusion transcripts. For evaluation, IFDlong pipeline achieved overall the best performance when compared with several existing tools in large-scale simulation studies. In both isoform and fusion transcript quantification, IFDlong is able to reach more than 0.8 Spearman's correlation with the truth, and more than 0.9 cosine similarity when distinguishing multiple alternative splicing events. In novel isoform simulation, IFDlong can successfully balance the sensitivity (higher than 90%) and specificity (higher than 90%). Furthermore, IFDlong has proved its accuracy and robustness in diverse in-house and public datasets on healthy tissues, cell lines and multiple types of diseases. Besides bulk long-RNA-seq, IFDlong pipeline has proved its compatibility to single-cell long-RNA-seq data. This new software may hold promise for significant impact on long-read transcriptome analysis. The IFDlong software is available at https://github.com/wenjiaking/IFDlong.

Utility Analyses of AVITI Sequencing Chemistry.

Background: DNA sequencing is a critical tool in modern biology. Over the last two decades, it has been revolutionized by the advent of massively parallel sequencing, leading to significant advances in the genome and transcriptome sequencing of various organisms. Nevertheless, challenges with accuracy, lack of competitive options and prohibitive costs associated with high throughput parallel short-read sequencing persist. Results: Here, we conduct a comparative analysis using matched DNA and RNA short-reads assays between Element Biosciences' AVITI and Illumina's NextSeq 550 chemistries. Similar comparisons were evaluated for synthetic long-read sequencing for RNA and targeted single-cell transcripts between the AVITI and Illumina's NovaSeq 6000. For both DNA and RNA short-read applications, the study found that the AVITI produced significantly higher per sequence quality scores. For PCR-free DNA libraries, we observed an average 89.7% lower experimentally determined error rate when using the AVITI chemistry, compared to the NextSeq 550. For short-read RNA quantification, AVITI platform had an average of 32.5% lower error rate than that for NextSeq 550. With regards to synthetic long-read mRNA and targeted synthetic long read single cell mRNA sequencing, both platforms' respective chemistries performed comparably in quantification of genes and isoforms. The AVITI displayed a marginally lower error rate for long reads, with fewer chemistry-specific errors and a higher mutation detection rate. Conclusion: These results point to the potential of the AVITI platform as a competitive candidate in high-throughput short read sequencing analyses when juxtaposed with the Illumina NextSeq 550.