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Current gold standard for the replacement of small-diameter blood vessel (ID

In order to achieve its nucleotide polymorphism (SNP) accurate typing, this paper establishes a molecular diagnostic technique based on fluorescent quantitative PCR for accurate genotyping of the nucleotide polymorphism (SNP) at the rs755555 locus of the SLC39A13 gene. Firstly, Taqman fluorescent ARMS-PCR detection primers and probes were designed for the rs755555 locus and the internal reference gene peptidylprolyl isomerase A (PPIA). Secondly, positive control plasmids were constructed. Finally, based on genotyping accuracy, the primer and probe combinations were optimized, and the PCR reaction system and conditions for the detection reagents were optimized. The optimal primer and probe combination for the wild-type was: WF1, R1, FP1, PIRF5, PIRR5, PIRP5; the optimal combination for the mutant type was: FMF3, R1, FP1, PIRF5, PIRR5, PIRP5. The optimal reaction system for detecting samples was: 0.1 μL each of upstream and downstream primers and probes for the SLC39A13 gene, 0.1 μL each of upstream and downstream primers and probes for the internal standard, 10 μL PerfectStart Ⅱ Probe qPCR SuperMix UDG, 5.4 μL purified water, and 4 μL sample genome. The feasibility of this detection system was confirmed through reproducibility experiments and the detection of 70 samples. This provides a technical foundation for the development of a detection kit for the polymorphism at the rs755555 locus of the SLC39A13 gene.

Abstract Deep learning-based MRI reconstruction models have achieved superior performance these days. Most recently, diffusion models have shown remarkable performance in image generation, in-painting, super-resolution, image editing and more. As a generalized diffusion model, cold diffusion further broadens the scope and considers models built around arbitrary image transformations such as blurring, down-sampling, etc. In this paper, we propose a k-space cold diffusion model that performs image degradation and restoration in k-space without the need for Gaussian noise. We provide comparisons with multiple deep learning-based MRI reconstruction models and perform tests on a well-known large open-source MRI dataset. Our results show that this novel way of performing degradation can generate high-quality reconstruction images for accelerated MRI.

Abstract Human economic activities drive the production and consumption of goods and services, contribute to the achievement of the United Nations Sustainable Development Goals (SDGs). However, the extent of economic growth’s influence on the SDGs remains unclear. To fill this knowledge gap, here, we quantified the environmental effects of economic activities and explored correlations between environmental effect and achieving SDGs. We developed six Environmental Footprint Indices, with a higher score indicating better efficiency or lower burden. Here we show that the various Environmental Footprint Indices had synergistic and trade-off effects on most SDG targets indices, but the synergistic effects prevailed. As income increased, the correlation between Environmental Footprint Indices and SDG target indices gradually strengthened. improved production efficiency and consumption changes notably advance SDGs, especially in low-income group countries. Our work provides scientific insights into the impact and prospects of environmental regulation required for achieving the SDGs by 2030.

Abstract Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 μM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819–60.761)) and mortality (HR 3.418, 95% CI (1.308–8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis.

Abstract Marine heatwaves (MHWs) represent anomalously warm temperature conditions of seawater that may affect marine life and ocean biogeochemistry. Under such conditions, phytoplankton communities may modify their structure and functions, and their resilience is not assured. This study characterizes the impact of MHWs on the phytoplankton spring bloom in the North‐Western Mediterranean Sea. Here, we synergistically combine autonomous observations from BioGeoChemical‐Argo floats, satellite‐based and marine ecosystem model data, and show that MHW events occurring during winter drastically inhibit phytoplankton carbon biomass in spring by up to 70%. Such reduction is related to the enhanced stratification of the water column under MHWs which hinders the renewal of nutrients from deep‐ocean reservoirs, thus preventing surface phytoplankton from blooming. This process negatively impacts particulate organic carbon stocks within the mixed layer, while severe events cause an earlier shift of phytoplankton phenology that provokes changes in zooplankton biomass distribution.

A novel (8.5Al3BC + 14.5Al2O3)/Al composite was fabricated with exceptional elevated-temperature properties and stiffness. The composite boasts an average Young’s modulus of 99 GPa, with ultimate tensile strength and elongation of the composite at 350°C averaging 188 MPa and 4.4%, respectively. The synergistic strengthening effect of Al3BC and γ-Al2O3 is responsible for the high-temperature properties, while they both contribute to the improvement of stiffness as they have a high initial Young’s modulus. This innovative composite design holds promising potential for advancements in material engineering and performance optimization.

Abstract Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. Trial registration ClinicalTrials.gov (NCT 04401800).

Abstract With the vigorous development of the energy Internet, all kinds of user information data are increasing day by day. How to comprehensively and deeply mine the effective information of users, develop a model to predict the behaviour characteristics of big data users, distinguish customer relationships, and provide an accurate basis for the next behaviour of users for various platforms have become one of the research hotspots of big data analysis of user behaviour. The data is sampled according to the feature vector of power user. The portrait mining of power user is conducted, and the user screening and analysis are conducted by using the measure of decision tree node purity in the model. The decision tree variable of the up–down stopping rule is generated. Then the results of the model and the Logistics model are tested and analysed, which can effectively predict the behaviour of power user. The proposed user strategy based on the characteristics of power consumption behaviour is analysed to verify the effectiveness of the scheme. The example shows that the model has a strong ability to distinguish and good stability than the traditional Logistics model, which can effectively predict the user's behaviour in advance, reduce user complaints, and help enterprises and users to form a long‐term mechanism of mutual benefit and reciprocity, which has a strong practical significance. This paper analyses the panorama of users through power big data technology and proposes a maturity model to evaluate the priority of users' electricity consumption. It emphasises the use of resources and methods provided in the power big data technology package to solve the practical problems of users' electricity consumption, and helps power companies to avoid market risks and improve service levels, which has strong practical significance.

Promoting the construction of Internet democratic politics in China requires an understanding of how multimodal connectedness can enhance citizens’ political participation. This study introduces the Orientations-Stimuli-Reasoning-Orientations-Responses (O-S-R-O-R) model, explaining the pathway from multimodal connectedness to political participation through “multimodal connectedness—political news attention/political news use—interpersonal political discussion—political trust—political participation.” Analyzing data from 2,379 participants in the context of Internet democratic politics, the study finds that the mediating variables fully mediate the relationship between multimodal connectedness and political participation. While political news attention promotes political participation, political trust has a significant negative impact. The study also compares the model across three age groups: young (18–29 years), middle-aged (30–39 years), and elderly (40–60 years). For the young and middle-aged groups, political news attention negatively impacts political participation, likely due to the fragmentation and distraction caused by real-time messages. Among the elderly, political trust negatively affects political participation, indicating a complex scenario where they are passionate about politics but lack adequate participation channels.

Background: Digital therapeutics (DTx) is an emerging and groundbreaking medical intervention that utilizes health software to treat or alleviate various diseases, disorders, conditions, or injuries. Although the potential of digital therapy is enormous, it is still in its nascent stage and faces multiple challenges and obstacles. The purpose of this study is to provide an overview of all DTx-related clinical trials in ClinicalTrials.gov and to promote the advancement of DTx. Methods: Two reviewers and one expert evaluated data from all DTx clinical trials on ClinicalTrials.gov as of August 8, 2023. Trials utilizing digital therapeutics independently or in combination with traditional approaches were included. Incomplete trials and those lacking an evidence-based foundation were excluded. Basic information about product launches and primary outcome measures was extracted and analyzed. Results: A total of 280 eligible trials were categorized into treating a disease (141, 50.4 %), managing a disease (120, 42.9 %), and improving a health function (19, 6.8 %). The focus was primarily on mental and behavioral disorders, neurological disorders, and endocrine, nutritional, and metabolic disorders. The number of trials has been increasing annually, yet trial design and conduct remain inconsistent. Randomized controlled trials (RCTs) accounted for 67.5 % of completed trials, and 36 trials (12.9 %) involved products already approved for marketing. Conclusions: The growth in clinical studies on DTx underscores their potential in healthcare. However, challenges persist in standardization, regulation, and clinical efficacy. There is a need for a harmonized global classification of digital therapeutics and standardized clinical trial protocols to ensure efficacy and improve healthcare services.

The community structure and ecological function of marine ecosystems are critically dependent on phytoplankton. However, our understanding of phytoplankton is limited due to the lack of detailed information on their morphology. To address this gap, we developed a framework that combines scanning electron microscopy (SEM) with photogrammetry to create realistic 3D (three-dimensional) models of phytoplankton. The workflow of this framework is demonstrated using two marine algal species, one dinoflagellate Prorocentrum micans and one diatom Halamphora sp. The resulting 3D models are made openly available and allow users to interact with phytoplankton and their complex structures virtually (digitally) and tangibly (3D printing). They also allow for surface area and biovolume calculations of phytoplankton, as well as the exploration of their light scattering properties, which are both important for ecosystem modeling. Additionally, by presenting these models to the public, it bridges the gap between scientific inquiry and education, promoting broader awareness on the importance of phytoplankton.

BackgroundOvertreatment design of clear aligner treatment (CAT) in extraction cases is currently primarily based on the clinical experience of orthodontists and is not supported by robust evidence on the underlying biomechanics. This study aimed to investigate the biomechanical effects of overtreatment strategies involving different maxillary anterior teeth intrusion patterns during anterior teeth retraction by CAT in extraction cases.Materials and methodsA finite element model of the maxillary dentition with the first premolar extracted was constructed. A loading method of clear aligners (CAs) based on the initial state field was proposed. The iterative method was used to simulate the long-term orthodontic tooth movement under the mechanical load exerted by the CAs. Three groups of CAs were utilized for anterior teeth retraction (G0: control group; G1: incisors intrusion group; G2: anterior teeth intrusion group). Tooth displacement and occlusal plane rotation tendency were analyzed.ResultsIn G0, CAT caused lingual tipping and extrusion of the incisors, distal tipping and extrusion of the canines, mesial tipping, and intrusion of the posterior teeth. In G1, the incisors showed minimal extrusion, whereas the canines showed increased extrusion and distal tipping tendency. G2 showed the smallest degree of posterior occlusal plane angle rotation, while the inclination tendency of the canines and second premolars decreased.Conclusion1. In CAT, tooth displacement tendency may change with increased wear time. 2. During anterior teeth retraction, the incisor intrusion pattern can provide effective vertical control for the lateral incisors but has little effect on the central incisors. Anterior teeth intrusion patterns can alleviate the inclination of canines and second premolars, resulting in partial relief of the roller-coaster effect.

Multiple parameter environment monitoring via wireless Internet of Thing sensors is growing rapidly, thanks to low power techniques of the node. More importantly, the ever more complex and highly efficient energy harvesting systems enable long-term continuous monitoring in inaccessible environments without needing to change the battery. This paper reviews existing energy harvesting modalities, including photovoltaic, piezoelectric, pyroelectric, electromagnetic, and vibration, together with circuit techniques of interfacing power management circuits for energy harvesters. Moreover, techniques used to interface with multiple mode energy harvesters to obtain a stable output power with optimal power efficiency are discussed as an emerging direction. The state-of-the-art energy harvesting systems together with future development trends are provided.

Abstract Objective: To quantify the full life cycle impacts of ultra-processed foods (UPF) for key environmental, economic and nutritional indicators to identify trade-offs between UPF contribution to broad-scope sustainability. Design: Using 24-h dietary recalls along with an input–output database for the Australian economy, dietary environmental and economic impacts were quantified in this national representative cross-sectional analysis. Food items were classified into non-UPF and UPF using the NOVA system, and dietary energy contribution from non-UPF and UPF fractions in diets was estimated. Thereafter, associations between nutritional, environmental and economic impacts of non-UPF and UPF fractions of diets were examined using a multi-dimensional nutritional geometry representation. Setting: National Nutrition and Physical Activity Survey 2011–2012 of Australia. Participants: Respondents (n 5344) aged > 18 years with 1 d of 24-h dietary recall data excluding respondents with missing values and outlier data points and under reporters. Results: Australian diets rich in UPF were associated with reduced nutritional quality, high greenhouse gas emissions, energy use, and increased employment and income associated with the food supply chains. The environmental and economic impacts associated with the UPF portion of diets become more distinct when the diets are standardised to average protein recommendation. Conclusion: Increased consumption of UPF has socio-economic benefits, but this comes with adverse effects on the environment and public health. Consideration of such trade-offs is important in identifying policy and other mechanisms regarding UPF for establishing healthy and sustainable food systems.

Xanthine oxidase (XOD) is a key enzyme that promotes the oxidation of xanthine/hypoxanthine to form uric acid, and the accumulation of uric acid leads to hyperuricaemia. The prevalence of gout caused by hyperuricaemia is increasing year by year. TAOZHI (TZ) can be used for the treatment of rheumatic arthralgia due to qi stagnation and blood stasis and contains a large number of polyphenolic components. The aim of this study was to investigate the relationship between chromatograms and XOD inhibition of 21 batches of TZ total polyphenol extract samples. Chemometric methods such as grey correlation analysis, bivariate correlation analysis, and partial least squares regression were used to identify the active ingredient groups in the total polyphenol extracts of TZ, which were validated using molecular docking techniques. The total polyphenol content contained in the 21 batches did not differ significantly, and all batches showed inhibitory effects on XOD. Spectroeffect correlation analysis showed that the inhibitory effect of TZ on XOD activity was the result of the synergistic effect of multiple components, and the active component groups screened to inhibit XOD were F2 (4-O-Caffeoylquinic acid), F4, and F10 (naringenin). The molecular docking results showed that the binding energies of all nine dockings were lower than −7.5 kcal/mol, and the binding modes included hydrogen bonding, hydrophobic forces, salt bridges, and π-staking, and the small molecules might exert their pharmacological effects by binding to XOD through the residue sites of the amino acids, such as threonine, arginine, and leucine. This study provides some theoretical basis for the development and utilisation of TZ total polyphenols.

Small extracellular vesicles (sEVs) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNAs (miRNAs) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cells-derived sEVs (AML-sEVs) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEVs. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEVs impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEVs-delivered miRNAs contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.

Abstract Recently developed enzymes for the depolymerization of polyethylene terephthalate (PET) such as FAST-PETase and LCC-ICCG are inhibited by the intermediate PET product mono(2-hydroxyethyl) terephthalate (MHET). Consequently, the conversion of PET enzymatically into its constituent monomers terephthalic acid (TPA) and ethylene glycol (EG) is inefficient. In this study, a protein scaffold (1TQH) corresponding to a thermophilic carboxylesterase (Est30) was selected from the structural database and redesigned in silico. Among designs, a double variant KL-MHETase (I171K/G130L) with a similar protein melting temperature (67.58 °C) to that of the PET hydrolase FAST-PETase (67.80 °C) exhibited a 67-fold higher activity for MHET hydrolysis than FAST-PETase. A fused dual enzyme system comprising KL-MHETase and FAST-PETase exhibited a 2.6-fold faster PET depolymerization rate than FAST-PETase alone. Synergy increased the yield of TPA by 1.64 fold, and its purity in the released aromatic products reached 99.5%. In large reaction systems with 100 g/L substrate concentrations, the dual enzyme system KL36F achieved over 90% PET depolymerization into monomers, demonstrating its potential applicability in the industrial recycling of PET plastics. Therefore, a dual enzyme system can greatly reduce the reaction and separation cost for sustainable enzymatic PET recycling.

Abstract In terms of pig farming, pig gut microbes have a significant effect on farmers and the farm environment. However, it is still unclear which microbial composition is more likely to contribute to this effect. This study collected a total of 136 samples, including pigs’ faeces samples, farmers’ faeces samples, samples from individuals who had no contact with any type of farm animal (referred to as ‘non-exposed’ persons), and environmental dust samples (collected from inside and outside pig houses and the farm) from two pig farms, pig farm A and pig farm B. Whereafter, 16S rRNA sequencing and taxonomic composition analysis were performed. According to the study, compared to non-exposed persons, pig farmers had a significantly higher abundance of 7 genera. In addition, the farmers were grouped according to the duration of their occupational exposure, and it was shown that 4 genera, including Turicibacter, Terrisporobacter, and Clostridium_sensu_stricto_1, exhibited a rise in more frequent contact with pigs. As compared to outside the pig house, the environmental dust has a greater concentration of the 3 bacteria mentioned before. Therefore, these 3 microbes can be considered as co-occurring microbes that may exist both in humans and the environment. Also, the 3 co-occurring microbes are involved in the fermentation and production of short-chain fatty acids and their effectiveness decreased as distance from the farm increased. This study shows that the 3 microbes where pig farmers co-occur with the environment come from pig farms, which provides fresh ideas for preventing the spread of microbial aerosols in pig farms and reducing pollution.

We examined Chinese stonefly specimens of the Rhopalopsole vietnamica ‘western assemblage’ group. A new species from Hainan Province, R. bawanglinga Li, Li & Yang, sp. nov. is described and illustrated from male and female adults, and it is compared to closely related taxa. The hitherto unknown female of R. hainana Li & Yang, 2010 is described. Morphological evidence is presented for the identity of R. dentiloba Wu, 1973, on the basis of topotypes from Yunnan Province, southwestern China.

Abstract Olfactory dysfunction represents a prodromal stage in Parkinson’s disease (PD). However, the mechanisms underlying hyposmia are not specified yet. In this study, we first observed an early olfactory dysfunction in mice with intragastric rotenone administration, consistent with dopaminergic neurons loss and α-synuclein pathology in the olfactory bulb. However, a much severer olfactory dysfunction was observed without severer pathology in olfactory bulb when the loss of dopaminergic neurons in the substantia nigra occurred. Then, we established the mice models by intrastriatal α-synuclein preformed fibrils injection and demonstrated the performance in the olfactory discrimination test was correlated to the loss of dopaminergic neurons in the substantia nigra, without any changes in the olfactory bulb analyzed by RNA-sequence. In mice with intranasal ferric ammonium citrate administration, we observed olfactory dysfunction when dopaminergic neurodegeneration in substantia nigra occurred and was restored when dopaminergic neurons were rescued. Finally we demonstrated that chemogenetic inhibition of dopaminergic neurons in the substantia nigra was sufficient to cause hyposmia and motor incoordination. Taken together, this study shows a direct relationship between nigral dopaminergic neurodegeneration and olfactory dysfunction in PD models and put forward the understandings that olfactory dysfunction represents the early stage of neurodegeneration in PD progression.

Abstract The burgeoning field of digital humanities has provided important modern technological means for text mining in literary works. Chinese classical poetry, as a treasure in the world’s artistic treasury, holds significant value in recognizing the heritage of world culture. In this study, taking the 1589 Tang poems from the Tang Poetry Road in Eastern Zhejiang as an example, we constructed a research framework that explores the aesthetics of classical Chinese poetry landscapes and spatial imagery at the urban agglomeration scale by utilizing geographic and analytical tools such as Python programming, Gephi co-occurrence semantic networks, and GIS kernel density analysis. The framework exhibits three key innovations: (1) a text processing approach that treats individual characters as semantic units in ancient poetry texts, (2) a combined approach of Python programming techniques and Gephi visualization tool for social network analysis, and (3) a study focusing on the integration of textual and spatial aspects of literary landscape heritage corridors at the urban cluster scale. The constructed framework greatly enhances the efficiency and accuracy of Tang poetry text mining, it enables the extraction of natural and cultural landscape spatial imagery along the Tang Poetry Road, the construction of scene depictions, the identification of key regions within the scenes, and the derivation of location-specific strategies. This study broadens the scope of exploring the cultural heritage value of Tang poetry literature and provides practical guidance for the development of cross-regional heritage corridors.

The objectives of this study were to optimize the ultrasonic-assisted flavonoid extraction process from PR and to establish fingerprints in order to analyze the spectrum–effect relationship of antioxidant activity. The ultrasonic-assisted flavonoid extraction process from PR was optimized using RSM, and the fingerprints of twenty-eight batches of flavonoids from PR were established using UHPLC. Meanwhile, the in vitro antioxidant activity of PR was evaluated in DPPH and ABTS free radical-scavenging experiments. Then, the peaks of the effective antioxidant components were screened using the spectrum–effect relationships. The results show that the optimal extraction yield of flavonoids from PR was 3.24 ± 0.01 mg/g when using 53% ethanol, a 1:26 (g/mL) solid–liquid ratio, and 60 min of ultrasonic extraction. Additionally, the clearance of two antioxidant indices by the flavonoids extracted from PR had different degrees of correlation and showed concentration dependence. Simultaneously, the similarity of the UHPLC fingerprints of twenty-eight batches of PR samples ranged from 0.801 to 0.949, and four characteristic peaks, namely peaks 4, 12, 21, and 24, were screened as the peaks of the components responsible for the antioxidant effect of PR using a GRA, a Pearson correlation analysis, and a PLS-DA. In this study, characteristic peaks of the antioxidant effects of PR were screened in an investigation of the spectrum–effect relationship to provide a scientific basis for the study of pharmacodynamic substances and the elucidation of the mechanism of action of the antioxidant effect of PR.

The robust carbon storage (CS) capacity of terrestrial ecosystems is crucial in mitigating climate change and holds indispensable significance for global sustainable development. The diverse topography of Central Asia (CA), comprising oases, grasslands, forests, deserts, and glaciers, has fostered industries like animal husbandry, irrigation agriculture, and mining. However, the fragile arid ecosystems of CA render it highly sensitive to climate change and human activities, with their impact on the sustainable development of multifunctional landscapes in this region remaining ambiguous in the future. This study linked land use changes with multiple socio-economic and ecological indicators to predict the dynamics of land use and changes in CS in CA. The findings reveal a significant spatial heterogeneity in CS, with considerable variations among five countries driven by differences in landscape composition. Kyrgyzstan and Kazakhstan, characterized by grasslands, demonstrate higher CS per unit area, whereas Turkmenistan, dominated by barren land, exhibits the lowest CS per unit area. Strategies involving innovative development and improved biodiversity conservation have proven effective in augmenting CS. Meanwhile, high economic and population growth stimulates the expansion of cropland and urban land, reducing the CS capacity of ecosystems. This study contributes to a more precise assessment of CS dynamics in CA. Furthermore, by elucidating the interrelationships between future socio-economic development and environmental conservation in CA, it offers solutions for enhancing the conservation of multifunctional landscapes in CA.

ObjectiveTo examine the utilization of and satisfaction to physical examination – one of items in basic public health services among community elderly in eastern, central and western China. Methods With stratified multi-stage random sampling and a self-designed questionnaire, an onsite interviewer-assisted self-administered survey was conducted among 3 334 elderly attendees (aged 65 years and above) of 20 primary medical institutions during November – December 2019 in eastern, central and western China (Zhejiang province, Shanxi province and Chongqing municipality). Results Of the 3 213 participants with eligible responses, 3 008 (93.6%) reported ever taking physical examination free of charge at community health service centers or township health centers during past one year. Among the 3 008 participants receiving the physical examination, 2 247 (74.7%) expressed the satisfaction to the check-up items of the physical examination. In terms of expected improvements for the physical examination, inclusion of more check up items was suggested by 49.6% of the participants, followed by increasing the frequency of physical examination, providing a more detailed physical examination report, and timely notification of the physical examination results which were suggested by 15.1%, 14.9%, and 12.3% of the participants, respectively. Conclusion The utilization ratio of national basic public health services-based physical examination is high among community elderly in China but items and service processes of the physical examination still need to be improved.

Systemic acquired resistance (SAR) is an inducible disease resistance phenomenon in plant species, providing plants with broad-spectrum resistance to secondary pathogen infections beyond the initial infection site. In Arabidopsis, SAR can be triggered by direct pathogen infection or treatment with the phytohormone salicylic acid (SA), as well as its analogues 2,6-dichloroisonicotinic acid (INA) and benzothiadiazole (BTH). The SA receptor non-expressor of pathogenesis-related protein gene 1 (NPR1) protein serves as a key regulator in controlling SAR signaling transduction. Similarly, in common wheat (Triticum aestivum), pathogen infection or treatment with the SA analogue BTH can induce broad-spectrum resistance to powdery mildew, leaf rust, Fusarium head blight, and other diseases. However, unlike SAR in the model plant Arabidopsis or rice, SAR-like responses in wheat exhibit unique features and regulatory pathways. The acquired resistance (AR) induced by the model pathogen Pseudomonas syringae pv. tomato strain DC3000 is regulated by NPR1, but its effects are limited to the adjacent region of the same leaf and not systemic. On the other hand, the systemic immunity (SI) triggered by Xanthomonas translucens pv. cerealis (Xtc) or Pseudomonas syringae pv. japonica (Psj) is not controlled by NPR1 or SA, but rather closely associated with jasmonate (JA), abscisic acid (ABA), and several transcription factors. Furthermore, the BTH-induced resistance (BIR) partially depends on NPR1 activation, leading to a broader and stronger plant defense response. This paper provides a systematic review of the research progress on SAR in wheat, emphasizes the key regulatory role of NPR1 in wheat SAR, and summarizes the potential of pathogenesis-related protein (PR) genes in genetically modifying wheat to enhance broad-spectrum disease resistance. This review lays an important foundation for further analyzing the molecular mechanism of SAR and genetically improving broad-spectrum disease resistance in wheat.

This research applies a perceived affordance approach to examine the distinctive role of social media technologies in shaping (mis)perceptions of political polarization. We argue that users’ perceptions of platform affordances influence both (a) their self-participation in uncivil political discussion on social media and (b) perceptions of others’ engagement, which eventually shape their perceptions of polarization. Our analysis of US survey data found that perceptions of lower privacy and stronger network association on Facebook are related to perceptions of a higher level of uncivil discussion by other users, which in turn predicts greater perceived polarization. Perceptions of higher anonymity relate to higher self-participation in uncivil discussion, which is surprisingly associated with perceptions of reduced polarization. Our follow-up experimental study illustrated that participants with more frequent engagement in uncivil discussion, irrespective of interacting with civil or uncivil comments, showed consistently higher levels of intrapersonal reflection, which reduces perceived polarization.

In the present scenario, Distributed Energy Resources (DERs) are included into power grid distribution networks to withstand power outages. Restoration is a smart and efficient method for self-healing systems to maintain functionality and re-configure themselves in response to outside breakdowns or attacks. Intelligent decision making framework is required for ensuring that the system as a whole survives external breakdowns and attacks by autonomously reconfiguring itself. Further, the power grid faces serious security concerns, network congestion delay, and packet loss due to improper grid adjustments. As a result, in this research Edge computing assisted Intelligent Decision Model (EC-IDM) has been proposed to address the issue of breakdowns and attacks in real time. The emergence of edge computing has substantially improved the smart grid's ability to operate effectively and communicate effectively by reducing the effects of security concerns, packet loss, latency, and overloaded networks. The integration Smart Grid's peripheral index (SSGPI) optimizes the system's performance and operating efficiency. This research presents a real-time EC-IDM for fixing the electricity grid that can automatically develop the restoration plan and identify the blackout scenario. For restoration choices across several time-and-space axes in EC-IDM, an improved hierarchical coordination technique and a local object optimization method are integrated to optimize breakdowns and attacks in real time. EC-IDM utilizes Smart grid self-healing using distributed automation (DA) to address issues of dependability and reliability of power. The simulation results demonstrates that the suggested approach achieves best in security concerns, optimizes network congestion delay, and packet loss security, improves efficiency and performance compared to the other conventional methods.

The purpose of this work was to use integrated bioinformatics analysis to screen for pyroptosis-related genes (PRGs) and possible immunological phenotypes linked to the development and course of IPF. Transcriptome sequencing datasets GSE70866, GSE47460 and GSE150910 were obtained from GEO database. From the GSE70866 database, 34 PRGs with differential expression were found in IPF as compared to healthy controls. In addition, a diagnostic model containing 4 genes PRGs (CAMP, MKI67, TCEA3 and USP24) was constructed based on LASSO logistic regression. The diagnostic model showed good predictive ability to differentiate between IPF and healthy, with ROC-AUC ranging from 0.910 to 0.997 in GSE70866 and GSE150910 datasets. Moreover, based on a combined cohort of the Freiburg and the Siena cohorts from GSE70866 dataset, we identified ten PRGs that might predict prognosis for IPF. We constructed a prognostic model that included eight PRGs (CLEC5A, TREM2, MMP1, IRF2, SEZ6L2, ADORA3, NOS2, USP24) by LASSO Cox regression and validated it in the Leuven cohort. The risk model divided IPF patients from the combined cohort into high-risk and low-risk subgroups. There were significant differences between the two subgroups in terms of IPF survival and GAP stage. There is a close correlation between leukocyte migration, plasma membrane junction, and poor prognosis in a high-risk subgroup. Furthermore, a high-risk score was associated with more plasma cells, activated NK cells, monocytes, and activated mast cells. Additionally, we identified HDAC inhibitors in the cMAP database that might be therapeutic for IPF. To summarize, pyroptosis and its underlying immunological features are to blame for the onset and progression of IPF. PRG-based predictive models and drugs may offer new treatment options for IPF.

The application of compressed sensing (CS)-enabled data reconstruction for accelerating magnetic resonance imaging (MRI) remains a challenging problem. This is due to the fact that the information lost in k-space from the acceleration mask makes it difficult to reconstruct an image similar to the quality of a fully sampled image. Multiple deep learning-based structures have been proposed for MRI reconstruction using CS, in both the k-space and image domains, and using unrolled optimization methods. However, the drawback of these structures is that they are not fully utilizing the information from both domains (k-space and image). Herein, we propose a deep learning-based attention hybrid variational network that performs learning in both the k-space and image domains. We evaluate our method on a well-known open-source MRI dataset (652 brain cases and 1172 knee cases) and a clinical MRI dataset of 243 patients diagnosed with strokes from our institution to demonstrate the performance of our network. Our model achieves an overall peak signal-to-noise ratio/structural similarity of 40.92 ± 0.29/0.9577 ± 0.0025 (fourfold) and 37.03 ± 0.25/0.9365 ± 0.0029 (eightfold) for the brain dataset, 31.09 ± 0.25/0.6901 ± 0.0094 (fourfold) and 29.49 ± 0.22/0.6197 ± 0.0106 (eightfold) for the knee dataset, and 36.32 ± 0.16/0.9199 ± 0.0029 (20-fold) and 33.70 ± 0.15/0.8882 ± 0.0035 (30-fold) for the stroke dataset. In addition to quantitative evaluation, we undertook a blinded comparison of image quality across networks performed by a subspecialty trained radiologist. Overall, we demonstrate that our network achieves a superior performance among others under multiple reconstruction tasks.

Abstract Global agricultural trade creates multiple telecoupled flows of nitrogen (N) and phosphorus (P). The flows of physical and virtual nutrients along with trade have discrepant effects on natural resources in different countries. However, existing literature has not quantified or analyzed such effects yet. Here we quantified the physical and virtual N and P flows embedded in the global agricultural trade networks from 1997 to 2016 and elaborated components of the telecoupling framework. The N and P flows both increased continuously and more than 25% of global consumption of nutrients in agricultural products were related to physical nutrient flows, while virtual nutrient flows were equivalent to one-third of the nutrients inputs into global agricultural system. These flows have positive telecoupling effects on saving N and P resources at the global scale. Reducing inefficient trade flows will enhance resource conservation, environmental sustainability in the hyper-globalized world.

Numerous polysaccharides isolated from plants have been used to augment traditional drugs in the treatment of cancer. In order to explore the influence to hepatocellular carcinoma, a novel cold water-soluble polysaccharide was separated from Rhodiola rosea L. root (RLP) and then its structure and anti-cancer activities were tested. The chemical compositions and high performance gel permeation chromatography (HPGPC) results indicated that RLP was an acid heteropolysaccharide with the molecular weight of about 1.15×106 Da. Furthermore, ion chromatography (IC), Fourier transform infrared (FT-IR) and nuclear magnetic resoance (NMR) further indicated that RLP was main composed of →2,4)-α-Rha(1→, →5)-α-L-Araf-(1→, α-D-Glu, →6)-β-D-Galp-(1→, β-D-Man and →4)-α-GalpA-(1→. In vivo antitumor activities of RLP were carried out by using H22 tumor-bearing mice model. The results shown that RLP (100 and 300 mg/kg) could inhibit tumor growth of H22 cells from 23.59 % to 45.52 % and protect thymuses and spleen without damage. In addition, according to cell cycle, AV-FITC/PI and JC-1, RLP could induce dose-dependent apoptosis of H22 cells via S phase arrested which was through a mitochondrial related pathway. Our data indicated that RLP has a broader application prospect in anti-tumor preparations.

Here, 0.3 wt.%Zr was introduced in an Al-4 wt.%Cu-0.5 wt.%Mn-0.1 wt.%Fe alloy to investigate its influence on the microstructure and mechanical properties of the alloy. The microstructures of both as-cast and T6-treated Al–Cu–Mn–Fe (ACMF) and Al–Cu–Mn–Fe–Zr (ACMFZ) alloys were analyzed. The intermetallic compounds formed through the casting procedure include Al2Cu and Al7Cu2Fe, and the Al2Cu phase dissolves into the matrix and re-precipitates as θ′ phase during the T6 process. The introduction of Zr results in the precipitation of L12-Al3Zr nanometric precipitates after T6, while the θ′ precipitates in ACMFZ alloy are much finer than those in ACMF alloy. The L12-Al3Zr precipitates were found coherently located with θ′, which was assumed beneficial for stabilizing the θ′ precipitates during the high-temperature tensile process. The tensile properties of ACMF and ACMFZ alloys at room temperature and elevated temperatures (200, 300, and 400 °C) were tested. Especially, the yield strength of ACMFZ alloys can reach 128 MPa and 65 MPa at 300 °C and 400 °C, respectively, which are 31% and 33% higher than those of ACMF alloys. The strengthening mechanisms of grain size, L12-Al3Zr, and θ′ precipitates on the tensile properties were discussed. This work may be referred to for designing Al–Cu alloys for application in high-temperature fields.

Fusarium crown rot (FCR), primarily caused by Fusarium pseudograminearum, has emerged as a new threat to wheat production and quality in North China. Genetic enhancement of wheat resistance to FCR remains the most effective approach for disease control. In this study, we phenotyped 435 Chinese wheat cultivars through FCR inoculation at the seedling stage in a greenhouse. Our findings revealed that only approximately 10.8% of the wheat germplasms displayed moderate or high resistance to FCR. A genome-wide association study (GWAS) using high-density 660K SNP led to the discovery of a novel quantitative trait locus on the long arm of chromosome 3B, designated as Qfcr.hebau-3BL. A total of 12 significantly associated SNPs were closely clustered within a 1.05 Mb physical interval. SNP-based molecular markers were developed to facilitate the practical application of Qfcr.hebau-3BL. Among the five candidate FCR resistance genes within the Qfcr.hebau-3BL, we focused on TraesCS3B02G307700, which encodes a protein kinase, due to its expression pattern. Functional validation revealed two transcripts, TaSTK1.1 and TaSTK1.2, with opposing roles in plant resistance to fungal disease. These findings provide insights into the genetic basis of FCR resistance in wheat and offer valuable resources for breeding resistant varieties.

A series of chromone-thiazolidine-2,4-dione derivatives (e1 ∼ 28) were synthesized and screened for their α-glucosidase inhibitory. All synthetic derivatives presented excellent α-glucosidase inhibitory with IC50 values ranging from 2.40 ± 0.11 to 5.66 ± 0.15 μM, comparing to positive control acarbose (IC50 value: 640.57 ± 5.13 μM). Among them, compound e28 displayed the strongest α-glucosidase inhibitory (IC50 value: 2.40 ± 0.11), ∼267 times stronger than positive control acarbose. Kinetic studies revealed that compound e28 was a reversible non-competitive inhibitor. CD spectra and 3D fluorescence spectra results explained that compound e28 changed the conformational changes of α-glucosidase. Molecular docking simulated the binding between compound e28 and α-glucosidase. In vitro cytotoxicity assay ascertained the good security of e28.

Thermally stable proteins find extensive applications in industrial production, pharmaceutical development, and serve as a highly evolved starting point in protein engineering. The thermal stability of proteins is commonly characterized by their melting temperature (Tm). However, due to the limited availability of experimentally determined Tm data and the insufficient accuracy of existing computational methods in predicting Tm, there is an urgent need for a computational approach to accurately forecast the Tm values of thermophilic proteins. Here, we present a deep learning-based model, called DeepTM, which exclusively utilizes protein sequences as input and accurately predicts the Tm values of target thermophilic proteins on a dataset consisting of 7790 thermophilic protein entries. On a test set of 1550 samples, DeepTM demonstrates excellent performance with a coefficient of determination (R2) of 0.75, Pearson correlation coefficient (P) of 0.87, and root mean square error (RMSE) of 6.24 ℃. We further analyzed the sequence features that determine the thermal stability of thermophilic proteins and found that dipeptide frequency, optimal growth temperature (OGT) of the host organisms, and the evolutionary information of the protein significantly affect its melting temperature. We compared the performance of DeepTM with recently reported methods, ProTstab2 and DeepSTABp, in predicting the Tm values on two blind test datasets. One dataset comprised 22 PET plastic-degrading enzymes, while the other included 29 thermally stable proteins of broader classification. In the PET plastic-degrading enzyme dataset, DeepTM achieved RMSE of 8.25 ℃. Compared to ProTstab2 (20.05 ℃) and DeepSTABp (20.97 ℃), DeepTM demonstrated a reduction in RMSE of 58.85% and 60.66%, respectively. In the dataset of thermally stable proteins, DeepTM (RMSE=7.66 ℃) demonstrated a 51.73% reduction in RMSE compared to ProTstab2 (RMSE=15.87 ℃). DeepTM, with the sole requirement of protein sequence information, accurately predicts the melting temperature and achieves a fully end-to-end prediction process, thus providing enhanced convenience and expediency for further protein engineering.

Constructing reliable and effective models to recognize human emotional states has become an important issue in recent years. In this article, we propose a double way deep residual neural network combined with brain network analysis, which enables the classification of multiple emotional states. To begin with, we transform the emotional EEG signals into five frequency bands by wavelet transform and construct brain networks by inter-channel correlation coefficients. These brain networks are then fed into a subsequent deep neural network block which contains several modules with residual connection and enhanced by channel attention mechanism and spatial attention mechanism. In the second way of the model, we feed the emotional EEG signals directly into another deep neural network block to extract temporal features. At the end of the two ways, the features are concatenated for classification. To verify the effectiveness of our proposed model, we carried out a series of experiments to collect emotional EEG from eight subjects. The average accuracy of the proposed model on our emotional dataset is 94.57%. In addition, the evaluation results on public databases SEED and SEED-IV are 94.55% and 78.91%, respectively, demonstrating the superiority of our model in emotion recognition tasks.

China, Germany and UK were the largest net importers of pesticide hazard loads embodied in commodities in 2015, while the USA, Brazil and Spain were the largest net exporters, according to a top-down multi-region input-output analysis of footprints for 82 countries and territories.

Abstract Formate can be synthesized electrochemically by CO2 reduction reaction (CO2RR) or formaldehyde oxidation reaction (FOR). The CO2RR approach suffers from kinetic-sluggish oxygen evolution reaction at the anode. To this end, an electrochemical system combining cathodic CO2RR with anodic FOR was developed, which enables the formate electrosynthesis at ultra-low voltage. Cathodic CO2RR employing the BiOCl electrode in H-cell exhibited formate Faradaic efficiency (FE) higher than 90% within a wide potential range from − 0.48 to − 1.32 V RHE. In flow cell, the current density of 100 mA cm−2 was achieved at − 0.67 V RHE. The anodic FOR using the Cu2O electrode displayed a low onset potential of − 0.13 V RHE and nearly 100% formate and H2 selectivity from 0.05 to 0.35 V RHE. The CO2RR and FOR were constructed in a flow cell through membrane electrode assembly for the electrosynthesis of formate, where the CO2RR//FOR delivered an enhanced current density of 100 mA cm−2 at 0.86 V. This work provides a promising pair-electrosynthesis of value-added chemicals with high FE and low energy consumption.

Drinking groundwater contamination by pathogenic viruses represents a serious risk to worldwide public health, particularly for enteric viruses, which exhibit high prevalence and occurrence during outbreaks. Understanding how enteric viruses adsorb in groundwater is essential to protecting human health and ensuring the sustainable use of water resources. The adsorption properties of Coxsackievirus A16 (CA16), a common gastrointestinal virus that spreads through groundwater, were investigated in this work. A typical batch equilibrium approach was used to investigate CA16 adsorption and factors that influence it. In a laboratory recognized nationally as a biosafety level 2 facility, stringent research protocols were followed to guarantee compliance with experimental standards. The variables that were investigated included the size of the sediment particles, the starting concentration of the virus, temperature, pH level, and humic acid content. The findings showed that the CA16 virus was more strongly attracted to finer sediment particles and that its adsorption increased as the size of the sediment particle decreased. Furthermore, it was discovered that higher temperatures improved the CA16 virus’s ability to bind to sediment particles. The pH of the aqueous environment has a significant effect on the effectiveness of virus adsorption; higher effectiveness was seen in acidic environments. Furthermore, it was found that the presence of humic acid decreased the ability of clay to adsorb CA16, suggesting that humic acid has a detrimental influence on clay’s ability to adsorb viruses. The examination of kinetic models demonstrated that, in every scenario examined, the adsorption process of CA16 adhered to the pseudo-second-order kinetics model. Additionally, the Langmuir and Freundlich isotherm models were used to assess the equilibrium data that were collected in this investigation. The outcomes amply proved that the most accurate representation of the adsorption equilibrium was given by the Langmuir isotherm model. The study offered a solid scientific foundation for treating groundwater and creating plans to stop the spread of viruses.

PurposeTo investigate retinal vascular changes in patients with diabetic retinopathy (DR) using the newly developed ultrawide rapid scanning swept-source optical coherence tomography angiography (SS-OCTA) device.MethodsThis cross-sectional, observational study enrolled 24 patients (47 eyes) with DR, 45 patients (87 eyes) with diabetes mellitus (DM) without DR, and 36 control subjects (71 eyes). All subjects underwent 24 × 20 mm SS-OCTA examination. Vascular density (VD) and the thickness of the central macula (CM; 1 mm diameter) and temporal fan-shaped areas of 1–3 mm (T3), 3–6 mm (T6), 6–11 mm (T11), 11–16 mm (T16), and 16–21 mm (T21) were compared among groups. The VD and the thicknesses of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed separately. The predictive values of VD and thickness changes in DM and DR patients were evaluated by receiver operating characteristic (ROC) curve analysis.ResultsThe average VDs of the SVC in the CM and the T3, T6, T11, T16, and T21 areas were significantly lower in the DR than in the control group, whereas only the average VD of the SVC in the T21 area was significantly lower in the DM group. The average VD of the DVC in the CM was significantly increased in the DR group, whereas the average VDs of the DVC in the CM and T21 area were significantly decreased in the DM group. Evaluation of the DR group showed significant increases in the thicknesses of SVC-nourishing segments in the CM and T3, T6, and T11 areas and significant increases in the thicknesses of DVC-nourishing segments in the CM and T3 and T6 areas. In contrast, none of these parameters showed significant changes in the DM group. ROC curve analysis showed that the average VD of the SVC in the CM, T3, and T21 had better ability to predict DR, with areas under the ROC curves (AUCs) of 0.8608, 0.8505, and 0.8353, respectively. The average VD of the DVC in the CM was also predictive of DR, with an AUC of 0.8407.ConclusionsThe newly developed ultrawide SS-OCTA device was better able to reveal early peripheral retinal vascular changes than traditional devices.

Senescence of bone marrow mesenchymal stem cells (BMMSCs) induced by chronic oxidative stress is an important factor contributes to the postmenopausal osteoporosis (PMOP). Mitochondrial quality control takes a pivotal role in regulating oxidative stress and cell senescence. Genistein is a major isoflavone in soy products, which is best known for its ability to inhibit bone loss in both postmenopausal women and ovariectomized (OVX) rodents. Here we show that OVX-BMMSCs displayed premature senescence, elevated reactive oxygen species (ROS) level and mitochondria dysfunction, while genistein rescued these phenotypes. Using network pharmacology and molecular docking, we identified estrogen-related receptor α (ERRα) as the potential target of genistein. Knockdown of ERRα greatly abolished the anti-senescence effect of genistein on OVX-BMMSCs. Further, the mitochondrial biogenesis and mitophagy induced by genistein were inhibited by ERRα knockdown in OVX-BMMSCs. In vivo, genistein inhibited trabecular bone loss and p16INK4a expression, upregulated sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor gamma coactivator one alpha (PGC1α) expression in the trabecular bone area of proximal tibia in OVX rats. Together, this study revealed that genistein ameliorates senescence of OVX-BMMSCs through ERRα-mediated mitochondrial biogenesis and mitophagy, which provided a molecular basis for advancement and development of therapeutic strategies against PMOP.

ABSTRACT: The objective of this study was to investigate whether dietary supplementation with benzoic acid, Enterococcus faecium, and essential oil complex (BEC) could help laying hens recover from coccidia and Clostridium perfringens type A challenge. A total of 60 (35-wk-old) Lohmann-laying hens were randomly assigned to 3 experimental groups (10 replicates with 2 hens per replicate): I) control group (CON), II) challenge group (CC), and III) BEC group (2,000 mg/kg BEC). The total experimental period was 8 wk. The results shown that the challenge layers had lower egg-laying rate and average daily feed intake (ADFI) (P < 0.05), and addition of BEC after challenge increased egg-laying rate (P < 0.05). The content of propionic acid (PA) and butyric acid (BA) in short-chain fatty acid (SCFA) was significantly decreased by challenge (P < 0.05). CC and BEC groups had lower villus height to crypt depth ratio (V/C) and higher pathological scores in duodenum (P < 0.05), whereas the BEC group had lower pathological scores in jejunum when compared with the CC group (P < 0.05). The challenge increased the concentration of proinflammatory cytokines (IL-1β and IL-6) (P < 0.05). An increase in the abundance of Bacteroidoes (genus), Bacteroidaceae (family), Bacteroidoes sp. Marseille P3166 (species), Bacteroidoes caecicola (species) was observed in the CC group, whereas the BEC group had higher abundance of Bacteroides caecigallinarum (species). The genera Faecalibacterium and Asterolplasma were positively correlated with egg-laying rate (r = 0.57, 0.60; P < 0.01); and the genera Bacteroides and Romboutsia were negatively correlated with egg-laying rate (r = −0.58, −0.74; P < 0.01). The genera Bacteroides, Lactobacillus, and Rombutzia were positively correlated with jejunal mucosa proinflammatory factor IL-1β level (r = 0.61, 0.60, 0.59; P < 0.01), which were negatively correlated with genera Rikenbacteriaceae RC9, Faecalibacterium, and Olsenlla (r = −0.56, −0.57, −0.61; P < 0.01). There genera UCG.005 was positively correlated with proinflammatory factor IL-6 level in jejunal mucosa (r = 0.58; P < 0.01), which was negatively correlated with Rikenbacteriaceae RC9 (r = −0.62; P < 0.01). The experiment results revealed that the addition of BEC to the diet restored the production performance of the laying hens. In addition, supplementation of 2,000 mg/kg BEC modulated gut health by reducing gut damage scores and modulating microbial composition, thereby promoting recovery of laying hens after coccidia and Clostridium perfringens challenge.

Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear.Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil.Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model.Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect.Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.

Actin cytoskeleton plays crucial roles in various cellular functions. Extracellular matrix (ECM) can modulate cell morphology by remodeling the internal cytoskeleton. To define how geometry of ECM regulates the organization of actin cytoskeleton, we plated individual NIH 3T3 cells on micropatterned substrates with distinct shapes and sizes. It was found that the stress fibers could form along the nonadhesive edges of T-shaped pattern, but were absent from the opening edge of V-shaped pattern, indicating that the organization of actin cytoskeleton was dependent on the mechanical environment. Furthermore, a secondary actin ring was observed on 50[Formula: see text][Formula: see text]m circular pattern while did not appear on 30[Formula: see text][Formula: see text]m and 40[Formula: see text][Formula: see text]m pattern, showing a size-dependent organization of actin cytoskeleton. Finally, osteoblasts, MDCK and A549 cells exhibited distinct organization of actin cytoskeleton on T-shaped pattern, suggesting a cell-type specificity in arrangement of actin cytoskeleton. Together, our findings brought novel insight into the organization of actin cytoskeleton on micropatterned environments.

Abstract Introduction Blood–brain barrier (BBB) dysfunction may occur at the onset of Alzheimer’s disease (AD). Pericytes are a vital part of the neurovascular unit and the BBB, acting as gatekeepers of the BBB. Amyloid β (Aβ) deposition and neurofibrillary tangles in the brain are the central pathological features of AD. CD36 promotes vascular amyloid deposition and leads to vascular brain damage, neurovascular dysfunction, and cognitive deficits. However, the molecular mechanism by which pericytes of the BBB are disrupted remains unclear. Objectives To investigate the effect of low-dose Aβ1-40 administration on pericyte outcome and the molecular mechanism of BBB injury. Methods We selected 6-month-old and 9-month-old APP/PS1 mice and wild-type (WT) mice of the same strain, age, and sex as controls. We assessed the BBB using PET/CT. Brain pericytes were extracted and cocultured with endothelial cells (bEnd.3) to generate an in vitro BBB model to observe the effect of Aβ1-40 on the BBB. Furthermore, we explored the intracellular degradation and related molecular mechanisms of Aβ1-40 in cells. Results BBB permeability and the number of pericytes decreased in APP/PS1 mice. Aβ1-40 increased BBB permeability in an in vivo model and downregulated the expression of CD36, which reversed the Aβ-induced changes in BBB permeability. Aβ1-40 was uptaked in pericytes with high CD36 expression. We observed that this molecule inhibited pericyte proliferation, caused mitochondrial damage, and increased mitophagy. Finally, we confirmed that Aβ1-40 induced pericyte mitophagy-dependent ferroptosis through the CD36/PINK1/Parkin pathway. Conclusion PDGFRβ (a marker of pericytes), CD36, and Aβ colocalized in vitro and in vivo, and Aβ1-40 caused BBB disruption by upregulating CD36 expression in pericytes. The mechanism by which Aβ1-40 destroys the BBB involves the induction of pericyte mitophagy-dependent ferroptosis through the CD36/PINK1/Parkin pathway.

In this paper, a numerical method is employed to assess tidal current energy resources in the Pearl River Estuary, China. The numerical model for tidal current simulation in the estuary is developed based on the MIKE 21 model, which enables numerical simulations in estuaries, coastal areas, and oceans. The model has a grid resolution that varies from about 2500 m at the open boundary to 500–1000 m inside the estuary. Extensive model validation is performed by comparing the model predictions with field observations of tidal level and velocity at various stations in the Pearl River Estuary. The tidal characteristics are thoroughly analyzed. Energy fluxes and power densities are calculated along selected cross sections to evaluate the feasibility of tidal energy development in the Pearl River Estuary. The results indicate that the distribution of annual average tidal current power density in the Pearl River Estuary generally aligns with the spatial distribution of tidal currents. The annual average power density of tidal energy is typically below 0.10 kW/m2. The theoretical potential of tidal current energy resources in the Pearl River Estuary is assessed to be approximately 11,000 kW.

Geometric errors are the main factors affecting the output accuracy of the parallel spindle head, and it is necessary to perform a sensitivity analysis to extract the critical geometric errors. The traditional sensitivity analysis method analyzes the output position and orientation errors independently, defining multiple sensitivity indices and making it difficult to determine critical geometric errors. In this paper, we propose sensitivity indices that can comprehensively consider position and orientation errors. First, the configuration of the hybrid machine tool is introduced, and the TCP position error model is derived. Then, the tool radius and the effective cutting length are introduced, and the sensitivity indices are defined. After that, the sensitivity analysis of the 3-DOF parallel spindle head is performed using the proposed sensitivity indices, and six critical geometric errors are extracted. The machining accuracy of the parallel spindle head can be greatly improved by improving the critical geometric errors. The proposed sensitivity analysis method can provide important guidance for machine tool accuracy design.

IntroductionThe study aimed to determine the effect of the scanning area used for high-speed ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA) on the detection rate of diabetic retinopathy (DR) lesions.MethodsThis prospective, observational study involved diabetic patients between October 2021 and April 2022. The participants underwent a comprehensive ophthalmic examination and high-speed ultra-widefield SS-OCTA using a 24 mm × 20 mm scanning protocol. A central area denoted as “12 mm × 12 mm-central” was extracted from the 24 mm × 20 mm image, and the remaining area was denoted as “12 mm~24mm-annulus.” The rates of detection of DR lesions using the two scanning areas were recorded and compared.ResultsIn total, 172 eyes (41 eyes with diabetes mellitus without DR, 40 eyes with mild to moderate non-proliferative diabetic retinopathy (NPDR), 51 eyes with severe NPDR, and 40 eyes with proliferative diabetic retinopathy (PDR) from 101 participants were included. The detection rates of microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), and neovascularization (NV) for the 12 mm × 12 mm central and 24 mm × 20 mm images were comparable (p > 0.05). The detection rate of NPAs for the 24 mm × 20 mm image was 64.5%, which was significantly higher than that for the 12 mm × 12 mm central image (52.3%, p < 0.05). The average ischemic index (ISI) was 15.26% for the 12 mm~24mm-annulus, which was significantly higher than that for the 12 mm × 12 mm central image (5.62%). Six eyes had NV and 10 eyes had IRMAs that only existed in the 12 mm~24mm-annulus area.ConclusionsThe newly developed high-speed ultra-widefield SS-OCTA can capture a 24 mm × 20 mm retinal vascular image during a single scan, which improves the accuracy of detecting the degree of retinal ischemia and detection rate of NV and IRMAs.