Search

Abstract Variations of individual lifespans within genetically identical populations in homogenous environments are remarkable, with the cause largely unknown. Here, we show the expression dynamic of the Caenorhabditis elegans fatty acid elongase ELO-6 during aging predicts individual longevity in isogenic populations. elo-6 expression is reduced with age. ELO-6 expression level exhibits obvious variation between individuals in mid-aged worms and is positively correlated with lifespan and health span. Interventions that prolong longevity enhance ELO-6 expression stability during aging, indicating ELO-6 is also a populational lifespan predictor. Differentially expressed genes between short-lived and long-lived isogenic worms regulate lifespan and are enriched for PQM-1 binding sites. pqm-1 in young to mid-aged adults causes individual ELO-6 expression heterogeneity and restricts health span and life span. Thus, our study identifies ELO-6 as a predictor of individual and populational lifespan and reveals the role of pqm-1 in causing individual health span variation in the mid-aged C. elegans.

Abstract Background Rapid on-site evaluation (ROSE) plays an important role during transbronchial sampling, providing an intraoperative cytopathologic evaluation. However, the shortage of cytopathologists limits its wide application. This study aims to develop a deep learning model to automatically analyze ROSE cytological images. Methods The hierarchical multi-label lung cancer subtyping (HMLCS) model that combines whole slide images of ROSE slides and serum biological markers was proposed to discriminate between benign and malignant lesions and recognize different subtypes of lung cancer. A dataset of 811 ROSE slides and paired serum biological markers was retrospectively collected between July 2019 and November 2020, and randomly divided to train, validate, and test the HMLCS model. The area under the curve (AUC) and accuracy were calculated to assess the performance of the model, and Cohen’s kappa (κ) was calculated to measure the agreement between the model and the annotation. The HMLCS model was also compared with professional staff. Results The HMLCS model achieved AUC values of 0.9540 (95% confidence interval [CI]: 0.9257–0.9823) in malignant/benign classification, 0.9126 (95% CI: 0.8756–0.9365) in malignancy subtyping (non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC], or other malignancies), and 0.9297 (95% CI: 0.9026–0.9603) in NSCLC subtyping (lung adenocarcinoma [LUAD], lung squamous cell carcinoma [LUSC], or NSCLC not otherwise specified [NSCLC-NOS]), respectively. In total, the model achieved an AUC of 0.8721 (95% CI: 0.7714–0.9258) and an accuracy of 0.7184 in the six-class classification task (benign, LUAD, LUSC, NSCLC-NOS, SCLC, or other malignancies). In addition, the model demonstrated a κ value of 0.6183 with the annotation, which was comparable to cytopathologists and superior to trained bronchoscopists and technicians. Conclusion The HMLCS model showed promising performance in the multiclassification of lung lesions or intrathoracic lymphadenopathy, with potential application to provide real-time feedback regarding preliminary diagnoses of specimens during transbronchial sampling procedures. Clinical trial number Not applicable.

Abstract Pressure dynamics can reflect the basic characteristics of fluid flow through underground porous formation. In this research, the oil–gas two-phase flow model for a double-porosity media formation with permeability-stress sensitivity was first established for three kinds of outer boundaries. The unified governing equation was deduced by utilizing the H function. The nonlinear mathematical model in consideration of permeability-stress sensitivity was linearized by implementing the canonical perturbation transformation and then solved by using the Laplace transformation. After that, a sequence of typical log–log curves of pressure dynamics influenced by various model parameters were plotted and analyzed. These curves reflect the typical characteristic of a V shape caused by the inter-porosity fluid flow from matrix toward natural fractures. Oil saturation and permeability-stress sensitivity coefficient have much influence on the pressure dynamics. Ultimately, the established model of oil–gas two-phase flow was validated through a well-test fitting interpretation for a real condensate gas well in a sandstone formation. This research can offer insights into the pressure dynamics dominated by the oil–gas two-phase flow in naturally fractured formations and the permeability-stress sensitivity effect.

Dynamic imaging of optical remote sensing satellites refers to the active acquisition of images while the satellite is maneuvering at a high angular velocity, which significantly enhances the efficiency and application value of remote sensing imagery. However, due to the influence of rapid maneuvering, the random error of star sensors significantly increases, resulting in a decrease in the geometric positioning accuracy of dynamic imaging remote sensing images. This paper proposes a dynamic fusion method for multisource attitude measurement data based on the noise adaptive estimation and bidirectional filter to achieve high-precision attitude determination and geometric positioning in dynamic imaging. Based on the measurement error model of star sensors, the weights of the star sensor and gyroscope are adaptively adjusted in multisource data fusion to reduce the impact of star sensor measurement errors on the gyroscope. Moreover, a bidirectional fusion filter that includes a low-velocity maneuvering stage is proposed to realize the optimal estimation of the satellite attitude parameter. The simulation data and onboard data of the Luojia3-01 (LJ3–01) satellite were tested to verify the effectiveness of the proposed method. The geometric positioning accuracy of the staring images of LJ3–01 improved from 10.048 m to 7.538 m. The registration accuracy of the sequential images improved from 3.568 pixels to 1.179 pixels. The proposed method can significantly improve the attitude determination accuracy and the geometric positioning accuracy of LJ3–01 satellite staring images. Moreover, for simulation data with various angular velocities, the attitude determination accuracies of the proposed method are better than 0.93”. The experimental results show that the proposed method can achieve high-precision attitude determination in dynamic imaging, reaching the accuracy in the traditional passive imaging.

Abstract. Background:. Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic–clinical–radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. Methods:. This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. Results:. Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276–13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086–0.405, P

Abstract Geoacoustic exploration is a rapidly evolving field investigating underground rock formations and sediment environments through acoustic waves. In this paper, we present a review of recent research progress, focusing on newly discovered physical phenomena, such as the reflection and refraction of acoustic waves at the interface between anisotropic rocks and between liquid and solid, the characteristics of electric-acoustic (and acoustic-electric) conversion of piezoelectric transducers, the physical mechanism of acoustic wave propagation in viscous media, and the generation of intrinsic noise. We developed new physical models, introduced a parallel transmission network describing piezoelectric transducers for electric-acoustic (and acoustic-electric) energy transfer, and derived new formulations and algorithms associated with the latest model. We will discuss the potential of abnormal incidence angle, acoustic attenuation, and acoustic Goos-Hänchen effect and propose a method of inversion of formation reflection coefficient using logging and seismic data acquired from anisotropic rocks with dip angle. We will also discuss the physical mechanism and potential applications of the intrinsic noise generated inside viscous solid media. Finally, we introduce a parallel/series lumped vibrational transmission network, explain the acoustic measurement process, and discuss applications of the Kaiser effect in petroleum engineering.

Myocardial ischemia is a serious threat to human health, and vascular dysfunction is its main cause. Buxu Tongyu (BXTY) Granule is an effective traditional Chinese medicine (TCM) for treating myocardial ischemia. However, the underlying mechanism of BXTY is still unclear. In this study, we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase (sGC)–3′,5′-cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin. The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice, including electrocardiogram abnormalities and changes in plasma enzymes. In addition, BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner. These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ, or with the PKG inhibitor KT 5823. Moreover, BXTY increased the protein expression of sGC-β1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells (MOVAs). NS 2028 or ODQ reversed these effects of BXTY. The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY. NS 2028, ODQ, or KT 5823 also reversed this effect of BXTY. In conclusion, BXTY can improve the symptoms of acute myocardial ischemia in mice, and activating the sGC–cGMP–PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

Abstract Study design A systematic review and Bayesian network meta-analysis (NMA). Objective To compare the effectiveness and safety of different posterior decompression techniques for LSS. Summary of background data Lumbar spinal stenosis (LSS) is one of the most common degenerative spinal diseases that result in claudication, back and leg pain, and disability. Currently, posterior decompression techniques are widely used as an effective treatment for LSS. Methods An electronic literature search was performed using the EMBASE, Web of Science, PubMed, and Cochrane Library databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was constructed to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. Results In all, 14 eligible studies comprising 1,260 patients with LSS were included. Five interventions were identified, namely, spinal processes osteotomy (SPO), conventional laminotomy/laminectomy (CL), unilateral laminotomy/laminectomy (UL), bilateral laminotomy/ laminectomy (BL), and spinous process-splitting laminotomy/laminectomy (SPSL). Among these, SPO was the most promising surgical option for decreasing back and leg pain and for lowering the Oswestry Disability Index (ODI). SSPL had the shortest operation time, while SPSL was associated with maximum blood loss. SPO and UL were superior to other posterior decompression techniques concerning lesser blood loss and shorter length of hospital stay, respectively. Patients who underwent BL had the lowest postoperative complication rates. Conclusion Overall, SPO was found to be a good surgical choice for patients with LSS.

Abstract The Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery. We present here the recommendations of a working group composed of experts from both the public and private sectors. Robust data management requires precise ontologies and standardized vocabulary while a centralized database architecture across laboratories facilitates data integration into high-value datasets. Lab automation and opening electronic lab notebooks to data mining push the boundaries of data sharing and data modeling. Important considerations for building robust machine-learning models include transparent and reproducible data processing, choosing the most relevant data representation, defining the right training and test sets, and estimating prediction uncertainty. Beyond data-sharing, cloud-based computing can be harnessed to build and disseminate machine-learning models. Important vectors of acceleration for hit and chemical probe discovery will be (1) the real-time integration of experimental data generation and modeling workflows within design-make-test-analyze (DMTA) cycles openly, and at scale and (2) the adoption of a mindset where data scientists and experimentalists work as a unified team, and where data science is incorporated into the experimental design.

The rhizosphere microbial community helps govern biogeochemical cycling and facilitates complex plant-soil feedback. Understanding the evolutionary dynamics of microbial community structure and functional genes during vegetation succession is crucial for quantifying and understanding ecosystem processes and functions in restored sandy deserts. In this study, the rhizosphere microbial community structure of 11–66-year-old dominant shrubs in a desert revegetation area was examined using shotgun metagenomic sequencing. The interactions between the microbial community structure, functional gene abundances, soil properties, and plant characteristics of different stand ages were comprehensively investigated. The abundance of unique species first increased before subsequently decreasing with stand age, with shared species accounting for only 47.33%–59.42% of the total operational taxonomic units (OTUs). Copiotrophs such as Actinobacteria and Proteobacteria were found to dominate the rhizosphere soil microbial community, with their relative abundance accounting for 75.28%–81.41% of the total OTUs. There was a gradual shift in dominant microbial functional genes being involved in cellular processes towards those involved in environmental information processing and metabolism as stand age increased. Additionally, temporal partitioning was observed in both the microbial co-occurrence network complexity and topological parameters within the rhizosphere soil. Redundancy analysis revealed that dissolved organic carbon was the primary determinant influencing shifts in microbial community structure. Understanding the evolution of microbial community structure and function contributes to identifying potential mechanisms associating the soil microbiome with dominant sand-fixing shrubs as well as understanding the rhizosphere microbiome assembly process. These results shed light on the role of the rhizosphere microbiome in biogeochemical cycling and other ecosystem functions following revegetation of temperate sandy deserts.

ABSTRACT Ceracris nigricornis Walker is an insect of the Acrididae, which can harm bamboo, rice, corn, sorghum and other crops, and can cause serious economic losses. In this study, based on 234 occurrence sites of C. nigricornis obtained from the Global Biodiversity Information Facility and literature, and data of three future climate scenarios presented by CMIP6, two niche models (GARP, MaxEnt) were used to predict the suitable area of C. nigricornis in China. The result shows that the main environmental factors affecting the distribution of C. nigricornis are min temperature of coldest month (bio6), mean temperature of coldest quarter (bio11), precipitation of driest month (bio14) and precipitation of wettest quarter (bio16). From the result of MaxEnt model, it can be seen that the suitable area of C. nigricornis in China is 128.91 × 104 km2 under current scenario. It will decrease by 3.19% in the 2050s and then increase by 12.04% in the 2090s under the SSP1‐2.6 scenario, increase by 5.79% in the 2050s and then decrease by 7.53% in the 2090s under the SSP2‐4.5 scenario, and increase by 33.03% in 2050s and then decrease by 23.31% in the 2090s under SSP5‐8.5 scenario. From the result of GARP model, it can be seen that the suitable area of C. nigricornis in China is 166.09 × 104 km2 under current scenario. It will increase by 8.41% in 2050s and then continue to increase by 6.11% in 2090s under SSP1‐2.6 scenario, increase by 23.84% in the 2050s and then decrease by 0.88% in the 2090s under the SSP2‐4.5 scenario, and increase by 34.37% in 2050s and then decrease by 1.75% in 2090s under SSP5‐8.5 scenario. The boundaries of suitable areas will expand to the north and southwest of China under future climate change scenarios, specially in Sichuan, Chongqing and Yunnan. Local forestry authorities should strengthen the monitoring of bamboo forests to prevent the damage caused by the introduction of C. nigricornis.

Previous studies suggest that learning experience influences students’ academic engagement and self-efficacy mediates the association between them, and the sub-types of self-efficacy are distinct and play different roles. However, the different roles of self-efficacy sub-types, especially in blended learning environments, have yet to be explored. The present study investigated the potential mechanism of sub-types of self-efficacy on the relationship between the learning experience and academic engagement in a smart classroom environment in the background of COVID-19. Three hundred-eight participants volunteered in this study and finished the survey, including the learning experience, self-efficacy, and academic engagement questionnaire. The results showed that learning experience significantly influences academic engagement, and sub-types of self-efficacy play different roles in the relationship between learning experience and academic engagement. Furthermore, only academic and behavioral self-efficacy mediated the relationship between them. The results of this study have specific implications for creating a sustainable blended learning environment and promoting students’ academic engagement.

IntroductionPantoea ananatis has emerged as a significant plant pathogen affecting various crops worldwide, causing substantial economic losses. Bacteriophages and their endolysins offer promising alternatives for controlling bacterial infections, addressing the growing concerns of antibiotic resistance.MethodsThis study isolated and characterized the Pantoea phage PA1 and investigated the role of PA1-LRP in directly damaging bacteria and assisting endolysin PA1-Lys in cell lysis, comparing its effect to exogenous transmembrane domains following the identification and analysis of the PA1-Lys and the PA1-LRP based on whole genome analysis of phage PA1. Additionally, this study also explored how hydrophobic region of PA1-LRP (HPP) contributes to bacterial killing when combined with PA1-Lys and examined the stability and lytic spectrum of PA1-Lys under various conditions.Results and discussionPhage PA1 belonging to the Chaseviridae family exhibited a broad host range against P. ananatis strains, with a latent period of 40 minutes and a burst size of 17.17 phages per infected cell. PA1-Lys remained stable at pH 6-10 and temperatures of 20-50°C and showed lytic activity against various Gram-negative bacteria, while PA1-Lys alone could not directly lyse bacteria, its lytic activity was enhanced in the presence of EDTA. Surprisingly, PA1-LRP inhibited bacterial growth when expressed alone. After 24 h of incubation, the OD600 value of pET28a-LRP decreased by 0.164 compared to pET28a. Furthermore, the lytic effect of co-expressed PA1-LRP and PA1-Lys was significantly stronger than each separately. After 24 h of incubation, compared to pET28a-LRP, the OD600 value of pET28a-Lys-LRP decreased by 0.444, while the OD420 value increased by 3.121. Live/dead cell staining, and flow cytometry experiments showed that the fusion expression of PA1-LRP and PA1-Lys resulted in 41.29% cell death, with bacterial morphology changing from rod-shaped to filamentous. Notably, PA1-LRP provided stronger support for endolysin-mediated cell lysis than exogenous transmembrane domains. Additionally, our results demonstrated that the HPP fused with PA1-Lys, led to 40.60% cell death, with bacteria changing from rod-shaped to spherical and exhibiting vacuolation. Taken together, this study provides insights into the lysis mechanisms of Pantoea phages and identifies a novel lysis-related protein, PA1-LRP, which could have potential applications in phage therapy and bacterial disease control.

Periodic drought adversely affects the growth and yield of summer crops in the Huang-Huai-Hai Plain. Drought-rewatering practice as one of the important agronomic measures to improve crop drought resistance. A field experiment was conducted to investigate practice physiological, biochemical, and molecular responses of maize seedling after two rounds of repeated drought and rewatering treatments. The results demonstrated that rewatering following repeated drought events had a compensatory effect on the photosynthetic rate (Pn) and on osmotic and antioxidant regulation. Specifically, the Pn and stomatal conductance (Gs) increased by 10.12 % and 5.61 %, respectively, compared to the control (CK) during the second round of treatment. Additionally, soluble protein (sPro) and proline (Pro) content rose significantly, with increases of 26.12 % and 343.49 % observed on day 5 of the second round, leading to a gradual reduction in leaf water content and osmosis. Following drought exposure, the activities of superoxide dismutase (SOD) and peroxidase (POD) contributed to the decreased levels of malondialdehyde (MDA), with both enzymes recovering during rewatering. In contrast, plant height, leaf area, and biomass were significantly reduced in the CK group. Notably, root length increased by 21.05 % after the drought-rewatering practice, enhancing the maize seedlings' ability to adapt to drought stress. Overall, maize seedlings exhibited enhanced adaptability to drought conditions following two cycles of drought-rewatering treatments.

The rice blast disease, caused by the fungus Magnaporthe oryzae, is a significant agricultural problem that adversely impacts rice production and food security. Understanding the precise molecular pathways involved in the interaction between the pathogen and its host is crucial for developing effective disease management strategies. This study examines the crucial function of the nucleolin MoNsr1 in regulating M. oryzae physiological functions. ΔMoNsr1 deletion mutants showed reduced fungal growth, asexual sporulation, and pathogenicity compared to the wild-type. Mutants exhibited impaired conidial germination and appressoria formation, reducing infection progression. Additionally, ΔMoNsr1 deletion mutant had less turgor pressure, confirming that MoNsr1 is essential for cell wall biogenesis and resistant to external stresses. Furthermore, ΔMoNsr1 deletion mutant showed enhanced sensitivity to oxidative stress, reactive oxygen species, and cold tolerance. Our results offer a thorough understanding of the function of MoNsr1 in the virulence and stress-resilient capability in M. oryzae. These findings provide insights into the novel targets and contribute to the emergence of innovative approaches for managing rice blast disease.

Diffusion magnetic resonance imaging (dMRI) allows non-invasive assessment of brain tissue microstructure. Current model-based tissue microstructure reconstruction techniques require a large number of diffusion gradients, which is not clinically feasible due to imaging time constraints, and this has limited the use of tissue microstructure information in clinical settings. Recently, approaches based on deep learning (DL) have achieved promising tissue microstructure reconstruction results using clinically feasible dMRI. However, it remains unclear whether the subtle tissue changes associated with disease or age are properly preserved with DL approaches and whether DL reconstruction results can benefit clinical applications. Here, we provide the first evidence that DL approaches to tissue microstructure reconstruction yield reliable brain tissue microstructure analysis based on clinically feasible dMRI scans. Specifically, we reconstructed tissue microstructure from four different brain dMRI datasets with only 12 diffusion gradients, a clinically feasible protocol, and the neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT) models were considered. With these results we show that disease-related and age-dependent alterations of brain tissue were accurately identified. These findings demonstrate that DL tissue microstructure reconstruction can accurately quantify microstructural alterations in the brain based on clinically feasible dMRI.

Abstract Background To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). Case presentation A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. Conclusions It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

Abstract Background Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. Methods The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator’s Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel–Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. Discussion Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. Trial registration This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Abstract This study evaluated the impacts of sulfamethoxazole (SMX) on antioxidant, immune, histopathological dynamic changes, and gut microbiota of zebrafish. SMX was carried out five groups: 0 (C), 3 mg/L (T3), 6 mg/L (T6), 12 mg/L (T12), and 24 mg/L (T24), with 5 replicates per group for an 8-weeks chronic toxicity test. It was found that SMX is considered to have low toxicity to adult zebrafish. SMX with the concentration not higher than 24 mg/L has no obvious inhibitory effect on the growth of fish. Under different concentrations of SMX stress, oxidative damage and immune system disorder were caused to the liver and gill, with the 12 and 24 mg/L concentration being the most significant. At the same time, it also causes varying degrees of pathological changes in both intestinal and liver tissues. As the concentration of SMX increases, the composition and abundance of the gut microbiota in zebrafish significantly decrease.

AbstractCamellia tetracocca H.T. Chang 1981 is an important wild relative of cultivated tea plants. Its leaves are widely used by local people to make tea, showing great economic and breeding values. We here report the complete chloroplast genome of C. tetracocca using Illumina sequencing technology. The complete chloroplast genome of C. tetracocca is 157,026 bp in length, and structurally contains a pair of inverted repeat regions (IRa and IRb, 26,052 bp) separated by a large single-copy region (LSC, 86,669 bp) and a small single-copy region (SSC, 18,253 bp). It is composed of 131 predicted genes, including 86 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. The overall GC content is 37.31%. Phylogenetic analysis among four Camellia species and 11 other close species reveals a close relationship between C. tetracocca and C. gymnogyna.

Homologous recombination (HR) repair for DNA double‐strand breaks (DSBs) is critical for maintaining genome stability and conferring the resistance of tumor cells to chemotherapy. Nuclear PTEN which contains both phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphatase and protein phosphatase plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses nonhomologous end joining (NHEJ) repair by directly dephosphorylating TP53‐binding protein 1 (53BP1). During DNA damage responses (DDR), tumor suppressor ARF (p14ARF) was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DSB sites. This was because SUMO1 that was conjugated to PTEN was recognized and bound by the SUMO‐interacting motif (SIM) of breast cancer type 1 susceptibility protein (BRCA1), which has been located to the core of 53BP1 foci on chromatin during S/G2 stage. Furthermore, these chromatin‐loaded PTEN directly and specifically dephosphorylated phosphothreonine‐543 (pT543) of 53BP1, resulting in the dissociation of the 53BP1 complex, which facilitated DNA end resection and ongoing HR repair. SUMOylation‐site‐mutated PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking the PTEN SUMOylation pathway with either a SUMOylation inhibitor or a p14ARF(2‐13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides a new mechanistic understanding of PTEN in HR repair and clinical intervention of chemoresistant tumors.

The KRAS/ERK pathway is crucial in cancer progression and chemotherapy resistance, yet its upstream regulatory mechanism remains elusive. We identified MSI2 as a new promoter of chemotherapy resistance in cancers. MSI2 directly binds to a specific class of mature miRNAs by recognizing the 'UAG' motif and interacts with the essential effector AGO2, highlighting MSI2 as a novel regulatory factor within the miRNA pathway. Specifically, MSI2 recruits UAG-miRNA miR-30a-3p to facilitate its loading onto AGO2, efficiently inhibiting the expression of CGRRF1. Further analysis reveals that CGRRF1 functions as a new ubiquitin E3 ligase for KRAS, mediating the ubiquitination and proteasome degradation of KRAS. Consequently, a novel regulatory axis involving MSI2-AGO2/miR-30a-3p-CGRRF1 positively regulates the KRAS/ERK pathway. Remarkably, platinum-based chemotherapy drugs significantly enhance the levels of phosphorylated ERK1/2 (p-ERK1/2) in cancer cells, and the EGFR inhibitor Gefitinib also increases p-ERK1/2 levels in Gefitinib-resistant cancer cells. Combining small-molecule inhibitors targeting MSI2, such as Ro 08-2750, efficiently alleviated chemoresistance in tumor cells exposed to Platinum and Gefitinib. These findings suggest that MSI2 could be a novel therapeutic target for developing strategies to counteract cancer resistance to treatment.

ABSTRACTThe aim of this study was to investigate acid hydrolysis-bound phenols from Rosa roxburghii Tratt and their biological activities in vitro. The optimal extraction parameters were as follows: HCl concentration of 7 mol/L, extraction time of 10 h and material-liquid ratio of 1:40 g/mL. The highest yield of bound polyphenols was 495.64 ± 11.66 mg GAE/100 g DW. There were 24 phenolic compounds and 14 flavonoids released by acid hydrolysis. The antioxidant study showed that the RRT-BPs had a certain scavenging ability of free radicals in a dose-dependent manner. RRT-BPs showed good inhibitory activity against α-glucosidase and pancreatic lipase, respectively, and RRT-PBs acted as anticompetitive and mixed inhibitors against α-glucosidase and pancreatic lipase, respectively. Our study suggests that acid-hydrolysed bound phenols have good prebiotic properties and can be used as a supplement to existing alkaline-hydrolysed bound phenols to prevent chronic diseases such as diabetes and obesity.

BackgroundFerroptosis is a crucial pathogenic mechanism in Parkinson’s disease, offering significant potential for pharmacological intervention. Despite its importance, the number of bibliometric analyses examining the relationship between ferroptosis and Parkinson’s disease remains limited. This study aims to elucidate the knowledge structure and primary research focuses within this field using various bibliometric tools search.Materials and methodsWe conducted a comprehensive literature son ferroptosis in Parkinson’s disease using the Web of Science Core Collection database. Bibliometric analyses and visualizations were performed with VOSviewer, examining the geographical and institutional distribution of publications, journal interconnections, and keyword prevalence. Furthermore, CiteSpace was used to visually explore and analyze journal interactions and citation dynamics. The bibliometrix R package facilitated the delineation of collaborative networks across different countries and the construction of visual network representations illustrating relationships among authors, keywords, and journals. Data visualization was further enhanced with Microsoft Office Excel 2021.ResultsRecently, there has been a significant increase in publications on ferroptosis, with China emerging as a leading contributor in this research area. Keyword analysis highlights the critical role of ferroptosis in the pathogenesis of Parkinson’s disease, identifying GPX4 as a key enzyme mitigating lipid peroxidation. This study also elucidates the connections and distinctions between ferroptosis and other cell death processes such as apoptosis, autophagy, and pyroptosis. Current research primarily focuses on immunotherapy, prognosis, oxidative stress, lipid peroxidation, and the tumor microenvironment.ConclusionThis study provides a comprehensive initial analysis of the research landscape, identifying current focal points and potential future directions for ferroptosis research in Parkinson’s disease. The findings leverage a variety of bibliometric methodologies to offer valuable insights into this emerging field.

Abstract Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies.

ObjectiveThe aim of the present study was to carry out a systematic research on bitterness quantification to provide a reference for scholars and pharmaceutical developers to carry out drug taste masking research. Significance: The bitterness of medications poses a significant concern for clinicians and patients. Scientifically measuring the intensity of drug bitterness is pivotal for enhancing drug palatability and broadening their clinical utility.MethodsThe current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to summarize the features, strengths, and applicability of quantitative bitterness assessment methods.ResultsIn our research, we systematically outlined the classification and key advancements in quantitative research methods for assessing drug bitterness, including in vivo quantification techniques such as traditional human taste panel methods, as well as in vitro quantification methods such as electronic tongue analysis. It focused on the quantitative methods and difficulties of bitterness of natural drugs with complex system characteristics and their difficulties in quantification, and proposes possible future research directions.ConclusionThe quantitative methods of bitterness were summarized, which laid an important foundation for the construction of a comprehensive bitterness quantification standard system and the formulation of accurate, efficient and rich taste masking strategies.

The aim of this study is to investigate the main active components of Gegen (Puerariae Lobatae Radix) on atherosclerosis and its mechanism of action. Bioinformatics analysis showed that β-sitosterol was the most likely active ingredient to mediate the anti-atherosclerotic effects. In vivo experiments showed that β-sitosterol inhibited plaque formation and platelet activation, and decreased serum total cholesterol (TC) and triglyceride (TG) levels. In vitro experiments showed that β-sitosterol can inhibit lipid deposition and phenotypic transformation of vascular smooth muscle cells (VSMCs). However, knocking down catalase (CAT), the direct target of β-sitosterol, not only promoted lipid deposition and phenotypic transformation of VSMCs, but also activated the PI3K/Akt/mTOR pathway, and the mTOR inhibitor (ink-128) can eliminate the effect of CAT knockdown, suggesting that β-sitosterol may inhibit lipid deposition and phenotypic transformation of VSMCs by activating CAT and silencing the PI3K/Akt/mTOR signaling pathway, thereby alleviating atherosclerosis.

In this paper, non-woven fabric and glass fiber fabric were used to prepare resin-based absorbing composite. The thermal expansion coefficient and the microwave absorbing properties of the absorbing composites with different glass fiber volume fraction were studied. The results show that the simulation results of the thermal expansion coefficient calculated by Schapery model are inconsistent with the experimental results, the metallographic results were studied to reveal that it is the added absorbent in the composite that partially replaced the resin at the interface between resin and fiber bundle causes the parameters of the material substituted in the Schapery model to be improper. A different simulation model was proposed to introduce a set of different parameters of the material to reduce the error between simulation and experiment results and the simulation results show that the error is reduced from a maximum of 53 % to a minimum of 3 %. Meanwhile the microwave absorbing properties show that the absorbing peaks of the composite materials move to low frequency with the increasing glass fiber volume fraction and the minimum reflection loss (RL) first increase and then decrease. The metallographic results show that the different distribution of absorbent in the composites within different reinforced fibers causes the movement of the absorbing peaks and the change of its minimum RL. Those research results lay a foundation for the further popularization and application of the absorbing composites.

In order to improve the mechanical properties of backfill, steel slag and straw fiber were used as materials to prepare backfill. The law of sand-cement ratio, mass concentration, steel slag content and straw fiber on strength and rheological parameters of backfill was analyzed by orthogonal test method, and the influence mechanism of steel slag content and straw fiber on physical properties of backfill was revealed. The results show that mass concentration exerts the most substantial impact on rheological parameters, emerging as a significant determinant. Moreover, the yield stress diminishes with escalating tailings-cement ratio, while it escalates with higher mass concentration, steel slag content and straw fiber content. Augmenting the tailings-cement ratio and steel slag content serves to impede the amplification effect of mass concentration on yield stress. Notably, the tailings-cement ratio emerges as the most influential factor affecting the uniaxial compressive strength (UCS) of the backfill, albeit the UCS diminishes with rising tailings-cement ratio. Elevating the mass concentration and steel slag content can counteract the debilitation caused by an increase in the tailings-cement ratio on the UCS of the backfill. Furthermore, heightened mass concentration can bolster the reinforcing impact of steel slag content on early UCS. The increase of tailings-cement ratio increases the size and range of the void inside the backfill, subsequently leading to the degradation of its macroscopic compressive strength. The adhesion between straw fiber and mortar matrix constitutes a pivotal factor in improving the integration of backfill, whereas steel slag contributes to improving the mechanical properties by enhancing the distribution of void structures within the backfill. This research not only offer data support and scientific guidance for the design of backfill ratio parameters but also facilitate the broader application of straw fiber and steel slag in mine backfilling operations.

Background Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic disorders are significantly influenced by ferroptosis, and targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role and mechanism of ferroptosis in keloid development. Methods Keloid tissues from keloid patients and normal skin tissues from healthy controls were collected. Iron content, lipid peroxidation (LPO) level, and the mRNA and protein expression of ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). Keloid fibroblasts (KFs) were isolated from keloid tissues, and treated with ferroptosis inhibitor ferrostatin-1 (fer-1) or ferroptosis activator erastin. Iron content, ferroptosis-related marker levels, LPO level, mitochondrial membrane potential, ATP content, and mitochondrial morphology in KFs were detected. Furthermore, the protein levels of α-smooth muscle actin (α-SMA), collagen I, and collagen III were measured to investigate whether ferroptosis affect fibrosis in KFs. Results We found that iron content and LPO level were substantially elevated in keloid tissues and KFs. SLC7A11, GPX4, and Nrf2 were downregulated and TFRC was upregulated in keloid tissues and KFs. Mitochondria in keloid tissues and KFs exhibited ferroptosis-related pathology. Fer-1 treatment reduced iron content, restrained ferroptosis and mitochondrial dysfunction in KFs, Moreover, ferrostatin-1 restrained the protein expression of α-SMA, collagen I, and collagen III in KFs. Whereas erastin treatment showed the opposite results. Conclusion Ferroptosis exists in keloid. Ferrostatin-1 restrained ECM deposition and fibrosis in keloid through inhibiting ferroptosis, and erastin induced ECM deposition and fibrosis through intensifying ferroptosis.

Abstract The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of “Humanistic Health Management” (HHM) is proposed. This concept is a healthcare plan that focuses on self‐health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.

IntroductionThis study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger (INCX) and L-type calcium channel (ICaL) of the SAN.MethodsSinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24 h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100 μg/mL TYHX, H/R+200 μg/mL TYHX, and H/R+400 μg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5 days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX.ResultsTYHX administration demonstrated improvements in the ignition phase of impaired SANCs. The half-maximal effective dose of TYHX, as determined by SANC beating frequency, was found to be 323.63 μg/mL. Inward current density of INCX increased in response to TYHX (200 and 400 μg/mL), while TYHX enhanced ICaL current density in H/R SANCs, with 400 μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of ICaL by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400 μg/mL, prolonged the fast inactivation time constant τ1 with 400 μg/mL, and extended the slow inactivation time constant τ2 with 100 and 400 μg/mL.Discussion and conclusionThe findings suggest that TYHX may hold promise as a therapeutic intervention for sinus node dysfunction, offering potential avenues for drug development aimed at safeguarding SAN function.

This study evaluated the nutrients, flavour and antioxidant capacity in the embryo, colloid and fruiting body of Dictyophora rubrovalvata. The embryo had the highest protein [2.91 ± 0.39 g.(100 g)-1] and polysaccharides (17.44 ± 1.49 mg.g-1), the fruiting body had the highest total phenol content (0.87 ± 0.17 mg.g-1), the colloid was rich in minerals [1.57 ± 0.16 g.(100 g)-1]. The antioxidant capacity of the embryo was higher than that of the other parts, in terms of different solvents, the antioxidant capacity of D. rubrovalvata extracted with ethanol was higher than that of water. 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing capacity were positively correlated with polysaccharides, proteins and polyphenols. The free amino acid content ranged from 7.44 to 11.52 mg.g-1, the distribution was fruiting body > embryo > colloid, of which glutamic acid content was the highest, and the flavour characteristics were mainly umami and sweetness. The nucleotide content of fruiting body and embryo was higher than in the colloid. In addition, the compositions of volatile flavour compounds were identified by headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), mainly alcohols, aldehydes and ketones, their distributions varied greatly among the three samples. These results indicated that different parts of D. rubrovalvata have different nutritional characteristics, the fruiting body has a high content of volatile and non-volatile components, the embryo and the colloid have good functional activity, laying a foundation for the functional development and comprehensive utilisation of D. rubrovalvata.

Abstract AcrIIA15 is an anti-CRISPR (Acr) protein that inhibits Staphylococcus aureus Cas9 (SaCas9). Although previous studies suggested it has dual functions, the structural and biochemical basis for its two activities remains unclear. Here, we determined the cryo-EM structure of AcrIIA15 in complex with SaCas9-sgRNA to reveal the inhibitory mechanism of the Acr’s C-terminal domain (CTD) in mimicking dsDNA to block protospacer adjacent motif (PAM) recognition. For the N-terminal domain (NTD), our crystal structures of the AcrIIA15-promoter DNA show that AcrIIA15 dimerizes through its NTD to recognize double-stranded (ds) DNA. Further, AcrIIA15 can simultaneously bind to both SaCas9-sgRNA and promoter DNA, creating a supercomplex of two Cas9s bound to two CTDs converging on a dimer of the NTD bound to a dsDNA. These findings shed light on AcrIIA15’s inhibitory mechanisms and its autoregulation of transcription, enhancing our understanding of phage-host interactions and CRISPR defense.

Sepsis-induced kidney injury (SAKI) has been frequently established as a prevailing complication of sepsis which is linked to unfavorable outcomes. Fatty acid-binding protein-4 (FABP4) has been proposed as a possible target for the treatment of SAKI. In the current work, we aimed to explore the role and underlying mechanism of FABP4 in lipopolysaccharide (LPS)-induced human renal tubular epithelial cell damage. In LPS-induced human kidney 2 (HK2) cells, FABP4 expression was tested by the reverse transcription-quantitative polymerase chain reaction and Western blot. Cell counting kit-8 method assayed cell viability. Inflammatory levels were detected using the enzyme-linked immunosorbent assay. Immunofluorescence staining measured the nuclear translocation of nuclear factor kappa B p65. Thiobarbituric acid-reactive substances assay and C11 BODIPY 581/591 probe were used to estimate the level of cellular lipid peroxidation. Fe2+ content was examined by the kit. In addition, the expression of proteins related to inflammation-, ferroptosis- and Janus kinase 2 (JAK2)/signal transducer, and activator of transcription 3 (STAT3) signaling was detected by the Western blot analysis. The results revealed that FABP4 was significantly upregulated in LPS-treated HK2 cells, the knockdown of which elevated the viability, whereas alleviated the inflammation and ferroptosis in HK2 cells challenged with LPS. In addition, down-regulation of FABP4 inactivated JAK2/STAT3 signaling. JAK2/STAT3 stimulator (colivelin) and ferroptosis activator (Erastin) partially restored the effects of FABP4 interference on LPS-triggered inflammation and ferroptosis in HK2 cells. Together, FABP4 knockdown inhibited ferroptosis to alleviate LPS-induced injury of renal tubular epithelial cells through suppressing JAK2/STAT3 signaling.

Abstract Background Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients. Methods We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions. Results Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15–1.28, p

Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl‐terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin‐protein ligase for DICER. This USP7‐MDM2‐DICER axis impaired histone γ‐H2AX signalling and the recruitment of DNA damage response (DDR) factors, possibly by influencing the processing of small DDR noncoding RNAs. We also showed that this negative regulation of DICER by USP7 via MDM2 was relevant to human tumours using cellular and clinical data. Our findings revealed a new way to understand the role of DICER in malignant tumour development and may offer new insights into the diagnosis, treatment and prognosis of cancers.

RNA interference (RNAi) is a specific post-transcriptional gene-silencing phenomenon, which plays an important role in the regulation of gene expression and the protection from transposable elements in eukaryotic organisms. In Drosophila melanogaster, RNAi can be induced by microRNA (miRNA), endogenous small interfering RNA (siRNA), or exogenous siRNA. However, the biogenesis of miRNA and siRNA in these RNAi pathways is aided by the double-stranded RNA binding proteins (dsRBPs) Loquacious (Loqs)-PB, Loqs-PD or R2D2. In this study, we identified three alternative splicing variants of Loqs, namely Loqs-PA, -PB, and -PC in the orthopteran Locusta migratoria. We performed in vitro and in vivo experiments to study the roles of the three Loqs variants in the miRNA- and siRNA-mediated RNAi pathways. Our results show that Loqs-PB assists the binding of pre-miRNA to Dicer−1 to lead to the cleavage of pre-miRNA to yield matured miRNA in the miRNA-mediated RNAi pathway. In contrast, different Loqs proteins participate in different siRNA-mediated RNAi pathways. In exogenous siRNA-mediated RNAi pathway, binding of Loqs-PA or LmLoqs-PB to exogenous dsRNA facilitates the cleavage of dsRNA by Dicer−2, whereas in endogenous siRNA-mediated RNAi pathway, binding of Loqs-PB or Loqs-PC to endogenous dsRNA facilitates the cleavage of dsRNA by Dicer−2. Our findings provide new insights into the functional importance of different Loqs proteins derived from alternative splicing variants of Loqs in achieving high RNAi efficiency in different RNAi pathways in insects.

The exacerbation of wildfires caused by global warming poses a significant threat to human health and environmental integrity. This review examines the particulate matter (PM) and gaseous pollutants resulting from fire incidents and their impacts on individual health, with a specific focus on the occupational hazards faced by firefighters. Of particular concern is the release of carbon-containing gases and fine particulate matter (PM2.5) from forest fires and urban conflagrations, which exceed the recommended limits and pose severe health risks. Firefighters exposed to these pollutants demonstrate an elevated risk of developing pulmonary and cardiovascular diseases and cancer compared to the general population, indicating an urgent need for enhanced protective measures and health management strategies for firefighters. Through a meticulous analysis of the current research findings, this review delineates future research directions, focusing on the composition and properties of these pollutants, the impacts of fire-emitted pollutants on human health, and the development of novel protective technologies.

Erwinia amylovora, the causative agent of fire blight, causes significant economic losses for farmers worldwide by inflicting severe damage to the production and quality of plants in the Rosaceae family. Historically, fire blight control has primarily relied on the application of copper compounds and antibiotics, such as streptomycin. However, the emergence of antibiotic-resistant strains and growing environmental concerns have highlighted the need for alternative control methods. Recently, there has been a growing interest in adopting bacteriophages (phages) as a biological control strategy. Phages have demonstrated efficacy against the bacterial plant pathogen E. amylovora, including strains that have developed antibiotic resistance. The advantages of phage therapy includes its minimal impact on microbial community equilibrium, the lack of a detrimental impact on plants and beneficial microorganisms, and its capacity to eradicate drug-resistant bacteria. This review addresses recent advances in the isolation and characterization of E. amylovora phages, including their morphology, host range, lysis exertion, genomic characterization, and lysis mechanisms. Furthermore, this review evaluates the environmental tolerance of E. amylovora phages. Despite their potential, E. amylovora phages face certain challenges in practical applications, including stability issues and the risk of lysogenic conversion. This comprehensive review examines the latest developments in the application of phages for controlling fire blight and highlights the potential of E. amylovora phages in plant protection strategies.

Background/Objectives: Small molecules that interfere with the interaction between acetylated protein tails and the tandem bromodomains of BET (bromodomain and extra-terminal) family proteins are pivotal in modulating immune/inflammatory and neoplastic diseases. This study aimed to develop a novel PET imaging tracer, [11C]GSK023, that targets the N-terminal bromodomain (BD1) of BET family proteins with high selectivity and potency, thereby enriching the chemical probe toolbox for epigenetic imaging. Methods: [11C]GSK023, a radio-chemical probe, was designed and synthesized to specifically target the BET BD1. In vivo PET imaging evaluations were conducted on rodents, focusing on the tracer’s distribution and binding specificity in various tissues. Blocking studies were performed to confirm the probe’s selectivity and specificity. Results: The evaluations revealed that [11C]GSK023 demonstrated good uptake in peripheral organs with limited brain penetration. Further blocking studies confirmed the probe’s high binding specificity and selectivity for the BET BD1 protein, underscoring its potential utility in epigenetic imaging. Conclusions: The findings suggest that [11C]GSK023 is a promising PET probe for imaging the BET BD1 protein, offering the potential to deepen our understanding of the roles of BET bro-modomains in disease and their application in clinical settings to monitor disease progression and therapeutic responses.

As the green bond market in China develops and its institutional structure improves, the green bond has emerged as a pivotal element within the broader framework of the green financial system. We focus on bond issuers in China’s A-shares from the years 2010 to 2021 and explore green bond issuance and the spillover effect of green technology innovation under the market attention perspective. Findings are that: (1) Green bond issuance can produce the spillover effect in the industry and significantly enhance peer enterprises’ green technology innovation. (2) From the viewpoint of market attention, analyst attention can significantly enhance the spillover effect of green bond issuance within the industry. The same is true for media attention and investor attention. (3) Further research shows that within the same industry, the spillover effect is more pronounced for state-owned enterprises, large-scale enterprises, and enterprises in regions with higher levels of green financial development. For the booming development of China’s green bond market and the sustainable development of enterprises, this paper provides theoretical and practical foundations.

In this paper, the PANI/PDA-Ti4O7 composite coating was prepared on 316L by constant current deposition with a current density of 2.8 mA·cm−2, in which the Ti4O7 powders were modified by PDA (polydopamine). The open-circuit potential of the obtained PANI/PDA-Ti4O7 composite coating is about 365 mVAg/AgCl, which is more positive than that of the bare 316L. During immersion in 1 M H2SO4 + 2 ppm HF for 200 h, the high stable corrosion potential and the lower Rf indicate that the composite coating has long-term corrosion resistance.

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33 +1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery.

Abstract Flexible wearable sensors have the characteristics of flexibility, comfort, and wearability, and have shown great potential in future electronic products. Despite significant efforts in developing stretchable electronic materials and structures, the development of flexible strain sensors with a wide temperature range, high sensitivity, broad detection range, and good interface stability remains challenging. Here, strain sensors with buckled structures are fabricated using high and low‐temperature resistant material Ti3C2Tx MXene/graphene, PDMS 184. The conductive material Ti3C2Tx MXene/graphene exhibits excellent interface interaction with PDMS 184, addressing not only the poor compatibility issue between the conductive material and the flexible substrate, but also demonstrating good stability and cycling performance. Buckled structure improves the stretchability and linearity of strain sensors. The fabricated strain sensor is suitable for a wide temperature range (−40 to 120 °C) and exhibits high stretchability (120% strain). The strain sensor demonstrates rapid response times at different temperatures: −40 (72.6 ms), 0 (62.7 ms), and 120 °C (52.7 ms). The strain sensor exhibits high sensitivity at different temperatures: −40 (GF = 0.38), 0 (GF = 0.24), 40 (GF = 0.66), and 120 °C (GF = 1.47). The strain sensor has a wide detection range (0.1% to 120%) and excellent cycling stability. In addition, Ti3C2Tx MXene/graphene strain sensors can accurately capture various human activities, such as blinking, speaking, finger bending, and wrist bending.

BackgroundTraditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV.MethodsWe retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens.ResultsThis study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P

Abstract Non‐small‐cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank‐binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417‐AGO2), which promotes NSCLC progression by increasing the formation of microRNA‐induced silencing complex (miRISC). High levels of pS417‐AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417‐AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib‐resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1‐mediated pS417‐AGO2 and suggest potential therapeutic approaches for NSCLC.

PurposeTo investigate the contrast sensitivity function (CSF) changes in simple high myopia (SHM) and evaluate the correlations between these changes with the early changes in the retinal microstructure.MethodsThis prospective study comprised 81 subjects, 20 with emmetropia (EM), 26 with low myopia and moderate myopia (LM/MM), and 35 with SHM. The area under the log CSF curve (AULCSF) and the cut-off spatial frequency (Cut-off SF) were employed as measures of CSF. Adaptive optics (AO) was employed to quantify the cone density, spacing, and regularity. The thickness and blood flow of the retinal sublayers were determined from vertical and horizontal optical coherence tomography angiography (OCTA) A-scans. Swept-source optical coherence tomography (SS-OCT) was employed to analyze the choroidal thickness (CT) and choroidal vascularity using a custom algorithm. Differences in the retinal and choroidal parameters, cone distribution, AULCSF, and Cut-off SF were compared among the three groups. Multivariate linear mixed models were used to elucidate the associations between photoreceptor morphological alterations, retinal and choroidal parameters, and AULCSF.ResultsThe AULCSF and Cut-off SF were significantly lower in the SHM group compared to the EM and LM groups (p

Transradial access (TRA) is a safe and comfortable approach and the preferred access for percutaneous coronary intervention. However, TRA is not widely used for peripheral interventions. Currently, there is a lack of data on patient selection, appropriate medical devices, complication prevention, and TRA adoption. Therefore, the Chinese Society of Interventional Oncology of the China Anti-Cancer Association organized nationwide experts to establish a Working Group of China Expert Consensus on TRA in percutaneous peripheral interventions in 2022, and jointly formulated this consensus to better promote the application of TRA in peripheral interventions to guide clinicians on patient selection, technical recommendations, and physician training. This consensus mainly focuses on the current situation, advantages and limitations of TRA in peripheral interventions, anatomical characteristics of the radial artery, patient selection, technical aspects, prevention and management of complications, radiation dose, and learning curve. A consensus was reached through a literature evaluation and by referring to the opinions of the expert group.