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Abstract Purpose Uveal melanoma (UM) is the most common intraocular malignancy in adults. Previous studies have examined the intra-tumoral heterogeneity. However, the spatial distribution of tumor cells within the tumor microenvironment and its relationship with tumor progression still remains largely unclear. Our study aimed to analyze the correlation between cell distribution patterns and the prognosis of UM. Methods In this paper, we performed spatial transcriptomics (ST) sequencing on two UM samples to describe the different cellular distribution patterns. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) functional enrichment analysis, and protein–protein interaction (PPI) network were performed to define the biological function of each cluster. Differentially expressed genes (DEGs) and survival analysis based on datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database further confirmed the correlation between cellular distribution and clinical prognosis. Results We found two different patterns of tumor cell distribution. The focal tumor cells have a distinct ribosome synthesis and rRNA pathway. In contrast, the subpopulation tented to distribute diffusely was related to fatty acids metabolism profile, presumably supporting tumor growth by providing energy. The scattered tumor cell cluster was associated with malignant biological behaviors and was involved in extensive cellular interactions, including COLLAGEN. Moreover, pseudo-time analysis showed that migration started from the basal region through cell differentiation. According to the TCGA and GEO database, genes expressed characteristically in the scattered tumor cell cluster were related to poor prognosis. Conclusions Our study drew the ST maps for UM for the first time. These findings revealed the distribution patterns of tumor cells associated with different biological functions and pointed towards specific tumor subpopulations with higher invasiveness as potential therapeutic targets. Together, our study displayed an overview of UM transcriptome and explored the intra-tumoral heterogeneity of UM at the spatial level.

ABSTRACT Objective Percutaneous pedicle screw fixation (PPSF) technique requires a very precise entry point of the Jamshidi needle, which leads to repeated adjustments, damaging the pedicle and increasing radiation exposure. This study was designed to propose an improved percutaneous pedicle screw fixation technique‐trajectory dynamic adjustment (TDA) technique, and evaluate its feasibility and assess the clinical outcomes. Method A total of 445 patients with lumbar spondylolisthesis or lumbar spinal stenosis associated with instability from June 2017 to May 2022 were included in the retrospective study. They were randomly separated into two groups. Two hundred thirty‐one patients underwent TDA technique (TDA group). Two hundred fourteen patients underwent traditional PPSF technique (PPSF group). All patients underwent postoperative CT to assess the accuracy of screw placement, superior facet joint violation (FJV). The evaluated clinical outcomes were needle insertion time, radiation exposure, blood loss, hospital stay, the Japanese Orthopedic Association (JOA) score, the Visual Analogue Scale (VAS) scores for lower back pain (LBP), and leg pain, lumbar interbody fusion rate, and postoperative complications. The independent‐sample t test and paired t‐test were used for continuous data. The contingency table and Mann–Whitney U test were used for categorical data. Results The time of the insertion in TDA group was significantly lower than that in PPSF group (p 0.05). Overall, there was no significant difference in the proportion of clinically acceptable screws between the two groups (p > 0.05). In addition, the lateral screw misplacement in TDA group was higher. Moreover, FJV rate was significantly lower than that in PPSF group (p 0.05). Conclusion Compared to traditional PPSF technique, TDA technique is a safer and more effective procedure which has shorter surgical time, lower radiation exposure, and lower facet joint violation rate.

Abstract Background Burn-hemorrhagic shock combined injury, a severe condition causing complex stress responses and metabolic disturbances that significantly affect clinical outcomes in both military and civilian settings, was modeled in swine to investigate the associated metabolomic and proteomic changes and identify potential biomarkers for disease prognosis. Methods Eight clean-grade adult male Landrace pigs (4–5 months, average weight 60–70 kg) were used to model burn-hemorrhagic shock combined injury. Serum samples collected at 0 h and 2 h post-injury were analyzed using metabolomic and proteomic measurements. The metabolomic and proteomic data were processed through partial least squares–discriminant analysis (PLS–DA) and the KEGG enrichment etc. Furthermore, the integrate analysis of the metabolomic and proteomic data was generalized by canonical correlation discriminant analysis, and the correlation between metabolites and mortality of the swine model was predicted using a multiple linear regression model by Pearson analysis. Results PLS–DA revealed a global shift in each of the metabolomic and proteomic profiles following injury. The levels of 87 signature metabolites including various types of amino acids, fatty acids and acyl-carnitines of different lengths, and many metabolites in the gluconeogenesis, glycolysis, and tricarboxylic acid (TCA) cycle are generally increased (P

The automatic detection of multimodal fake news has recently garnered significant attention. However, the existing detection methods mainly focus on merging textual and visual features, but fail to make full use of multimodal numbers from the perspective of multi-granularity. Additionally, emerging pre-trained multimodal learning models and powerful contrastive learning methodologies remain underutilized in this domain. To address these challenges, we introduce a multimodal fake news detection framework (FMC) that integrates multi-granularity feature fusion with contrastive learning. Initially, FMC utilizes a range of pre-trained models to extract textual and visual features at various levels of granularity. Subsequently, a multi-granularity fused multimodal news representation is created through cross-modal alignment and textual–visual co-attention . The final step involves classifying the news as true or fake, leveraging a combination of multi-head self-attention mechanisms and a contrastive learning auxiliary task. This contrastive learning auxiliary task specifically aims to minimize the distance between similar news representations that share the same label in the multimodal feature space, and maximize the distance between representations of differing labels. Comprehensive experiments conducted on three real-world datasets have demonstrated the superior effectiveness of our proposed framework, significantly surpassing the performance of current state-of-the-art methods.

Visual tactile fusion sensing technology is an integrated sensor biomimetic technology that combines visual camera image information and tactile sensor perception information of objects and environments, inspired by the coordinated regulation of human visual and tactile movements and behaviors. With the development of computer vision, neural networks, and tactile perception technology, the introduction of visual touch fusion sensing technology in the control and working process of intelligent robots has gradually become a research hotspot. The basic principles and development status of visual tactile sensors was summarized based on different tactile sensing modes, including diffuse reflection of light rays in reflective layers, tracking and detection of marked points/objects, optical waveguides, and bionics. At the same time, the application status of visual touch fusion sensors in object recognition and detection, object slip and grasping stability detection, and robot grasping fields was summarized. Finally, the following prospects were proposed for visual touch fusion technology: 1) development of multimodal perception technology; 2) innovation in human-computer interaction methods; 3) improvement of control accuracy for intelligent robots; 4) drive the consumption of electronic products.

Abstract Background Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP). Methods This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used. Results Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P 0.05 for all interactions). Conclusion Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products. Among these genera, Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites. However, there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera. In this study, we first investigated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters (BGCs). The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques. The findings unveiled that the majority (95.4%) of the gene cluster families (GCFs) encoded by Allokutzneria and Kibdelosporangium were genus-specific, including NRPS GCFs encoding siderophores. The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity, with the culture medium having a big impact on the metabolic profiles. Besides, an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917, with two of them, including a novel one (N-deoxy arthrobactin A), being experimentally validated. The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.

Abstract Background To examine if pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and to assess if PBT has any subsequent impact on pregnancy outcomes. Methods A retrospective, single-center study was carried out at Beijing Tongren Hospital, focusing on women of childbearing age diagnosed with UM and treated with iodine-125 plaque brachytherapy. Both the outcomes of pregnancies and the health status of the fetuses were monitored. Survival analyses were conducted using the Kaplan-Meier method, with endpoints being metastasis and death. Results A total of 13 patients who had full-term pregnancies and 96 non-pregnant women matched by age and tumor size were included. The mean follow-up time was 67.0 ± 27.7 months (median:66.0 months, range:21.0 to 116.0 months). In the pregnant group, two patients developed metastases, one of whom died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15–2.86; P = 0.576) and overall survival (HR: 0.48, 95% CI: 0.06–3.66; P = 0.464). All pregnant patients carried the pregnancy to term and delivered healthy children with no report of placental or infant metastases to date. Conclusion Pregnancy does not appear to negatively impact the prognosis of UM patients undergoing PBT. PBT showed no observable detriment to maternal fertility and exhibited no teratogenic effects on the fetus. However, the long-term implications of PBT on pregnancy remain uncertain, necessitating additional, prolonged follow-up studies.

[Introduction] Facing the advancement of the national "carbon peaking and carbon neutrality" strategy, energy in various regions of China will develop towards low-carbon utilization based on its unique resource endowment. In order to understand the development level of low-carbon energy, it is necessary to conduct evaluation research on low-carbon energy utilization. [Method] This paper first analyzed the evaluation objects of energy low-carbon utilization; then classified and organized the evaluation indicators of energy low-carbon utilization. This paper sorted out and introduced the characteristics of each evaluation method and model, and explained the role of energy low-carbon utilization evaluation research. [Result] The evaluation objects of energy low-carbon utilization can be divided into energy system evaluation and regional energy evaluation. The evaluation indicators are summarized from three aspects: energy low-carbon indicators, energy utilization indicators and energy security indicators, and the subjective and objective weighting evaluation methods are rationally used. It is possible to more comprehensively and accurately assess and understand the situation of low-carbon energy utilization. [Conclusion] The current energy low-carbon utilization evaluation is usually only reflected as a part of the evaluation index system. With the development of low-carbon energy and the increase in the proportion of clean energy, the evaluation of low-carbon energy utilization will become more and more important.

IntroductionThe rapid advancement of digital technology has catalyzed the emergence of “digital villages,” presenting both new opportunities and challenges for the digital transformation of agriculture. This transformation has become a core driving force behind sustainable agricultural development. This paper utilizes panel data from 30 provincial-level administrative regions of mainland China (excluding Tibet) for the period 2011 to 2020 to explore how digital rural development (DRD) impacts agricultural green total factor productivity (AGTFP) and examines its underlying mechanisms.MethodsRegarding variable measurement, the study employs the entropy weighting method to quantify the DRD and uses an extended Data Envelopment Analysis-Malmquist model to assess AGTFP. For the research approach, the study constructs a two-way fixed effects model to evaluate the impact of DRD on AGTFP and explores the underlying mechanisms. Specifically, the study conducts benchmark regression analysis, endogeneity tests, robustness tests, mechanism examinations, and heterogeneity tests.Results(1) DRD significantly enhances AGTFP, a conclusion that remains robust following the province-year clustering robust standard error estimates, winsorization tests, and excluding COVID-19-affected years. (2) Mechanistic analysis indicates that DRD primarily boosts AGTFP by promoting the development of digital inclusive finance (DIF) and facilitating the integration of primary, secondary, and tertiary industries (IPST). (3) Heterogeneity tests show that the positive impact of DRD on AGTFP is more pronounced in regions with higher levels of informatization and central regions of China.DiscussionTo harness DRD’s potential more effectively in fostering sustainable agricultural development, policymakers should concentrate on DIF and the IPST. Additionally, the government should pay close attention to disparities in informatization levels and resource allocation across regions and develop targeted strategies accordingly. Fundamentally, this study aims to elucidate China’s efficacy in rural digitalization and the green transformation of agriculture to an international audience. It seeks to provide insights and guidance on formulating more scientific, efficient, and sustainable strategies for agricultural development worldwide, thereby promoting green agricultural growth and supporting rural revitalization.

EcGUS has drawn considerable attention for its role as a target in alleviating serious GIAEs. In this study, a series of 72 (thio)urea derivatives were designed, synthesised, and biologically assayed. The bioassay results revealed that E-9 (IC50 = 2.68 μM) exhibited a promising inhibitory effect on EcGUS, surpassing EcGUS inhibitor D-saccharic acid-1,4-lactone (DSL, IC50 = 45.8 μM). Additionally, the inhibitory kinetic study indicated that E-9 (Ki = 1.64 μM) acted as an uncompetitive inhibitor against EcGUS. The structure-activity relationship revealed that introducing an electron-withdrawing group into the benzene ring at the para-position is beneficial for enhancing inhibitory activity against EcGUS. Furthermore, molecular docking analysis indicated that E-9 has a strong affinity to EcGUS by forming interactions with residues Asp 163, Tyr 472, and Glu 504. Overall, these results suggested that E-9 could be a potent EcGUS inhibitor, providing valuable insights and guidelines for the development of future inhibitors targeting EcGUS.

Background With the gradual deepening of the comprehensive reform of community health services, the prevention and control of single diseases for the entire population in the community is also constantly being optimized, However, there is still a lack of appropriate evaluation methods in the community to reflect its prevention and control effectiveness evaluation. Objective By analyzing and exploring the cost effect of the existing whole-population prevention and control measures of osteoporosis in Fenglin community, from 2016 to 2022, this paper answers the initial results and possible problems of the whole-population prevention and control of single disease in the community. Methods This study conducted a cost-effectiveness analysis on 4 293 community residents who received osteoporosis prevention and treatment in Fenglin community from 2016 to 2022. Divide the research object into three states based on bone density values: healthy, low bone mass, and osteoporosis, and construct a Markov model to analyze the influencing factors of different state transitions. And based on the predicted values of the Markov model combined with quality adjusted life years (QALY) , the increment of quality adjusted life years (QALY) is calculated. All costs invested in prevention and control work from 2016 to 2022 are counted, and the effectiveness of prevention and control is evaluated by the cost/quality adjusted life year increment ratio. Quality adjusted life years (QALY) are obtained by calculating the health utility value and expected life determined through literature search. Results The total cost of osteoporosis prevention and treatment in Fenglin community was 33 814 102.15 yuan. The total quality-adjusted life years of 4 293 community osteoporosis prevention and treatment population were 77 098.288 9 at the first diagnosis, the average per capita was 17.959, and the standard deviation was 9.34. At the second diagnosis, the total quality-adjusted life years were 79 616.936 1, the mean per capita was 18.546, the standard deviation was 9.342, and the difference between the two diagnoses was 2 518.647 2. The incremental cost-effectiveness ratio (ICER) is 2 132.907 0 yuan /QALY, and the incremental cost-effectiveness ratio (ICER) is less than 1 times (66 965.10 yuan) per capita GDP, indicating that the intervention scheme is fully cost-effective. Conclusion This study combined Markov model and quality-adjusted life years (QALY) to make a preliminary evaluation of the prevention and treatment effect of osteoporosis in Fenglin community. The results showed that the intervention program of osteoporosis prevention and treatment in Fenglin community was worth investing, and provided a certain basis for the accurate prevention and treatment decision of osteoporosis in the future.

Abstract Aim Recent imaging studies have found significant abnormalities in the brain’s functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. Methods We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. Results In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P

Abstract Understanding the alterations in soil microbial communities in response to climate warming and their controls over soil carbon (C) processes is crucial for projecting permafrost C-climate feedback. However, previous studies have mainly focused on microorganism-mediated soil C release, and little is known about whether and how climate warming affects microbial anabolism and the subsequent C input in permafrost regions. Here, based on a more than half-decade of in situ warming experiment, we show that compared with ambient control, warming significantly reduces microbial C use efficiency and enhances microbial network complexity, which promotes soil heterotrophic respiration. Meanwhile, microbial necromass markedly accumulates under warming likely due to preferential microbial decomposition of plant-derived C, further leading to the increase in mineral-associated organic C. Altogether, these results demonstrate dual roles of microbes in affecting soil C release and stabilization, implying that permafrost C-climate feedback would weaken over time with dampened response of microbial respiration and increased proportion of stable C pool.

Abstract Background A growing number of studies have demonstrated that the polar regions have the potential to be a significant repository of microbial resources and a potential source of active ingredients. Genome mining strategy plays a key role in the discovery of bioactive secondary metabolites (SMs) from microorganisms. This work highlighted deciphering the biosynthetic potential of an Arctic marine-derived strain Aspergillus sydowii MNP-2 by a combination of whole genome analysis and antiSMASH as well as feature-based molecular networking (MN) in the Global Natural Products Social Molecular Networking (GNPS). Results In this study, a high-quality whole genome sequence of an Arctic marine strain MNP-2, with a size of 34.9 Mb was successfully obtained. Its total number of genes predicted by BRAKER software was 13,218, and that of non-coding RNAs (rRNA, sRNA, snRNA, and tRNA) predicted by using INFERNAL software was 204. AntiSMASH results indicated that strain MNP-2 harbors 56 biosynthetic gene clusters (BGCs), including 18 NRPS/NRPS-like gene clusters, 10 PKS/PKS-like gene clusters, 8 terpene synthse gene clusters, 5 indole synthase gene clusters, 10 hybrid gene clusters, and 5 fungal-RiPP gene clusters. Metabolic analyses of strain MNP-2 grown on various media using GNPS networking revealed its great potential for the biosynthesis of bioactive SMs containing a variety of heterocyclic and bridge-ring structures. For example, compound G-8 exhibited a potent anti-HIV effect with an IC50 value of 7.2 nM and an EC50 value of 0.9 nM. Compound G-6 had excellent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U1975, SGC-7901, A549, MOLT-4, and HL60 cell lines, with IC50 values ranging from 0.10 to 3.3 µM, and showed significant anti-viral (H1N1 and H3N2) activities with IC50 values of 15.9 and 30.0 µM, respectively. Conclusions These findings definitely improve our knowledge about the molecular biology of genus A. sydowii and would effectively unveil the biosynthetic potential of strain MNP-2 using genomics and metabolomics techniques.

Numerous studies have suggested potential associations between maternal subclinical hypothyroidism (SCH) and adverse metabolic outcomes in offspring, however, the underlying mechanism remains unclear. In this study, we generated a maternal SCH mouse model by administering 50 ppm 6-propyl-2-thiouracil (PTU) in the drinking water of pregnant mice until delivery. This model was used to investigate the mechanisms influencing glucose metabolism in offspring. RNA sequencing (RNA-seq) revealed a substantial increase in ARRDC3 expression in the livers of the offspring of the SCH model mice, which may contribute to insulin resistance. Additionally, the phosphorylation levels of key proteins in the insulin signalling pathway, such as protein kinase B (Akt), glycogen synthase kinase 3 beta (GSK-3β), and Forkhead box protein O1 (FoxO1), were correspondingly reduced in the SCH offspring. Moreover, overexpression of ARRDC3 in Hepa1‒6 cells suppressed the Akt/GSK-3β/FoxO1 signalling pathway and increased the expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), which was consistent with the molecular changes observed in SCH offspring. Our results also indicated that the upregulation of ARRDC3 in SCH offspring may result from increased H3K27 acetylation of the ARRDC3 promoter region, driven by elevated expression of P300. Importantly, adequate L-T4 supplementation during pregnancy improved insulin sensitivity and reversed the molecular alterations in the insulin signalling pathway observed in SCH offspring. In conclusion, exposure to intrauterine SCH resulted in altering the P300-ARRDC3 axis in offspring and impaired insulin sensitivity by disrupting the Akt/GSK-3β/FoxO1 signalling pathway. Timely L-T4 supplementation during pregnancy is an effective strategy to prevent insulin resistance in offspring of SCH mothers. This study elucidates potential molecular mechanisms behind insulin resistance in SCH offspring and suggests novel therapeutic targets for treating metabolic disorders related to maternal SCH.

Abstract Thermally activated delayed fluorescence (TADF) molecules are regarded as promising materials for realizing high‐performance organic light‐emitting diodes (OLEDs). The connecting groups between donor (D) and acceptor (A) units in D–A type TADF molecules could affect the charge transfer and luminescence performance of TADF materials in aggregated states. In this work, we design and synthesize four TADF molecules using planar and twisted linkers to connect the aza‐azulene donor (D) and triazine acceptor (A). Compared with planar linkers, the twisted ones (Az‐NP‐T and Az‐NN‐T) can enhance A–A aggregation interaction between adjacent molecules to balance hole and electron density. As a result, highly efficient and stable deep‐red top‐emission OLEDs with a high electroluminescence efficiency of 57.3% and an impressive long operational lifetime (LT95 ∼ 30,000 h, initial luminance of 1000 cd m−2) are obtained. This study provides a new strategy for designing more efficient and stable electroluminescent devices through linker aggregation engineering in donor–acceptor molecules.

Both carbon-based single atom catalysts (SACs) and dual atom catalysts (DACs) have garnered significant attention in the field of electrochemical reactions because of the impressive attributes, including exceptional catalytic activity, selectivity, and cost-effectiveness. The ability to modulate the electronic structure and geometric construction of active sites within SACs/DACs is paramount for unleashing their complete potential, which in turn can ultimately dictate catalytic behavior with unprecedented precision. In this review, the recent major developments of the regulation strategies for modulating electronic structure and geometric construction of carbon-based SACs/DACs are summarized. For the SACs, the recently reported modulation methods are categorized into four strategies, including adjusting the density of single atoms, defect engineering, confinement effect and strain engineering. And for the DACs, the five methods contain bonded dual-atom adjustment, non-bonded and bridged dual-atom adjustment, metal and nonmetal dual-atom adjustment, bilayer dual-atom adjustment and homogeneous dual-atom adjustment. The recently developed synthetic strategies are comprehensively summarized, especially their electronic structure and geometric configuration are discussed in detail, the different catalytic applications of electrochemical reactions, and their unique catalytic mechanism are highlighted. Finally, the challenges and prospects of SACs/DACs for tailoring their electronic structures and geometric arrangements are further discussed.

AIM: To evaluate dry eye disease (DED) symptomatology and mental health status in different COVID-19 patients. METHODS: A cross-sectional observational design was used. Totally 123 eligible adults (46.34% of men, age range, 18-59y) with COVID-19 included in the study from August to November, 2022. Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were used in this study. RESULTS: OSDI scores were 6.82 (1.25, 15.91) in asymptomatic carriers, 7.35 (2.50, 18.38) in mild cases, and 16.67 (4.43, 28.04) in recurrent cases, with 30.00%, 35.56%, and 57.89%, respectively evaluated as having DED symptoms (χ2=7.049, P=0.029). DEQ-5 score varied from 2.00 (0, 6.00) in asymptomatic carriers, 3.00 (0, 8.00) in mild cases, and 8.00 (5.00, 10.00) in recurrent cases, with 27.50%, 33.33%, and 55.26%, respectively assessed as having DED symptoms (χ2=8.532, P=0.014). The prevalence of clinical anxiety (50.00%) and depression (47.37%) symptoms were also significantly higher in patients with recurrent infection (χ2=24.541, P

Abstract Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.

Abstract Background Myopericytoma is a rare spindle cell tumor of mesenchymal origin, typically benign, characterized by concentric proliferation of tumor cells around blood vessels within subcutaneous tissue. It primarily occurs in middle-aged adults and is often located in distal extremities, although cases have been reported in proximal extremities and head-neck regions. However, occurrences within the oral cavity are exceedingly rare. To date, literature reviews have identified only two cases in children under 10 years old and reported only five cases of myopericytoma occurring in the lip region. We provide a comprehensive review and analysis of all documented cases to better understand this condition. Case presentation A 7-year-old girl presented to oral and maxillofacial surgery with the discovery of a painless mass on the inner aspect of the upper lip. The diagnosis of myopericytoma was confirmed by histological examination (HE staining), alcian blue staining, and immunohistochemistry. Conclusions Following surgical excision, there were no signs of recurrence at a 3-month follow-up. The pathological diagnosis of myopericytoma is quite challenging, and immunohistochemical testing is necessary.

The compromised egg quality and leg abnormality during the end of the laying cycle (after 40 weeks) have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium (Ca) butyrate, produced by fermentation by Clostridium butyricum, on production, eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at 50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength (P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet (both P 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker (P

ObjectiveThis study reviews the development of rhubarb processing and the current status of pharmacological research. We summarized the effects of different processing methods on the active compounds, pharmacological effects, and toxicity of rhubarb, as well as the clinical application of different concoctions, providing reference for further pharmacological research and clinical application of rhubarb.MethodsA comprehensive literature review was conducted using databases such as Pubmed, Embase, National Science and Technology Library, Web of science, CNKI, China Science and Technology Journal Database, SinoMed, and the Pharmacopoeia of the People’s Republic of China. Search terms included “rhubarb”, “raw rhubarb”, “wine rhubarb”, “cooked rhubarb”, “rhubarb charcoal”, “herbal processing”, “compounds”, “pharmacological effects”, “inflammation”, “gastrointestinal bleeding”, and “tumor”.ResultsHistorical records of rhubarb processing date back to the Han Dynasty, with continual innovations. Currently, the types of rhubarb used in traditional Chinese medicine have stabilized to three species: Rheum palmatum L., Rheum tanguticum Maxim.ex Balf. and Rheum officinale Baill. Common concoctions include raw rhubarb, wine rhubarb, cooked rhubarb and rhubarb charcoal. The active compounds of rhubarb are known to defecation, exhibit antibacterial and anti-inflammatory properties, regulate coagulation, protect the digestive system, and possess anti-tumor activities. Guided by Chinese medicine theory, the use of different rhubarb concoctions can enhance specific effects such as purgation to eliminate accumulation, clearing heat and toxins, cooling blood to stop hemorrhages, activating blood circulation to remove blood stasis, and inducing dampness to descend jaundice, thereby effectively treating various diseases. The therapeutic impact of these concoctions on diseases reflects not only in the changes to the active compounds of rhubarb but also in the formulations of traditional Chinese medicine. Processing has also shown advantages in reducing toxicity.ConclusionDifferent processing methods alter the active compounds of rhubarb, thereby enhancing its various pharmacological effects and meeting the therapeutic needs of diverse diseases. Selecting an appropriate processing method based on the patient’s specific conditions can maximize its pharmacological properties and improve clinical outcomes.

ObjectiveThis study evaluates the research developments concerning Rehmanniae Radix in ovarian hypofunction diseases. It explores the processing methods of Rehmanniae Radix, the variations in its compounds before and after processing, the mechanism of Rehmanniae Radix and its active compounds in improving ovarian function, and the advancements in clinical applications of traditional Chinese medicine (TCM) compound that include Rehmanniae Radix.MethodsComprehensive literature search was conducted using databases such as China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, National Science and Technology Library, the Pharmacopoeia of the People’s Republic of China, Pubmed, and the Web of Science Database. The search utilized the following Medical Subject Headings (MeSH) and keywords: “Rehmanniae Radix,” “Drying Rehmannia Root,” “Rehmannia glutinosa,” “Rehmanniae Radix Praeparata,” “Traditional Chinese Medicine Processing,” “Pharmacological Effects,” “Ovarian Aging,” “Diminished ovarian reserve,” “Premature ovarian insufficiency,” “Premature Ovarian Failure,” “Ovarian hypofunction diseases”.ResultsThe ancient Chinese medical books document various processing techniques for Rehmanniae Radix. Contemporary research has identified changes in its compounds processing and the resultant diverse therapeutic effects. When processed into Rehmanniae Radix Praeparata, it is noted for its ability to invigorate the kidney. TCM compound containing Rehmanniae Radix is frequently used to treat ovarian hypofunction diseases, demonstrating significant clinical effectiveness. The key changes in its compounds processing include cyclic dilute ether terpene glycosides, phenylethanol glycosides, sugars, and 5-hydroxymethylfurfural. Its pharmacological action is primarily linked to the improvement of granulosa cell proliferation, antioxidative and anti-aging properties, and modulation of the immune and inflammatory microenvironment. Furthermore, Rehmanniae Radix also offers therapeutic benefits for cardiovascular and cerebrovascular diseases, osteoporosis and cognitive dysfunction caused by low estrogen levels. Thereby Rehmanniae Radix mitigates both the short-term and long-term health risks associated with ovarian hypofunction diseases.ConclusionProcessed Rehmanniae Radix has shown potential to improve ovarian function, and its compound prescriptions have a definite effect on ovarian dysfunction diseases. Therefore Rehmanniae Radix was garnering interest for both basic and clinical research, with promising application prospects as a future therapeutic agent for ovarian hypofunction diseases. However, further studies on its toxicology and the design of standardized clinical trials are necessary to fully establish its efficacy and safety.

IntroductionThe study aimed to investigate the potential effects of varying wheat levels in broiler diets on growth performance, intestinal barrier, and cecal microbiota.MethodsDay-old male broilers were fed the same diet until 10 d of age. Then they were randomly assigned to 1) the low-level wheat group, where inclusion of 15.0% and 25.0% wheat in the grower and finisher diet, respectively, 2) the medium-level wheat group with 30.0% and 40.0% of wheat in the grower and finisher periods; and 3) the high-level wheat dietary group, in which the grower and finisher diets contained 55.77% and 62.38% of wheat, respectively.ResultsDietary treatments unaffected the body weight at 39 d, whereas incorporating high wheat in diets significantly increased the feed intake and reduced the feed conversion ratio from 10 to 39 d (p

Abstract Background To investigate the relationship between body weight and Axial length in guinea pigs. Methods Forty pigmented guinea pigs were randomly divided into two groups, namely control group and negative lens-induced myopization (LIM) group. After measuring the baseline axial length and body weight (BW), guinea pigs of LIM group received bilateral negative lens-induced myopization using − 10.0 diopters lenses. One week later, the lenses were removed and biometric and ophthalmoscopic examinations were repeated. Results Two groups of guinea pigs showed no statistical difference in initial body weight and eye axis length. Compared to the control group, the lens-induced group had a lower weight (P = 0.02) and a longer axial length (P 0.05). Conclusion In guinea pigs of the same age, axial length was not correlated with body weight. Also, baseline body weight had no impact on natural axial length growth or lens-induced myopia. Lens-induction caused a significant reduction in body weight gain.

Abstract Background Previous studies have indicated a possible link between obesity and myopia, although the results have varied. The objective of this study was to investigate the correlation between a new measure of obesity, the weight-adjusted waist index (WWI), and myopia. Method This cross-sectional study included individuals between the ages of 12 and 25 who participated in a noncycloplegic vision examination as part of the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2008. WWI was calculated as waist circumference divided by the square root of body weight. Myopia was characterized by a spherical equivalent (SE) of ≤ − 0.5 diopters (D) and further categorized into mild (-3.00D

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Digital government is a crucial strategic choice for achieving sustainable development worldwide. Notably, the underdeveloped state of digital government in developing countries is a significant concern. To address this, we constructed a Pressure-Action-Resources analytical framework based on the Pressure-Response model. The study analyzed the multifaceted paths that drive the development of digital government in 31 provincial-level administrative regions in China from 2015 to 2021 using the dynamic QCA method. The study results indicate that: 1) single condition has an obvious asymmetric causality and dynamic effect on the development of digital government. Technology management capabilities and data open capabilities are gradually becoming necessary for the further development of digital government; 2) development of digital government is characterized by “multiple concurrency” and multiple equivalent paths. There are three types of driving paths for the high-level development of digital government: The Timely Transformation model, the ‘Pressure-Resource’ model, and the Proactive Transformation model; 3) each driver pathway is clearly influenced by the digital government strategy and major public health emergencies at certain points in time; and 4) under certain conditions, digital transformation attention and technology management capabilities can be substituted for each other. In addition, under certain conditions, the pressure of intergovernmental competition can be substituted for each other with a combination of conditions of citizen demand pressure and digital transformation attention. The above findings enrich the perceptions of existing research and provide useful insights into how developing countries can better implement digital government policies.

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites.

At present, a large number of rumors are mixed in with various kinds of news, such as current affairs, politics, social economy, and military activities, which seriously reduces the credibility of Internet information and hinders the positive development of various fields. In previous research on rumors, most scholars have focused their attention on the textual features, contextual semantic features, or single-emotion features of rumors but have not paid attention to the chain reaction caused by the hidden emotions in comments in social groups. Therefore, this paper comprehensively uses the emotional signals in rumor texts and comments to extract emotional features and determines the relationship between them to establish dual-emotion features. The main research achievements include the following aspects: (1) this study verifies that, in the field of affective characteristics, the combination of rumor-text emotion and comment emotion is superior to other baseline affective characteristics, and the detection performance of each component is outstanding; (2) the results prove that the combination of dual-emotion features and a semantic-feature-based detector (BiGRU and CNN) can improve the effectiveness of the detector; (3) this paper proposes reconstructing the dataset according to time series to verify the generalization ability of dual affective features; (4) the attention mechanism is used to combine domain features and semantic features to extract more fine-grained features. A large number of data experiments show that the dual-emotion features can be effectively compatible with an existing rumor detector, enhance the detector’s performance, and improve the detection accuracy.

In recent years, as the power grid continues to expand, the issue of asymmetrical short-circuit currents exceeding limits on the 220 kV medium-voltage side has become increasingly severe, and traditional current-limiting methods have certain limitations. Therefore, this paper explores the potential benefits and feasibility of installing a Fast Switching Fault Current Limiter (FSFCL) at the neutral point of a 220 kV transformer to effectively limit asymmetrical short-circuit currents on the medium-voltage side. The paper first analyzes the current-limiting performance of the FSFCL under different installation configurations, transformer operating conditions, and fault conditions through theoretical calculations. Subsequently, through simulation studies, the impact of different limiting reactance values on the overvoltage effect at the neutral point is discussed. The results show that the installation of the FSFCL has a significant effect on suppressing the asymmetrical short-circuit current on the medium-voltage side of the transformer, but this measure has also led to an increase in the voltage at the grounded neutral point. Finally, taking the No. 2 main transformer of a certain 220 kV substation as an example, to achieve the expected current-limiting effect, the limiting reactance value of the FSFCL needs to be at least 4 ohms. At this reactance value, the overvoltage level at the neutral point remains well below the withstand limit of its insulating material. Additionally, given the existing overvoltage protection devices at the neutral point, no further overvoltage protection measures are required.

Background/Objectives: Marrubium vulgare L. (M. vulgare), the white horehound, is well known for treating inflammation-related diseases. Methods: In this context, we investigated the efficacy of M. vulgare ingredients in treating Alzheimer’s disease using various in vitro and in silico antioxidant, anti-inflammatory, anti-cholinesterase, and anti-tyrosinase mechanisms. Results: In our results, sixty-one components were tentatively identified using gas and liquid chromatography (GC-MS and LC-MSn) and categorized as hydrocarbons, fatty acids, and polyphenolics. The extract inhibited linoleic oxidation with an IC50 value of 114.72 µg/mL, captured iron (Fe2+) ions with an IC50 value of 164.19 µg/mL, and displayed reducing power. In addition, the extract showed radical-scavenging ability towards DPPH•, NO•, ABTS•+, and H2O2 assays compared to L-ascorbic acid and butylated hydroxytoluene. The DPPH• was scavenged by 77.62% at 100 µg/mL, and NO•, ABTS•+, and H2O2 were scavenged with IC50 values of 531.66, 117.51, and 143.10 µg/mL, respectively. M. vulgare also exhibited discriminating anti-inflammatory potency against cyclooxygenase (COX-2) with IC50 values of 619.15 µg/mL compared to celecoxib (p > 0.05). Notably, three Alzheimer’s biomarkers, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase were significantly inhibited. The molecular docking study supposed that the phenylethanoid glycosides of samioside and forsythoside B inhibited AChE and tyrosinase enzymes with low binding affinities of −9.969 and −8.804 kcal/mol, respectively. Marruboside was a proper inhibitor of COX and BChE enzymes with a binding score of −10.218 and −10.306 kcal/mol, respectively. Conclusions: M. vulgare extract showed significant inhibitory actions, which suggest that it could have a promising potential as an anti-Alzheimer agent.

Abstract Polyhedral distortion, associated closely with the atomic arrangement and interatomic interactions, drives many unique behaviors in solids, such as phase transition and negative thermal expansion. In thermoelectric heteroanionic oxides, the anionic polyhedra are widely present, but their effect on thermal transport is rarely investigated. Here, we report an anomalous thermal conduction induced by local symmetry distortion in layered oxyselenides via solving the Boltzmann transport equation based on first-principles calculations. We found interestingly that lighter BiCuSeO exhibits lower thermal conductivity than heavier BiAgSeO. Due to the different distorted degrees of CuSe4 and AgSe4 tetrahedrons, Cu prefers the in-plane vibration, while Ag has more tendency of out-of-plane vibration. Thus, the heat-carrying phonons dominated by the rattling-like vibration of Cu are significantly suppressed, resulting in lower thermal conductivity of BiCuSeO. This study highlights the importance of polyhedral distortion in regulating thermal conduction in layered heteroanionic materials.

ABSTRACT: The skeleton is a vital organ providing structural support in poultry. Weakness in bone structure can lead to deformities, osteoporosis, cage fatigue, and fractures, resulting in economic losses. Research has substantiated that genetic factors play a significant role in influencing bone quality. The discovery of genetic markers associated with bone quality holds paramount importance for enhancing genetic traits related to the skeletal system in poultry. This study analyzed nine phenotypic indicators of tibia quality in 120-day-old ducks. The phenotypic correlation revealed a high correlation among diameter, Perimeter, and weight (0.69–0.78), and a strong correlation was observed between toughness and breaking strength (0.62). Then, we conducted a genome-wide association analysis of the phenotypic indicators to elucidate the genetic basis of tibial quality in Nonghua ducks. Among the 11 candidate genes that were annotated, TAPT1, BST1, and STIM2 were related to the diameter indicator, ZNF652, IGF2BP1, CASK, and GREB1L were associated with the weight and toughness indicators. RFX8, GLP1R, and DNAAF5 were identified for ash, calcium, and phosphorus content, respectively. Finally, KEGG and GO analysis for annotated genes were performed. STIM2 and BST1 were enriched into the Calcium signalling pathway and Niacin and nicotinamide metabolic pathway, which may be key candidate genes affecting bone quality phenotypes. Gene expression analysis of the candidate genes, such as STIM2, BST1, TAPT1, and CASK showed higher expression levels in bones compared to other tissues. The obtained results can contribute to new insights into tibial quality and provide new genetic biomarkers that can be employed in duck breeding.

Spongiactinospora rosea is a rare actinomycete derived from sponges belonging to the Streptosporangiaceae family. Genomic analysis of the strain S. rosea LHW63015 revealed that it contains 41 secondary metabolite biosynthetic gene clusters (BGCs), including four cryptic type II polyketide synthases (T2PKS) BGCs. By using a metabolite mining approach in conjunction with LC-MS guided isolation, we identified three previously undescribed sulfur-bridged angucycline dimers, namely spongisulfins A-C (1–3), a configurational isomeric new angucycline monomer, rubiginone A3 (4), as well as three known related analogs (5–7). Comprehensive analyses of 1D/2D NMR, HR-ESIMS, single-crystal X-ray diffraction and ECD calculations were performed to elucidate their structures. Further sequence analyses of the chain length factors (CLF) protein and biosynthetic gene clusters (BGCs) identified the angucycline-type T2PKS BGC spo in the genome. Additionally, a dextran sulfate sodium salt (DSS)-induced Drosophila melanogaster reporter line (gstd1-GFP) model was established to evaluate the gut epithelium protective activities of these isolated compounds. The results demonstrated that spongisulfin A (1), with a concentration of 5 nM, significantly alleviated the high mortality caused by 5 % DSS treatment, and exerted its gut protective activity by modulating the ROS level through alleviation the expression of gstd1 in the gut.

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.

Abstract Introduction Measurement of the largest basal dimension (LBD) of intraocular tumors is important as a prognostic parameter. To evaluate the potential value of true color ultra-widefield fundus photography for measuring tumors, we compared LBD measurements of choroidal and retinal tumors using a color ultra-widefield fundus camera with clinical estimation based on indirect ophthalmoscopy and standardized ophthalmic ultrasound. Methods The LBD of 148 choroidal and retinal tumors in 148 patients seen at Tongren Hospital were measured using ultra-widefield fundus photography and compared with measurements obtained using B-scan ultrasonography and clinical estimates based on indirect ophthalmoscopy. Results Paired t-tests and Bland–Altman plots reveal that measurements from ultra-widefield fundus photographic images are not statistically different from clinical estimates and ultrasound measurements. The results also showed that, although not statistically significant, when the tumor boundary was clear, the height was