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Urban agglomerations are the key areas to promote carbon dioxide (CO2) reduction. Understanding the association of CO2 emission of urban agglomerations and their influencing factors is significant to promote the synergistic management of carbon reduction in the Yangtze River Economic Belt (YREB). Based on the CO2 emission data of the three major urban agglomerations in the YREB from 2010 to 2020, this study summarised characteristics of the CO2 emission association structure of the three major urban agglomerations, explored the factors affecting the spatial association of CO2 emissions of in each urban agglomeration, and proposed countermeasures to promote the collaborative CO2 reduction of the urban agglomerations in the YREB accordingly. Results show that the CO2 emissions and correlations of the three urban agglomerations increase year by year, and the CO2 emission correlations have the spatial characteristics of “dense in the east and sparse in the west,” and the network correlation characteristics differ significantly among urban agglomerations. The CO2 emission linkage of the YREB has formed a block division with urban agglomerations as the boundary, and the linkages between urban agglomerations are relatively weak. The status and role of each city in the synergistic emission reduction network are different, and the formation paths and influencing factors of CO2 emission association are different among urban agglomerations; therefore, differentiated synergistic emission reduction policies need to be formulated for each region. The above findings provide realistic support for constructing a synergistic CO2 reduction strategy in a first-before-supporting and differentiated manner.

Abstract An approximate 236‐year interval in major seismic activity near the southern Xianshuihe fault terminated on 5 September 2022 until a destructive M6.8 Luding earthquake. The strike‐slip mainshock, accompanied by potent normal‐faulting aftershocks, fell short of the previously anticipated M7+ event. Utilizing deep‐learning and source inversion techniques, we analyzed dense near‐field seismograms to examine detailed fault structures and rupture characteristics. Our high‐quality relocated catalog with 7,388 events revealed that the earthquake ruptured an unmapped multiscale fault network. The analysis of the mainshock and 43 ML ≥ 2.8 aftershocks suggests normal‐faulting events relate to the vertical movement of the Gongga Mountain. The sequence length, seismic gaps, and asperities derived from seismicity and waveform modeling imply that the rupture of the M6.8 quake was incomplete, indicating a high risk of a future M6+ event at the northern Moxi segment. These findings hold crucial implications for assessing future seismic hazards in this region.

BackgroundPapillary thyroid cancer (PTC) is the most common endocrine malignancy worldwide. The treatment of PTC has attracted extensive attention and discussion from the public and scholars. However, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric and knowledge map analysis to reveal the dynamic scientific developments in the PTC therapy field.MethodsWe retrieved publications related to PTC therapy from the Web of Scientific Core Collection (WoSCC) on May 1, 2023. The bibliometric package in R software, VOSviewer and CiteSpace software were used to analyze countries/regions, institutions, journals, authors, references, and keywords. Then, we systematized and summarized the research landscape, global trends and hot topics of research.ResultsThis bibliometric analysis spanned from 2012 to 2022 and involved 18,501 authors affiliated with 3,426 institutions across 87 countries/regions, resulting in the publication of 3,954 papers in 860 academic journals. Notably, the number of publications and citations related to PTC therapy research has exhibited a steady increase over the past decade. China and the United States have emerged as leading contributors in terms of publication count, with the United States also being the most cited country. Furthermore, among the top 10 institutions with the highest number of published papers, half were located in China. Among the journals, Thyroid is ranked first in terms of total publications and citations. The most productive individual author was Miyauchi Akira. While previous research primarily focused on surgery and radioactive iodine therapy, the increasing emphasis on health awareness and advancements in medical technology have led to the emergence of active surveillance, thermal ablation, and genomic analysis as prominent areas of research.ConclusionIn conclusion, this comprehensive and quantitative bibliometric analysis elucidates the research trends and hotspots within PTC therapy, drawing from a substantial body of publications. This study provides valuable insights into the historical and current landscape of PTC therapy research while also offering guidance for future research directions. This study serves as a valuable resource for researchers and practitioners seeking new avenues of exploration in the field.

Cancer patients commonly suffer from loneliness, poor spiritual status, and fear of death; however, these evaluations are rarely revealed in urological cancer patients. Thus, this study aimed to assess the loneliness, spiritual well-being, and death perception, as well as their risk factors in urological cancer patients. A total of 324 urological (including renal, bladder, and prostate) cancer patients and 100 healthy controls were included. The University of California and Los Angeles loneliness scale (UCLA-LS), functional assessment of chronic illness therapy-spiritual well-being (FACIT-Sp), and death attitude profile-revised (DAP-R) scores were evaluated. The results showed that the UCLA-LS score was higher, but the FACIT-Sp score was lower in urological cancer patients than in healthy controls. According to the DAP-R score, fear of death, death avoidance, and approaching death acceptance were elevated, but neutral acceptance was lower in urological cancer patients than in healthy controls. Among urological cancer patients, the UCLA-LS score was highest but the FACIT-Sp score was lowest in bladder cancer patients; regarding the DAP-R score, fear of death and death avoidance were highest, but approaching death acceptance was lowest in bladder cancer patients. Interestingly, single/divorced/widowed status, bladder cancer diagnosis, higher pathological grade, surgery, systemic treatment, and local treatment were independent factors for higher UCLA-LS score or lower FACIT-Sp score. In conclusion, urological cancer (especially bladder cancer) patients bear increased loneliness and reduced spiritual well-being; they also carry higher fear of death, death avoidance, and approaching death acceptance but lower neutral acceptance of death.

Background: There have been individual case reports of aripiprazole in recent years, both domestically and internationally, but no analysis of the characteristics of the occurrence of adverse reactions/events of drug-induced liver injury with aripiprazole using spontaneous reports has been seen.Methods: Using a retrospective study approach, the 452 adverse reaction/event reports of aripiprazole-induced liver injury collected by the China Adverse Drug Reaction Monitoring System from 1 January 2012 to 31 December 2016 were analyzed and evaluated, and exploring it’s the clinical characteristics and related risk factors for liver injury occurrence.Results: Among 452 cases of aripiprazole-induced liver injury ADR/ADE reports, there were 121 cases classified as serious, accounting for 26.8% of the total. There were 250 male and 202 female patients, with a male-to-female ratio of 1.24:1. The age of patients ranged from 11 to 77 years old, with an average age of (34.56 ± 12.81) years old, and a high proportion of young adults in the total population. Some patients had used the drug off-label or at a higher than recommended dosage. The onset of liver injury was generally within 15–90 days after continuous use, while some patients are also accompanied by nausea, vomiting, and weight gain. 70% of the combined drug instructions listed that may cause liver injury.Conclusion: In clinical practice, healthcare professionals should pay closely attention to the adverse reactions and risk factors of liver injury caused by aripiprazole. If there are potential risk factors for liver injury, early and regular monitoring of liver function should be carried out to reduce the occurrence of adverse reactions.

In recent years, new food processing technologies (such as ultrasound, high-pressure homogenization, and pulsed electric fields) have gradually appeared in the public 's field of vision. These technologies have made outstanding contributions to changing the structure and function of protein complexes. As a relatively mature physical field, ultrasound has been widely used in food-related fields. However, with the gradual deepening of related research, it is found that the combination of different fields often makes some characteristics of the product better than the product under the action of a single field, which will not only lead to a broader application prospect of the product, but also make the product a better solution in some special fields. There are usually synergistic and antagonistic effects when multiple fields are combined, and these effects will also gradually enlarge the interaction between different components of the protein complex system. In this paper, while explaining the mechanism of ultrasonic combined with other fields affecting the steric hindrance and shielding site of protein complex system, we will further explain the effect of this effect on the function and application of protein complex system.

Lentinula edodes (L. edodes), one of the most popular edible mushrooms in China, is adversely affected by high temperature. Heat shock proteins (HSPs) play a crucial role in regulating the defense responses against the abiotic stresses in L. edodes. Some HSPs in L. edodes have been described previously, but a genome-wide analysis of these proteins is still lacking. Here, the HSP genes across the entire genome of the L. edodes mushroom were identified. The 34 LeHSP genes were subsequently classified into six subfamilies according to their molecular weights and the phylogenetic analysis. Sequence analysis showed that LeHSP proteins from the same subfamily have conserved domains and one to five similar motifs. Except for Chr 5 and 9, 34 LeHSPs genes were distributed on the other eight chromosomes. Three pairs of paralogs were identified because of sequence alignment and were confirmed as arising from segmental duplication. In LeHSPs’ promoters, different numbers of heat shock elements (HSEs) were predicted. The expression profiles of LeHSPs in 18N44 and 18 suggested that the thermo-tolerance of strain 18N44 might be related to high levels of LeHSPs transcript in response to heat stress. The quantitative real-time PCR (qRT-PCR) analysis of the 16 LeHSP genes in strains Le015 and Le027 verified their stress-inducible expression patterns under heat stress. Therefore, these comprehensive findings provide useful in-depth information on the evolution and function of LeHSPs and lay a theoretical foundation in breeding thermotolerant L. edodes varieties.

Aiming at the problem of autonomous obstacle avoidance of fixed-wing UAVs in a complex, dense and multi-obstacle environment, a path planning algorithm for fixed-wing UAVs based on a safe flight corridor is proposed. The difficulty of avoiding dense obstacles lies in the choice of obstacle circumvention and traversal: although circumvention is safer, the flight cost is greater; although the traversal cost is lower, the safety threat is higher. How to quickly solve the optimal path is the core issue. This paper firstly defines a safe flight corridor innovatively based on the maneuvering characteristics of fixed-wing UAVs and the Dubins curves. By comprehensively considering UAV flight safety and flight costs, an obstacle threat evaluation function is constructed. Secondly, in view of the computational complexity caused by the dense obstacles, an obstacle clustering algorithm based on obstacle density is proposed, and the nonlinear evaluation function in a high dynamic environment is quickly approximated by Monte Carlo sampling method. Finally, simulations verify the effectiveness of the proposed algorithm in solving dense obstacle avoidance for fixed-wing UAVs.

High melting point paraffin wax (HPW) is a novel desensitizer that has the potential to achieve low sensitivity of energetic crystals, such as 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). However, first-principles calculations confirmed that interface deterioration occurred due to a weak interfacial connection. In this work, the polydopamine (PDA)/HPW/PDA with a sandwich-like interfacial structure was prepared using three simple steps to improve safety performance, thermal stability, and mechanical properties. The theoretical and experimental results suggested that the PDA acted as a double-sided tape to adhere to the adjacent HMX/HPW layer or HPW/polymer binder layer, thus substantially enhancing the interfacial interaction. While maintaining higher safety performance (impact energy: 11∼13 ​J) than that of HMX (5 ​J), the new design improved the β-δ polymorphic transition temperature of HMX to 219.4 ​°C for HMX@PDA@HPW@PDA, which was higher than that of HMX@HPW (202.8 ​°C) and core@double-shell HMX@PDA@HPW (208.9 ​°C). Among the modified energetic composites, polymer-bonded explosives (PBXs) based on HMX@PDA@HPW@PDA exhibited the optimum mechanical performance, including the storage modulus and tensile fracture energy, which were 43.5% and 77.1% higher than those of PBXs based on raw HMX, respectively. The achieved favorable systematical enhancement in thermal stability, mechanical properties, and safety performance shows that such a sandwich-like interfacial structure has great potential for application for HMX-based formulation used in complex environments.

Abstract Face detection is the basic step of many face analysis tasks. In practice, face detectors usually run on mobile devices with limited memory and computing resources. Therefore, it is important to keep face detectors lightweight. To this end, current methods usually focus on directly designing lightweight detectors. Nevertheless, it is not fully explored whether the resource consumption of these lightweight detectors can be further suppressed without too much sacrifice on accuracy. In this study, we propose to apply the network pruning method to the lightweight face detection network, to further reduce its parameters and floating point operations. To identify the channels of less importance, we perform network training with sparsity regularisation on channel scaling factors of each layer. Then, we remove the connections and corresponding weights with near‐zero scaling factors after sparsity training. We apply the proposed pruning pipeline to a state‐of‐the‐art face detection method, EagleEye, and get a shrunken EagleEye model, which has a reduced number of computing operations and parameters. The shrunken model achieves comparable accuracy as the unpruned model. By using the proposed method, the shrunken EagleEye achieves a 56.3% reduction of parameter size with almost no accuracy loss on the WiderFace dataset.

Context Keguan-1 (KG-1) plays a vital role in enhancing the curative effects, improving quality of life, and reducing the development of acute lung injury (ALI).Objective To unravel the protective effect and underlying mechanism of KG-1 against ALI.Materials and methods C57BL/6J mice were intratracheally instilled with lipopolysaccharide to establish the ALI model. Then, mice in the KG-1 group received a dose of 5.04 g/kg for 12 h. The levels of proinflammatory cytokines, chemokines, and pathological characteristics were determined to explore the effects of KG-1. Next, untargeted metabolomics was used to identify the differential metabolites and involved pathways for KG-1 anti-ALI. Network pharmacology was carried out to predict the putative active components and drug targets of KG-1 anti-ALI.Results KG-1 significantly improved the levels of TNF-α (from 2295.92 ± 529.87 pg/mL to 1167.64 ± 318.91 pg/mL), IL-6 (from 4688.80 ± 481.68 pg/mL to 3604.43 ± 382.00 pg/mL), CXCL1 (from 4361.76 ± 505.73 pg/mL to 2981.04 ± 526.18 pg/mL), CXCL2 (from 5034.09 ± 809.28 pg/mL to 2980.30 ± 747.63 pg/mL), and impaired lung histological damage. Untargeted metabolomics revealed that KG-1 significantly regulated 12 different metabolites, which mainly related to lipid, amino acid, and vitamin metabolism. Network pharmacology showed that KG-1 exhibited anti-ALI effects through 17 potentially active components acting on seven putative drug targets to regulate four metabolites.Discussion and conclusions This work elucidated the therapeutic effect and underlying mechanism by which KG-1 protects against ALI from the view of the metabolome, thus providing a scientific basis for the usage of KG-1.

Egg custard is a common dish on the dining table and exhibits a uniform porous structure after freeze-drying. The protein within egg custard is a rich source of carbon and nitrogen, and the custard’s unique microstructure and adjustable electrical properties make it a potential porous carbon precursor. Herein, nitrogen in situ doped porous carbons (NPCs) and potassium-carbonate-modified NPCs (PNPCs) are obtained through a simple gelation and carbonization process using egg white as the raw material. The unique morphologies of the porous carbon are inherited from the protein and include fibrous clusters, honeycomb holes, and a grooved skeleton. Their excellent impedance matching and effective internal loss make the obtained porous carbons good candidates for lightweight electromagnetic (EM) wave absorbers without the need to dope with metal elements. As a representative porous carbon, PNPC10-700 has multiple structures, including fibrous clusters, honeycomb holes, and a porous skeleton. Moreover, it achieves a maximum reflection loss value of −66.15 dB (with a thickness of 3.77 mm) and a broad effective absorption bandwidth of 5.82 GHz (from 12.18 to 18.00 GHz, with a thickness of 2.5 mm), which surpasses the reported values in most of the literature. Thus, gelation combined with the further carbonization of egg white (protein) is a new method for designing the morphology and EM properties of porous carbon absorbers.

The fracture surface characteristics and the associated micromechanisms governing the fish-eye crack initiation of a Ti-6Al-4V alloy under very high cycle fatigue (VHCF) loading are investigated. Microscopic observation revealed that the crack initiation area of fish-eye center is covered by ragged-like mountains and dimples containing various irregular rods/particles, grooves and microvoids. These micro-ductile characteristics primarily result from the nucleation and coalescence of microvoids and grooves at αs/βr interface inside βtrans. This could be due to the incompatibility of both micro-plastic deformation and slips in αs and βr. The βtrans plays a dominant role in the fish-eye crack initiation and early propagation process of the Ti-6Al-4V alloy in the VHCF regime.

Angiopoietin-like protein 4 (ANGPTL4) is a potential circulating mediator connecting nutritional factors and fat metabolism, however, information is lacking on the exact role of ANGPTL4 on triglyceride metabolism in the thigh muscles and livers of broilers. The objective of this study was to determine the changes in the triglyceride metabolism in the thigh muscles and livers of broilers injected intravenously with ANGPTL4. In experiment 1, 36 male Arbor Acres broilers at 35 days of age were randomly allocated into six treatments with six replicates. The broilers were subjected to intravenous injection of polyhistidine-small ubiquitin-related modifier-ANGPTL4 (His-SUMO-ANGPTL4) once at a dose of 0, 20, 100, 500, 2 500, or 12 500 ng/kg body weight (BW), respectively. The results showed that the injection of His-SUMO-ANGPTL4 at a dose of 500, 2 500 and 12 500 ng/kg BW decreased (P < 0.05) the broilers' heart-fatty acid-binding protein (H-FABP) mRNA expression in the thigh muscle. All of the His-SUMO-ANGPTL4 broiler injected groups had a lower (P < 0.05) adipocyte-fatty acid-binding protein mRNA expression in the thigh muscle. In experiment 2, 18 male Arbor Acres broilers at 35 days of age were randomly allocated into three treatments with six replicates. The broilers were given an injection of normal saline (NS), His-SUMO, or His-SUMO-ANGPTL4 (500 ng/kg BW) once. The results showed that the broilers receiving an injection of ANGPTL4 at a dose of 500 ng/kg BW decreased (P < 0.05) the H-FABP mRNA expression in the thigh muscle. Besides, the broilers given an injection of ANGPTL4 at a dose of 500 ng/kg BW increased (P < 0.05) the fatty acid synthase mRNA expression and activity and decreased (P < 0.05) the microsomal triglyceride transfer protein mRNA expression in the liver. However, the concentrations of the high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, insulin, growth hormone and leptin in the serum were not affected by the ANGPTL4 injection. In conclusion, ANGPTL4 has the ability to change the triglyceride metabolism in the thigh muscles and livers of broilers.

Highlights Long-term (9-years) biochar amendment field and greenhouse pot experiments were conducted. DGT/DIFS/SPRRI were used to in-situ assess P availability, resupply, and release risk to the environment. Long-term biochar addition significantly decreased rice rhizosphere available P and its release risk to the environment. Fe/Al-P and unavailable P dominated the mobility and resupply of P.

Abstract Background Current evidence‐based guidelines support stereotactic radiosurgery (SRS) for patients with up to four brain metastases (BMs). However, debate continues about how many tumors may be treated by SRS alone. Methods This retrospective study included non–small cell lung cancer (NSCLC) patients with BMs treated with gamma knife as the initial treatment for cerebral lesions. The patients were followed up to obtain their survival information. The outcomes were statistically analyzed to compare the differences in survival between the

Lentinula edodes, one of the most highly regarded edible mushrooms in China, is susceptible to damage from high temperatures. However, a mutant strain derived from L. edodes, known as Le023M, has shown exceptional thermotolerance. Compared to the original strain Le023, Le023M exhibited accelerated mycelial recovery following heat stress. Through RNA-seq analysis, the majority of differentially expressed genes (DEGs) were found to be associated with functions such as “protein refolding”, “protein unfolding”, “protein folding”, and “response to heat”, all of which are closely linked to heat shock proteins. Furthermore, qRT-PCR results revealed significant accumulation of heat shock-related genes in Le023M under heat stress. GC-MS analysis indicated elevated levels of trehalose, aspartate, and glutamate in Le023M when subjected to heat stress. The highly expressed genes involved in these metabolic pathways were predominantly found in Le023M. Collectively, these findings highlight the following: (i) the crucial role of heat shock proteins (HSPs) in the thermo-resistant mechanisms of Le023M; (ii) the potential of trehalose accumulation in Le023M to enhance mycelium resistance to heat stress; and (iii) the induction of aspartate and glutamate accumulation in response to heat stress. These results shed light on the molecular mechanisms underlying the thermotolerance of Le023M, providing valuable insights for further understanding and improving heat stress response in L. edodes. The findings also highlight the potential applications of Le023M in the cultivation and production of L. edodes under high-temperature conditions.

Model high-protein nutrition bars (HPNBs) were formulated by incorporating whey protein isolate (WPI) and casein (CN) at various extrusion temperatures (50, 75, 100, 125, and 150 °C) with a protein content of 45 g per 100 g. The free sulfhydryl groups, amino groups, hardness, and microstructures of HPNBs were analyzed periodically at 37 °C over a storage period of 45 days. Specifically, sulfhydryl group, amino group and surface hydrophobicity of extruded whey protein isolate (WPE) and extruded casein (CE) were significantly reduced (P

In recent years, the concept of bound states in continuum (BIC) in metasurfaces has become a topic of interest. BIC involves the physical mechanics of wave optics, metamaterial sensors and other high-quality factor (Q-factor) applications. In this paper, the basic concept of BIC is introduced, followed by a brief description of the progression of the research regarding the application of BIC in terahertz (THz) metasurfaces. Subsequently, an all-dielectric metasurface consisting of tetramer clusters with dual terahertz resonances is proposed. The materials used for the substrate and the tetramer cluster are quartz and silicon, respectively. Quasi-BIC works by varying the cylinder radius on the metasurface structure. The transmission spectra are analyzed under different structural and material parameters with control variables. When the metasurface is applied as a refractive-index sensor, the Q-factor is 2303.77 and the figure of merit (FOM) is 7022.90, which are calculated using the asymmetric parameter k = 0.8 μm. Additionally, when the incident wave is x- or y-polarized, resonance peaks with the same frequencies can be obtained, and the overall trend of the transmission spectrum remains the same.

Introduction: Quorum sensing (QS) is a bacterial intracellular and intercellular communication system that regulates virulence factor production, biofilm formation, and antibiotic sensitivity. Quorum-sensing inhibitors (QSIs) are a novel class of antibiotics that can effectively combat antibiotic resistance. Autoinducer-2 (AI-2) is a universal signaling molecule that mediates inter- and intraspecies QS systems among different bacteria. Furthermore, LsrK plays an important role in regulating the activity and stability of the intracellular AI-2 signaling pathway. Thus, LsrK is considered an important target for the development of QSIs.Methods: We designed a workflow integrating molecular dynamic (MD) simulations, virtual screening, LsrK inhibition assays, cell-based AI-2-mediated QS interference assays, and surface plasmon resonance (SPR)-based protein affinity assays to screen for potential LsrK kinase inhibitors.Results: MD simulation results of the LsrK/ATP complex revealed hydrogen bonds and salt bridge formation among four key residues, namely, Lys 431, Tyr 341, Arg 319, and Arg 322, which are critical for the binding of ATP to LsrK. Furthermore, MD simulation results indicated that the ATP-binding site has an allosteric pocket that can become larger and be occupied by small molecule compounds. Based on these MD simulation results, a constraint of forming at least one hydrogen bond with Arg 319, Arg 322, Lys 431, or Tyr 341 residues was introduced when performing virtual screening using Glide’s virtual screening workflow (VSW). In the meantime, compounds with hydrophobic group likely to interact with the allosteric hydrophobic pocket are preferred when performing visual inspection. Seventy-four compounds were selected for the wet laboratory assays based on virtual screening and the absorption, distribution, metabolism, and excretion (ADME) properties of these compounds. LsrK inhibition assays revealed 12 compounds inhibiting LsrK by more than 60% at a 200 μM concentration; four of these (Y205-6768, D135-0149, 3284–1358, and N025-0038) had IC50 values below 50 μM and were confirmed as ATP-competitive inhibitors. Six of these 12 LsrK inhibitors exhibited high AI-2 QS inhibition, of which, Y205-6768 had the highest activity with IC50 = 11.28 ± 0.70 μM. The SPR assay verified that compounds Y205-6768 and N025-0038 specifically bound to LsrK. MD simulation analysis of the docking complexes of the four active compounds with LsrK further confirmed the importance of forming hydrogen bonds and salt bridges with key basic amino acid residues including Lys 431, Tyr 341, Arg 319, and Arg 322 and filling the allosteric hydrophobic pocket next to the purine-binding site of LsrK.Discussion: Our study clarified for the first time that there is an allosteric site near the ATP-binding site of Lsrk and that it enriches the structure–activity relationship information of Lsrk inhibitors. The four identified compounds showed novel structures, low molecular weights, high activities, and novel LsrK binding modes, rendering them suitable for further optimization for effective AI-2 QSIs. Our work provides a valuable reference for the discovery of QSIs that do not inhibit bacterial growth, thereby avoiding the emergence of drug resistance.

Understanding the changes in community structure of fishery resources in island reef waters is crucial for effective fishery resource management, as these waters constitute a critical link in maintaining the sustainable development of offshore fishery resources. The study analyzed the structure of the fish community in the waters surrounding Dachen Island by using data collected during four voyage surveys conducted between September 2020 and April 2021. The study utilized co-occurrence network analysis, multiple regression trees, and functional diversity analysis to investigate the short-term and local scale changes in fish community structure. The results showed that the fish community in the waters adjacent to Dachen Island can be categorized into two groups: annual and stage-use species. The stage-use species include Scoliodon laticaudus, Trichiurus lepturus, Tetraodontidae, and others, which are used during the summer and autumn stages of bait migration. Additionally, Dasyatidae and others, which used during the winter and spring stages of reproductive migration. Furthermore, the study found that the habitats dominated by nearshore rocky habitats and distant deep habitats formed the local scale variation in community structure in island waters. The integrated analysis of species α-diversity and functional diversity provided a basis for understanding the mechanisms of biodiversity action. Our study aims to provide a theoretical framework for the development of fishery resource management strategies based on the life cycle of fish, and to serve as a reference for the prioritization of key protection areas for fishery resources in island and reef environments. Overall, the study’s findings can promote the understanding of community structure dynamics in island waters. Additionally, these findings can offer valuable insights into the restoration of habitats and the implementation of marine ranching activities in Dachen Island. Moreover, the outcomes can serve as a theoretical foundation for the development of appropriate management and conservation strategies for fisheries resources.

Background: Farnesoid X receptor (FXR) is a key metabolic target of bile acids (BAs) and is also a target for drugs against several liver diseases. However, the contribution of FXR in the pathogenesis of cholestasis is still not fully understood. The purpose of this study is to provide a comprehensive insight into the metabolic properties of FXR-involved cholestasis in mice.Materials and methods: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model and FXR−/− mice were established to investigate the effect of FXR on cholestasis. The effect of FXR on liver and ileal pathology was evaluated. Simultaneously, Untargeted metabolomics combined with 16s rRNA gene sequencing analysis was applied to reveal the involvement of FXR in the pathogenesis of cholestasis.Results: The results showed that ANIT (75 mg/kg) induced marked cholestasis in WT and FXR −/− mice. It is noteworthy that FXR−/− mice developed spontaneous cholestasis. Compared with WT mice, significant liver and ileal tissue damage were found. In addition, 16s rRNA gene sequencing analysis revealed gut microbiota dysbiosis in FXR−/− mice and ANIT-induced cholestasis mice. Differential biomarkers associated with the pathogenesis of cholestasis caused by FXR knockout were screened using untargeted metabolomics. Notably, Lactobacillus_ johnsonii_FI9785 has a high correlation with the differential biomarkers associated with the pathogenesis and progression of cholestasis caused by FXR knockout.Conclusion: Our results implied that the disorder of the intestinal flora caused by FXR knockout can also interfere with the metabolism. This study provides novel insights into the FXR-related mechanisms of cholestasis.

Microplastics (MPs) as emerging contaminants have become a major global concern, however, the distribution and origin of MPs in Qinghai-Tibet Plateau (QTP) and their impacts on ecosystem are poorly known. Hence, we systematically evaluated the profile of MPs on the representative metropolitan locations of Lhasa and Huangshui Rivers and the scenic sites of Namco and Qinghai Lake. The average abundance of MPs in the water samples was 7020 items/m3, which was 34 and 52 times higher than those for the sediment (206.7 items/m3) and soil samples (134.7 items/m3), respectively. Huangshui River had the highest levels, followed by Qinghai Lake, Lhasa River and Namco. Human activities rather than altitude and salinity impacted the distribution of MPs in those areas. Besides the consumption of plastic products by locals and tourists, laundry wastewater and exogenous tributary inputs, the unique prayer flag culture also contributed to the MPs emission in QTP. Notably, the stability and fragment of MPs were crucial for their fate. Multiple assessment models were employed to evaluate the risk of MPs. PERI model took MP concentration, background value and toxicity into account, comprehensively describing the risk differences of each site. The large PVC proportion in Qinghai Lake posed the highest risk. Furthermore, concerns should be raised about PVC, PE and PET in Lhasa and Huangshui Rivers, and PC in Namco Lake. Risk quotient suggested that aged MPs in sediments slowly released biotoxic DEHP and should be cleaned up promptly. The findings offer baseline data of MPs in QTP and ecological risks, providing important support for the prioritization of future control measures.

To prevent damage to human life and health caused by high temperatures and extreme weather and to promote sustainable urban development, it is necessary to optimize the layout of urban development elements to improve the urban wind–heat environment. Taking the high-density urban area of Shanghai as an example, this study used wavelet analysis to investigate the cyclic changes of the average annual temperature of Shanghai from 1950 to 2022 and the average annual wind speed of Shanghai from 2000 to 2020. The correlation between the urban heat environment and the urban development elements was analyzed using geographically weighted regression. The correlation was then examined using BP neural network, and finally, the impacts of different urban spatial patterns on the wind environment were analyzed using CFD numerical simulation. The results show that the average annual temperature of Shanghai city has an overall upward trend, with significant cycles of 44 and 32 years that are shortening over time. The average annual wind speed has a downward trend, with a significant main cycle of 22 years. Greening and water coverage, as well as the floor area ratio, have a significant reducing effect on surface temperature, whereas building density is positively correlated with surface temperature. Building density has a significant reducing effect on wind speed, whereas the effect of floor area ratio is not significant. The effect of building density on wind speed is significantly weakened, whereas the effect of the floor area ratio is not significant. This study provides valuable references for Shanghai and other high-density cities to optimize urban spatial patterns in order to improve the safety and comfort of the urban wind–heat environments. This study is of significant importance and value in promoting sustainable urban development, protecting the health of urban residents, and advancing spatial justice and equal well-being.

Participatory crowdsensing (PCS) is an innovative data sensing paradigm that leverages the sensors carried in mobile devices to collect large-scale environmental information and personal behavioral data with the user’s participation. In PCS, task assignment and path planning pose complex challenges. Previous studies have only focused on the assignment of individual tasks, neglecting or overlooking the associations between tasks. In practice, users often tend to execute similar tasks when choosing assignments. Additionally, users frequently engage in tasks that do not match their abilities, leading to poor task quality or resource wastage. This paper introduces a multi-task assignment and path-planning problem (MTAPP), which defines utility as the ratio of a user’s profit to the time spent on task execution. The optimization goal of MATPP is to maximize the utility of all users in the context of task assignment, allocate a set of task locations to a group of workers, and generate execution paths. To solve the MATPP, this study proposes a grade-matching degree and similarity-based mechanism (GSBM) in which the grade-matching degree determines the user’s income. It also establishes a mathematical model, based on similarity, to investigate the impact of task similarity on user task completion. Finally, an improved ant colony optimization (IACO) algorithm, combining the ant colony and greedy algorithms, is employed to maximize total utility. The simulation results demonstrate its superior performance in terms of task coverage, average task completion rate, user profits, and task assignment rationality compared to other algorithms.

A large-scale physical model experiment was conducted to study the interaction between regular waves and submerged horizontal cylinders, breaking through the bottleneck of a low Reynolds number in a traditional small water tank. The surface pressure distribution and overall force of submerged horizontal cylinders at different submerged depths in waves with different heights and periods under a high Reynolds number were analyzed, and the variation in first- and second-order wave forces with wave height periods was analyzed. Subsequently, the influence of the cylinder on the wave field was analyzed, and the reflection coefficient was obtained through the three-point separation method. According to the analysis of the experimental results, the horizontal and vertical forces acting on the submerged cylinder per linear meter are similar, with the horizontal force slightly greater than the vertical force; at the same time, the submerged cylinder has a certain reflection effect on long-period waves. The summary, analysis, and display of relevant experimental results provide validation support for the current high-precision mathematical model as much as possible.

Due to their versatile and unique properties, tantalum-based thin films have been extensively studied. However, tantalum is susceptible to oxidation due to its higher chemical activity, which is crucial regardless of whether oxidations of Ta are beneficial or detrimental. Therefore, the oxidation of Ta during material processing, especially without conscious means, should be taken seriously. In this study, pure Ta films were fabricated by magnetron sputtering under set procedure parameters. The effects of base pressure and substrate temperature on the degree of oxidation of Ta films were investigated. The results revealed that the magnitude of the base pressure directly affects the oxidation state of the as-deposited Ta films. When preferably avoiding the oxidation of sputtered Ta films, the base pressure should be controlled below 4.4 × 10−4 Pa. The substrate temperature has little effect on the oxidation state of the as-deposited Ta films under a base pressure ranging from about 10−2 Pa to 10−4. We hope that this study can provide some references for controlling the oxidation states of Ta involved in relevant film preparation.

With the rapid development of smart grids, the deployment number of transmission lines has significantly increased, posing significant challenges to the detection and maintenance of power facilities. Unmanned aerial vehicles (UAVs) have become a common means of power inspection. In the context of drone power inspection, drone clusters are used as relays for long-distance communication to expand the communication range and achieve data transmission between patrol drones and base stations. Most of the communication occurs in the air-to-air channel between UAVs, which requires high reliability of communication between drone relays. Therefore, the main focus of this paper is on decoding schemes for drone air-to-air channels. Given the limited computing resources and battery capacity of a drone, as well as the large amount of power data that needs to be transmitted between drone relays, this paper aims to design a high-accuracy and low-complexity decoder for LDPC long-code decoding. We propose a novel shared-parameter neural-network-normalized minimum sum decoding algorithm based on codebook quantization, applying deep learning to traditional LDPC decoding methods. In order to achieve high decoding performance while reducing complexity, this scheme utilizes codebook-based weight quantization and parameter sharing methods to improve the neural-network-normalized minimum sum (NNMS) decoding algorithm. Simulation experimental results show that the proposed method has a better BER performance and low computational complexity. Therefore, the LDPC decoding algorithm designed effectively meets the drone characteristics and the high channel decoding performance requirements. This ensures efficient and reliable data transmission on the data link between drone relays.

Floccularia luteovirens, a rare wild edible and medicinal fungus, is endemic to the Tibetan plateau. However, attempts to artificially domesticate this species have not been successful, resulting in extremely limited utilization of this valuable resource. This paper presents the geographical distribution of F. luteovirens, along with its ecological and biological characteristics. It explores population relations, symbiotic relationships, soil microbial community relations, fruiting body occurrence conditions, nutritional metabolism, and reproductive patterns. The cultivation techniques, as well as the edible and medicinal value of this mushroom, are also reviewed. Through an overall analysis of the physiological characteristics and current research status of F. luteovirens, the paper discusses its development prospects. The aim is to provide a reference for other researchers and promote its artificial domestication, resource development, and utilization.

Dengue virus (DENV) is a major mosquito-borne human pathogen in tropical countries; however, there are currently no targeted antiviral treatments for DENV infection. Compounds 27 and 29 have been reported to be allosteric inhibitors of DENV RdRp with potent inhibitory effects. In this study, the structures of compounds 27 and 29 were optimized using computer-aided drug design (CADD) approaches. Nine novel compounds were synthesized based on rational considerations, including molecular docking scores, free energy of binding to receptor proteins, predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) parameters, structural diversity, and feasibility of synthesis. Subsequently, the anti-DENV activity was assessed. In the cytopathic effect (CPE) assay conducted on BHK-21 cells using the DENV2 NGC strain, both SW-b and SW-d demonstrated comparable or superior activity against DENV2, with IC50 values of 3.58 ± 0.29 μM and 23.94 ± 1.00 μM, respectively, compared to that of compound 27 (IC50 = 19.67 ± 1.12 μM). Importantly, both SW-b and SW-d exhibited low cytotoxicity, with CC50 values of 24.65 μmol and 133.70 μmol, respectively, resulting in selectivity indices of 6.89 and 5.58, respectively. Furthermore, when compared to the positive control compound 3′-dATP (IC50 = 30.09 ± 8.26 μM), SW-b and SW-d displayed superior inhibitory activity in an enzyme inhibitory assay, with IC50 values of 11.54 ± 1.30 μM and 13.54 ± 0.32 μM, respectively. Molecular dynamics (MD) simulations elucidated the mode of action of SW-b and SW-d, highlighting their ability to enhance π–π packing interactions between benzene rings and residue W795 in the S1 fragment, compared to compounds 27 and 29. Although the transacylsulphonamide fragment reduced the interaction between T794 and NH, it augmented the interaction between R729 and T794. In summary, our study underscores the potential of SW-b and SW-d as allosteric inhibitors targeting the DENV NS5 RdRp domain. However, further in vivo studies are warranted to assess their pharmacology and toxicity profiles.

To illustrate data uncertainty, intuitionistic fuzzy sets simply use membership and non-membership degrees. However, in some cases, a more complex strategy is required to deal with imprecise data. One of these techniques is generalized intuitionistic fuzzy sets (GIFSs), which provide a comprehensive framework by adding extra factors that provide a more realistic explanation for uncertainty. GIFSs contain generalized membership, non-membership, and hesitation degrees for establishing symmetry around a reference point. In this paper, we applied a generalized intuitionistic fuzzy set approach to investigate ambiguity in the parameter of the Lomax life distribution, seeking a more symmetric assessment of the reliability measurements. Several reliability measurements and associated cut sets for a novel L-R type fuzzy sets are derived after establishing the scale parameter as a generalized intuitionistic fuzzy number. Additionally, the study includes a range of reliability measurements, such as odds, hazards, reliability functions, etc., that are designed for the Lomax distribution within the framework of generalized intuitionistic fuzzy sets. These reliability measurements are an essential tool for evaluating the reliability characteristics of various types of complex systems. For the purpose of interpretation and application, the results are visually displayed and compared across different cut set values using a numerical example.

Abstract Purpose Currently, the prognostic value of molecular subtypes in ductal carcinoma in situ (DCIS) remains unclear. In this study, we explored whether molecular subtypes could predict second breast events (SBEs) in patients after breast‐conserving surgery (BCS). Methods From January 2008 to December 2016, 291 DCIS patients treated with BCS were retrospectively analyzed. Patients were classified into four molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and triple‐negative breast cancer (TNBC). The SBE incidence was calculated by the competing risk model and compared by Gray's test. The disease‐free survival rates were estimated by the Kaplan–Meier method and compared by the log‐rank test. Prognostic factors were evaluated by univariate and multivariate COX proportional hazards regression model. Results With a median follow‐up of 66 months, 12 SBEs were identified. The 5‐year overall SBE incidence of luminal A, luminal B, HER2 overexpression, and TNBC was 2.18%, 4.25%, 15.15%, and 0.00%, respectively. In the univariate analysis, the HER2 overexpression subtype was the predictor of overall (p = 0.005), in situ (p = 0.004), and ipsilateral SBEs (p = 0.008). Patients with endocrine therapy were less likely to develop in situ SBEs (p = 0.039). Additionally, patients with closed (

Highlights Biochar amendment significantly increased DNRA rate in the paddy soil. Increased DNRA rate was due to enhanced C availability and enriched DNRA bacteria. Biochar amendment shifted more nitrate partitioning toward DNRA process. Potential of straw-derived biochar in alleviating N loss was superior to straw itself.

Diagnosis assistant is an effective way to reduce the workloads of professional doctors. The rich professional knowledge plays a crucial role in diagnosis. Therefore, it is important to introduce the relevant medical knowledge into diagnosis assistant. In this paper, diagnosis assistant is treated as a classification task, and a Graph-based Structural Knowledge-aware Network (GSKN) model is proposed to fuse Electronic Medical Records (EMRs) and medical knowledge graph. Considering that different information in EMRs affects the diagnosis results differently, the information in EMRs is categorized into general information, key information and numerical information, and is introduced to GSKN by adding an enhancement layer to the Bidirectional Encoder Representation from Transformers (BERT) model. The entities in EMRs are recognized, and Graph Convolutional Neural Networks (GCN) is employed to learn deep-level graph structure information and dynamic representation of these entities in the subgraphs. An interactive attention mechanism is utilized to fuse the enhanced textual representation and the deep representation of these subgraphs. Experimental results on Chinese Obstetric Electronic Medical Records (COEMRs) and open dataset C-EMRs demonstrate the effectiveness of our model.

Abstract Background Osteoarthritis (OA) is the main cause of older pain and disability. Intra-articular injections of ozone (O3) commonly have been found to have antioxidative and anti-inflammatory effects to reduce pain and improve function in knee osteoarthritis. It has been reported that reduced autophagy in chondrocytes plays an important role in the development of OA. This study aimed to probe the role of O3 on the autophagy in chondrocytes treated with IL-1β. Methods Primary chondrocytes were isolated from Wistar rats cartilage within 3 days. The OA chondrocytes model was induced via treatment with IL-1β for 24 h. Then the cells were treated with O3 and GW9662, the inhibitor of PPARγ. Cell viability was assessed by CCK-8. Further, the cells subjected to Western blot analysis, qRT-PCR and immunofluorescence assay. The numbers of autophagosomes were observed via transmission electron microscopy. Results 30 μg/ml O3 improved the viability of chondrocytes treated with IL-1β. The decreased level of autophagy proteins and the numbers of autophagosomes improved in IL-1β-treated chondrocytes with O3 via activating PPARγ/mTOR. In addition, the qRT-PCR results showed that O3 decreased the levels of IL-6, TNF-α and MMP-3, MMP-13 in chondrocytes treated with IL-1β. Conclusions 30 μg/ml O3 improved autophagy via activating PPARγ/mTOR signaling and suppressing inflammation in chondrocytes treated with IL-1β.

Abstract Regardless of the advances in surgical techniques, parastomal hernia is still an inevitable complication for many patients with low rectal cancer undergoing abdominal perineal resection (APR). Extraperitoneal colostomy (EPC) seems to be a effective method to reduce the risk of parastomal hernia. We propose a new approach to simplify and standardize laparoscopic EPC to make this operation easy to perform. We used the technique of laparoscopic TEP groin hernia repair to produce an extraperitoneal tunnel, which can not only facilitate precise visualization of the extraperitoneal tunnel but also utilize the intact posterior rectus abdominis sheath as biologic materials to maintain soft-tissue augmentation, with a satisfactory result. With laparoscopy, we can create adequate space without insufficient dissection of the extraperitoneal tunnel while avoiding damage to the retrorectus sheath. At the time of writing, we had performed this method in four patients, without any complications. This technique is effective at preventing parastomal hernia without extra costs.

Abstract The flexural behavior of basalt fiber (BF)/polypropylene fiber (PF)-reinforced concrete (BPRC) was investigated. When the content of BF and PF is 0.1%, the addition of fibers increases the compressive strength of concrete. A BF content of 0.1% has the most obvious effect on improving the compressive strength, but a hybrid fiber content of 0.2% exhibits a negative effect on the compressive strength. The addition of BF and PF can increase the flexural strength and the expansion tortuosity of the fracture cracks, thus enhancing the ductility of concrete. The hybrid fibers with content of 0.1% are most beneficial to increase the flexural strength. However, the ductility of concrete and the tortuosity of fracture crack decrease with the matrix strength, and the improvement proportion of fibers on the flexural strength also decreases. When the BF and PF are mixed, compared to the case of single fiber added, there is no significant change in the damage of BF, whereas the damage of PF is more severe. The flexural toughness index FTδ effectively characterizes the change in the flexural toughness of BPRC. The hybrid fiber contents of 0.1% and 0.2% exhibit the most significant improving effect on FT-l/600 and FT-l/150, respectively. Considering the influence of fibers on the compressive strength, flexural strength and flexural toughness of concrete, a hybrid content of 0.1% is the optimal choice of fiber content. A prediction model for flexural strength of BPRC is proposed based on the composite material theory.

In the process of fault diagnosis for the core components of the integrated modular avionics power conversion module, selecting appropriate features can effectively improve the efficiency and classification accuracy of the model, and greatly reduce the computational complexity of the learning algorithm. This paper first designs a typical Sepic structure DC-DC converter model to simulate the typical fault types of the DC-DC converter; secondly, the corresponding original data is obtained through simulation; after data preprocessing, feature extraction and using multiple feature selection fusion algorithm, BP neural network method is used finally for fault diagnosis analysis of DC-DC converter. The simulation verifies the effectiveness of the above method.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase ( SEPHS1 ) by investigating its expression in 33 human malignancies and its relationship to tumor immunity. Methods: The expression of selenophosphate synthase 1 ( SEPHS1 ) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression. Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC ( P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC. Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

Background: Diabetic nephropathy (DN) is a widespread diabetic complication and a major cause of terminal kidney disease. There is no doubt that DN is a chronic disease that imposes substantial health and economic burdens on the world’s populations. By now, several important and exciting advances have been made in research on etiopathogenesis. Therefore, the genetic mechanisms underlying these effects remain unknown.Methods: The GSE30122, GSE30528, and GSE30529 microarray datasets were downloaded from the Gene Expression Omnibus database (GEO). Analyses of differentially expressed genes (DEGs), enrichment of gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed. Protein-protein interaction (PPI) network construction was completed by the STRING database. Hub genes were identified by Cytoscape software, and common hub genes were identified by taking intersection sets. The diagnostic value of common hub genes was then predicted in the GSE30529 and GSE30528 datasets. Further analysis was carried out on the modules to identify transcription factors and miRNA networks. As well, a comparative toxicogenomics database was used to assess interactions between potential key genes and diseases associated upstream of DN.Results: Samples from 19 DNs and 50 normal controls were identified in the GSE30122 dataset. 86 upregulated genes and 34 downregulated genes (a total of 120 DEGs). GO analysis showed significant enrichment in humoral immune response, protein activation cascade, complement activation, extracellular matrix, glycosaminoglycan binding, and antigen binding. KEGG analysis showed significant enrichment in complement and coagulation cascades, phagosomes, the Rap1 signaling pathway, the PI3K-Akt signaling pathway, and infection. GSEA was mainly enriched in the TYROBP causal network, the inflammatory response pathway, chemokine receptor binding, the interferon signaling pathway, ECM receptor interaction, and the integrin 1 pathway. Meanwhile, mRNA-miRNA and mRNA-TF networks were constructed for common hub genes. Nine pivotal genes were identified by taking the intersection. After validating the expression differences and diagnostic values of the GSE30528 and GSE30529 datasets, eight pivotal genes (TYROBP, ITGB2, CD53, IL10RA, LAPTM5, CD48, C1QA, and IRF8) were finally identified as having diagnostic values.Conclusion: Pathway enrichment analysis scores provide insight into the genetic phenotype and may propose molecular mechanisms of DN. The target genes TYROBP, ITGB2, CD53, IL10RA, LAPTM5, CD48, C1QA, and IRF8 are promising new targets for DN. SPI1, HIF1A, STAT1, KLF5, RUNX1, MBD1, SP1, and WT1 may be involved in the regulatory mechanisms of DN development. Our study may provide a potential biomarker or therapeutic locus for the study of DN.

BackgroundSystemic sclerosis (SSc) is a rare autoimmune disease characterized by extensive skin fibrosis. There are no effective treatments due to the severity, multiorgan presentation, and variable outcomes of the disease. Here, integrated bioinformatics was employed to discover tissue-specific expressed hub genes associated with SSc, determine potential competing endogenous RNAs (ceRNA) regulatory networks, and identify potential targeted drugs.MethodsIn this study, four datasets of SSc were acquired. To identify the genes specific to tissues or organs, the BioGPS web database was used. For differentially expressed genes (DEGs), functional and enrichment analyses were carried out, and hub genes were screened and shown in a network of protein-protein interactions (PPI). The potential lncRNA–miRNA–mRNA ceRNA network was constructed using the online databases. The specifically expressed hub genes and ceRNA network were validated in the SSc mouse and in normal mice. We also used the receiver operating characteristic (ROC) curve to determine the diagnostic values of effective biomarkers in SSc. Finally, the Drug-Gene Interaction Database (DGIdb) identified specific medicines linked to hub genes.ResultsThe pooled datasets identified a total of 254 DEGs. The tissue/organ-specifically expressed genes involved in this analysis are commonly found in the hematologic/immune system and bone/muscle tissue. The enrichment analysis of DEGs revealed the significant terms such as regulation of actin cytoskeleton, immune-related processes, the VEGF signaling pathway, and metabolism. Cytoscape identified six gene cluster modules and 23 hub genes. And 4 hub genes were identified, including Serpine1, CCL2, IL6, and ISG15. Consistently, the expression of Serpine1, CCL2, IL6, and ISG15 was significantly higher in the SSc mouse model than in normal mice. Eventually, we found that MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1 may be promising RNA regulatory pathways in SSc. Besides, ten potential therapeutic drugs associated with the hub gene were identified.ConclusionsThis study revealed tissue-specific expressed genes, SERPINE1, CCL2, IL6, and ISG15, as effective biomarkers and provided new insight into the mechanisms of SSc. Potential RNA regulatory pathways, including MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1, contribute to our knowledge of SSc. Furthermore, the analysis of drug-hub gene interactions predicted TIPLASININ, CARLUMAB and BINDARIT as candidate drugs for SSc.

With the economic and social development of China, the scale of the power grid continues to expand. Rapid location and diagnosis of power failures have become significant for China to maintain its stable development of power system. In recent years, the Internet of Things (IoT) based on 5G technology has been applied to power grid more widely. Meanwhile, given the fact that the blockchain is traceable and tamper-resistant, the combination of the blockchain and IoT is considered to locate power failures quickly and assist professional maintenance personnel to deduce the cause of failures, minimizing economic loss. With the foundation of IoT sensor node data, this paper designs a decentralized electronic certificate scheme based on blockchain and Interplanetary File System (IPFS) to collect data of each node of the power system and store it in the blockchain. The model of data sharding, storage and certificate optimizes the utilization of storage space of the blockchain, reducing the time required for system access to nodes. Traceability of data stored on blockchain data is employed to quickly and accurately trace faults of the power system, providing strong technical support for the safe and stable operation of China’s power system.

Introduction: This work was carried out to understand if a heterogeneous biocatalytic hydrogenation system could be implemented in a slurry mode continuous flow reactor, as a “slot-in” alternative to a metal/carbon catalyst with minimal process or chemical engineering development.Method: Biocatalytic hydrogenation was compared to metal (Pd/C) catalysed hydrogenation for ketone to chiral alcohol conversion in both a continuous flow reactor (Coflore ACR, AM Technology) and analogous scaled down batch reactions.Results and discussion: Initial results demonstrated that batch reactions can achieve high conversions in 30 min, with relatively low biocatalyst loadings, meeting critical criteria for operation as continuous slurry mode process. Further results demonstrated full conversion of quinuclidinone to (3R)-quinuclidinol in continuous flow under mild conditions (35°C, 2 bar H2). On intensification of the process to higher substrate loading (50 mM), conversion was similar to with Pd/C, however the biocatalytic system achieved far higher turnover frequency and total turnover number (65 min−1 and 20,000, respectively) than the metal system (0.16 min−1, 37). Comparison to an analogous batch reaction highlights that the biocatalytic system has promise for further optimisation and intensification in the scalable Coflore ACR. Overall, biocatalytic hydrogenation is shown to offer a decarbonised biocatalytic route and a “slot-in” replacement to metal catalysts for hydrogenation reactions in continuous flow reactors.

Porphyrins and their derivatives have been extensively applied in various fields owing to their photophysical and electrochemical properties. However, the drawbacks of self-aggregation and self-quenching in aqueous media limit their biological applications. Porphyrinic metal-organic frameworks (PMOFs) have attracted considerable attention because the introduction of porphyrins as organic linker into frameworks overcomes the limitations of free porphyrins. This review summarizes the strategies for the construction of PMOFs and their biological applications. The challenges and chances displayed by this class of emerging materials are also discussed.

Objectives: This study aims to explore the effect of music therapy on pain, anxiety and physiologic parameters in patients undergoing prostate biopsy. Design and setting: A systematic review and meta-analysis of randomized controlled trials. Interventions: Five databases were systematically searched. The included studies reported randomized controlled trials comparing the effects of music therapy and non-music therapy on pain, anxiety, and physiologic parameters in patients undergoing prostate biopsy. The random-effects meta-analyses were performed for data synthesis. Main outcome measures: The primary outcome was pain; secondary outcomes included anxiety and physiologic parameters. Results: We analyzed seven eligible studies involving 662 males undergoing prostate biopsy. We synthesized the mean difference between music and control groups in different outcomes. Compared with control groups, music therapy reduced pain (visual analog scale score, mean difference [95% CI]: −0.92 [−1.68 to −0.17], P = 0.017, low quality) and anxiety (State-Trait Anxiety Inventory equivalent scale score, mean difference [95% CI]: −4.37 [−7.72 to −1.03], P = 0.010, low quality) after the prostate biopsy. In terms of the physiological parameters, music therapy only slightly reduced heart rate, but not blood pressure and respiratory rate after the prostate biopsy. Conclusions: Low quality of evidence showed that music therapy during prostate biopsy might reduce pain and anxiety. However, a good standard of music intervention was lacking. Cost-effective analyses are warranted to better delineate the value of music therapies for prostate biopsy.

Both eutrophication and salinization are growing global environmental problems in freshwater ecosystems, threatening the water quality and various aquatic organisms. However, little is known about their interactive effects on theses stressors and the role of lake depth on these interactions. We used field surveys to compared zooplankton assemblages over four seasons in eight Yunnan Plateau lakes with different trophic states, salinization levels, and water depths. The results showed that: 1) the species number (S), density (DZoop), and biomass (BZoop) of zooplankton exhibited strong seasonal dynamics, being overall higher in the warm seasons. 2) Data collected over four seasons and summer data both revealed highly significant positive relationships of S, DZoop, and BZoop with total nitrogen (TN), total phosphorus (TP), and phytoplankton chlorophyll a (Chl a). 3) S, DZoop, and BZoop displayed a unimodal relationship with salinity, peaking at 400–1000 μS/cm (conductivity, to reflect salinity). 4) The two large-sized taxa (cladocerans and copepods) generally increased at low-moderate levels of TN, TP, Chl a, and Cond and was constant or decreased at high levels. The average body mass (biomass/density) of crustaceans decreased with increasing TN, TP, Chl a, and conductivity. Our findings indicate that zooplankton may be more vulnerable in deep lakes than in shallow lakes when exposed to conductivity stress even under mesotrophic conditions, and the overall decrease in size in zooplankton assemblages under the combined stress of eutrophication and salinization may result in a lowered grazing effect on phytoplankton.

Introduction: Nemonoxacin is an innovative quinolone antibiotic for treatment of community-acquired pneumonia (CAP). As more data are available from clinical studies, it is necessary to perform an integrative pharmacokinetic/pharmacodynamic (PK/PD) analysis to support and justify the optimal dosing regimen of nemonoxacin in clinical practice.Methods and Results: We developed a population PK model using non-linear mixed effect model based on the data of 195 Chinese subjects receiving nemonoxacin in phase I to III clinical trials. The base model was a standard two-compartment PK model defined by clearance (12 L/h) and central volume of distribution (86 L). Covariates included creatinine clearance (CLcr), body weight (BW), sex, disease status and food. Compared to the subject with BW 60 kg, Cmax and AUC0‐24, ss reduced by 24% and 19% in the subject with BW 80 kg, respectively. Compared to the subject with CLcr 150 ml/min, AUC0‐24, ss and T1/2 increased by 28% and 24%, respectively in the subject with CLcr 30 ml/min. Compared to the fasted status, Tmax of nemonoxacin increased by 1.2 h in the subject with fed status. Effects of sex and disease status on PK parameters were small (change of PK parameters ≤19%). AUC0–24/MIC and %T > MIC were identified as the optimal PK/PD indices for predicting clinical efficacy. The AUC0-24/MIC target was 63.3, 97.8, and 115.7 against Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, respectively. The %T > MIC target was 7.96% against Klebsiella pneumoniae. Monte Carlo simulation showed that treatment with nemonoxacin 500 mg q24 h could attain a PK/PD cutoff value higher than the MIC90 against S. pneumoniae and S. aureus. The corresponding cumulative fraction of response (CFR) was greater than 93%, while nemonoxacin 750 mg q24 h would provide higher PK/PD cutoff value against Haemophilus parainfluenzae, and higher CFR (83%) than 500 mg q24 h.Conclusion: Integrative PK/PD analysis justifies the reliable clinical and microbiological efficacy of nemonoxacin 500 mg q24 h in treating CAP caused by S. pneumoniae, S. aureus, and K. pneumoniae, irrespective of patient sex, mild renal impairment, empty stomach or not. However, nemonoxacin 750 mg q24 h would provide better efficacy than 500 mg q24 h for the CAP caused by H. parainfluenzae in terms of CFR.

Abstract Benefiting from the advantageous features of structural diversity and resource renewability, organic electroactive compounds are considered as attractive cathode materials for aqueous Zn‐ion batteries (ZIBs). In this review, we discuss the recent developments of organic electrode materials for aqueous ZIBs. Although the proton (H+) storage chemistry in aqueous Zn‐organic batteries has triggered an overwhelming literature surge in recent years, this topic remains controversial. Therefore, our review focuses on this significant issue and summarizes the reported electrochemical mechanisms, including pure Zn2+ intercalation, pure H+ storage, and H+/Zn2+ co‐storage. Moreover, the impact of H+ storage on the electrochemical performance of aqueous ZIBs is discussed systematically. Given the significance of H+ storage, we also highlight the relevant characterization methods employed. Finally, perspectives and directions on further understanding the charge storage mechanisms of organic materials are outlined. We hope that this review will stimulate more attention on the H+ storage chemistry of organic electrode materials to advance our understanding and further its application.

Abstract Background Type 1 long interspersed elements, or LINE-1, are the only retroelements that replicate autonomously in human cells. The retrotransposition process of LINE-1 can trigger the activation of the innate immune system and has been proposed to play a role in the development of several autoimmune diseases, including Aicardi-Goutières syndrome (AGS). In contrast, all known AGS-associated proteins, except MDA5, have been reported to affect LINE-1 activity. Thus, MDA5 is likely to also function as a LINE-1 suppressor. Results MDA5 was found to potently suppress LINE-1 activity in a reporter-based LINE-1 retrotransposition assay. Although MDA5 is an endogenous RNA sensor able to activate the innate immune system, increased interferon (IFN) expression only contributed in part to MDA5-mediated LINE-1 suppression. Instead, MDA5 potently regulated the promoter activity of LINE-1 5′-UTR, as confirmed by transiently expressed myc-tagged MDA5 or knockdown of endogenous MDA5 expression. Consequently, MDA5 effectively reduced the generation of LINE-1 RNA and the subsequent expression of LINE-1 ORF1p and ORF2p. Interestingly, despite MDA5 being a multi-domain protein, the N-terminal 2CARD domain alone is sufficient to interact with LINE-1 5′-UTR and inhibit LINE-1 promoter activity. Conclusion Our data reveal that MDA5 functions as a promoter regulator; it directly binds to the LINE-1 5′-UTR and suppresses its promoter activity. Consequently, MDA5 reduces LINE-1 RNA and protein levels, and ultimately inhibits LINE-1 retrotransposition. In contrast, MDA5-induced IFN expression only plays a mild role in MDA5-mediated LINE-1 suppression. In addition, the N-terminal 2CARD domain was found to be a functional region for MDA5 upon inhibition of LINE-1 replication. Thus, our data suggest that besides being an initiator of the innate immune system, MDA5 is also an effector against LINE-1 activity, potentially forming a feedback loop by suppressing LINE-1-induced innate immune activation.