The responses of CO2 emission to nitrogen application and earthworm addition in the soybean cropland.

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.

BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres for minimally invasive bone repair.

Minimally invasive, efficient, and satisfactory treatment for irregular and lacunar bone defects is still a challenge. Alginate hydrogels serve as promising stem cell (SC) delivery systems for bone regeneration but are limited by low cellular viability, poor osteogenic differentiation, and insufficient mechanical support. Herein, we developed a BMSCs-laden mechanically reinforced bioactive sodium alginate composite hydrogel microspheres (BCHMs) system via a microfluidic method that possesses 1) a uniform size and good injectability to meet clinical bone defects with complex shapes, 2) high cellular viability maintenance and further osteogenic induction capacity, and 3) improved mechanical properties. As the main matrix, the sodium alginate hydrogel maintains the high viability of encapsulated BMSCs and efficient substance exchange. Enhanced mechanical properties and osteogenic differentiation of the BCHMs in vitro were observed with xonotlite (Ca6Si6O17(OH)2, CSH) nanowires incorporated. Furthermore, BCHMs with 12.5 % CSH were injected into rat femoral bone defects, and satisfactory in situ regeneration outcomes were observed. Overall, it is believed that BCHMs expand the application of polysaccharide science and provide a promising injectable bone substitute for minimally invasive bone repair.

Robust and sensitive conductive nanocomposite hydrogel with bridge cross-linking-dominated hierarchical structural design.

Conductive hydrogels have a remarkable potential for applications in soft electronics and robotics, owing to their noteworthy attributes, including electrical conductivity, stretchability, biocompatibility, etc. However, the limited strength and toughness of these hydrogels have traditionally impeded their practical implementation. Inspired by the hierarchical architecture of high-performance biological composites found in nature, we successfully fabricate a robust and sensitive conductive nanocomposite hydrogel through self-assembly-induced bridge cross-linking of MgB2 nanosheets and polyvinyl alcohol hydrogels. By combining the hierarchical lamellar microstructure with robust molecular B─O─C covalent bonds, the resulting conductive hydrogel exhibits an exceptional strength and toughness. Moreover, the hydrogel demonstrates exceptional sensitivity (response/relaxation time, 20 milliseconds; detection lower limit, ~1 Pascal) under external deformation. Such characteristics enable the conductive hydrogel to exhibit superior performance in soft sensing applications. This study introduces a high-performance conductive hydrogel and opens up exciting possibilities for the development of soft electronics.

A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Lipidomics reveals serum lipid metabolism disorders in CTD-induced liver injury.

BACKGROUND: Cantharidin (CTD), the main toxic component of Mylabris, has been extensively used for tumor treatment in recent years. CTD-induced liver toxicity has attracted significant interest in clinic. METHODS: In this study, biochemical parameters and liver pathological changes were analyzed after CTD was administered to mice by gavage. Subsequently, a lipidomic approach was used to investigate serum lipid metabolism disorders, and the mechanism underlying CTD-induced liver injury in mice was explored. RESULTS: The results showed that the levels of TC and LDL-C were significantly increased after CTD intervention. Besides, pathological results showed inflammatory cell infiltration and hepatocyte necrosis in the liver. Furthermore, lipidomics found that a total of 18 lipid metabolites were increased and 40 were decreased, including LPC(20:4), LPC(20:3), PC(22:6e/2:0), PE(14:0e/21:2), PC(18:2e/22:6), glycerophospholipids, CE(16:0), CE(18:0) Cholesterol esters and TAG(12:0/12:0/22:3), TAG(16:1/16:2/20:4), TAG(18:1/18:1/20:0), TAG(16:2/18:2/18:2), TAG(18:0/18:0/20:0), TAG(13:1/19:0/19:0) glycerolipids. Metabolic pathway analysis found that glycerophospholipid, glycerol ester and glycosylphosphatidylinositol (GPI)-anchored biosynthetic metabolic pathways were dysregulated and the increase in PE caused by glycophoric metabololism and GPI may be the source of lipid metabolism disorders caused by CTD. Overall, the present study provided new insights into the mechanism of CTD-induced liver injury and increased drug safety during clinical application.

Occluded Facial Pain Assessment in the ICU using Action Units Guided Network.

Untreated pain in critically ill patients can lead to immunosuppression and increased metabolic activity, with severe clinical consequences such as tachypnea and delirium. Continuous pain assessment is challenging due to nursing shortages and intensive care unit (ICU) workload. Mechanical ventilation equipment obscures the facial features of many patients in the ICU, making previous facial pain detection methods based on full-face images inapplicable. This paper proposes a facial Action Units (AUs) guided pain assessment network for faces under occlusion. The network consists of an AU-guided (AUG) module, a texture feature extraction (TFE) module, and a pain assessment (PA) module. The AUG module automatically detects AUs in the non-occluded areas of the face. In contrast, the TFE module detects the facial landmarks and crops prior knowledge patches, a random exploration patch, and a global feature patch. Then these patches are fed into two convolutional networks to extract texture features. Afterward, the designed AU guidances and texture features are fused in the PA module to assess the pain state. Extensive validation is conducted on a public dataset and two datasets created in this work. The proposed network architecture achieves superior performance in binary classification, four-class classification, and intensity regression tasks. In addition, we have successfully applied the network to actual data collected in the laboratory environment with excellent results.

TNFSF15 facilitates the differentiation of CD11b+ myeloid cells into vascular pericytes in tumors.

OBJECTIVE: Immature vasculature lacking pericyte coverage substantially contributes to tumor growth, drug resistance, and cancer cell dissemination. We previously demonstrated that tumor necrosis factor superfamily 15 (TNFSF15) is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis. The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b+ cells and further into pericytes. METHODS: A model of Lewis lung cancer was established in mice with red fluorescent bone marrow. After TNFSF15 treatment, CD11b+ myeloid cells and vascular pericytes in the tumors, and the co-localization of pericytes and vascular endothelial cells, were assessed. Additionally, CD11b+ cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells. RESULTS: We observed elevated percentages of bone marrow-derived CD11b+ myeloid cells and vascular pericytes in TNFSF15-treated tumors, and the latter cells co-localized with vascular endothelial cells. TNFSF15 protected against CD11b+ cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways. CONCLUSIONS: TNFSF15 facilitates the production of CD11b+ cells in the bone marrow and promotes the differentiation of these cells into pericytes, which may stabilize the tumor neovasculature.

Automatic Positive and Negative Emotion Regulation in Adolescents with Major Depressive Disorder.

INTRODUCTION: Adolescents with major depressive disorder (MDD) exhibit hypoactivity to positive stimuli and hyperactivity to negative stimuli in terms of neural responses. Automatic emotion regulation (AER) activates triple networks (i.e., the central control network, default mode network, and salience network). Based on previous studies, we hypothesized that adolescents with MDD exhibit dissociable spatiotemporal deficits during positive and negative AER. METHODS: We first collected EEG data from 32 adolescents with MDD and 35 healthy adolescents while they performed an implicit emotional Go/NoGo task. Then, we characterized the spatiotemporal dynamics of cortical activity during AER. RESULTS: In Go trials, MDD adolescents exhibited reduced N2 amplitudes, enhanced theta power for positive pictures, and stronger bottom-up information flow from the left orbitofrontal cortex (OFC) to the right superior frontal gyrus compared to top-down information flow than the controls. In contrast, in NoGo trials, MDD adolescents exhibited elevated P3 amplitudes, enhanced theta power, and stronger top-down information flows from the right middle frontal gyrus to the right OFC and the left insula than the controls. CONCLUSION: Overall, adolescents with MDD exhibited impaired automatic attention to positive emotions and impaired automatic response inhibition. These findings have potential implications for the clinical treatment of adolescents with MDD.

The Current Progress of Tetrahedral DNA Nanostructure for Antibacterial Application and Bone Tissue Regeneration.

Recently, programmable assembly technologies have enabled the application of DNA in the creation of new nanomaterials with unprecedented functionality. One of the most common DNA nanostructures is the tetrahedral DNA nanostructure (TDN), which has attracted great interest worldwide due to its high stability, simple assembly procedure, high predictability, perfect programmability, and excellent biocompatibility. The unique spatial structure of TDN allows it to penetrate cell membranes in abundance and regulate cellular biological properties as a natural genetic material. Previous studies have demonstrated that TDNs can regulate various cellular biological properties, including promoting cells proliferation, migration and differentiation, inhibiting cells apoptosis, as well as possessing anti-inflammation and immunomodulatory capabilities. Furthermore, functional molecules can be easily modified at the vertices of DNA tetrahedron, DNA double helix structure, DNA tetrahedral arms or DNA tetrahedral cage structure, enabling TDN to be used as a nanocarrier for a variety of biological applications, including targeted therapies, molecular diagnosis, biosensing, antibacterial treatment, antitumor strategies, and tissue regeneration. In this review, we mainly focus on the current progress of TDN-based nanomaterials for antimicrobial applications, bone and cartilage tissue repair and regeneration. The synthesis and characterization of TDN, as well as the biological merits are introduced. In addition, the challenges and prospects of TDN-based nanomaterials are also discussed.

Litter inputs exert greater influence over soil respiration and its temperature sensitivity than roots in a coniferous forest in north-south transition zone.

The changes in carbon inputs of litter and roots to forest soils caused by climate change will result in a serious cascade effect on soil respiration and its temperature sensitivity (Q10). To differentiate and quantify the effects of surface litter and living roots on soil respiration and Q10, and further explore the role of abiotic factors and microbial properties on soil respiration and Q10, a short-term (two years) detritus input and removal treatment experiment was conducted in a coniferous forest of central China. Soil temperature, soil moisture, C/N, microbial biomass and community composition were analyzed to explore the drive mechanisms of soil respiration and Q10 in response to carbon inputs. The results showed that litter addition increased soil respiration by 22 %, while litter or roots removal did not affect soil respiration, which might be ascribed to the "priming effects" mediated by fresh plant litter. We also found that litter addition increased Q10, while litter removal decreased Q10. Litter addition significantly enhanced the microbial biomass for any single functional group and altered soil microbial community composition. Structural equation model further proved that microbial biomass and community composition exerted stronger impacts on Q10 than do soil abiotic factors. Soil moisture, microbial biomass and community structure were main factors in predicting soil respiration. The study highlights the important role of litter inputs compared with living roots in carbon cycling in short-term and deepens our understanding on the complex relationships among soil respiration, soil micro-environment and microbial community composition.

Cropland abandonment alleviates soil carbon emissions in the North China Plain.

Land use change could profoundly influence the terrestrial ecosystem carbon (C) cycle. However, the effects of agricultural expansion and cropland abandonment on soil microbial respiration remain controversial, and the underlying mechanisms of the land use change effect are lacking. In this study, we conducted a comprehensive survey in four land use types (grassland, cropland, orchard, and old-field grassland) of North China Plain with eight replicates to explore the responses of soil microbial respiration to agricultural expansion and cropland abandonment. We collected surface soil (0-10 cm in depth) in each land use type to measure soil physicochemical property and microbial analysis. Our results showed that soil microbial respiration was significantly increased by 15.10 mg CO2 kg-1 day-1 and 20.06 mg CO2 kg-1 day-1 due to the conversion of grassland to cropland and orchard, respectively. It confirmed that agricultural expansion might exacerbate soil C emissions. On the contrary, the returning of cropland and orchard to old-field grassland significantly decreased soil microbial respiration by 16.51 mg CO2 kg-1 day-1 and 21.47 mg CO2 kg-1 day-1, respectively. Effects of land use change on soil microbial respiration were predominately determined by soil organic and inorganic nitrogen contents, implying that nitrogen fertilizer plays an essential role in soil C loss. These findings highlight that cropland abandonment can effectively mitigate soil CO2 emissions, which should be implemented in agricultural lands with low grain production and high C emissions. Our results improve mechanistic understanding on the response of soil C emission to land use changes.

The memory effect of micro/nano-structures activating osteogenic differentiation of BMSCs.

Degradable bioceramics such as hydroxyapatite (HA) are usually used as bone grafts due to their excellent osteoconductive ability. Recent studies have proved that decorated micro/nano-structures on HA could enhance its osteogenic capacity by directly activating osteogenic differentiation of bone marrow-derived stem cells (BMSCs) or by indirectly activating the osteoimmune microenvironment. However, it is still unclear whether the degradation process of HA affects the activation effect of micro/nano-structures. In this study, we first demonstrate that the enhanced osteogenic properties activated by micro/nano-structures could be memorized and continue to play a role even after the removal of micro/nano-structures. More interestingly, this topography-triggered osteogenic memory effect (TTOME) could be regulated through the stimulation time, indicating the importance of the rational maintenance of micro/nano-structures as well as the degradation process of bioceramics. These findings provide a perspective of the design of bone implants with a biodegradable surface topography.

Drivers of nematode diversity in forest soils across climatic zones.

Nematodes are the most abundant multi-cellular animals in soil, influencing key processes and functions in terrestrial ecosystems. Yet, little is known about the drivers of nematode abundance and diversity in forest soils across climatic zones. This is despite forests covering approximately 30% of the Earth's land surface, providing many crucial ecosystem services but strongly varying in climatic conditions and associated ecosystem properties across biogeographic zones. Here, we collected nematode samples from 13 forests across a latitudinal gradient. We divided this gradient into temperate, warm-temperate and tropical climatic zones and found that, across the gradient, nematode abundance and diversity were mainly influenced by soil organic carbon content. However, mean annual temperature and total soil phosphorus content in temperate zones, soil pH in warm-temperate zones, and mean annual precipitation in tropical zones were more important in driving nematode alpha-diversity, biomass and abundance. Additionally, nematode beta-diversity was higher in temperate than in warm-temperate and tropical zones. Together, our findings demonstrate that the drivers of nematode diversity in forested ecosystems are affected by the spatial scale and climatic conditions considered. This implies that high resolution studies are needed to accurately predict how soil functions respond if climate conditions move beyond the coping range of soil organisms.

Silk fibroin scaffolds: A promising candidate for bone regeneration.

It remains a big challenge in clinical practice to repair large-sized bone defects and many factors limit the application of autografts and allografts, The application of exogenous scaffolds is an alternate strategy for bone regeneration, among which the silk fibroin (SF) scaffold is a promising candidate. Due to the advantages of excellent biocompatibility, satisfying mechanical property, controllable biodegradability and structural adjustability, SF scaffolds exhibit great potential in bone regeneration with the help of well-designed structures, bioactive components and functional surface modification. This review will summarize the cell and tissue interaction with SF scaffolds, techniques to fabricate SF-based scaffolds and modifications of SF scaffolds to enhance osteogenesis, which will provide a deep and comprehensive insight into SF scaffolds and inspire the design and fabrication of novel SF scaffolds for superior osteogenic performance. However, there still needs more comprehensive efforts to promote better clinical translation of SF scaffolds, including more experiments in big animal models and clinical trials. Furthermore, deeper investigations are also in demand to reveal the degradation and clearing mechanisms of SF scaffolds and evaluate the influence of degradation products.

Case report: Eosinophilic pneumonia associated with vedolizumab therapy in a patient with ulcerative colitis.

Extraintestinal manifestations are common in patients with inflammatory bowel disease, while respiratory involvement is less common. Vedolizumab is a new class of anti-integrin biological agents approved for treating inflammatory bowel disease. In this report, we present the case of a 38-year-old patient with ulcerative colitis for 7 years who developed cough, fever, and pulmonary infiltrates after taking vedolizumab. There was a spontaneous improvement in clinical symptoms and radiological abnormalities after discontinuing vedolizumab and introducing steroids. Despite the rarity of vedolizumab-induced eosinophilic pneumonia, the case reports indicate that patients with unexplained respiratory symptoms that are taking vedolizumab should be fully contemplated.

Mussel-Inspired Polydopamine-Based Multilayered Coatings for Enhanced Bone Formation.

Repairing bone defects remains a challenge in clinical practice and the application of artificial scaffolds can enhance local bone formation, but the function of unmodified scaffolds is limited. Considering different application scenarios, the scaffolds should be multifunctionalized to meet specific demands. Inspired by the superior adhesive property of mussels, polydopamine (PDA) has attracted extensive attention due to its universal capacity to assemble on all biomaterials and promote further adsorption of multiple external components to form PDA-based multilayered coatings with multifunctional property, which can induce synergistic enhancement of new bone formation, such as immunomodulation, angiogenesis, antibiosis and antitumor property. This review will summarize mussel-inspired PDA-based multilayered coatings for enhanced bone formation, including formation mechanism and biofunction of PDA coating, as well as different functional components. The synergistic enhancement of multiple functions for better bone formation will also be discussed. This review will inspire the design and fabrication of PDA-based multilayered coatings for different application scenarios and promote deeper understanding of their effect on bone formation, but more efforts should be made to achieve clinical translation. On this basis, we present a critical conclusion, and forecast the prospects of PDA-based multilayered coatings for bone regeneration.

Construction of a Hierarchical Micro-/Submicro-/Nanostructured 3D-Printed Ti6Al4V Surface Feature to Promote Osteogenesis: Involvement of Sema7A through the ITGB1/FAK/ERK Signaling Pathway.

Constructing hierarchical hybrid structures is considered a facile method to improve the osseointegration of implants. Herein, a hierarchical micro-/submicro-/nanostructured surface feature of Ti6Al4V implants (3DAT group) was successfully constructed by combining the inherently formed three-dimensional (3D)-printed microscale topography, acid-etched sub-micropits, and anodized nanotubes. Compared with the classical SLA surface, the microscale topography and sub-micropits increased the three-dimensional space for the cell growth and mechanical stability of implants, while the modification of nanotubes dramatically improved the surface hydrophilicity, protein adsorption, and biomineralization. Most importantly, the 3DAT surface feature possessed excellent osteogenic performance in vitro and in vivo, with the involvement of semaphorin 7A (Sema7A) as revealed by RNA-seq through the ITGB1/FAK/ERK signaling pathway. The present study suggested that the hierarchically structured surface design strategy could accelerate the osseointegration rate of 3D-printed Ti6Al4V implants, promising personalized reconstruction of bone defects.

Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation.

The human rhomboid-5 homolog-1 (RHBDF1) is a multi-transmembrane protein present mainly on the endoplasmic reticulum. RHBDF1 has been implicated in the activation of epidermal growth factor receptor (EGFR)-derived cell growth signals and other activities critical to cellular responses to stressful conditions, but details of this activation mechanism are unclear. Here, we report a RHBDF1 mRNA transcript alternative splicing variant X6 (RHBDF1 X6 or RHX6) that antagonizes RHBDF1 activities. We found that while the RHBDF1 gene is marginally expressed in breast tumor-adjacent normal tissues, it is markedly elevated in the tumor tissues. In sharp contrast, the RHX6 mRNA represents the primary RHBDF1 variant in normal breast epithelial cells and tumor-adjacent normal tissues but is diminished in breast cancer cells and tumors. We demonstrate that, functionally, RHX6 acts as an inhibitor of RHBDF1 activities. We show that artificially overexpressing RHX6 in breast cancer cells leads to retarded proliferation, migration, and decreased production of epithelial-mesenchymal transition-related adhesion molecules. Mechanically, RHX6 is able to inhibit the maturation of TACE, a protease that processes pro-TGFα, a pro-ligand of EGFR, and to prevent intracellular transportation of pro-TGFα to the cell surface. Additionally, we show that the production of RHX6 is under the control of the alternative splicing regulator RNA binding motif protein-4 (RBM4). Our findings suggest that differential splicing of the RHBDF1 gene transcript may have a regulatory role in the development of epithelial cell cancers.