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Abstract Background Medical service efficiency is an important indicator for measuring the equity of medical services. Therefore, this study primarily focuses on investigating the spatiotemporal domain to explore both spatial and temporal characteristics, as well as influencing factors that affect medical service efficiency across diverse provinces in China. Methods The super Epsilon-based Measure (EBM) unexpected model has previously been utilized to quantify energy eco-efficiency, carbon emission efficiency, and green development efficiency. However, limited studies have applied this method to assess the efficiency of healthcare services. Therefore, this study investigates the application of the super-EBM-unexpected model in evaluating medical service efficiency, and further integrates spatial econometric models to explore the influencing factors of medical service efficiency and aims to identify potential avenues for improvement. Results The average efficiency of medical services in the 31 provinces of China ranges from 0.6 to 0.7, indicating predominantly low efficiency values. However, economically developed coastal areas exhibit relatively high efficiency levels above 1. Conversely, regions with relatively lower levels of economic development demonstrate lower efficiency rates at approximately 0.3. Evidently, substantial regional disparities exist. For the influencing factors, the enhancement of residents' living standards can effectively foster the medical service efficiency, while residential living standards of nearby areas can also exert an impact in this region. The influence of educational attainment on medical service efficiency exhibits a significant inhibitory effect. Conclusions The majority of China's 31 provinces exhibit suboptimal medical service efficiency, with notable regional disparities. Future policy initiatives should be tailored to address the unique challenges faced by regions with lower levels of economic development, prioritizing enhancements in both the efficacy and quality of their healthcare systems.

The outbreak of the COVID-19 has seriously affected the whole society, and vaccines were the most effective means to contain the epidemic. This paper aims to determine the top 100 articles cited most frequently in COVID-19 vaccines and to analyze the research status and hot spots in this field through bibliometrics, to provide a reference for future research. We conducted a comprehensive search of the Web of Science Core Collection database on November 29, 2023, and identified the top 100 articles by ranking them from highest to lowest citation frequency. In addition, we analyzed the year of publication, citation, author, country, institution, journal, and keywords with Microsoft Excel 2019 and VOSviewer 1.6.18. Research focused on vaccine immunogenicity and safety, vaccine hesitancy, and vaccination intention.

The thermal problems closely related to the development of human life, scientific technology and engineering production are greatly influenced by the thermal properties of carrier media, while most traditional natural substances are incompetent to achieve the flexible and diverse on-demand thermal control that is increasingly needed. Stimulated by materials science and physics, the combination of thermal metamaterial (artificial composite with peculiar thermalphyscial properties) and transformation thermotics (theoretical method of pre-designing heat distribution at will) has promoted heat transfer research enter a novel phase. Aiming at macroscopic heat transfer that is one of the most fundamental cases in thermal science and directly affects various thermal management and thermal rectification problems, in this review, we retrace the progress of transformed thermal meta-devices for manipulating macroscopic thermal field from the various aspects combining theoretical calculation, numerical simulation and experimental verification. Apart from the devices containing single field manipulation function or applicable to single thermal field, we further take a look at multifunctional transformed thermal meta-devices including devices that suitable for different physical fields and containing various forms of thermal field manipulation. Moreover, we review the explorations of practical application of transformed thermal meta-devices. Finally, we point out some limitations and challenges together with potential future directions in this fascinating area.

Abscisic acid (ABA) is one of the many naturally occurring phytohormones widely found in plants. This study focused on refining APAn, a series of previously developed agonism/antagonism switching probes. Twelve novel APAn analogues were synthesized by introducing varied branched or oxygen-containing chains at the C-6′ position, and these were screened. Through germination assays conducted on A. thaliana, colza, and rice seeds, as well as investigations into stomatal movement, several highly active ABA receptor antagonists were identified. Microscale thermophoresis (MST) assays, molecular docking, and molecular dynamics simulation showed that they had stronger receptor affinity than ABA, while PP2C phosphatase assays indicated that the C-6′-tail chain extending from the 3′ channel effectively prevented the ligand–receptor binary complex from binding to PP2C phosphatase, demonstrating strong antagonistic activity. These antagonists showed effective potential in promoting seed germination and stomatal opening of plants exposed to abiotic stress, particularly cold and salt stress, offering advantages for cultivating crops under adverse conditions. Moreover, their combined application with fluridone and gibberellic acid could provide more practical agricultural solutions, presenting new insights and tools for overcoming agricultural challenges.

Our study investigated the effects of dietary arginine supplementation on the growth performance, antioxidant capacity, intestinal digestive enzyme activity, muscle transcriptome, and gut health of Chinese perch (Siniperca chuatsi). Four isonitrogenous and isolipidic diets (50% crude protein, 11% crude lipid) with graded levels (2.61%, 2.99%, 3.37%, and 3.82%) of arginine were formulated and processed. A total of 360 Chinese perch (approximately 45–46 g) were randomly divided into four groups with triplicates of 30 fish per cage in each group. Our results revealed that although there was no significant improvement in the growth performance of Chinese perch, their antioxidant capacity and nutritional metabolism were significantly improved. Compared to the control group (without arginine supplementation, 2.61% group), feeding graded arginine levels could significantly (P < 0.05) decrease serum glucose and malondialdehyde (MDA) contents, as well as increase total superoxide dismutase (TSOD) activity. Fish fed a 3.37% arginine diet had the highest TSOD activity in the serum and liver. The intestinal morphological structure was clearer and more uniform in the 2.99% and 3.37% arginine groups. Fish fed with 3.82% arginine had significantly decreased (P < 0.05) muscle valine, glutamate, tyrosine, and total non-essential amino acid contents, with decreased (P < 0.05) intestinal amylase activity. Transcriptome analysis showed that graded arginine levels significantly (P < 0.05) influenced muscle gene expression involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of energy metabolism (amino acid, glucose, fatty acid), signaling pathways (mTOR, PI3K-Akt, MAPK, foxO, and insulin pathway), etc. The microbial community structure did not change significantly. Mycoplasma showed the highest abundance in the control group, and Cetobacterium had the highest abundance in the dietary arginine supplementation groups. Network analysis showed that the network complexity of the control group was higher than those of arginine groups. Our finding would help advance the field of arginine nutrition and guide the development of future fish feeds. Based on antioxidant and intestinal health indicators, the optimal dietary arginine requirement for Chinese perch was 2.99%–3.37% of the dry diet (6.08%–6.79% of dietary protein).

The triphenylphosphonium (TPP) cation has been widely used as a carrier for mitochondria-targeting molecules. We synthesized two commonly employed targeting systems, namely, ω-triphenylphosphonium fatty acids (group 2) and ω-triphenylphosphonium fatty alcohols (group 3), to assess the impact of the TPP module on the biological efficacy of mitochondria-targeting molecules. We evaluated their fungicidal activities against nine plant pathogenic fungi in comparison to alkyl-1-triphenylphosphonium compounds (group 1). All three compound groups exhibited fungicidal activity and displayed a distinct “cut-off effect”, which depended on the length of the carbon chain. Specifically, group 1 compounds showed a cut-off point at C10 (compound 1–7), while group 2 and 3 compounds exhibited cut-off points at C15 (compound 2–12) and C14 (compound 3–11), respectively. Notably, group 1 compounds displayed significantly higher fungicidal activity compared to groups 2 and 3. However, group 2 and 3 compounds showed similar activity to each other, although susceptibility may depend on the pathogen tested. Initial investigations into the mechanism of action of the most active compounds suggested that their fungicidal performance may be primarily attributed to their ability to damage the membrane, as well as uncoupling activity and inhibition of fungal respiration. Our findings suggest that the TPP module used in delivery systems as aliphatic acyl or alkoxyl derivatives with carbon chains length < 10 will contribute negligible fungicidal activity to the TPP-conjugate compared to the effect of high level of accumulation in mitochondria due to its mitochondria-targeting ability. These results provide a foundation for utilizing TPP as a promising carrier in the design and development of more effective mitochondria-targeting drugs or pesticides.

The national botanic garden is not only a primary means of global ex situ conservation but also a key indicator of biodiversity conservation capacity in a country. To understand the contributions of national botanic gardens from around the world to plant diversity conservation, we generated a long time-series dataset to investigate the spatiotemporal development of national botanic gardens and then explored their functional expansion from 1593 to 2023. The results showed that the development of national botanic gardens was driven by the development demands of human society and could be divided into three stages, i.e., the initial exploration stage of early botanic gardens (1593–1765), the colonial development stage of modern botanic gardens (1765–1945), and the rapid development stage of modern botanic gardens (1945–2023). The first national botanic garden was established in Western Europe, followed by other national botanic gardens being established in the rest of the world. The functions of national botanic gardens evolved from the collection of medicinal and plant resources to multiple purposes, including scientific research, plant diversity conservation, education, and dissemination of knowledge. Contemporary national botanical gardens have played a crucial role in plant diversity conservation and scientific research on the response and adaptation of plant diversity to global change. Future development and management of national botanic gardens will play a crucial role in achieving future targets of the post-2020 global biodiversity framework, which meets the UN Sustainable Development Goals.

IntroductionAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ–mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer’s disease.

IntroductionIssues related to fat, oil, and grease from kitchen waste (KFOG) in lipid-containing wastewater are intensifying globally. We reported a novel denitrifying bacterium Pseudomonas CYCN-C with lipid-utilizing activity and high nitrogen-removal efficiency. The aim of the present study was aim to explore the metabolic mechanism of the simultaneous lipid-utilizing and denitrifying bacterium CYCN-C at transcriptome level.MethodsWe comparatively investigated the cell-growth and nitrogen-removal performances of newly reported Pseudomonas glycinae CYCN-C under defined cultivation conditions. Transcriptome analysis was further used to investigate all pathway genes involved in nitrogen metabolism, lipid degradation and utilization, and cell growth at mRNA levels.ResultsCYCN-C could directly use fat, oil, and grease from kitchen waste (KFOG) as carbon source with TN removal efficiency of 73.5%, significantly higher than that (60.9%) with sodium acetate. The change levels of genes under defined KFOG and sodium acetate were analyzed by transcriptome sequencing. Results showed that genes cyo, CsrA, PHAs, and FumC involved in carbon metabolism under KFOG were significantly upregulated by 6.9, 0.7, 26.0, and 19.0-folds, respectively. The genes lipA, lipB, glpD, and glpK of lipid metabolic pathway were upregulated by 0.6, 0.4, 21.5, and 1.3-folds, respectively. KFOG also improved the denitrification efficiency by inducing the expression of the genes nar, nirB, nirD, and norR of denitrification pathways.ConclusionIn summary, this work firstly provides valuable insights into the genes expression of lipid-utilizing and denitrifying bacterium, and provides a new approach for sewage treatment with reuse of KFOG wastes.

Background & Aims: The machinery that prevents colorectal cancer liver metastasis (CRLM) in the context of liver regeneration (LR) remains elusive. Ceramide (CER) is a potent anti-cancer lipid involved in intercellular interaction. Here, we investigated the role of CER metabolism in mediating the interaction between hepatocytes and metastatic colorectal cancer (CRC) cells to regulate CRLM in the context of LR. Methods: Mice were intrasplenically injected with CRC cells. LR was induced by 2/3 partial hepatectomy (PH) to mimic the CRLM in the context of LR. The alteration of corresponding CER-metabolizing genes was examined. The biological roles of CER metabolism in vitro and in vivo were examined by performing a series of functional experiments. Results: Induction of LR augmented apoptosis but promoted matrix metalloproteinase 2 (MMP2) expression and epithelial-mesenchymal transition (EMT) to increase the invasiveness of metastatic CRC cells, resulting in aggressive CRLM. Up-regulation of sphingomyelin phosphodiesterase 3 (SMPD3) was determined in the regenerating hepatocytes after LR induction and persisted in the CRLM-adjacent hepatocytes after CRLM formation. Hepatic Smpd3 knockdown was found to further promote CRLM in the context of LR by abolishing mitochondrial apoptosis and augmenting the invasiveness in metastatic CRC cells by up-regulating MMP2 and EMT through promoting the nuclear translocation of β-catenin. Mechanistically, we found that hepatic SMPD3 controlled the generation of exosomal CER in the regenerating hepatocytes and the CRLM-adjacent hepatocytes. The SMPD3-produced exosomal CER critically conducted the intercellular transfer of CER from the hepatocytes to metastatic CRC cells and impeded CRLM by inducing mitochondrial apoptosis and restricting the invasiveness in metastatic CRC cells. The administration of nanoliposomal CER was found to suppress CRLM in the context of LR substantially. Conclusions: SMPD3-produced exosomal CER constitutes a critical anti-CRLM mechanism in LR to impede CRLM, offering the promise of using CER as a therapeutic agent to prevent the recurrence of CRLM after PH.

Drought stress profoundly affects plant growth and development, posing a significant challenge that is extensively researched in the field. Thioredoxins (TRXs), small proteins central to redox processes, are crucial to managing both abiotic and biotic stresses. In this research, the VyTRXy gene, cloned from wild Yanshan grapes, was validated as a functional TRX through enzyme activity assays. VyTRXy was found to bolster photosynthesis, augment levels of osmotic regulators, stimulate antioxidant enzyme activities, and strengthen drought resilience in transgenic plants. These enhancements were evidenced by higher survival rates, optimized photosynthetic metrics, increased proline levels, augmented chlorophyll concentration, reduced electrolyte leakage, and decreased malondialdehyde and hydrogen peroxide (H2O2) levels. Furthermore, there was a surge in the activities of enzymes such as catalase, ascorbate peroxidase, glutathione peroxidase, dehydroascorbate reductase, and glutathione reductase, along with an increased expression of TRX peroxidase. Notably, under drought stress, there was a marked elevation in the expression of stress-responsive genes, including the adversity stress-inducible expression gene (NtRD29A) and DRE-binding protein (NtDREB), in transgenic tobacco. This investigation is pivotal in the quest for drought-resistant grapevine varieties and provides significant insights into the molecular functionality of VyTRXy in enhancing grapevine drought tolerance.

Abstract Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

Abstract The detection of road infrared targets is essential for autonomous driving. Different from RGB images, the acquisition of infrared images is unaffected by visible light. However, the signal‐to‐noise ratio still presents significant challenges. This study demonstrates an improved infrared target detection model for road infrared target detection. An advanced EfficientNet is incorporated to replace the conventional structure and enhance feature extraction. A Dilated‐Residual U‐Net is also introduced to reduce the noise of infrared images. Meanwhile, the k‐means algorithm and data enhancement are implemented to improve the detection performance. The experimental results show that the mean average precision of the proposed model is observed to be 0.89 for the infrared road dataset with an average detection speed of 10.65 s−1.

Alzheimer’s disease (AD) is a leading cause of dementia, impacting millions worldwide. However, its complex neuropathologic features and heterogeneous pathophysiology present significant challenges for diagnosis and treatment. To address the urgent need for early AD diagnosis, this review focuses on surface-enhanced Raman scattering (SERS)-based biosensors, leveraging the excellent optical properties of nanomaterials to enhance detection performance. These highly sensitive and noninvasive biosensors offer opportunities for biomarker-driven clinical diagnostics and precision medicine. The review highlights various types of SERS-based biosensors targeting AD biomarkers, discussing their potential applications and contributions to AD diagnosis. Specific details about nanomaterials and targeted AD biomarkers are provided. Furthermore, the future research directions and challenges for improving AD marker detection using SERS sensors are outlined.

The control and regulation of thermal fields is of great significance in solving various thermal management problems in human life. Benefitting from the emerging space transformation technique and thermal meta-material, thermal meta-structures with unique thermal control capabilities have been rapidly developed in recent years. However, the exploration of the functional diversity of thermal meta-materials and structures is still inadequate; most related works are still limited to the single-field control effect and lack sensitivity to external environment changes. For the designed functional structures, observation and analysis of energy fluctuations and irreversible heat loss during the regulation process of the diffusive thermal field are also scare. Therefore, in this current work, we design a thermal meta-regulator (based on the space transformation theory) that is capable of differently distributing thermal energy according to the heat input direction and switching field control pattern with the change of ambient temperature. In addition to the common indicator of temperature, we also introduce the local entropy production rate and the total entropy production in the thermo-dynamic category to carry out entropy analysis of the energy processes involved in the thermal meta-regulator, making a multi-angle evaluation of the structural performance. Furthermore, we use the statistical response surface method to explore the comprehensive/interaction effect of multiple influencing factors on the thermal meta-regulator; the derived regression equations can be used to accurately predict the structural effects under different design schemes and temperature conditions. Our work further enriches the diversity and flexibility of thermal field manipulation manners and the demonstrated functions are also expected to be realized in other physical fields.

Abstract One-dimensional and two-dimensional materials are widely used to compose the conductive network atop soft substrate to form flexible strain sensors for several wearable electronic applications. However, limited contact area and layer misplacement hinder the rapid development of flexible strain sensors based on 1D or 2D materials. To overcome these drawbacks above, we proposed a hybrid strategy by combining 1D carbon nanotubes (CNTs) and 2D graphene nanoplatelets (GNPs), and the developed strain sensor based on CNT-GNP hierarchical networks showed remarkable sensitivity and tenability. The strain sensor can be stretched in excess of 50% of its original length, showing high sensitivity (gauge factor 197 at 10% strain) and tenability (recoverable after 50% strain) due to the enhanced resistive behavior upon stretching. Moreover, the GNP-CNT hybrid thin film shows highly reproducible response for more than 1000 loading cycles, exhibiting long-term durability, which could be attributed to the GNPs conductive networks significantly strengthened by the hybridization with CNTs. Human activities such as finger bending and throat swallowing were monitored by the GNP-CNT thin film strain sensor, indicating that the stretchable sensor could lead to promising applications in wearable devices for human motion monitoring.

Depression, one of the most common causes of disability, has a high prevalence rate in patients with metabolic syndrome. Type 2 diabetes patients are at an increased risk for depression. However, the molecular mechanism coupling diabetes to depressive disorder remains largely unknown. Here we found that the neuroinflammation, associated with high-fat diet (HFD)-induced diabetes and obesity, activated the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) in hippocampal neurons. This factor repressed brain-derived neurotrophic factor (BDNF) expression and caused depression-like behaviors in male mice. Besides, the loss of C/EBPβ expression in C/EBPβ heterozygous knockout male mice attenuated HFD-induced depression-like behaviors, whereas Thy1-C/EBPβ transgenic male mice (overexpressing C/EBPβ) showed depressive behaviors after a short-term HFD. Furthermore, HFD impaired synaptic plasticity and decreased surface expression of glutamate receptors in the hippocampus of wild-type (WT) mice, but not in C/EBPβ heterozygous knockout mice. Remarkably, the anti-inflammatory drug aspirin strongly alleviated HFD-elicited depression-like behaviors in neuronal C/EBPβ transgenic mice. Finally, the genetic delivery of BDNF or the pharmacological activation of the BDNF/TrkB signaling pathway by 7,8-dihydroxyflavone reversed anhedonia in a series of behavioral tests on HFD-fed C/EBPβ transgenic mice. Therefore, our findings aim to demonstrate that the inflammation-activated neuronal C/EBPβ promotes HFD-induced depression by diminishing BDNF expression.

Brain derived neurotrophic factor (BDNF) has multiple biological functions which are mediated by the activation of two receptors, tropomyosin receptor kinase B (TrkB) receptor and the p75 neurotrophin receptor, involving in physiological and pathological processes throughout life. The diverse presence and activity of BDNF indicate its potential role in the pathogenesis, progression and treatment of both neurological and psychiatric disorders. This review is to provide a comprehensive assessment of the current knowledge and future directions in BDNF-associated research in the central nervous system (CNS), with an emphasis on the physiological and pathological functions of BDNF as well as its potential treatment effects in CNS diseases, including depression, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and cerebral ischemic stroke.

During the service of pressure vessels, a variety of structural damage will occur, among which the corrosion pit formed by the corrosion of the loaded materials is the most important defect. In addition, cracks are formed due to the stress concentration in the pit position, which may propagate and result in fracturing and leakage. Stress intensity factor, as an important parameter to characterize the cracks, is widely used in engineering to judge the safety and reliability of the mechanical structures. Thereby, with reference to the two-parameter pit-crack model, the change rule of the nominal stress intensity factor of crack in the presence of pit-crack was discussed with ANSYS finite element software. The results show that the existence of pit-crack increases the nominal stress intensity factor of crack, but the effect decreases with the increase of pit-crack spacing and trends to be stable. Moreover, the effects of the pit parameters and the length-depth ratio of cracks on the stress intensity factor have obvious interval characteristics. Generally, the research results could provide reference for the failure evaluation of pressure vessels with pit-cracks.

The discovery of a new two-dimensional van der Waals layered MoSi2N4 material inspires many attentions. Here, the authors report intercalation strategies to explore a much wider range of MA2Z4 family and predict amount of materials accessible to experimental verifications with emergent topological, magnetic or Ising superconductivity properties.

Abstract Exploring new materials and methods to achieve high utilization of sulfur with lean electrolyte is still a common concern in lithium‐sulfur batteries. Here, high‐density oxygen doping chemistry is introduced for making highly conducting, chemically stable sulfides with a much higher affinity to lithium polysulfides. It is found that doping large amounts of oxygen into NiCo2S4 is feasible and can make it outperform the pristine oxides and natively oxidized sulfides. Taking the advantages of high conductivity, chemical stability, the introduced large Li–O interactions, and activated Co (Ni) facets for catalyzing Sn2–, the NiCo2(O–S)4 is able to accelerate the Li2S‐S8 redox kinetics. Specifically, lithium‐sulfur batteries using free‐standing NiCo2(O–S)4 paper and interlayer exhibit the highest capacity of 8.68 mAh cm–2 at 1.0 mA cm–2 even with a sulfur loading of 8.75 mg cm–2 and lean electrolyte of 3.8 µL g–1. The high‐density oxygen doping chemistry can be also applied to other metal compounds, suggesting a potential way for developing more powerful catalysts towards high performance of Li–S batteries.

Abstract Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.

Recently, rapid development of intelligent wearable electronic equipment has triggered great needs for flexible and lightweight portable energy storage systems. Here, we demonstrate a low-cost ($ 0.5 m-2) and low density carbonized facial tissue paper (FCP) for high-conductive NiCo2S4 nanotubes assisted novel ultra-flexible solid-state supercapacitors (SSCs). The hydrothermal synthesized FCP-900@NiCo2S4 electrodes in this paper only have a density of 5 mg cm−2 and show large specific capacitance of 3115 mF cm−2 at 2 mA cm−2. Based on the high performance of FCP-900@NiCo2S4 electrodes, the as assembled SSCs can deliver an energy density of 1.2 mWh cm−3, high power density of 58.16 mW cm−3. It also shows great bending-state capacitive performance with high capacitance retention after 5000 cycles, providing a new opportunity for developing high-performance flexible wearable energy storage devices.

Energy conservation has always been a prominent design goal for hierarchical routing protocols supporting sink mobility. Advertising the current position of mobile sink introduces control packet overhead which ultimately results in an increase in energy consumption and shorter network lifetime. Energy harvesting through ambient sources have enabled the utilization of rechargeable devices for Wireless Sensor Networks to perpetually remain operational. The modifications in the hierarchical structure of wireless sensor networks along with energy scavenging approaches could possibly minimize the control packet overhead and also provide a significant improvement in energy conservation. In this paper, we propose a novel Harvested Energy Scavenging and Transfer capabilities in Opportunistic Ring Routing protocol which uses a distinguishing approach of hybrid (ring + cluster) topology in which the network architecture is initially supported by the formation of a virtual ring structure and then a two-tier routing topology is used in the virtual ring as an overlay by grouping nodes into clusters. The rate of energy gain from solar harvesting and radio frequency transfer is the criterion for selecting cluster heads. The role of cluster heads is exploited to advertise the mobile sink current position as well as forward the aggregated data towards mobile sink using energy transfer based opportunistic routing. The simulation results reveal that our scheme considerably outperforms the existing benchmarks in terms of control packet overhead, energy conservation, network lifetime, packet delivery ratio and average end-end delay.

Experimental and numerical studies of a linear high-loaded turbine cascade with a dual−cavity tip structure are presented in this paper. The experimental conditions contained an increase in the outlet Mach number from 0.42 to 0.92, a change in the incidence angle from −15° to 15° and an increase in the relative clearance size from 0.36% to 1.4%. The ability of the dual−cavity tip to control leakage losses and vortices is assessed using the total pressure coefficient and the Q-criterion. This research indicates that the leakage vortex interacts strongly with the passage vortex, and the change in working conditions affects the balance between the two vortices and thus the flow field structure. The experimental and numerical results prove that the dual−cavity tip can reduce losses in all operating conditions, with the best control effect reduced by 0.025 in a large clearance size condition. In addition, the leakage control effect of the blade tip structure is more influenced by the incoming flow angle and clearance size than the Mach number.

The title compound, a major animal feed supplement, abbreviated as HMTBA and alternatively called dl-methionine hydroxy analogue, C5H10O3S, (I), was isolated in pure anhydrous monomeric form. The melting point is 302.5 K and the compound crystallizes in the monoclinic space group P21/c, with two conformationally non-equivalent molecules [(IA) and (IB)] in the asymmetric unit. The crystal structure is formed by alternating polar and non-polar layers running along the bc plane and features an extensive hydrogen-bonding network within the polar layers. The Hirshfeld surface analysis revealed a significant contribution of non-polar H...H and H...S interactions to the packing forces for both molecules.

Adult female mosquitoes rely on olfactory cues like carbon dioxide and other small molecules to find vertebrate hosts to acquire blood. The molecular physiology of the mosquito olfactory system is critical for their host preferences. Many laboratory strains of the yellow fever mosquito Aedes aegypti have been established since the late 19th century. These strains have been used for most molecular studies in this species. Some earlier comparative studies have identified significant physiological differences between different laboratory strains. In this study, we used a Y-tube olfactometer to determine the attraction of females of seven different strains of Ae. aegypti to a human host: UGAL, Rockefeller, Liverpool, Costa Rica, Puerto Rico, and two odorant receptor co-receptor (Orco) mutants Orco2 and Orco16. We performed RNA-seq using antennae of Rockefeller, Liverpool, Costa Rica, and Puerto Rico females. Our results showed that female Aedes aegypti from the Puerto Rico strain had significantly reduced attraction rates toward human hosts compared to all other strains. RNA-seq analyses of the antenna transcriptomes of Rockefeller, Liverpool, Costa Rica, and Puerto Rico strains revealed distinct differences in gene expression between the four strains, but conservation in gene expression patterns of known human-sensing genes. However, we identified several olfaction-related genes that significantly vary between strains, including receptors with significantly different expression in mosquitoes from the Puerto Rico strain and the other strains.

Radiation enteritis (RE) is a common complication in cancer patients receiving radiotherapy. Although studies have shown the changes of this disease at clinical, pathological and other levels, the dynamic characteristics of local microbiome and metabolomics are hitherto unknown. We aimed to examine the multi-omics features of the gut microecosystem, determining the functional correlation between microbiome and lipid metabolites during RE activity. By delivering single high-dose irradiation, a RE mouse model was established. High-throughput 16S rDNA sequencing and global lipidomics analysis were performed to examine microbial and lipidomic profile changes in the gut microecosystem. Spearman correlation analysis was used to determine the functional correlation between bacteria and metabolites. Clinical samples were collected to validate the above observations. During RE activity, the intestinal inflammation of the mice was confirmed by typical signs, symptoms, imaging findings and pathological evidences. 16S datasets revealed that localized irradiation dramatically altered the gut microbial composition, resulting in a decrease ratio of Bacteroidetes to Firmicutes. Lipidomics analysis indicated the remarkable lipidomic profile changes in enteric epithelial barrier, determining that glycerophospholipids metabolism was correlated to RE progression with the highest relevance. Spearman correlation analysis identified that five bacteria-metabolite pairs showed the most significant functional correlation in RE, including Alistipes-PC(36:0e), Bacteroides-DG(18:0/20:4), Dubosiella-PC(35:2), Eggerthellaceae-PC(35:6), and Escherichia-Shigella-TG(18:2/18:2/20:4). These observations were partly confirmed in human specimens. Our study provided a comprehensive description of microbiota dysbiosis and lipid metabolic disorders in RE, suggesting strategies to change local microecosystem to relieve radiation injury and maintain homeostasis.

TO (transformation optics)-based transformation thermotics offers an advanced way to design the propagation path of heat flux at will, which is valuable for the regulation and utilization of thermal energy. Thermal concentrator as one of the typical representatives has great application potential in fuel cells, solar thermal collectors, heat storages, and other energy related devices due to its advantageous functionality and efficiency. However, most existing TO-based thermal concentrators only perform the same thermal rectification effect in different environments, which is limited in industrial applications and insufficient to meet diverse requirements. In this work, based on the improved temperature-dependent transformation thermotics theory and taking thermal protection issue into account, we designed an intelligent thermal concentrator, which can spontaneously exhibit different working states corresponding to different environmental conditions; investigation and optimization of structural sensitivity were also carried out toward two impact factors. In addition, the proposed model was theoretically realized referring to wedge-like shaped materials, and two thermal control apparatus were enumerated as extensions of current work. The proposed intelligent thermal concentrator possessing nonlinear characteristic as well as active functionality can provide reference for energy collection equipment in industrial application, and the revealed methodology can be expanded to design other types of TO-based devices in thermal even multi-physical field.

Nanoscale thermal cloaks have great potential in the thermal protection of microelectronic devices, for example, thermal shielding of thermal components close to the heat source. Researchers have used graphene, crystalline silicon film, and silicon carbide to design a variety of thermal cloaks in different ways. In our previous research, we found that the porous structure has lower thermal conductivity compared to bulk silicon; thus, so we tried to use the porous structure to construct the functional region to control the heat flux. We first calculated the thermal conductivity of crystalline silicon and porous silicon films by means of nonequilibrium molecular dynamics, proving that the porous structure satisfied the conditions for building a thermal cloak. A rectangular cloak with a porous structure was constructed, and a crystalline silicon film was used as a reference to evaluate its performance by the index of the ratio of thermal cloaking. We found that the thermal cloak built with a porous structure could produce an excellent cloaking effect. Lastly, we explain the mechanism of the cloaking phenomenon produced by a porous structure with the help of phonon localization theory. Porous structures have increased porosity compared to bulk silicon and are not conducive to phonon transport, thus producing strong phonon localization and reducing thermal conductivity. Our research expands the construction methods of nanocloaks, expands the application of porous structure materials, and provides a reference for the design of other nanodevices.

Abstract The rapid onset of resistance to cetuximab (CTX) limits its clinical utility in colorectal cancer (CRC) patients. This study aims to understand a potential role of mismatch repair gene mutL homolog 1 (MLH1) in CTX response. Functional analysis of MLH1 in Her‐2/phosphoinositide 3‐kinases (PI3K)/PKB protein kinase (AKT)‐regulated CTX sensitivity is performed using human CRC specimens, CRC cell lines with different MLH1 expression levels, and a subcutaneous xenograft model. Overexpression, knockdown, small interfering RNA, and inhibitors are used to examine the role of MLH1 and HER‐2 downstream signaling and apoptotic targets in CTX sensitivity. Reduced MLH1 expression is correlated with unfavorable prognosis in cetuximab‐treated patients. MLH1 loss decreases CTX sensitivity through Her‐2/PI3K/AKT signaling and apoptosis resistance in culture and in xenografts, while MLH1 overexpression increases CTX sensitivity. Blocking Her‐2 signaling increases CTX sensitivity of microsatellite instability CRC in vitro and in vivo. MLH1 loss induces activation of Her‐2/PI3K/AKT signaling and leads to cetuximab resistance in colon cancer.

Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.

Abstract Background Autophagy is a conserved catabolic process with complicated roles in tumor development. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF-β) family of regulatory proteins, plays a crucial role in human malignancies. However, whether BMP4 contributes to the regulation of autophagy in hepatocellular carcinoma (HCC) progression remains elusive. Methods Functional analysis of BMP4 on HCC proliferation and autophagy was performed both in vitro and in vivo in HepG2 and HCCLM3 cells. Autophagic activity was estimated by Western blot for autophagic marker proteins and by transmission electron microscopy (TEM). Transfection of mRFP-GFP-LC3 adenovirus was applied to observe autophagic flux and high content screening was used for quantification. The signaling pathway of BMP4-regulated HCC proliferation and autophagy was investigated by Western blot. Results BMP4 treatment promoted HCC cells proliferation and induced autophagy. The in vivo xenograft model supported that BMP4 overexpression promoted the growth of HCC cells and autophagy induction while BMP4 knockdown exerted the opposite effect. 3-MA pre-treatment or knockdown of Beclin-1 (BECN1) blocked HCC autophagy by decreasing the expression of LC3-II and subsequently attenuated BMP4-induced autophagy and cells proliferation enhanced by BMP4 in vitro and in vivo. Mechanistic study revealed that the induction of autophagy by BMP4 was mediated through activating the JNK1/Bcl2 pathway. Furthermore, the JNK1 inhibitor and knockdown of JNK1 could attenuate autophagy induced by BMP4 and eliminated BMP4-promoted HCC cells growth. Conclusions BMP4 promoted HCC proliferation by autophagy activation through JNK1/Bcl-2 signaling.

As a typical representative of transformation thermodynamics, which is the counterpart of transformation optics, the thermal cloak has been explored extensively while most current research focuses on the structural design instead of adaptability and practicability in a dynamic environment. The evaluation of energy processes involved in the thermal cloak under dynamic conditions are also lacking, which is essential to the engineering application of this functional structure. In this paper, based on the dynamic environment of a sinusoidal form with ambient amplitude, distribution density, phase, and temperature difference as variables, we evaluated the cloaking performance and environmental response of a 2D thermal cloak. Considering the heat dissipation and energy loss in the whole procedure, local entropy production rate and response entropy were introduced to analyze the different influences of each environmental parameter on the cloaking system. Moreover, we constructed a series of comprehensive schemes to obtain the fitting equation as well as an appropriate scope to apply the thermal cloak. The results are beneficial to the novel use of the concept of entropy and valuable for further improving the working efficiency and potential engineering applications of the thermal cloak.

The Three Gorges Dam (TGD) is a remarkable, far-reaching project in China. This study was conducted to assess the impact of TGD on changes in the ecological environment, snail distribution and schistosomiasis transmission in Dongting Lake area.Hydrological data were collected from 12 monitoring sites in Hunan section of Yangtze River before and after TGD was established. Data on snail distribution and human schistosomiasis infection were also collected. Correlation analyses were performed to detect the significance of snail distribution to changes in ecological environmental factors and human schistosomiasis infection.A series of ecological environmental factors have changed in Dongting Lake area following the operation of TGD. Volume of annual runoff discharged into Dongting Lake declined by 20.85%. Annual sediment volume discharged into the lake and the mean lake sedimentation rate decreased by 73.9% and 32.2%, respectively. From 2003 to 2015, occurrence rate of frames with living snails and mean density of living snails decreased overall by 82.43% and 94.35%, respectively, with annual decrements being 13.49% and 21.29%. Moreover, human infection rate of schistosomiasis had decreased from 3.38% in 2003 to 0.44% in 2015, with a reduction of 86.98%. Correlation analyses showed that mean density of living snails was significantly associated with water level (r = 0.588, p

Introduction: The life history of Aedes aegypti presents diverse challenges to its diuretic system. During the larval and pupal life stages mosquitoes are aquatic. With the emergence of the adult they become terrestrial. This shifts the organism within minutes from an aquatic environment to a terrestrial environment where dehydration has to be avoided. In addition, female mosquitoes take large blood meals, which present an entirely new set of challenges to salt and water homeostasis.Methods: To determine differences in gene expression associated with these different life stages, we performed an RNA-seq analysis of the main diuretic tissue in A. aegypti, the Malpighian tubules. We compared transcript abundance in 4th instar larvae to that of adult females and analyzed the data with a focus on transcripts that encode proteins potentially involved in diuresis, like water and solute channels as well as ion transporters. We compared our results against the model of potassium- and sodium chloride excretion in the Malpighian tubules proposed by Hine et al. (2014), which involves at least eight ion transporters and a proton-pump.Results: We found 3,421 of a total number of 17,478 (19.6%) unique transcripts with a P < 0.05 and at least a 2.5 fold change in expression levels between the two groups. We identified two novel transporter genes that are highly expressed in the adult Malpighian tubules, which have not previously been part of the transport model in this species and may play important roles in diuresis. We also identified candidates for hypothesized sodium and chloride channels. Detoxification genes were generally higher expressed in larvae.Significance: This study represents the first comparison of Malpighian tubule transcriptomes between larval and adult A. aegypti mosquitoes, highlighting key differences in their renal systems that arise as they transform from an aquatic filter-feeding larval stage to a terrestrial, blood-feeding adult stage.