Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study.

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Tobacco crop rotation enhances the stability and complexity of microbial networks.

Introduction: The effects of continuous cropping and rotation cropping, two important tobacco cultivation practices, on soil microbial communities at different stages remain unclear. Different planting patterns have been shown to influence soil physical and chemical properties, which in turn can affect the composition and diversity of soil microbial communities. Methods: In order to investigate the impact of different planting methods on soil microbial community structure, we selected two representative planting methods: continuous cropping (tobacco) and rotational cropping (tobacco-maize). These methods were chosen as the focal points of our research to explore the potential effects on soil microbial communities. High-throughput sequencing technology was employed to investigate the structure of soil microbial communities, as well as their relationships with soil environmental factors, by utilizing the 16S rRNA, ITS, and 18S genes. Furthermore, the interaction among microorganisms was explored through the application of the Random Matrix Theory (RMT) molecular ecological network approach. Results: There was no significant difference in α diversity, but significant difference in ß diversity based on Jaccard distance test. Compared to continuous cropping, crop rotation significantly increased the abundance of beneficial prokaryotes Verrucomicrobia and Rhodanobacter. These findings indicate that crop rotation promotes the enrichment of Verrucomicrobia and Rhodanobacter in the soil microbial community. AP and NH4-N had a greater effect on the community structure of prokaryotes and fungi in tobacco soil, while only AP had a greater effect on the community structure of protist. Molecular ecological network analysis showed that the network robustness and Cohesion of rotation were significantly higher than that of continuous cropping, indicating that the complexity and stability of molecular ecological networks were higher in the rotational, and the microbial communities cooperated more effectively, and the community structure was more stable. Discussion: From this point of view, rotational cropping is more conducive to changing the composition of soil microbial community, enhancing the stability of microbial network structure, and enhancing the potential ecological functions in soil.

Improved YOLO-FastestV2 wheat spike detection model based on a multi-stage attention mechanism with a LightFPN detection head.

The number of wheat spikes has an important influence on wheat yield, and the rapid and accurate detection of wheat spike numbers is of great significance for wheat yield estimation and food security. Computer vision and machine learning have been widely studied as potential alternatives to human detection. However, models with high accuracy are computationally intensive and time consuming, and lightweight models tend to have lower precision. To address these concerns, YOLO-FastestV2 was selected as the base model for the comprehensive study and analysis of wheat sheaf detection. In this study, we constructed a wheat target detection dataset comprising 11,451 images and 496,974 bounding boxes. The dataset for this study was constructed based on the Global Wheat Detection Dataset and the Wheat Sheaf Detection Dataset, which was published by PP Flying Paddle. We selected three attention mechanisms, Large Separable Kernel Attention (LSKA), Efficient Channel Attention (ECA), and Efficient Multi-Scale Attention (EMA), to enhance the feature extraction capability of the backbone network and improve the accuracy of the underlying model. First, the attention mechanism was added after the base and output phases of the backbone network. Second, the attention mechanism that further improved the model accuracy after the base and output phases was selected to construct the model with a two-phase added attention mechanism. On the other hand, we constructed SimLightFPN to improve the model accuracy by introducing SimConv to improve the LightFPN module. The results of the study showed that the YOLO-FastestV2-SimLightFPN-ECA-EMA hybrid model, which incorporates the ECA attention mechanism in the base stage and introduces the EMA attention mechanism and the combination of SimLightFPN modules in the output stage, has the best overall performance. The accuracy of the model was P=83.91%, R=78.35%, AP= 81.52%, and F1 = 81.03%, and it ranked first in the GPI (0.84) in the overall evaluation. The research examines the deployment of wheat ear detection and counting models on devices with constrained resources, delivering novel solutions for the evolution of agricultural automation and precision agriculture.

Single-cell transcriptome dissecting the microenvironment remodeled by PD1 blockade combined with photodynamic therapy in a mouse model of oral carcinogenesis.

Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4-nitroquinoline 1-oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single-cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor-promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor-promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment-associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families.

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside.

Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.

Schistosomiasis transmission in Zimbabwe: Modelling based on machine learning.

Zimbabwe, located in Southern Africa, faces a significant public health challenge due to schistosomiasis. We investigated this issue with emphasis on risk prediction of schistosomiasis for the entire population. To this end, we reviewed available data on schistosomiasis in Zimbabwe from a literature search covering the 1980-2022 period considering the potential impact of 26 environmental and socioeconomic variables obtained from public sources. We studied the population requiring praziquantel with regard to whether or not mass drug administration (MDA) had been regularly applied. Three machine-learning algorithms were tested for their ability to predict the prevalence of schistosomiasis in Zimbabwe based on the mean absolute error (MAE), the root mean squared error (RMSE) and the coefficient of determination (R2). The findings revealed different roles of the 26 factors with respect to transmission and there were particular variations between Schistosoma haematobium and S. mansoni infections. We found that the top-five correlation factors, such as the past (rather than current) time, unsettled MDA implementation, constrained economy, high rainfall during the warmest season, and high annual precipitation were closely associated with higher S. haematobium prevalence, while lower elevation, high rainfall during the warmest season, steeper slope, past (rather than current) time, and higher minimum temperature in the coldest month were rather related to higher S. mansoni prevalence. The random forest (RF) algorithm was considered as the formal best model construction method, with MAE = 0.108; RMSE = 0.143; and R2 = 0.517 for S. haematobium, and with the corresponding figures for S. mansoni being 0.053; 0.082; and 0.458. Based on this optimal model, the current total schistosomiasis prevalence in Zimbabwe under MDA implementation was 19.8%, with that of S. haematobium at 13.8% and that of S. mansoni at 7.1%, requiring annual MDA based on a population of 3,003,928. Without MDA, the current total schistosomiasis prevalence would be 23.2%, that of S. haematobium 17.1% and that of S. mansoni prevalence at 7.4%, requiring annual MDA based on a population of 3,521,466. The study reveals that MDA alone is insufficient for schistosomiasis elimination, especially that due to S. mansoni. This study predicts a moderate prevalence of schistosomiasis in Zimbabwe, with its elimination requiring comprehensive control measures beyond the currently used strategies, including health education, snail control, population surveillance and environmental management.

Plastome evolution of Engelhardia facilitates phylogeny of Juglandaceae.

BACKGROUND: Engelhardia (Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of Engelhardia, the maternal genome evolution and phylogeny of Engelhardia in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight Engelhardia species and the outgroup Rhoiptelea chiliantha, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of Engelhardia and the whole Juglandaceae family. RESULTS: The 13 Engelhardia plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (TrnK-rps16, ndhF-rpl32, and ycf1) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only rpl22 and psaI genes showed positive selection (Ka/Ks > 1). Phylogenetic results fully supported Engelhardia as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The Engelhardia originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn't support rapid radiation occurred in the evolution history of Engelhardia. CONCLUSION: Our study fully supported the taxonomic treatment of at the section for Engelhardia species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of Engelhardia and the whole Juglandaceae family.

Unveiling a new oceanic anoxic event at the Norian/Rhaetian boundary (Late Triassic).

The latest Triassic was characterised by protracted biotic extinctions concluding in the End-Triassic Extinction (~ 200 Ma) and a global carbon cycle perturbation. The onset of declining diversity is closely related to reducing conditions that spread globally from upper Sevatian (uppermost Norian) to across the Norian-Rhaetian boundary, likely triggered by unusually high volcanic activity. We correlate significant organic carbon cycle perturbations to an increase of CO2 in the ocean-atmosphere system, likely outgassed by the Angayucham igneous province, the onset of which is indicated by the initiation of a rapid decline in 87Sr/86Sr and 188Os/187Os seawater values. A possible causal mechanism involves elevated CO2 levels causing global warming and accelerating chemical weathering, which increased nutrient discharge to the oceans and greatly increased biological productivity. Higher export production and oxidation of organic matter led to a global O2 decrease in marine water across the Norian/Rhaetian boundary (NRB). Biotic consequences of dysoxia/anoxia include worldwide extinctions in some fossil groups, such as bivalves, ammonoids, conodonts, radiolarians.

Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile.

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Skeletal Muscle Index-Based Cachexia Index as a Predictor of Prognosis in Patients With Cancer: A Meta-Analysis and Systematic Review.

CONTEXT: Cachexia is associated with poor survival rates. In the clinical setting, the diagnosis of cancer cachexia is challenging. The cachexia index (CXI), a new index for predicting survival time, is a promising tool for diagnosing cancer cachexia; however, its efficacy in predicting patient survival has not been validated. OBJECTIVE: This meta-analysis and systematic review aimed to explore the CXI's prognostic value in patients with cancer. DATA SOURCES: The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched for relevant studies to determine the association between CXI findings and prognosis. DATA EXTRACTION: The outcomes were overall survival (OS), progression-, disease-, and recurrence-free survival (PFS/DFS/RFS) rates, and the rate of complete response. DATA ANALYSIS: The QUality In Prognostic Studies (QUIPS) tool was used to evaluate the quality of the included trials. This meta-analysis comprised 14 studies involving 2777 patients. A low CXI was associated with decreased OS (hazard ratio [HR] 2.34, 95% confidence interval [CI] 2.01-2.72; P < .001), PFS/DFS/RFS (HR 1.93, 95% CI 1.68-2.22; P < .001), and complete response (odds ratio [OR] 0.49, 95% CI 0.36-0.66; P < .001). Patients with a low CXI had a lower body mass index (mean difference [MD] -0.75, 95% CI -1.00 to 0.50; P < .001), skeletal muscle index (standardized MD -0.80, 95% CI -0.98 to -0.61; P < .001), and serum albumin level (MD -0.23, 95% CI -0.26 to -0.20; P < .001); and a higher neutrophil-lymphocyte ratio (MD 1.88, 95% CI 1.29-2.47; P < .001) and more advanced disease stages (OR 0.80, 95% CI 0.71-0.91; P = .001). CONCLUSION: A low CXI was found to be associated with poor survival in patients with cancer. While the CXI is a promising marker for predicting cancer cachexia, further studies are required to verify its usefulness.

Antibiotic resistance characterization, virulence factors and molecular characteristics of Bacillus species isolated from probiotic preparations in China.

OBJECTIVES: The aim of this study was to determine the phenotypic and molecular characteristics of antibiotic-resistant Bacillus spp. isolated from probiotic preparations in China. METHODS: Bacillus strains were isolated from probiotic preparations and then identified using 16S rDNA sequencing. Drug sensitivity tests were conducted to determine their susceptibility to seven antibiotics. Whole genome sequencing was performed on the most resistant strains, followed by analysis of their molecular characteristics, resistance genes, and virulence factors. RESULTS: In total, we isolated 21 suspected Bacillus species from seven compound probiotics, which were identified by 16S rDNA as 12 Bacillus licheniformis, six Bacillus subtilis and three Bacillus cereus. The determination of antimicrobial susceptibility showed widespread resistance to chloramphenicol (95.2%), erythromycin (85.7%) and gentamicin (42.9%). Whole genome sequencing of seven resistant strains revealed that J-6-A (Bacillus subtilis) and J-7-A (Bacillus cereus) contained a plasmid. The resistance gene analysis revealed that each strain contained more than ten resistance genes, among which J-7-A was the most. The streptomycin resistance gene strA was detected in all strains. The chloramphenicol resistance genes ykkC and ykkD were found in J-1-A to J-5-A and were first reported in Bacillus subtilis. The erythrocin resistance gene ermD was detected in strains J-1-A to J-4-A. There were also more than 15 virulence factors and gene islands (GIs) involved in each strain. CONCLUSIONS: These results confirm the potential safety risks of probiotics and remind us to carefully select probiotic preparations containing strains of Bacillus species, especially Bacillus cereus, to avoid the potential spread of resistance and pathogenicity.

Cell-free DNA: a promising biomarker in infectious diseases.

Infectious diseases pose serious threats to public health worldwide. Conventional diagnostic methods for infectious diseases often exhibit low sensitivity, invasiveness, and long turnaround times. User-friendly point-of-care tests are urgently needed for early diagnosis, treatment monitoring, and prognostic prediction of infectious diseases. Cell-free DNA (cfDNA), a promising non-invasive biomarker widely used in oncology and pregnancy, has shown great potential in clinical applications for diagnosing infectious diseases. Here, we discuss the most recent cfDNA research on infectious diseases from both the pathogen and host perspectives. We also discuss the technical challenges in this field and propose solutions to overcome them. Additionally, we provide an outlook on the potential of cfDNA as a diagnostic, treatment, and prognostic marker for infectious diseases.

Phytochemical and biological studies on rare and endangered plants endemic to China. Part XXXVI. Tsugaforrestiacids A-O: Structurally diverse C-18 carboxylated diterpenoids from the twigs and needles of the 'vulnerable' conifer Tsuga forrestii and their inhibitory effects on ATP-citrate lyase.

An extensive phytochemical investigation on the EtOAc-soluble fraction of the 90% MeOH extract from the twigs and needles of the 'vulnerable' Chinese endemic conifer Tsuga forrestii (Forrest's hemlock) led to the isolation and characterization of 50 structurally diverse diterpenoids, including 15 unreported C-18 carboxylated ones (tsugaforrestiacids A-O, 1-15, resp.). Among them, compounds 1-7 are abieten-18-oic acids, compound 8 is an abieten-18-succinate, and compounds 10-12 are podocarpen-18-oic acids, whereas compounds 13-15 are pimarane-type, isopimarane-type, and totarane-type diterpenoid acids, respectively. Their structures and absolute configurations were determined by a combination of spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) data, and single crystal X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the ATP-citrate lyase (ACL), a key enzyme in cellular metabolism. Tsugaforrestiacids E (5) and H (8) were found to have significant inhibitory effects against ACL, with IC50 values of 5.3 and 6.2 µM, respectively. The interactions of the bioactive molecules with the ACL enzyme were examined by molecular docking studies. The isolated diterpenoids also provide chemotaxonomic evidence to support the delimitation of Tsuga from its closest sister group (Nothotsuga). The above findings highlight the importance of protecting plant species with unique and diverse secondary metabolites, which may be potential sources of new therapeutic agents for the treating ACL-associated diseases.

Changes in the ocular surface microbiome of patients with coronavirus disease 2019 (COVID-19).

Purpose: To elucidate the reasons behind the increased incidence of ocular disease in patients with coronavirus disease 2019 (COVID-19), this study delved deeper into the specific effects of COVID-19 on patients' ocular surface microbiome (OSM) and investigated its relationship with the increased incidence of ocular disease. Methods: In this study, conjunctival sac swabs were collected from 43 participants for 16S rRNA amplicon sequencing. The participants were categorized into three groups based on their COVID-19 status: the control group (C group) consisted of 15 participants who showed no evidence of COVID-19, the experimental group (E group) included 15 participants who tested positive for COVID-19, and the COVID-19 recovery period group (R group) comprised 13 participants. Results: In the comparison of alpha diversity, group E had a higher Shannon, Chao1 and Goods coverage index. When comparing beta diversity, groups E and R were more similar to each other. At the phylum level, although the OSM of the three groups was dominated by Proteobacteria, Actinobacteriota, Bacteroidota and Firmicutes, the compositional proportions were significantly different. At the genus level, the dominant species in the three OSM groups were significantly different, with Pseudomonas becoming the dominant genus in groups E and R compared to group C, and the abundance of Ralstonia decreasing significantly. Conclusion: This study provides additional evidence supporting the association between the OSM and COVID-19, which contributes to our understanding of the potential mechanisms underlying ocular symptoms and complications associated with COVID-19 in the future.

Three-dimensional pore structure of the decellularized parsley scaffold regulates myogenic differentiation for cell cultured meat.

Decellularized plant scaffolds have been used to develop edible scaffolds for cell cultured meat because of their natural structures similar to that of mammalian tissues. However, their diverse three-dimensional (3D) porous structures may lead to differences in myogenic differentiation of skeletal muscle cells. In this study, parsley plant tissues were decellularized and modified by type A gelatin and transglutaminase while retaining, respectively, longitudinal fibrous and transverse honeycomb pore structures. The effects of the structure of the decellularized parsley scaffold on the proliferation and myogenic differentiation of C2C12 cells were investigated and the quality of cell cultured meat was evaluated. The results showed that fibrous pore structure guided cells to be arranged in parallel, whereas honeycomb pore structure connected cells in a circular pattern. After induced differentiation, the fibrous scaffolds were more inclined to form multinucleated myotubes with higher expression of myogenic genes and proteins, and the final cell-based meat contained higher total protein content. Decellularized plant scaffolds with fibrous pore structure were more suitable for myogenic differentiation of C2C12 cells, providing support to the development of edible scaffolds for cultured meat. PRACTICAL APPLICATION: This study investigated the different three-dimensional (3D) pore structure of parsley parenchyma to gain insight into how the 3D pore structure of decellularized plant scaffolds regulates myogenic differentiation, which is expected to address the unstable myogenic differentiation of skeletal muscle cells on decellularized plant scaffolds in cell culture meat production.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Online Measurement of Melt-Pool Width in Direct Laser Deposition Process Based on Binocular Vision and Perspective Transformation.

Direct laser deposition (DLD) requires high-energy input and causes poor stability and portability. To improve the deposited layer quality, conducting online measurements and feedback control of the dimensions, temperature, and other melt-pool parameters during deposition is essential. Currently, melt-pool dimension measurement is mainly based on machine vision methods, which can mostly detect only the deposition direction of a single melt pool, limiting their measurement range and applicability. We propose a binocular-vision-based online measurement method to detect the melt-pool width during DLD. The method uses a perspective transformation algorithm to align multicamera measurements into a single-coordinate system and a fuzzy entropy threshold segmentation algorithm to extract the melt-pool true contour. This effectively captures melt-pool width information in various deposition directions. A DLD measurement system was constructed, establishing an online model that maps the melt-pool width to the offline deposited layer width, validating the accuracy of the binocular vision system in measuring melt-pool width at different deposition angles. The method achieved high accuracy for melt-pool measurements within certain deposition angle ranges. Within the 30°-60° measurement range, the average error is 0.056 mm, with <3% error. The proposed method enhances the detectable range of melt-pool widths, improving cladding layers and parts.